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Biosci Trends. 2024 Sep 16;18(4):379-387. doi: 10.5582/bst.2024.01230. Epub 2024 Aug 25.
ABSTRACT
The prognostic significance of the signet-ring cell component in gallbladder carcinoma (GBC) has not been systematically evaluated. The aim of this study was to assess the similarities and differences between gallbladder signet-ring cell carcinoma (GBSRCA) and gallbladder adenocarcinoma (GBAC) in terms of clinicopathological features and long-term survival. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed 6,612 patients diagnosed with gallbladder cancer between 2000 and 2021. The cohort included 147 patients with GBSRCA and 6,465 with GBAC. Patients with GBSRCA were significantly younger, with 33.3% being age 60 or younger compared to 23.9% of patients with GBAC (p = 0.009). There was a higher proportion of females in the GBSRCA group (77.6%) compared to the GBAC group (70.1%, p = 0.049). GBSRCA was associated with a more advanced tumor stage (T3-T4: 56.5% vs. 44.4%, P = 0.004), higher rates of lymph node metastasis (43.5% vs. 28.0%, P < 0.001), and poorer differentiation status (poorly to undifferentiated: 80.3% vs. 29.7%, P < 0.001). Survival analysis revealed that patients with GBSRCA had significantly worse overall survival (OS) and cancer-specific survival (CSS) compared to patients with GBAC (p < 0.001). GBSRCA was an independent prognostic factor for OS (P = 0.001) in the entire cohort, while the T stage and N stage were independent prognostic factors for OS and CSS in patients with GBSRCA. Even after propensity score matching, patients with GBSRCA still had a poorer prognosis.
PMID:39183029 | DOI:10.5582/bst.2024.01230
Cancer Sci. 2024 Oct;115(10):3481-3482. doi: 10.1111/cas.16235. Epub 2024 Aug 14.
NO ABSTRACT
PMID:39143649 | PMC:PMC11447876 | DOI:10.1111/cas.16235
Ann Surg Oncol. 2024 Nov;31(12):7896-7897. doi: 10.1245/s10434-024-15952-z. Epub 2024 Aug 14.
ABSTRACT
BACKGROUND: Open radical cholecystectomy is the current "gold standard" for the management of gallbladder cancer. In well-selected patients, robotic radical cholecystectomy (RRC) can be a suitable alternative offering immediate postoperative benefits, such as less blood loss, shorter hospital stay, and fewer complications, while being oncologically equivalent. However, it requires a longer learning curve.1 METHODS: This video demonstrates the technical equivalence of the robotic approach when performing portal lymphadenectomy (station 8, 12, and 13) with emphasis on retraction techniques to emulate the open approach. In the case presented, a 40-year-old female patient had an intraluminal gallbladder mass with periportal nodes as revealed by computed tomography. Patient underwent a RRC with portal lymphadenectomy, performed on the DaVinci Xi robotic system. The surgery can be divided into five major steps: (1) Station 16b1 node sampling in the inter-aortocaval region; (2) Right portal lymphadenectomy (station 13, 12b, 12p); (3) Left portal lymphadenectomy (station 8a, 8p, 12a, 12p); (4) Anterior portal lymphadenectomy (station 12a, 12b); and (5) Cholecystectomy with liver wedge resection. The technical nuances of each of these steps is compared with its counterpart in the open approach to demonstrate equivalence. The key element in achieving a thorough oncological clearance is to replicate the retraction techniques of the open approach on the robotic platform by using vessel tapes for portal lymphadenectomy.
CONCLUSIONS: There remains little doubt regarding the feasibility and early postoperative benefits of RRC.2 This video demonstrates the equivalence of a standardized technique of robotic portal lymphadenectomy and liver wedge resection to the open approach. However, prospective studies are needed to further evaluate the long-term benefits of the procedure.
PMID:39141145 | DOI:10.1245/s10434-024-15952-z
Surgery. 2024 Oct;176(4):1016-1017. doi: 10.1016/j.surg.2024.07.006. Epub 2024 Aug 9.
NO ABSTRACT
PMID:39122593 | DOI:10.1016/j.surg.2024.07.006
Ann Surg Oncol. 2024 Nov;31(12):7898-7899. doi: 10.1245/s10434-024-16006-0. Epub 2024 Aug 7.
ABSTRACT
BACKGROUND: Radical resection is the only curative treatment for perihilar cholangiocarcinoma (Klatskin tumor), the most common type of bile duct cancer.1,2 Because Klatskin tumors require major hepatectomy including segment 1, extensive lymphadenectomy, and bile duct reconstruction, laparoscopic surgery has technical challenges, especially with small and multiple bile ducts.2-5 The robotic platform has great freedom of movement, making it effective for dissection and suturing in minimally invasive Klatskin tumor resection.2,3,6 However, few cases have been reported, prompting this video demonstration.
METHODS: A 74-year-old woman was referred to surgery after biliary drainage due to obstructive jaundice. Adenocarcinoma was diagnosed via endobiliary brushing, with magnetic resonance imaging and computed tomography (CT) showing a polypoid mass in the gallbladder and a 3-cm enhancing mass in the perihilar area. No signs of distant metastasis were present. Thus, robotic left hepatectomy including segment 1, partial hepatectomy of segment 5, and bile duct resection were performed (see video).
RESULTS: The total operative time was 419 min, with an estimated blood loss of 300 ml. Computed tomography on postoperative day 5 showed no abnormal findings, and the patient was discharged on postoperative day 10 without complications. The final pathologic results confirmed the double primary adenocarcinomas with clear resection margins of 6.4 cm and 3.8 cm, respectively, and 11 lymph nodes all were negative for malignancy.
CONCLUSIONS: This case exemplifies the safety and effectiveness of robotic surgery for Klatskin tumors, even with concomitant gallbladder cancer, and demonstrates the benefits and potential of this technique in complex surgical procedures.
PMID:39112737 | DOI:10.1245/s10434-024-16006-0
2024 Oct 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–.
ABSTRACT
Pancreaticoduodenectomy, commonly known as the Whipple procedure, is a complex and technically challenging surgery primarily used to treat malignancies in the pancreatic head, periampullary region, and distal bile duct. The procedure involves the resection of the pancreatic head and uncinate process, duodenum, proximal jejunum, distal bile duct, gallbladder, and usually part of the stomach, followed by restoring bilioenteric continuity (see Image. Pancreaticoduodenectomy [Whipple Procedure]). While predominantly performed for malignant conditions, it is also indicated for benign conditions like chronic pancreatitis, large symptomatic cysts, or premalignant lesions such as intrapancreatic mucinous neoplasms.
