A Prospective Phase II Efficacy and Safety Study of Anlotinib in Metastatic or Locally Advanced Pheochromocytoma/ Paraganglioma : Open-label Single-arm, Exploratory Trial

Posted: November 24th, 2021, 3:00pm GMT

Condition: Advanced or Metastatic Paraganglioma/ Pheochromocytoma
Intervention: Drug: Anlotinib
Sponsor: Nanjing First Hospital, Nanjing Medical University
Recruiting
21DIF039: Prone to Supine Breast MRI II, P2S2 Breast MRI Trial

Posted: November 23rd, 2021, 3:00pm GMT

Condition: Breast Cancer Female
Intervention: Procedure: Supine MRI
Sponsors: Dartmouth-Hitchcock Medical Center; CairnSurgical, Inc.
Not yet recruiting

Google - Adrenal Cancer

Ask the Doctors: No such thing as harmless tobacco products - Tulsa World

Posted: November 26th, 2021, 4:00am GMT

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Posted: November 25th, 2021, 3:11pm GMT

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Posted: November 25th, 2021, 10:00am GMT

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Posted: November 25th, 2021, 8:58am GMT

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Posted: November 25th, 2021, 7:10am GMT

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Posted: November 25th, 2021, 4:00am GMT

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Posted: November 24th, 2021, 4:39pm GMT

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Posted: November 24th, 2021, 4:38pm GMT

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Posted: November 24th, 2021, 11:00am GMT

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Posted: November 24th, 2021, 9:50am GMT

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Posted: November 23rd, 2021, 5:12pm GMT

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Posted: November 23rd, 2021, 2:24pm GMT

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Posted: November 23rd, 2021, 9:56am GMT

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Posted: November 19th, 2021, 1:19pm GMT

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Posted: November 18th, 2021, 9:45am GMT

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Wilms Tumor Protein Market: Size, Growth, Facts, Figures and Trends 2021-2027 | Top Vendors : GlaxoSmithKline Plc, Sellas Life Sciences Group Ltd, Inovio Pharmaceuticals Inc, Otsuka Holdings Co Ltdâ€¦. – LSMedia - LSMedia

Posted: November 16th, 2021, 5:52pm GMT

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TAK-981 Shown Safe With Efficacy Signal in Solid Tumors and Lymphomas - Targeted Oncology

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Causes and Risk Factors of Carcinoid Tumors - Verywell Health

Posted: November 15th, 2021, 6:19pm GMT

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Patients with RCC, Melanoma Taking ICIs Can Safely Receive COVID-19 Vaccination - OncLive

Posted: November 15th, 2021, 5:57pm GMT

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RT vs. EP in elderly outpatients undergoing colonoscopy | DDDT - Dove Medical Press

Posted: November 15th, 2021, 1:53pm GMT

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ACUPUNCTURE/CHIROPRACTIC: What causes belly fat? - Journal Advocate

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Posted: November 15th, 2021, 1:02pm GMT

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Von Hippellindau Syndrome Market 2021 Trends, Size, Growth Insight, Share, Emerging Technologies, Share, Competitive, Regional| Lily, Bedford Laboratories, Direct Therapeutics, DNAtrix – Energy Siren - Energy Siren

Posted: November 15th, 2021, 8:25am GMT

Von Hippellindau Syndrome Market 2021 Trends, Size, Growth Insight, Share, Emerging Technologies, Share, Competitive, Regional| Lily, Bedford Laboratories, Direct Therapeutics, DNAtrix – Energy Siren Energy Siren
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Posted: November 15th, 2021, 8:25am GMT

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MidMichigan Health: How does anxiety relate to cancer? - Midland Daily News

Posted: November 15th, 2021, 8:05am GMT

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Planning for Surgery? You Might Not Need All Those Tests Beforehand. - The New York Times

Posted: November 15th, 2021, 8:00am GMT

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Posted: November 15th, 2021, 3:00am GMT

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Schuylkill Valley community turns out to support young cancer patient [video] - Reading Eagle

Posted: November 14th, 2021, 4:42pm GMT

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Posted: November 14th, 2021, 4:42pm GMT

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Checkpoint Blockade Drives Progress in Endometrial Cancer Treatment - www.oncnursingnews.com/

Posted: November 13th, 2021, 2:02pm GMT

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Posted: November 13th, 2021, 2:00am GMT

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Posted: November 12th, 2021, 9:44pm GMT

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Posted: November 12th, 2021, 2:30am GMT

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Posted: November 11th, 2021, 4:32pm GMT

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PubMed - Adrenal Cancer

Safe provision of elective endocrine surgery operations amid the COVID-19 crisis

Fetched: November 26th, 2021, 5:00am GMT by I Christakis

Ann R Coll Surg Engl. 2021 Nov 25:1-9. doi: 10.1308/rcsann.2021.0220. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to determine the impact of the COVID-19 pandemic on the provision of clinical services (perioperative clinical outcomes and productivity) of the department of endocrine and general surgery at a teaching hospital in the UK.

METHODS: A retrospective chart review was conducted of all patients who were operated in our department during two periods: 1 April to 31 October 2019 (pre-COVID-19 period) and 1 April to 31 October 2020 (COVID-19 period). The perioperative clinical outcomes and productivity of our department for the two time periods were compared.

RESULTS: In the pre-COVID-19 period, 130 operations were carried out, whereas in the COVID-19 group, this reduced to 89. The baseline characteristics between the two groups did not significantly differ. Parathyroid operations decreased significantly by 68% between the two study periods. Overall, during the COVID-19 phase, the department maintained 68% of its operating workload compared with the respective 2019 time period. The clinical outcomes for the patients who had a thyroid/parathyroid/adrenal operation were not statistically different for the two study periods. There were no COVID-19 related perioperative complications for any of the operated patients and no patient tested positive for COVID-19 while an inpatient. For the COVID-19 group, the department maintained 67% of its outpatient appointments for endocrine surgery and 26% for general surgery pathologies.

CONCLUSIONS: The COVID-19 pandemic significantly reduced the clinical activity of our department. However, it is possible to continue providing clinical services for urgent/cancer cases with the appropriate safety measures in place.

PMID:34822257 | DOI:10.1308/rcsann.2021.0220
Aldosterone-producing nodules and CYP11B1 signaling correlate in primary aldosteronism

Fetched: November 26th, 2021, 5:00am GMT by Jui-Hsiang Lin

Endocr Relat Cancer. 2021 Nov 1:ERC-21-0287.R2. doi: 10.1530/ERC-21-0287. Online ahead of print.

ABSTRACT

Autonomous cortisol secretion (ACS) could be found in some patients with unilateral primary aldosteronism (uPA). However, the histopathological patterns of uPA with concurrent ACS has not been well elucidated. The adrenal gland with the adenoma from 61 uPA patients who underwent unilateral adrenalectomy were assessed by immunohistochemistry. Bioinformatics analysis, including the Cancer Genome Atlas (TCGA) and Kyoto Encyclopedia of Genes and Genomes (KEGG), was applied. The prevalence of multiple aldosterone-producing nodules or micronodules (mAPN/mAPM) was 65.6% (40/61) among our uPA patients. Concurrent ACS was identified in 32% of this uPA cohort; they were associated with the interaction of larger tumor size (> 1.98 cm) and mAPN/mAPM (OR= 3.08, p= 0.004). Transcriptome analysis uncovered a dominant enrichment of HSD3B7 over-expression (p= 0.004) in the adenomas of the histopathologically classical adrenal uPA lesions with concomitant mAPN/mAPM, compared with those uPA adenomas without concurrent surrounding mAPN/mAPM. We identified a novel linkage of enhanced steroidogenic genes of HSD3B7 expression concurrent with downstream higher CYP11B1 expression; further relationship was confirmed by immunohistochemical staining and validated by TCGA bioinformatics. The presence of mAPN/mAPM in uPA patients had lower rate for biochemical success after adrenalectomy (p=0.047). In summary, two thirds of uPA patients had concomitant mAPN/mAPM; 1/3 of uPA patients had concurrent ACS. Steroidogenic HSD3B7/ CYP11B1 signaling was associated with uPA adenomas with surrounding mAPN/mAPM. Interaction of larger adenoma size with the presence of mAPN/mAPM was linked to co-existent ACS. Such uPA patients with concomitant mAPN/mAPM had lower rate of biochemical success.

PMID:34821221 | DOI:10.1530/ERC-21-0287
Atypical presentation of a congenital metastatic neuroblastoma with severe renal impact: case report

Fetched: November 26th, 2021, 5:00am GMT by Gisele L Fiscella

Arch Argent Pediatr. 2021 Dec;119(6):e626-e630. doi: 10.5546/aap.2021.e626.

ABSTRACT

Neuroblastoma is a neural crest-derived tumor and the most common malignant tumor in neonates. Its clinical presentation can be quite variable. In some cases, it presents as an aggressive metastatic disease whilst in others it is a finding in scans performed for other reasons. The following report presents the case of a premature newborn, diagnosed postnatally with metastatic congenital neuroblastoma, with an atypical and torpid course, including severe renal injury and dialysis requirement.

PMID:34813244 | DOI:10.5546/aap.2021.e626
Monoallelic deleterious MUTYH germline variants as a driver for tumorigenesis

Fetched: November 25th, 2021, 5:00am GMT by Rodrigo Araujo Sequeira Barreiro

J Pathol. 2021 Nov 23. doi: 10.1002/path.5829. Online ahead of print.

ABSTRACT

MUTYH encodes a glycosylase involved in the base excision repair of DNA. Biallelic pathogenic germline variants in MUTYH cause an autosomal recessive condition known as MUTYH-associated adenomatous polyposis and consequently increase the risk of colorectal cancer. However, reports of increased cancer risk in individuals carrying only one defective MUTYH allele are controversial and based on studies involving few individuals. Here, we describe a comprehensive investigation of monoallelic pathogenic MUTYH germline variants in 10,389 cancer patients across 33 different tumour types and 117,000 healthy individuals. Our results indicate that monoallelic pathogenic MUTYH germline variants can lead to tumorigenesis through a mechanism of somatic loss of heterozygosity of the functional MUTYH allele in the tumour. We confirmed that the frequency of monoallelic pathogenic MUTYH germline variants is higher in individuals with cancer than in the general population, although this frequency is not homogeneous among tumour types. We also demonstrated that the MUTYH mutational signature is present only in tumours with loss of the functional allele and found that the characteristic MUTYH base substitution (C>A) increases stop-codon generation. We identified key genes that are affected during tumorigenesis. In conclusion, we propose that carriers of the monoallelic pathogenic MUTYH germline variant are at a higher risk of developing tumours, especially those with frequent loss of heterozygosity events, such as adrenal adenocarcinoma, although the overall risk is still low. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID:34816434 | DOI:10.1002/path.5829
Live birth after in-vitro maturation of oocytes in a patient with specific ovarian insufficiency caused by long-term mitotane treatment for adrenocortical carcinoma

Fetched: November 25th, 2021, 5:00am GMT by Hélène Bry-Gauillard

Reprod Biomed Online. 2021 Oct 17:S1472-6483(21)00516-2. doi: 10.1016/j.rbmo.2021.10.004. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: How should the fertility of a woman with persistent specific ovarian dysfunction after long-term mitotane exposure be managed?

DESIGN: Case report. A 33-year-old woman who underwent surgery for adrenocortical carcinoma and treated with mitotane was referred for infertility. She rapidly became amenorrhoeic while taking mitotane, a condition that persisted for 5 years after cessation. Repeated serum hormone evaluation showed collapsed androgen levels, low oestradiol, high gonadotrophins (LH 69 and 63; FSH 23 and 43 IU/l), relatively high inhibin B level and slightly decreased anti-Müllerian hormone levels (1.4 and 0.7 ng/ml). An ultrasound scan revealed an antral follicle count of 13, contrasting with high serum gonadotrophin levels. After failure to obtain follicular growth after ovarian stimulation, in-vitro maturation (IVM) of immature oocytes aspirated from the antral follicles was carried out for microinjection with the spermatozoa of the patient's partner.

RESULTS: Two cycles of unstimulated egg retrieval were carried out, producing seven IVM oocytes, which were microinjected. A total of three cleavage-stage embryos were vitrified and unsuccessfully transferred after endometrial preparation using hormone replacement therapy (HRT). After a 20-month break, two new attempts were carried out under HRT with the aim of achieving a fresh embryo transfer. The last attempt succeeded after transfer of a single day-2 embryo, and the patient delivered a healthy baby.

CONCLUSION: Persistent specific impaired ovarian function 5 years after withdrawal of mitotane, and the first live birth after IVM in this situation, are reported. The question of fertility preservation before long-term mitotane treatment is raised.

PMID:34815159 | DOI:10.1016/j.rbmo.2021.10.004
Transfer learning for fluence map prediction in adrenal stereotactic body radiation therapy

Fetched: November 24th, 2021, 5:00am GMT by Wentao Wang

Phys Med Biol. 2021 Nov 22. doi: 10.1088/1361-6560/ac3c14. Online ahead of print.

ABSTRACT

OBJECTIVE: To design a deep transfer learning framework for modeling fluence map predictions for stereotactic body radiation therapy (SBRT) of adrenal cancer and similar sites that usually have a small number of cases.

APPROACH: We developed a transfer learning framework for adrenal SBRT planning that leverages knowledge in a pancreas SBRT planning model. Treatment plans from the two sites had different dose prescriptions and beam settings but both prioritized gastrointestinal sparing. A base framework was first trained with 100 pancreas cases. This framework consists of two convolutional neural networks (CNN), which predict individual beam doses (BD-CNN) and fluence maps (FM-CNN) sequentially for 9-beam intensity-modulated radiation therapy (IMRT) plans. Forty-five adrenal plans were split into training/validation/test sets with the ratio of 20/10/15. The base BD-CNN was re-trained with transfer learning using 5/10/15/20 adrenal training cases to produce multiple candidate adrenal BD-CNN models. The base FM-CNN was directly used for adrenal cases. The deep learning (DL) plans were evaluated by several clinically relevant dosimetric endpoints, producing a percentage score relative to the clinical plans.

MAIN RESULTS: Transfer learning significantly reduced the number of training cases and training time needed to train such a DL framework. The adrenal transfer learning model trained with 5/10/15/20 cases achieved validation plan scores of 85.4/91.2/90.7/89.4, suggesting that model performance saturated with 10 training cases. Meanwhile, a model using all 20 adrenal training cases without transfer learning only scored 80.5. For the final test set, the 5/10/15/20-case models achieved scores of 73.5/75.3/78.9/83.3.

SIGNIFICANCE: It is feasible to use deep transfer learning to train an IMRT fluence prediction framework. This technique could adapt to different dose prescriptions and beam configurations. This framework potentially enables DL modeling for clinical sites that have a limited dataset, either due to few cases or due to rapid technology evolution.

PMID:34808605 | DOI:10.1088/1361-6560/ac3c14
Management of Incidentalomas

Fetched: November 24th, 2021, 5:00am GMT by Keely Reidelberger

Surg Clin North Am. 2021 Dec;101(6):1081-1096. doi: 10.1016/j.suc.2021.06.006.

ABSTRACT

Incidental findings are common in the evaluation of surgical patients. Understanding the appropriate assessment and management of these frequent occurrences is important for the provision of comprehensive quality care. This review details the epidemiology, considerations, and recommendations for management of common incidental manifestations in surgical patients, including Meckel diverticulum, adrenal incidentaloma, thyroid nodule, solitary pulmonary nodule, small bowel intussusception, gallstones, and incidental appendectomy.

PMID:34774270 | DOI:10.1016/j.suc.2021.06.006
Rare tumors in pediatrics. First report in Argentina

Fetched: November 24th, 2021, 5:00am GMT by Alejandra Casanovas

Arch Argent Pediatr. 2021 Dec;119(6):401-407. doi: 10.5546/aap.2021.eng.401.

ABSTRACT

INTRODUCTION: Collaborative clinical trials have enlarged the knowledge base about pediatric tumors; however, this is not the case for rare tumors (RT).

OBJECTIVE: To describe the prevalence, clinical characteristics, and course of RT in pediatric patients diagnosed at Hospital Garrahan.

MATERIAL AND METHODS: Descriptive, retrospective study of patients aged 0-18 years diagnosed with a RT and admitted between January 2007 and December 2017.

RESULTS: Out of 1657 patients diagnosed with solid tumors, 164 (9.9 %) were RT; 71.95 % (118) of patients were younger than 14 years and 81.7 % (130) were males. In order of frequency, RT were thyroid carcinoma (60), adrenal carcinoma (14), lung tumors (14), melanoma (13), salivary gland cancer (11), gastrointestinal tumors (8), non-germ cell gonadal tumors (7), pancreatic tumors (7), renal carcinomas (6), nasopharyngeal carcinomas (5), pheochromocytoma and paraganglioma (5), and thymic carcinoma in 1 patient. Treatment depended on tumor type and stage. The median follow-up was 34.9 months (range: 1-128.5 months); 133 patients (78.7 %) are alive and only 10 patients (6 %) were lost-to-follow-up.

CONCLUSION: The prevalence of RT was 9.9 %. Twenty-seven percent occurred in adolescents. The most frequent tumors included thyroid carcinoma, adrenal carcinoma, and melanoma. Treatment and course varied based on tumor histology. Predisposing molecular alterations were found in 5.3 % of patients; 3.5 % had a history of cancer.

PMID:34813233 | DOI:10.5546/aap.2021.eng.401
Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment

Fetched: November 23rd, 2021, 5:00am GMT by Emilia Modolo Pinto

Front Endocrinol (Lausanne). 2021 Nov 5;12:756523. doi: 10.3389/fendo.2021.756523. eCollection 2021.

ABSTRACT

Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline TP53 variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline TP53 variants, loss of maternal chromosome 11 and duplication of the paternal copy [paternal uniparental disomy, (UPD)] occurs early in tumorigenesis and explains the overexpression of IGF2, the hallmark of pediatric ACT. Beckwith-Wiedemann syndrome (BWS) is also associated with overexpression of IGF2 due to disruption of the 11p15 loci, including segmental UPD. Here, we report six children with ACT with wild type TP53 and germline paternal 11p15 UPD. Median age of five girls and one boy was 3.2 years (range 0.5-11 years). Two patients met the criteria for BWS before diagnosis of ACT. However, ACT was the first and only manifestation of paternal 11p15 UPD in four children. Tumor weight ranged from 21.5 g to 550 g. Despite poor prognostic features at presentation, such as pulmonary metastasis, bilateral adrenal involvement, and large tumors, all patients are alive 8-21 years after cancer diagnosis. Our observations suggest that children with ACT and wild type TP53, irrespective of their age, should be screened for germline abnormalities in chromosome 11p15.

PMID:34803919 | PMC:PMC8602920 | DOI:10.3389/fendo.2021.756523
A Young Man with a Rare Case of Adrenal Incidentaloma

Fetched: November 23rd, 2021, 5:00am GMT by Usama Bin Khalid

J Coll Physicians Surg Pak. 2021 Dec;31(12):1497-1499. doi: 10.29271/jcpsp.2021.12.1497.

ABSTRACT

Adrenal incidentalomas (AIs) are adrenal masses discovered as incidental finding, often on imaging studies, unrelated to adrenal disorders. Sometimes, they are discovered as part of work-up for adrenal pathology. AIs are mostly nonfunctional (hormonally silent), but can also be functional (hormonally active). The differential diagnosis includes many primary, metastatic, benign and malignant conditions. The current case is a young male, who went to a peripheral health facility with complaints of dysuria and burning micturition. His laboratory and radiological investigations suggested a urinary tract infection with an incidental finding of adrenal mass. After referral, his detailed work-up was done at Endocrine Clinic of Armed Forces Institute of Pathology (AFIP), Rawalpindi, which revealed history of episodic headaches and palpitations with paroxysmal spikes of high blood pressure up to 200/120 mmHg. Adrenalectomy was performed by laparoscopic surgery. Histopathological examination confirmed the diagnosis of pheochromocytoma with PASS score of 5/20. This is one of the rare cases of adrenal incidentaloma, often an autopsy finding. Pheochromocytoma needs to be investigated in all cases of AIs. Key Words: Adrenal incidentaloma, Pheochromocytoma, Urinary tract infection.

PMID:34794295 | DOI:10.29271/jcpsp.2021.12.1497
ACR Appropriateness Criteria Adrenal Mass Evaluation: 2021 Update

Fetched: November 20th, 2021, 5:00am GMT by Expert Panel on Urological Imaging

J Am Coll Radiol. 2021 Nov;18(11S):S251-S267. doi: 10.1016/j.jacr.2021.08.010.

ABSTRACT

The appropriate evaluation of adrenal masses is strongly dependent on the clinical circumstances in which it is discovered. Adrenal incidentalomas are masses that are discovered on imaging studies that have been obtained for purposes other than adrenal disease. Although the vast majority of adrenal incidentalomas are benign, further radiological and biochemical evaluation of these lesions is important to arrive at a specific diagnosis. Patients with a history of malignancy or symptoms of excess hormone require different imaging evaluations than patients with incidentalomas. This document reviews imaging approaches to adrenal masses and the various modalities utilized in evaluation of adrenal lesions. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

PMID:34794587 | DOI:10.1016/j.jacr.2021.08.010
Imaging findings of primary adrenal tumors in pediatric patients

Fetched: November 20th, 2021, 5:00am GMT by H Nursun Özcan

Diagn Interv Radiol. 2021 Nov;27(6):811-815. doi: 10.5152/dir.2021.20701.

ABSTRACT

Apart from neuroblastomas, adrenal tumors are rarely seen in children. The most common adrenal tumors are adrenocortical carcinoma and pheochromocytoma. Adrenocortical carcinoma is usually a large heterogeneous, well-marginated mass with solid/cystic areas and calcifications, with poor prognosis. Most of the pheochromocytomas are benign tumors and usually show intense contrast enhancement, the pattern of which may be diffuse, mottled, or peripheral on computed tomography and magnetic resonance imaging. The purpose of this article is to evaluate primary nonneurogenic adrenal tumors.

PMID:34792039 | DOI:10.5152/dir.2021.20701
Radiological characteristics and diagnostic impact of duplicated right adrenal veins on adrenal venous sampling in primary aldosteronism

Fetched: November 20th, 2021, 5:00am GMT by Hiromitsu Tannai

Diagn Interv Radiol. 2021 Nov;27(6):754-761. doi: 10.5152/dir.2021.21388.

ABSTRACT

PURPOSE: We aimed to analyze the prevalence and radiological characteristics of duplicated right adrenal veins (DRAVs) and evaluate the diagnostic impact of adrenal venous sampling (AVS) in primary aldosteronism.

METHODS: DRAVs were retrospectively identified among patients who underwent segmental AVS between April 2017 and March 2020. DRAVs were defined as main or accessory according to the drainage area. The diameter, position, hormone levels, and treatment plan based on AVS were compared between main and accessory RAVs, using the Wilcoxon rank-sum test.

RESULTS: Fourteen of 432 patients (3.2%) were diagnosed with DRAVs. On venography, the mean diameters of the main and accessory side were 3±0.63 mm and 2.1±0.41 mm, respectively, and were significantly different (p < 0.001). The mean relative position in craniocaudal direction of main and accessory veins from the adrenal caudal edge on computed tomography was 65.5%±16.0%, and 48.1%±16.8%, respectively, which was significantly different (p = 0.007). The left-right positions and hormone levels were not significantly different. Based on conventional AVS, the treatment plan between DRAVs was not changed in six of eight patients, but changed from surgery to medication in two patients with right aldosterone-producing adenoma (APA)/microadenoma based on segmental AVS findings.

CONCLUSION: DRAVs, in which the main RAV was thicker and more cranially located than the accessory RAV were rare. Depending on blood sampled from either of DRAVs, the diagnosis made through conventional AVS might change treatment approach from surgery to medication, especially with right APA. Hence, their identification is important to make an accurate subtyping by AVS.

PMID:34792030 | DOI:10.5152/dir.2021.21388
Are the washout values currently accepted for lesion characterization in dedicated adrenal CT adequate for diagnosis?

Fetched: November 20th, 2021, 5:00am GMT by Elif Gündoğdu

Diagn Interv Radiol. 2021 Nov;27(6):694-702. doi: 10.5152/dir.2021.20508.

ABSTRACT

PURPOSE: We aimed to investigate the accuracy of density characteristics and washout values of lesions detected on computed tomography (CT) at the cutoff values obtained from the literature by taking the pathological results of adrenalectomy specimens as reference and to determine the cutoff values of parameters evaluated on CT for the differentiation of adenoma and nonadenoma lesions in the study group.

