Rare Cancer News & Clinical Trials

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Permalink for 'Erratum: [Corrigendum] PF‑2341066 combined with celecoxib promotes apoptosis and inhibits proliferation in human cholangiocarcinoma QBC939 cells'

Erratum: [Corrigendum] PF‑2341066 combined with celecoxib promotes apoptosis and inhibits proliferation in human cholangiocarcinoma QBC939 cells

Fetched: February 17th, 2024, 5:00am GMT by Chen Chen

Exp Ther Med. 2024 Jan 24;27(3):111. doi: 10.3892/etm.2024.12399. eCollection 2024 Mar.

ABSTRACT

[This corrects the article DOI: 10.3892/etm.2018.5967.].

PMID:38361523 | PMC:PMC10867725 | DOI:10.3892/etm.2024.12399

Characterizing the burden of biliary tract cancers across 28 hospitals in Ontario, Canada

Fetched: February 17th, 2024, 5:00am GMT by Woo Jin Choi

Cancer. 2024 Feb 15. doi: 10.1002/cncr.35249. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The incidence of biliary tract cancers (BTC) appears to be increasing worldwide. We analyzed the characteristics of BTC-related hospitalizations under medical services across 28 hospitals in Ontario, Canada.

METHODS: This study uses data collected by GEMINI, a hospital research data network. BTC-related hospitalizations from 2015 to 2021 under the Department of Medicine or intensive care unit were captured using the International Classification of Diseases, 10th revision, codes for intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, and gallbladder cancers.

RESULTS: A total of 4596 BTC-related hospitalizations (2720 iCCA, 1269 extrahepatic cholangiocarcinoma, 607 gallbladder cancers) were analyzed. The number of unique patients with BTC-related hospitalizations increased over time. For iCCA-related hospitalizations, the total number of hospitalizations increased (from 385 in 2016 to 420 in 2021, p = .005), the hospital length of stay decreased over the study period (mean 10 days [SD, 12] in 2016 to 9 days [SD, 8] in 2021, p = .04), and the number of in-hospital deaths was stable (from 68 [18%] in 2016 to 55 [13%] in 2021, p = .62). Other outcomes such as 30-day readmissions, medical imaging tests, intensive care unit-specific hospitalizations, and length of stay were stable over time for all cohorts. The cost of hospitalization for the BTC cohort increased from median $8203 CAD (interquartile range, 5063-15,543) in 2017 to $8507 CAD (interquartile range, 5345-14,755) in 2021.

CONCLUSIONS: This real-world data analysis showed a rising number of patients with BTC-related hospitalizations and rising number of iCCA-related hospitalizations across 28 hospitals in Ontario between 2015 and 2021.

PMID:38361443 | DOI:10.1002/cncr.35249

Novel Adiponectin Receptor Agonist Inhibits Cholangiocarcinoma via Adenosine Monophosphate-activated Protein Kinase

Fetched: February 17th, 2024, 5:00am GMT by Khac Cuong Bui

Curr Med Chem. 2024 Jan 23. doi: 10.2174/0109298673254969231122114107. Online ahead of print.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) has a poor prognosis and only limited palliative treatment options. The deficiency of adiponectin and adenosine monophosphate-activated protein kinase (AMPK) signaling was reported in several malignancies, but the alteration of these proteins in CCA is still unclear.

OBJECTIVES: This study aimed to assess the role of adiponectin and AMPK signaling in CCA. Furthermore, AdipoRon, a novel adiponectin receptor (AdipoR) agonist, was evaluated in vitro and in vivo as a new anti-tumor therapy for CCA.

METHODS: The expression of AdipoR1 and p-AMPKα in human tissue microarrays (TMAs) was evaluated by immunohistochemistry staining (IHC). The effect of 2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)- 4-piperidinyl]-acetamide (AdipoRon) was investigated in vitro with proliferation, crystal violet, migration, invasion, colony formation, senescence, cell cycle and apoptosis assays and in vivo using a CCA engineered mouse model (AlbCre/LSL-KRASG12D/p53L/L). RT-qPCR and western blot methods were applied to study molecular alterations in murine tissues.

RESULTS: AdipoR1 and p-AMPKα were impaired in human CCA tissues, compared to adjacent non-tumor tissue. There was a positive correlation between the AdipoR1 and p-AMPKα levels in CCA tissues. Treatment with AdipoRon inhibited proliferation, migration, invasion and colony formation and induced apoptosis in a time- and dose-dependent manner in vitro(p<0.05). In addition, AdipoRon reduced the number of CCA and tumor volume, prolonged survival, and decreased metastasis and ascites in the treated group compared to the control group (p<0.05).

CONCLUSIONS: AdipoR1 and p-AMPKα are impaired in CCA tissues, and AdipoRon effectively inhibits CCA in vitro and in vivo. Thus, AdipoRon may be considered as a potential anti-tumor therapy in CCA.

PMID:38361349 | DOI:10.2174/0109298673254969231122114107

Advances in targeted therapy of cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Yuhang Li

Ann Med. 2024 Dec;56(1):2310196. doi: 10.1080/07853890.2024.2310196. Epub 2024 Feb 15.

ABSTRACT

Cholangiocarcinoma (CCA) is a malignant tumor originating in the bile duct and its branching epithelium. Due to its high heterogeneity, there are no specific clinical indications at the early stage, the diagnosis is often in advanced CCA. With surgical resection, the 5-year postoperative survival rate (long-term survival rate) is very poor. The regimen of gemcitabine combined with platinum has been used as the first-line chemotherapy for advanced patients. In recent years, targeted therapy for a variety of malignant tumors has made great progress, showing good efficacy and safety in advanced CCA. However, the current targeted therapy of CCA still has many challenges, such as adverse reactions, drug resistance, and individual differences. Therefore, the researches need to further explore the targeted therapy mechanism of CCA malignancies in depth, develop more effective and safe drugs, and accurately formulate plans based on patient characteristics to further improve patient prognosis in the future. This article reviews the recent progress of targeted therapy for CCA, aiming to provide a strategy for the research and clinical work of targeted therapy for CCA.

PMID:38359439 | PMC:PMC10877652 | DOI:10.1080/07853890.2024.2310196

Biliary Disorders, Anomalies, and Malignancies in Children

Fetched: February 16th, 2024, 5:01am GMT by Curtis L Simmons

Radiographics. 2024 Mar;44(3):e230109. doi: 10.1148/rg.230109.

ABSTRACT

Biliary abnormalities in children are uncommon, and the spectrum of biliary disorders is broader than in adult patients. Unlike in adults, biliary disorders in children are rarely neoplastic and are more commonly rhabdomyosarcoma rather than cholangiocarcinoma. Pediatric biliary disorders may be embryologic or congenital, such as anatomic gallbladder anomalies, anomalous pancreaticobiliary tracts, various cholestatic processes, congenital cystic lesions, or genetic conditions. They may also be benign, such as biliary filling anomalies, biliary motility disorders, and biliary inflammatory and infectious disorders. Distinguishing these entities with a single imaging modality is challenging. US is the primary imaging modality for initial evaluation of biliary abnormalities in children, due to its wide availability, lack of ionizing radiation, and low cost and because it requires no sedation. Other examinations such as MRI, CT, and nuclear medicine examinations may provide anatomic and functional information to narrow the diagnosis further. Hepatobiliary-specific contrast material with MRI can provide better assessment of biliary anatomy on delayed images than can traditional MRI contrast material. MR cholangiopancreatography (MRCP) allows visualization of the intra- and extrahepatic biliary ducts, which may not be possible with endoscopic retrograde cholangiopancreatography (ERCP). Suspected biliary atresia requires multiple modalities for diagnosis and timely treatment. Determining the type of choledochal cyst calls for a combination of initial US and MRCP. Many benign and malignant biliary masses require biopsy for definitive diagnosis. Knowledge of the imaging appearances of different pediatric biliary abnormalities is necessary for appropriate imaging workup, providing a diagnosis or differential diagnosis, and guiding appropriate management. ^©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

PMID:38358937 | DOI:10.1148/rg.230109

FATP5 is indispensable for the growth of intrahepatic cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Diyala Shihadih

Mol Cancer Res. 2024 Feb 15. doi: 10.1158/1541-7786.MCR-23-0389. Online ahead of print.

ABSTRACT

Altered lipid metabolism is a common hallmark of various cancers, including Intrahepatic Cholangiocarcinoma (ICC), a highly lethal carcinoma that lacks effective treatment options. To elucidate the lipid metabolism changes in ICC, we coupled the expression of the firefly luciferase gene (FFL) to AKT1 (AKT-FFL) via an IRES linker, and then hydrodynamically injected mice with AKT-FFL and Notch1 intracellular cytoplasmic domain (NICD) to establish a luciferase-positive ICC model. This model not only enabled us to monitor and quantify tumor growth by injecting the mice with luciferin, but also allowed us to assess the fatty acid uptake rate by injecting the mice with free fatty acid luciferin (FFA-Luc). The ICC model exhibited robust uptake of exogenous fatty acids compared with the HCC model induced by AKT-FFL/ neuroblastoma Ras (Ras). Lipidomics analysis showed a dramatically higher level of fatty acid in ICC, further supporting the increased fatty acids uptake. Mechanistic studies identified FATP5 as the predominant mediator of fatty acid uptake required for ICC growth using Fatp5 knockout mice and AAV-based shRNA silencing of Fatp5. Our study discovered a novel therapeutic target for the treatment of ICC and shed light on the contributions of lipid metabolism to ICC development. Implications: This study provides the first in vivo evidence that FATP5 is a potential therapeutic target for treating ICC.

PMID:38358323 | DOI:10.1158/1541-7786.MCR-23-0389

Pancreatic Resection for Pancreatic Tumors our Experience at Suburban Hospital

Fetched: February 16th, 2024, 5:01am GMT by Prabhat B Nichkaode

Ann Afr Med. 2023 Oct-Dec;22(4):537-543. doi: 10.4103/aam.aam_165_22.

ABSTRACT

INTRODUCTION: Resection of pancreatic tissue is necessary for many pancreatic diseases. The most common form of cancer, pancreatic duct adenocarcinoma, manifests with early metastases and is thought to be resistant to other currently known treatment regimens. Such tumors present a complex and difficult management and handling challenge for a surgeon. Surgical resection affords a better prognosis with a median survival of 14-20 months following resection and up to 25% 5-year survival rates. In this study, data from 75 pancreatic resections for diverse malignant pancreatic lesions will be presented.

METHODS: At a teaching institute in Central India, this ongoing longitudinal study began in 2009 and was carried on till 2018. Only 75 of the 122 patients who underwent pancreatic resection were deemed appropriate for the current study. All patients were thoroughly examined after being admitted before being given the option of surgery. There were 22 female patients and 53 male patients. The age range for the group was 34-67 years. Results from a range of different malignancies and various pancreatic resection procedures are presented in this study.

RESULTS: One of the most aggressive cancers, pancreatic adenocarcinoma, responds to surgical treatment better than other alternative techniques. Out of 75 patients in our series, 32 had pancreatic head cancer, 28 had periampullary cancer, 2 had duodenal cancer, 8 had distal cholangiocarcinoma, and 1 had mucin-producing cystadenocarcinoma. Four patients had pancreatic cancer in both the body and tail. Fifty-three men and 22 women, ages 34-67 years, Whipple's operation and distal pancreatectomy were the most frequent procedures. In our series, survival ranged from 18 to 24 months, and the 5-year survival rate was 12%, which is primarily seen with periampullary carcinoma.

CONCLUSION: The sole option for long-term survival or a cure for pancreatic cancer is surgery. Chemoradiation is ineffective as a first line of treatment. However, some reports contend that palliative chemotherapy actually improves the quality of life. The biology of the illness rules and determines the result; the kind of surgery performed had no bearing on survival, morbidity, or fatality.

CONTEXT: The above study was taken up in the context of - pancreatic tumors and pathological types, how imaging helps in deciding the plan of surgical management without biopsy. Outcomes of pancreatic resections for pancreatic cancer.

SETTINGS AND DESIGN: In a suburban hospital which is a tertiary care center, this longitudinal prospective study was conducted from 2009 to 2018.

PMID:38358158 | PMC:PMC10775925 | DOI:10.4103/aam.aam_165_22

Permalink for 'Cholangiocarcinoma across England: Temporal changes in incidence, survival and routes to diagnosis by region and level of socioeconomic deprivation'

Cholangiocarcinoma across England: Temporal changes in incidence, survival and routes to diagnosis by region and level of socioeconomic deprivation

Fetched: February 16th, 2024, 5:01am GMT by Daniela Tataru

JHEP Rep. 2023 Dec 15;6(3):100983. doi: 10.1016/j.jhepr.2023.100983. eCollection 2024 Mar.

ABSTRACT

BACKGROUND & AIMS: While cholangiocarcinoma (CCA) incidence and mortality rates are increasing globally, whether there are regional/temporal variations in these rates for different biliary tract cancer (BTC) subtypes, or whether they differ by sex, socioeconomic status, or route to diagnosis (RtD) remains unknown. In this work, we aimed to perform an in-depth analysis of data on the incidence, mortality, survival and RtD of CCA and other BTCs.

METHODS: Data on all BTCs diagnosed in England between 2001 and 2018 were extracted from NHS Digital's National Cancer Registration Dataset. Age-standardised incidence rates (ASRs), mortality rates (ASMRs) and net survival rates were calculated, and Kaplan-Meier overall survival estimates and RtD trends were analysed. Analyses were stratified by sex, socioeconomic deprivation, tumour subtype and region.

RESULTS: The ASR for CCA rose from 2.9 in 2001-2003 to 4.6 in 2016-2018 and from 1.0 to 1.8 for gallbladder cancers (GBCs). ASMR trends mirror those of incidence, with most deaths due to iCCA. Over 20% of patients with CCA were under 65 years old. The ASRs and ASMRs were consistently higher in the most socioeconomically deprived group for CCA and GBC. The most common RtD was the emergency route (CCA 49.6%, GBC 46.2% and ampulla of Vater cancer 43.0%). The least deprived patients with CCA and ampulla of Vater cancer had better overall survival (p <0.001). Net survival rates rose for all BTCs, with 3-year net survival for CCA increasing from 9.2% in 2001 to 12.6% in 2016-2018. There was notable geographical variation in ASRs, ASMRs and net survival for all BTCs.

CONCLUSIONS: BTC incidence and mortality rates are increasing, with differences observed between tumour types, socioeconomic deprivation groups, RtDs and geographical regions. This highlights the need for targeted interventions, earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals.

IMPACT AND IMPLICATIONS: Cholangiocarcinoma (CCA) incidence and mortality rates are rising globally, particularly for intrahepatic CCA. However, it has not previously been reported if, within a single country, there are temporal and regional differences in incidence, mortality and survival rates for different biliary tract subtypes, and whether these differ by sex, socioeconomic status, or route of diagnosis. In this study we show that mortality rates for patients with CCA continue to rise and are almost 40% higher in the most socioeconomically deprived compared to the least; additionally, we observed regional variation within England in incidence, mortality and survival. This study is relevant to researchers and policy makers as it highlights regional variation and inequality, as well as emphasising the need for earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals.

PMID:38357420 | PMC:PMC10865079 | DOI:10.1016/j.jhepr.2023.100983

Associations between income and survival in cholangiocarcinoma: A comprehensive subtype-based analysis

Fetched: February 16th, 2024, 5:01am GMT by Calvin X Geng

Ann Hepatobiliary Pancreat Surg. 2024 Feb 15. doi: 10.14701/ahbps.23-136. Online ahead of print.

ABSTRACT

BACKGROUNDS/AIMS: Socioeconomic determinants of health are incompletely characterized in cholangiocarcinoma (CCA). We assessed how socioeconomic status influences initial treatment decisions and survival outcomes in patients with CCA, additionally performing multiple sub-analyses based on anatomic location of the primary tumor.

METHODS: Observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results (SEER)-18 Database. In total, 5,476 patients from 2004-2015 with a CCA were separated based on median household income (MHI) into low income (< 25th percentile of MHI) and high income (> 25th percentile of MHI) groups. Seventy-three percent of patients had complete follow up data, and were included in survival analyses. Survival and treatment outcomes were calculated using R-studio.

RESULTS: When all cases of CCA were included, the high-income group was more likely than the low-income to receive surgery, chemotherapy, and local tumor destruction modalities. Initial treatment modality based on income differed significantly between tumor locations. Patients of lower income had higher overall and cancer-specific mortality at 2 and 5 years. Non-cancer mortality was similar between the groups. Survival differences identified in the overall cohort were maintained in the intrahepatic CCA subgroup. No differences between income groups were noted in cancer-specific or overall mortality for perihilar tumors, with variable differences in the distal cohort.

CONCLUSIONS: Lower income was associated with higher rates of cancer-specific mortality and lower rates of surgical resection in CCA. There were significant differences in treatment selection and outcomes between intrahepatic, perihilar, and distal tumors. Population- based strategies aimed at identifying possible etiologies for these disparities are paramount to improving patient outcomes.

PMID:38356257 | DOI:10.14701/ahbps.23-136

Permalink for 'Clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling of patients with biliary tract cancer, especially with intrahepatic cholangiocarcinoma'

Clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling of patients with biliary tract cancer, especially with intrahepatic cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Takafumi Yanaidani

Clin Endosc. 2024 Feb 15. doi: 10.5946/ce.2023.139. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC.

METHODS: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022.

RESULTS: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy.

CONCLUSIONS: EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

PMID:38356172 | DOI:10.5946/ce.2023.139

Permalink for 'Systemic chemotherapy plus transarterial chemoembolization versus systemic chemotherapy alone for unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study'

Systemic chemotherapy plus transarterial chemoembolization versus systemic chemotherapy alone for unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study

Fetched: February 16th, 2024, 5:01am GMT by Nan Jiang

Radiol Med. 2024 Feb 15. doi: 10.1007/s11547-024-01781-3. Online ahead of print.

ABSTRACT

PURPOSE: Systemic chemotherapy (SYS) is the first-line treatment of unresectable intrahepatic cholangiocarcinoma (ICC). However, the survival benefit of SYS is still limited. This study compared the efficacy and safety of patients with unresectable ICC treated with transarterial chemoembolization (TACE) plus SYS to SYS alone.

MATERIAL AND METHODS: The multicenter retrospective cohort study included patients aged ≥ 18 years old with pathologically diagnosed ICC. Patients with unmeasurable lesions, not receiving SYS treatment, Child-Pugh grade C, Eastern Cooperative Oncology Group performance status score of 3 or higher, prior liver resection, incomplete medical information, or discontinuation of the first SYS treatment were excluded. Data collection was mainly from the hospital system, and the survival outcome of patients was obtained through follow-up. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Propensity score matching at a 1:1 ratio using the nearest neighbor matching algorithm was performed to reduce selection bias between the TACE plus SYS and SYS alone groups. The Cox proportional hazards model was used to identify prognostic factors associated with OS and to estimate their hazard ratios. Modified Response Evaluation Criteria in Solid Tumors criteria were utilized to evaluate the response of tumors to therapy.

RESULTS: Between June 2016 and February 2023, 118 unresectable ICC patients from three hospitals were included in this study. Of them, 37 were in the TACE plus SYS group and 81 were in the SYS alone group. The median OS in the combination group was 11.3 months, longer than the 6.4 months in the SYS alone group (P = 0.011). A greater objective response rate (ORR) and disease control rate (DCR) were observed in the combination group than in the SYS alone group (ORR, 48.65 vs. 6.17%, P < 0.001; DCR, 89.19 vs. 62.96%, P = 0.004). There were 16 patients in each group after matching, and the matched results remained consistent regarding OS and tumor response. Adverse events (AEs) were similar in the two groups after matching.

CONCLUSION: Compared to SYS alone, the combination treatment of TACE plus SYS was more effective than SYS alone in improving OS, ORR, and DCR without any significant increase in AEs. TACE plus SYS may be a viable treatment option for patients with unresectable ICC.

PMID:38355907 | DOI:10.1007/s11547-024-01781-3

Permalink for 'Comparison contrast-enhanced CT with contrast-enhanced US in diagnosing combined hepatocellular-cholangiocarcinoma: a propensity score-matched study'

Comparison contrast-enhanced CT with contrast-enhanced US in diagnosing combined hepatocellular-cholangiocarcinoma: a propensity score-matched study

Fetched: February 16th, 2024, 5:01am GMT by Jie Yang

Insights Imaging. 2024 Feb 14;15(1):44. doi: 10.1186/s13244-023-01576-6.

ABSTRACT

OBJECTIVES: To develop and compare noninvasive models for differentiating between combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and HCC based on serum tumor markers, contrast-enhanced ultrasound (CEUS), and computed tomography (CECT).