The procedure was first performed by Walter Kausch in Germany and later refined by Allen Whipple in the United States and has become a cornerstone in managing pancreatic and periampullary cancers. Advances in surgical techniques, including minimally invasive approaches like laparoscopy with or without robotic assistance, have improved outcomes, yet the Whipple procedure remains associated with significant morbidity and mortality. Successful outcomes hinge on meticulous patient selection, comprehensive preoperative preparation, skilled surgical and anesthetic techniques, and coordinated postoperative care.
J Gastrointest Surg. 2024 Oct 10:S1091-255X(24)00666-8. doi: 10.1016/j.gassur.2024.10.006. Online ahead of print.
ABSTRACT
BACKGROUND: Gallbladder cancer (GBC) has been associated with high rates of recurrence and dismal prognosis even after curative-intent resection. The prognostic utility of the modified ALBI (mALBI) score among individuals undergoing curative-intent resection for GBC has not been determined.
METHODS: Patients undergoing radical resection for GBC between 2000-2022 were identified from an international, multi-institutional database. Preoperative albumin and bilirubin levels were used to calculate the mALBI score. The relationship between mALBI, overall survival (OS), and recurrence-free survival (RFS) was examined.
RESULTS: Among 269 patients undergoing radical resection for GBC, 59.9% of patients had mALBI grade 1, 17.8% had grade 2a, 17.5% had grade 2b, and 4.8% had mALBI grade 3. Following surgery, patients with high mALBI (Grade 2b/3) had worse 5-year OS (19.2% vs. 54.4%, p<0.001) and RFS (17.8% vs. 42.0%, p<0.001) compared with patients with a low mALBI (Grade 1/2a) score. On multivariable analysis, after controlling for relevant clinicopathologic variables, a high mALBI score remained independently associated with higher hazards of death and recurrence (OS: HR 2.38, 95%CI 1.50-3.79; RFS: HR 2.12, 95%CI 1.41-3.20) compared with individuals with a low mALBI score following curative-intent resection for GBC. Of note, mALBI was associated with incrementally worse survival within T2, T3, and N+ categories, whereas classic AJCC subclassifications failed to distinguish patients relative to long-term survival.
CONCLUSION: The mALBI score presents a simple, objective measure of hepatic functional reserve and may be a useful prognostic tool as applied to patients undergoing curative-intent resection for GBC.
PMID:39395615 | DOI:10.1016/j.gassur.2024.10.006
JCO Glob Oncol. 2024 Oct;10:e2400090. doi: 10.1200/GO.24.00090. Epub 2024 Oct 10.
ABSTRACT
PURPOSE: Gallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on ERBB2 alterations.
METHODS: Patients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets.
RESULTS: A total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% v 44%; P = .0003). The prevalence of ERBB2 alterations was comparable between the two cohorts (15% v 9%; P = .42). Overall, ERBB2 alterations were present in 14% of patients (8% with ERBB2 amplification, 4% ERBB2 mutation, 1.5% concurrent amplification and mutation, and 0.4% ERBB2 fusion). Notably, patients with GBC that harbored ERBB2 alterations had better overall survival (OS) versus their ERBB2-wild type counterparts (22.3 months v 11.8 months; P = .024).
CONCLUSION: The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.
PMID:39388662 | DOI:10.1200/GO.24.00090
Int J Cancer. 2024 Oct 9. doi: 10.1002/ijc.35179. Online ahead of print.
ABSTRACT
There is a paucity of literature regarding the effect of anesthetic techniques on antitumor immunity, especially in gall bladder malignancies. We designed a study to compare the effect of propofol-based total intravenous anesthesia and sevoflurane-based general anesthesia-on antitumor immunity, including tumor growth factor-β (TGF-β), T-helper cell profile, and inflammatory markers. A pilot prospective randomized trial was conducted in 64 patients undergoing surgery for gall bladder malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of ASA physical status I-III fulfilling the inclusion criteria were randomized to either group S (sevoflurane-based general anesthesia) or group T (propofol-based total intravenous anesthesia). Preoperative (morning of surgery) and postoperative (24 h and 1 month after surgery) blood samples were obtained. Demographic profile and preoperative parameters were comparable between both groups. There was a statistically significant difference in the postoperative value of TGF-β (higher in group T). There was a statistically significant difference in postoperative interleukin-17A value (indicative of TH17 cells), and it was found to be higher in group S. Propofol-based TIVA increases serum TGF-β levels. At the same time, Sevoflurane modulates T-helper cells-based immunity to increase TH17 cells in patients with gall bladder cancer. Multiple larger studies will be required to validate the results and provide useful recommendations.
PMID:39381899 | DOI:10.1002/ijc.35179
Clin Gastroenterol Hepatol. 2024 Oct 4:S1542-3565(24)00866-8. doi: 10.1016/j.cgh.2024.07.046. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: Cholelithiasis is the most well-recognized risk factor for gallbladder cancer (GBC), the predominant biliary-tract malignancy; however, credibility on other modifiable exposures remains uncertain. We performed a field-wide systematic review and meta-analysis on environmental factors associated with GBC.
METHODS: We systematically searched Medline/PubMed and Embase up to May 8, 2023, to identify randomized and non-randomized studies examining environmental factors for GBC. We conducted random-effects meta-analyses focusing on longitudinal studies. Evidence from case-control studies was considered complementary. Evidence credibility was graded by prespecified criteria including the random-effects estimate, 95% confidence interval, P-value, statistical heterogeneity, small-study effects, and robustness to unmeasured confounding.
RESULTS: We identified 215 eligible primary studies and performed 350 meta-analyses across seven domains: lifestyle; reproductive; metabolic; dietary; infections; interventions; contaminants, and occupational exposures. Based on longitudinal evidence, body-mass index (RR per 5-unit increase 1.27; 95% CI, 1.21‒1.33), hip circumference (RR per 5-cm increase 1.16; 1.11‒1.22), infection of bile ducts (RR 31.7; 24.8-40.6), high parity (RR 1.48, 1.30‒1.68), obesity (RR 1.70; 1.44‒2.01), overweight (RR 1.28; 1.14‒1.43), waist circumference (RR per 5-cm increase 1.14; 1.10‒1.18), and waist-to-height ratio (RR per 0.1 increase 1.49; 1.36‒1.64) were robustly associated with increased GBC risk, while high education (RR 0.63; 0.49‒0.82) was associated with reduced risk (moderate-to-high credibility). Another 39 significant associations showed lower credibility, including different exposure scenarios of tobacco smoking, alcohol consumption and insufficient physical activity.
CONCLUSIONS: This study offers a detailed appraisal and mapping of the evidence on modifiable factors for GBC. Further high-quality prospective studies are essential to validate emerging associations and inform preventive strategies in high-incidence areas.
PMID:39370088 | DOI:10.1016/j.cgh.2024.07.046
J Cancer Res Clin Oncol. 2024 Oct 6;150(10):447. doi: 10.1007/s00432-024-05975-0.