METHODS: Hospital records and standard CT imaging data (noncontrast early phase [65 s] and late phase [15 min] ) of 84 patients with 87 lesions who underwent adrenalectomy between January 2012 and December 2018 were retrospectively reevaluated by two radiologists in consensus. The patients were categorized as having adenoma and nonadenoma lesions according to the pathology results. The sensitivity, specificity and diagnostic accuracy of CT parameters (density values and washout percentages) were evaluated. Differences in the CT parameters (size, noncontrast and early-late enhancement density and absolute and relative washout values) were investigated. The optimal cutoff values of CT parameters were determined by ROC analysis.

RESULTS: Noncontrast CT had a specificity of 87.75% and 95.9%, sensitivity of 60% and 48.6%, diagnostic accuracy of 77.7% and 89.47% for adenomas, at the cutoff values of ≤10 HU and ≤0 HU, respectively. For absolute washout value ≥ 60%, the sensitivity, specificity and accuracy were 64.7%, 52.38% and 56.75%, respectively; while these rates were 76.47%, 56.52% and 62.16%, respectively, for relative washout value ≥40%. Adenomas and nonadenomas showed significant difference in terms of size (p < 0.0001), unenhanced attenuation (p < 0.0001), relative washout (p = 0.020) and delay enhancement (p < 0.001). But there were no differences in terms of absolute washout (p = 0.230) and early enhancement (p = 0.264). The cutoff values for the differentiation of adenomas and nonadenomas were as follows: size ≤44 mm, noncontrast density <20 HU, early-phase density ≥45 HU, delayed-phase density ≤44 HU, absolute washout 74.83% and relative washout 57.76%.

CONCLUSION: The current washout criteria used in the differentiation of adenoma and nonadenoma lesions in dynamic CT imaging can give false negative and positive results. According to the existing criteria, the most reliable parameter in adenoma-nonadenoma differentiation is ≤ 0 HU noncontrast CT density value.

PMID:34792022 | DOI:10.5152/dir.2021.20508
Adrenocortical Carcinoma: The Value of Lymphadenectomy

Fetched: November 19th, 2021, 5:00am GMT by Joshua Tseng

Ann Surg Oncol. 2021 Nov 18. doi: 10.1245/s10434-021-11051-5. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) staging does not account for the number of positive nodes. The prognostic value of quantitative metastatic nodal burden is unknown.

METHODS: The National Cancer Database was retrospectively queried from 2004-2016 to identify patients with Stage I-III ACC undergoing adrenalectomy. Patients who underwent lymphadenectomy (LAD) were further studied. Demographics, TNM staging, tumor characteristics, and surgical approach were analyzed.

RESULTS: 386 LADs were identified. The median number of nodes examined was 2 (IQR 2-6), with no difference by surgical approach '[laparoscopic, 3 (1-3); robotic, 1.5 (1-4.5); open, 2 (1-7), p = 0.493]. In LADs with cN0 disease, positive nodes were seen in 17.5% of patients; an average of 6 (1-12) nodes were examined in patients who upstaged to pN1 disease compared with an average of 2 (1-6) nodes in those who remained pN0. Median survival was incrementally worse for patients with more positive nodes (62.8 vs. 21.9 vs. 13.7 vs. 11.3 vs. 10.7 months for 0, 1, 2, 3, and ≥ 4 positive nodes, respectively, p < 0.01). On multivariate analysis, significant prognostic factors for poor survival included older age, ≥ 2 comorbidities, pT3, and pT4. The strongest prognostic factor for poor survival was the number of positive nodes (1 node, hazards ratio [HR] 2.3, 95% confidence interval [CI] 1.5-3.6; 2 nodes, HR 1.3, 95% CI 0.6-3.0; 3 nodes, HR 3.0, 95% CI 1.1-8.0; ≥ 4 nodes, HR 4.0, 95% CI 2.5-6.2). Lymphadenectomy was associated with improved survival (HR 0.82, 95% CI 0.67-0.99).

CONCLUSIONS: Higher quantitative metastatic nodal burden is a robust prognostic factor for worse survival in ACC.

PMID:34792698 | DOI:10.1245/s10434-021-11051-5
Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies

Fetched: November 14th, 2021, 5:00am GMT by Marco Lo Iacono

Cancers (Basel). 2021 Oct 20;13(21):5255. doi: 10.3390/cancers13215255.

ABSTRACT

Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. Although it is known that mitotane destroys the adrenal cortex and impairs steroidogenesis, its exact mechanism of action is still unclear. The most used cell models are H295-derived cell strains and SW13 cell lines. The diverging results obtained in presumably identical cell lines highlight the need for a stable in vitro model and/or a standard methodology to perform experiments on H295 strains. The presence of several enzymatic targets responsive to mitotane in mitochondria and mitochondria-associated membranes causes progressive alteration in mitochondrial structure when cells were exposed to mitotane. Confounding factors of culture affecting in vitro experiments could reduce the significance of any molecular mechanism identified in vitro. To ensure experimental reproducibility, particular care should be taken in the choice of culture conditions: aspects such as cell strains, culture serum, lipoproteins concentration, and culture passages should be carefully considered and explicated in the presentation of results. We aimed to review in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. If the concerns pointed out in this review will be overcome, the new insights into mitotane mechanism of action observed in-vitro could allow the identification of novel pharmacological molecular pathways to be used to implement personalized therapy.

PMID:34771418 | PMC:PMC8582505 | DOI:10.3390/cancers13215255
Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity

Fetched: November 14th, 2021, 5:00am GMT by Ondrej Vit

Molecules. 2021 Oct 29;26(21):6567. doi: 10.3390/molecules26216567.

ABSTRACT

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal medulla or sympathetic or parasympathetic paraganglia, respectively. To identify new therapeutic targets, we performed a detailed membrane-focused proteomic analysis of five human paraganglioma (PGL) samples. Using the Pitchfork strategy, which combines specific enrichments of glycopeptides, hydrophobic transmembrane segments, and non-glycosylated extra-membrane peptides, we identified over 1800 integral membrane proteins (IMPs). We found 45 "tumor enriched" proteins, i.e., proteins identified in all five PGLs but not found in control chromaffin tissue. Among them, 18 IMPs were predicted to be localized on the cell surface, a preferred drug targeting site, including prostate-specific membrane antigen (PSMA), a well-established target for nuclear imaging and therapy of advanced prostate cancer. Using specific antibodies, we verified PSMA expression in 22 well-characterized human PPGL samples. Compared to control chromaffin tissue, PSMA was markedly overexpressed in high-risk PPGLs belonging to the established Cluster 1, which is characterized by worse clinical outcomes, pseudohypoxia, multiplicity, recurrence, and metastasis, specifically including SDHB, VHL, and EPAS1 mutations. Using immunohistochemistry, we localized PSMA expression to tumor vasculature. Our study provides the first direct evidence of PSMA overexpression in PPGLs which could translate to therapeutic and diagnostic applications of anti-PSMA radio-conjugates in high-risk PPGLs.

PMID:34770976 | PMC:PMC8587166 | DOI:10.3390/molecules26216567
Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer

Fetched: November 14th, 2021, 5:00am GMT by Anna M Wulf

Int J Mol Sci. 2021 Oct 29;22(21):11718. doi: 10.3390/ijms222111718.

ABSTRACT

Neuroblastoma is a common extracranial solid tumour of childhood, responsible for 15% of cancer-related deaths in children. Prognoses vary from spontaneous remission to aggressive disease with extensive metastases, where treatment is challenging. Tumours are thought to arise from sympathoadrenal progenitor cells, which derive from an embryonic cell population called neural crest cells that give rise to diverse cell types, such as facial bone and cartilage, pigmented cells, and neurons. Tumours are found associated with mature derivatives of neural crest, such as the adrenal medulla or paraspinal ganglia. Sympathoadrenal progenitor cells express anaplastic lymphoma kinase (ALK), which encodes a tyrosine kinase receptor that is the most frequently mutated gene in neuroblastoma. Activating mutations in the kinase domain are common in both sporadic and familial cases. The oncogenic role of ALK has been extensively studied, but little is known about its physiological role. Recent studies have implicated ALK in neural crest migration and sympathetic neurogenesis. However, very few downstream targets of ALK have been identified. Here, we describe pathological activation of ALK in the neural crest, which promotes proliferation and migration, while preventing differentiation, thus inducing the onset of neuroblastoma. Understanding the effects of ALK activity on neural crest cells will help find new targets for neuroblastoma treatment.

PMID:34769149 | PMC:PMC8584162 | DOI:10.3390/ijms222111718
Pulmonary sarcomatoid carcinoma mimicking pleural mesothelioma: A case report

Fetched: November 13th, 2021, 5:00am GMT by Le Wang

Medicine (Baltimore). 2021 Nov 12;100(45):e27813. doi: 10.1097/MD.0000000000027813.

ABSTRACT

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is an extremely rare biphasic tumor characterized by a mixture of malignant epithelial and mesenchymal cells. Owing to the rarity, as well as the lack of typical manifestations and imaging signs, the rate of misdiagnosis is high. Herein, we present a case of PSC misdiagnosed as pleural mesothelioma in a 59-year-old man.

PATIENT CONCERNS: A 59-year-old man presented with recurrent coughing, fever, and chest pain.

DIAGNOSIS: Chest computed tomography showed 2 large and dense masses involving the inferior lobes of right lung, along with slight irregular pleural thickening and a small amount of effusion.

INTERVENTIONS: Chest computed tomography-guided tumor biopsy was performed. PSC was confirmed based on histopathology and immunohistochemistry. The patient refused treatment due to economic reasons.

OUTCOMES: The patient developed adrenal, multiple lung and brain metastasis. The overall survival time was 11 months.

CONCLUSIONS: PSC, despite its rarity, should be considered in the differential diagnosis of lung cancer. Besides, biopsy, histopathology, and specific immunohistochemical staining of larger tissue specimens can be contributing to the accurate diagnosis of PSC.

PMID:34766593 | PMC:PMC8589231 | DOI:10.1097/MD.0000000000027813
A Rare Case of Addison's Disease Presenting With Intermittent Pancytopenia and Cardiac Tamponade

Fetched: November 13th, 2021, 5:00am GMT by Haoyang Wang

AACE Clin Case Rep. 2021 May 21;7(6):353-356. doi: 10.1016/j.aace.2021.05.005. eCollection 2021 Nov-Dec.

ABSTRACT

OBJECTIVE: To report the first case, to our knowledge, of intermittent pancytopenia and cardiac tamponade occurring together in association with Autoimmune Addison's Disease (AAD).

METHODS: A 21 year-old woman presented on three different occasions with multiple complaints. Her evaluation was significant for intermittent pancytopenia (white blood cell, 1.3-3.0 × 10³/μL [normal 4.5-11 × 10³]; hemoglobin, 8.8-9.6 g/dL [11-16]; and platelets, 102-117 × 10³/μL [150-400 × 10³/μL]) and pericardial effusion with cardiac tamponade. Further investigation including a morning serum cortisol level of 0.6 μg/dL (5.27-22.45 μg/dL), adrenocorticotropic hormone level of 1027 pg/mL (normal 6-50 pg/mL), and positive 21-hydroxylase antibodies confirmed the diagnosis of primary adrenal insufficiency due to AAD. Treatment with steroids resulted in prompt hemodynamic recovery with normalization of all blood cell lines.

RESULTS: The diagnosis of AAD is often delayed or overlooked. Pancytopenia occurring in AAD is most likely due to either marrow suppression in the setting of acute illness and exacerbated by hypoadrenalism or possibly an autoimmune-mediated marrow reaction. Pericarditis with cardiac tamponade has been described in AAD occurring in the setting of polyglandular autoimmune syndrome type II. The pathogenesis involves autoimmune inflammation of the pericardium, which precipitates an acute inflammatory reaction and rapid fluid accumulation.

CONCLUSION: Pericarditis with cardiac tamponade and intermittent neutropenia may be rare manifestations of an Addisonian crisis.

PMID:34765731 | PMC:PMC8573284 | DOI:10.1016/j.aace.2021.05.005
Congenital adrenal hyperplasia presented with bilateral testicular tumor: A case report

Fetched: November 13th, 2021, 5:00am GMT by Abazar Akbarzadeh Pasha

Caspian J Intern Med. 2021;12(Suppl 2):S431-S434. doi: 10.22088/cjim.12.0.431.

ABSTRACT

BACKGROUND: Congenital adrenal hyperplasia (CAH) refers to group of congenital diseases resulting from impaired adrenal steroidogenesis, and its most common cause is 21-hydroxylase deficiency. Testicular adrenal residual tumor (TART) is one of the major complications of CAH, possibly resulting from ectopic remnants of intra-testicular adrenal tissue which is stimulated by excessive secretion of adrenocorticotropic hormone (ACTH). This tumor can be misdiagnosed as Leydig cell tumor (LCT) in these people.

CASE PRESENTATION: The patient we are presenting is a 20-year-old man with a history of precocious puberty and a height below 3% of the population who underwent radical left testicular orchiectomy with a complaint of bilateral testicular mass, which is reported LCT in the pathology report. In preoperative imaging examinations, bilateral adrenal hyperplasia is observed. In hormonal examinations, the patient is diagnosed with CAH and has been treated with corticosteroids for one year.

CONCLUSION: In patients who present with bilateral testicular mass, it is the best image by abdominopelvic CT scan before surgery to detect CAH.

PMID:34760099 | PMC:PMC8559653 | DOI:10.22088/cjim.12.0.431
Shrinkage of a pituitary metastasis of melanoma induced by pembrolizumab: a case report

Fetched: November 13th, 2021, 5:00am GMT by Giuseppe Giuffrida

J Med Case Rep. 2021 Nov 11;15(1):555. doi: 10.1186/s13256-021-03150-4.

ABSTRACT

BACKGROUND: Pituitary metastases are rare, often deriving from lung or breast cancer owing to the upper vena cava proximity. Pituitary metastases can manifest with signs and symptoms of pituitary tumors, consequent to mass effect (headache, visual impairment) and/or hormonal alterations (hyperprolactinemia, hypopituitarism, and diabetes insipidus). Immune checkpoint inhibitors burst immunity against tumors, significantly increasing patients' survival, but their autoimmune side effects frequently involve the skin, the gastrointestinal tract, and the endocrine glands (pituitary, thyroid, pancreas).

CASE PRESENTATION: A 77-year-old Caucasian man had undergone trans-nasal sphenoidal surgery for a nonsecreting pituitary macroadenoma in 2001, without remnant or endocrine deficits. In 2016, he was operated for a shoulder melanoma. In February 2018, imaging evaluation demonstrated metastases in lung, liver, and femur. Therefore, treatment with pembrolizumab (anti-programmed death 1) was scheduled in May 2018, but, before starting this therapy, a brain computed tomography performed for a sudden loss of consciousness detected a sellar mass of 17 × 12 mm, which extended to the pituitary stalk and compressed the optic chiasma. Focused magnetic resonance imaging confirmed the size and characteristics of the lesion, while emergency evaluation of the hormonal profile demonstrated an impairment of adrenal and thyroid function. The pituitary lesion demonstrated a remarkable shrinkage (8 × 6 mm), which was confirmed by subsequent imaging evaluations.

CONCLUSIONS: This is the first case reporting on effectiveness of immune checkpoint inhibitors in a patient with pituitary metastasis from a melanoma.

PMID:34758866 | PMC:PMC8582141 | DOI:10.1186/s13256-021-03150-4
Stress and spirituality in relation to HPA axis gene methylation among US Black women: results from the Black Women's Health Study and the Study on Stress, Spirituality and Health

Fetched: November 13th, 2021, 5:00am GMT by Alexandra E Shields

Epigenomics. 2021 Nov;13(21):1711-1734. doi: 10.2217/epi-2021-0275. Epub 2021 Nov 2.

ABSTRACT

Background: Few epigenetics studies have been conducted within the Black community to examine the impact of diverse psychosocial stressors and resources for resiliency on the stress pathway (hypothalamus-pituitary-adrenal axis). Methods: Among 1000 participants from the Black Women's Health Study, associations between ten psychosocial stressors and DNA methylation (DNAm) of four stress-related genes (NR3C1, HSDB1, HSD11B2 and FKBP5) were tested. Whether religiosity or spirituality (R/S) significantly modified these stress-DNAm associations was also assessed. Results: Associations were found for several stressors with DNAm of individual CpG loci and average DNAm levels across each gene, but no associations remained significant after false discovery rate (FDR) correction. Several R/S variables appeared to modify the relationship between two stressors and DNAm, but no identified interaction remained significant after FDR correction. Conclusion: There is limited evidence for a strong signal between stress and DNAm of hypothalamus-pituitary-adrenal axis genes in this general population cohort of US Black women.

PMID:34726080 | PMC:PMC8579940 | DOI:10.2217/epi-2021-0275
CYP11B1 variants influence skeletal maturation via alternative splicing

Fetched: November 11th, 2021, 5:00am GMT by Olja Grgic

Commun Biol. 2021 Nov 9;4(1):1274. doi: 10.1038/s42003-021-02774-y.

ABSTRACT

We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10^-12). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10^-40), exon 4 inclusion (P = 4.29 × 10^-34), and decreased exon 3 and 5 splicing (P = 7.85 × 10^-43), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-β-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.

PMID:34754074 | PMC:PMC8578655 | DOI:10.1038/s42003-021-02774-y
Machine intelligence in non-invasive endocrine cancer diagnostics

Fetched: November 11th, 2021, 5:00am GMT by Nicole M Thomasian

Nat Rev Endocrinol. 2021 Nov 9:1-15. doi: 10.1038/s41574-021-00543-9. Online ahead of print.

ABSTRACT

Artificial intelligence (AI) has illuminated a clear path towards an evolving health-care system replete with enhanced precision and computing capabilities. Medical imaging analysis can be strengthened by machine learning as the multidimensional data generated by imaging naturally lends itself to hierarchical classification. In this Review, we describe the role of machine intelligence in image-based endocrine cancer diagnostics. We first provide a brief overview of AI and consider its intuitive incorporation into the clinical workflow. We then discuss how AI can be applied for the characterization of adrenal, pancreatic, pituitary and thyroid masses in order to support clinicians in their diagnostic interpretations. This Review also puts forth a number of key evaluation criteria for machine learning in medicine that physicians can use in their appraisals of these algorithms. We identify mitigation strategies to address ongoing challenges around data availability and model interpretability in the context of endocrine cancer diagnosis. Finally, we delve into frontiers in systems integration for AI, discussing automated pipelines and evolving computing platforms that leverage distributed, decentralized and quantum techniques.

PMID:34754064 | PMC:PMC8576465 | DOI:10.1038/s41574-021-00543-9
Inhaled and intranasal ciclesonide for the treatment of covid-19 in adult outpatients: CONTAIN phase II randomised controlled trial

Fetched: November 11th, 2021, 5:00am GMT by Nicole Ezer

BMJ. 2021 Nov 2;375:e068060. doi: 10.1136/bmj-2021-068060.

ABSTRACT

OBJECTIVE: To determine if inhaled and intranasal ciclesonide are superior to placebo at decreasing respiratory symptoms in adult outpatients with covid-19.

DESIGN: Randomised, double blind, placebo controlled trial.

SETTING: Three Canadian provinces (Quebec, Ontario, and British Columbia).

PARTICIPANTS: 203 adults aged 18 years and older with polymerase chain reaction confirmed covid-19, presenting with fever, cough, or dyspnoea.

INTERVENTION: Participants were randomised to receive either inhaled ciclesonide (600 μg twice daily) and intranasal ciclesonide (200 μg daily) or metered dose inhaler and nasal saline placebos for 14 days.

MAIN OUTCOME MEASURES: The primary outcome was symptom resolution at day 7. Analyses were conducted on the modified intention-to-treat population (participants who took at least one dose of study drug and completed one follow-up survey) and adjusted for stratified randomisation by sex.

RESULTS: The modified intention-to-treat population included 203 participants: 105 were randomly assigned to ciclesonide (excluding two dropouts and one loss to follow-up) and 98 to placebo (excluding three dropouts and six losses to follow-up). The median age was 35 years (interquartile range 27-47 years) and 54% were women. The proportion of participants with resolution of symptoms by day 7 did not differ significantly between the intervention group (42/105, 40%) and control group (34/98, 35%); absolute adjusted risk difference 5.5% (95% confidence interval -7.8% to 18.8%). Results might be limited to the population studied, which mainly included younger adults without comorbidities. The trial was stopped early, therefore could have been underpowered.

CONCLUSION: Compared with placebo, the combination of inhaled and intranasal ciclesonide did not show a statistically significant increase in resolution of symptoms among healthier young adults with covid-19 presenting with prominent respiratory symptoms. As evidence is insufficient to determine the benefit of inhaled and intranasal corticosteroids in the treatment of covid-19, further research is needed.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04435795.

PMID:34728476 | PMC:PMC8561042 | DOI:10.1136/bmj-2021-068060
SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma

Fetched: November 10th, 2021, 5:01am GMT by Jean Pierre Bayley

J Med Genet. 2021 Nov 8:jmedgenet-2020-107656. doi: 10.1136/jmedgenet-2020-107656. Online ahead of print.

ABSTRACT

BACKGROUND: Traditional genotype-phenotype correlations for the succinate dehydrogenase-complex II (SDH) genes link SDHB variants to thoracic-abdominal pheochromocytoma-paraganglioma (PPGL) and SDHD variants to head and neck paraganglioma (HNPGL). However, in a recent study we found strong and specific genotype-phenotype associations for SDHD variants. In the present study we zoom in on the genotype-phenotype associations of SDHB gene variants, considering the impact of individual gene variants on disease risk and risk of malignancy.

METHODS: We analysed two large independent data sets, including a total of 448 patients with PPGL and HNPGL, and studied the association of missense or truncating SDHB variants with tumour incidence, age of onset and malignancy risk using binomial testing and Kaplan-Meier analysis.

RESULTS: Compared with missense variants, truncating SDHB variants were significantly and consistently more common in patients with PPGL, by a 20 percentage point margin. Malignancy was also significantly more common in truncating versus missense variant carriers. No overall differences in age of PPGL onset were noted between carriers of the two variant types, although some individual variants may differ in certain cases. Missense variants were marginally over-represented among patients with HNPGL, but the difference was not statistically significant.

CONCLUSION: SDHB truncating variants convey an elevated risk for development of both PPGL and malignancy compared with missense variants. These results further support earlier robust associations between truncating variants and PPGL, and also suggest that the two variant types differ in their impact on complex II function, with PPGL/HNPGL tissues displaying differing sensitivities to changes in complex II function.

PMID:34750193 | DOI:10.1136/jmedgenet-2020-107656
Clinical impact of HSD3B1 polymorphism by metastatic volume and somatic HSD3B1 alterations in advanced prostate cancer

Fetched: November 10th, 2021, 5:01am GMT by Masaki Shiota

Andrologia. 2021 Nov 8:e14307. doi: 10.1111/and.14307. Online ahead of print.

ABSTRACT

This study aimed to investigate the significance of HSD3B1 gene status including germline polymorphism and somatic alterations in prostate cancer. Patients with prostate cancer treated with androgen-deprivation therapy, as well as tissues from metastatic prostate cancer, were included. Genomic DNA was extracted from cancer tissues and whole blood samples, and HSD3B1 (rs1047303, 1245C) was genotyped by Sanger sequencing. The association of HSD3B1 genotype with progression-free survival according to metastatic volume was examined. Copy number alteration and gene expression of HSD3B1 were examined in prostate cancer cells and public datasets. Among 194 patients, 121 and 73 patients were categorized into low- and high-volume diseases respectively. In multivariate analysis, the adrenal-permissive genotype (AC/CC) was significantly associated with increased risk of progression compared with the adrenal-restrictive genotype (AA) in low volume, but not high-volume diseases. Somatic mutation in HSD3B1 was detected at least in two cases of castration-resistant prostate cancer tissues. HSD3B1 amplification and overexpression were detected in castration-resistant prostate cancer cells and tissues. The current findings suggest that both germline and somatic alterations of HSD3B1 may cooperatively promote castration resistance in prostate cancer and HSD3B1 as a promising biomarker for precision medicine, warranting further investigations.

PMID:34747051 | DOI:10.1111/and.14307
Primary neuroendocrine prostate cancer with adrenal gland metastasis

Fetched: November 10th, 2021, 5:01am GMT by Antonio Yaromin Muñoz López

Urol Case Rep. 2021 Oct 12;40:101896. doi: 10.1016/j.eucr.2021.101896. eCollection 2022 Jan.