METHODS: From January 2010 to December 2021, patients with pathologically confirmed cHCC-CCA or HCC who underwent both preoperative CEUS and CECT were retrospectively enrolled. Propensity scores were calculated to match cHCC-CCA and HCC patients with a near-neighbor ratio of 1:2. Two predicted models, a CEUS-predominant (CEUS features plus tumor markers) and a CECT-predominant model (CECT features plus tumor markers), were constructed using logistic regression analyses. Model performance was evaluated by the area under the curve (AUC), sensitivity, specificity, and accuracy.

RESULTS: A total of 135 patients (mean age, 51.3 years ± 10.9; 122 men) with 135 tumors (45 cHCC-CCA and 90 HCC) were included. By logistic regression analysis, unclear boundary in the intratumoral nonenhanced area, partial washout on CEUS, CA 19-9 > 100 U/mL, lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT were independent factors for a diagnosis of cHCC-CCA. The CECT-predominant model showed almost perfect sensitivity for cHCC-CCA, unlike the CEUS-predominant model (93.3% vs. 55.6%, p < 0.001). The CEUS-predominant model showed higher diagnostic specificity than the CECT-predominant model (80.0% vs. 63.3%; p = 0.020), especially in the ≤ 5 cm subgroup (92.0% vs. 70.0%; p = 0.013).

CONCLUSIONS: The CECT-predominant model provides higher diagnostic sensitivity than the CEUS-predominant model for CHCC-CCA. Combining CECT features with serum CA 19-9 > 100 U/mL shows excellent sensitivity.

CRITICAL RELEVANCE STATEMENT: Combining lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT with serum CA 19-9 > 100 U/mL shows excellent sensitivity in differentiating cHCC-CCA from HCC.

KEY POINTS: 1. Accurate differentiation between cHCC-CCA and HCC is essential for treatment decisions. 2. The CECT-predominant model provides higher accuracy than the CEUS-predominant model for CHCC-CCA. 3. Combining CECT features and CA 19-9 levels shows a sensitivity of 93.3% in diagnosing cHCC-CCA.

PMID:38353807 | PMC:PMC10866845 | DOI:10.1186/s13244-023-01576-6

Permalink for 'Multimodal prehabilitation program in patients with resectable perihilar cholangiocarcinoma: keypoints for an implementation protocol and literature review'

Multimodal prehabilitation program in patients with resectable perihilar cholangiocarcinoma: keypoints for an implementation protocol and literature review

Fetched: February 16th, 2024, 5:01am GMT by Victor Lopez-Lopez

Langenbecks Arch Surg. 2024 Feb 14;409(1):61. doi: 10.1007/s00423-024-03251-w.

ABSTRACT

BACKGROUND: Postoperative complications after perihilar cholangiocarcinoma surgical procedure are still very high. The implementation of a multimodal prehabilitation program could improve these outcomes. Based on our experience and that of the literature in hepatobiliary and pancreatic surgery, we propose a protocol to promote its implementation.

METHODS: First, we performed a retrospective analysis of the implementation feasibility of a multimodal prehabilitation program in patients' candidates for elective perihilar cholangiocarcinoma surgery in our center. Second, we conducted a literature search of publications in PubMed until December 2022. Relevant data about hepato-pancreato-biliary surgery and prehabilitation programs in features and postoperative outcomes was analyzed.

RESULTS: Since October 2020, 11 patients were evaluated for prehabilitation in our hospital. Two of them could not be resected intraoperatively due to disease extension. The median hospital stay was 10 days (iqr, 7-11). There were no major complications and 1 patient died. Of a total of 17 articles related to prehabilitation in hepato-biliary-pancreatic surgery, no reports focusing exclusively on perihilar cholangiocarcinoma were found. Six of the studies had nutritional therapies in addition to physical interventions, and 12 studies used home-based exercise therapy.

CONCLUSIONS: Based on our experience and the data obtained from other studies, a prehabilitation program could be useful to improve perioperative physical and mental fitness in patients' candidates for elective perihilar cholangiocarcinoma surgery. However, more well-designed studies are needed to allow us to obtain more evidence.

PMID:38353791 | DOI:10.1007/s00423-024-03251-w

Characteristics and malignancy rates of adult patients diagnosed with choledochal cyst in the West: a systematic review

Fetched: February 16th, 2024, 5:01am GMT by Grace C Bloomfield

J Gastrointest Surg. 2024 Jan;28(1):77-87. doi: 10.1016/j.gassur.2023.11.007.

ABSTRACT

BACKGROUND: The approach to patients with choledochal cysts (CCs) remains varied and subject to institutional practices. Owing to the rarity of the disease, the optimal treatment remains poorly defined, particularly in the adult population. This study aimed to review the literature on adult patients with CCs to evaluate trends of diagnosis and management in Western countries.

METHODS: A literature search of 3 electronic databases was performed on adult patients diagnosed with CCs in Western institutions. A review of published literature was completed with comprehensive screening by 2 independent reviewers. Studies were analyzed, and data on surgical approach, malignancies, and follow-up were collected. Findings are presented in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

RESULTS: Of the 3488 articles retrieved, 21 studies evaluated Western adults with CCs for a combined population of 1337 patients. The most common Todani subtypes included types I (64%) and IV (22%). Symptoms at presentation included abdominal pain and jaundice, although many were asymptomatic. Ultrasound was used most frequently for diagnosis, followed by computed tomography and endoscopic cholangiopancreatography. The combined malignancy rate was 10.9%, with cholangiocarcinoma being the most prevalent. Complete extrahepatic cyst resection was standard for type I and IV CCs. Among malignancies, 18.5% and 16.4% were observed in patients with prior resection and internal drainage, respectively.

CONCLUSIONS: A significant proportion of patients who undergo resection of CC disease harbor malignancy. Cancer risk seems reduced but not eliminated with complete resection, which remains the standard treatment. Additional studies are needed to standardize guidelines for the diagnosis and postoperative care of patients in Western countries.

PMID:38353080 | DOI:10.1016/j.gassur.2023.11.007

Predicting risk of recurrence after resection of stage I intrahepatic cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Jun Kawashima

J Gastrointest Surg. 2024 Jan;28(1):18-25. doi: 10.1016/j.gassur.2023.10.002.

ABSTRACT

BACKGROUND: Early-stage intrahepatic cholangiocarcinoma (ICC) is often an indication of curative-intent resection. Although patients with early-stage ICC generally have a better prognosis than individuals with advanced ICC, the incidence and risk factors of recurrence after early-stage ICC remain unclear.

METHODS: A multi-institutional database was used to identify patients who underwent surgery between 2000 and 2018 for ICC with pathologically confirmed stage I disease. Cox regression analysis was used to identify clinicopathological factors associated with recurrence, and an online prediction model was developed and validated.

RESULTS: Of 430 patients diagnosed with stage I ICC, approximately one-half of patients (n = 221, 51.4%) experienced recurrence after curative-intent resection. Among patients with a recurrence, most (n = 188, 85.1%) experienced it within 12 months. On multivariable analysis, carcinoembryonic antigen (hazard ratio [HR], 1.011; 95% CI, 1.004-1.018), systemic immune-inflammation index (HR, 1.036; 95% CI, 1.019-1.056), no lymph nodes evaluated (HR, 1.851; 95% CI, 1.276-2.683), and tumor size (HR, 1.101; 95% CI, 1.053-1.151) were associated with greater hazards of recurrence. A predictive model that included these weighted risk factors demonstrated excellent prognostic discrimination in the test (12-month recurrence-free survival [RFS]: low risk, 80.1%; intermediate risk, 60.3%; high risk, 37.7%; P = .001) and validation (12-month RFS: low risk, 84.5%; intermediate risk, 63.5%; high risk, 47.1%; P = .036) datasets. The online predictive model was made available at [https:]

CONCLUSIONS: Patients with stage I ICC without vascular invasion or lymph node metastasis had a relatively high incidence of recurrence. An online tool can risk stratify patients relative to recurrence risk to identify individuals best suited for alternative treatment approaches.

PMID:38353070 | DOI:10.1016/j.gassur.2023.10.002

Clinical outcomes for previously treated patients with advanced biliary tract cancer: a meta-analysis

Fetched: February 16th, 2024, 5:01am GMT by Mayur M Amonkar

Future Oncol. 2024 Feb 14. doi: 10.2217/fon-2023-0006. Online ahead of print.

ABSTRACT

Aim: A systematic review and meta-analysis were performed to evaluate the efficacy of treatments for previously treated advanced biliary tract cancer (BTC) patients. Materials & methods: Databases were searched for studies evaluating treatments for advanced (unresectable and/or metastatic) BTC patients who progressed on prior therapy. Pooled estimates of objective response rate (ORR), median overall survival (OS) and median progression-free survival (PFS) were calculated using random effects meta-analysis. Results: Across 31 studies evaluating chemotherapy or targeted treatment regimens in an unselected advanced BTC patient population, pooled ORR was 6.9%, median OS was 6.6 months and median PFS was 3.2 months. Conclusion: The efficacy of conventional treatments for previously treated advanced BTC patients is poor and could be improved by novel therapies.

PMID:38353044 | DOI:10.2217/fon-2023-0006

Obstructive Jaundice Secondary to Hepatic Hilar Tuberculosis Without Pulmonary Involvement

Fetched: February 16th, 2024, 5:01am GMT by Mohammad N Kloub

Eur J Case Rep Intern Med. 2024 Jan 19;11(2):004277. doi: 10.12890/2024_004277. eCollection 2024.

ABSTRACT

Tuberculosis (TB) is primarily a respiratory infection with huge mortality and morbidity worldwide. Extrapulmonary TB infection is common, affecting lymph nodes, pleura, and abdomen, but the prima-ry biliary presentation without lung involvement is exceedingly rare. We report on a 38-year-old male patient presented with isolated obstructive jaundice secondary to TB infection. This case highlights the importance of considering TB infection in the differential diagnosis of obstructive jaundice, especially in the endemic area. We also provide a literature review on TB infection, mainly in the biliary tract.

LEARNING POINTS: Tuberculosis (TB) can affect the biliary system, mimicking cholangiocarcinoma without pulmonary involvement.Early recognition of biliary TB and treatment can prevent permanent complications and invasive intervention requirements.Using standard anti-tuberculous medications has shown high efficiency in treating and eradicating mycobacterial infection in such locations.

PMID:38352819 | PMC:PMC10860912 | DOI:10.12890/2024_004277

Permalink for 'Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations'

Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations

Fetched: February 16th, 2024, 5:01am GMT by Anouk Lindley

Cancer Res Treat. 2024 Feb 7. doi: 10.4143/crt.2023.1197. Online ahead of print.

ABSTRACT

PURPOSE: Pemigatinib is a fibroblast growth factor receptor-2 (FGFR2) inhibitor approved for use in patients with previously treated cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements. This ongoing global Expanded Access Program (EAP) allows physicians in regions where pemigatinib is not commercially available to request pemigatinib for patients with locally advanced or metastatic CCA who, in the physician's opinion, could benefit from pemigatinib treatment.

MATERIALS AND METHODS: Eighty-nine patients from Europe, North America, and Israel were treated from January 2020 through September 2021.

RESULTS: Patients had FGFR gene fusions (68.5%), rearrangements (12.4%), translocations (5.6%), amplifications (2.2%), and other alterations (11.2%). Median duration of treatment in the EAP was 4.0 months (range, 0.1-13.6). The most frequently reported adverse event (AE) was hyperphosphatemia (22.5%); the most common serious AE was cholangitis (3.4%). Treatment discontinuation was associated with reports of AEs for seven patients (7.9%). AEs associated with pemigatinib were consistent with those observed in clinical trials.

CONCLUSION: Efficacy was not assessed in this EAP. However, some patients remained on treatment for up to a year, suggesting that they observed a benefit from treatment. Patients with CCA should undergo molecular testing to identify those who could benefit from targeted treatments such as pemigatinib.

PMID:38351684 | DOI:10.4143/crt.2023.1197

Long-Term Outcomes of Incidental Liver Malignancies in Simultaneous Liver-Kidney Transplant Recipients

Fetched: February 16th, 2024, 5:01am GMT by Diana Rodríguez-Espinosa

Transplant Proc. 2024 Feb 12:S0041-1345(24)00004-6. doi: 10.1016/j.transproceed.2024.01.004. Online ahead of print.

ABSTRACT

BACKGROUND: The pretransplant diagnosis of liver malignancies in nodular cirrhotic livers remains a diagnostic challenge despite current advances. Although the prognostic impact of incidental hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCC) in liver transplant recipients is well documented, there are no data on the impact in simultaneous liver kidney transplant (LKT) recipients.

METHODS: This is a single-center observational, retrospective study of all LKT performed from May 1993 to April 2022. Among these patients, demographic data, immunosuppressive therapy, rejection episodes, and prevalence of incidental HCC or iCC were evaluated.

RESULTS: One hundred eight LKTs were performed and 6 were excluded. There were 13 patients with incidental carcinomas in the explanted liver: one of them with both an HCC and iCC, one with an iCC, and the remaining with an HCC. One case of iCC died. No other recurrences occurred. There were no cases of incidental HCC nor iCC in patients with a hereditary or metabolic LKT indication. We found no differences in the 5-year patient survival, and death-censored kidney and liver graft survival rates for those LKT with an incidental HCC and those without it (76.9% vs 84.2%, P = .5; 100% vs 91.6%, P = .28; and 100% vs 94.7%, P = 0.39, respectively). Finally, there were no significant associations between explant carcinoma and rejections of the liver (7.7% vs 17.9%, P = .34) or kidney graft (0% vs 16.8%, P = 0.11).

CONCLUSION: Despite a high prevalence of incidental HCC or iCC, patient, kidney, and liver graft 5-year survival were unaffected by incidental HCC.

PMID:38350821 | DOI:10.1016/j.transproceed.2024.01.004

S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway

Fetched: February 16th, 2024, 5:01am GMT by TianYi Chen

Cancer Lett. 2024 Feb 11;587:216709. doi: 10.1016/j.canlet.2024.216709. Online ahead of print.

ABSTRACT

Patients diagnosed with lymph node (LN) metastatic liver cancer face an exceedingly grim prognosis. In-depth analysis of LN metastatic patients' characteristics and tumor cells' interactions with human lymphatic endothelial cells (HLECs), can provide important biological and therapeutic insights. Here we identify at the single-cell level that S100A6 expression differs between primary tumor and their LN metastasis. Of particular significance, we uncovered the disparity in S100A6 expression between tumors and normal tissues is greater in intrahepatic cholangiocarcinoma (ICC) patients, frequently accompanied by LN metastases, than that in hepatocellular carcinoma (HCC), with rare occurrence of LN metastasis. Furthermore, in the infrequent instances of LN metastasis in HCC, heightened S100A6 expression was observed, suggesting a critical role of S100A6 in the process of LN metastasis. Subsequent experiments further uncovered that S100A6 secreted from tumor cells promotes lymphangiogenesis by upregulating the expression and secretion of vascular endothelial growth factor-D (VEGF-D) in HLECs through the RAGE/NF-kB/VEGF-D pathway while overexpression of S100A6 in tumor cells also augmented their migration and invasion. Taken together, these data reveal the dual effects of S100A6 in promoting LN metastasis in liver cancer, thus highlighting its potential as a promising therapeutic target.

PMID:38350547 | DOI:10.1016/j.canlet.2024.216709

Exosomal circ_0037104 derived from Hu-MSCs inhibits cholangiocarcinoma progression by sponging miR-620 and targeting AFAP1

Fetched: February 16th, 2024, 5:01am GMT by Zilin Yuan

J Biochem Mol Toxicol. 2024 Feb;38(2):e23656. doi: 10.1002/jbt.23656.

ABSTRACT

Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as circular RNAs (circRNAs) and microRNAs (miRNAs), between different cells. Human umbilical cord-derived mesenchymal stem cells (Hu-MSCs) can migrate to tumor sites and exert complex functions throughout tumor progression. In this study, we successfully isolated Hu-MSCs from human umbilical cords based on their surface marker expression. Hu-MSC-derived exosomes significantly reduced the invasion, migration, and proliferation of cholangiocarcinoma (CCA) cells. Furthermore, circ_0037104 was downregulated in CCA and inhibited the proliferation and metastasis of CCA cells. Then, we investigated the effect of Hu-MSC-derived exosomal circ_0037104 on CCA. Circ_0037104 mainly regulates miR-620 and enhances APAF1 expression, inhibiting CCA cell proliferation and metastasis. Overall, Hu-MSC exosomal circ_0037104 contributes to the progression and stemness of CCA cells via miR-620/APAF1. In conclusion, Hu-MSC-derived exosomal circ_0037104 sponges miR-620 directly and negatively targets APAF1 to suppress CCA.

PMID:38348717 | DOI:10.1002/jbt.23656

Application of AI on cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Jianhao Huang

Front Oncol. 2024 Jan 29;14:1324222. doi: 10.3389/fonc.2024.1324222. eCollection 2024.

ABSTRACT

Cholangiocarcinoma, classified as intrahepatic, perihilar, and extrahepatic, is considered a deadly malignancy of the hepatobiliary system. Most cases of cholangiocarcinoma are asymptomatic. Therefore, early detection of cholangiocarcinoma is significant but still challenging. The routine screening of a tumor lacks specificity and accuracy. With the application of AI, high-risk patients can be easily found by analyzing their clinical characteristics, serum biomarkers, and medical images. Moreover, AI can be used to predict the prognosis including recurrence risk and metastasis. Although they have some limitations, AI algorithms will still significantly improve many aspects of cholangiocarcinoma in the medical field with the development of computing power and technology.

PMID:38347839 | PMC:PMC10859478 | DOI:10.3389/fonc.2024.1324222

Primary Sclerosing Cholangitis Limited to Intrahepatic Bile Ducts Has Distinctly Better Prognosis

Fetched: February 16th, 2024, 5:01am GMT by Vijay S Are

Dig Dis Sci. 2024 Feb 12. doi: 10.1007/s10620-023-08260-1. Online ahead of print.

ABSTRACT

BACKGROUND: There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic).

AIMS: This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC.

METHODS: Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement.

RESULTS: Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC.

CONCLUSIONS: Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.

PMID:38347369 | DOI:10.1007/s10620-023-08260-1

Permalink for 'Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features'

Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features

Fetched: February 16th, 2024, 5:01am GMT by Diamantis I Tsilimigras

Ann Surg Oncol. 2024 Feb 12. doi: 10.1245/s10434-024-15013-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited.

METHODS: Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases.

RESULTS: Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients.

CONCLUSIONS: Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.

PMID:38347332 | DOI:10.1245/s10434-024-15013-5

Permalink for 'The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma'

The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Stephan Spahn

Nat Commun. 2024 Feb 12;15(1):1287. doi: 10.1038/s41467-024-45247-6.

ABSTRACT

Fibroblast growth factor receptor (FGFR)-2 can be inhibited by FGFR-selective or non-selective tyrosine kinase inhibitors (TKIs). Selective TKIs are approved for cholangiocarcinoma (CCA) with FGFR2 fusions; however, their application is limited by a characteristic pattern of adverse events or evocation of kinase domain mutations. A comprehensive characterization of a patient cohort treated with the non-selective TKI lenvatinib reveals promising efficacy in FGFR2-driven CCA. In a bed-to-bench approach, we investigate FGFR2 fusion proteins bearing critical tumor-relevant point mutations. These mutations confer growth advantage of tumor cells and increased resistance to selective TKIs but remain intriguingly sensitive to lenvatinib. In line with clinical observations, in-silico analyses reveal a more favorable interaction pattern of lenvatinib with FGFR2, including an increased flexibility and ligand efficacy, compared to FGFR-selective TKIs. Finally, the treatment of a patient with progressive disease and a newly developed kinase mutation during therapy with a selective inhibitor results in a striking response to lenvatinib. Our in vitro, in silico, and clinical data suggest that lenvatinib is a promising treatment option for FGFR2-driven CCA, especially when insurmountable adverse reactions of selective TKIs or acquired kinase mutations occur.

PMID:38346946 | PMC:PMC10861557 | DOI:10.1038/s41467-024-45247-6

Permalink for 'Air embolism after biliary stent removal during endoscopic retrograde cholangiopancreatography for cholangitis after biliary reconstruction: a case report'

Air embolism after biliary stent removal during endoscopic retrograde cholangiopancreatography for cholangitis after biliary reconstruction: a case report

Fetched: February 16th, 2024, 5:01am GMT by Kosuke Takahashi

Nihon Shokakibyo Gakkai Zasshi. 2024;121(2):144-153. doi: 10.11405/nisshoshi.121.144.