ABSTRACT
BACKGROUND: Gallbladder carcinoma is the most common malignant tumor of the biliary system, and has a poor overall prognosis. Poor prognosis in patients with gallbladder carcinoma is associated with the aggressive nature of the tumor, subtle clinical symptoms, ineffective adjuvant treatment, and lack of reliable biomarkers.
PURPOSE: Therefore, evaluating the prognostic factors of patients with gallbladder carcinoma can help improve diagnostic and treatment methods, allowing for tailored therapies that could benefit patient survival.
METHODS: This article systematically reviews the factors affecting the prognosis of gallbladder carcinoma, with the aim of evaluating prognostic risk in patients.
CONCLUSION: A comprehensive and in-depth understanding of prognostic indicators affecting patient survival is helpful for assessing patient survival risk and formulating personalized treatment plans.
PMID:39369366 | PMC:PMC11456552 | DOI:10.1007/s00432-024-05975-0
Cancer Immunol Immunother. 2024 Oct 3;73(12):240. doi: 10.1007/s00262-024-03831-1.
ABSTRACT
BACKGROUND: Lenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC).
METHODS: Patients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety.
RESULTS: A total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2-20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2-26.9) and 6.1 (95% CI: 4.9-7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil-lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported.
CONCLUSION: Anti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.
PMID:39358463 | PMC:PMC11447189 | DOI:10.1007/s00262-024-03831-1
World J Surg Oncol. 2024 Oct 1;22(1):263. doi: 10.1186/s12957-024-03533-z.
ABSTRACT
BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignancy, with limited survival profiles after curative surgeries. This study aimed to develop a practical model for predicting the postoperative overall survival (OS) in GBC patients.
METHODS: Patients from three hospitals were included. Two centers (N = 102 and 100) were adopted for model development and internal validation, and the third center (N = 85) was used for external testing. Univariate and stepwise multivariate Cox regression were used for feature selection. A nomogram for 1-, 3-, and 5-year postoperative survival rates was constructed accordingly. Performance assessment included Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier curves were utilized to evaluate the risk stratification results of the nomogram. Decision curves were used to reflect the net benefit.
RESULTS: Eight factors, TNM stage, age-adjusted Charlson Comorbidity Index (aCCI), body mass index (BMI), R0 resection, blood platelet count, and serum levels of albumin, CA125, CA199 were incorporated in the nomogram. The time-dependent C-index consistently exceeded 0.70 from 6 months to 5 years, and time-dependent ROC revealed an area under the curve (AUC) of over 75% for 1-, 3-, and 5-year survival. The calibration curves, Kaplan-Meier curves and decision curves also indicated good prognostic performance and clinical benefit, surpassing traditional indicators TNM staging and CA199 levels. The reliability of results was further proved in the independent external testing set.
CONCLUSIONS: The novel nomogram exhibited good prognostic efficacy and robust generalizability in GBC patients, which might be a promising tool for aiding clinical decision-making.
PMID:39354502 | PMC:PMC11445856 | DOI:10.1186/s12957-024-03533-z
Diagn Pathol. 2024 Sep 27;19(1):129. doi: 10.1186/s13000-024-01550-w.
ABSTRACT
BACKGROUND: Distinguishing reactive atypia from dysplasia in cholecystectomy specimens can be histologically challenging. The aim of this study was to evaluate the utility of IMP3, p53, and S100P immunostains in differentiating reactive atypia from dysplasia in cholecystectomies.
METHODS: Fifty-four cholecystectomies were reviewed and characterized into 5 groups: 2 normal, 29 reactive atypia, 16 low-grade dysplasia, 2 high-grade dysplasia, and 5 adenocarcinoma. IMP3, p53, and S100P immunostains were performed and evaluated. IMP3 (nuclear) and S100P (nuclear or nuclear/cytoplasmic) were categorized into negative or positive expression, and p53 was categorized into wild-type and aberrant/mutant expression. Chi-square test was used for statistical analysis.
RESULTS: The patients were mostly middle-aged women (mean 44, range 19-87 years, 81% female), with predominantly Hispanic White ethnicity (80%). The majority of the normal and reactive atypia cases showed negative IMP3 (100% and 75.9%, respectively) and wild-type p53 (100% and 89.7%, respectively) staining. Over half (56.3%) of the low-grade dysplasia and all the high-grade dysplasia cases showed IMP3 positivity. Aberrant p53 staining pattern was seen in half of both low and high-grade dysplasia cases. Adenocarcinoma showed IMP3 positivity in 80% and p53 aberrancy in all cases. S100P showed no statistical significance among the diagnostic categories. Significant differences in staining patterns were found between reactive atypia vs. low-grade dysplasia, and reactive atypia vs. low-grade + high-grade dysplasia using a combination of IMP3 and p53 stains (all p < 0.05).
CONCLUSIONS: In challenging cholecystectomies, IMP3 positivity or aberrant p53 expression may serve as a useful adjunct to support a diagnosis of dysplasia over reactive atypia.
PMID:39334193 | PMC:PMC11429068 | DOI:10.1186/s13000-024-01550-w
Front Oncol. 2024 Sep 12;14:1387952. doi: 10.3389/fonc.2024.1387952. eCollection 2024.
ABSTRACT
BACKGROUND: Irreversible electroporation has been proved as a feasible and safe method against tumor in liver. However, few studies focused on tumors adjacent to perihepatic important structure like vessels, biliary system and gall bladder. These structures limit the effectiveness of conventional treatments. The aim of this article is to analyze the clinical outcomes of patients with hepatic tumors at the special sites who received IRE treatment and provide reliable evidence for broadening the scope of IRE's clinical application.
METHODS: The clinical information of patients who underwent IRE ablation for tumors adjacent to perihepatic important structure between February 2017 and December 2021 was collected and retrospectively analyzed. All patients underwent contrast-enhanced CT or MRI for further evaluation at the 1-month follow-up and every 3 months thereafter. Post-ablation complications, recurrence, progression-free survival and overall survival were evaluated to analyze the prognosis of IRE ablation adjacent to perihepatic important structure. Categorical variables are presented as numbers followed by percentages. Continuous data are presented as the mean ± deviation. The tumor size and IRE ablation size were evaluated by the maximum diameters.
RESULTS: Thirty-two patients who underwent IRE ablation for tumor adjacent to perihepatic important structure were studied in this research. There were 39 lesions in 32 patients treated with IRE ablation. Fourteen of them (35.9%) were located adjacent to the porta hepatis, and 8 of them (20.5%) were located adjacent to the hepatocaval confluence. Subcapsular lesions accounted for 15.4% (6 of 39 lesions). The other 11 lesions were in the para gallbladder (5 of 39 lesions, 12.8%), the caudate lobe (5 of 39 lesions, 12.8%) and the colonic hepatic flexure (1 of 39 lesions, 2.6%). According to the Clavien-Dindo classification system for complications, all relative patients with cancer experienced complications below class III except one patient who developed postoperative hemorrhagic shock and improved after timely treatment. Recurrence in situ was observed in 5 of 32 (15.6%) patients. The median PFS of the patients who received IRE ablation was 384 days, and the median OS was 571 days.