ABSTRACT

Primary neuroendocrine differentiation in prostate cancer occurs infrequently and represents a therapeutic challenge at present due to the poor prognosis involved. We present the case of a patient with de novo neuroendocrine prostate cancer who later developed metastases to adrenals bilaterally which were initially managed surgically.

PMID:34745894 | PMC:PMC8551851 | DOI:10.1016/j.eucr.2021.101896
Cushings syndrome in pregnancy caused by an adrenal adenoma

Fetched: November 10th, 2021, 5:01am GMT by Zuzana Koudelková

Ceska Gynekol. 2021;86(5):331-334. doi: 10.48095/cccg2021331.

ABSTRACT

OBJECTIVE: The description of a rare case of Cushings syndrome caused by an adrenal adenoma in pregnancy with successful treatment.

CASE PRESENTATION: 30-ear-old Gravida 3 female was admitted to our hospital with hypertension at the 18th week of gestation. Hormonal analyses revealed primary Cushings syndrome with high plasma cortisol levels and low levels of adrenocorticotropic hormone. Magnetic resonance imaging demonstrated a mass on the right-side of the adrenal gland. Adrenalectomy was performed in the 28th week of gestation and the following histopathology revealed an adrenocortical adenoma. Pregnancy continued until the 38th week of gestation with glucocorticoid replacement therapy and the patient gave birth vaginally to a healthy boy in the 38th week of gestation.

CONCLUSION: Cushings syndrome in pregnancy rarely occurs; dia-gnosis may be dismissed or determined after birth in most cases. Misdia-gnosis of Cushings syndrome is common because of physiological increase of corticotropin hormones and cortisol levels and overlapping symptoms that can occur even during physiological pregnancy. Cushings syndrome should have a place in the differential dia-gnosis of hypertension in pregnancy (especially before the 20th week of gestation). Analysis of the urinary free cortisol level and circadian rhythm blood cortisol can provide a reasonable strategy to dia-gnose Cushings syndrome in pregnant women. Early dia-gnosis and surgical treatment can significantly reduce maternal and fetal complications.

PMID:34736331 | DOI:10.48095/cccg2021331
Common Diagnostic Challenges and Pitfalls in Genitourinary Organs, With Emphasis on Immunohistochemical and Molecular Updates

Fetched: November 10th, 2021, 5:01am GMT by Liwei Jia

Arch Pathol Lab Med. 2021 Nov 1;145(11):1387-1404. doi: 10.5858/arpa.2021-0107-RA.

ABSTRACT

CONTEXT.—: Lesions in the genitourinary (GU) organs, both benign and malignant, can demonstrate overlapping morphology, and practicing surgical pathologists should be aware of these potential pitfalls and consider a broad differential diagnosis for each specific type of lesion involving the GU organs. The following summary of the contents presented at the 6th Annual Chinese American Pathologists Association (CAPA) Diagnostic Course (October 10-11, 2020), supplemented with relevant literature review, exemplifies the common diagnostic challenges and pitfalls for mass lesions of the GU system of adults, including adrenal gland, with emphasis on immunohistochemical and molecular updates when relevant.

OBJECTIVE.—: To describe the common mass lesions in the GU system of adults, including adrenal gland, with emphasis on the diagnostic challenges and pitfalls that may arise in the pathologic assessment, and to highlight immunohistochemical workups and emerging molecular findings when relevant.

DATA SOURCES.—: The contents presented at the course and literature search comprise our data sources.

CONCLUSIONS.—: The diagnostic challenges and pitfalls that arise in the pathologic assessment of the mass lesions in the GU system of adults, including adrenal gland, are common. We summarize the contents presented at the course, supplemented with relevant literature review, and hope to provide a diagnostic framework to evaluate these lesions in routine clinical practice.

PMID:34673910 | DOI:10.5858/arpa.2021-0107-RA
Synchronous oligometastatic renal cell carcinoma-what is the role of surgery?

Fetched: November 6th, 2021, 5:00am GMT by P Ivanyi

Urologe A. 2021 Nov 4. doi: 10.1007/s00120-021-01700-8. Online ahead of print.

ABSTRACT

BACKGROUND: Long-term remission can be achieved by surgery in patients with metastatic renal cell carcinoma (mRCC), without chronic toxicity due to systemic treatment. Data on metastasectomy are mostly based on observations of metachronous metastasis. However, it is unclear whether patients with synchronous oligometastasis may also benefit from surgery alone as an alternative to highly effective systemic treatment combined with resection of the primary tumor.

MATERIALS AND METHODS: The authors performed an unstructured literature search in PubMed including systematic reviews and meta-analyses. Results are discussed in regard of the current data and clinical practice.

RESULTS AND DISCUSSION: Although there is no uniform definition for oligometastasis in mRCC, cytoreductive nephrectomy in selected patients seems to be mandatory before metastasectomy is performed in primary oligometastatic RCC. In particular, in those patients with oligometastasis of the lung, bone, central nervous system, liver, adrenal gland, and thyroid, metastasectomy appears to be an important therapeutic option. Ultimately, among the therapeutic options, surgery is also an important therapeutic approach in primary oligometastatic mRCC. A balanced consideration between surgery, other local therapies, and modern systemic treatment demands interdisciplinary decision-making that takes into account the patients' preference.

PMID:34738151 | DOI:10.1007/s00120-021-01700-8
Familial Hypercholesterolemia: Genes and Beyond

Fetched: November 5th, 2021, 5:00am GMT by Bruce A. Warden

2021 Oct 23. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Genetic disorders resulting in familial hypercholesterolemia (FH) include autosomal dominant hypercholesterolemia (ADH), polygenic hypercholesterolemia, as well as other rare conditions such as autosomal recessive hypercholesterolemia (ARH). All of these disorders cause elevations in low-density lipoprotein (LDL)-cholesterol (LDL-C) and, as a result, greatly increase the risk of cardiovascular disease (CVD). Genetic loci involved in ADH include the LDLR, which codes for the LDL receptor (LDLR), APOB, which codes for apolipoprotein B-100 (apoB-100), the major protein component of LDL, PCSK9, which codes for Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), the low abundance circulatory protein that terminates the lifecycle of the LDLR, and apolipoprotein E (APOE), which synthesizes the main protein of triglyceride rich lipoproteins. Importantly, a large percentage of people with the severe hypercholesterolemic phenotype do not possess a readily identifiable gene defect and many likely have polygenic hypercholesterolemia. Thus, identification of a specific genetic pathologic variant is not a necessary condition for the diagnosis of a genetic hypercholesterolemia. Several formal diagnostic criteria exist for FH and include lipid levels, family history, personal history, physical exam findings, and genetic testing. As all individuals with severe hypercholesterolemia are at high risk for CVD, treatment is centered on dietary and lifestyle modifications and early institution of lipid-lowering pharmacotherapy. Treatment should initially be statin-based, but most patients require adjunctive medications such as ezetimibe and PCSK9 blocking monoclonal antibodies. Three large cardiovascular outcome trials have shown a reduction in atherosclerotic CVD when ezetimibe or PCSK9 blocking monoclonal antibodies were added to a background of statin therapy and consequently have assisted in shaping international guidelines and consensus recommendations. Novel therapeutics recently developed, include: inclisiran – a small interfering ribonucleic acid (siRNA)-based gene-silencing technology that inhibits PCSK9 production (approved in the European Union only thus far), bempedoic acid – an inhibitor of adenosine triphosphate (ATP)-citrate lyase (FDA approved for heterozygous FH and patients with prior CVD and elevated LDL-C), and evinacumab – a fully human monoclonal antibody inhibiting angiopoietin-like 3 (ANGPTL3) (FDA approved for homozygous FH only). Patients with extreme and unresponsive elevations in LDL-C will require more aggressive therapies such as lipoprotein apheresis and agents for the treatment of severe hypercholesterolemia such as microsomal triglyceride transfer protein (MTP) inhibitors and evinacumab. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:26844336 | Bookshelf:NBK343488
Non-Pharmaceutical Intervention Options for Type 2 Diabetes: Complementary Health Approaches and Integrative Health (Including Natural Products and Mind/Body Practices)

Fetched: November 5th, 2021, 5:00am GMT by Skye A. McKennon

2021 Oct 20. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Complementary health approaches, otherwise known as non-mainstream practices, are commonly used by patients with diabetes. Natural products, including dietary supplements, are the most frequently used complementary approach by patients with diabetes. While popular, there are regulatory, safety, and efficacy concerns regarding natural products. Commonly used dietary supplements for diabetes can be categorized as hypoglycemic agents, carbohydrate absorption inhibitors, and insulin sensitizers. Hypoglycemic agents of interest include banaba, bitter melon, fenugreek, and gymnema. American ginseng, banaba, berberine, chromium, cinnamon, gymnema, milk thistle, prickly pear cactus, soy, and vanadium are insulin sensitizers that have been studied in patients with diabetes. The carbohydrate absorption inhibitors aloe vera gel, fenugreek, flaxseed, prickly pear cactus, soy, and turmeric may be used in patients with diabetes. Mind body therapies including yoga, massage, and tai chi have preliminary evidence to support use in patients with diabetes. Deceptive marketing tactics may be employed by sellers of natural products. Consumers and clinicians must be aware of potential risks and make informed choices. Resources such as the Food and Drug Administration’s (FDA’s) MedWatch may be helpful. The FDA’s online health fraud website informs consumers on various types of fraud and how to avoid them. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905290 | Bookshelf:NBK279062
Hypophysitis

Fetched: November 5th, 2021, 5:00am GMT by Alessandro Prete

2021 Oct 15. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Hypophysitis is an inflammation of the pituitary gland and is a rare cause of hypopituitarism. It can be primary (idiopathic) or secondary to sella and parasellar lesions, systemic diseases, or drugs (mainly immune checkpoint inhibitors). Primary hypophysitis has five histologic variants: lymphocytic, granulomatous, xanthomatous, IgG4-related, and necrotizing. Lymphocytic hypophysitis is the most common form; it is likely an autoimmune disease and is more frequently observed in females during pregnancy or postpartum. Granulomatous hypophysitis is the second most common variant and possible secondary causes of granulomatous infiltration of the pituitary should be excluded before concluding that a case of granulomatous hypophysitis is idiopathic. Xanthomatous, necrotizing, and IgG4-related hypophysitis are very rare and the latter is often the manifestation of a systemic disease with multi-organ involvement (IgG4-related disease). Immune checkpoint inhibitors are monoclonal antibodies increasingly used for the treatment of solid and hematological malignancies. They cause a T-lymphocyte activation and proliferation that lead to the anti-tumor response, and may cause autoimmune manifestations known as part of what is called “immune-related adverse events”. A significant number of patients treated with immune checkpoint inhibitors develop immune-related hypophysitis and require prompt diagnosis and treatment. Regardless of the etiology, patients with hypophysitis present with various signs and symptoms caused by the pituitary inflammation that can lead to hypopituitarism and compression of sella and parasellar structures. Contrary to other causes of hypopituitarism, adrenocorticotropic hormone and thyroid-stimulating hormone deficiencies are very frequent in the early stages of hypophysitis and must be identified immediately. The diagnosis of hypophysitis is based on clinical, laboratory, and radiological data; while pituitary biopsy is the gold standard test for diagnosing primary hypophysitis, it should be reserved only for selected cases. Magnetic resonance imaging is the technique of choice for suspected hypophysitis, and the main differential diagnoses are pituitary adenomas in adults, germinomas, and Langerhans cell histiocytosis in adolescents, and metastases in those receiving immune checkpoint inhibitors. The mainstay of treatment of patients with hypophysitis is pituitary hormone replacement. Those with severe signs and symptoms of sella compression should be treated with high-dose glucocorticoids, which usually cause an excellent initial response, although relapse of the pituitary inflammation is common. Pituitary surgery should be considered in patients who do not respond to glucocorticoids and have progressive and debilitating symptoms. Pituitary fibrosis and atrophy often develop in the late stage of the disease, with persistent hypopituitarism. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:30160871 | Bookshelf:NBK519842
Characterisation of the onset and severity of adrenal and thyroid dysfunction associated with CTLA4-related hypophysitis

Fetched: November 5th, 2021, 5:00am GMT by Khyatisha Seejore

Eur J Endocrinol. 2021 Nov 1:EJE-21-0760.R1. doi: 10.1530/EJE-21-0760. Online ahead of print.

ABSTRACT

CONTEXT: Use of the CTLA4 inhibitor, ipilimumab, has proven efficacious in treatment of melanoma, renal carcinoma and non-small cell lung cancer, however, is associated with frequent immune-related adverse events (irAE). Ipililumab-induced hypophysitis (IIH) is a well-recognized and not infrequent endocrine irAE.

OBJECTIVE: To investigate the timing of onset and severity of adrenal and thyroid hormone dysfunction around the development of IIH in patients treated for melanoma.

DESIGN: Retrospectively review of hormone levels in consecutive adult patients treated with ipilimumab (3mg/kg) for advanced melanoma as monotherapy or in combination with a PD-1 inhibitor.

RESULTS: Of 189 patients, 24 (13%; 13 males; 60.5±12.2 years) presented with IIH at a median of 16.1 (range: 6.7-160) weeks after commencing treatment, occurring in 14 (58%) after the fourth infusion. At presentation of IHH, corticotroph deficiency was characterised by an acute and severe decrease in cortisol levels to ≤83 nmol/l (≤3μg/dL) in all patients, often only days after a previously recorded normal cortisol level. Free T4 levels were observed to decline from 12 weeks prior to the onset of cortisol insufficiency, with recovery of thyroid hormone levels by 12 weeks after presentation of IIH. A median fall in fT4 level of 20% was observed at a median of 3 weeks (IQR: 1.5-6 weeks) prior to the diagnosis of IIH.

CONCLUSION: IIH is characterised by an acute severe decline in cortisol levels to ≤83 nmol/l at presentation. A fall in fT4 can herald the development of ACTH deficiency and can be a valuable early indicator of IIH.

PMID:34735371 | DOI:10.1530/EJE-21-0760
Management recommendations for pancreatic manifestations of von Hippel-Lindau disease

Fetched: November 5th, 2021, 5:00am GMT by Shachar Laks

Cancer. 2021 Nov 4. doi: 10.1002/cncr.33978. Online ahead of print.

ABSTRACT

Von Hippel-Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018-2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL-related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility of biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL-related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL-related pancreatic manifestations.

PMID:34735022 | DOI:10.1002/cncr.33978
Posterior Retroperitoneoscopic adrenalectomy in the prone position. Initial experience.

Fetched: November 5th, 2021, 5:00am GMT by Arturo Domínguez

Arch Esp Urol. 2021 Nov;74(9):859-866.

ABSTRACT

OBJECTIVE: Transperitoneal laparoscopic adrenalectomy (TLA) is considered the treatment of choice for small and benign adrenal tumors. In the recent years, posterior retroperitoneoscopic adrenalectomy (PRA) has gained popularity due to its advantages over TLA, presenting a shorter surgical time and a faster recovery without increasing complications. Conversely, a greater learning curve is considered because the use of a different and unusual surgical field.

MATERIAL AND METHODS: Our objective is to describe the PRA technique to ass our initial experience evaluating its feasibility, safety and effectiveness in a prospective series of patients. A total of 11 (9 left and 2 right) PRA performed between March 2017 and February 2020 were analyzed.

RESULTS: Median age was 55 (36-65) years with a median BMI of 25.69 (20.8-34.5) Kg/m2. 54.55% had ASA≥3. 63.37% of adrenal tumors were hormonally functional. The tumor mean size was 4 cm (0.6-8) and cortical adenoma was the predominant pathological anatomy (72.72%). No pheochromocytoma was operated. Median operative time was 87 minutes (35-125) with an intraoperative bleeding of 50 (0-300) mL. No patient presented intraoperative complications or reconversion. Median length of stay was 1 (1-6) days. Only one patient presented postoperative complications.

CONCLUSION: The PRA is feasible, reproducible and safe, even during the initial learning curve, presenting a clear early recovery with a shorter surgical time.

PMID:34726622
Approach to the Patient with an Incidental Adrenal Mass

Fetched: November 5th, 2021, 5:00am GMT by Xin He

Med Clin North Am. 2021 Nov;105(6):1047-1063. doi: 10.1016/j.mcna.2021.06.009. Epub 2021 Sep 9.

ABSTRACT

Adrenal masses are frequently incidentally identified from cross-sectional imaging studies, which are performed for other reasons. The intensity of the approach to the patient with such a mass is tailored to the clinical situation, ranging from a quick evaluation to a detailed work-up. In all cases, the three components of the evaluation are clinical assessment, review of the images, and biochemical testing with the goal of ruling out malignancy and identifying hormonally active lesions. This article incorporates recent information to produce a logical, systematic assessment of these patients with risk stratification and proportionate follow-up.

PMID:34688414 | DOI:10.1016/j.mcna.2021.06.009
Comparison between surgery and thermal ablation for adrenal metastases: a retrospective study

Fetched: November 4th, 2021, 5:00am GMT by Lin Xie

Int J Hyperthermia. 2021;38(1):1541-1547. doi: 10.1080/02656736.2021.1993356.

ABSTRACT

PURPOSE: To retrospectively compare the efficacy and safety of surgical resection (SR) and thermal ablation for the treatment of adrenal metastases.

METHODS: From January 2008 to December 2018, 133 patients with adrenal metastases who underwent SR (n = 76) or thermal ablation (n = 57) were enrolled. The mean tumor size was 58.00 ± 10.65 mm (22-80 mm) in the SR group and 58.03 ± 12.76 mm (34-89 mm) in the thermal ablation group. Local progression-free survival (LPFS) and safety were compared between the two groups using the Kaplan-Meier method and log-rank tests. Cox proportional hazard regression models were used to evaluate the prognostic factors of LPFS. Complications, hospitalization days, and blood loss were also assessed.

RESULTS: The median follow-up was 29.0 months (range, 20.4-37.6 months). No treatment-related mortality was observed. The 1-, 3- and 5-year LPFS rates were 74.0%, 62.8%, and 31.4% in the SR group and 72.8%, 68.7%, and 51.5% in the ablation group, with the median LPFS of 41.5 months (95% CI: 9.3-23.4 months) vs. 47.9 months (95% CI 20.6-75.8 months), respectively (p = 0.784). Tumor size ≥3 cm was the only significant risk factor for LPFS (p = 0.031). The ablation group was superior to the SR group with a lower major complication rate (4.1% vs. 14.5%, p = 0.03), less blood loss (1 ml vs. 100 ml, p < 0.001), and a shorter hospital stay (2 d vs. 6 d, p < 0.001).

CONCLUSION: Thermal ablation provided a similar LPFS and less comorbidities than SR, indicating that it is an effective and safe treatment for adrenal metastases.

PMID:34727828 | DOI:10.1080/02656736.2021.1993356
Hyperparathyroidism in Chronic Kidney Disease

Fetched: November 4th, 2021, 5:00am GMT by Tilman B. Drüeke

2021 Oct 18. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Chronic kidney disease (CKD) is associated with a mineral and bone disorder (CKD-MBD) which starts early in the course of the disease and worsens with its progression. The main initial serum biochemistry abnormalities are increases in fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) and decreases in 1,25 dihydroxy vitamin D (calcitriol) and soluble α-Klotho (Klotho), allowing serum calcium and phosphate to stay normal. Subsequently, serum 25 hydroxy vitamin D (calcidiol) decreases and in late CKD stages hyperphosphatemia develops in the majority of patients. Serum calcium may stay normal, decrease, or increase. More recent reports showed that sclerostin, Dickkopf-1, and activin A also play an important role in the pathogenesis of CKD-MBD. Both the synthesis and the secretion of PTH are continuously stimulated in the course of CKD, resulting in secondary hyperparathyroidism. In addition to the above systemic disturbances, downregulation of vitamin D receptor, calcium-sensing receptor, and Klotho expression in parathyroid tissue further enhances PTH overproduction. Last but not least, miRNAs have also been shown to be involved in the hyperparathyroidism of CKD. The chronic stimulation of parathyroid secretory function is not only characterized by a progressive rise in serum PTH but also by parathyroid gland hyperplasia. It results from an increase in parathyroid cell proliferation which is not fully compensated by a concomitant increase in parathyroid cell apoptosis. Parathyroid hyperplasia is initially of the diffuse, polyclonal type. In late CKD stages it often evolves towards a nodular, monoclonal or multiclonal type of growth. Enhanced parathyroid expression of transforming growth factor-α and its receptor, the epidermal growth factor receptor, is involved in polyclonal hyperplasia. Chromosomal changes have been found to be associated with clonal outgrowth in some, but not the majority of benign parathyroid tumors removed from patients with end-stage kidney disease. In initial CKD stages skeletal resistance to the action of PTH may explain why low bone turnover predominates in a significant proportion of patients, together with other conditions inhibiting bone turnover such as reduced calcitriol levels, sex hormone deficiency, diabetes, Wnt inhibitors, and uremic toxins. High turnover bone disease (osteitis fibrosa) occurs only later on, when increased serum PTH levels are able to overcome skeletal PTH resistance. The diagnosis of secondary uremic hyperparathyroidism and osteitis fibrosa relies mainly on serum biochemistry. X-ray and other imaging methods of the skeleton provide diagnostically relevant information only in severe forms. From a therapeutic point of view, it is important to prevent the development of secondary hyperparathyroidism as early as possible in the course of CKD. A variety of prophylactic and therapeutic approaches are available, as outlined in the final part of the chapter. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905209 | Bookshelf:NBK278975
Hypertensive crisis precatheter ablation for resistant atrial fibrillation: a case of undiagnosed bilateral pheochromocytomas

Fetched: November 3rd, 2021, 5:00am GMT by Nina Dhillon

BMJ Case Rep. 2021 Oct 29;14(10):e244484. doi: 10.1136/bcr-2021-244484.

ABSTRACT

A 63-year-old man with hypertension was referred for catheter ablation of persistent atrial fibrillation. He was diagnosed with paroxysmal atrial fibrillation approximately 6 years prior. Over the previous 12 months, his atrial fibrillation had become persistent despite medication optimisation for rate control and elective cardioversion. Sinus rhythm was restored briefly. The decision was made to pursue catheter ablation and isolation of the pulmonary veins. On anaesthetic induction, the patient suffered from a hypertensive crisis. The procedure was aborted, and the patient was admitted to hospital for investigations of secondary hypertension. Ultimately, the patient was diagnosed with bilateral pheochromocytomas. This case outlines the diagnostic challenges and cardiac comorbidities associated with bilateral pheochromocytomas.

PMID:34716146 | PMC:PMC8559091 | DOI:10.1136/bcr-2021-244484
A comparison of robotic and laparoscopic minimally invasive adrenalectomy for adrenal malignancies

Fetched: November 2nd, 2021, 5:00am GMT by Jonathan J Hue

Surg Endosc. 2021 Nov 1. doi: 10.1007/s00464-021-08827-x. Online ahead of print.

ABSTRACT

BACKGROUND: Although guidelines recommend open adrenalectomy for most resectable adrenal malignancies, minimally invasive adrenalectomies are performed. Robotic adrenalectomies have become more popular recently, but there is a paucity of literature comparing laparoscopic and robotic resections.

METHODS: Patients who underwent a planned minimally invasive adrenalectomy for adrenal malignancies (adrenocortical carcinoma, malignant pheochromocytoma, other carcinoma) were identified in the National Cancer Database. The primary outcome was the conversion rate from minimally invasive to open. Other post-operative outcomes and survival were compared.

RESULTS: 416 patients (76.5%) underwent a laparoscopic adrenalectomy and 128 (23.5%) underwent a robotic operation. Demographics and clinical characteristics were similar. Approximately 19% of tumors resected by a minimally invasive approach were > 10 cm. The intra-operative conversion rate was decreased among robotic adrenalectomies relative to laparoscopic on univariate (7.8% vs. 18.3%, p = 0.005) and multivariable (odds ratio 0.39, p = 0.01) analyses. Using marginal standardization, there was a stepwise increase in the conversion rate as tumor size increased (< 5, 5-10, > 10 cm) for laparoscopic (7.5%, 18.0%, 33.2%) and robotic (3.1%, 8.3%, 17.3%) adrenalectomies. Operations which required conversion had a greater margin positivity rate, greater length of stay, and an association with poor overall survival.