ABSTRACT

A 62-year-old male patient underwent pancreaticoduodenectomy with modified Child reconstruction for distal cholangiocarcinoma. After eight years, a contrast-enhanced computed tomography (CT) revealed a recurrent lesion at the biliojejunal anastomosis, and a biliary stent was placed for obstructive cholangitis in the right posterior segment of the liver. A right hepatectomy was planned for a local recurrent lesion;thus, percutaneous transhepatic portal embolization was performed on the portal vein's right branch to enlarge the left liver. However, he was referred to our department for endoscopic retrograde biliary drainage for the subsequent cholangitis and liver abscess appearance. A double-balloon enteroscope under CO2 insufflation was used to reach the bile duct-jejunal anastomosis. After removing the bile duct stent with grasping forceps, his general condition suddenly deteriorated, causing cardiopulmonary arrest. He was diagnosed with air embolism based on the findings of air in the heart, aorta, and brain on CT after the return of spontaneous circulation. Treatment for the air embolism and subsequent complications continued in the intensive care unit, but he eventually died 114 days after the onset of the air embolism due to his deteriorating general condition. Pathological autopsy revealed cholangiocarcinoma that extends from the porta hepatis to the posterior segment. Additionally, the proximity between the bile duct and vein extended by the adenocarcinoma and the fibrous obstruction of the vein were revealed, indicating the possibility of a bile duct-vein shunt.

PMID:38346762 | DOI:10.11405/nisshoshi.121.144

Permalink for 'High dose proton and photon-based radiation therapy for 213 liver lesions: a multi-institutional dosimetric comparison with a clinical perspective'

High dose proton and photon-based radiation therapy for 213 liver lesions: a multi-institutional dosimetric comparison with a clinical perspective

Fetched: February 16th, 2024, 5:01am GMT by Marco Lorenzo Bonù

Radiol Med. 2024 Feb 12. doi: 10.1007/s11547-024-01788-w. Online ahead of print.

ABSTRACT

BACKGROUND: Stereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported.

METHODS: Primary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV.

RESULTS: 213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients.

CONCLUSIONS: Cyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off.

PMID:38345714 | DOI:10.1007/s11547-024-01788-w

Permalink for 'Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab'

Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab

Fetched: February 16th, 2024, 5:01am GMT by Margherita Rimini

Target Oncol. 2024 Feb 12. doi: 10.1007/s11523-024-01032-5. Online ahead of print.

ABSTRACT

BACKGROUND: The results reported in the TOPAZ-1 phase III trial led to the approval of the combination of cisplatin and gemcitabine with durvalumab as the new first-line standard of care for patients with locally advanced or metastatic cholangiocarcinoma.

OBJECTIVE: We performed a clustering analysis to classify patients into different groups based on their mutation profile, correlating the results of the analysis with clinical outcomes.

METHODS: We selected 51 patients with cholangiocarcinoma who were treated with the combination of chemotherapy and durvalumab and who were screened using the next-generation sequencing-based FoundationOne gene panel. We conducted mutation-based clustering of tumors and a survival analysis.

RESULTS: Three main clusters were identified. Cluster 1 is mostly characterized by mutations in genes belonging to the chromatin modification pathway, altered in 100% of patients. Cluster 2 is characterized by the alteration of several pathways, among which DNA damage control, chromatin modification, RTK/RAS, cell-cycle apoptosis, TP53, and PI3K were the most affected. Finally, most altered pathways in cluster 3 were RTK/RAS and cell-cycle apoptosis. Overall response rate was 4/13 (31%), 12/24 (50%), and 0/10 (0%) in cluster 1, cluster 2, and cluster 3, respectively, and the difference between the three clusters was statistically significant (p = 0.0188).

CONCLUSIONS: By grouping patients into three clusters with distinct molecular and genomic alterations, our analysis showed that patients included in cluster 2 had higher overall response rates, whereas patients included in cluster 3 had no objective response. Further investigations on larger and external cohorts are needed in order to validate our results.

PMID:38345693 | DOI:10.1007/s11523-024-01032-5

5-Hydroxymethylcytosine (5-hmC) loss is a marker of malignancy in biliary neoplasms

Fetched: February 16th, 2024, 5:01am GMT by Miguel S Gonzalez-Mancera

Am J Clin Pathol. 2024 Feb 12:aqae001. doi: 10.1093/ajcp/aqae001. Online ahead of print.

ABSTRACT

OBJECTIVES: Adenocarcinomas of the biliary tract frequently present diagnostic challenges because of their histologic overlap with benign and preinvasive lesions. The molecular profiles of biliary adenocarcinomas vary by anatomical location. Variations in IDH1/2, common in intrahepatic cholangiocarcinoma, can lead to defective production of 5-hydroxymethylcytosine (5-hmC). Limited ancillary studies are available for biliary adenocarcinomas, and loss of 5-hmC staining could serve as a helpful ancillary diagnostic tool for biliary tract malignancies.

METHODS: We evaluated 93 cases-20 benign biliary lesions, 15 preinvasive biliary neoplasms, 46 invasive biliary carcinomas, and 12 pancreatic adenocarcinomas-for 5-hmC staining. Preoperative biopsies from 16 cases of biliary carcinoma were also stained. Sixteen nonneoplastic/reactive bile duct biopsies served as controls.

RESULTS: Loss of 5-hmC was seen in 41 of 46 (89.1%) biliary malignancies vs 0 of 20 benign tumors (P < .001), for a sensitivity and specificity of 89.1% and 100%, respectively. Intrahepatic cholangiocarcinoma showed loss of 5-hmC in 11 of 13 (84.6%) cases, similar to the 30 of 33 (90.9%) cases in other biliary adenocarcinomas (P = .61). Similarly, 5-hmC loss was more frequent in distal bile duct adenocarcinomas than in pancreatic ductal adenocarcinomas, at 15 of 17 (88.2%) vs 4 of 12 (33.3%), respectively (P = .0045). There was no difference in the frequency of 5-hmC loss in patients that received neoadjuvant therapy vs those who did not (90.9% vs 88.6%, P > .99). 5-hmC immunohistochemistry in preoperative biopsies was concordant with the resection specimen in 81.3% (13/16) of cases.

CONCLUSIONS: Loss of 5-hmC is not unique to intrahepatic cholangiocarcinoma among biliary carcinomas, but is a useful diagnostic marker differentiating malignancies of the biliary tree from benign mimics.

PMID:38345293 | DOI:10.1093/ajcp/aqae001

Surgical treatment and prognostic factors in perihilar tumors

Fetched: February 16th, 2024, 5:01am GMT by A N Polyakov

Khirurgiia (Mosk). 2024;(2):14-23. doi: 10.17116/hirurgia202402114.

ABSTRACT

OBJECTIVE: To study the results of surgical treatment in patients with perihilar tumors.

MATERIAL AND METHODS: We analyzed 98 patients with perihilar tumors who underwent surgery.

RESULTS: We prefer percutaneous transhepatic biliary drainage (n=58) for jaundice. Retrograde interventions were performed in 18 cases (20.5%), complications grade III-IV were more common (p=0.037) in the last group. Postoperative mortality was 12%. Complications developed in 81 patients (82.7%), grade ≥3 - in 39 (39.8%) cases. Portal vein resection (n=26) increased the incidence of complications grade ≥III (p=0.035) and portal vein thrombosis (p=0.0001). Chemotherapy after surgery was performed in 47 patients (48.0%), photodynamic therapy - in 7 (7.1%) patients. A 5-year overall survival was 28.1%, the median survival - 29 months. R2 resection and/or M1 stage (n=12) significantly worsened the prognosis and overall survival (16.5 vs. 31 months, p=0.0055). Lymph node (LN) lesion, microscopic status (R0 vs. R1) of resection margin, technique of decompression and isolated resection of extrahepatic bile ducts did not affect the prognosis, and we combined appropriate patients (n=72) for analysis. SI resection and excision of ≥6 lymph nodes were independent positive factors for disease-free survival (p=0.042 and p=0.007, respectively). Blood transfusion and high preoperative neutrophil-lymphocyte index (NLI ≥2.15) worsened overall (p=0.009 and p=0.002, respectively) and disease-free survival (p=0.002 and 0.007, respectively). The absence of adjuvant therapy worsened disease-free survival alone (p=0.024).

CONCLUSION: SI liver resection, adequate lymph node dissection and adjuvant therapy should be used for perihilar tumors. Isolated resection of extrahepatic bile ducts is permissible in some cases. Blood transfusion and NLI ≥2.15 are independent negative prognostic factors.

PMID:38344956 | DOI:10.17116/hirurgia202402114

Combined Hepatocellular-Cholangiocarcinoma: Biology, Diagnosis, and Management

Fetched: February 16th, 2024, 5:01am GMT by Liangtao Ye

Liver Cancer. 2023 Apr 24;13(1):6-28. doi: 10.1159/000530700. eCollection 2024 Feb.

ABSTRACT

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-iCCA) is a rare type of primary liver cancer displaying characteristics of both hepatocytic and cholangiocytic differentiation.

SUMMARY: Because of its aggressive nature, patients with cHCC-iCCA exhibit a poorer prognosis than those with HCC. Surgical resection and liver transplantation may be considered curative treatment approaches; however, only a minority of patients are eligible at the time of diagnosis, and postoperative recurrence rates are high. For cases that are not eligible for surgery, locoregional and systemic therapy are often administered based on treatment protocols applied for HCC or iCCA. Owing to the rarity of this cancer, there are still no established standard treatment protocols; therefore, the choice of therapy is often personalized and guided by the suspected predominant component. Further, the genomic and molecular heterogeneity of cHCC-iCCA can severely compromise the efficacy of the available therapies.

KEY MESSAGES: In the present review, we summarize the latest advances in cHCC-iCCA and attempt to clarify its terminology and molecular biology. We provide an overview of the etiology of cHCC-iCCA and present new insights into the molecular pathology of this disease that could contribute to further studies aiming to improve the patient outcomes through new systemic therapies.

PMID:38344449 | PMC:PMC10857821 | DOI:10.1159/000530700

Clinical management of intrahepatic cholangiocarcinoma: surgical approaches and systemic therapies

Fetched: February 16th, 2024, 5:01am GMT by Samantha M Ruff

Front Oncol. 2024 Jan 24;14:1321683. doi: 10.3389/fonc.2024.1321683. eCollection 2024.

ABSTRACT

Intrahepatic cholangiocarcinoma (ICCA) is a rare and aggressive malignant tumor that arises from the biliary tracts in the liver. Upfront surgery with adjuvant capecitabine in patients with resectable disease is often the standard treatment. Unfortunately, only 20% of patients present with resectable disease and many individuals will develop recurrence or metastatic disease after curative-intent resection. Patients with advanced or metastatic ICCA often require multidisciplinary care with a combination of cytotoxic chemotherapy, targeted therapy, and/or locoregional therapies. Gemcitabine plus cisplatin is currently first line therapy for advanced or metastatic ICCA. In recent years, efforts have been focused to develop more effective targeted therapy, most commonly with FGFR and IDH inhibitors for ICCA. Despite these efforts, ICCA still carries a poor prognosis. We herein review the current clinical management of ICCA focusing on surgical technique and systemic therapies.

PMID:38344197 | PMC:PMC10853998 | DOI:10.3389/fonc.2024.1321683

Update on the Diagnosis and Treatment of Combined Hepatocellular Cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Kai-Jian Chu

J Clin Transl Hepatol. 2024 Feb 28;12(2):210-217. doi: 10.14218/JCTH.2023.00189. Epub 2023 Nov 15.

ABSTRACT

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a unique type of liver tumor that contains both hepatocellular carcinoma and cholangiocarcinoma components within a single tumor. The fifth edition of the World Health Organization classification provides a definition and diagnostic criteria for cHCC-CCA. However, the heterogeneous histomorphology and presentation resulting from variation of the proportion of each component poses challenges for clinical diagnosis and treatment. A diagnosis of cHCC-CCA may be suggested by the synchronous elevation of serum tumor markers for hepatocellular carcinoma and cholangiocarcinoma, a mixed enhancement pattern on imaging, and a discrepancy between the elevation of tumor marker and the imaging enhancement pattern. Histopathological examination using hematoxylin and eosin staining is considered the gold standard for diagnosing cHCC-CCA, and comprehensive examination of resection or biopsy specimens is crucial for an accurate diagnosis. Currently, there is no standard treatment for cHCC-CCA, and surgery is the mainstay. Anatomic hepatectomy with lymphadenectomy is among the recommended surgical procedures. The role of liver transplantation in the management of cHCC-CCA is still uncertain. Transarterial chemoembolization may be effective for unresectable cHCC-CCA, particularly for hypervascular tumors. However, the available evidence does not support systemic therapy for advanced cHCC-CCA. The prognosis of cHCC-CCA is generally poor, and there is no established staging system. Further research is needed to better understand the histogenesis and clinical management of cHCC-CCA. This review provides an overview of the current literature on cHCC-CCA with a focus on its clinical characteristics, pathological diagnosis, and management.

PMID:38343605 | PMC:PMC10851068 | DOI:10.14218/JCTH.2023.00189

Chemical constituents from the roots of Zygostelma benthamii (Apocynaceae) and their anti-proliferative activities

Fetched: February 16th, 2024, 5:01am GMT by Tanakiat Chompupong

Nat Prod Res. 2024 Feb 12:1-5. doi: 10.1080/14786419.2024.2314640. Online ahead of print.

ABSTRACT

Phytochemical investigation of the roots of Zygostelma benthamii Baill. (Apocynaceae) led to the isolation of eleven known compounds. The isolated compounds were identified by analysis of physical and spectroscopic data. We report three phenolic compounds (1-3), four triterpenoids (4-7), one coumarin (8), one lignan (9), one pregnane terpenoid (10), and one diterpenoid (11). It is the first time that Zygostelma benthamii is investigated, and this is therefore the first study of the Zygostelma genus. In addition, compound 7 and 11 are reported from the Apocynaceae family for the first time. Compounds 6, 7, 10 and 11 were evaluated against several cancer cell lines (KKU-M213B, KKU-100, KKU-M055, and A549) and Vero cells. Compound 10 showed strong anti-proliferative activity against all the selected cell lines, with IC50 values in the range of 1.70-6.8 µg/mL.

PMID:38343384 | DOI:10.1080/14786419.2024.2314640

Innovative explorations: unveiling the potential of organoids for investigating environmental pollutant exposure

Fetched: February 16th, 2024, 5:01am GMT by Yuanhang Zhang

Environ Sci Pollut Res Int. 2024 Feb 12. doi: 10.1007/s11356-024-32256-7. Online ahead of print.

ABSTRACT

As the economy rapidly develops, chemicals are widely produced and used. This has exacerbated the problems associated with environmental pollution, raising the need for efficient toxicological evaluation techniques to investigate the toxic effects and mechanisms of toxicity of environmental pollutants. The progress in the techniques of cell culture in three dimensions has resulted in the creation of models that are more relevant in terms of biology and physiology. This enables researchers to study organ development, toxicology, and drug screening. Adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs) can be obtained from various mammalian tissues, including cancerous and healthy tissues. Such stem cells exhibit a significant level of tissue memory and ability to self-assemble. When cultivated in 3D in vitro environments, the resulting organoids demonstrate a remarkable capacity to recapitulate the cellular composition and function of organs in vivo. Recently, many tumors' tissue-derived organoids have been widely used in research on tumor pathogenesis, drug development, precision medicine, and other fields, including those derived from colon cancer, cholangiocarcinoma, liver cancer, and gastric cancer. However, the application of organoid models for evaluating the toxicity of environmental pollutants is still in its infancy. This review introduces the characteristics of the toxicity responses of organoid models upon exposure to pollutants from the perspectives of organoid characteristics, tissue types, and their applications in toxicology; discusses the feasibility of using organoid models in evaluating the toxicity of pollutants; and provides a reference for future toxicological studies on environmental pollutants based on organoid models.

PMID:38342830 | DOI:10.1007/s11356-024-32256-7

Permalink for 'Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: A joint analysis of the French PEMI-BIL and Italian PEMI-REAL cohort studies'

Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: A joint analysis of the French PEMI-BIL and Italian PEMI-REAL cohort studies

Fetched: February 16th, 2024, 5:01am GMT by Alessandro Parisi

Eur J Cancer. 2024 Feb 6;200:113587. doi: 10.1016/j.ejca.2024.113587. Online ahead of print.

ABSTRACT

BACKGROUND: Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting.

MATERIAL AND METHODS: A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included.

RESULTS: Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs.

CONCLUSIONS: These results confirm the effectiveness and safety of pemigatinib in a real-world setting.

PMID:38340384 | DOI:10.1016/j.ejca.2024.113587

Permalink for 'Cholangiocarcinoma Insights: Established Foundations and Cutting-Edge Innovations from Dr. James Cleary's Pioneering Research'

Cholangiocarcinoma Insights: Established Foundations and Cutting-Edge Innovations from Dr. James Cleary's Pioneering Research

Fetched: February 16th, 2024, 5:01am GMT by Viviana Cortiana

Cancers (Basel). 2024 Feb 1;16(3):632. doi: 10.3390/cancers16030632.

ABSTRACT

This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary's illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary.

PMID:38339383 | PMC:PMC10854507 | DOI:10.3390/cancers16030632

Emerging Therapies in Management of Cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Jessica Speckart

Cancers (Basel). 2024 Jan 31;16(3):613. doi: 10.3390/cancers16030613.

ABSTRACT

Cholangiocarcinoma is a heterogeneous group of biliary tract cancers that has a poor prognosis and globally increasing incidence and mortality. While surgical resection remains the only curative option for the treatment of cholangiocarcinoma, the majority of cancers are unresectable at the time of diagnosis. Additionally, the prognosis of cholangiocarcinoma remains poor even with the current first-line systemic therapy regimens, highlighting the difficulty of treating locally advanced, metastatic, or unresectable cholangiocarcinoma. Through recent developments, targetable oncogenic driver mutations have been identified in the pathogenesis of cholangiocarcinoma, leading to the utilization of molecular targeted therapeutics. In this review, we comprehensively discuss the latest molecular therapeutics for the treatment of cholangiocarcinoma, including emerging immunotherapies, highlighting promising developments and strategies.

PMID:38339363 | PMC:PMC10854763 | DOI:10.3390/cancers16030613

THBS1 and THBS2 Enhance the In Vitro Proliferation, Adhesion, Migration and Invasion of Intrahepatic Cholangiocarcinoma Cells

Fetched: February 16th, 2024, 5:01am GMT by Eleonora Corbella

Int J Mol Sci. 2024 Feb 1;25(3):1782. doi: 10.3390/ijms25031782.

ABSTRACT

In intrahepatic cholangiocarcinoma (iCCA), thrombospondin 1 (THBS1) and 2 (THBS2) are soluble mediators released in the tumor microenvironment (TME) that contribute to the metastatic spreading of iCCA cells via a lymphatic network by the trans-differentiation of vascular endothelial cells to a lymphatic-like phenotype. To study the direct role of THBS1 and THBS2 on the iCCA cells, well-established epithelial (HuCCT-1) and mesenchymal (CCLP1) iCCA cell lines were subjected to recombinant human THBS1 and THBS2 (rhTHBS1, rhTHBS2) for cellular function assays. Cell growth, cell adhesion, migration, and invasion were all enhanced in both CCLP1 and HuCCT-1 cells by the treatment with either rhTHBS1 or rhTHBS2, although they showed some variability in their intensity of speeding up cellular processes. rhTHBS2 was more intense in inducing invasiveness and in committing the HuCCT-1 cells to a mesenchymal-like phenotype and was therefore a stronger enhancer of the malignant behavior of iCCA cells compared to rhTHBS1. Our data extend the role of THBS1 and THBS2, which are not only able to hinder the vascular network and promote tumor-associated lymphangiogenesis but also exacerbate the malignant behavior of the iCCA cells.

PMID:38339060 | PMC:PMC10855656 | DOI:10.3390/ijms25031782

Portal vein stenting in recurrent or locally advanced peri-hilar cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Mario De Bellis

Eur J Surg Oncol. 2024 Jan 30;50(3):107984. doi: 10.1016/j.ejso.2024.107984. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent or locally advanced peri-hilar cholangiocarcinoma (PHCC) usually involves the portal vein (PV) leading to significant stenosis. With disease progression, clinical symptoms such as ascites, bleeding, and hepatic insufficiency are usually observed. Little is know about the benefit of PV stenting in relieving the symptoms associated to portal hypertension and allowing anticancer therapies. The aim of this study is to review our experience in PV stenting for PHCC patients.

METHODS: From 2014 to 2022, data from PHCC patients underwent PV stenting at Verona University Hospital, Italy, were reviewed. The indications were: gastrointestinal bleeding from esophagus-gastric varices, ascites not responsive to medical therapy, severe thrombocytopenia, liver insufficiency (hepatic jaundice, coagulopathy, and/or hyperammoniemia), or asymptomatic high-grade PV stenosis. Cavernous transformation and intrahepatic thrombosis in both sides of the liver were considered contraindication. Systematic anticoagulation therapy was not administered.