CONCLUSION: IRE ablation is a feasible and safe treatment strategy for tumors adjacent to perihepatic important structure. With improved equipment, optimized therapeutic parameters and long-term clinical trials, IRE will play an increasingly important role in the treatment of tumors in liver.
PMID:39328209 | PMC:PMC11424374 | DOI:10.3389/fonc.2024.1387952
Radiology. 2024 Sep;312(3):e231810. doi: 10.1148/radiol.231810.
ABSTRACT
A 45-year-old female patient who was previously healthy presented after several weeks of fullness in the right upper quadrant of the abdomen. The patient did not experience pain, nausea, vomiting, or jaundice, and had no contributory past medical or surgical history, including no history of malignancy. Upon examination, vital signs were within normal limits and the patient appeared well, with soft palpable fullness in the right upper quadrant. The abdomen was nontender and nondistended. Laboratory investigation revealed no abnormalities, with a normal complete blood cell count and normal serum tumor markers that included α-fetoprotein (<2.0 ng/mL; reference, <8.3 ng/mL), cancer antigen 19-9 (21.6 U/mL; reference, <35 U/mL), and carcinoembryonic antigen (1.3 ng/mL; reference, <5 ng/mL). CT of the abdomen and pelvis was performed with intravenous contrast material in the emergency department. Subsequently, combined MRI and MR cholangiopancreatography of the abdomen was performed with and without intravenous contrast material for further evaluation. CT of the chest performed during the same encounter was unremarkable.
PMID:39315902 | DOI:10.1148/radiol.231810
United European Gastroenterol J. 2024 Sep 20. doi: 10.1002/ueg2.12656. Online ahead of print.
ABSTRACT
BACKGROUND: Combined Immuno-chemotherapy consisting of gemcitabine, cisplatin and the programmed death-ligand one inhibitor durvalumab (GCD) is the new standard of care for patients with biliary tract cancers (BTC) based on positive results of the TOPAZ-1 study.
OBJECTIVE: We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort.
METHODS: Patients with BTC treated with GCD from 9 German centers were included. Clinicopathological baseline parameters, overall survival (OS), response rate and adverse events (AEs) were retrospectively analyzed. The prognostic impact was determined by Kaplan-Meier analyses and Cox regression models.
RESULTS: A total of 165 patients treated with GCD between 2021 and 2024 were included in the study. Median OS and median progression-free survival were 14 months (95% CI 10.3-17.7) and 8 months (95% CI 6.8-9.2), respectively. The best overall response rate was 28.5% and disease control rate was 65.5%. While extrahepatic and intrahepatic BTC showed similar outcomes, mOS was significantly shorter in patients with gall bladder cancer (GB-CA) with 9 months (95% CI 5.5-12.4; p = 0.02). In univariate analyses age ≥70 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥1, status post cholecystectomy, GB-CA and high baseline CRP values were significantly associated with OS. ECOG PS ≥ 1 and GB-CA remained independent prognostic factors for OS in multivariable cox regression analysis. AEs have been reported in 130 patients (78.8%), including 149 grade 3-4 AEs (25.5%). One patient died of severe infectious pneumonia. Immune-related (ir)AEs occurred in 17 patients (10.3%), including 9 grade 3-4 irAEs (2.2%), which led to treatment interruption in 4 patients.
CONCLUSIONS: Immuno-chemotherapy in patients with BTC was feasible, effective and safe in a real-life scenario. Our results were comparable to the phase 3 clinical trial results (TOPAZ-1). Reduced efficacy was noted in patients with GB-CA and/or a reduced performance status that warrants further investigation.
PMID:39301763 | DOI:10.1002/ueg2.12656
Int J Clin Oncol. 2024 Sep 19. doi: 10.1007/s10147-024-02616-x. Online ahead of print.
ABSTRACT
BACKGROUND: Biliary tract cancer (BTC) comprises a heterogeneous group of malignancies with poor prognosis because of the limited treatment options. With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests have been widely introduced into daily clinical practice.
PATIENTS AND METHODS: We performed a retrospective, multicenter, observation cohort study. The genomic and clinical data of 85 BTC patients, who underwent CGP testing from August 2021 to September 2023, were analyzed.
RESULTS: There were 62 (73%) cases in which treatment recommendations were raised during expert meetings, including 34 intrahepatic cholangiocarcinoma (ICC), 20 extrahepatic cholangiocarcinoma (ECC) and 8 gall bladder carcinoma (GBC). The drug accessibility rate of the BTC patients was 15.3% (13 cases): ten ICCs, two ECCs, and one GBC. Five ICC patients (three male and two female) with the FGFR2 fusion gene were treated with pemigatinib. Those patients who received a genomically matched therapy had significantly longer median overall survival than those patients who not received. (n = 13; not reached [95% CI not reached-not reached] vs n = 72; 8.6 months [95% CI 6.6-10.0]; hazard ratio 0.24 [95% CI 0.12-0.49], p = 0.013). The median observation period of pemigatinib treatment was 15.4 months (range 10.1-27.4). The responses were classified as PR in three patients, SD in one patient and PD in one patient. The median progression free survival is 9.0 months. No patient had grade 3/4 AEs requiring discontinuation of the treatment.
CONCLUSION: The drug accessibility rate of ICC is high and pemigatinib is effective and well-tolerated in ICC patients harboring FGFR2 gene fusions.
PMID:39297909 | DOI:10.1007/s10147-024-02616-x
Sci Rep. 2024 Sep 19;14(1):21845. doi: 10.1038/s41598-024-72880-4.
ABSTRACT
The gallbladder (GB) is a small pouch and a deep tissue placed under the liver. GB Cancer (GBC) is a deadly illness that is complex to discover in an initial phase. Initial diagnosis can significantly enhance the existence rate. Non-ionizing energy, low cost, and convenience make the US a general non-invasive analytical modality for patients with GB diseases. Automatic recognition of GBC from US imagery is a significant issue that has gained much attention from researchers. Recently, machine learning (ML) techniques dependent on convolutional neural network (CNN) architectures have prepared transformational growth in radiology and medical analysis for illnesses like lung, pancreatic, breast, and melanoma. Deep learning (DL) is a region of artificial intelligence (AI), a functional medical tomography model that can help in the initial analysis of GBC. This manuscript presents an Automated Gall Bladder Cancer Detection using an Artificial Gorilla Troops Optimizer with Transfer Learning (GBCD-AGTOTL) technique on Ultrasound Images. The GBCD-AGTOTL technique examines the US images for the presence of gall bladder cancer using the DL model. In the initial stage, the GBCD-AGTOTL technique preprocesses the US images using a median filtering (MF) approach. The GBCD-AGTOTL technique applies the Inception module for feature extraction, which learns the complex and intrinsic patterns in the pre-processed image. Besides, the AGTO algorithm-based hyperparameter tuning procedure takes place, which optimally picks the hyperparameter values of the Inception technique. Lastly, the bidirectional gated recurrent unit (BiGRU) model helps classify gall bladder cancer. A series of simulation analyses were performed to ensure the performance of the GBCD-AGTOTL technique on the GBC dataset. The experimental outcomes inferred the enhanced abilities of the GBCD-AGTOTL in detecting gall bladder cancer.