CONCLUSION: In contrast to most clinical guidelines, minimally invasive adrenalectomies are being performed on large malignant tumors. A laparoscopic approach was associated with a greater conversion rate and subsequent poor outcomes. If a surgeon is not planning an open adrenalectomy, but adrenal malignancy is a possibility, robotic adrenalectomy may be the preferred approach for resectable adrenal tumors.

PMID:34724582 | DOI:10.1007/s00464-021-08827-x
Palliative Radiotherapy Provided Good Pain Relief for Painful Adrenal Metastasis

Fetched: November 2nd, 2021, 5:00am GMT by Masashi Endo

Case Rep Oncol. 2021 Sep 6;14(3):1266-1270. doi: 10.1159/000518778. eCollection 2021 Sep-Dec.

ABSTRACT

Adrenal metastases often occur in patients with metastasized lung cancer, but symptoms rarely develop. A 45-year-old man presented with right abdominal pain requiring strong opioids due to large right adrenal metastasis of lung adenocarcinoma. The tumor was 7.3 × 5.6 × 8.4 cm in size. He was treated with palliative radiotherapy (RT) up to 39 Gy in 13 fractions for this lesion without severe adverse effects. After RT, he had good pain relief, and opioids were no longer needed. Palliative RT for a large adrenal tumor can provide a good analgesic effect without relevant toxicity.

PMID:34720926 | PMC:PMC8460938 | DOI:10.1159/000518778
Severe oral ulcerative and lichenoid lesions associated with adrenal insufficiency in a patient treated with nivolumab: Report of a case and review of literature

Fetched: October 31st, 2021, 5:00am GMT by Marcella Ferreira Gobbi

Spec Care Dentist. 2021 Oct 30. doi: 10.1111/scd.12660. Online ahead of print.

ABSTRACT

Nivolumab, an antibody against anti-programmed death type 1, has been used for treatment of advanced non-small cell lung cancer with improvement of overall survival. Usually, diarrhea, cutaneous rash, and pruritus are reported as the most common immune-related adverse effects of nivolumab therapy. Oral lesions and secondary adrenal insufficiency sometimes occur but usually are rare events. We report a case of a patient treated with nivolumab who then showed persistent oral ulcerative and lichenoid lesions, which were refractory to topical corticosteroids. The oral lesions were concomitant to nivolumab-induced adrenal insufficiency. These adverse events led to nivolumab discontinuation, which favored oral lesion healing and adrenal insufficiency remission. Through a brief review of the literature concerning nivolumab toxicity in the oral cavity, we discuss the clinical aspect and management of these lesions.

PMID:34717001 | DOI:10.1111/scd.12660
A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART, SWOG S1609)

Fetched: October 31st, 2021, 5:00am GMT by Sylvia Adams

Clin Cancer Res. 2021 Oct 29:clincanres.2182.2021. doi: 10.1158/1078-0432.CCR-21-2182. Online ahead of print.

ABSTRACT

PURPOSE: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately eight months for metastatic disease. We report results for advanced MpBC treated with ipilimumab+nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013).

METHODS: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity.

RESULTS: Overall, 17 evaluable patients enrolled. Median age was 60 years (26-85); median number of prior therapy lines, 2 (0-5). ORR was 18%; 3/17 patients achieved objective responses (1 complete, 2 partial responses) (2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+ and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AEs), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE); with adrenal insufficiency observed in all three responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1 and absent TILs.

CONCLUSION: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.

PMID:34716198 | DOI:10.1158/1078-0432.CCR-21-2182
Long-term follow-up of a case of MEN1 and literature review

Fetched: October 30th, 2021, 5:00am GMT by Qian Xu

Neuro Endocrinol Lett. 2021 Oct 29;42(6):369-374. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the diagnosis and treatment of Multiple Endocrine Neoplasia Type 1 (MEN1), improve our understanding of the disease and highlight the importance of life-long follow-up of affected individuals.

METHODS: A retrospective analysis was performed on 1 MEN1 patient with long-term follow-up at the First Affiliated Hospital of Anhui Medical University.

RESULTS: A 51-year-old woman was diagnosed with MEN1 14 years ago, but exhibited a suspected disease course of at least 20 years. Prior to admission, the patient reported a cough lasting for two months. The patient's thyroid hormone, sex hormone, insulin, cortisol, parathyroid hormone, and ACTH circadian rhythm findings were within normal ranges. The patient exhibited elevated blood calcium levels. Examination led to the detection of thymoma and pancreatic neoplasms, whereas no obvious abnormalities were detected in her parathyroid gland or adrenal gland as determined via computed tomography (CT). Genetic analyses revealed a mutation in the MEN1 gene in this patient. As the patient had no relevant clinical symptoms, she refused surgical treatment, and follow-up was continued. It was learned through follow-up that the patient underwent anterior mediastinal lesion resection and partial rib resection in June 2020 because she re-examined the chest CT showed that the anterior mediastinal mass was significantly larger than that in 2019. Pathology suggested neuroendocrine tumors. The patient is currently recovering well.

CONCLUSION: MEN1 is an uncommon condition in clinical settings, and it is important that clinicians be made aware of this disorder so that they can provide patients with appropriate and timely treatments.

PMID:34713690
Impact of the Coronavirus Disease Pandemic on the Annual Thyroid, Parathyroid, and Adrenal Surgery Volume in a Tertiary Referral Endocrine Surgery Center in 2020

Fetched: October 30th, 2021, 5:00am GMT by Fatih Tunca

Sisli Etfal Hastan Tip Bul. 2021 Sep 24;55(3):286-293. doi: 10.14744/SEMB.2021.64920. eCollection 2021.

ABSTRACT

OBJECTIVE: The purpose of the study was to evaluate the impact of the coronavirus disease (COVID-19) pandemic on endocrine surgical volumes.

METHODS: There were periodic surgical restriction sin our country in 2020 due to the pandemic. Endocrine surgery volumes at the Division of Endocrine Surgery, Istanbul Medical Faculty were compared between 2019 and 2020.

RESULTS: The surgical volume reduction in 2020 compared to 2019 was 20%, 54.5%, and 40% for thyroid, parathyroid, and adrenal surgery, respectively. Surgical volume for thyroidectomy for benign nodular goiter and parathyroidectomy significantly decreased, whereas adrenal surgery showed no significant difference in 2020 compared to 2019. No significant difference was found in the rates of thyroid cancer and adrenocortical cancer surgery in 2020compared to 2019.

CONCLUSION: The COVID-19 outbreak led to a significant reduction in the annual rates of parathyroidectomy and thyroidectomy for benign goiter, whereas the volume of thyroid cancer and adrenal surgeries were similar to the previous year.

PMID:34712068 | PMC:PMC8526220 | DOI:10.14744/SEMB.2021.64920
Analysis of the Li-Fraumeni Spectrum Based on an International Germline TP53 Variant Data Set: An International Agency for Research on Cancer TP53 Database Analysis

Fetched: October 29th, 2021, 5:00am GMT by Christian P Kratz

JAMA Oncol. 2021 Oct 28:e214398. doi: 10.1001/jamaoncol.2021.4398. Online ahead of print.

ABSTRACT

IMPORTANCE: Li-Fraumeni syndrome is a cancer predisposition syndrome that is associated with a high, lifelong risk of a broad spectrum of cancers that is caused by pathogenic TP53 germline variants. A definition that reflects the broad phenotypic spectrum that has evolved since the gene discovery is lacking, and mechanisms leading to phenotypic differences remain largely unknown.

OBJECTIVE: To define the phenotypic spectrum of Li-Fraumeni syndrome and conduct phenotype-genotype associations across the phenotypic spectrum.

DESIGN, SETTING, AND PARTICIPANTS: We analyzed and classified the germline variant data set of the International Agency for Research on Cancer TP53 database that contains data on a cohort of 3034 persons from 1282 families reported in the scientific literature since 1990. We defined the term Li-Fraumeni spectrum to encompass (1) phenotypic Li-Fraumeni syndrome, defined by the absence of a pathogenic/likely pathogenic TP53 variant in persons/families meeting clinical Li-Fraumeni syndrome criteria; (2) Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in persons/families meeting Li-Fraumeni syndrome testing criteria; (3) attenuated Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in a person/family with cancer who does not meet Li-Fraumeni syndrome testing criteria; and (4) incidental Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in a person/family without a history of cancer. Data analysis occurred from November 2020 to March 2021.

MAIN OUTCOMES AND MEASURES: Differences in variant distribution and cancer characteristics in patients with a germline TP53 variant who met vs did not meet Li-Fraumeni syndrome testing criteria.

RESULTS: Tumor spectra showed significant differences, with more early adrenal (n = 166, 6.5% vs n = 0), brain (n = 360, 14.17% vs n = 57, 7.46%), connective tissue (n = 303, 11.92% vs n = 56, 7.33%), and bone tumors (n = 279, 10.98% vs n = 3, 0.39%) in patients who met Li-Fraumeni syndrome genetic testing criteria (n = 2139). Carriers who did not meet Li-Fraumeni syndrome genetic testing criteria (n = 678) had more breast (n = 292, 38.22% vs n = 700, 27.55%) and other cancers, 45% of them occurring after age 45 years. Hotspot variants were present in both groups. Several variants were exclusively found in patients with Li-Fraumeni syndrome, while others where exclusively found in patients with attenuated Li-Fraumeni syndrome. In patients who met Li-Fraumeni syndrome genetic testing criteria, most TP53 variants were classified as pathogenic/likely pathogenic (1757 of 2139, 82.2%), whereas 40.4% (404 of 678) of TP53 variants identified in patients who did not meet the Li-Fraumeni syndrome genetic testing criteria were classified as variants of uncertain significance, conflicting results, likely benign, benign, or unknown.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that this new classification, Li-Fraumeni spectrum, is a step toward understanding the factors that lead to phenotypic differences and may serve as a model for other cancer predisposition syndromes.

PMID:34709361 | PMC:PMC8554692 | DOI:10.1001/jamaoncol.2021.4398
S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study

Fetched: October 29th, 2021, 5:00am GMT by Yasir S Elhassan

Eur J Endocrinol. 2021 Oct 1:EJE-21-0510.R2. doi: 10.1530/EJE-21-0510. Online ahead of print.

ABSTRACT

OBJECTIVE: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on ENSAT tumour stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC.

DESIGN: Multicentre retrospective study on ACC patients who underwent adrenalectomy.

METHODS: The S-GRAS score was calculated as a sum of the following points: tumour Stage (1-2=0; 3=1; 4=2), Grade (Ki67 index 0-9%=0; 10-19%=1; ≥20%=2 points), Resection (R)-status (R0=0; RX=1; R1=2; R2=3), Age (<50yr=0; ≥50yr=1), Symptoms (no=0; yes=1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's C-index and Royston-Sauerbrei's R2D statistic.

RESULTS: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index=0.73, R2D=0.30, and C-index=0.79, R2D=0.45, respectively, all P<0.01 vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n=481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5.

CONCLUSION: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

PMID:34709200 | DOI:10.1530/EJE-21-0510
Association between PD-L1 inhibitor, tumor site and adverse events of potential immune etiology within the US FDA adverse event reporting system

Fetched: October 29th, 2021, 5:00am GMT by Omar Abdel-Rahman

Immunotherapy. 2021 Dec;13(17):1407-1417. doi: 10.2217/imt-2021-0068. Epub 2021 Oct 28.

ABSTRACT

Objective: To analyze tumor- and treatment-related factors that might impact the development of certain adverse events (AEs) of potential immune etiology among patients receiving PD-L1 inhibitors. Methods: The FDA Adverse Event Reporting System (FAERS) was accessed, and AE reports related to the use of PD-L1 inhibitors were reviewed. Associations between treatment, tumor type and occurrence of AEs of special interest were analyzed through multivariable logistic regression analysis. Results: A total of 80,304 AE reports were included in the current analysis. Diagnosis with lung cancer was associated with a higher probability of pneumonitis; diagnosis with melanoma was associated with a higher probability of hepatitis, hypophysitis/hypopituitarism and uveitis; and diagnosis with genitourinary cancers was associated with a higher probability of nephritis, adrenal insufficiency and myocarditis. Conclusion: Within this cohort limited to AEs reported to the FAERS, there is an association between different AEs of special interest, agent(s) used and tumor(s) treated.

PMID:34709083 | DOI:10.2217/imt-2021-0068
Impact of Breath-Hold MR-Guided Radiotherapy (MRgRT(BH)) vs. Free-Breathing CT Image-Guided Radiotherapy (CT-IGRT(FB)) on Gastrointestinal Sparing and Dose Conformality in Adrenal SBRT

Fetched: October 28th, 2021, 5:00am GMT by L L Rodriguez

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e527. doi: 10.1016/j.ijrobp.2021.07.1438.

ABSTRACT

PURPOSE/OBJECTIVE(S): To quantitatively compare plan quality between mid-inspiration breath-hold (BH) MR-guided radiotherapy (MRgRTBH) and free-breathing (FB) CT-based intensity modulated radiotherapy (CT-IGRTFB) for the ablative treatment of adrenal malignancies. We hypothesized that MRgRTBH would provide improved target coverage and lower organ-at-risk (OAR) doses due to smaller target volumes compared to CT-IGRTFB.

MATERIALS/METHODS: Twenty adrenal metastasis patients were treated on a 0.35T MR-Linac with real-time sagittal tracking at four frames per second for gated BH delivery. All patients underwent IMRT planning to a median prescription dose of 50 Gy (range: 40-50 Gy) in 5 fractions. For MRgRTBH, the CTV was delineated on the primary 3D TRUFI scan with no internal target volume (ITV). Each patient was retrospectively replanned using a 3-arc, VMAT CT-IGRTFB treatment on a c-arm Linac (HD MLC). 4DCT respiratory evaluation was performed during MRgRTBH simulation. The average intensity projection CT was used to determine the ITV for the CT-IGRTFB plan. All plans used a 5 mm ITV to PTV margin. Target volume metrics used were: target coverage (TC) (PTV V100%/PTV vol), PTV D95%/Rx, PTV D90%/Rx, PTV D80%/Rx, homogeneity index (HI) (PTV D2%/ D98%), high dose conformity (PITV), low dose conformity (D2cm), and gradient (R50%). Additional dose metrics were evaluated for mean ipsilateral kidney and 0.5 cc gastrointestinal (GI) OARs.

RESULTS: The Wilcoxon signed-rank test showed a statistically significant increase (P < 0.05) in PTV volumes for CT-IGRTFB over MRgRTBH, with median (range) at 91.9 cc (32.0 - 481.4 cc) versus 53.6 cc (20.6 - 377.4 cc); a 71% relative increase for CT attributable to the need for an ITV. Target coverage metrics were only marginally worse for CT-IGRTFB (P > 0.05). There were significant reductions (P < 0.05) in conformality metrics for CT-IGRTFB in PITV (10%) and R50% (24%) relative to MRgRTBH, due to the significant increase in target volumes for CT-IGRTFB. Low dose conformality was equivalent for D2cm. MRgRTBH exhibited significant reductions (P < 0.05) in the median dose to 0.5 cc of the large bowel (15%), small bowel (28%) and duodenum (45%) over CT-IGRTFB.

CONCLUSION: Intrafraction BH motion management of MRgRTBH enabled significant reductions of target volumes (P < 0.05) compared to the ITV-approach for CT-IGRTFB. Marginally improved target coverage (P > 0.05) and significant GI OAR sparing (P < 0.05) resulted from the smaller target volumes and reduced OAR-to-PTV proximity. MRgRTBH was shown to be dosimetrically superior for OAR sparing to the small bowel, the large bowel and the duodenum (P < 0.05). Adaptive MRgRTBH was used for all patients, but only initial treatment doses were considered in quantifying the impact of gated BH versus ITV for this study.

PMID:34701666 | DOI:10.1016/j.ijrobp.2021.07.1438
Significant Incidental Findings Unrelated to the Primary Cancer on CT Simulation Treatment Planning Scans

Fetched: October 28th, 2021, 5:00am GMT by C Nguyen

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e508. doi: 10.1016/j.ijrobp.2021.07.1395.

ABSTRACT

PURPOSE/OBJECTIVE(S): Incidental tumor findings on radiographic imaging are rare and often do not manifest symptoms such as a lump or associated pain. These tumors may represent major clinically relevant findings that need additional imaging and testing. Although some studies published metastatic disease of the primary cancer, we are not aware of publications in the U.S. focusing solely on major, significant findings, and unrelated to the primary disease during radiotherapy planning. In this paper, we introduce several cases where CT planning images revealed significant clinical findings unrelated to the primary cancer that required further investigation. All patients with these major findings were followed-up for diagnostic imaging, examination, and proper referral.

MATERIALS/METHODS: To simulate real-life situation when CT treatment planning is performed in a radiation oncology department, the radiation oncologist reviewed a total of 115 patients with CT treatment planning that was performed during the 2-year period of 2017-2018. These CTs were performed during routine radiotherapy planning for curative purposes: brain tumors (n = 10 or 9%), head and neck cancer (n = 15 or 13%), lung cancer (n = 30 or 26%), breast cancer (n = 35 or 30%), prostate cancer (n = 25 or 22%).

RESULTS: We report incidental but significant findings on radiotherapy planning CT scans unrelated to the primary cancer. A total of 4 abnormal findings (3 neoplasms and 1 benign) were discovered from a total of 115 CT scans done for radiotherapy planning. The 3 neoplasms were: hepatocellular carcinoma, thyroid cancer, and large adrenal adenoma. The one benign finding was extensive eventration of the left hemi-diaphragm.

CONCLUSION: CT planning scans are routinely performed separately in the radiation oncology department for proper treatment mapping of cancer patients. These CT images are usually stored in the RO department server and not in radiology PACS system. At the present time, it is not known how many percent of radiation oncologists routinely check CT scans for incidental findings. The 4 case reports stated in this article demonstrate that although rare, there are malignancies/abnormalities unrelated to the primary cancer that could be missed in the CT planning process. We therefore recommend that radiation oncologists take charge of this issue and implement a method of proper interpretation of CT simulation images by either the radiation oncologists responsible for the case, or designated diagnostic radiologists (if such arrangement exists), to ensure that incidental findings are not missed. In any radiation oncology (RO) department, a routine QA (quality assurance) checklist often includes: consultation note, verification of pathology, consent form, verification of dosimetry, verification of physics report etc., we believe that proper interpretation of CT simulation images for incidental findings should be part of the QA checklist in a modern RO department.

PMID:34701619 | DOI:10.1016/j.ijrobp.2021.07.1395
Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy for Abdominopelvic Metastases

Fetched: October 28th, 2021, 5:00am GMT by D D Yang

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e483-e484. doi: 10.1016/j.ijrobp.2021.07.1339.

ABSTRACT

PURPOSE/OBJECTIVE(S): Stereotactic body radiation therapy (SBRT) can be an effective method for treating metastases. However, the proximity of organs at risk (OARs) to the target can limit the safe delivery of ablative doses, particularly in the abdomen and pelvis where there can be significant interfraction and intrafraction motion. Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may allow for safer delivery of ablative radiation to abdominopelvic metastases. We report the feasibility and early outcomes of patients with abdominopelvic metastases treated with SMART using a 0.35T MR Linac in a (1) retrospective cohort and (2) a prospective phase 1 trial.

MATERIALS/METHODS: We identified 44 patients in the retrospective cohort and enrolled 13 patients onto the phase 1 protocol, all with abdominopelvic metastases. Patients with metastases of the liver, kidneys, or adrenal glands were excluded and were enrolled on companion phase 1 trials. Patients were treated between 10/29/19-2/18/21. For the retrospective cohort, dose prescription and coverage were at the discretion of the treating physician, with 67% of sites receiving 40 Gy/5 fractions. For the phase 1 cohort, patients were treated to 40 Gy/5 fractions daily with goal PTV coverage of V40 ≥95% (ideal) and V30 ≥95% (acceptable).

RESULTS: Overall, the 44 patients in the retrospective cohort were treated to 49 sites of abdominopelvic disease, and the 13 patients in the phase 1 cohort received treatment to one site of abdominopelvic disease each on protocol. The most common histology was prostate adenocarcinoma (57%). In total, 308 fractions were delivered, with 138 (45%) using a breath hold and 170 (55%) using free breathing. Online adaptation was necessary for 269/308 fractions (87%) to either satisfy critical OAR metrics (62%) or improve target coverage (38%). Additionally, there were two instances when on-board MRI allowed for the detection of bowel which had displaced the target to such a degree as to interfere with safe treatment delivery, even when utilizing adaptive planning. These two treatments were postponed to either later the same day or a subsequent day. Patients spent an average of 61 minutes in the treatment room. With median follow-up of 150 days (interquartile range 90-224 days), there were no deaths and one local failure (a patient with urothelial carcinoma who received 35 Gy/5 fractions at 102 days after start of SBRT). There was one grade ≥3 treatment-related toxicity (colonic hemorrhage in a patient with serous ovarian cancer who received 40 Gy/5 fractions at 86 days after start of SBRT in the setting of thrombocytopenia).

CONCLUSION: SMART is a feasible method for delivering ablative doses of radiation. Adaptive planning was necessary in a large portion of cases. Early data suggest a high rate of local control and low risk of significant toxicity. Longer-term results of the phase 1 protocol will be reported in the future.

PMID:34701560 | DOI:10.1016/j.ijrobp.2021.07.1339
Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (SMART) With Median Biologically Effective Dose of 100 Gy10 for Oligometastases

Fetched: October 28th, 2021, 5:00am GMT by M D Chuong

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e475-e476. doi: 10.1016/j.ijrobp.2021.07.1322.

ABSTRACT

PURPOSE/OBJECTIVE(S): Randomized data show an overall survival (OS) benefit of stereotactic ablative body radiation therapy (SABR) in addition to chemotherapy (CT) in selected patients with oligometastasis (OM). While ablative dose can be safely delivered to some lesions, others in proximity to some organs at risk (OARs) such as bowel may be treated with non-ablative dose to limit toxicity. Stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting OARs, which may improve long-term disease control.

MATERIALS/METHODS: The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Patients with < 3 months (mo.) follow-up after SMART were excluded. Local control (LC), freedom from distant progression (FFDP), progression free survival (PFS), and OS were estimated using the Kaplan-Meier method. LC was evaluated using RECIST 1.1 criteria. Acute toxicity was defined as within 90 days of SMART and evaluated using CTCAE v4 criteria.

RESULTS: 101 patients with 114 OM lesions were treated on a 0.35T-MR Linac at 2 institutions between 2018-2020. Median age was 62 years (range 23-89), and 99% were ECOG 0-1 performance status. The primary tumor was definitively managed in 34.7%, most commonly in the lung (30.7%), colon/rectum (22.8%), cervix/uterus/ovary (13.9%), or breast (5.9%). About 50% received CT for OM prior to SMART. SMART was delivered to 1 (87.7%) or 2 (10.5%) lesions, mostly involving abdominal/pelvic lymph nodes (40.4%), liver (17.5%), lung (17.5%), or adrenal gland (11.4%). All were treated without fiducial markers and with real-time tissue tracking and automated beam gating, typically in breath hold. The median prescribed RT dose was 45 Gy (range 24-60Gy) in a median 5 fractions (range 3-15). The median biologically effective dose (BED10) was 100 Gy10 (range 41.4-180). The median PTV was 14.5 cm³ (range 1.5-567.8). Median follow-up was 10 months (range 3-25) from SMART. One-year LC, FFDP, PFS, and OS were 88%, 38.2%, 36.1%, and 90.6%, respectively. Median PFS and OS were 9 months and not reached, respectively. No acute/late grade 3+ toxicities were recorded.

CONCLUSION: To our knowledge, this represents the largest analysis of SMART for OM. A median prescribed BED10 of 100 Gy10 resulted in excellent early LC and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. These outcomes are noteworthy given the predominance of OM, especially LNs, treated with dose escalation in proximity to gastrointestinal OARs; such lesions are notably underrepresented in SABR OM trials. Prospective evaluation of dose-escalated SMART for OM is warranted.

PMID:34701541 | DOI:10.1016/j.ijrobp.2021.07.1322
Outcomes and Toxicities in Oligometastatic Patients Treated With Stereotactic Body Radiotherapy for Adrenal Gland Metastases: A Multi-Institutional Study

Fetched: October 28th, 2021, 5:00am GMT by A Baydoun

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e474. doi: 10.1016/j.ijrobp.2021.07.1319.

ABSTRACT

PURPOSE/OBJECTIVE(S): Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment approach in oligometastatic patients with adrenal gland metastases (AGM). Nevertheless, most of the literature reporting SBRT outcomes for AGM comes from published single institutional experience, and no specific guidelines are yet established to guide patients' inclusion and dosimetric planning.