RESULTS: Technical success was achieved in all 16 (100 %) patients. The improvement of clinical symptoms were observed in 12 (75 %) patients. Anticancer therapy was administrated in 11 (69 %) patients. 2 (13 %) complications were observed: 1 biliary injury and 1 recurrent cholangitis that required a percutaneous trans-hepatic biliary drainage placement. Stent occlusion for tumor progression occurred in 1 patient and a re-stenting procedure was successfully performed. No case of thrombotic stent occlusion was observed during follow up. The 1-year stent patency was 86 % and the median patency period was 8 months (IQR, 4-12).

CONCLUSION: PV stenting is a feasible and safe palliative treatment that improves clinical condition, allow anticancer therapies, and provide a better quality of life.

PMID:38335874 | DOI:10.1016/j.ejso.2024.107984

Is Repeat Resection for Recurrent Intrahepatic Cholangiocarcinoma Warranted? Outcomes of an International Analysis

Fetched: February 16th, 2024, 5:01am GMT by Matthew L Holzner

Ann Surg Oncol. 2024 Feb 9. doi: 10.1245/s10434-024-14975-w. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort.

PATIENTS AND METHODS: Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival.

RESULTS: Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001].

CONCLUSIONS: Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.

PMID:38334851 | DOI:10.1245/s10434-024-14975-w

ASO Author Reflections: Robotic Approach for Perihilar Cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Benedetto Ielpo

Ann Surg Oncol. 2024 Feb 9. doi: 10.1245/s10434-024-15006-4. Online ahead of print.

NO ABSTRACT

PMID:38334849 | DOI:10.1245/s10434-024-15006-4

Advances in research and application of photodynamic therapy in cholangiocarcinoma (Review)

Fetched: February 16th, 2024, 5:01am GMT by Yufeng Li

Oncol Rep. 2024 Mar;51(3):53. doi: 10.3892/or.2024.8712. Epub 2024 Feb 9.

ABSTRACT

Cholangiocarcinoma (CCA) is a disease characterized by insidious clinical manifestations and challenging to diagnose. Patients are usually diagnosed at an advanced stage and miss the opportunity for radical surgery. Therefore, effective palliative therapy is the main treatment approach for unresectable CCA. Current common palliative treatments include biliary drainage, chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, these treatments only offer limited improvement in quality of life and survival. Photodynamic therapy (PDT) is a novel local treatment method that is considered a safe tumor ablation method for numerous cancers. It has shown good efficacy in various studies of CCA and is expected to become an important treatment for CCA. In the present study, the mechanisms of PDT in the treatment of CCA were systematically explored and the progress in the research of photosensitizers was discussed. The current study focused on the various PDT protocols and their therapeutic effects in CCA, with the objective of providing a new horizon for future research and clinical applications of PDT in the treatment of CCA.

PMID:38334150 | DOI:10.3892/or.2024.8712

Permalink for 'Automatic origin prediction of liver metastases via hierarchical artificial-intelligence system trained on multiphasic CT data: a retrospective, multicentre study'

Automatic origin prediction of liver metastases via hierarchical artificial-intelligence system trained on multiphasic CT data: a retrospective, multicentre study

Fetched: February 16th, 2024, 5:01am GMT by Hongjie Xin

EClinicalMedicine. 2024 Feb 1;69:102464. doi: 10.1016/j.eclinm.2024.102464. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: Currently, the diagnostic testing for the primary origin of liver metastases (LMs) can be laborious, complicating clinical decision-making. Directly classifying the primary origin of LMs at computed tomography (CT) images has proven to be challenging, despite its potential to streamline the entire diagnostic workflow.

METHODS: We developed ALMSS, an artificial intelligence (AI)-based LMs screening system, to provide automated liver contrast-enhanced CT analysis for distinguishing LMs from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as subtyping primary origin of LMs as six organ systems. We processed a CECT dataset between January 1, 2013 and June 30, 2022 (n = 3105: 840 HCC, 354 ICC, and 1911 LMs) for training and internally testing ALMSS, and two additional cohorts (n = 622) for external validation of its diagnostic performance. The performance of radiologists with and without the assistance of ALMSS in diagnosing and subtyping LMs was assessed.

FINDINGS: ALMSS achieved average area under the curve (AUC) of 0.917 (95% confidence interval [CI]: 0.899-0.931) and 0.923 (95% [CI]: 0.905-0.937) for differentiating LMs, HCC and ICC on both the internal testing set and external testing set, outperformed that of two radiologists. Moreover, ALMSS yielded average AUC of 0.815 (95% [CI]: 0.794-0.836) and 0.818 (95% [CI]: 0.790-0.842) for predicting six primary origins on both two testing sets. Interestingly, ALMSS assigned origin diagnoses for LMs with pathological phenotypes beyond the training categories with average AUC of 0.761 (95% [CI]: 0.657-0.842), which verify the model's diagnostic expandability.

INTERPRETATION: Our study established an AI-based diagnostic system that effectively identifies and characterizes LMs directly from multiphasic CT images.

FUNDING: National Natural Science Foundation of China, Guangdong Provincial Key Laboratory of Medical Image Processing.

PMID:38333364 | PMC:PMC10847157 | DOI:10.1016/j.eclinm.2024.102464

Adjuvant therapy with toceranib for hepatocellular carcinoma and cholangiocarcinoma in a Pomeranian

Fetched: February 16th, 2024, 5:01am GMT by Lee Choi

Vet Med (Praha). 2023 Feb 23;68(2):83-89. doi: 10.17221/49/2022-VETMED. eCollection 2023 Feb.

ABSTRACT

A 10-year-old spayed female Pomeranian dog was referred for hepatic mass evaluation. Blood tests revealed mildly elevated alkaline phosphatase activities. Computed tomography revealed a mass with multiple nodules on the right hepatic medial lobe adjacent to the caudal vena cava; histopathology confirmed mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of incomplete resection, adjuvant therapy was recommended. As tumour cells showed PDGFR-α, c-Kit, and FGFR1 overexpression, the anticancer effect of tyrosine kinase inhibitors was evaluated on the cells; toceranib was the most effective and was administered starting with an extra-labelled dose. The dog remained stable for 2.3 years with mild adverse effects. To our knowledge, this is the first successful clinical application of toceranib in a dog with mixed HCC-CC.

PMID:38332765 | PMC:PMC10847815 | DOI:10.17221/49/2022-VETMED

Pathological complete response following neoadjuvant chemotherapy for locally advanced intrahepatic cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Yoshitaka Shimamaki

Surg Case Rep. 2024 Feb 9;10(1):35. doi: 10.1186/s40792-024-01832-x.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cases when found are often advanced with vascular invasion, and radical resection is often difficult. Despite curative resection, the postoperative recurrence rate of patients with histological lymph node metastasis is high, and their prognosis is poor. Therefore, there is an urgent need to establish multidisciplinary treatment that combines chemotherapy and surgical resection. The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced ICC is unclear. In this report, a case of locally advanced ICC in which pathological complete response (pCR) was achieved after NAC is described.

CASE PRESENTATION: A 79-year-old woman was admitted to a local hospital with appetite loss. Computed tomography showed a 100 × 90 mm low-contrast tumor in the left hepatic lobe and segment 1 with invasion to the inferior vena cava (IVC), and several lymph nodes along the left gastric artery and lesser curvature were enlarged. Therefore, she was treated with a combined chemotherapy regimen of gemcitabine and cisplatin. After four courses, the tumor size decreased to 30 × 60 mm without invasion to the IVC. Left hepatectomy extending to segment 1 with bile duct resection combined with middle hepatic vein resection (H1234-B-MHV), dissection of regional lymph nodes and pyloroplasty were performed. After radical resection, pCR was achieved. She is alive with no evidence of disease, 2 years after surgery.

CONCLUSIONS: In this case, a patient with locally advanced ICC achieved pCR to NAC. NAC may be effective for ICC. Patients who achieve pCR may have a better prognosis.

PMID:38332333 | PMC:PMC10853132 | DOI:10.1186/s40792-024-01832-x

TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma

Fetched: February 16th, 2024, 5:01am GMT by Panagiotis Papoutsoglou

EMBO Rep. 2024 Feb 8. doi: 10.1038/s44319-024-00075-z. Online ahead of print.

ABSTRACT

Cholangiocarcinoma is a devastating liver cancer characterized by high aggressiveness and therapy resistance, resulting in poor prognosis. Long non-coding RNAs and signals imposed by oncogenic pathways, such as transforming growth factor β (TGFβ), frequently contribute to cholangiocarcinogenesis. Here, we explore novel effectors of TGFβ signalling in cholangiocarcinoma. LINC00313 is identified as a novel TGFβ target gene. Gene expression and genome-wide chromatin accessibility profiling reveal that nuclear LINC00313 transcriptionally regulates genes involved in Wnt signalling, such as the transcriptional activator TCF7. LINC00313 gain-of-function enhances TCF/LEF-dependent transcription, promotes colony formation in vitro and accelerates tumour growth in vivo. Genes affected by LINC00313 over-expression in CCA tumours are associated with KRAS and TP53 mutations and reduce overall patient survival. Mechanistically, ACTL6A and BRG1, subunits of the SWI/SNF chromatin remodelling complex, interact with LINC00313 and affect TCF7 and SULF2 transcription. We propose a model whereby TGFβ induces LINC00313 in order to regulate the expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and promotes cholangiocarcinogenesis.

PMID:38332153 | DOI:10.1038/s44319-024-00075-z

Methylthioadenosine Phosphorylase Genomic Loss in Advanced Gastrointestinal Cancers

Fetched: February 16th, 2024, 5:01am GMT by Natalie Y L Ngoi

Oncologist. 2024 Feb 8:oyae011. doi: 10.1093/oncolo/oyae011. Online ahead of print.

ABSTRACT

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI cancers. We compared the clinical outcomes of patients with GI cancer harboring MTAP-loss and MTAP-intact tumors in a retrospective study.

RESULTS: The prevalence of MTAP-loss in GI cancers is 8.30%. MTAP-loss was most prevalent in pancreatic ductal adenocarcinoma (PDAC) at 21.7% and least in colorectal carcinoma (CRC) at 1.1%. MTAP-loss tumors were more prevalent in East Asian patients with PDAC (4.4% vs 3.2%, P = .005) or intrahepatic cholangiocarcinoma (IHCC; 6.4% vs 4.3%, P = .036). Significant differences in the prevalence of potentially targetable genomic alterations (ATM, BRAF, BRCA2, ERBB2, IDH1, PIK3CA, and PTEN) were observed in MTAP-loss tumors and varied according to tumor type. MTAP-loss PDAC, IHCC, and CRC had a lower prevalence of microsatellite instability or elevated tumor mutational burden. Positive PD-L1 tumor cell expression was less frequent among MTAP-loss versus MTAP-intact IHCC tumors (23.2% vs 31.2%, P = .017).

CONCLUSION: In GI cancers, MTAP-loss occurs as part of 9p21 loss and has an overall prevalence of 8%. MTAP-loss occurs in 22% of PDAC, 15% of IHCC, 8.7% of gastroesophageal adenocarcinoma, 2.4% of hepatocellular carcinoma, and 1.1% of CRC and is not mutually exclusive with other targetable mutations.

PMID:38330461 | DOI:10.1093/oncolo/oyae011

Safety Profile and Adverse Event Management for Futibatinib, an Irreversible FGFR1-4 Inhibitor: Pooled Safety analysis of 469 patients

Fetched: February 16th, 2024, 5:01am GMT by Funda Meric-Bernstam

Clin Cancer Res. 2024 Feb 8. doi: 10.1158/1078-0432.CCR-23-2646. Online ahead of print.

ABSTRACT

PURPOSE: Futibatinib, a covalently-binding inhibitor of fibroblast growth factor receptor (FGFR)1-4 gained approval for the treatment of refractory, advanced intrahepatic cholangiocarcinoma (iCCA) harboring an FGFR2 fusion/other rearrangement. An integrated analysis was performed to evaluate safety and provide guidance on management of futibatinib-associated adverse events (AEs) in patients with unresectable/metastatic tumors, including iCCA.

PATIENTS AND METHODS: Data from three global phase 1 or 2 studies of futibatinib (NCT02052778; JapicCTI-142552) were pooled. AEs were graded per NCI CTCAE v4.03, where applicable. Safety was analyzed for patients receiving any futibatinib starting dose (overall population) and in those receiving the approved starting dose of 20 mg once daily (QD).

RESULTS: In total, 469 patients with one of 33 known tumor types were analyzed, including 318 patients who received futibatinib 20 mg QD. AEs of clinical interest (AECIs; any grade/grade ≥3) in the overall population included hyperphosphatemia (82%/19%), nail disorders (27%/1%), hepatic AEs (27%/11%), stomatitis (19%/3%), palmar-plantar erythrodysesthesia syndrome (PPES; 13%/3%), rash (9%/0%), retinal disorders (8%/0%), and cataract (4%/1%). Median time to onset of grade ≥3 AECIs ranged from 9 days (hyperphosphatemia) to 125 days (cataract). Grade ≥3 hyperphosphatemia, hepatic AEs, PPES, and nail disorders resolved to grade ≤2 within a median of 7, 7, 8, and 28 days, respectively. Discontinuations due to treatment-related AEs were rare (2%), and no treatment-related deaths occurred. AE management included phosphate-lowering medication and dose adjustments.

CONCLUSIONS: Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with appropriate clinical management.

PMID:38329716 | DOI:10.1158/1078-0432.CCR-23-2646

Permalink for 'ASO Author Reflections: Minimally Invasive Approach and Oncologic Benefit in Intrahepatic Cholangiocarcinoma (iCCA) With Risk of Very Early Recurrence: Is it Time to Consider Technique as a Key Element of Onco-Surgical Strategy?'

ASO Author Reflections: Minimally Invasive Approach and Oncologic Benefit in Intrahepatic Cholangiocarcinoma (iCCA) With Risk of Very Early Recurrence: Is it Time to Consider Technique as a Key Element of Onco-Surgical Strategy?

Fetched: February 16th, 2024, 5:01am GMT by Francesca Ratti

Ann Surg Oncol. 2024 Feb 8. doi: 10.1245/s10434-024-14972-z. Online ahead of print.

NO ABSTRACT

PMID:38329658 | DOI:10.1245/s10434-024-14972-z

Permalink for 'Adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients: a dose-finding study (HORA EST HCC trial)'

Adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients: a dose-finding study (HORA EST HCC trial)

Fetched: February 16th, 2024, 5:01am GMT by Pim Hendriks

Eur J Nucl Med Mol Imaging. 2024 Feb 8. doi: 10.1007/s00259-024-06630-z. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (¹⁶⁶Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume).

METHODS: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2-5 cm, RFA was followed by (super-)selective infusion of ¹⁶⁶Ho-MS on day 5-10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of ¹⁶⁶Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort.

RESULTS: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3-71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1-4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127-145]). No local recurrences were found within 1-year follow-up.

CONCLUSION: Adjuvant (super-)selective infusion of ¹⁶⁶Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2-5 cm.

TRIAL REGISTRATION: Clinicaltrials.gov NCT03437382 . (registered: 19-02-2018).

PMID:38329507 | DOI:10.1007/s00259-024-06630-z

Clinical Implications of Naples Prognostic Score for Patients with Resected Cholangiocarcinoma: A Real-World Experience

Fetched: February 16th, 2024, 5:01am GMT by Benjie Xu

J Inflamm Res. 2024 Feb 2;17:655-667. doi: 10.2147/JIR.S446735. eCollection 2024.

ABSTRACT

PURPOSE: The Nutritional Prognostic Score (NPS) is a composite indicator that effectively reflects the preoperative nutritional and inflammation status of patients. Its prognostic value has been extensively confirmed in various types of tumors. Our study aims to investigate the clinical implications of the NPS in the postoperative patients with cholangiocarcinoma (CCA).

PATIENTS AND METHODS: Data on clinicopathological characteristics were collected from CCA patients who underwent radical surgery between 2014 and 2019 at Harbin Medical University Cancer Hospital. NPS was calculated using relevant indicators to categorize the patients, and association of NPS with clinicopathological characteristics and survival outcomes were analyzed. To assess differences in survival rates between different groups, we utilized the Kaplan-Meier method. Independent prognostic risk factors were identified by Cox regression analysis. A CONomogram was created, and its accuracy in survival prediction was evaluated using receiver operating characteristic (ROC) curves. Independent verification was conducted in the validation group.

RESULTS: For this study, a cohort of 232 patients was enlisted and subsequently divided into training group (N=162) and validation group (N=70). An evident correlation was detected between NPS and preoperative malnutrition. Patients with higher NPS exhibited a worse overall survival (OS), with 5-year OS rates of 79.1%, 33.1%, and 10.6%. Multivariate analysis revealed that NPS was an independent risk factor for OS in resected CCA patients (P<0.001). The NPS-based Nomogram was developed to accurately assess the risk of patients.

CONCLUSION: The NPS was identified as a significant risk factor that impacts the prognosis of patients with resected CCA. In order to improve prognosis management, the NPS-based Nomogram has been demonstrated to be a precise and efficient tool.

PMID:38328562 | PMC:PMC10849881 | DOI:10.2147/JIR.S446735

Intussusception of Gastrojejunostomy After Pancreatoduodenectomy With Billroth II Reconstruction

Fetched: February 16th, 2024, 5:01am GMT by Alejandro Martinez-Esteban

Cureus. 2024 Jan 8;16(1):e51880. doi: 10.7759/cureus.51880. eCollection 2024 Jan.

ABSTRACT

Gastrojejunal anastomosis or gastrojejunostomy (GJ) is a surgical procedure used for allowing gastric emptying, especially in cases where complex reconstructions are needed. One of the less common complications but one of the most relevant in morbidity is the intussusception of the GJ. It requires a high index of suspicion, preoperative optimization of the patient, diagnostic corroboration, and identification of associated complications with the use of contrasted imaging. It was described for the first time by Bozzi in 1914; currently, multiple cases have been described in the literature, being more frequent in bariatric surgeries and reconstructions after distal gastrectomy. In hepatopancreaticobiliary surgery, it is an even uncommon complication. We present the case of a 60-year-old man with intussusception of the efferent loop of the GJ after a pylorus-preserving pancreatoduodenectomy with a Billroth II reconstruction in the setting of malignancy of the extrahepatic bile duct along with our emergency surgical treatment.

PMID:38327972 | PMC:PMC10849266 | DOI:10.7759/cureus.51880

Liver transplantation meets gastrointestinal cancer

Fetched: January 10th, 2024, 5:01am GMT by Sven H Loosen

Z Gastroenterol. 2024 Jan;62(1):62-72. doi: 10.1055/a-2226-0123. Epub 2024 Jan 9.

ABSTRACT

Liver transplantation (LT) has emerged as a standard of care for patients with end-stage liver disease, providing a life-saving intervention for patients with severely compromised liver function in both the acute and chronic setting. While LT has also become a routine procedure for early-stage hepatocellular carcinoma (HCC), offering a potential cure by treating both the tumor and the underlying liver disease, its relevance in the context of other malignancies such as cholangiocellular carcinoma (CCA), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) or liver metastases is still the subject of intense debate and no definite recommendations have yet been established. This review summarizes the current therapeutic standards in the context of LT for gastrointestinal malignancies and provides a reflection and outlook on current scientific and clinical developments.

PMID:38195110 | DOI:10.1055/a-2226-0123

Permalink for 'Laparoscopic Living donor liver transplantation in irresectable intrahepatic cholangiocarcinoma in primary sclerosing cholangitis associated liver cirrhosis'

Laparoscopic Living donor liver transplantation in irresectable intrahepatic cholangiocarcinoma in primary sclerosing cholangitis associated liver cirrhosis

Fetched: January 10th, 2024, 5:01am GMT by Jan Bednarsch

Z Gastroenterol. 2024 Jan;62(1):50-55. doi: 10.1055/a-2221-6126. Epub 2024 Jan 9.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor and usually associated with a poor oncological prognosis. The current gold standard is the surgical resection of the tumor with subsequent adjuvant therapy. However, in case of irresectability e.g. in case of liver cirrhosis, a palliative treatment regime is conducted.This report demonstrates the case of an irresectable iCCA in liver cirrhosis due to primary sclerosing cholangitis (PSC) treated by living-donor liver transplantation (LDLT) facilitated by minimal invasive donor hepatectomy. No postoperative complications were observed in the donor and the donor was released on the 6^th postoperative day. Further, after a follow-up of 1.5 years, no disease recurrence was detected in the recipient.According to the recent international literature, liver transplantation can be evaluated in case of small solitary iCCA (< 3 cm) in cirrhosis. Less evidence is provided for transplantation in advanced tumors which are surgically not resectable due to advanced liver disease or infiltration of major vessels, however some reports display adequate long-term survival after strict patient selection. The selection criteria comprise the absence of distant metastases and locoregional lymph node metastases as well as partial remission or stable disease after neoadjuvant chemotherapy. Due to no established graft allocation for iCCA in Germany, LDLT is currently the best option to realize transplantation in these patients. Developments in the last decade indicate that LDLT should preferentially be performed in minimal invasive manner (laparoscopic or robotic) as this approach is associated with less overall complications and a shorter hospitalization. The presented case illustrates the possibilities of modern surgery and the introduction of transplant oncology in the modern therapy of patients combining systemic therapy, surgical resection and transplantation to achieve optimal long-term results in patients which were initially indicated for palliative treatment.