PMID:39300284 | PMC:PMC11413303 | DOI:10.1038/s41598-024-72880-4
Clin Case Rep. 2024 Sep 15;12(9):e9427. doi: 10.1002/ccr3.9427. eCollection 2024 Sep.
ABSTRACT
KEY CLINICAL MESSAGE: Cystic artery pseudoaneurysm is a rare phenomenon associated with cholecystitis. We describe the successful management of angioembolisation and cholecystectomy.
ABSTRACT: Cystic artery pseudoaneurysm (CAP) is a rare but clinically significant condition with various etiological factors. Cholecystitis is a prominent cause, often leading to inflammation-induced arterial wall erosion and pseudoaneurysm formation. CAP can present with a range of symptoms, including hemobilia, upper GI bleeding, and jaundice. Despite its rarity, CAP warrants attention in emergency care due to its potential for life-threatening arterial bleeding. Timely diagnosis is crucial, with imaging techniques playing a key role. Depending on the clinical context, management options include endovascular embolization and surgical intervention. Due to the limited cases, standard protocols remain elusive. A 64-year-old woman presented with abdominal pain, anorexia, and weight loss, prompting an evaluation for possible gallbladder cancer. She experienced sudden abdominal pain and upper gastrointestinal bleeding (hematemesis). Laboratory findings revealed leukocytosis, anemia, and abnormal liver function tests. Imaging showed gallbladder wall thickening, luminal contraction, and a pseudoaneurysm in the cystic artery. The patient underwent angioembolization followed by cholecystectomy, confirming acute cholecystitis and CAP with thrombosis. This case underscores the importance of early recognition and appropriate management in CAP, particularly when accompanied by acute cholecystitis.
PMID:39286756 | PMC:PMC11402787 | DOI:10.1002/ccr3.9427
Surg Open Sci. 2024 Aug 22;21:17-21. doi: 10.1016/j.sopen.2024.08.001. eCollection 2024 Sep.
ABSTRACT
BACKGROUND: The role of neoadjuvant therapy (NAT) in gallbladder cancer (GBC) is not well established. We sought to evaluate the effect of NAT on postoperative outcomes following surgical resection of GBC. We hypothesized that patients receiving NAT would have similar rates of 30-day mortality, readmission, and postoperative complications (e.g. bile leakage and liver failure) compared to those who did not receive NAT.
METHODS: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Procedure-Targeted Hepatectomy database was queried for patients that underwent surgery for GBC. Propensity scores were calculated to match patients in a 1:2 ratio based on age, comorbidities, functional status, and tumor staging.
RESULTS: A total of 37 patients undergoing NAT were matched to 74 patients without NAT. There was no difference in any matched characteristics. Compared to the NAT group, the no NAT cohort had similar rates of postoperative bile leakage (NAT 13.5 % vs. no NAT 10.8 %, p = 0.31), postoperative liver failure (5.4 %, vs. 8.1 %, p = 0.60), 30-day readmission (10.8 % vs. 10.8 %, p = 1.00), and 30-day mortality (10.8 % vs. 2.7 %, p = 0.075). All 30-day complications were similar except for a higher rate of postoperative blood transfusion (NAT 32.4 % vs. no NAT 10.8 %, p = 0.005).
CONCLUSION: In patients undergoing surgical resection for GBC, those with and without NAT had similar rates of readmission and 30-day mortality, however NAT was associated with an increased risk for transfusion. Despite use of a large national database, this study may be underpowered to adequately assess the effect of NAT on perioperative GBC outcomes and thus warrants further investigation.
PMID:39279889 | PMC:PMC11402315 | DOI:10.1016/j.sopen.2024.08.001
Am J Case Rep. 2024 Sep 16;25:e944286. doi: 10.12659/AJCR.944286.
ABSTRACT
BACKGROUND Autoimmune pancreatitis (AIP) is identified as an outlier in the clinical practice of chronic pancreatitis caused by autoimmune system dysfunction. AIP is classified into 3 subtypes: AIP type 1 and AIP type 2, which are both sensitive to corticosteroids, and the recently introduced AIP type 3. CASE REPORT We present a case of a patient who presented with painless obstructive jaundice. Computed tomography (CT) revealed hyperdense gallbladder material, further dilatation of intrahepatic bile ducts, and distention of the bile duct (15 mm). Based on the available clinical data, which were strongly compatible with pancreatic cancer, Whipple surgery was selected as the treatment for this case. The consequent histopathological report revealed areas of pancreatic parenchyma with fibrous connective tissue development and dense inflammatory cell infiltration with lymphocytes and plasmacytes, which showcased IgG4 positivity. The clinical results suggested a diagnosis of AIP type 1, and the patient was referred to his treating physician for further treatment of AIP. Preoperative histological examination of the pancreas, along with evaluation of the radiological and serological features, could have aided in determining the diagnosis of AIP type 1 pancreatitis despite the unique abnormality of this particular case. CONCLUSIONS Given the aforementioned conditions, AIP, even as a rare clinical entity, emerges as a canonical ailment and should be considered a viable possibility in clinical practice since it can exclude the patient from an unnecessary surgery.
PMID:39279197 | PMC:PMC11416134 | DOI:10.12659/AJCR.944286
Cancers (Basel). 2024 Aug 30;16(17):3036. doi: 10.3390/cancers16173036.
ABSTRACT
The objective of this study is to investigate the surgical, clinical and pathological outcomes of left hemi-hepatectomy during cytoreductive surgery (CRS) in patients with primary ovarian cancer. The electronic medical charts of patients with primary ovarian cancer who received CRS including left hemi-hepatectomy from 2000 to 2023 were reviewed and retrospectively analyzed. A total of 17 patients underwent left hemi-hepatectomy for resection of a deep peritoneal implant in the round ligament of the liver during primary CRS. Among these 17 patients, hepatic parenchymal invasion was confirmed in 10 patients (58.8%). Tumor distribution of others is as follows: Glisson's capsule, hilum, falciform ligament and gall bladder. Fourteen patients (82.4%) achieved CRS; the remaining three patients had residual tumors less than 1 cm. The median period to subsequent chemotherapy was 21 days (range, 12-35 days). No specific complications related to left hepatectomy were identified such as liver failure or bile leakage. Left hemi-hepatectomy for complete surgical resection of a deep peritoneal implant of the round ligament of the liver is surgically feasible and safe.