MATERIALS/METHODS: The Consortium for Oligometastases Research (CORE) is currently the largest retrospective series of patients with oligometastases (OM). Among CORE patients, those treated with SBRT for AGM were included. Adrenal metastatic burden (AMB) was defined as the sum of all adrenal GTV if more than one OM is present. BED10 was calculated with tumor alpha/beta ratio of 10. Competing risk analysis was used to estimate the risk of local recurrence (LR) and widespread progression (WP) over time, using death from any cause as a competing risk factor. Kaplan-Meier method was used to estimate the overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). Univariable and multivariable regression was used to quantify the relationship between potential predictors and the main endpoints. A P-value threshold of 0.05 was used for statistical significance.

RESULTS: 46 patients with 57 adrenal lesions were included. Median follow-up was 18.2 months. The most common primary malignancy was NSCLC. The mean (standard deviation) age at diagnosis was 65.84 (10.84) years, with 25 (53.2%) male patients and 22 (46.8%) female patients. 8 out of the 46 patients had developed more than one AGM. The most used fractionation scheme was 30 - 35 Gy in 3 - 5 fractions, and the mean prescribed BED10 was 69.37 Gy10. Median LRFS, PFS, and OS were 15.3, 5.29, and 19.1 months, respectively. The 1-year and 5-year LRFS were 65% and 25.4%, respectively. The 1-year and 5-year OS were 70% and 33%, respectively. Only 1 patient developed a Grade 3 GI toxicity. On multivariable regression, a minimum received PTV dose > 46 Gy10 was associated with an improved OS (HR 0.42, 95% CI [0.20 - 0.89], P = 0.024) and LRFS (HR 0.37, [0.18 - 0.76], P = 0.006), after adjusting for primary site. A prescribed BED10 more than 70 Gy10 was an independent prognostic factor of a lower LR rate (HR 0.31, [0.102-0.94], P = 0.039). Interestingly, AMB greater than 10 cc was an independent predictor of a lower risk WP (HR 0.29, [0.11 - 0.80], P = 0.017), after adjusting for primary histology and number of OM.

CONCLUSION: SBRT to AGM is a safe procedure that achieves a satisfactory local control and survival in oligometastatic patients. The current results suggest that patients should be treated with a prescription BED10 dose of at least 70 Gy10, and a minimum PTV dose > 46 Gy10, if safely achievable. Paradoxically, AMB > 10cc was favorable, and a high AMB should not preclude the administration of a definitive course of SBRT. Prospective studies are needed to determine comprehensive criteria for patients SBRT eligibility and dosimetric planning.

PMID:34701539 | DOI:10.1016/j.ijrobp.2021.07.1319
Phase II Clinical Trial Evaluating Complete Metastasis Ablation After Progression on Checkpoint Inhibition

Fetched: October 28th, 2021, 5:00am GMT by K He

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e471-e472. doi: 10.1016/j.ijrobp.2021.07.1314.

ABSTRACT

PURPOSE/OBJECTIVE(S): Retrospective and prospective studies in patients with oligometastatic non-small-cell lung cancer (NSCLC) suggested clinical benefit after complete metastatic ablation (CMA). So far, no studies have addressed the toxicity and efficacy of CMA to oligometastatic lesions in patients that progressed during immune checkpoint inhibitors (ICIs) therapy. Here, we report results of a single arm- radiotherapy (RT) to oligometastatic lesions from our ongoing phase II trial (NCT02710253).

MATERIALS/METHODS: This study enrolled patients that progressed within 6 months of ICI therapy and developed oligo-metastases. Treatment intervention allowed for any dose and fractions of RT per the treating physician to all metastatic sites, with irradiation for up to 6 sites. Primary endpoints of this study are time to new lesion development, and disease control rate (DCR) by RECIST 1.1. Secondary endpoints are toxicity, progression-free survival (PFS), overall survival (OS) and absolute lymphocyte counts (ALC).

RESULTS: Of the 30 patients initially enrolled in this study, 26 patients (N = 21 NSCLC; N = 5 melanoma) were included in the analysis as they had completed imaging follow-up. A total of 64 lesions were irradiated with a mean of 2.5 lesions per patient. Most frequent location of irradiated was lung (n = 45), followed by adrenal (n = 7), liver (n = 4), bone (n = 4) and others (n = 4); 50% of patients received SBRT. At a median follow-up time of 23.0 months (range, 5.0-44.7 months), 12 patients had no new lesions, while 14 patients developed new lesions in lung (50%), bone (25%), brain (21%). Median time to new lesion development was 14.6 months. DCR was 77% (complete response 19%, partial response 19%, stable disease 38%); median PFS was 10.1 months and median OS was not reached. No toxicities greater than grade 2 was observed. Pre-RT ALC is an independent risk factor for time to new lesion development (P = 0.006, HR = 0.1, 95% CI, 0.02-0.51). Patients without new lesion development had significantly higher baseline ALC (P = 0.011) and more ALC after RT at 1 month (P = 0.025), 3 months (P = 0.006), 6 months (P = 0.002) and 12 months (P = 0.045) compared to patients with new lesions. Other factors including age, gender, SBRT, baseline tumor size, performance status and tumor histology did not affect the time to new lesion development.

CONCLUSION: In patients with oligometastatic lesions that progressed on ICI, CMA may be a valid treatment option that generates clinical benefits. By eradicating gross sites of disease by converting area sites into in-situ vaccines, T cells are able to access microscopic metastasis. Larger randomized trials are indicated to further define the role of CMA for ICIs resistance.

PMID:34701533 | DOI:10.1016/j.ijrobp.2021.07.1314
Adrenal Stereotactic Body Radiation Therapy in the Management of Oligometastatic Lung Cancer: Patient Selection Matters

Fetched: October 28th, 2021, 5:00am GMT by Y Zhou

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e462-e463. doi: 10.1016/j.ijrobp.2021.07.1296.

ABSTRACT

PURPOSE/OBJECTIVE(S): Adrenal metastases are commonly identified in the context of primary lung cancer. Recent literature has shown stereotactic body radiation therapy (SBRT) to improve progression free survival (PFS) in the setting of oligometastatic disease. Multiple studies have shown the efficacy and safety of adrenal SBRT. However, patient selection criteria are not well defined. We investigated the various patient selection criteria for adrenal SBRT and their associations with PFS.

MATERIALS/METHODS: We examined a cohort of patients with stage IV oligometastatic primary lung cancer with adrenal metastases who were consecutively treated with 5-fraction SBRT (n = 19). Multiple characteristics were selected for examination prior to data collection and PFS calculation. We considered 1) age 2) performance status 3) size greater than 4cm 4) presence of other metastases at adrenal metastasis diagnosis 5) presence of brain metastases at adrenal metastasis diagnosis 6) time to adrenal metastasis progression from primary diagnoses.

RESULTS: Eighteen patients completed their treatments of 5-fraction adrenal SBRT with a median dose of 4500 cGy (range from 3500 cGy to 500 cGy). One patient had a course of SBRT to each adrenal gland. Completion rate was 100% and there was no grade two or higher acute toxicities. Small bowel 0.03cc max dose ranged from 230 cGy to 3410 cGy with a median dose of 2350 cGy. Median PFS was 4.7 months. PFS was the same for patients with and without brain metastases at adrenal progression (P = 0.133). There were also no significant differences found in PFS when observing patients with adrenal progression within one year and greater than one year of initial diagnosis (P = 0.474). Similarly, PFS did not change when comparing patients with adrenal lesions greater than 4cm to patients with adrenal lesion less than or equal to 4cm (P = 0.477). PFS trended towards significance for patients older than 70 compared to patients who were 70 or younger (6.6 months vs 12.4 months, P = 0.09). Additionally, PFS was significant for patients with ECOG 2 or higher compared to patients with ECOG less than 2 (1.4 months vs 11.5 months, P = 0.027). Patients without additional metastatic disease at the time of progression had better PFS than patients with additional metastatic disease (18 months vs 7 months, P = 0.016).

CONCLUSION: Patients with an ECOG score of 0 or 1 who did not have additional metastases at the time of adrenal metastasis exhibited a higher progression free survival rate after adrenal SBRT. Despite the small sample size, this study showed that appropriate patient selection for adrenal SBRT can lead to good long-term progression free survival with very minimal toxicity if any.

PMID:34701511 | DOI:10.1016/j.ijrobp.2021.07.1296
$Permalink for 'Stereotactic Radiation Therapy With Concurrent Immune Checkpoint Inhibitor Therapy in Patients With Relapsed or Refractory Central Nervous System Lymphoma'$
Stereotactic Radiation Therapy With Concurrent Immune Checkpoint Inhibitor Therapy in Patients With Relapsed or Refractory Central Nervous System Lymphoma

Fetched: October 28th, 2021, 5:00am GMT by M G Milligan

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e300-e301. doi: 10.1016/j.ijrobp.2021.07.945.

ABSTRACT

PURPOSE/OBJECTIVE(S): Relapsed or refractory central nervous system lymphoma (CNSL) after high-dose methotrexate-based therapy is a challenging clinical entity with limited treatment options. Salvage systemic therapy and whole brain radiation therapy (WBRT) are commonly employed but are associated with significant toxicity and poor outcomes. Prior studies have shown that primary CNSLs frequently exhibit increased expression of PD-L1, and immune checkpoint inhibitor (ICI) therapy may be active in this setting. We assessed the safety and efficacy of concurrent ICI therapy and hypo-fractionated stereotactic radiation therapy (SRT) in patients with relapsed or refractory CNSL.

MATERIALS/METHODS: We retrospectively analyzed the records of patients with relapsed or refractory CNSL treated with SRT + ICI at our institution from 2017 to 2020. ICI therapy included pembrolizumab 200 mg IV q3weeks or nivolumab 3 mg/mg IV q2weeks. Linac-based SRT was delivered in 5 daily fractions of 5 Gy. CTVs included all grossly enhancing disease on T1 weighted post-contrast MR scans, with 3 mm uniform PTV expansions. Patients were followed for symptomatic and radiographic response. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier analysis.

RESULTS: Seven consecutive patients with relapsed or recurrent CNSL were analyzed: 6 with primary CNSL, 1 with secondary CNSL. Patients presented at a median age of 72.2 years (range: 40.9 - 89.9) after a median of 2 prior courses of systemic therapy. Five patients had a solitary intracranial lesion and 2 had multiple lesions. None had active extracranial disease. Median pre-SRT Karnofsky Performance Status (KPS) was 60 (range 50 - 90). All 7 patients completed SRT and received concurrent and adjuvant ICI therapy. Median follow-up after completion of SRT was 9.1 months. Acute toxicities of SRT and ICI therapy were minimal, including fatigue (3 patients), diarrhea (2), and adrenal insufficiency requiring oral steroids (1). Five patients (71.4%) achieved symptomatic improvement after SRT including 2 patients (28.5%) with a clinical complete response (CR). Median post-SRT KPS was 70 (range: 60 - 100). Six patients had follow-up imaging, and all had an objective response including 3 (50%) with a radiographic CR. The median time to best radiographic response was 2.0 months (range 0.3 - 3.7 months), and all treated lesions remained controlled on all subsequent imaging. Three patients (42.9%) experienced out-of-field intracranial recurrence. Median PFS was 7.7 months (95% CI: 4.0 - 11.4 months) and median OS was 12.6 months (95% CI: 7.5 - 12.7 months) post-SRT.

CONCLUSION: Among patients with relapsed or refractory CNSL, SRT + ICI appears to be well tolerated and offers excellent symptomatic and radiographic local control. Further studies are needed to identify appropriate candidates for salvage SRT + ICI, and to evaluate the clinical efficacy and neurocognitive impact of this approach.

PMID:34701129 | DOI:10.1016/j.ijrobp.2021.07.945
Indications for Plan Adaptation in Patients with Adrenal Metastases Treated With Stereotactic MR-Guided Adaptive Radiation Therapy (SMART)

Fetched: October 28th, 2021, 5:00am GMT by R Herrera

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e261-e262. doi: 10.1016/j.ijrobp.2021.07.860.

ABSTRACT

PURPOSE/OBJECTIVE(S): Stereotactic body radiation therapy (SBRT) is increasingly utilized in patients with oligometastatic and oligoprogressive disease; however, concerns about interfractional changes in gastrointestinal (GI) anatomy limit broad adoption and dose-escalation in the context of adrenal metastases. The objective of this study is to evaluate the need and indications for daily adaptive replanning in this patient population.

MATERIALS/METHODS: Consecutive patients with adrenal metastases treated using respiratory-gated stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) at a single institution were evaluated. Breath-hold 3D-MRI was acquired prior to each fraction to visualize the anatomy-of-the-day. To quantify the indication for adaptation, dose prediction (i.e., calculation of initial plan on the anatomy of the day) was performed. If adaptation was indicated (i.e., critical organ at risk [OAR] dose constraints were exceeded and/or desired target coverage was not achieved), the plan was reoptimized using the original beam parameters with adjustment of individual beam fluence. Comparisons between the predictive and adaptive dose were performed to evaluate adaptive replanning decision-making based on pre-defined institutional criteria. Dose differences between the predictive and adaptive doses were compared by paired sample t test.

RESULTS: 16 patients with adrenal metastases underwent a total of 80 SMART fractions to a median dose of 50 Gy in 5 fractions. The median PTV was 58.9 cc (Range: 16.1 - 377.4 cc). Plan adaptation was performed in 15/16 patients at least once during the treatment course due to predefined GI OAR dose constraints being exceeded, after accounting for the anatomy of the day. The indications for adaptation were to improve target coverage in 19/80 fractions (24%), or reduce dose to at least one critical GI OAR in 33 fractions (41%), and for both conditions in 9 fractions (11%). The most commonly affected GI OAR for plan adaptation was the stomach for left-sided metastases (6/7 patients, 86 %) and duodenum for right-sided metastases (3/9 patients, 33 %). Plan adaptation allowed for dose-escalation to the GTV with statistically significant increase in the minimum dose (42 Gy vs. 34 Gy, P < 0.001). No patients experienced acute or late grade ≥3 CTCAE v4.0 treatment-related toxicities.

CONCLUSION: SMART enabled dose-escalation with simultaneous OAR sparing in response to changes in the anatomy-of-the-day for patients with adrenal metastases. SMART using an ablative prescription dose should be explored in future prospective studies for targets in proximity to historically dose-limiting GI OARs.

PMID:34701039 | DOI:10.1016/j.ijrobp.2021.07.860
Radiomic Feature Changes in Adrenal Lesions Treated With MR-Guided Stereotactic Body Radiation Therapy

Fetched: October 28th, 2021, 5:00am GMT by M N Mills

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):S98-S99. doi: 10.1016/j.ijrobp.2021.07.229.

ABSTRACT

PURPOSE/OBJECTIVE(S): Magnetic resonance image guided stereotactic body radiotherapy (MRgSBRT) is an advanced technology that may provide radiomic feature changes during treatment of adrenal lesions feasible for adaptation.

MATERIALS/METHODS: A prospectively maintained database was retrospectively reviewed for 24 patients with adrenal lesions who underwent MRgSBRT. Histogram features (n = 7, Table 1) were extracted from MRgSBRT images (TRueFISP sequence, 1.5mm/3mm voxel size/slice thickness) from adrenal malignancy patients scanned at simulation (SIM) approximately 14 days before SBRT start, and prior to each of 5 daily fractions (F1-F5) of 8-12 Gy to Gross Tumor Volume (GTV). Tumor ROI was derived by 3mm radial erosion of GTV in 3D. Each scan was divided by median intensity in kidney for image normalization. Significance of changes SIM-F1 and F1-F5 were assessed using two-sided paired t-test. Response to treatment was assessed via follow up CT scan roughly 3 months after MRgSBRT via RECIST v1.1, with overall response rate (ORR) including complete and partial response. Radiomics features were tested for association with clinical variables using the Kruskal-Wallis test.

RESULTS: Patients had a median age of 67 years (19-80). The majority of adrenal lesions were metastatic sites (88%), while there were 2 patients with primary adrenocortical carcinoma and 1 patient with pheochromocytoma. All patients were treated with MRgSBRT in 5 fractions to a median dose of 50 Gy (40-60). Of 23 evaluable cases, rates of complete response (CR), partial response (PR), and stable disease (SD) were 13%, 35%, and 52%, respectively. Median follow up was 9.7 months (1-22). Significant changes in MRgSBRT of the tumors were observed after treatment (F1-F5, Table 1) with an increase in image signal median and interquartile range (IQR) consistent with radiation response. No signal changes were seen prior to treatment (SIM-F1). Erosion of GTV to remove tissue borders was required to observe the changes F1-F5 (P = 0.08 median,0.67 IQR for full GTV volume). For association to outcome considering varying dose per fraction, signal ratios were calculated between F1 and fraction closest to 40 Gy cumulative dose. There was a significant relationship between IQR ratio and ORR (CR/PR cases: mean 0.94 ± 0.03, SD cases: mean 1.11 ± 0.06, P = 0.011).

CONCLUSION: Significant increases in image signal median and IQR were identified in patients with adrenal lesions undergoing MRgSBRT, consistent with radiation response. MRgSBRT radiomic feature changes may allow for better personalization of radiotherapy going forward.

PMID:34700674 | DOI:10.1016/j.ijrobp.2021.07.229
Population Based Phase II Trial of Stereotactic Ablative Radiotherapy (SABR) for up to 5 Oligometastases: Preliminary Results of the SABR-5 Trial

Fetched: October 28th, 2021, 5:00am GMT by R A Olson

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):S4. doi: 10.1016/j.ijrobp.2021.07.044.

ABSTRACT

PURPOSE/OBJECTIVE(S): After the publication of the landmark SABR-COMET trial, concerns were raised over toxicity of SABR for oligometastases. This population-based study was designed as a bridge from phase II to phase III trials, while assessing the toxicity profile of SABR in a larger cohort from a provincial cancer program.

MATERIALS/METHODS: From November 2016 to July 2020, 399 patients were enrolled in this single arm, phase II trial of SABR in patients with oligometastatic or oligo-progressive disease. During this period, patients were only eligible for SABR in these settings on trial within our province, and therefore this analysis is population-based, with resultant minimal selection bias in comparison to previously published SABR series. The primary endpoint was toxicity and we hypothesized grade 4 toxicity < 5%. Grade 2 or higher toxicities were prospectively collected, and were rated as unrelated, unlikely, possibly, probably, or definitely related to SABR. Toxicities rated as possibly, probably, or definitely related to SABR were analyzed in this study. The radiotherapy details are previously published in the protocol; because of previously published high grade toxicity in this setting, all cases underwent individual peer review and organs at risk were prioritized over the planning target volumes.

RESULTS: The mean age was 68 years (SD 10.9, range 30-97). The participants were mostly male (69%). The most common histologies were prostate cancer (33%), colorectal cancer (14%), breast cancer (11%), and lung cancer (9%). The number of SABR treated sites were one (69%), two (22%), and three or more (9%). The most common sites of SABR were lung (33%), non-spine bone (28%), spine (14%), lymph nodes (13%), liver (5%) and adrenal (3%). Grade 2, 3, and 4 toxicity cumulative incidences were 11.4%, 4.6%, and 0.5%, respectively. There were no grade 5 toxicities. Grade 2 or higher specific toxicity included 4.8% pain, 1.3% pneumonitis, and 0.8% neuropathy. There were no reported gastrointestinal fistula, perforation, or hemorrhage. Cumulative incidence and prevalence of toxicity at 1 & 3 years will be updated and presented.

CONCLUSION: The incidence of grade 2+ SABR toxicity on this population-based study was 16.5%, which is lower than that reported on SABR-COMET (29%). Importantly, there were no grade 5 toxicities attributed to SABR in this study to date. Severe (grade 3 or higher) toxicities were uncommon (5.0%). These results are encouraging that, in a population-based program with rigorous peer review quality assurance, SABR treatment for oligometastases has acceptable rates of toxicity. This supports further enrollment in randomized phase III trials.

PMID:34700549 | DOI:10.1016/j.ijrobp.2021.07.044
Stereotactic body radiation therapy (SBRT) for patients with oligometastatic/oligoprogressive adrenal metastases: Outcomes and toxicities profile in a monoinstitutional study

Fetched: October 27th, 2021, 5:00am GMT by Giuseppe Facondo

Cancer Treat Res Commun. 2021 Oct 21;29:100481. doi: 10.1016/j.ctarc.2021.100481. Online ahead of print.

ABSTRACT

AIMS: To evaluate survival outcomes and toxicology profiles in oligometastatic/oligoprogressive patients treated with SBRT for adrenal metastases.

METHODS: We retrospectively analyzed 25 metastatic adrenal lesions in 24 oligometastatic/oligoprogressive patients undergoing ablative Stereotactic Body Radiation Therapy (SBRT) between February 2010 and November 2019 in our department. The primary endpoint was overall survival (OS). Secondary endpoints were local overall response rate (ORR), acute and late toxicities.

RESULTS: The most common primary tumor was non-small cell lung cancer (54%). Twenty-one patients received chemo or immuno-therapy. The median planning target volume (PTV) was 41.7 cm³. Median SBRT dose was 36 Gy. Median dose per fraction was 15 Gy. Median survival was 35-months with OS outcomes ranging from 6-months (100%), 1-year (87.5%) and 2-years (66.7%). ORR based on RECIST criteria was 66.5%. 12 patients experienced acute toxicities, mostly grade 1-2 (8 patients, 32%).

CONCLUSIONS: SBRT for oligometastatic/oligoprogressive patients with adrenal metastases showed acceptable survival outcomes and a safe toxicity profile.

PMID:34700142 | DOI:10.1016/j.ctarc.2021.100481
Reprogramming of glucocorticoid receptor function by hypoxia

Fetched: October 27th, 2021, 5:00am GMT by Tineke Vanderhaeghen

EMBO Rep. 2021 Oct 26:e53083. doi: 10.15252/embr.202153083. Online ahead of print.

ABSTRACT

Here, we investigate the impact of hypoxia on the hepatic response of glucocorticoid receptor (GR) to dexamethasone (DEX) in mice via RNA-sequencing. Hypoxia causes three types of reprogramming of GR: (i) much weaker induction of classical GR-responsive genes by DEX in hypoxia, (ii) a number of genes is induced by DEX specifically in hypoxia, and (iii) hypoxia induces a group of genes via activation of the hypothalamic-pituitary-adrenal (HPA) axis. Transcriptional profiles are reflected by changed GR DNA-binding as measured by ChIP sequencing. The HPA axis is induced by hypothalamic HIF1α and HIF2α activation and leads to GR-dependent lipolysis and ketogenesis. Acute inflammation, induced by lipopolysaccharide, is prevented by DEX in normoxia but not during hypoxia, and this is attributed to HPA axis activation by hypoxia. We unfold new physiological pathways that have consequences for patients suffering from GC resistance.

PMID:34699114 | DOI:10.15252/embr.202153083
Clinical Findings in Pheochromocytoma

Fetched: October 27th, 2021, 5:00am GMT by Gulali Aktas

J Coll Physicians Surg Pak. 2021 Nov;31(11):1382-1383. doi: 10.29271/jcpsp.2021.11.1382.

ABSTRACT

Null.

PMID:34689507 | DOI:10.29271/jcpsp.2021.11.1382
Adult Retroperitoneal Mature Cystic Teratoma Masquerading as Non-Endocrine Primary Adrenal Tumor

Fetched: October 27th, 2021, 5:00am GMT by Fatima Tuz Zahra Shakir

J Coll Physicians Surg Pak. 2021 Nov;31(11):1351-1353. doi: 10.29271/jcpsp.2021.11.1351.

ABSTRACT

Teratomas belong to non-seminomatous germ cell tumors and originate from totipotent germ cells. They are mostly made up of tissues derived from all three layers, i.e., endoderm, mesoderm and ectoderm. They can be mature teratomas, which are benign or immature teratomas, having malignant potential. Extra-gonadal mature cystic teratomas are uncommon, particularly in retroperitoneum. Other sites are sacrococcygeal, mediastinal, and pineal regions. They are mostly detected in females in reproductive age group. In this case report, we discuss a female patient being worked up for persistent vomiting and food indigestion, initially managed on the line of acid peptic disease. She was found to have a large retroperitoneal mass in adrenal region producing mass effect on intestines. Later on, it was discovered to be mature cystic teratoma on histopathological evaluation. Key Words: Mature teratoma, Adrenal gland, Retroperitoneum.