PMID:38195108 | DOI:10.1055/a-2221-6126

Permalink for 'Tumour stage and overall survival in patients with intrahepatic cholangiocarcinoma and primary sclerosing cholangitis - a retrospective cohort study'

Tumour stage and overall survival in patients with intrahepatic cholangiocarcinoma and primary sclerosing cholangitis - a retrospective cohort study

Fetched: January 10th, 2024, 5:01am GMT by Christoph Schramm

Z Gastroenterol. 2024 Jan;62(1):37-42. doi: 10.1055/a-2207-5519. Epub 2024 Jan 9.

ABSTRACT

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) carry increased risks for malignancy, among which cholangiocarcinoma (CCA) is the most frequent. We aimed to characterise a cohort of patients with PSC and intrahepatic CCA (iCCA) and to compare this cohort with CCA in different localisations.

METHODS: We performed a retrospective analysis of our medical database from 01.01.2007 to 30.06.2023 and differentiated CCA according to its localisation within the biliary tract into iCCA, perihilar CCA (pCCA), distal CCA (dCCA), and gallbladder carcinoma (GBC).

RESULTS: We identified 8 (28%) patients with iCCA, 14 (48%) patients with pCCA, 6 (21%) patients with GBC, and 1 (3%) patient with dCCA without significant differences in gender distribution and mean age. Mean time between diagnosis of PSC and CCA was 158±84 months for iCCA, 93±94 months for pCCA, and 77±69 months for GBC (p=0.230). At the time of CCA diagnosis, advanced-stage disease was present in 6 (75%) patients with iCCA, 13 (93%) patients with pCCA, and 2 (40%) patients with GBC (p=0.050). Only 5 (63%) patients with iCCA received curatively intended surgery, of whom 4 (80%) patients developed recurrence after a mean time of 38±31 months. Mean survival time in patients with iCCA (35±33 months) lay between patients with pCCA (14±8 months) and patients with GBC (57±58 months), but the difference was not statistically significant (p=0.131).

CONCLUSION: Patients with PSC and iCCA showed an advanced tumour stage at diagnosis and limited long-time survival, which was classified between pCCA with worse prognosis and GBC with better prognosis.

PMID:38195106 | DOI:10.1055/a-2207-5519

Permalink for 'Intraperitoneal PD-1 monoclonal antibody for the treatment of advanced primary liver cancer with malignant ascites: a single-arm, single-center, phase Ib trial'

Intraperitoneal PD-1 monoclonal antibody for the treatment of advanced primary liver cancer with malignant ascites: a single-arm, single-center, phase Ib trial

Fetched: January 10th, 2024, 5:01am GMT by C Chen

ESMO Open. 2024 Jan 8;9(1):102206. doi: 10.1016/j.esmoop.2023.102206. Online ahead of print.

ABSTRACT

BACKGROUND: Advanced primary liver cancer patients with malignant ascites have a poor prognosis and lack effective treatment plans. This phase Ib study aims to explore the safety and clinical efficacy of intraperitoneal anti-programmed cell death protein 1 (PD-1) antibody in these patients.

PATIENTS AND METHODS: Patients received sintilimab 100 mg intraperitoneally plus best supportive care on days 1, 8, and 15 in three cycles of 4 weeks. The course was repeated every 28 days until intolerable toxicity had developed or disease progression. The primary endpoint was safety, while the secondary endpoints were objective response rate (ORR), ascites control rate (ACR), and overall survival (OS).

RESULTS: From February 2021 through November 2022, a total of 21 patients (14 hepatocellular carcinoma and 7 cholangiocarcinoma) were enrolled to receive intraperitoneal sintilimab. Twelve patients had adverse events (AEs). The most common grade 3 AEs were fatigue, rash, and abdominal pain. No grade ≥4 AEs occurred in any patients. ORR was only evaluated in 13 patients, including partial response in 4, stable disease in 7, and progressive disease in 2. A reduction in the median maximum diameter of the tumor after treatment was observed; however, there was no statistical significance among patients. The objective remission rate of ascites was 43.75%, and the median OS for all 21 patients was 17.6 weeks.

CONCLUSIONS: This exploratory study represents the first trial to demonstrate the safety and clinical efficacy of intraperitoneal anti-PD-1 antibody administration. No unexpected safety concerns were identified. A large, multicenter, prospective study is needed to confirm the promising clinical efficacy.

PMID:38194882 | DOI:10.1016/j.esmoop.2023.102206

Permalink for 'To assess the quantitative features of focal liver lesions in gadoxetic acid enhanced MRI and to determine whether these features can accurately differentiate benign form malignant lesions'

To assess the quantitative features of focal liver lesions in gadoxetic acid enhanced MRI and to determine whether these features can accurately differentiate benign form malignant lesions

Fetched: January 10th, 2024, 5:01am GMT by Dorota N Rybczynska

Eur J Radiol. 2024 Jan 6;171:111288. doi: 10.1016/j.ejrad.2024.111288. Online ahead of print.

ABSTRACT

PURPOSE: The study aims at assessing the quantitative features which distinguish focal liver lesions (FLLs) in gadoxetic acid (GA) enhanced liver MRI and at determining whether these features can accurately differentiate benign from malignant lesions.

MATERIAL AND METHODS: 107 patients with 180 unequivocal FLLs in previous examinations were included in a single-center retrospective study. All patients underwent a MRI test of the liver with GA. 99 benign and 74 malignant lesions were included. The group of benign lesions consisted of 60 focal nodular hyperplasias (FNH), 22 hemangiomas (HMG), 6 hepatic adenomas (HA), and 11 other benign lesions (1 angiomyolipioma, 6 lesions histopathology diagnoses as benign without further specification, or ones lacking features of malignancy, and 4 lesions radiologically diagnosed as benign which remained stable in the follow-up studies). The group of malignant lesions consisted of primary 51 hepatocellular carcinomas, 12 metastases, and 11 metastases from melanoma malignum (MM meta). 7 FLLs were excluded (4 cases of uncertain histopathological diagnosis, 2 cholangiocarcinomas, and 1 regenerative nodule). For the included lesions ROI (region of interest) measurements were taken by two observers in the T2-w, ADC (apparent diffusion coefficient) and in the T1-w sequence in the hepatobiliary phase (HBP). The interobserver agreement was evaluated with the Wilcoxon test. The Kruskal - Wallis, Mann - Whitney U and post hoc Dunn's tests were applied to assess if there were any significant differences in the ROI values between individual lesions. The variables with the p values of < 0.05 were considered statistically significant.

RESULTS: We found significant differences in the ROI values between lesions with p < 0.0001. Strikingly high ROI values in the T2-w sequence were found for HMG. The lowest ADC values were encountered for metastases and MM metastases. The highest ROI values in the HBP were found for FNH, and the lowest for metastases. We also found statistically significant differences in the ROI values between benign and malignant lesions with benign lesions presenting statistically higher ROI values compared to malignant lesions.

CONCLUSIONS: There were significant differences in the ROI values among different types of FLLs. The predominant quantitative feature in the T2-w sequence was a strikingly high ROI value for HMG. Benign lesions presented statistically higher ROI values in the T2-w, ADC, and HBP sequences compared to malignant lesions. This was true for all lesions except for HA.

PMID:38194844 | DOI:10.1016/j.ejrad.2024.111288

Identification of the function of FOSB in cholangiocarcinoma using bioinformatics analysis

Fetched: January 10th, 2024, 5:01am GMT by Yihang Zhao

Transl Cancer Res. 2023 Dec 31;12(12):3629-3640. doi: 10.21037/tcr-23-829. Epub 2023 Dec 1.

ABSTRACT

BACKGROUND: Exploring the potential mechanism of cholangiocarcinoma (CCA) metabolic reprogramming is significant for guiding clinical treatment. However, related research and exploration are still lacking. Therefore, we aimed to identify a reliable metabolism-related gene or biomarker of CCA using bioinformatics analysis.

METHODS: The GSE26566, GSE45001, and GSE132305 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differently expressed genes (DEGs) between CCA tissues and adjacent tissues were screened out. The key gene was identified through enrichment and functional analysis, and its immune and clinical correlation was investigated utilizing the Tumor Immune Evaluation Resource (TIMER2.0), the Tumor-Immune System Interactions Database (TISIDB), the Gene Expression Profiling Interactive Analysis (GEPIA2), and the Kaplan-Meier Plotter. Finally, immunohistochemistry (IHC) was performed to validate the results.

RESULTS: By analysis, the expression of FBJ murine osteosarcoma viral oncogene homolog B (FOSB) was significantly downregulated in CCA tissues when compared with adjacent tissues. Moreover, the expression levels of FOSB positively correlated with tumor-infiltrating immune cells in most tumors, and patients with high FOSB expression tended to have a better prognosis. The FOSB and SIRT3/HIF1A axes have similar expression trends and metabolic functions in CCA cells, and the correlation between of them was preliminarily explored by IHC experiments.

CONCLUSIONS: The expression levels of FOSB are closely related to the prognosis of CCA patients, which may be a predictive indicator for prognosis and immunotherapy.

PMID:38192979 | PMC:PMC10774044 | DOI:10.21037/tcr-23-829

Permalink for 'Precision therapy for intrahepatic cholangiocarcinoma: A case report on adjuvant treatment in a recurrent patient after surgery and literature review'

Precision therapy for intrahepatic cholangiocarcinoma: A case report on adjuvant treatment in a recurrent patient after surgery and literature review

Fetched: January 10th, 2024, 5:01am GMT by Bao Ying

Oncol Lett. 2023 Dec 13;27(2):56. doi: 10.3892/ol.2023.14189. eCollection 2024 Feb.

ABSTRACT

A 37-year-old female patient was diagnosed with intrahepatic cholangiocarcinoma (ICC), with the lesion located in the right lobe of the liver. Despite radical resection, postoperative adjuvant chemotherapy and a combination of adjuvant chemotherapy and immunotherapy, the patient continued to experience multiple instances of intrahepatic tumor metastases. Furthermore, the patient exhibited significant adverse reactions to systemic chemotherapy and had poor treatment tolerance. Guidance from paraffin section fluorescence in situ hybridization gene sequencing was used to select a combination of immunotherapy and targeted therapy treatments with programmed cell death 1 (PD-1)/PD-1 ligand 1 antibody durvalumab and the targeted drug pemigatinib. The patient tolerated the treatment and has continued to survive for 28 months. According to imaging evaluations, the lesions continued to decrease, with some disappearing completely. The tumor marker carbohydrate antigen 19-9 remained normal for >9 weeks during the treatment. This report described the patient's treatment process in detail and briefly reviewed relevant literature on the treatment progress of postoperative patients with ICC.

PMID:38192668 | PMC:PMC10773204 | DOI:10.3892/ol.2023.14189

Permalink for 'The value of an MRI-based radiomics model in predicting the survival and prognosis of patients with extrahepatic cholangiocarcinoma'

The value of an MRI-based radiomics model in predicting the survival and prognosis of patients with extrahepatic cholangiocarcinoma

Fetched: January 9th, 2024, 5:01am GMT by Limin Wang

Cancer Med. 2024 Jan 8. doi: 10.1002/cam4.6832. Online ahead of print.

ABSTRACT

OBJECTIVES: The study aimed to establish radiomics models based on magnetic resonance imaging (MRI) multiparameter images to predict the survival and prognosis of patients with extrahepatic cholangiocarcinoma (ECC).

METHODS: Seventy-eight patients with ECC confirmed by pathology were collected retrospectively. The radiomics model_a/b/c were constructed based on the 1/2/3-year survival of patients with ECC. The best texture features were selected according to postoperative survival time and ECC patient status to calculate the radiomics score (Rad-score). A cutoff value was selected, and patients were divided into high-risk and low-risk groups.

RESULTS: Model_a, model_b, and model_c were used to predict 1-, 2-, and 3-year postoperative survival rates, respectively. The area under the curve values in the training and test groups were 1.000 and 0.933 for model_a, 0.909 and 0.907 for model_b, 1.000 and 0.975 for model_c, respectively. The survival prediction model based on the Rad-score showed that the postoperative mortality risk differed significantly between risk groups (p < 0.0001).

CONCLUSIONS: The MRI radiomics model could be used to predict the survival and prognosis of patients with ECC.

PMID:38186299 | DOI:10.1002/cam4.6832

Permalink for 'Combined High Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-Institutional Cohort Study'

Combined High Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-Institutional Cohort Study

Fetched: January 9th, 2024, 5:01am GMT by Jung Ho Im

Cancer Res Treat. 2024 Jan 2. doi: 10.4143/crt.2023.886. Online ahead of print.

ABSTRACT

PURPOSE: The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.

MATERIALS AND METHODS: Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.

RESULTS: The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30-110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified 2 risk factors, EQD2 of ≥60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors; group 1, EQD2 ≥60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 <60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p<0.05).

CONCLUSION: Combined high dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

PMID:38186240 | DOI:10.4143/crt.2023.886

Molecular profiling of biliary tract cancers reveals distinct genomic landscapes between circulating and tissue tumor DNA

Fetched: January 9th, 2024, 5:01am GMT by Clémence Astier

Exp Hematol Oncol. 2024 Jan 8;13(1):2. doi: 10.1186/s40164-023-00470-7.

ABSTRACT

Biliary tract cancers (BTCs) are heterogeneous malignancies with dismal prognosis due to tumor aggressiveness and poor response to limited current therapeutic options. Tumor exome profiling has allowed to successfully establish targeted therapeutic strategies in the clinical management of cholangiocarcinoma (CCA). Still, whether liquid biopsy profiling could inform on BTC biology and patient management is unknown. In order to test this and generate novel insight into BTC biology, we analyzed the molecular landscape of 128 CCA patients, using a 394-gene NGS panel (Foundation Medicine). Among them, 32 patients had matched circulating tumor (ct) DNA and tumor DNA samples, where both samples were profiled. In both tumor and liquid biopsies, we identified an increased frequency of alterations in genes involved in genome integrity or chromatin remodeling, including ARID1A (15%), PBRM1 (9%), and BAP1 (14%), which were validated using an in-house-developed immunohistochemistry panel. ctDNA and tumor DNA showed variable concordance, with a significant correlation in the total number of detected variants, but some heterogeneity in the detection of actionable mutations. FGFR2 mutations were more frequently identified in liquid biopsies, whereas KRAS alterations were mostly found in tumors. All IDH1 mutations detected in tumor DNA were also identified in liquid biopsies. These findings provide novel insights in the concordance between the tumor and liquid biopsies genomic landscape in a large cohort of patients with BTC and highlight the complementarity of both analyses when guiding therapeutic prescription.

PMID:38191492 | DOI:10.1186/s40164-023-00470-7

Isocitrate Dehydrogenase Mutations in Cancer: Mechanisms of Transformation and Metabolic Liability

Fetched: January 9th, 2024, 5:01am GMT by Kathryn Gunn

Cold Spring Harb Perspect Med. 2024 Jan 8:a041537. doi: 10.1101/cshperspect.a041537. Online ahead of print.

ABSTRACT

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are metabolic enzymes that interconvert isocitrate and 2-oxoglutarate (2OG). Gain-of-function mutations in IDH1 and IDH2 occur in a number of cancers, including acute myeloid leukemia, glioma, cholangiocarcinoma, and chondrosarcoma. These mutations cripple the wild-type activity of IDH and cause the enzymes to catalyze a partial reverse reaction in which 2OG is reduced but not carboxylated, resulting in production of the (R)-enantiomer of 2-hydroxyglutarate ((R)-2HG). (R)-2HG accumulation in IDH-mutant tumors results in profound dysregulation of cellular metabolism. The most well-characterized oncogenic effects of (R)-2HG involve the dysregulation of 2OG-dependent epigenetic tumor-suppressor enzymes. However, (R)-2HG has many other effects in IDH-mutant cells, some that promote transformation and others that induce metabolic dependencies. Herein, we review how cancer-associated IDH mutations impact epigenetic regulation and cellular metabolism and discuss how these effects can potentially be leveraged to therapeutically target IDH-mutant tumors.

PMID:38191174 | DOI:10.1101/cshperspect.a041537

Permalink for 'Examination of Diagnostic Performance of New IgG4 Rapid Test Compared with IgG- and IgG4-ELISAs to Investigate Epidemiology of Strongyloidiasis in Northeast Thailand'

Examination of Diagnostic Performance of New IgG4 Rapid Test Compared with IgG- and IgG4-ELISAs to Investigate Epidemiology of Strongyloidiasis in Northeast Thailand

Fetched: January 9th, 2024, 5:01am GMT by Phattharaphon Wongphutorn

Am J Trop Med Hyg. 2024 Jan 9:tpmd230518. doi: 10.4269/ajtmh.23-0518. Online ahead of print.

ABSTRACT

Strongyloidiasis, caused by Strongyloides stercoralis, is a neglected tropical disease with a global distribution. The infection can be fatal in immunocompromised individuals, and accurate diagnosis leading to timely treatment can save lives. Serodiagnosis is a sensitive method for diagnosis and is recommended for screening high-risk individuals. A point-of-care rapid test will facilitate the screening activities, especially in low-resource settings. This study aims to apply a new IgG4 immunochromatographic test using S. stercoralis recombinant antigen (SsRapid® cassette test) and to compare it with in-house IgG and IgG4 enzyme-linked immunosorbent assays (IgG- and IgG4-ELISAs) using native Strongyloides ratti antigen to investigate the epidemiology of strongyloidiasis in northeast Thailand. A total of 300 people participated, with 136 males and 164 females of a similar mean age. The reference tests were fecal examinations using the formalin-ethyl acetate concentration technique and an agar plate culture technique. The prevalence of S. stercoralis determined by SsRapid (81.7%) was significantly higher than that by fecal examinations (43.3%) or by antibody detection by IgG-ELISA (53.0%) or IgG4-ELISA (44.0%). The diagnostic sensitivities of SsRapid, IgG-ELISA, and IgG4-ELISA were found to be 93.9%, 77.7%, and 63.1%, respectively. The rate of positive tests by the SsRapid was significantly correlated to the levels of Strongyloides-specific IgG4 and IgG antibodies. By all diagnostic methods, male participants had a significantly higher prevalence of strongyloidiasis than females. Age was significantly associated with the concentration of specific serum IgG but not with the SsRapid grading score. In conclusion, SsRapid was shown to be a sensitive and valuable diagnostic test for the epidemiology study of strongyloidiasis.

PMID:38190756 | DOI:10.4269/ajtmh.23-0518

Permalink for 'Exploring the Clinical Utility of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive Multidisciplinary Clinic'

Exploring the Clinical Utility of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive Multidisciplinary Clinic

Fetched: January 9th, 2024, 5:01am GMT by Julia Purchla

J Am Coll Surg. 2024 Jan 8. doi: 10.1097/XCS.0000000000000948. Online ahead of print.

ABSTRACT

INTRODUCTION: Molecular profiling of intrahepatic cholangiocarcinoma (ICC) can detect actionable molecular alterations and guide targeted therapies. We explore the clinical utility of molecular profiling of ICC in our comprehensive multidisciplinary clinic.

METHODS: Patients with a tissue diagnosis of ICC seen between 2019 and 2023 were identified. A retrospective review was performed to identify their molecular profiles and targeted therapy. The association between the detection of actionable molecular alterations and overall survival (OS) from the first clinic visit date was studied. Patients with an OS of less than two months were excluded.

RESULTS: Among 194 ICC patients, 125 had molecular profiling. Actionable molecular alterations were detected in 56 (45%) patients, including microsatellite instability (n=3), high tumor mutational burden (TMB > 10 muts/Mb) (n=5), IDH1/2 mutations (n=22 and n=6, respectively), BRAF V600E mutations (n=2), PIK3CA mutations (n=7), BRCA1/2 mutations (n=5), MET amplification (n=2), FGFR2/3 fusions (n=13), ERBB2 overexpression (n=6), and ROS1 fusion (n=1). Twenty-one patients received targeted therapies during their treatment course. Survival analysis revealed that for 120 patients with molecular profiling, the detection of an actionable molecular alteration was associated with improved mean OS (34.1 vs. 23.6 months, p=0.008). Among 70 patients with non-metastatic ICC, the detection of an actionable molecular alteration was associated with improved mean OS (32.1 vs. 27.5 months, p=0.02).