PMID:39272893 | PMC:PMC11394477 | DOI:10.3390/cancers16173036
Sci Rep. 2024 Sep 13;14(1):21439. doi: 10.1038/s41598-024-72830-0.
ABSTRACT
In this study, we successfully established a novel gallbladder cancer cell line, designated as GBC-X1, derived from a primary tumor of a gallbladder cancer patient. By comprehensively analyzing the cell line's phenotype, molecular characteristics, biomarkers, and histological characteristics, we confirmed that GBC-X1 serves as a valuable model for investigating the pathogenesis of gallbladder cancer and developing therapeutic agents. GBC-X1 has been continuously cultured for one year, with over 60 stable passages. Morphologically, GBC-X1 exhibits typical features of epithelial tumors. The population doubling time of GBC-X1 is 32 h. STR analysis validated a high consistency between GBC-X1 and the patient's primary tumor. Karyotype analysis revealed an abnormal hypertetraploid karyotype for GBC-X1, characterized by representative karyotypes of 98, XXXX del (4) p (12) del (5) p (21) der (10). Under suspension culture conditions, GBC-X1 efficiently forms tumor balls, while subcutaneous inoculation of GBC-X1 cells into NXG mice leads to xenograft formation with a rate of 80%. Drug sensitivity testing demonstrated that GBC-X1 is resistant to oxaliplatin and sensitive to 5-FU, gemcitabine, and paclitaxel. Immunohistochemistry revealed positive expression of CK7, CK19, E-cadherin, MMP-2, CD44, SOX2, and TP53 in GBC-X1 cells, weak positive expression of Vimentin, and a Ki67 positive rate of 35%. Our research highlights GBC-X1 as a novel gallbladder cancer cell line and emphasizes its potential as an effective experimental model for investigating the pathogenesis of gallbladder cancer and drug development.
PMID:39271742 | PMC:PMC11399391 | DOI:10.1038/s41598-024-72830-0
Ann Med. 2024 Dec;56(1):2402072. doi: 10.1080/07853890.2024.2402072. Epub 2024 Sep 12.
ABSTRACT
Curative resection stands as the sole potential cure for gallbladder cancer (GBC); nevertheless, a dearth of knowledge persists regarding long-term follow-up data and prognostic factors that hinder achieving a cure post-surgery. A retrospective cohort study was conducted by analyzing pathologically confirmed initial resections for GBC between 2000 and 2013 across three Chinese medical centers. The concept of observed cure refers to a 10-year survival period devoid of any disease recurrence. Employing a semiparametric proportional hazards mixture cure model enabled the identification of clinicopathological factors impeding a cure for GBC post-surgery. In our current study, a total of 331 patients were included, with a follow-up period exceeding a decade. The median overall survival (OS) was recorded at 31.6 months, with 39 patients (11.78%) achieving a 10-year OS, classified as 10-year survivors. Within this subset, 36 patients reached a 10-year relapse-free survival, denoting cure, and yielding an observed cure rate of 10.88%. Notably, factors such as combined surgical resection involving invaded organs, positive lymph node metastasis, and R1 resection (below 1%) were identified as virtually precluding a cure. Additionally, patients with T3-4 stage, hepatic invasion, advanced AJCC stage or poor tumor differentiation exhibited a low likelihood of achieving cure (below 5%). The discovery of these prognostic factors holds significant value in tailoring individualized treatment strategies and enhancing clinical decision-making processes.
PMID:39262385 | PMC:PMC11395872 | DOI:10.1080/07853890.2024.2402072
J Surg Oncol. 2024 Sep 10. doi: 10.1002/jso.27867. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: Sarcomas developing in the visceral organs are extremely rare, with no previous reports to describe their national epidemiology. We analyzed Japanese domestic statistics for visceral sarcoma, using the National Cancer Registry (NCR) in Japan, a population-based database launched in 2016.
METHODS: We identified 3245 cases of visceral sarcomas in the NCR dated 2016-2019 to analyze demographic and disease information, initial diagnostic process, volume and type of the hospitals, treatment, and prognosis.
RESULTS: Visceral sarcoma shows a higher prevalence in the older generation (60+ years), with a significant male predominance (p = 0.006). Leiomyosarcomas occurred frequently in the gastrointestinal tract (N = 240; 39.5%), and angiosarcomas in the liver, gall bladder, pancreas, and spleen (N = 244; 43.9%). Visceral sarcomas were often treated in facilities of lower volume without specific adjuvant treatments (p < 0.001). The cumulative 3-year overall survival was 44.8%, and several factors such as surgery or absence of chemotherapy positively affected survival.
CONCLUSIONS: This is the first nationwide study in Japan to analyze the inclusive epidemiology of visceral sarcomas. Visceral sarcomas are characterized by senior and male predominance with relatively poor prognosis, often managed in nonspecialized facilities and rarely with adjuvant therapies. Several histologic subtypes had the propensity to develop in specific organs.
PMID:39257202 | DOI:10.1002/jso.27867
J Gastrointest Cancer. 2024 Dec;55(4):1628-1633. doi: 10.1007/s12029-024-01112-9. Epub 2024 Sep 10.
ABSTRACT
PURPOSE: Patients with advanced cholangiocarcinoma, including gallbladder cancer, typically have a poor prognosis owing to limited effective chemotherapy options. The field of genotype-directed therapy in patients with cholangiocarcinoma is advancing. However, limited clinical data are currently available to evaluate the efficacy of molecularly targeted therapy.
METHODS: Herein, we report the case of a 67-year-old man diagnosed with human epidermal growth factor receptor-2 (HER2)-positive and tumor mutation burden-high (TMB-H) cholangiocarcinoma. The HER2-positive and TMB-H characteristics were identified using comprehensive genomic profiling after showing resistance to gemcitabine and S-1 therapy. In the absence of clinical trials for HER2-positive cancer at that time, the patient was treated with pembrolizumab, which is used for TMB-H solid tumors in clinical practice.
RESULTS: After receiving pembrolizumab, the patient experienced significant shrinkage in the primary tumor and liver metastases. Thus far, the patient has been receiving pembrolizumab for approximately 10 months.
CONCLUSION: To our knowledge, this is the first report showing the efficacy of pembrolizumab in a patient with cholangiocarcinoma harboring both HER2-positive and TMB-H.
PMID:39254819 | DOI:10.1007/s12029-024-01112-9
Pharmacol Res. 2024 Oct;208:107401. doi: 10.1016/j.phrs.2024.107401. Epub 2024 Sep 7.
ABSTRACT
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used for glucose lowering and weight-loss. However, their association with gastrointestinal cancer remains uncertain. This meta-analysis assesses the risk of gastrointestinal cancer in patients treated with GLP-1 RAs.