PMID:34689496 | DOI:10.29271/jcpsp.2021.11.1351
Autophagy-Related Proteins Are Differentially Expressed in Adrenal Cortical Tumor/Pheochromocytoma and Associated with Patient Prognosis

Fetched: October 27th, 2021, 5:00am GMT by Hye Min Kim

Int J Mol Sci. 2021 Sep 28;22(19):10490. doi: 10.3390/ijms221910490.

ABSTRACT

The aim of this research was to evaluate the expression and concomitant implications of LC3A, LC3B, beclin-1, and p62, which are key components of autophagy in human adrenal gland tumors. Tissue microarray was made for 321 cases of adrenal gland tumor (adrenal cortical adenoma (ACA): 115, adrenal cortical carcinoma (ACC): 17, and pheochromocytoma (PCC): 189). Immunohistochemical staining was performed for beclin-1, p62, LC3A, and LC3B, and the results were compared with the patients' clinicopathologic parameters. LC3A, LC3B, beclin-1, and LC3B isolated single positive cells (ISPC) positivity rates were higher in PCC than in adrenal cortical tumor (ACT), whereas p62 positivity was lower in PCC than in ACT. The proportion of positive LC3B (ISPC) was higher in ACC than in ACA. In addition, the proportion of cells positive for p62 and LC3B (ISPC) was significantly higher in PCCs with a GAPP score of ≥3. In univariate Cox analysis, p62 positivity (p = 0.014) and the presence of p62 (ISPC) (p = 0.001) were associated with shorter disease-free survival in PCC. Moreover, p62 positivity was predictive of shorter overall survival (OS) in patients with PCC by multivariate analysis (relative risk, 6.240; 95% CI, 1.434-27.15; p = 0.015). Differences were found in the expression of autophagy-related proteins according to adrenal gland tumor types. Compared to ACT, the proportion of LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity was higher in PCC, whereas p62 positivity was lower. Similarly, p62 positivity in PCC was associated with patient prognosis of OS.

PMID:34638836 | PMC:PMC8508962 | DOI:10.3390/ijms221910490
Endocrine and neuroendocrine tumors

Fetched: October 27th, 2021, 5:00am GMT by Philipp Riss

Chirurg. 2021 Nov;92(11):996-1002. doi: 10.1007/s00104-021-01512-8. Epub 2021 Oct 7.

ABSTRACT

Endocrine tumors and here in particular gastrointestinal neuroendocrine neoplasms (GEP-NET), pheochromocytomas (PC), paragangliomas (PGL) and thyroid tumors are prime examples of the importance of molecular pathology and molecular biology for the diagnostics, classification and ultimately also the (surgical) treatment of these diseases. The GEP-NETs are graded using the Ki-67 index. This determines the type of molecular imaging (DOTA/DOPA/FDG-PET/CT), the possible treatment (surgical and/or radiopeptide therapy), antiproliferative and symptom-controlling treatment with somatostatin analogues and ultimately also the prognosis. The PC/PGLs can be hereditary (MEN2A, VHL, NF1, SDH mutations), which significantly influences the surgical treatment and preoperative medication. Molecular imaging is very important and can lead the way in cases of borderline biochemistry. Adrenal carcinomas can also be genetically determined. In the case of thyroid tumors, the pathology of the C‑cell (C-cell hyperplasia, medullary thyroid carcinoma) should be emphasized. In the case of hereditary diseases (FMTC, MEN2), early prophylactic surgery is often necessary and prevents the occurrence of advanced carcinomas; however, the determination of the extent of resection in follicular lesions or the distinction between noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and follicular variants of papillary thyroid carcinoma can also be determined with the help of specific markers. Overall, molecular pathology has an increasingly more important role in these entities and is also the topic of ongoing research projects.

PMID:34618164 | DOI:10.1007/s00104-021-01512-8
Adrenocortical carcinoma, case report

Fetched: October 26th, 2021, 5:00am GMT by Yeniseik D Cortés-Vázquez

Cir Cir. 2021;89(5):664-668. doi: 10.24875/CIRU.20000693.

ABSTRACT

The adrenocortical carcinoma is rare and aggressive. It has a bimodal presentation, predominantly female, > 20% of cases will be diagnosed incidentally. 43-year-old male, with colic pain in the left flank, weight loss and intermittent fever. Computed tomography with a tumor on the left adrenal with liver metastases, block resection surgery was performed, pathological report of adrenocortical carcinoma with a 7 points of Weiss score and Ki67 40%. Adrenocortical carcinoma is a rare and aggressive neoplasm; the clinical presentation is variable. Systemic therapy is important even in patients with localized disease and independent of surgical approach.

PMID:34665162 | DOI:10.24875/CIRU.20000693
Inherited/Genetically-Associated Pheochromocytoma/ Paraganglioma Syndromes and COVID-19

Fetched: October 26th, 2021, 5:00am GMT by Ioannis Ilias

Medicina (Kaunas). 2021 Sep 28;57(10):1033. doi: 10.3390/medicina57101033.

ABSTRACT

In some subjects with inherited pheochromocytoma/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1α) stabilization/activation could lead to an increase in angiotensin converting enzymes (ACE). This would result in the stimulation of angiotensin (AT) II production and, hence, reduce the availability of ACE 2. The latter would provide decreased numbers of binding sites for the spike protein of SARS-CoV-2 and, therefore, result in less points of viral entry into cells. Thus, subjects with HIF1α-associated PPG syndromes may benefit from an inherent protective effect against COVID-19. Such an implication of HIF1α vis-à-vis COVID-19 could open ways of therapeutic interventions.

PMID:34684070 | PMC:PMC8538054 | DOI:10.3390/medicina57101033
Real-World Incidence of Immune-Related Adverse Events Associated with Nivolumab Plus Ipilimumab in Patients with Advanced Renal Cell Carcinoma: A Retrospective Observational Study

Fetched: October 26th, 2021, 5:00am GMT by Satoshi Washino

J Clin Med. 2021 Oct 18;10(20):4767. doi: 10.3390/jcm10204767.

ABSTRACT

Real-world incidence of immune-related adverse events (irAEs) associated with nivolumab plus ipilimumab in patients with renal cell carcinoma (RCC) has been rarely demonstrated. The present study aims to report the safety outcomes of this combination therapy in the real-life population. We conducted a multi-institutional retrospective observational study that assessed the incidence and severity of irAEs associated with nivolumab plus ipilimumab in 41 Japanese patients with metastatic and/or locally advanced RCC. The irAEs were classified into endocrine and non-endocrine irAEs. The median age and follow-up period were 68 years and 13.0 months, respectively. Endocrine irAEs were observed in 66% of patients, including hypopituitarism in 44%, hyperthyroidism in 41%, and primary hypothyroidism in 22%, while non-endocrine irAEs were observed in 54%. All patients experiencing hypopituitarism presented with adrenocorticotropic hormone deficiency, causing secondary adrenal insufficiency, which required permanent corticosteroid replacement therapy. There was an association between the incidence of endocrine irAEs and high-grade non-endocrine irAEs other than skin-related irAEs (p = 0.027). When patients experienced two or more endocrine irAEs, they had a 35% chance of experiencing high-grade non-endocrine irAEs other than skin-related irAEs. Nivolumab plus ipilimumab may lead to a high prevalence of endocrine irAEs in "real-world" patients. Endocrine irAEs may be associated with non-endocrine irAEs other than skin-related irAEs.

PMID:34682890 | PMC:PMC8541457 | DOI:10.3390/jcm10204767
Clinical Outcome of RAMPS for Left-Sided Pancreatic Ductal Adenocarcinoma: A Comparison of Anterior RAMPS versus Posterior RAMPS for Patients without Periadrenal Infiltration

Fetched: October 26th, 2021, 5:00am GMT by Jaewoo Kwon

Biomedicines. 2021 Sep 22;9(10):1291. doi: 10.3390/biomedicines9101291.

ABSTRACT

Radical antegrade modular pancreatosplenectomy (RAMPS) is considered an effective procedure for left-sided pancreatic ductal adenocarcinoma (PDAC). However, whether there are differences in perioperative outcomes, pathologies, or survival outcomes between anterior RAMPS (aRAMPS) and posterior RAMPS (pRAMPS) has not been reported previously. We retrospectively reviewed and compared the demographic, perioperative, histopathologic, and survival data of patients who underwent aRAMPS or pRAMPS for PDAC. We also compared these two groups among patients without periadrenal infiltration or adrenal invasion. A total of 112 aRAMPS patients and 224 pRAMPS patients were evaluated. Periadrenal infiltration, neoadjuvant treatment, and concurrent vessel resection were more prevalent in the pRAMPS group. After excluding patients with periadrenal infiltration, 106 aRAMPS patients were compared with 157 pRAMPS patients. There were no significant differences between the aRAMPS and pRAMPS groups in the pathologic tumor size, resection margin, proportion of tangential margin in the R1 resection, and number of harvested lymph nodes. The median overall survival and disease-free survival also did not differ significantly between the two groups. We cautiously suggest that pRAMPS will not necessarily provide more beneficial histopathologic outcomes and survival rates for left-sided PDAC cases without periadrenal infiltration. If periadrenal infiltration is not suspected, aRAMPS alone should be sufficiently effective.

PMID:34680407 | PMC:PMC8533130 | DOI:10.3390/biomedicines9101291
Advanced hepatocellular carcinoma with response to lenvatinib after atezolizumab plus bevacizumab

Fetched: October 26th, 2021, 5:00am GMT by Shigeki Yano

Medicine (Baltimore). 2021 Oct 22;100(42):e27576. doi: 10.1097/MD.0000000000027576.

ABSTRACT

RATIONALE: Various treatments are available for treating hepatocellular carcinoma (HCC). The immune checkpoint inhibitor combination of atezolizumab plus bevacizumab was recently approved for the treatment of unresectable HCC, but there are few reports on the failure of the combination treatment. Here, we present a case of unresectable HCC with adrenal metastasis that was eventually operated on after lenvatinib (LEN) treatment that followed failed treatment with atezolizumab plus bevacizumab.

PATIENT CONCERNS: A 68-year-old man was diagnosed with non-alcoholic steatohepatitis-based HCC with adrenal metastasis.

DIAGNOSIS: Cirrhosis was classified as Child-Pugh score of 5. HCC was diagnosed as Barcelona Clinic Liver Cancer stage C.

INTERVENTIONS: We initiated treatment with atezolizumab plus bevacizumab. Liver dysfunction appeared 2 days after the first administration but was improved by intravenous rehydration and did not appear after the second course. The HCC shrank, but the adrenal metastasis grew bigger after the fourth course, so we changed the therapy to LEN. After HCC and adrenal metastasis were necrotic by LEN, conversion surgery was performed.

OUTCOMES: After successful conversion therapy, the general condition of the patient was good, and has been carefully followed for 4 months to date without any evidence of further recurrences.

LESSONS: This case showed that even if atezolizumab plus bevacizumab is not effective, multidisciplinary treatment such as LEN and conversion surgery is possible. Given the efficacy of LEN after atezolizumab plus bevacizumab, it is important to consider that there is a possibility of cure even when first-line treatment is not effective for a patient with unresectable HCC.

PMID:34678902 | PMC:PMC8542139 | DOI:10.1097/MD.0000000000027576
Mediastinal Thyroid Carcinoma and Graves' Disease: A Rare Presentation

Fetched: October 26th, 2021, 5:00am GMT by Sara Lomelino Pinheiro

Case Rep Endocrinol. 2021 Oct 12;2021:6584616. doi: 10.1155/2021/6584616. eCollection 2021.

ABSTRACT

BACKGROUND: Mediastinal thyroid carcinoma is extremely rare, with few cases reported in the literature. Case Report. A 73-year-old man presented with weight loss for 6 months. Imaging by computed tomography (CT) documented a large mediastinal mass below the thyroid gland and pulmonary metastases. Neck ultrasound found two spongiform nodules in the right thyroid lobe, and fine-needle aspiration citology (FNAC) of these nodules revealed they are benign. Endobronchial ultrasound-guided needle biopsy of the mediastinal mass was compatible with papillary thyroid cancer. A few weeks later, the patient developed overt hyperthyroidism due to Graves' disease, which was treated with antithyroid drugs. ^99mPertechnetate scintigraphy showed increased diffuse uptake in the thyroid parenchyma but the absence of uptake in the paratracheal mass and in the lung nodules. The patient was not considered eligible for surgical intervention or therapy with tyrosine kinase inhibitor due to tracheal and mediastinal vessel invasion and was treated with palliative radiotherapy. Two months later, restaging PET-FDG showed an intense uptake in the right lobe of the thyroid gland, lymph nodes, lungs, bone, muscle, myocardial, kidney, and adrenal gland.

CONCLUSION: In this case, thyroid carcinoma presented as a mediastinal mass with concurrent hyperthyroidism due to Graves' disease. Although uncommon, the clinicians should be aware of these situations. Obtaining a prompt histological examination of an intrathoracic mass is crucial to ensure an early diagnosis and treatment.

PMID:34676120 | PMC:PMC8526269 | DOI:10.1155/2021/6584616
Endosonographic predictors of malignancy in a left adrenal gland in lung cancer patients - a comparison of EUS-b, CT and PET-CT

Fetched: October 26th, 2021, 5:00am GMT by Stanisław Orzechowski

Pol Arch Intern Med. 2021 Oct 22. doi: 10.20452/pamw.16127. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients with resectable lung cancer require invasive evaluation of enlarged left adrenal gland (LAG). There are only few studies showing utility of endosonography with single ultrasound bronchoscope (EUS-b) in LAG assessment. Combination of CT, PET-CT and EUS-b and ultrasonographic predictors of malignancy (M1b/c) in LAG are not well known.

PATIENTS AND METHODS: A two center cohort retrospective study was performed from 2012 to 2019. Enlarged LAGs were evaluated by CT, PET-CT and EUS-b. Then, a complete endoscopic mediastinal staging was performed, enlarged LAGs were sampled by EUS-b-FNA. Patients were followed up for 6-months.

RESULTS: During the diagnosis of 2176 staged LCP, 113 (5.19%) enlarged LAGs were biopsied. 51 (45.13%) were positive for malignancy, predominantly adenocarcinoma (46.9%). Endosonography up-staged 7 (6.2%) patients, and down-staged 11 (9.37%) after false CT or PET-CT findings. No complications were noted after any biopsies. Radiological predictors of LAG metastases had the highest yield if cut offs were set as follows: HU>23, SUV>4.2 and LAG size >25mm. Hypoechogenic LAGs with loss of sea-gull shape in EUS-b indicated 28.67 times bigger likelihood of metastases. The sensitivity, specificity, accuracy, NPV and PPV for all measured ultrasound predictors were: 86.21%, 85.45%, 85.84%, 85.45%, 86.21%, combined with radiological measurements: 93.10%, 94.55%, 93.81%, 92.86% and 94.74%, respectively.

CONCLUSIONS: Hypoechogenicity and loss of sea-gull shape in EUS-b are the most reliable predictors of malignancy in enlarged LAG. A combination of radiological assessment based on CT/PET-CT and EUS-b findings improves noninvasive diagnostics for LAG metastases in LCP.

PMID:34674520 | DOI:10.20452/pamw.16127
Comparison of clinical characteristics between sporadic gastrinoma and multiple endocrine neoplasia type 1-related gastrinoma

Fetched: October 26th, 2021, 5:00am GMT by Y Guo

Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Oct 25;24(10):875-882. doi: 10.3760/cma.j.cn.441530-20210719-00291.

ABSTRACT

Objective: To compare clinical characteristics of sporadic gastrinoma and multiple endocrine neoplasia type 1 (MEN1)-related gastrinoma. Methods: A retrospective cohort study was conducted. Patients with clinical manifestations of Zollinger-Ellison syndrome, pathological diagnosis as neuroendocrine neoplasm (NEN) and complete clinical and follow-up data were enrolled. Patients with only high gastric acid secretion but without evidence of NEN, or with other concurrent non-NEN tumors were excluded. According to the above criteria, the clinicopathological data of 52 cases of gastrinoma diagnosed from April 2003 to December 2020 in the First Affiliated Hospital, Sun Yat-sen University, were collected. Patients who met the diagnostic criteria of gastrinoma and met one of the following conditions were diagnosed as MEN1-related gastrinoma: (1) the presence of pathogenic mutations in the MEN1 gene confirmed by genetic testing; (2) NENs involving two or more endocrine glands, namely, pituitary, parathyroid, thymic, pancreatic, and adrenal NENs; (3) NEN and at least one first-degree relatives diagnosed as MEN1. The remaining gastrinomas were defined as sporadic gastrinoma. Student's t test and chi-square test were used for statistical analysis. Clinicopathological characteristics, endoscopic findings, imaging characteristics, treatment, and prognosis of sporadic and MEN1-related gastrinoma were compared. Results: Among 52 patients with gastrinoma, 33 were sporadic gastrinoma and 19 were MEN1-related gastrinoma. The common symptoms of both sporadic and MEN1-related gastrinomas were diarrhea (24/33, 72.7%; 17/19, 89.5%) and abdominal pain (19/33, 57.6%; 9/19, 47.4%). Compared with sporadic gastrinoma, MEN1-related gastrinoma needed longer time for diagnosis [(7.4±4.9) years vs. (3.9±5.2) years, t=-2.355, P=0.022), were more likely multiple tumors [47.4% (9/19) vs. 15.2% (5/33), χ(2)=6.361, P=0.012], had smaller diameter [(1.7±1.0) cm vs. (3.1±1.8) cm, t=2.942, P=0.005), presented the lower tumor grade [G1: 83.3% (15/18) vs. 39.4% (13/33); G2: 11.1% (2/18) vs. 54.5% (18/33); G3: 5.6% (1/18) vs. 6.1% (2/33), Z=-2.766, P=0.006], were less likely to have serum gastrin which was 10 times higher than normal [11.8% (2/17) vs. 56.0% (14/33), χ(2)=8.396, P=0.004], had higher probability of complication with type 2 gastric neuroendocrine tumors (g-NET) [31.6% (6/19) vs. 3.0%(1/33), χ(2)=6.163, P=0.013], and had lower rate of liver metastasis [21.1% (4/19) vs. 51.5% (17/33), χ(2)=4.648, P=0.031). There was no obvious difference between sporadic gastrinomas and MEN1-related gastrinomas in endoscopic findings. Both types presented enlarged and swollen gastric mucosa under the stimulation of high gastric acid, and multiple ulcers in the stomach and duodenum could be seen. Gastrinoma with type 2 g-NET presented multiple polypoid raised lesions in the fundus and body of the stomach. (68)Ga-SSR-PET/CT scan had a 100% detection rate for both types while (18)F-FDG-PET/CT scan had a higher detection rate for sporadic gastrinoma compared with MEN1-related gastrinoma [57.9% (11/19) vs. 20.0% (3/15), χ(2)=4.970, P=0.026]. Among the patients with sporadic gastrinoma, 19 received surgical treatment, 1 underwent endoscopic submucosal dissection, 8 underwent transcatheter arterial embolization (TAE), and 5 underwent surgery combined with TAE. Among patients with MEN1-related gastrinoma, 13 received surgical treatment, and the other 6 received conservative treatment. The median follow-up of all the patients was 21.5 (1-129) months, and the 5-year survival rate was 88.4%. The 5-year survival rate of patients with sporadic and MEN1-related gastrinomas was 89.5% and 80.0% respectively (P=0.949). The 5-year survival rate of patients with and without liver metastasis was 76.2% vs. 100%, respectively (P=0.061). Conclusions: Compared with sporadic gastrinoma, MEN1-related gastrinoma has longer diagnosis delay, smaller tumor diameter, lower tumor grading, lower risk of liver metastasis, and is more likely to complicate with type 2 g-NET, while there is no difference in survival between the two tumor types.

PMID:34674462 | DOI:10.3760/cma.j.cn.441530-20210719-00291
Cancers Detected During the Evaluation Before Bariatric Surgery in Obese Patients: a High-Risk Population for Cancers and Their Prevalence

Fetched: October 26th, 2021, 5:00am GMT by Kerim Güzel

Obes Surg. 2021 Dec;31(12):5391-5395. doi: 10.1007/s11695-021-05747-6. Epub 2021 Oct 21.

ABSTRACT

PURPOSE: The purpose of the present study was to determine the types and prevalence of cancers in obese patients who have risks for cancer with multidisciplinary evaluation in managing the patients before bariatric surgery.

MATERIALS AND METHODS: The study had a descriptive cross-sectional method conducted by examining patients' files retrospectively. The frequency and types of diseases with cancer during the multidisciplinary evaluation of the study group with a BMI ≥ 40 kg/m² before bariatric surgery were used as the study data.

RESULTS: A total of 1354 (64.97%) of these patients underwent bariatric surgery (for obesity), and 730 (35.02%) cases underwent metabolic surgery (type 2 diabetic patients). Eighteen patients had thyroid papillary cancer (0.86%) and colon cancer was detected in 8 people (0.38%), breast cancer in 6 people (0.47%), stomach cancer in 5 people (0.23%), kidney cancer in 3 people (0.1%) 4), lung cancer in 2 people (0.09%), pancreatic cancer in 2 people (0.09%), adrenal cancer in 2 people (0.09%), and neuroendocrine tumor in 1 person (0.04%).

CONCLUSION: It was found that obesity and some cancers are related. Weight loss to be achieved with obesity surgery can reduce the risk of obesity-related cancers.

PMID:34674140 | DOI:10.1007/s11695-021-05747-6
Fat-containing pelvic lesions in females

Fetched: October 26th, 2021, 5:00am GMT by Nikoo Fattahi

Abdom Radiol (NY). 2021 Oct 21. doi: 10.1007/s00261-021-03299-y. Online ahead of print.

ABSTRACT

Pelvic tumors are common in females and have a broad differential diagnosis. The clinical management of pelvic tumors varies widely-from observation to surgical resection-and imaging plays a pivotal role in diagnosis and clinical decision-making in these cases. In particular, imaging can help determine the organ of origin and tissue content of these tumors, which are the most important steps to narrowing the differential diagnosis. Fat has a characteristic appearance and is often easily identified on ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI). The amount and distribution of intralesional fat varies in different types of tumors. Macroscopic intralesional fat is often easily recognized by its hyperechoic appearance on US and low attenuation on CT similar to subcutaneous fat. On MRI, macroscopic fat is hyperintense on T1-weighted (T1W) images, with characteristic signal loss on fat-saturated sequences and India-ink artifact on opposed-phase T1W images. Macroscopic fat is the hallmark of teratomas, which are the most common ovarian neoplasms. Uterine lipoleiomyomas, peritoneal loose bodies, intraperitoneal and extraperitoneal primary lipomatous tumors such as lipoma and liposarcomas, and extra-adrenal myelolipomas are other pelvic masses distinguished by the presence of macroscopic fat. However, the imaging diagnosis of pelvic masses containing minimal or microscopic fat, such as immature ovarian teratomas, steroid cell ovarian neoplasms, and extramedullary hematopoiesis, can present a diagnostic challenge owing to their nonspecific appearance on US or CT. Obtaining MRI with in-phase and opposed-phase dual-echo T1W sequences and depicting chemical shift artifacts can be helpful in distinguishing these lesions.

PMID:34673996 | DOI:10.1007/s00261-021-03299-y
Castration failure in prostate carcinoma due to a functioning adrenocortical carcinoma

Fetched: October 26th, 2021, 5:00am GMT by Vishal Navani

Endocrinol Diabetes Metab Case Rep. 2021 Oct 1;2021:21-0036. doi: 10.1530/EDM-21-0036. Online ahead of print.

ABSTRACT

SUMMARY: We report concurrent metastatic prostatic adenocarcinoma (PC) and functioning androgen-secreting adrenocortical carcinoma (ACC) in a 77-year-old man. The failure to achieve adequate biochemical castration via androgen deprivation therapy (ADT) as treatment for PC metastases, together with elevated DHEA-S, androstenedione, and discordant adrenal tracer uptake on FDG-PET and PSMA-PET, suggested the presence of a concurrent functional primary adrenal malignancy. On histopathological analysis, scant foci of PC were present throughout the ACC specimen. Castration was achieved post adrenalectomy with concurrent drop in prostate-specific antigen. We outline the literature regarding failure of testosterone suppression on ADT and salient points regarding diagnostic workup of functioning adrenal malignancies.