CONCLUSION: Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multi-center studies.

PMID:38189646 | DOI:10.1097/XCS.0000000000000948

Permalink for 'Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis'

Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis

Fetched: January 9th, 2024, 5:01am GMT by Matheus de Oliveira Veras

Endosc Int Open. 2024 Jan 5;12(1):E23-E33. doi: 10.1055/a-2204-8316. eCollection 2024 Jan.

ABSTRACT

Background and study aims Recurrent biliary stent occlusion and tumor ingrowth remain a major concern among patients with malignant biliary obstruction (MBO) with significant impact on patient morbidity and survival. Intraductal radiofrequency ablation (RFA) has emerged as a promising treatment that seeks to extend stent patency. This study aimed to evaluate the impact of RFA on overall survival (OS) and stent patency among patients with unresectable MBO. Methods A comprehensive search of electronic databases was performed for randomized controlled trials (RCTs) comparing RFA plus biliary stent (RFA+S) versus biliary stent alone (S-alone). Outcomes assessed included overall survival, stent patency, and adverse events (AEs) with mean difference (MD) calculated from pooled proportions. Subgroup analyses were performed for hilar strictures and cholangiocarcinoma (CCA). Results Six RCTs (n=439 patients) were included and demonstrated improved survival among patients who received RFA+S (MD 85.80 days; 95% confidence interval [CI] 35.02-136.58; I 2 =97%; P <0.0009). The pooled MD for total stent patency was 22.25 days (95% CI 17.38-61.87; I 2 =97%; P =0.27). There was no difference in AEs between RFA+S vs S-alone ( P >0.05). On subgroup analyses, RFA+S was associated with improved stent patency (MD 76.73 days; 95% CI 50.11-103.34; I 2 =67%; P <0.01) and OS (MD 83.14 (95% CI 29.52-136.77; I 2 =97%; P <0.01] for CCA. For hilar strictures, stent patency was improved among patients with RFA+S [MD 83.71 days (95% CI 24.85-142.56; I 2 =84%; P <0.01]. Conclusions RFA+S improved OS in the treatment of MBO when compared with S-alone. Moreover, the RFA therapy prolonged stent patency in hilar strictures and CCA, with similar rates of AEs.

PMID:38188927 | PMC:PMC10769587 | DOI:10.1055/a-2204-8316

Permalink for 'Safety and feasibility of laparoscopic radical resection for bismuth types III and IV hilar cholangiocarcinoma: a single-center experience from China'

Safety and feasibility of laparoscopic radical resection for bismuth types III and IV hilar cholangiocarcinoma: a single-center experience from China

Fetched: January 9th, 2024, 5:01am GMT by Jianjun Wang

Front Oncol. 2023 Dec 18;13:1280513. doi: 10.3389/fonc.2023.1280513. eCollection 2023.

ABSTRACT

BACKGROUND: Surgery represents the only cure for hilar cholangiocarcinoma (HC). However, laparoscopic radical resection remains technically challenging owing to the complex anatomy and reconstruction required during surgery. Therefore, reports on laparoscopic surgery (LS) for HC, especially for types III and IV, are limited. This study aimed to evaluate the safety and feasibility of laparoscopic radical surgery for Bismuth types III and IV HC.

METHODS: The data of 16 patients who underwent LS and 9 who underwent open surgery (OS) for Bismuth types III and IV HC at Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, between December 2017 and January 2022 were analyzed. Basic patient information, Bismuth-Corlette type, AJCC staging, postoperative complications, pathological findings, and follow-up results were evaluated.

RESULTS: Sixteen patients underwent LS and 9 underwent OS for HC. According to the preoperative imaging data, there were four cases of Bismuth type IIIa, eight of type IIIb, and four of type IV in the LS group and two of type IIIa, four of type IIIb, and three of type IV in the OS group (P>0.05). There were no significant differences in age, sex, ASA score, comorbidity, preoperative percutaneous transhepatic biliary drainage rate, history of abdominal surgery, or preoperative laboratory tests between the two groups (P>0.05). Although the mean operative time and mean intraoperative blood loss were higher in the LS group than in OS group, the differences were not statistically significant (P=0.121 and P=0.115, respectively). Four patients (25%) in the LS group and two (22.2%) in the OS group experienced postoperative complications (P>0.05). No significant differences were observed in other surgical outcomes and pathologic findings between the two groups. Regarding the tumor recurrence rate, there was no difference between the groups (P>0.05) during the follow-up period (23.9 ± 13.3 months vs. 17.8 ± 12.3 months, P=0.240).

CONCLUSION: Laparoscopic radical resection of Bismuth types III and IV HC remains challenging, and extremely delicate surgical skills are required when performing extended hemihepatectomy followed by complex bilioenteric reconstructions. However, this procedure is generally safe and feasible for hepatobiliary surgeons with extensive laparoscopy experience.

PMID:38188306 | PMC:PMC10766688 | DOI:10.3389/fonc.2023.1280513

Roles of Rictor alterations in gastrointestinal tumors (Review)

Fetched: January 9th, 2024, 5:01am GMT by Ruizhen Cao

Oncol Rep. 2024 Feb;51(2):37. doi: 10.3892/or.2024.8696. Epub 2024 Jan 8.

ABSTRACT

Gastrointestinal tumors account for five of the top 10 causes of mortality from all cancers (colorectal, liver, stomach, esophageal and pancreatic cancer). Mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in various human cancers. As a core component of the mTOR complex 2 (mTORC2), Rictor is a key effector molecule of the PI3K/Akt pathway. A high alteration rate of Rictor has been observed in gastrointestinal tumors, and such Rictor alterations are often associated with resistance to chemotherapy and related adverse clinical outcomes. However, the exact roles of Rictor in gastrointestinal tumors remain elusive. The aim of the present study was to critically discuss the following: i) Mutation and biological characteristics of Rictor in tumors with a detailed overview of Rictor in cell proliferation, angiogenesis, apoptosis, autophagy and drug resistance; ii) the role of Rictor in tumors of the digestive system, particularly colorectal, hepatobiliary, gastric, esophageal and pancreatic cancer and cholangiocarcinoma; and iii) the current status and prospects of targeted therapy for Rictor by inhibiting Akt activation. Despite the growing realization of the importance of Rictor/mTORC2 in cancer, the underlying mechanistic details remain poorly understood; this needs to change in order for the development of efficient targeted therapies and re‑sensitization of therapy‑resistant cancers to be made possible.

PMID:38186315 | DOI:10.3892/or.2024.8696

A case of rapidly progressing sarcomatous intrahepatic cholangiocarcinoma with suddenly appearing lymph node metastasis

Fetched: January 8th, 2024, 5:01am GMT by Eisho Kanemitsu

Surg Case Rep. 2024 Jan 8;10(1):9. doi: 10.1186/s40792-023-01804-7.

ABSTRACT

BACKGROUND: The sarcomatous variant of carcinoma is relatively rare in intrahepatic cholangiocarcinoma (ICC). Sarcomatous ICC (SICC) is associated with a poorer prognosis compared with ICC. SICC is rarely diagnosed before surgery due to non-descriptive findings; it progresses rapidly, resulting in miserable prognosis. Here, we report a case of rapidly progressing SICC that showed a clinically significant tumor growth rate.

CASE PRESENTATION: A 77-year-old woman who had undergone ileocecal resection for cecal cancer 5 years previously was found to have elevated levels of the tumor marker carbohydrate antigen 19-9. Although an abdominal computed tomography (CT) scan did not detect any liver mass lesions until 3 months before this serum examination, the subsequent CT scan revealed a hypodensity 20 mm mass lesion in the right anterior section. Contrast-enhanced CT and magnetic resonance imaging revealed peripheral enhancement in the arterial-to-equilibrium phase. Fluorodeoxyglucose positron emission tomography revealed uptake in the lesion. None of the imaging modalities showed lymph node swelling or distant metastases. She underwent hepatectomy under the diagnosis of ICC or an atypical metastasis from previous cecal cancer. Although preoperative images showed no suspicious lymph node metastasis 3 weeks prior, the hilar lymph node swelled 3 cm and contained adenocarcinoma. Consequently, the patient underwent right anterior sectionectomy and lymph node dissection of the hepatoduodenal ligament. Histopathological examination revealed that the liver tumor was a poorly differentiated adenocarcinoma with sarcomatous pattern. While the patient received adjuvant gemcitabine and S-1 therapy, lymph node metastasis appeared in the mediastinum 13 months after the surgery. She received gemcitabine + cisplatin + S-1 therapy but died 20 months after surgery.

CONCLUSION: SICC and lymph node metastasis clinically appeared within 3 months and 3 weeks, respectively. Suspected ICC that rapidly progresses should be considered SICC and treated with early resection. SICC is often missed in clinical diagnosis and has a poor prognosis, even after curative resection. While an alternative strategy involving preoperative biopsy and neoadjuvant therapy may be beneficial, it should be approached with discretion due to the potential risks of tumor progression and peritoneal dissemination.

PMID:38185762 | PMC:PMC10772016 | DOI:10.1186/s40792-023-01804-7

Enzymatic synthesis of phenolic acid glucosyl esters to test activities on cholangiocarcinoma cells

Fetched: January 8th, 2024, 5:01am GMT by Eko Suyanto

Appl Microbiol Biotechnol. 2024 Dec;108(1):1-13. doi: 10.1007/s00253-023-12895-5. Epub 2024 Jan 6.

ABSTRACT

While glycoside hydrolase family 1 (GH1) enzymes mostly catalyze hydrolysis reactions, rice Os9BGlu31 preferentially catalyzes transglycosylation to transfer a glucosyl moiety to another aglycone moiety to form a new glycosylated compound through a retaining mechanism. In this study, Os9BGlu31 was used to synthesize eight phenolic acid glucosyl esters, which were evaluated for activities in cholangiocarcinoma cells. The transglycosylation products of Os9BGlu31 wild type and its mutant variants were detected, produced on a milligram scale, and purified, and their structures were characterized by NMR spectroscopy. The transglycosylation products were evaluated by antioxidant and anti-proliferative assays, followed by an anti-migration assay for the selected phenolic acid glucosyl ester. Os9BGlu31 mutants produced higher yield and activity than wild-type enzymes on phenolic acids to produce phenolic acid glucosyl esters. Among these, gallic acid glucosyl ester (β-glucogallin) had the highest antioxidant activity and anti-proliferative activity in cholangiocarcinoma cells. It also inhibited the migration of cholangiocarcinoma cells. Our study demonstrated that rice Os9BGlu31 transglucosidase is a promising enzyme for glycosylation of bioactive compounds in one-step reactions and provides evidence that β-glucogallin inhibits cell proliferation and migration of cholangiocarcinoma cells. KEY POINTS: • Os9BGlu31 transglucosidases produced phenolic acid glucosyl esters for bioactivity testing. • Phenolic acid glucosyl esters were tested for cytotoxicity in cholangiocarcinoma cells. • β-Glucogallin displayed the highest inhibition of cholangiocarcinoma cell growth.

PMID:38183488 | DOI:10.1007/s00253-023-12895-5

Degradation of AZGP1 suppresses apoptosis and facilitates cholangiocarcinoma tumorigenesis via TRIM25

Fetched: January 8th, 2024, 5:01am GMT by Hyeseon Yun

J Cell Mol Med. 2024 Jan 6. doi: 10.1111/jcmm.18104. Online ahead of print.

ABSTRACT

Alpha-2-Glycoprotein 1, Zinc-binding (AZGP1, ZAG) is a secreted protein that is synthesized by adipocytes and epithelial cells; it is downregulated in several malignancies such as breast, prostate, liver and lung cancers. However, its function remains unclear in cholangiocarcinoma (CCA). Here, we evaluated the impact AZGP1 in CCA using Gene Expression Omnibus (GEO) and GEPIA. In addition, we analysed AZGP1 expression using quantitative reverse transcription PCR and western blotting. Expression of AZGP1 was nearly deficient in CCA patients and cell lines and was associated with poor prognosis. AZGP1 overexpression upregulated apoptosis markers. Co-immunoprecipitation experiments showed that AZGP1 interacts with tripartite motif-containing protein 25 (TRIM25), and tissue microarray and bioinformatic analysis showed that AZGP1 is negatively correlated with TRIM25 expression in CCA. Thereafter, TRIM25 knockdown led to AZGP1 upregulation and induced cancer cell apoptosis. TRIM25 targets AZGP1 for degradation by catalysing its ubiquitination. AZGP1 overexpression significantly suppressed tumour growth in a xenograft mouse model. This study findings suggest that AZGP1 is a potential therapeutic target or a diagnostic biomarker for treating patients with CCA.

PMID:38183356 | DOI:10.1111/jcmm.18104

Permalink for 'Risk factors associated with loss to follow-up of patients with intrahepatic cholangiocarcinoma at one year after surgery: A retrospective analysis'

Risk factors associated with loss to follow-up of patients with intrahepatic cholangiocarcinoma at one year after surgery: A retrospective analysis

Fetched: January 7th, 2024, 5:01am GMT by Jing Gu

Asian J Surg. 2024 Jan 4:S1015-9584(23)02142-5. doi: 10.1016/j.asjsur.2023.12.174. Online ahead of print.

NO ABSTRACT

PMID:38182502 | DOI:10.1016/j.asjsur.2023.12.174

TYROBP as a molecular target in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm

Fetched: January 6th, 2024, 5:01am GMT by Wei Jia

Medicine (Baltimore). 2024 Jan 5;103(1):e36843. doi: 10.1097/MD.0000000000036843.

ABSTRACT

Cholangiocarcinoma occurs when there is a malignant tumor in the bile duct system. Renal cancer originates from renal tubular epithelial cells. Abdominal aortic aneurysm (AAA) is a permanently localized dilation caused by a lesion or injury to abdominal aortic wall. However, the relationship between TYROBP and cholangiocarcinoma, renal cancer and AAA remains unclear. The profiles of cholangiocarcinoma dataset GSE107943, renal cell carcinoma dataset GSE213324, and AAA dataset GSE47472 were downloaded from the GEO database using the platforms GPL18573, GPL24676, and GPL10558. DEGs were screened, WGCNA was performed as well as construction and analysis of PPI network. Functional enrichment analysis, GSEA, heat map of gene expression, survival analysis, and immune infiltration analysis were performed. The most relevant diseases to core genes were found by CTD. The GSE107943 dataset identified 3383 DEGs for cholangiocarcinoma, GSE47472 identified 95 DEGs for abdominal aortic aneurysm, and GSE213324 identified 10245 DEGs for renal cell carcinoma. For the GSE107943 cholangiocarcinoma dataset, GO analysis revealed enrichment in immune response, cell adhesion, extracellular space, and oxidoreductase activity. KEGG analysis indicated enrichment in metabolic pathways, the PI3K-Akt signaling pathway, cell apoptosis, the cell cycle, and the NF-kappa B signaling pathway. In the GSE47472 AAA dataset, GO analysis showed enrichment in neuroblast differentiation, cardiac muscle myofilament complex, and alkaline binding. KEGG analysis indicated enrichment in mRNA surveillance pathway and purine metabolism. In the GSE213324 renal cell carcinoma dataset, GO analysis indicated enrichment in immune system processes, cell adhesion, and membrane parts. KEGG analysis showed enrichment in cytokine-cytokine receptor interaction, calcium signaling pathway, and hematopoietic cell lineage. Furthermore, for cholangiocarcinoma (GSE107943), enriched terms associated with DEGs were in metabolic pathways, cell apoptosis, and the cell cycle. For AAA (GSE47472), enriched terms were in alkaline binding and cellular redox homeostasis. For renal cell carcinoma (GSE213324), enriched terms were in biological adhesion, regulation of immune system processes, and cell surface. Common core genes (ADH6, AGXT, CYP3A43, TYROBP) were identified for cholangiocarcinoma, renal cell carcinoma, and AAA. ADH6 and TYROBP were associated with cholangiocarcinoma, AAA, renal tumors, kidney diseases, atherosclerosis, and inflammation. TYROBP is abnormally expressed in cholangiocarcinoma, renal cancer and abdominal aortic aneurysm.

PMID:38181271 | PMC:PMC10766282 | DOI:10.1097/MD.0000000000036843

Permalink for 'Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma'

Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma

Fetched: January 6th, 2024, 5:01am GMT by Masahiko Kinoshita

Ann Surg Oncol. 2024 Jan 5. doi: 10.1245/s10434-023-14833-1. Online ahead of print.

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear.

PATIENTS AND METHODS: This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies.

RESULTS: Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group.

CONCLUSIONS: Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs.

PMID:38180706 | DOI:10.1245/s10434-023-14833-1

Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma

Fetched: January 5th, 2024, 5:01am GMT by Martijn E H M Wagemans

J Nucl Med. 2024 Jan 4:jnumed.123.265597. doi: 10.2967/jnumed.123.265597. Online ahead of print.

ABSTRACT

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: ⁹⁰Y-glass, ⁹⁰Y-resin, and ¹⁶⁶Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative ⁹⁰Y PET/CT and quantitative ¹⁶⁶Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [¹⁸F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six ⁹⁰Y-glass, 8 ⁹⁰Y-resin, and 7 ¹⁶⁶Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for ⁹⁰Y-glass, 1.5 GBq for ⁹⁰Y-resin, and 7.0 GBq for ¹⁶⁶Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for ⁹⁰Y-glass than for ⁹⁰Y-resin and ¹⁶⁶Ho microspheres (mean tumor-absorbed dose, 197 Gy for ⁹⁰Y-glass vs. 73 Gy for ⁹⁰Y-resin and 50 Gy for ¹⁶⁶Ho; mean treated-normal-liver-absorbed dose, 79 Gy for ⁹⁰Y-glass vs. 37 Gy for ⁹⁰Y-resin and 31 Gy for ¹⁶⁶Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [¹⁸F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.

PMID:38176716 | DOI:10.2967/jnumed.123.265597

Permalink for 'Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma'

Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma

Fetched: January 5th, 2024, 5:01am GMT by Margaret Wheless

Curr Treat Options Oncol. 2024 Jan 5. doi: 10.1007/s11864-023-01153-5. Online ahead of print.

ABSTRACT

Biliary tract cancers are molecularly and anatomically diverse cancers which include intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, and gallbladder cancer. While recognized as distinct entities, the rarer incidence of these cancers combined with diagnostic challenges in classifying anatomic origin has resulted in clinical trials and guideline recommended strategies being generalized patients with all types of biliary tract cancer. In this review, we delve into the unique aspects, subtype-specific clinical trial outcomes, and multidisciplinary management of patients with extrahepatic cholangiocarcinoma. When resectable, definitive surgery followed by adjuvant chemotherapy (sometimes with selective radiation/chemoradiation) is current standard of care. Due to high recurrence rates, there is growing interest in the use of upfront/neoadjuvant therapy to improve surgical outcomes and to downstage patients who may not initially be resectable. Select patients with perihilar cholangiocarcinoma are being successfully treated with novel approaches such as liver transplant. In the advanced disease setting, combination gemcitabine and cisplatin remains the standard base for systemic therapy and was recently improved upon with the addition of immune checkpoint blockade to the chemotherapy doublet in the recently reported TOPAZ-1 and KEYNOTE-966 trials. Second-line all-comer treatments for these patients remain limited in both options and efficacy, so clinical trial participation should be strongly considered. With increased use of molecular testing, detection of actionable mutations and opportunities to receive indicated targeted therapies are on the rise and are the most significant driver of improved survival for patients with advanced stage disease. Though these targeted therapies are currently reserved for the second or later line, future trials are looking at moving these to earlier treatment settings and use in combination with chemotherapy and immunotherapy. In addition to cross-disciplinary management with surgical, medical, and radiation oncology, patient-centered care should also include collaboration with advanced endoscopists, palliative care specialists, and nutritionists to improve global patient outcomes.

PMID:38177560 | DOI:10.1007/s11864-023-01153-5

Pseudocirrhosis: A Case Series with Clinical and Radiographic Correlation and Review of the Literature

Fetched: January 5th, 2024, 5:01am GMT by Gal Sadlik

Dig Dis Sci. 2024 Jan 4. doi: 10.1007/s10620-023-08226-3. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Pseudocirrhosis is a poorly understood acquired morphologic change of the liver that occurs in the setting of metastatic malignancy and radiographically resembles cirrhosis. Pseudocirrhosis has been primarily described in metastatic breast carcinoma, with few case reports arising from other primary malignancies. We present 29 cases of pseudocirrhosis, including several cases from primary malignancies not previously described.

METHODS: Radiologic, clinical, demographic, and biomedical data were collected retrospectively and analyzed. We compared clinical and radiologic characteristics and outcomes between patients with pseudocirrhosis arising in metastatic breast cancer and non-breast primary malignancies.