METHODS: We searched Medline/PubMed, Embase, and Scopus databases from inception to November 15, 2023, for randomized controlled trials (RCTs) with at least 24 weeks of safety follow-up. Pooled risk ratios (RRs) were calculated using fixed- and random-effect models. Risk of bias was assessed using the revised Cochrane risk-of-bias tool, and certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.
RESULTS: We included 90 RCTs with 124,791 participants, with an average follow-up of 3.1 years per participant. No significant association was found between GLP-1 RAs and the risk of any gastrointestinal cancer (RRrandom=0.99, 95 % CI: 0.86-1.13), or site-specific gastrointestinal cancers including biliary tract (RR=0.98, 0.54-1.78), colorectal (RR=1.13, 0.92-1.39), gallbladder (RR=1.32, 0.43-4.00), gastric (RR=0.88, 0.58-1.33), hepatic (RR=0.79, 0.51-1.21), oesophageal (RR=0.70, 0.38-1.28), pancreatic (RR=1.05, 0.77-1.43), and small intestine cancer (RR=0.78, 0.20-3.04). The corresponding absolute risk differences excluded important impacts on risk. Additional analyses, limited to placebo-controlled trials, high-dose studies, or those with a follow-up duration of ≥5 years, confirmed these findings. Risk of bias was generally low and the certainty of evidence was high for all outcomes.
CONCLUSIONS: This meta-analysis found no significant impact of GLP-1 RAs on gastrointestinal cancer risk. Long-term safety monitoring of these agents remains important.
SYSTEMATIC REVIEW REGISTRATION: CRD42023476762.
PMID:39251099 | DOI:10.1016/j.phrs.2024.107401
Int J Cancer. 2024 Sep 6. doi: 10.1002/ijc.35171. Online ahead of print.
ABSTRACT
Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3-8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4-17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5-16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3-35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3-14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2-12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8-100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6-17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.
PMID:39239866 | DOI:10.1002/ijc.35171
F1000Res. 2023 Oct 16;11:696. doi: 10.12688/f1000research.110362.2. eCollection 2022.
ABSTRACT
Psammocarcinoma is an uncommon subtype of low-grade serous carcinoma. It is characterized by the presence of extensive psammoma bodies and can have either an ovarian or peritoneal origin. To our knowledge fewer than 30 cases of primary peritoneal psammocarcinoma (PPP) have been reported in the English literature. We report a rare case of PPP in a 74-year-old female, discovered fortuitously within a laparotomy for gallbladder lithiasis. At laparotomy, multiple nodular implants involving the omentum, the peritoneum and a magma of intestinal loops in the right iliac fossa were noted. A biopsy from nodules was performed. Gross examination showed multiple nodules of different sizes in the fat tissue. Pathologic examination showed massive psammoma bodies representing more than 75% of the tumor. The final diagnosis was psammocarcinoma. Our patient was referred to the gynecologic department for further investigation and to ascertain whether the tumor arose from the ovaries or peritoneum. Hysterectomy, bilateral adnexectomy and omentectomy were performed. Macroscopic examination showed that both ovaries were intact having a normal size. No invasion of ovarian stroma was shown in microscopic examination. The patient died of SARS-CoV-2 (COVID-19) six days after the surgery. PPP is a rare type of low-grade serous carcinoma. The behavior of this tumor is unclear, and the treatment is not standardized because of its rarity and lack of long-term follow-up. More cases need to be studied for better understanding and improvement of the management protocols.
PMID:39233872 | PMC:PMC11372342 | DOI:10.12688/f1000research.110362.2
Immunotherapy. 2024;16(14-15):949-953. doi: 10.1080/1750743X.2024.2382670. Epub 2024 Sep 4.
ABSTRACT
The occurrence of immune-related cholecystitis and the subsequent immunotherapy re-challenge has been rarely reported. A patient diagnosed with recurrent nasopharyngeal carcinoma, developed immune-related cholecystitis after the sixth and eighth cycles of camrelizumab respectively. The patient's symptoms and laboratory test results showed improvement after conservative treatment. Then we chose zimberelimab, a fully humanized PD-1 antibody, as a replacement for camrelizumab in maintenance therapy and successfully completed 37 cycles of zimberelimab (240 mg every 2 weeks per cycle). Surprisingly, the patient experienced no immune-related adverse event and remained in complete remission with a progression-free survival of 28.8 months. The use of Zimberelimab as rechallenge immunotherapy may be an optional choice after managing immune-related cholecystitis induced by other PD-1 antibodies.
PMID:39229795 | DOI:10.1080/1750743X.2024.2382670
Pathology. 2024 Oct;56(6):804-813. doi: 10.1016/j.pathol.2024.03.010. Epub 2024 Jun 4.
ABSTRACT
Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and humans. However, little is known about the prevalence of HNF6 and HNF4α expression in carcinomas of the hepatobiliary tract and pancreas. We aimed to reveal the diagnostic utility of HNF6 and HNF4α immunolabelling in adenocarcinomas of these organs. We investigated HNF6 and HNF4α expression by immunohistochemistry using a total of 480 adenocarcinomas of the digestive system, including 282 of the hepatobiliary tract and pancreas and 198 of the gastrointestinal tract. HNF6 expression was primarily restricted to intrahepatic cholangiocarcinomas (CCs) (63%, n=80) and gallbladder adenocarcinomas (43%, n=88), among others. Notably, small duct intrahepatic CCs almost invariably expressed HNF6 (90%, n=42), showing stark contrast to a low prevalence in large duct intrahepatic CCs (10%, n=21; p<0.0001). HNF6 expression was infrequent in extrahepatic CCs (9%, n=55) and pancreatic ductal adenocarcinomas (7%, n=58), and it was rare in adenocarcinomas of the gastrointestinal tract [oesophagus/oesophagogastric junction (EGJ) (2%, n=45), stomach (2%, n=86), duodenum (0%, n=25), and colorectum (0%, n=42)]. In contrast, HNF4α was widely expressed among adenocarcinomas of the digestive system, including intrahepatic CCs (88%), extrahepatic CCs (94%), adenocarcinomas of the gallbladder (98%), pancreas (98%), oesophagus/EGJ (96%), stomach (98%), duodenum (80%), and colorectum (100%). HNF6 was frequently expressed in and almost restricted to intrahepatic CCs of small duct type and gallbladder adenocarcinomas, while HNF4α was expressed throughout adenocarcinomas of the digestive system. HNF6 immunolabelling may be useful in distinguishing small duct intrahepatic CCs from other types of CC as well as metastatic gastrointestinal adenocarcinomas.
PMID:38926048 | DOI:10.1016/j.pathol.2024.03.010
World J Gastroenterol. 2024 Aug 28;30(32):3739-3742. doi: 10.3748/wjg.v30.i32.3739.