LEARNING POINTS: Failure to achieve castration with androgen deprivation therapy is rare and should prompt careful review to identify the underlying cause. All adrenal lesions should be evaluated for hormone production, as well as assessed for risk of malignancy (either primary or secondary). Adrenocortical carcinomas are commonly functional, and can secrete steroid hormones or their precursors (androgens, progestogens, glucocorticoids and mineralocorticoids). In this case, a co-incident, androgen-producing adrenocortical carcinoma was the cause of failure of testosterone suppression from androgen deprivation therapy as treatment for metastatic prostate cancer. Pathological adrenal androgen production contributed to the progression of prostate cancer.

PMID:34673545 | PMC:PMC8558880 | DOI:10.1530/EDM-21-0036

Google - Adrenocortical Carcinoma

Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial - The Lancet

Posted: November 24th, 2021, 9:33pm GMT

Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial The Lancet
Prognostic Value of LHFPL6 in Gastric Cancer | PGPM - Dove Medical Press

Posted: November 19th, 2021, 11:17am GMT

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COVID-19 targets human adrenal glands - The Lancet

Posted: November 18th, 2021, 9:30pm GMT

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Adrenocortical Carcinoma Treatment Market: Opportunities, Demand and Forecasts, 2021-2026 - Northwest Diamond Notes

Posted: November 17th, 2021, 9:45am GMT

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Posted: November 16th, 2021, 6:05pm GMT

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Posted: November 16th, 2021, 9:50am GMT

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Posted: November 13th, 2021, 10:57am GMT

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Posted: November 12th, 2021, 5:27pm GMT

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Posted: November 12th, 2021, 10:42am GMT

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PubMed - Adrenocortical Carcinoma

Adrenocortical carcinoma in a patient with neurofibromatosis type 1: A case report

Fetched: November 26th, 2021, 5:00am GMT by Mohammad Najafi-Semnani

Caspian J Intern Med. 2021 Fall;12(4):613-617. doi: 10.22088/cjim.12.4.613.

ABSTRACT

BACKGROUND: Neurofibromatosis type 1 (NF-1) is a genetic disorder. A heterogeneous group of benign and malignant neoplasms are associated with NF-1. Adrenocortical carcinoma (ACC) is an extremely rare invasive malignancy. The association of ACC with NF1 is not well understood.

CASE PRESENTATION: We report a case of ACC in the context of NF1 in a 39- year-old woman who referred with the chief complaint of a mass in left abdomen. A left adrenal lesion was diagnosed by CT scan. Biochemical tests showed no abnormality. Adrenalectomy was done and histological and immunohistochemical findings confirmed ACC. Due to the absence of metastasis, clinical stage II was considered for the tumor. On follow-up after six months, she was still alive and well and with no evidence of metastasis. The age of patient and lack of secretion of adrenal cortical hormones in this case were unlike most ACCs.

CONCLUSION: Also, modified Weiss score for malignancy of adrenocortical neoplasms, clinical staging system and different modality of treatment is discussed.

PMID:34820071 | PMC:PMC8590407 | DOI:10.22088/cjim.12.4.613
Live birth after in-vitro maturation of oocytes in a patient with specific ovarian insufficiency caused by long-term mitotane treatment for adrenocortical carcinoma

Fetched: November 25th, 2021, 5:00am GMT by Hélène Bry-Gauillard

Reprod Biomed Online. 2021 Oct 17:S1472-6483(21)00516-2. doi: 10.1016/j.rbmo.2021.10.004. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: How should the fertility of a woman with persistent specific ovarian dysfunction after long-term mitotane exposure be managed?

DESIGN: Case report. A 33-year-old woman who underwent surgery for adrenocortical carcinoma and treated with mitotane was referred for infertility. She rapidly became amenorrhoeic while taking mitotane, a condition that persisted for 5 years after cessation. Repeated serum hormone evaluation showed collapsed androgen levels, low oestradiol, high gonadotrophins (LH 69 and 63; FSH 23 and 43 IU/l), relatively high inhibin B level and slightly decreased anti-Müllerian hormone levels (1.4 and 0.7 ng/ml). An ultrasound scan revealed an antral follicle count of 13, contrasting with high serum gonadotrophin levels. After failure to obtain follicular growth after ovarian stimulation, in-vitro maturation (IVM) of immature oocytes aspirated from the antral follicles was carried out for microinjection with the spermatozoa of the patient's partner.

RESULTS: Two cycles of unstimulated egg retrieval were carried out, producing seven IVM oocytes, which were microinjected. A total of three cleavage-stage embryos were vitrified and unsuccessfully transferred after endometrial preparation using hormone replacement therapy (HRT). After a 20-month break, two new attempts were carried out under HRT with the aim of achieving a fresh embryo transfer. The last attempt succeeded after transfer of a single day-2 embryo, and the patient delivered a healthy baby.

CONCLUSION: Persistent specific impaired ovarian function 5 years after withdrawal of mitotane, and the first live birth after IVM in this situation, are reported. The question of fertility preservation before long-term mitotane treatment is raised.

PMID:34815159 | DOI:10.1016/j.rbmo.2021.10.004
Adrenocortical Carcinoma Discovered with Point-of-care Ultrasound

Fetched: November 24th, 2021, 5:00am GMT by Mark McIntyre

Clin Pract Cases Emerg Med. 2021 Nov;5(4):482-484. doi: 10.5811/cpcem.2021.5.51875.

ABSTRACT

CASE PRESENTATION: A 34-year-old woman presented to the emergency department with bilateral lower extremity edema and shortness of breath. She had been seen by her primary care provider. Lab work and a follow-up with endocrinology had been unrevealing. Using point-of-care ultrasound we identified a cystic mass in the right upper quadrant prompting further imaging.

DISCUSSION: Abdominal and pelvic computed tomography confirmed a mass in the right posterior liver, which was later identified as an adrenocortical carcinoma. Ultrasound is an important diagnostic tool in the setting of lower extremity edema and can be used to assess for heart failure, liver failure, obstructive nephropathy, venous thrombosis, and soft tissue infection. In this case, ultrasound helped expedite the diagnosis and treatment of a rare malignancy.

PMID:34813452 | DOI:10.5811/cpcem.2021.5.51875
Metastatic liver cancer with hormone secretion: a case report

Fetched: November 23rd, 2021, 5:00am GMT by Cheng Quan

Gland Surg. 2021 Oct;10(10):3053-3057. doi: 10.21037/gs-21-296.

ABSTRACT

Adrenocortical carcinoma (ACC) is a very rare and challenging malignancy with a dismal prognosis. The patients usually suffer from primary or metastatic tumors, and about half of the tumors have hormone secretion function to cause Cushing's syndrome (CS) and hypercortisolism. The optimal management and clinical outcomes of ACC remain ill-defined due to the rarity of the disease. Due to the failure of effective treatment, surgery remains the main treatment for ACC, which includes distant resectable metastases and ACC recurrent. We reported a 34-year-old woman who was diagnosed with left-sided ACC at another hospital and then underwent left adrenalectomy for ACC 2 years ago. Then she was admitted to our hospital with CS caused by adrenocorticotropic hormone (ACTH) secretion from an ACC metastatic to the liver. She underwent a complete resection of the tumors in the liver and was discharged without any severe complications after hormone replacement therapy. Unfortunately, six months after the hepatectomy, she eventually died due to progressive deterioration and the refusal of further treatment. ACC is a rare and challenging disease with few durable systemic options. Due to the difficulty of full cure, prompt serial follow-up after the operation is probably crucial for a better prognosis.

PMID:34804891 | PMC:PMC8575703 | DOI:10.21037/gs-21-296
Pheochromocytoma and Adrenocortical Carcinoma: Morphological Characteristics in Endoscopic Ultrasound Imaging

Fetched: November 23rd, 2021, 5:00am GMT by Neslihan Özkul

Ultrasound Int Open. 2021 Nov 17;7(2):E64-E70. doi: 10.1055/a-1626-1678. eCollection 2021 Aug.

ABSTRACT

Purpose Pheochromocytoma (PCC) and adrenocortical carcinoma (ACC) are two rare endocrine diseases. Early diagnosis is crucial to significantly reduce morbidity and mortality. In this study, we used endoscopic ultrasound (EUS) for high-resolution imaging to investigate the endosonographic morphology pattern of PCC and ACC. Materials and Methods This retrospective cohort study included 58 PCC/ACC lesions diagnosed by EUS imaging at two tertiary care centers between 1997 and 2015. The following groups were defined by histology or by the presence of a pheochromocytoma-associated syndrome without histological proof: bPCC (benign PCC), mPCC (malignant PCC), and ACC. Results In our cohort, mPCC tended to be larger at the time of diagnosis (n=5; 39.9±41.9 mm) than bPCC (n=46; 27.3 ±20.8 mm, P=0.548). ACC lesions were significantly larger (n=7; 50.6±14.8 mm) than bPCC and mPCC (n=51; 28.5±23.3 mm, P=0.002). In EUS, bPCC and ACC lesions frequently appeared to have a round shape and nodular structure. bPCC and ACC tended to be more hyperechoic (P=0.112 and P=0.558, respectively) and heterogeneous (P=0.501 and P=0.098, respectively) than mPCC. Compared to PCC, ACC did not show high hyperperfusion (P=0.022). In contrast to adenoma, all tumor entities showed hypo-/anechoic areas within the tumor (P<0.05). Conclusion No significant differences in EUS morphology were found to reliably distinguish benign from malignant PCC and ACC lesions. However, EUS may be a reasonable alternative or complementary method to conventional imaging techniques for the early detection of these tumor entities.

PMID:34804773 | PMC:PMC8598390 | DOI:10.1055/a-1626-1678
ASO Author Reflections: Adrenocortical Carcinoma-All We Need Are Nodes

Fetched: November 22nd, 2021, 5:00am GMT by J Tseng

Ann Surg Oncol. 2021 Nov 20. doi: 10.1245/s10434-021-11090-y. Online ahead of print.

NO ABSTRACT

PMID:34802104 | DOI:10.1245/s10434-021-11090-y
Primary pleomorphic liposarcoma of the liver: a case report and literature review

Fetched: November 20th, 2021, 5:00am GMT by Yuri Terunuma

Surg Case Rep. 2021 Nov 19;7(1):244. doi: 10.1186/s40792-021-01322-4.

ABSTRACT

BACKGROUND: Primary liposarcoma arising from the liver is exceedingly rare. There have been very few reports documenting primary hepatic liposarcoma, especially of the pleomorphic subtype. Surgery is currently the only established treatment method, and the prognosis remains poor. In this report, we present an unusual case of hepatic liposarcoma of the pleomorphic subtype with literature review. In addition, we discuss theories regarding pathogenesis and the pathological and clinical features of primary hepatic liposarcoma to better outline this rare entity.

CASE PRESENTATION: An asymptomatic 65-year-old female was found to have a right hepatic mass on a computed tomography scan 2 years after surgical resection of the left adrenal gland and kidney for adrenocortical carcinoma. Laboratory examinations were unremarkable. Magnetic resonance imaging demonstrated a 16-mm mass in the right hepatic lobe. Adrenocortical carcinoma metastasis was suspected. Laparoscopic partial hepatectomy completely removed the tumor with clear margins. Macroscopically, the surgical specimen contained a nodular, yellow-white mass lesion 20 mm in diameter. On pathologic examination, pleomorphic, spindle-shaped tumor cells containing hypochromatic, irregularly shaped nuclei of various sizes formed fascicular structures. Scattered lipoblasts intervened in varying stages. Mitotic cells were frequent. Ki-67 labeling index was 15%. Immunohistochemically, the tumor cells were diffusely positive for vimentin and focally positive for CD34 and alpha-SMA; lipoblasts were focally positive for S-100. Tumor cells were nonreactive for SF-1, inhibin alpha, desmin, HHF35, HMB45, Melan A, MITF, c-kit, DOG1, cytokeratin AE1/AE3, h-caldesmon, STAT6, CD68, MDM2, CDK4, c17, DHEAST, 3BHSD, CD31, Factor 8, and ERG. From these findings, primary hepatic liposarcoma of pleomorphic subtype was diagnosed. The tumor recurred intrahepatically 3 years later, and the patient died 5 months after recurrence.

CONCLUSIONS: In our report, we discussed the rarity, theories regarding pathogenesis, and a review of the literature of this atypical condition. To the best of our search, this is the 14th case of primary hepatic liposarcoma and the 2nd case of the pleomorphic subtype reported throughout the world. Further research regarding the etiology of this unusual clinical entity is warranted to establish effective diagnostic and management protocols.

PMID:34797454 | PMC:PMC8603980 | DOI:10.1186/s40792-021-01322-4
Adrenocortical Carcinoma: The Value of Lymphadenectomy

Fetched: November 19th, 2021, 5:00am GMT by Joshua Tseng

Ann Surg Oncol. 2021 Nov 18. doi: 10.1245/s10434-021-11051-5. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) staging does not account for the number of positive nodes. The prognostic value of quantitative metastatic nodal burden is unknown.

METHODS: The National Cancer Database was retrospectively queried from 2004-2016 to identify patients with Stage I-III ACC undergoing adrenalectomy. Patients who underwent lymphadenectomy (LAD) were further studied. Demographics, TNM staging, tumor characteristics, and surgical approach were analyzed.

RESULTS: 386 LADs were identified. The median number of nodes examined was 2 (IQR 2-6), with no difference by surgical approach '[laparoscopic, 3 (1-3); robotic, 1.5 (1-4.5); open, 2 (1-7), p = 0.493]. In LADs with cN0 disease, positive nodes were seen in 17.5% of patients; an average of 6 (1-12) nodes were examined in patients who upstaged to pN1 disease compared with an average of 2 (1-6) nodes in those who remained pN0. Median survival was incrementally worse for patients with more positive nodes (62.8 vs. 21.9 vs. 13.7 vs. 11.3 vs. 10.7 months for 0, 1, 2, 3, and ≥ 4 positive nodes, respectively, p < 0.01). On multivariate analysis, significant prognostic factors for poor survival included older age, ≥ 2 comorbidities, pT3, and pT4. The strongest prognostic factor for poor survival was the number of positive nodes (1 node, hazards ratio [HR] 2.3, 95% confidence interval [CI] 1.5-3.6; 2 nodes, HR 1.3, 95% CI 0.6-3.0; 3 nodes, HR 3.0, 95% CI 1.1-8.0; ≥ 4 nodes, HR 4.0, 95% CI 2.5-6.2). Lymphadenectomy was associated with improved survival (HR 0.82, 95% CI 0.67-0.99).

CONCLUSIONS: Higher quantitative metastatic nodal burden is a robust prognostic factor for worse survival in ACC.

PMID:34792698 | DOI:10.1245/s10434-021-11051-5
Imaging findings of primary adrenal tumors in pediatric patients

Fetched: November 19th, 2021, 5:00am GMT by H Nursun Özcan

Diagn Interv Radiol. 2021 Nov;27(6):811-815. doi: 10.5152/dir.2021.20701.

ABSTRACT

Apart from neuroblastomas, adrenal tumors are rarely seen in children. The most common adrenal tumors are adrenocortical carcinoma and pheochromocytoma. Adrenocortical carcinoma is usually a large heterogeneous, well-marginated mass with solid/cystic areas and calcifications, with poor prognosis. Most of the pheochromocytomas are benign tumors and usually show intense contrast enhancement, the pattern of which may be diffuse, mottled, or peripheral on computed tomography and magnetic resonance imaging. The purpose of this article is to evaluate primary nonneurogenic adrenal tumors.

PMID:34792039 | DOI:10.5152/dir.2021.20701
Virilizing Adrenocortical Carcinoma Resected With Negative Margins Treated With Surgery Alone

Fetched: November 16th, 2021, 5:00am GMT by Tyler Fields

Am Surg. 2021 Nov 13:31348211050840. doi: 10.1177/00031348211050840. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma is a rare malignancy. A virilizing adrenocortical carcinoma is even more unique of a diagnosis. In this report, we present a rare case of this uncommon tumor with an interesting presentation, clearly documented physical exam changes over a span of at least 8 years, and a technically challenging case. We also briefly review the management of adrenocortical carcinoma. The tumor was successfully resected with no planned adjuvant treatment at this time. The patient had recurrence of menstrual cycle post-operatively and required no steroid supplementation.

PMID:34779264 | DOI:10.1177/00031348211050840
Adrenocortical Carcinoma in Childhood: A Systematic Review

Fetched: November 14th, 2021, 5:00am GMT by Maria Riedmeier

Cancers (Basel). 2021 Oct 20;13(21):5266. doi: 10.3390/cancers13215266.

ABSTRACT

Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%-local recurrence, 19% (n = 65)-distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.

PMID:34771430 | PMC:PMC8582500 | DOI:10.3390/cancers13215266
Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies

Fetched: November 14th, 2021, 5:00am GMT by Marco Lo Iacono

Cancers (Basel). 2021 Oct 20;13(21):5255. doi: 10.3390/cancers13215255.

ABSTRACT

Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. Although it is known that mitotane destroys the adrenal cortex and impairs steroidogenesis, its exact mechanism of action is still unclear. The most used cell models are H295-derived cell strains and SW13 cell lines. The diverging results obtained in presumably identical cell lines highlight the need for a stable in vitro model and/or a standard methodology to perform experiments on H295 strains. The presence of several enzymatic targets responsive to mitotane in mitochondria and mitochondria-associated membranes causes progressive alteration in mitochondrial structure when cells were exposed to mitotane. Confounding factors of culture affecting in vitro experiments could reduce the significance of any molecular mechanism identified in vitro. To ensure experimental reproducibility, particular care should be taken in the choice of culture conditions: aspects such as cell strains, culture serum, lipoproteins concentration, and culture passages should be carefully considered and explicated in the presentation of results. We aimed to review in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. If the concerns pointed out in this review will be overcome, the new insights into mitotane mechanism of action observed in-vitro could allow the identification of novel pharmacological molecular pathways to be used to implement personalized therapy.

PMID:34771418 | PMC:PMC8582505 | DOI:10.3390/cancers13215255
Bilateral adrenal hypermetabolism with (18)F-FDG PET/CT as an incidental finding in suspected recurrence of adrenocortical carcinoma

Fetched: November 10th, 2021, 5:01am GMT by J Márquez Fernández

Rev Esp Med Nucl Imagen Mol (Engl Ed). 2021 Nov-Dec;40(6):383-384. doi: 10.1016/j.remnie.2021.03.006. Epub 2021 Mar 18.

NO ABSTRACT

PMID:34752376 | DOI:10.1016/j.remnie.2021.03.006
The role of molecular profiling in adrenocortical carcinoma

Fetched: November 10th, 2021, 5:01am GMT by Juliane Lippert

Clin Endocrinol (Oxf). 2021 Nov 8. doi: 10.1111/cen.14629. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with still partially unknown pathogenesis, heterogenous clinical behaviour and no effective treatment for advanced stages. Therefore, there is an urgent clinical unmet need for better prognostication strategies, innovative therapies and significant improvement of the management of the individual patients. In this review, we summarize available studies on molecular prognostic markers and markers predictive of response to standard therapies as well as newly proposed drug targets in sporadic ACC. We include in vitro studies and available clinical trials, focusing on alterations at the DNA, RNA and epigenetic levels. We also discuss the potential of biomarkers to be implemented in a clinical routine workflow for improved ACC patient care.

PMID:34750847 | DOI:10.1111/cen.14629
Adrenocortical Cancer: A 20-Year Experience of a Single Referral Center in Prognosis and Outcomes

Fetched: November 6th, 2021, 5:00am GMT by Christos Parianos

Horm Metab Res. 2021 Nov;53(11):709-716. doi: 10.1055/a-1666-9026. Epub 2021 Nov 5.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare but very aggressive endocrine malignancy with poor survival. Histopathology is important for diagnosis, while in some cases immunohistochemical markers and gene profiling of the resected tumor may be superior to current staging systems to determine prognosis. We aimed to present the 20-year experience at a tertiary hospital in patients with ACCs and correlate the immunohistochemical characteristics of ACCs with the clinical and morphological characteristics of the tumors and the survival of the patients. Forty-five patients with ACC were included in the study. All the resections were R0. The tumor size and weight, the disease stage (ENSAT classification), Weiss score and Helsinki score were examined along with immunohistochemical expression of inhibin-A, melan A, calretinin, Ki67, synaptophysin, p53, vimentin, CKAE1/AE3. The male to female ratio was 1:1.37. The median age at diagnosis was 55.5 years (IQR 19-77). The median size of ACCs was 9 cm (IQR 3.5-22 cm) and the median weight 127 g (IQR 18-1400 g). The median follow up period was 18 months (IQR 1-96). Ki67 varied from<1% to 75% (median: 16.4%). The expression of melan-A and lower expression of Ki-67 (≤4) were independently associated with longer OS time (p=0.01 and p=0.04, respectively). In multivariable analysis, tumor volume>400 cm³ (p=0.046), Weiss score>5 (p=0.007) and overexpression of p53 (p=0.036) were independent risk factors for shorter survival. Adrenocortical carcinoma is a rare and very aggressive endocrine malignancy. The most important factors that determine long-term prognosis of ACC are the disease stage at diagnosis, the Weiss score, and the Ki67 index. Immunohistochemical markers such as melan A could also serve as prognostic factors.

PMID:34740271 | DOI:10.1055/a-1666-9026
EMX2OS plays a prognosis-associated enhancer RNA role in gastric cancer

Fetched: November 4th, 2021, 5:00am GMT by Ge-Xin Liu

Medicine (Baltimore). 2021 Oct 15;100(41):e27535. doi: 10.1097/MD.0000000000027535.

ABSTRACT

Enhancer RNAs (eRNAs), a subclass of lncRNAs, are derived from enhancer regions. The function of eRNAs has been reported by many previous studies. However, the role of eRNAs in gastric cancer, especially the prognosis-associated eRNAs, has not been studied yet.In this study, we have used a novel approach to screened key eRNAs in gastric cancer. Kaplan-Meier correlation analysis and Co-expression analysis were used to find the most significant survival-associated eRNAs. Enrichment analysis is applied to explore the key functions and pathways of screened eRNAs. The correlation and survival analysis are used to evaluate targeted genes in the pan-cancer analysisA total of 63 prognostic-associated eRNAs in gastric cancer were identified, the top 6 eRNAs were LINC01714, ZNF192P1, AC079760.2, LINC01645, EMX2OS, and AC114489.2. The correlation analysis demonstrated the top 10 screened eRNAs and their targeted genes. The results demonstrated that EMX2OS was ranked as the top eRNA according to the results of the Kaplan-Meier analysis. The correlation analysis demonstrated that eRNA EMX2OS is correlated with age, grade, stage, and cancer status. The pan-cancer analysis demonstrated that EMX2OS was associated with poor survival outcomes in adrenocortical carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, stomach adenocarcinoma, and uveal melanoma.In this study, survival-related eRNAs were screened and the correlation between survival-related eRNAs and their targeted genes was demonstrated. EMX2OS plays a prognosis-associated eRNA role in gastric cancer, which might be a novel therapeutic target in clinical practice.

PMID:34731149 | PMC:PMC8519253 | DOI:10.1097/MD.0000000000027535
The landscape of prognostic and immunological role of myosin light chain 9 (MYL9) in human tumors

Fetched: November 4th, 2021, 5:00am GMT by Minghe Lv

Immun Inflamm Dis. 2021 Nov 2. doi: 10.1002/iid3.557. Online ahead of print.

ABSTRACT

INTRODUCTION: Recent studies have shown that myosin light chain 9 (MYL9) plays a vital role in immune infiltration, tumor invasion, and metastasis; however, the prognostic and immunological role of MYL9 has not been reported. The purpose of this study was to explore the potential prognostic and immunological roles of MYL9 in human cancers by public datasets mainly including the cancer genome atlas (TCGA) and Gene expression omnibus.

METHODS: The expression pattern and prognostic value of MYL9 were analyzed across multiple public datasets in different cancer. The correlations between MYL9 expression and immune infiltration among multiple cancers were analyzed by using the TIMER2.0. The MYL9-related gene enrichment analysis was implemented by mainly using KEGG and GO datasets.

RESULTS: MYL9 was lowly expressed in most cancers, such as breast cancer, lung adenocarcinoma and squamous cell carcinoma, and stomach adenocarcinoma; but it was highly expressed in several cancers, such as cholangiocarcinoma, head and neck squamous cell carcinoma, and liver hepatocellular carcinoma. Furthermore, MYL9 expression was distinctively associated with prognosis in adrenocortical carcinoma, colon adenocarcinoma, brain glioma, lung cancer, ovarian cancer, gastric cancer, breast cancer, blood cancer, and prostate cancer patients. The expressions of MYL9 were significantly associated with the infiltration of cancer-associated fibroblasts, B cell, CD8⁺ T cell, CD4⁺ T cell, macrophage, neutrophil, dendritic cell in different tumors as well as immune markers. In addition, we found that the functional mechanisms of MYL9 involved muscle contraction and focal adhesion.