RESULTS: Among the 29 patients, 14 had breast cancer and 15 had non-breast primaries including previously never reported primaries associated with pseudocirrhosis, melanoma, renal cell carcinoma, appendiceal carcinoid, and cholangiocarcinoma. Median time from cancer diagnosis to development of pseudocirrhosis was 80.8 months for patients with primary breast cancer and 29.8 months for non-breast primary (p = 0.02). Among all patients, 15 (52%) had radiographic features of portal hypertension. Radiographic evidence of portal hypertension was identified in 28.6% of breast cancer patients, compared to 73.3% of those with non-breast malignancies (p = 0.03).

CONCLUSION: Pseudocirrhosis has most commonly been described in the setting of metastatic breast cancer but occurs in any metastatic disease to the liver. Our study suggests that portal hypertensive complications are more common in the setting of non-breast primary cancers than in metastatic breast cancer. Prior exposure to multiple chemotherapeutic agents, and agents known to cause sinusoidal injury, is a common feature but not essential for the development of pseudocirrhosis.

PMID:38175453 | DOI:10.1007/s10620-023-08226-3

Cohort study to assess geographical variation in cholangiocarcinoma treatment in England

Fetched: January 5th, 2024, 5:01am GMT by Sophie Jose

World J Gastrointest Oncol. 2023 Dec 15;15(12):2077-2092. doi: 10.4251/wjgo.v15.i12.2077.

ABSTRACT

BACKGROUND: Outcomes for cholangiocarcinoma (CCA) are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types. Beyond curative surgery, which is only an option for a minority of patients diagnosed at an early stage, few systemic therapy options are currently recommended to relieve symptoms and prolong life. Stent insertion to manage disease complications requires highly specialised expertise. Evidence is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA patients.

AIM: To assess geographic variation in treatments received amongst CCA patients in England.

METHODS: Data used in this cohort study were drawn from the National Cancer Registration Dataset (NCRD), Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset. A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the NCRD. Potentially curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of interest. Linear probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis, and for socio-demographic and clinical characteristics at diagnosis.

RESULTS: Of 8853 CCA patients, 1102 (12.4%) received potentially curative surgery. The mean [95% confidence interval (CI)] percentage-point difference from the population average ranged from -3.96 (-6.34 to -1.59)% to 3.77 (0.54 to 6.99)% across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics, showing statistically significant variation. Amongst 7751 who did not receive surgery, 1542 (19.9%) received systemic therapy, with mean [95%CI] percentage-point difference from the population average between -3.84 (-8.04 to 0.35)% to 9.28 (1.76 to 16.80)% across Cancer Alliances after adjustment, again showing the presence of statistically significant variation for some regions. Stent insertion was received by 2156 (27.8%), with mean [95%CI] percentage-point difference from the population average between -10.54 (-12.88 to -8.20)% to 13.64 (9.22 to 18.06)% across Cancer Alliances after adjustment, showing wide and statistically significant variation from the population average. Half of 8853 patients (n = 4468) received no treatment with either surgery, systemic therapy or stent insertion.

CONCLUSION: Substantial regional variation in treatments received by CCA patients was observed in England. Such variation could be due to differences in case-mix, clinical practice or access to specialist expertise.

PMID:38173436 | PMC:PMC10758644 | DOI:10.4251/wjgo.v15.i12.2077

Intrahepatic cholangiocarcinoma; histological diversity and the role of the pathologist

Fetched: January 5th, 2024, 5:01am GMT by Mina Komuta

J Liver Cancer. 2024 Jan 3. doi: 10.17998/jlc.2023.12.11. Online ahead of print.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) is one of the primary liver cancers (PLC) and presents with tumor heterogeneity. About 50% of iCCAs comprise actionable mutations, which completely change patient management. In addition, the precise diagnosis of iCCA, including subtype, has become crucial, and pathologists play an important role in this regard. This review focuses on iCCA heterogeneity; looking at different perspectives to guide diagnosis and optimal treatment choice.

PMID:38171533 | DOI:10.17998/jlc.2023.12.11

Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control

Fetched: January 4th, 2024, 5:01am GMT by Men-Bao Qian

Clin Microbiol Rev. 2024 Jan 3:e0000923. doi: 10.1128/cmr.00009-23. Online ahead of print.

ABSTRACT

SUMMARYClonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.

PMID:38169283 | DOI:10.1128/cmr.00009-23

Survival analysis of patients with extrahepatic cholangiocarcinoma: a nomogram for clinical and MRI features

Fetched: January 4th, 2024, 5:01am GMT by Yanyan Zeng

BMC Med Imaging. 2024 Jan 2;24(1):7. doi: 10.1186/s12880-023-01188-y.

ABSTRACT

BACKGROUND: This study aimed to establish a predictive model to estimate the postoperative prognosis of patients with extrahepatic cholangiocarcinoma (ECC) based on preoperative clinical and MRI features.

METHODS: A total of 104 patients with ECC confirmed by surgery and pathology were enrolled from January 2013 to July 2021, whose preoperative clinical, laboratory, and MRI data were retrospectively collected and examined, and the effects of clinical and imaging characteristics on overall survival (OS) were analyzed by constructing Cox proportional hazard regression models. A nomogram was constructed to predict OS, and calibration curves and time-dependent receiver operating characteristic (ROC) curves were employed to assess OS accuracy.

RESULTS: Multivariate regression analyses revealed that gender, DBIL, ALT, GGT, tumor size, lesion's position, the signal intensity ratio of liver to paraspinal muscle (SIRLiver/Muscle), and the signal intensity ratio of spleen to paraspinal muscle (SIRSpleen/Muscle) on T2WI sequences were significantly associated with OS, and these variables were included in a nomogram. The concordance index of nomogram for predicting OS was 0.766, and the AUC values of the nomogram predicting 1-year and 2-year OS rates were 0.838 and 0.863, respectively. The calibration curve demonstrated good agreement between predicted and observed OS. 5-fold and 10-fold cross-validation show good stability of nomogram predictions.

CONCLUSIONS: Our nomogram based on clinical, laboratory, and MRI features well predicted OS of ECC patients, and could be considered as a convenient and personalized prediction tool for clinicians to make decisions.

PMID:38166729 | PMC:PMC10763420 | DOI:10.1186/s12880-023-01188-y

Permalink for 'Development and validation of a clinical prediction model for the risk of distal metastasis in intrahepatic cholangiocarcinoma: a real-world study'

Development and validation of a clinical prediction model for the risk of distal metastasis in intrahepatic cholangiocarcinoma: a real-world study

Fetched: January 4th, 2024, 5:01am GMT by Caixia Fang

BMC Gastroenterol. 2024 Jan 2;24(1):1. doi: 10.1186/s12876-023-03084-9.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant and easily metastatic bile duct tumor with poor prognosis. We aimed at studying the associated risk factors affecting distal metastasis of CCA and using nomogram to guide clinicians in predicting distal metastasis of CCA.

METHODS: Based on inclusion and exclusion criteria, 345 patients with CCA were selected from the Fifth Medical Center of Chinese PLA General Hospital and were divided into distal metastases (N = 21) and non-distal metastases (N = 324). LASSO regression models were used to screen for relevant parameters and to compare basic clinical information between the two groups of patients. Risk factors for distal metastasis were identified based on the results of univariate and multivariate logistic regression analyses. The nomogram was established based on the results of multivariate logistic regression, and we drawn the corresponding correlation heat map. The predictive accuracy of the nomogram was evaluated by receiver operating characteristic (ROC) curves and calibration plots. The utility of the model in clinical applications was illustrated by applying decision curve analysis (DCA), and overall survival(OS) analysis was performed using the method of Kaplan-meier.

RESULTS: This study identified 4 independent risk factors for distal metastasis of CCA, including CA199, cholesterol, hypertension and margin invasion, and developed the nomogram based on this. The result of validation showed that the model had significant accuracy for diagnosis with the area under ROC (AUC) of 0.882 (95% CI: 0.843-0.914). Calibration plots and DCA showed that the model had high clinical utility.

CONCLUSIONS: This study established and validated a model of nomogram for predicting distal metastasis in patients with CCA. Based on this, it could guide clinicians to make better decisions and provide more accurate prognosis and treatment for patients with CCA.

PMID:38166611 | PMC:PMC10759461 | DOI:10.1186/s12876-023-03084-9

Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in the caudate lobe: a report of seven cases

Fetched: January 4th, 2024, 5:01am GMT by Yuichi Takano

Clin J Gastroenterol. 2024 Jan 3. doi: 10.1007/s12328-023-01906-7. Online ahead of print.

ABSTRACT

The caudate lobe of the liver is located deep within the body and surrounded by major blood vessels, such as inferior vena cava, portal vein, and hepatic veins. Thus, percutaneous biopsy is technically challenging. Herein, we report seven patients with focal liver lesions in the caudate lobe who underwent endoscopic ultrasound-guided tissue acquisition (EUS-TA). Their median age was 56 (25-79) years, consisting five males and two females, and the median lesion size was 44 (19-77) mm. Transgastric EUS-TA was performed in all patients. The needles used were 22G and 25G in six patients and one patient, and the median procedure time was 18 (13-30) min. In all patients, adequate specimens were collected, and pathological diagnosis was possible (three intrahepatic cholangiocarcinoma, two metastatic tumors from pancreatic cancer, one hepatocellular carcinoma, and one focal nodular hyperplasia). No adverse events associated with the procedure were observed. EUS-TA can be the first choice for tissue acquisition of the caudate lobe lesions.

PMID:38170391 | DOI:10.1007/s12328-023-01906-7

Permalink for 'Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis'

Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis

Fetched: January 4th, 2024, 5:01am GMT by Haishan Deng

Dig Dis Sci. 2024 Jan 3. doi: 10.1007/s10620-023-08210-x. Online ahead of print.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor with a high mortality rate. Resistance to chemotherapy remains a major challenge related to cancer treatment, and increasing the sensitivity of cancer cells to therapeutic drugs is a major focus of cancer treatment.

AIMS: We purposed to explore the role of Metformin in CCA involved in chemotherapeutic sensitivity and Pyruvate kinase M2 (PKM2) through regulating mitochondrial apoptosis in the present study.

METHODS: CCA cell lines of HCC9810 and RBE were treated with Metformin companied with antagonists or agonists of PKM2, cells sensitivity to Gemcitabine, cell migration and invasion along with apoptosis, which is mediated by JC-1 and LDH were assayed.

RESULTS: Our results indicated that Metformin and Gemcitabine exhibit synergistic effect on inhibition of cholangiocarcinoma cell viability, cell migration and invasion as well as promotion apoptosis of cholangiocarcinoma cells. In vivo, Metformin combined with Gemcitabine has cooperation in inhibiting the growth of cholangiocarcinoma cell-derived tumors. Moreover, Metformin and Gemcitabine inhibited expression of PKM2 and PDHB in HCC9810 and RBE.

CONCLUSION: Our study suggested that Metformin may increase the response of cholangiocarcinoma cells to Gemcitabine by suppressing PKM2 to activate mitochondrial apoptosis.

PMID:38170336 | DOI:10.1007/s10620-023-08210-x

The value of contrast-enhanced magnetic resonance imaging for diagnosis of extrahepatic cholangiocarcinoma

Fetched: January 4th, 2024, 5:01am GMT by Ting Yang

Heliyon. 2023 Dec 10;10(1):e23448. doi: 10.1016/j.heliyon.2023.e23448. eCollection 2024 Jan 15.

ABSTRACT

RATIONALE AND OBJECTIVES: To establish a diagnostic model based on contrast-enhanced magnetic resonance imaging (MRI) and clinical characteristics for diagnosing extrahepatic cholangiocarcinoma (eCCA).

MATERIALS AND METHODS: From April 2014 to September 2021, consecutive patients with extrahepatic bile duct lesions who underwent contrast-enhanced MRI within 1 month before pathological examination were retrospectively enrolled. Two radiologists blinded to clinicopathological information independently evaluated MR images. Univariable and multivariable logistic regression analyses were performed to identify significant clinicoradiological features associated with eCCA, which were subsequently incorporated into a diagnostic model. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve.

RESULTS: A total of 182 patients (mean age, 60.8 ± 10.0 years, 117 men) were included, 144 (79 %) of whom had pathologically confirmed eCCA. Diffusion restriction (odds ratio [OR], 8.32; 95 % confidence interval [CI]: 2.88, 25.82; P < 0.001), indistinct outer margin (OR, 4.01; 95 % CI: 1.40, 11.84; P = 0.010), cholelithiasis (OR, 0.34; 95 % CI: 0.12, 1.00; P = 0.049), serum ln(carbohydrate antigen 125) (OR, 4.95; 95 % CI: 1.61, 18.55; P = 0.010), and serum ln(direct bilirubin) (OR, 1.82; 95 % CI: 1.29, 2.63; P < 0.001) were independently associated with eCCA. Incorporating the above 5 variables, a diagnostic model achieved an AUC of 0.912 (95 % CI: 0.859, 0.965), with well-fitted calibration curve (P = 0.815) and good clinical utility. Additionally, the sensitivity, specificity and accuracy of the model were 83.33 %, 86.84 %, and 84.07 %, respectively.

CONCLUSION: The proposed model integrating two MRI features (i.e., indistinct outer margin and diffusion restriction) and three clinical characteristics (i.e., cholelithiasis, lnCA125 and lnDBIL) enabled accurate diagnosis of eCCA. This tool holds the potential to facilitate an early diagnosis and thereby allow timely treatment interventions and improved clinical outcomes for patients with eCCA.

PMID:38169769 | PMC:PMC10758830 | DOI:10.1016/j.heliyon.2023.e23448

Permalink for 'Minimally Invasive Approach Provides Oncological Benefit in Patients with High Risk of Very Early Recurrence (VER) After Surgery for Intrahepatic Cholangiocarcinoma (iCCA)'

Minimally Invasive Approach Provides Oncological Benefit in Patients with High Risk of Very Early Recurrence (VER) After Surgery for Intrahepatic Cholangiocarcinoma (iCCA)

Fetched: January 3rd, 2024, 5:00am GMT by Francesca Ratti

Ann Surg Oncol. 2024 Jan 2. doi: 10.1245/s10434-023-14807-3. Online ahead of print.

ABSTRACT

BACKGROUND: Surgery for intrahepatic cholangiocarcinoma (iCCA) is jeopardized by significant risk of early recurrence (≤ 6 months). The aim of the present study is to analyze the oncological benefit provided by laparoscopic over open approach for iCCA in patients with high risk of very early recurrence (VER).

MATERIALS AND METHODS: A total of 532 liver resections (LR) were performed for iCCA [265 by minimally invasive surgery (MIS) and 267 with open approach, matched through a 1:1 propensity score] and stratified using the postoperative prediction model of VER. Outcomes were compared between open and laparoscopic approaches, specifically evaluating oncological benefit.

RESULTS: The percentage of patients with high risk of VER was similar (32.7% in the laparoscopic group and 35.3% in the open group, pNS). The number of retrieved nodes as well as the rate and depth of negative resection margins were comparable between laparoscopic and open. The surgery-adjuvant treatment interval was shorter in laparoscopic patients in the overall series, as well in the subgroup of high risk of VER. The rate of patients starting adjuvant treatments within 2 months from surgery was higher in laparoscopic group compared with open group. In VER high-risk group both disease-free survival (DFS) and overall survival (OS) were significantly improved in MIS compared with open group (p = 0.032 and p = 0.026, respectively).

CONCLUSIONS: In patients with high risk of VER, laparoscopy translates into an advantage in terms of recurrence-free survival, likely related to lower biological impact of surgery, together with a shorter interval between surgery and start of adjuvant treatments, even allowing for a higher number of patients to start adjuvant therapies within 2 months from resection.

PMID:38165575 | DOI:10.1245/s10434-023-14807-3

The performance of biliary stents in malignant biliary strictures

Fetched: January 3rd, 2024, 5:00am GMT by Bartosz Ostrowski

Pol Arch Intern Med. 2024 Jan 2:16653. doi: 10.20452/pamw.16653. Online ahead of print.

ABSTRACT

INTRODUCTION: Endoscopic stenting is a commonly applied method of treatment in patients with malignant biliary strictures. It involves the use of plastic stents (PS) or self-expandable metal stents (SEMS).

OBJECTIVES: The aim of the study was to compare the effectiveness of SEMS versus PS in the endoscopic drainage of malignant stricture of the biliary tree and its sequels for future optimalisation of this treatment method.

PATIENTS AND METHODS: Data of consecutive 618 patients with malignant biliary stricture in whom 1271 endoscopic retrograde cholangiopancreatography (ERCP) procedures with biliary stenting have been done within 2012-2017 with at least 3-year follow-up were retrospectively derived from hospital database.

RESULTS: The main indications for stenting were pancreatic cancer (37%) and cholangiocarcinoma (34%). The use of SEMS resulted in a greater decline of serum bilirubin compared to PS (37% vs. 32% of baseline concentration). Consequently, the hospital stay was shorter by more than two days (SEMS 9.5 vs PS 11.8 days; P<0.001). The patency time of SEMS was more than twice longer compared to plastic stents (118 vs 46 days; P<0.001) and the procedure-related complications were less frequent (19.3% vs 12.9%, respectively in SEMS and PS group; P=0.001). SEMS proved also to be cost-effective; the hospital profit was 1375 USD for the single hospitalization with SEMS vs PS insertion.

CONCLUSIONS: In patients with malignant strictures of the biliary tree SEMS outperform plastic stents. SEMS should be used as a treatment of choice for biliary drainage in that group of patients.

PMID:38165229 | DOI:10.20452/pamw.16653

Body composition is associated with postoperative complications in perihilar cholangiocarcinoma

Fetched: January 3rd, 2024, 5:00am GMT by Guanwu Wang

Cancer Med. 2024 Jan 1. doi: 10.1002/cam4.6878. Online ahead of print.

ABSTRACT

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a malignant tumor of the hepatobiliary system which is still associated with a challenging prognosis. Postoperative complications play a crucial role in determining the overall prognosis of patients with pCCA. Changes in body composition (BC) have been shown to impact the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC, postoperative complications and oncological outcome in patients with pCCA.

METHODS: All patients with pCCA who underwent curative-intent surgery for pCCA between 2010 and 2022 were included in this analysis. BC was assessed using preoperative computed tomography and analyzed with the assistance of a 3D Slicer software. Univariate and multivariate binary logistic regression analyses were conducted to examine the relationship between BC and clinical characteristics including various measurements of postoperative complications and Cox regressions and Kaplan-Meier analysis to evaluate oncological risk factors in the study cohort.

RESULTS: BC was frequently altered in patients undergoing curative-intent liver resection for pCCA (n = 204) with 52.5% of the patients showing obesity, 55.9% sarcopenia, 21.6% sarcopenic obesity, 48.5% myosteatosis, and 69.1% visceral obesity. In multivariate analysis, severe postoperative complications (Clavien-Dindo ≥3b) were associated with body mass index (BMI) (Odds ratio (OR) = 2.001, p = 0.024), sarcopenia (OR = 2.145, p = 0.034), and myosteatosis (OR = 2.097, p = 0.017) as independent predictors. Furthermore, sarcopenia was associated with reduced overall survival (OS) in pCCA patients (sarcopenia vs. no-sarcopenia, 21 months vs. 32 months, p = 0.048 log rank).

CONCLUSIONS: BC is highly associated with severe postoperative complications in patients with pCCA and shows tendency to be associated impaired overall survival. Preoperative assessment of BC and interventions to improve BC might therefore be key to improve outcome in pCCA patients undergoing surgical therapy.

PMID:38164056 | DOI:10.1002/cam4.6878

Germline genetic associations for hepatobiliary cancers

Fetched: January 3rd, 2024, 5:00am GMT by Perapa Chotiprasidhi

Cell Mol Gastroenterol Hepatol. 2023 Dec 30:S2352-345X(23)00226-6. doi: 10.1016/j.jcmgh.2023.12.010. Online ahead of print.

ABSTRACT

Hepatobiliary cancers (HBC) include hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma, which originate from the liver, bile ducts, and gallbladder. They are responsible for a substantial burden of cancer-related deaths worldwide. Despite knowledge of risk factors and advancements in therapeutics and surgical interventions, the prognosis for most patients with HBC remains bleak. There is evidence from familial aggregation and case-control studies to suggest a familial risk component in HBC susceptibility. Recent progress in genomics research has led to the identification of germline variants including single nucleotide polymorphisms (SNPs) and pathogenic or likely pathogenic (P/LP) variants in cancer-associated genes associated with HBC risk. These findings emerged from genome-wide association studies and next-generation sequencing techniques such as whole-exome sequencing. Patients with other cancer types, including breast, colon, ovarian, prostate, and pancreatic cancer, are recommended by guidelines to undergo germline genetic testing, but similar recommendations are lagging in HBC. This prompts the question of whether multi-gene panel testing should be integrated into clinical guidelines for HBC management. Here, we review the hereditary genetics of HBC, explore studies investigating SNPs and P/LP variants in HBC patients, discuss the clinical implications and potential for personalized treatments and impact on patient's family members, and conclude that additional studies are needed to examine how genetic testing can be applied clinically.

PMID:38163482 | DOI:10.1016/j.jcmgh.2023.12.010

$Permalink for 'Case Report: A novel mixture of dose-fractioned radiation and immunotherapy for treatment of cholangiocarcinoma'$

Case Report: A novel mixture of dose-fractioned radiation and immunotherapy for treatment of cholangiocarcinoma

Fetched: January 3rd, 2024, 5:00am GMT by Ningyu Wang

Front Immunol. 2023 Dec 12;14:1273962. doi: 10.3389/fimmu.2023.1273962. eCollection 2023.

ABSTRACT

Malignant tumors of the biliary tract exhibit a high degree of malignancy and heterogeneity with a poor overall prognosis. Immunotherapy has limited benefits for patients with cholangiocarcinoma. Radiation therapy can change the tumor microenvironment, but its effect heavily depends on radiation dose and fraction. We report a case of advanced intrahepatic cholangiocarcinoma in a 43-year-old male patient, with a huge liver mass of 16.5 cm in diameter, with bone and liver metastases at the first diagnosis. First-line treatment with chemotherapy and PD1 inhibitor was sustained only for 8 months. In second-line treatment, radiotherapy was administered, with 5 Gy in 5 fractions administered to the entire tumor area and 25 Gy in 5 fractions to the solid lesions of the tumor. After the completion of radiotherapy, programmed cell death 1 inhibitor combined with tyrosine kinase inhibitor was maintained. The patient achieved a progression-free-survival time of 12 months and an overall survival time of 25 months. The success of our case suggests that mixed low- and high-dose radiation can significantly improve tumor control and survival time. In clinical practice, based on the characteristics of the tumor and existing treatment options, the rational combination of existing treatment regimens can improve the prognosis of cholangiocarcinoma.

PMID:38162668 | PMC:PMC10756898 | DOI:10.3389/fimmu.2023.1273962

Primary hepatic adenosquamous carcinoma: a case report and review of the literature

Fetched: January 3rd, 2024, 5:00am GMT by Haidong Ai

Front Oncol. 2023 Dec 15;13:1328886. doi: 10.3389/fonc.2023.1328886. eCollection 2023.

ABSTRACT

Primary hepatic adenosquamous carcinoma is considered a rare subtype of intrahepatic cholangiocarcinoma, with fewer than 100 domestic and international cases reported. This malignancy exhibits a high degree of malignancy, strong invasiveness, and an unfavorable prognosis due to its propensity for early lymph node and intrahepatic metastasis. The etiology of this disease remains uncertain, and preoperative diagnosis is exceedingly challenging owing to the nonspecific clinical features and lack of specificity in imaging studies. Radical surgical resection is the most effective treatment for non-metastatic tumors, while targeted adjuvant therapy administered postoperatively can enhance therapeutic efficacy and delay tumor recurrence. This article documents the diagnostic and therapeutic course of a case of primary hepatic adenosquamous carcinoma treated at our medical institution, along with a comprehensive synthesis of the clinical characteristics and advances in the diagnosis and treatment of this disease, aiming to augment understanding and serve as a reference for future clinical endeavors.

PMID:38162486 | PMC:PMC10757360 | DOI:10.3389/fonc.2023.1328886

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version)

Fetched: January 3rd, 2024, 5:00am GMT by Han Wang

J Clin Transl Hepatol. 2023 Dec 28;11(7):1553-1564. doi: 10.14218/JCTH.2023.00118. Epub 2023 Jul 24.

ABSTRACT

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5^th edition of the World Health Organization Classification of Tumours of the Digestive System.

PMID:38161496 | PMC:PMC10752808 | DOI:10.14218/JCTH.2023.00118

Current level of shared decision-making in hepatobiliary surgical oncology (SAPACHA)

Fetched: January 3rd, 2024, 5:00am GMT by Britte H E A Ten Haaft

HPB (Oxford). 2023 Dec 20:S1365-182X(23)02044-0. doi: 10.1016/j.hpb.2023.12.009. Online ahead of print.

ABSTRACT

BACKGROUND: Shared decision-making (SDM) may improve patient autonomy and health outcomes. This study assessed the level of SDM at both ends of the spectrum of hepatobiliary surgery to identify needs and opportunities for improvement.

METHODS: A mixed-methods study was performed. Consultations regarding surgery for perihilar cholangiocarcinoma (pCCA) or hepatocellular adenoma (HCA) were prospectively included between September 2020 and December 2022. The level of patient involvement in treatment decision-making was assessed objectively by analysis of audio-recorded consultations using the OPTION-5 instrument. The perceived level of SDM was appreciated by patients (SDM-Q-9) and surgeons (SDM-Q-doc) through questionnaires. Higher scores indicated higher levels of SDM. Outcomes were compared between patient groups and two focus groups were held.

RESULTS: Ten pCCA- and nine HCA-patients were included in the quantitative part of the study. Median OPTION-5, SDM-Q-9 and SDM-Q-doc scores were 35% (IQR: 25-45%), 86% (IQR: 76-96%), and 73% (IQR: 71-78%), respectively. SDM-Q-9 scores among HCA-patients (79% [IQR: 71-82%]) were significantly lower than in pCCA-patients (96% [IQR: 93-100%], p < 0.001). In focus groups, patients reported a lack of information, support, and expressed positive attitudes towards decision support tools (DSTs).

CONCLUSION: Patient involvement and information provision among HPB-surgical patients show room for improvement, particularly for HCA-patients. DSTs may be helpful for this purpose.

PMID:38161079 | DOI:10.1016/j.hpb.2023.12.009

Permalink for 'Impact of the course of the segment 4 hepatic artery on proximal ductal margin status in right hepatectomy for perihilar cholangiocarcinoma'

Impact of the course of the segment 4 hepatic artery on proximal ductal margin status in right hepatectomy for perihilar cholangiocarcinoma

Fetched: January 3rd, 2024, 5:00am GMT by Kentaro Togasaki

Surgery. 2023 Dec 29:S0039-6060(23)00895-4. doi: 10.1016/j.surg.2023.11.029. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between the course of the segment 4 hepatic artery and proximal ductal margin status in the right hepatectomy (H15678-B) for perihilar cholangiocarcinoma is unclear. This study aimed to evaluate proximal ductal margin status according to the course of the segment 4 hepatic artery in patients with perihilar cholangiocarcinoma treated with right hepatectomy.

METHODS: Consecutive patients with perihilar cholangiocarcinoma who underwent a right hepatectomy between January 2006 and August 2021 were retrospectively reviewed. The course of the segment 4 hepatic artery was classified based on the positional relationship with the umbilical portion of the left portal vein into R-UP and L-UP types. The R-UP type had the segment 4 hepatic artery running along the right caudal position of the umbilical portion of the left portal vein, whereas the L-UP type had the segment 4 hepatic artery running along the left cranial position of the umbilical portion of the left portal vein, with or without another branch running along the right caudal position of the umbilical portion of the left portal vein. Proximal ductal margin status after the right hepatectomy was compared between types.

RESULTS: Among 102 patients, 72 (70.5%) were R-UP type, and 30 (29.5%) were L-UP type. Rates of negative proximal ductal margin were higher with the L-UP type (27/30, 90.0%) than with the R-UP type (51/72, 70.8%; P = .04). On multivariate analysis, Bismuth-Corlette type II and IIIa (risk ratio 4.13, 95% confidence interval 1.52-11.5; P = .005) and L-UP type (risk ratio 4.03, 95% confidence interval 1.18-18.8; P = .04) were independent predictors of negative proximal ductal margin after a right hepatectomy for perihilar cholangiocarcinoma.

CONCLUSION: For the course of the segment 4 hepatic artery, L-UP type rather than R-UP type might be anatomically advantageous for achieving negative proximal ductal margin in a right hepatectomy for perihilar cholangiocarcinoma.

PMID:38160087 | DOI:10.1016/j.surg.2023.11.029

Permalink for 'A Standardized Interrupted Parachute Suture Technique in Hepaticojejunostomy for Patients With Perihilar Cholangiocarcinoma'

A Standardized Interrupted Parachute Suture Technique in Hepaticojejunostomy for Patients With Perihilar Cholangiocarcinoma

Fetched: January 3rd, 2024, 5:00am GMT by Naokazu Chiba

Anticancer Res. 2024 Jan;44(1):167-171. doi: 10.21873/anticanres.16799.

ABSTRACT

BACKGROUND/AIM: Although hepaticojejunostomy is a relatively uncomplicated surgical procedure, its postoperative complications can range from a prolonged hospital stay to death. In hepatectomy, including resection of the perihilar bile duct for perihilar cholangiocarcinoma, the difficulty of performing hepaticojejunostomy and the complication rate increase due to the characteristics of surgery required for perihilar cholangiocarcinoma. In this study, we standardized the interrupted parachute suture technique and examined its safety and efficacy.

PATIENTS AND METHODS: The greatest advantage of our technique is the use of interrupted sutures, and the anterior bile duct is threaded prior to completing the posterior anastomosis. Therefore, the field of vision is better when threading the bile duct and intestinal tract, and the needle handling procedure can be performed relatively stress-free regardless of the type of hepatectomy.

RESULTS: In patients who underwent hepaticojejunostomy, postoperative biliary complications, such as anastomotic leakage, biliary stricture, hemobilia, and jejunal bleeding, were not observed.

CONCLUSION: The interrupted suture is easy to implement in biliary reconstruction and can facilitate any type of hepatic resection. In addition, the standardized technique was efficient and safe and did not increase the incidence of postoperative complications.

PMID:38159997 | DOI:10.21873/anticanres.16799

Gene expression signatures of stepwise progression of Hepatocellular Carcinoma

Fetched: January 3rd, 2024, 5:00am GMT by Manisri Porukala

PLoS One. 2023 Dec 29;18(12):e0296454. doi: 10.1371/journal.pone.0296454. eCollection 2023.

ABSTRACT

The molecular pathogenesis of Hepatocellular Carcinoma (HCC) is a complex process progressing from premalignant stages to cancer in a stepwise manner. Mostly, HCC is detected at advanced stages, leading to high mortality rates. Hence, characterising the molecular underpinnings of HCC from normal to cancer state through precancerous state may help in early detection and improve its prognosis and treatment. In this work, we analysed the transcriptomic profile of tumour and premalignant samples from HCC or chronic liver disease patients, who had undergone either total or partial hepatectomy. The normal samples from patients with metastatic cancer/polycystic liver disease/ cholangiocarcinoma were also included. A gene co-expression network approach was applied to identify hierarchical changes: modules, pathways, and genes related to different trajectories of HCC and patient survival. Our analysis shows that the progression from premalignant conditions to tumour is accompanied by differences in the downregulation of genes associated with HNF4A activity and the immune system and upregulation of cell cycle genes, bringing about variability in patient outcomes. However, an increase in immune and cell cycle activity is observed in premalignant samples. Interestingly, co-expression modules and genes from premalignant stages are associated with survival. THBD, a classical marker for dendritic cells, is a predictor of survival at the premalignant stage. Further, genes linked to microtubules, kinetochores, and centromere are altered in both premalignant and tumour conditions and are associated with survival. Our analysis revealed a three-way molecular axis of liver function, immune pathways, and cell cycle driving HCC pathogenesis.

PMID:38157373 | PMC:PMC10756545 | DOI:10.1371/journal.pone.0296454

Association of Cholangiocarcinoma among People with Periductal Fibrosis

Fetched: January 3rd, 2024, 5:00am GMT by Hathaiwan Moungthard

Asian Pac J Cancer Prev. 2023 Dec 1;24(12):4147-4154. doi: 10.31557/APJCP.2023.24.12.4147.

ABSTRACT

BACKGROUND: Cholangiocarcinoma (CCA) is a highly fatal tumor, and the most favorable chance for long-term survival lies in curative resection. Periductal fibrosis (PDF), a precancerous condition associated with chronic inflammation of the bile ducts, can serve as a screening marker for CCA using hepatobiliary ultrasonography (US). However, limited studies have explored the relationship between PDF and CCA. This study aimed to investigate the association between PDF and CCA in a population at risk in Northeast Thailand.

METHODS: The study included participants enrolled in the Cholangiocarcinoma Screening and Care Program (CASCAP) between 2013 and 2021 who underwent US. Histological evaluations were conducted following the standard protocol of the tertiary hospital at Khon Kaen University, Thailand. PDF was defined as the presence of fibrosis in the peripheral (PDF1), segmental (PDF2), or main bile duct (PDF3), diagnosed by well-trained general practitioners or radiologists. The association between PDF and CCA was assessed using multiple logistic regression, calculating adjusted odds ratios (AORs) and 95% confidence intervals (CIs).

RESULTS: Out of 751,061 participants, the overall prevalence of PDF was 115,267 (15.35%), with an overall CCA rate of 0.11%. The rates of CCA were 0.1%, 0.15%, and 0.27% in participants with PDF1, PDF2, and PDF3, respectively. After adjusting for gender, age at enrollment, education levels, history of O. viverrini infection, smoking, and alcohol consumption, the AORs for CCA were 0.94 (95% CI: 0.74 - 1.20), 1.4 (95% CI: 1.03 - 1.91), and 2.52 (95% CI: 1.38 - 4.58) for participants with PDF1, PDF2, and PDF3, respectively.

CONCLUSION: Our findings demonstrate a significant association between fibrosis of the segmental and main bile ducts (PDF2 and PDF3) and CCA, with the strongest association observed in participants with PDF3. Hepatobiliary US screening could serve as a valuable tool for early detection of CCA, enabling timely curative treatment.

PMID:38156850 | DOI:10.31557/APJCP.2023.24.12.4147

Cost-Effectiveness Analysis of Ultrasound Surveillance for Cholangiocarcinoma in an Endemic Area of Thailand

Fetched: January 3rd, 2024, 5:00am GMT by Pavinee Laopachee

Asian Pac J Cancer Prev. 2023 Dec 1;24(12):4117-4125. doi: 10.31557/APJCP.2023.24.12.4117.

ABSTRACT

OBJECTIVE: This research aimed to analyze the cost-effectiveness of ultrasound surveillance for Cholangiocarcinoma (CCA) in a high-risk population residing in the northern region of Thailand and compare these results with the non-surveillance patients who presented with CCA.

METHODS: This was a retrospective descriptive study of two groups monitored and treated for CCA in the same institute, but differing as to whether ultrasound was included in the surveillance. The ultrasound surveillance group comprised those who participated in the cohort study of CCA at Chulabhorn Hospital from 2011 to 2017. Whereas, the non-ultrasound surveillance group consisted of patients treated for CCA at Chulabhorn Hospital from 2009 to 2015 (and not part of the first group). Historical data and societal perspectives were analyzed and interpreted using a decision tree model. The results of one-way sensitivity analyses of probability and cost parameters affecting the change in incremental cost-effectiveness ratio (ICER) were analyzed and presented using tornado diagrams.

RESULT: The ultrasound surveillance group had the quality-adjusted life years gained (QALY gained) of 0.117 years, resulting in the incremental cost-effectiveness ratio (ICER) of 152,985 Thai Baht (THB) or equal to 4,222.6 US-dollars (USD) /QALY gained which is about when compared to the non-ultrasound surveillance group. Moreover, the ICER value was within the willingness to pay (WTP) calculated for Thailand of 4,416.2 USD (160,000 THB) /QALY gained. The probability of non-diagnostic CCA in non-ultrasound surveillance group and the cost of abdominal ultrasound were found to be major factors affecting the ICER.

CONCLUSION: Ultrasound surveillance of CCA was cost-effective in Thailand. This information can be helpful for national policy planning in regard to Thai populations at high risk of CCA. Further study is recommended to assess cost-effectiveness in other areas with lower incidences of CCA.

PMID:38156846 | DOI:10.31557/APJCP.2023.24.12.4117

Permalink for 'Nestin may be a candidate marker for differential diagnosis between small duct type and large duct type intrahepatic cholangiocarcinomas'

Nestin may be a candidate marker for differential diagnosis between small duct type and large duct type intrahepatic cholangiocarcinomas

Fetched: December 29th, 2023, 5:01am GMT by Motoko Sasaki

Pathol Res Pract. 2023 Dec 22;253:155061. doi: 10.1016/j.prp.2023.155061. Online ahead of print.

ABSTRACT

BACKGROUNDS/AIMS: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small and large duct types. These two subtypes show distinct differences in various clinicopathological features and possible cell origin and pathways of carcinogenesis, however, a differential diagnosis may be sometimes difficult. Given the type IV intermediate filament, Nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and small duct type iCCAs, the significance of nestin as a differential diagnostic marker between small and large duct types of iCCAs was addressed in the present study.

METHODS: Nestin expression was immunohistochemically assessed in the sections from 36 patients with small duct-type iCCA, 30 with large duct-type iCCA, and 27 with extrahepatic cholangiocarcinoma (CCA). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in small duct type iCCAs.

RESULTS: Nestin expression was detected in 17 small duct type iCCAs (47.2%), one large duct type iCCA (3.8%) and zero extrahepatic CCA. Nestin expression was significantly more frequent in the patients with small duct type iCCAs than in those with large duct type iCCA and extrahepatic CCA (p < 0.01). In 10 liver biopsies, all samples with nestin expression were small duct type iCCAs. Nestin-positive small duct type iCCAs were characterized by a higher histological grade, compared to Nestin-negative small duct type iCCAs (p < 0.01). Nestin-positive small duct type iCCAs tended to have 2 or more genetic alterations, but there was no statistic difference (p > 0.05).

CONCLUSION: Different nestin expression may reflect differences between small duct type iCCA and large duct type/extrahepatic CCA and may be a useful diagnostic marker for small duct type iCCAs.

PMID:38154357 | DOI:10.1016/j.prp.2023.155061

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Fetched: February 16th, 2024, 5:01am GMT by Jessica Speckart

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Fetched: February 16th, 2024, 5:01am GMT by Mario De Bellis

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Fetched: February 16th, 2024, 5:01am GMT by Benedetto Ielpo

Fetched: February 16th, 2024, 5:01am GMT by Yufeng Li

Fetched: February 16th, 2024, 5:01am GMT by Hongjie Xin

Fetched: February 16th, 2024, 5:01am GMT by Lee Choi

Fetched: February 16th, 2024, 5:01am GMT by Yoshitaka Shimamaki

Fetched: February 16th, 2024, 5:01am GMT by Panagiotis Papoutsoglou

Fetched: February 16th, 2024, 5:01am GMT by Natalie Y L Ngoi

Fetched: February 16th, 2024, 5:01am GMT by Funda Meric-Bernstam

Fetched: February 16th, 2024, 5:01am GMT by Francesca Ratti

Fetched: February 16th, 2024, 5:01am GMT by Pim Hendriks

Fetched: February 16th, 2024, 5:01am GMT by Benjie Xu

Fetched: February 16th, 2024, 5:01am GMT by Alejandro Martinez-Esteban

Fetched: January 10th, 2024, 5:01am GMT by Sven H Loosen

Fetched: January 10th, 2024, 5:01am GMT by Jan Bednarsch

Fetched: January 10th, 2024, 5:01am GMT by Christoph Schramm

Fetched: January 10th, 2024, 5:01am GMT by C Chen

Fetched: January 10th, 2024, 5:01am GMT by Dorota N Rybczynska

Fetched: January 10th, 2024, 5:01am GMT by Yihang Zhao

Fetched: January 10th, 2024, 5:01am GMT by Bao Ying

Fetched: January 9th, 2024, 5:01am GMT by Limin Wang

Fetched: January 9th, 2024, 5:01am GMT by Jung Ho Im

Fetched: January 9th, 2024, 5:01am GMT by Clémence Astier

Fetched: January 9th, 2024, 5:01am GMT by Kathryn Gunn

Fetched: January 9th, 2024, 5:01am GMT by Phattharaphon Wongphutorn

Fetched: January 9th, 2024, 5:01am GMT by Julia Purchla

Fetched: January 9th, 2024, 5:01am GMT by Matheus de Oliveira Veras

Fetched: January 9th, 2024, 5:01am GMT by Jianjun Wang

Fetched: January 9th, 2024, 5:01am GMT by Ruizhen Cao

Fetched: January 8th, 2024, 5:01am GMT by Eisho Kanemitsu

Fetched: January 8th, 2024, 5:01am GMT by Eko Suyanto

Fetched: January 8th, 2024, 5:01am GMT by Hyeseon Yun

Fetched: January 7th, 2024, 5:01am GMT by Jing Gu