CONCLUSION: MYL9 can serve as a prognostic signature in pan-cancer and is associated with immune infiltration. This pan-cancer study is the first to show a relatively comprehensive understanding of the prognostic and immunological roles of MYL9 across different cancers.

PMID:34729929 | DOI:10.1002/iid3.557
Long non-coding RNA H19 expression correlates with autophagy process in adrenocortical carcinoma

Fetched: November 3rd, 2021, 5:00am GMT by Pietro Di Fazio

Cancer Invest. 2021 Nov 16:1-14. doi: 10.1080/07357907.2021.2001483. Online ahead of print.

ABSTRACT

Adrenocortical carcinoma (ACC) is characterized by poor prognosis and high mortality. The suppression of the long-non-coding RNA H19, counterbalanced by IGF2 over-expression, leads to down-regulation of the autophagy markers, high proliferation rate and metastatic potential in patients affected by ACC. The administration of the deacetylase inhibitors (DACi) panobinostat, trichostatin A (TSA) and SAHA affected the cell viability of H295R monolayer and spheroids and induced the over-expression of H19 and autophagy transcripts. H19 knock down in H295R cells was not able to modulate the expression level of autophagy transcripts. Instead, H19 knock down was able to impede the ability of DACi to modulate the protein level of the autophagy markers. Furthermore, the administration of higher concentration of DACi was able to down-regulate the protein level of Beclin1 and p62 and to induce the conversion of LC3B-I into the active LC3B-II form, thus confirming an active autophagic process. Neither the active protein level nor the activity of caspases 8 and 3 was prompted by the DACi, thus excluding the involvement of the executioners of apoptosis in H295R decay. The DACi restore H19, the autophagy markers and trigger cell death in ACC cells. The re-activation of autophagy would represent a novel strategy for the treatment of patients affected by this severe malignancy.

PMID:34726962 | DOI:10.1080/07357907.2021.2001483
Adrenocortical carcinoma

Fetched: November 3rd, 2021, 5:00am GMT by Masashi Hasebe

QJM. 2021 Nov 2:hcab276. doi: 10.1093/qjmed/hcab276. Online ahead of print.

NO ABSTRACT

PMID:34726762 | DOI:10.1093/qjmed/hcab276
Adrenocortical Carcinoma Treatment (Adult) (PDQ): Patient Version

Fetched: November 3rd, 2021, 5:00am GMT by PDQ Adult Treatment Editorial Board

2021 Oct 27. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–.

ABSTRACT

This PDQ cancer information summary has current information about the treatment of adult adrenocortical carcinoma. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Adult Treatment Editorial Board.

PMID:26389225 | Bookshelf:NBK65782
A comparison of robotic and laparoscopic minimally invasive adrenalectomy for adrenal malignancies

Fetched: November 2nd, 2021, 5:00am GMT by Jonathan J Hue

Surg Endosc. 2021 Nov 1. doi: 10.1007/s00464-021-08827-x. Online ahead of print.

ABSTRACT

BACKGROUND: Although guidelines recommend open adrenalectomy for most resectable adrenal malignancies, minimally invasive adrenalectomies are performed. Robotic adrenalectomies have become more popular recently, but there is a paucity of literature comparing laparoscopic and robotic resections.

METHODS: Patients who underwent a planned minimally invasive adrenalectomy for adrenal malignancies (adrenocortical carcinoma, malignant pheochromocytoma, other carcinoma) were identified in the National Cancer Database. The primary outcome was the conversion rate from minimally invasive to open. Other post-operative outcomes and survival were compared.

RESULTS: 416 patients (76.5%) underwent a laparoscopic adrenalectomy and 128 (23.5%) underwent a robotic operation. Demographics and clinical characteristics were similar. Approximately 19% of tumors resected by a minimally invasive approach were > 10 cm. The intra-operative conversion rate was decreased among robotic adrenalectomies relative to laparoscopic on univariate (7.8% vs. 18.3%, p = 0.005) and multivariable (odds ratio 0.39, p = 0.01) analyses. Using marginal standardization, there was a stepwise increase in the conversion rate as tumor size increased (< 5, 5-10, > 10 cm) for laparoscopic (7.5%, 18.0%, 33.2%) and robotic (3.1%, 8.3%, 17.3%) adrenalectomies. Operations which required conversion had a greater margin positivity rate, greater length of stay, and an association with poor overall survival.

CONCLUSION: In contrast to most clinical guidelines, minimally invasive adrenalectomies are being performed on large malignant tumors. A laparoscopic approach was associated with a greater conversion rate and subsequent poor outcomes. If a surgeon is not planning an open adrenalectomy, but adrenal malignancy is a possibility, robotic adrenalectomy may be the preferred approach for resectable adrenal tumors.

PMID:34724582 | DOI:10.1007/s00464-021-08827-x
Prognostic and Immunological Role of Key Genes of Ferroptosis in Pan-Cancer

Fetched: November 2nd, 2021, 5:00am GMT by Zhi-Zhou Shi

Front Cell Dev Biol. 2021 Oct 13;9:748925. doi: 10.3389/fcell.2021.748925. eCollection 2021.

ABSTRACT

Solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and apoptosis inducing factor mitochondria associated 2 (AIFM2) are the key regulators in ferroptosis. However, the expression patterns and prognostic roles of these genes in pan-cancer are still largely unclear. The expression patterns and prognostic roles of SLC7A11, GPX4, and AIFM2 and the relationships between the expression levels of these genes and immune infiltration levels in pan-cancer were analyzed by using TIMER, gene expression profiling interactive analysis (GEPIA), Oncomine, and Kaplan-Meier databases. Our results showed that both SLC7A11 and GPX4 were overexpressed in colorectal cancer, and SLC7A11 was overexpressed in lung cancer. High levels of SLC7A11 and AIFM2 were significantly linked with the shortened disease-free survival and overall survival (OS) in adrenocortical carcinoma (ACC), respectively. And high expression of SLC7A11, GPX4, and AIFM2 were significantly correlated with the shortened OS of acute myeloid leukemia patients. In esophageal carcinoma (ESCA), GPX4 expression was significantly associated with the infiltration of macrophage and myeloid dendritic cell, and AIFM2 expression was significantly associated with the infiltration of CD4⁺ T cell. Importantly, GPX4 expression was positively correlated with the expression levels of monocyte markers (CD14 and CD115) and M2 macrophage markers (VSIG4 and MS4A4A) both in ESCA and in head and neck squamous cell carcinoma (HNSC). In summary, SLC7A11, GPX4, and AIFM2 are dysregulated in many types of cancers, and are candidate prognostic biomarkers for many types of cancers, and can be used to evaluate the infiltration of immune cells in tumor tissues.

PMID:34722530 | PMC:PMC8548644 | DOI:10.3389/fcell.2021.748925
Yes-associated protein 1 as a prognostic biomarker and its correlation with telomerase in various cancers

Fetched: November 2nd, 2021, 5:00am GMT by Hye-Ran Kim

Osong Public Health Res Perspect. 2021 Oct;12(5):324-332. doi: 10.24171/j.phrp.2021.0207. Epub 2021 Sep 17.

ABSTRACT

OBJECTIVE: The aims of this study were to investigate the expression of Yes-associated protein 1 (YAP1), its prognostic significance, and the correlation between YAP1 and telomerase in various cancers.

METHODS: The Gene Expression Profiling Interactive Analysis database was used to analyze RNA sequencing data and the survival rate of patients with various cancers in The Cancer Genome Atlas (TCGA) database. PrognoScan was used to analyze the prognostic value of YAP1 expression in various cancers. Tumor Immune Estimation Resource was used to determine the correlation between YAP1 expression and telomerase in various cancer types based on TCGA data.

RESULTS: The analysis suggested that YAP1 was differentially expressed between tissues of various cancers and non-tumor tissues. High YAP1 expression was also related to a poor prognosis in adrenocortical carcinoma, bladder urothelial carcinoma, and pancreatic adenocarcinoma. Moreover, YAP1 expression was correlated with the expression of telomerase reverse transcriptase and telomerase RNA component in various cancer types.

CONCLUSION: These results suggest that YAP1 is a potential biomarker with prognostic significance and relevance for oncogene research in various cancer types. The correlation between the expression of YAP1 and telomere-associated genes will help to understand their cancer-promoting mechanisms and interactions.

PMID:34719224 | PMC:PMC8561022 | DOI:10.24171/j.phrp.2021.0207
S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study

Fetched: October 29th, 2021, 5:00am GMT by Yasir S Elhassan

Eur J Endocrinol. 2021 Oct 1:EJE-21-0510.R2. doi: 10.1530/EJE-21-0510. Online ahead of print.

ABSTRACT

OBJECTIVE: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on ENSAT tumour stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC.

DESIGN: Multicentre retrospective study on ACC patients who underwent adrenalectomy.

METHODS: The S-GRAS score was calculated as a sum of the following points: tumour Stage (1-2=0; 3=1; 4=2), Grade (Ki67 index 0-9%=0; 10-19%=1; ≥20%=2 points), Resection (R)-status (R0=0; RX=1; R1=2; R2=3), Age (<50yr=0; ≥50yr=1), Symptoms (no=0; yes=1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's C-index and Royston-Sauerbrei's R2D statistic.

RESULTS: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index=0.73, R2D=0.30, and C-index=0.79, R2D=0.45, respectively, all P<0.01 vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n=481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5.

CONCLUSION: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

PMID:34709200 | DOI:10.1530/EJE-21-0510
The Role of Adjuvant Radiotherapy in Non-Metastatic Adrenocortical Carcinoma: Analysis of a National Hospital-Based Registry

Fetched: October 28th, 2021, 5:00am GMT by E Chen

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e261. doi: 10.1016/j.ijrobp.2021.07.859.

ABSTRACT

PURPOSE/OBJECTIVE(S): Adrenocortical carcinoma (ACC) is a rare tumor, and the treatment paradigm has been largely based on small retrospective studies. The use of post-operative radiation therapy (PORT) is controversial. Using a national hospital-based registry, this study aims to further characterize the patient population who may benefit from PORT.

MATERIALS/METHODS: The National Cancer Database was queried for ACC by site and histology as specified by the ICD-O-3. Only patients with histologic confirmation were included. Patients with metastatic disease, non-oncologic surgical procedures, or death within 30 days of surgery were excluded. Patients were stratified by receipt of PORT. Those who received radiation to other sites, presumably for metastatic disease, were excluded. Analysis between groups was done by chi-square test, Fisher's exact test, and student's t-test. Optimal-full propensity score matching for the receipt of PORT was performed. Survival analysis was done using the Kaplan-Meier method with differences compared by the log-rank test. Cox-proportional hazards models were generated to determine significant predictors of survival.

RESULTS: A total of 1557 patients were diagnosed with ACC from 2004-2017. The mean age was 61.1 (40-90), 59% were female, the median follow up was 11.1 months, and 24.5% had distant metastasis. 755 patients with histologically confirmed non-metastatic ACC underwent oncologic surgery, with 95 (12.6%) receiving PORT. Compared to those who underwent surgery alone, patients who received PORT were more likely to have a diagnosis in 2009 or later (75.8 vs 46.4%; P < 0.0001), a Charlson Deyo comorbidity score (CDCC) of 0 (82.1 vs 67.7%; P = 0.004), a higher clinical T stage (20.0 vs 11.5%; P = 0.0004), a higher pathologic T stage (39.0 vs 18.6%; P < 0.0001), lymphovascular invasion (34.6 vs 15.0%; P < 0.0001), positive resection margins (37.9 vs 18.2%; P < 0.0001), and chemotherapy (51.6 vs 27.0%; P < 0.0001). On propensity matched analysis, patients who received PORT had worse median survival compared to those who underwent surgery alone (19.5 vs 22.8 months; P = 0.042). On multivariate analysis, factors associated with survival included clinical T4 stage (HR 2.06, 95% CI 1.01-4.19), CDCC > 0 (HR 1.28, 95% CI 1.02-1.60), and negative resection margins (HR 0.66, 95% CI 0.54-0.79); PORT was not significantly associated with survival (P = 0.65). There was no difference in survival between PORT and surgery alone even for patients with positive resection margins (HR 0.77 95% CI 0.52-1.15).

CONCLUSION: Use of PORT in treating ACC has significantly increased in recent years, especially for disease with high-risk features; however, results of our analysis suggest radiation therapy does not confer a survival benefit in the adjuvant setting. Given the rarity of the disease and lack of prospective randomized data, the decision for PORT should be individualized.

PMID:34701038 | DOI:10.1016/j.ijrobp.2021.07.859
Radiomic Feature Changes in Adrenal Lesions Treated With MR-Guided Stereotactic Body Radiation Therapy

Fetched: October 28th, 2021, 5:00am GMT by M N Mills

Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):S98-S99. doi: 10.1016/j.ijrobp.2021.07.229.

ABSTRACT

PURPOSE/OBJECTIVE(S): Magnetic resonance image guided stereotactic body radiotherapy (MRgSBRT) is an advanced technology that may provide radiomic feature changes during treatment of adrenal lesions feasible for adaptation.

MATERIALS/METHODS: A prospectively maintained database was retrospectively reviewed for 24 patients with adrenal lesions who underwent MRgSBRT. Histogram features (n = 7, Table 1) were extracted from MRgSBRT images (TRueFISP sequence, 1.5mm/3mm voxel size/slice thickness) from adrenal malignancy patients scanned at simulation (SIM) approximately 14 days before SBRT start, and prior to each of 5 daily fractions (F1-F5) of 8-12 Gy to Gross Tumor Volume (GTV). Tumor ROI was derived by 3mm radial erosion of GTV in 3D. Each scan was divided by median intensity in kidney for image normalization. Significance of changes SIM-F1 and F1-F5 were assessed using two-sided paired t-test. Response to treatment was assessed via follow up CT scan roughly 3 months after MRgSBRT via RECIST v1.1, with overall response rate (ORR) including complete and partial response. Radiomics features were tested for association with clinical variables using the Kruskal-Wallis test.

RESULTS: Patients had a median age of 67 years (19-80). The majority of adrenal lesions were metastatic sites (88%), while there were 2 patients with primary adrenocortical carcinoma and 1 patient with pheochromocytoma. All patients were treated with MRgSBRT in 5 fractions to a median dose of 50 Gy (40-60). Of 23 evaluable cases, rates of complete response (CR), partial response (PR), and stable disease (SD) were 13%, 35%, and 52%, respectively. Median follow up was 9.7 months (1-22). Significant changes in MRgSBRT of the tumors were observed after treatment (F1-F5, Table 1) with an increase in image signal median and interquartile range (IQR) consistent with radiation response. No signal changes were seen prior to treatment (SIM-F1). Erosion of GTV to remove tissue borders was required to observe the changes F1-F5 (P = 0.08 median,0.67 IQR for full GTV volume). For association to outcome considering varying dose per fraction, signal ratios were calculated between F1 and fraction closest to 40 Gy cumulative dose. There was a significant relationship between IQR ratio and ORR (CR/PR cases: mean 0.94 ± 0.03, SD cases: mean 1.11 ± 0.06, P = 0.011).

CONCLUSION: Significant increases in image signal median and IQR were identified in patients with adrenal lesions undergoing MRgSBRT, consistent with radiation response. MRgSBRT radiomic feature changes may allow for better personalization of radiotherapy going forward.

PMID:34700674 | DOI:10.1016/j.ijrobp.2021.07.229
Pan-cancer analysis reveals the expression, genetic alteration and prognosis of pyroptosis key gene GSDMD

Fetched: October 27th, 2021, 5:00am GMT by Shizheng Qiu

Int Immunopharmacol. 2021 Oct 29;101(Pt A):108270. doi: 10.1016/j.intimp.2021.108270. Online ahead of print.

ABSTRACT

BACKGROUND: Gasdermins (GSDMs)-mediated pyroptosis is widely involved in activating anti-tumor immunity and suppressing tumor growth. However, whether gasdermin D (GSDMD)-mediated pyroptosis affects patient prognosis in pan-cancer remains unknown.

METHODS: We performed analyses of the RNA expression, genetic alteration, prognosis and immune infiltration of GSDMD in pan-cancer. In order to explore the relationship between pyroptosis and tumors, we calculated the correlation between GSDMD and pyroptosis key genes in pan-cancer. We also investigated the enrichment pathway of GSDMD-related genes.

RESULTS: GSDMD was differentially expressed in the vast majority of cancer, and could be used as a prognostic marker in adrenocortical carcinoma (ACC), kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), skin cutaneous melanoma (SKCM) and rectum adenocarcinoma (READ). Strong evidence indicated the significant correlation of GSDMD with almost all immune checkpoints and immune cells. Pyroptosis-related genes strongly associated with GSDMD in ACC, KIRC, LGG, LIHC and SKCM, suggesting that GSDMD-mediated pyroptosis might play a critical role in the five cancers.

CONCLUSION: All the evidence supported the potential role of GSDMD-mediated pyroptosis in cancer. Our results provided new insights into GSDMD as a prognostic marker and potential therapeutic target for cancer.

PMID:34700129 | DOI:10.1016/j.intimp.2021.108270
Informing therapeutic lymphadenectomy: Location of regional metastatic lymph nodes in adrenocortical carcinoma

Fetched: October 27th, 2021, 5:00am GMT by Alaa Sada

Am J Surg. 2021 Oct 19:S0002-9610(21)00604-8. doi: 10.1016/j.amjsurg.2021.10.014. Online ahead of print.

ABSTRACT

BACKGROUND: The anatomic boundaries of lymphadenectomy for adrenocortical carcinoma (ACC) are not defined.

METHODS: Adults undergoing resection of ACC were included. Locations were categorized based on positive LN locations on final pathology.

RESULTS: Of 231 resected ACC, 6% had positive LN during initial resection. Positive LN in left ACC (n = 7) were: 2 para-aortic, 2 left renal-hilar, 1 para-aortic and left renal-hilar and 1 unknown, while for right ACC (n = 7): 2 para-caval, 1 para-caval and right renal-hilar, 1 inter-aortocaval, 1 celiac, 1 para-aortic, and 1 unknown. Of 55 resections for recurrent ACC, positive LN in left ACC (n = 2) were: 1 para-aortic, and 1 para-aortic with left renal-hilar, while LN for right ACC (n = 7): 2 inter-aortocaval, 2 right renal-hilar, 2 para-caval and one retrocrural.

CONCLUSION: The most common LN metastases are para-caval for right, and para-aortic and left renal-hilar for left ACC. Further studies are necessary to determine the boundaries of lymphadenectomy in ACC resection.

PMID:34696848 | DOI:10.1016/j.amjsurg.2021.10.014
Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Fetched: October 26th, 2021, 5:00am GMT by Ji-Yong Sung

Int J Mol Sci. 2021 Oct 14;22(20):11101. doi: 10.3390/ijms222011101.

ABSTRACT

Understanding the telomere maintenance mechanism (TMM) in immortal cancer cells is vital for TMM-targeted therapies in clinical settings. In this study, we classified four telomere maintenance mechanisms into telomerase, ALT, telomerase + ALT, and non-defined telomere maintenance mechanism (NDTMM) across 31 cancer types using 10,704 transcriptomic datasets from The Cancer Genome Atlas. Our results demonstrated that approximately 50% of the total cohort displayed ALT activity with high telomerase activity in most cancer types. We confirmed significant patient prognoses according to distinct TMMs in six cancer types: adrenocortical carcinoma (ACC), PAAD, HNSC, SARC, GBM, and metastatic cancer. Patients with metastasis had a poor prognosis in the ALT group (p < 0.006) subjected to RAS protein signal transduction. Glioblastoma patients had poor prognosis in NDTMM (p < 0.0043) and showed high levels of myeloid leukocyte activation. Pancreatic adenocarcinoma (p < 0.04) and head and neck squamous cell carcinoma (p < 0.046) patients had a good prognosis in the ALT group with high immune cell activation. Furthermore, we showed that master transcriptional regulators might affect the selection of the TMM pathway and explained why different telomere maintenance mechanisms exist. Furthermore, they can be used to segregate patients and predict responders to different TMM-targeted therapeutics.

PMID:34681758 | PMC:PMC8538844 | DOI:10.3390/ijms222011101
ATP1A1 Mutant in Aldosterone-Producing Adenoma Leads to Cell Proliferation

Fetched: October 26th, 2021, 5:00am GMT by Kazuhiro Kobuke

Int J Mol Sci. 2021 Oct 12;22(20):10981. doi: 10.3390/ijms222010981.

ABSTRACT

The molecular mechanisms by which ATP1A1 mutation-mediated cell proliferation or tumorigenesis in aldosterone-producing adenomas (APAs) have not been elucidated. First, we investigated whether the APA-associated ATP1A1 L104R mutation stimulated cell proliferation. Second, we aimed to clarify the molecular mechanisms by which the ATP1A1 mutation-mediated cell proliferated. We performed transcriptome analysis in APAs with ATP1A1 mutation. ATP1A1 L104R mutation were modulated in human adrenocortical carcinoma (HAC15) cells (ATP1A1-mutant cells), and we evaluated cell proliferation and molecular signaling events. Transcriptome and immunohistochemical analysis showed that Na/K-ATPase (NKA) expressions in ATP1A1 mutated APA were more abundant than those in non-functioning adrenocortical adenoma or KCNJ5 mutated APAs. The significant increase of number of cells, amount of DNA and S-phase population were shown in ATP1A1-mutant cells. Fluo-4 in ATP1A1-mutant cells were significantly increased. Low concentration of ouabain stimulated cell proliferation in ATP1A1-mutant cells. ATP1A1-mutant cells induced Src phosphorylation, and low concentration of ouabain supplementation showed further Src phosphorylation. We demonstrated that NKAs were highly expressed in ATP1A1 mutant APA, and the mutant stimulated cell proliferation and Src phosphorylation in ATP1A1-mutant cells. NKA stimulations would be a risk factor for the progression and development to an ATP1A1 mutant APA.

PMID:34681640 | PMC:PMC8537586 | DOI:10.3390/ijms222010981
Immunotherapies in Genitourinary Oncology: Where Are We Now? Where Are We Going?

Fetched: October 26th, 2021, 5:00am GMT by Albert Jang

Cancers (Basel). 2021 Oct 10;13(20):5065. doi: 10.3390/cancers13205065.

ABSTRACT

For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette-Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials.

PMID:34680214 | PMC:PMC8533722 | DOI:10.3390/cancers13205065
Castration failure in prostate carcinoma due to a functioning adrenocortical carcinoma

Fetched: October 26th, 2021, 5:00am GMT by Vishal Navani

Endocrinol Diabetes Metab Case Rep. 2021 Oct 1;2021:21-0036. doi: 10.1530/EDM-21-0036. Online ahead of print.

ABSTRACT

SUMMARY: We report concurrent metastatic prostatic adenocarcinoma (PC) and functioning androgen-secreting adrenocortical carcinoma (ACC) in a 77-year-old man. The failure to achieve adequate biochemical castration via androgen deprivation therapy (ADT) as treatment for PC metastases, together with elevated DHEA-S, androstenedione, and discordant adrenal tracer uptake on FDG-PET and PSMA-PET, suggested the presence of a concurrent functional primary adrenal malignancy. On histopathological analysis, scant foci of PC were present throughout the ACC specimen. Castration was achieved post adrenalectomy with concurrent drop in prostate-specific antigen. We outline the literature regarding failure of testosterone suppression on ADT and salient points regarding diagnostic workup of functioning adrenal malignancies.

LEARNING POINTS: Failure to achieve castration with androgen deprivation therapy is rare and should prompt careful review to identify the underlying cause. All adrenal lesions should be evaluated for hormone production, as well as assessed for risk of malignancy (either primary or secondary). Adrenocortical carcinomas are commonly functional, and can secrete steroid hormones or their precursors (androgens, progestogens, glucocorticoids and mineralocorticoids). In this case, a co-incident, androgen-producing adrenocortical carcinoma was the cause of failure of testosterone suppression from androgen deprivation therapy as treatment for metastatic prostate cancer. Pathological adrenal androgen production contributed to the progression of prostate cancer.

PMID:34673545 | PMC:PMC8558880 | DOI:10.1530/EDM-21-0036

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