ABSTRACT
Gallbladder cancer (GBC) is a rare disease with a poor prognosis. Simple cholecystectomy may be an adequate treatment only for very early disease (Tis, T1a), whereas reoperation is recommended for more advanced disease (T1b and T2). Radical cholecystectomy should have two fundamental objectives: To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes. However, recent studies have shown that compared with lymph node dissection alone, liver resection does not improve survival outcomes. The oncological roles of lymphadenectomy and liver resection is distinct. Therefore, for patients with incidental GBC without liver invasion, hepatic resection is not always mandatory.
PMID:39221070 | PMC:PMC11362876 | DOI:10.3748/wjg.v30.i32.3739
Eur J Surg Oncol. 2024 Aug 22;50(11):108614. doi: 10.1016/j.ejso.2024.108614. Online ahead of print.
ABSTRACT
BACKGROUND: This study aimed to elucidate the clinical value of combined pancreaticoduodenectomy (PD) for advanced gallbladder cancer according to the mode of cancer spread in the pancreaticoduodenal region.
METHODS: Patients who underwent combined PD for advanced gallbladder cancer were retrospectively reviewed. The mode of cancer spread in the pancreaticoduodenal region was defined as involvement of peripancreatic organs/structures alone, peripancreatic nodal metastasis alone, or both. Surgical outcomes were compared among these modes of spread.
RESULTS: Fifty-seven patients were included. Rates of severe morbidity and mortality were 52.6% and 3.5%, respectively. The mode of cancer spread was involvement of peripancreatic organs/structures alone in 16 patients, peripancreatic nodal metastasis alone in 17, and both in 24; R0 resection rates differed significantly among the groups (87.5% vs. 94.1% vs. 37.5%; p < 0.001). Overall survival (OS) was significantly worse in patients with both modes of spread (5-year OS, 8.3%) than in those with involvement of peripancreatic organs/structures alone (5-year OS, 37.9%; p < 0.001) and those with peripancreatic nodal metastasis alone (5-year OS, 29.4%; p = 0.011). OS was similar between pM0 patients with both modes of spread and pM1 patients (5-year OS, 16.7% vs. 8.7%; p = 0.605). Multivariate analysis identified mode of cancer spread as an independent prognostic factor (p = 0.006).
CONCLUSIONS: Combined PD could be oncologically justified for advanced gallbladder cancer with involvement of peripancreatic organs/structures alone or peripancreatic nodal metastasis alone in the pancreaticoduodenal region. This procedure would not be indicated in patients with both modes of spread.
PMID:39213694 | DOI:10.1016/j.ejso.2024.108614
Cancer Treat Res. 2024;192:147-163. doi: 10.1007/978-3-031-61238-1_8.
ABSTRACT
Gallbladder carcinoma (GBC) is the most common biliary epithelial malignancy, with an estimated incidence of 1.13 cases per 100,000 in the United States (Hundal and Shaffer in Clin Epidemiol 6:99-109, 2014 1; Henley et al. in Cancer Epidemiol Biomarkers Prev 24:1319-1326, 2015 2). The insidious nature and late presentation of this disease place it among the most lethal invasive neoplasms. Gallbladder cancer spreads early by lymphatic or hematogenous metastasis, as well as by direct invasion into the liver. While surgery may be curative at early stages, both surgical and nonsurgical treatments remain largely unsuccessful in patients with more advanced diseases (Rahman et al. in Cancer Med 6:874-880, 2017 3).
PMID:39212920 | DOI:10.1007/978-3-031-61238-1_8
Cureus. 2024 Aug 28;16(8):e68049. doi: 10.7759/cureus.68049. eCollection 2024 Aug.
ABSTRACT
Carcinoma of the gallbladder is an uncommon malignancy with a poor prognosis overall. Histologically, adenocarcinoma is the most common type of gallbladder carcinoma. Adenosquamous carcinoma is a rare histological type of gallbladder carcinoma comprising both the glandular and squamous elements. Adenosquamous carcinoma shows more aggressive behavior than adenocarcinomas and is often detected in a late advanced stage. Treatment is usually extended surgical resection but has a poor prognosis. We present a rare case of adenosquamous carcinoma with lymphovascular invasion in a 72-year-old male who was managed with extended cholecystectomy.
PMID:39206332 | PMC:PMC11357704 | DOI:10.7759/cureus.68049
Surg Endosc. 2024 Sep;38(9):4846-4857. doi: 10.1007/s00464-024-11162-6. Epub 2024 Aug 15.
ABSTRACT
INTRODUCTION: Minimally invasive oncological resections have become increasingly widespread in the surgical management of cancers. However, the role of minimally invasive surgery (MIS) for gallbladder cancer (GBC) remains unclear. We aim to perform a systematic review and network meta-analysis of existing literature to evaluate the safety and feasibility of laparoscopic and robotic surgery in the management of GBC compared to open surgery (OS) by comparing outcomes.
METHODS: A literature search of the PubMed/MEDLINE (2000 to December 2021) and EMBASE (2000 to December 2021) databases was conducted. The primary outcome studied was overall survival, and secondary outcomes studied were postoperative morbidity, severe complications, incidence of bile leak, length of hospital stay, operation time, R0 resection rate, local recurrence and lymph node yield.
RESULTS: Thirty-two full-text articles met the eligibility criteria and were included in the final analysis with a total of 5883 patients undergoing either OS or MIS (laparoscopic or robotic) for GBC. 1- and 2-stage meta-analyses did not reveal any significant differences between OS, laparoscopic and robotic surgery in terms of overall survival, R0 resection, lymph node harvest, local recurrence and post-operative complications. Patients who underwent OS had significantly longer hospitalization stay and intra-operative blood loss compared to those who underwent laparoscopic or robotic surgery. Network meta-analysis did not reveal any significant differences between post-operative and survival outcomes of laparoscopic vs robotic surgery groups.
CONCLUSION: This network meta-analysis suggests that both laparoscopic and robotic surgery are safe and effective approaches in the surgical management of GBC, with post-operative and survival outcomes comparable to OS. An MIS approach may also lead to shorter hospitalization stay, less intraoperative blood loss and post-operative complications compared to OS. There was no obvious benefit of either MIS approach (laparoscopic versus robotic) over the other.
PMID:39148006 | DOI:10.1007/s00464-024-11162-6
Vet Sci. 2024 Aug 12;11(8):371. doi: 10.3390/vetsci11080371.
ABSTRACT
Gallbladder neuroendocrine neoplasms (GB NENs) are among the rarest cancers reported in humans and dogs. This review provides a detailed review of the canine GB NEN literature and an interspecies comparison of demographics, clinical pathophysiology, pathobiology, and therapeutic response of GB NENs. The aim of this work is to explore the relevance of dogs as a spontaneous model for human GB NENs.
PMID:39195825 | PMC:PMC11360110 | DOI:10.3390/vetsci11080371
Zhonghua Yi Xue Za Zhi. 2024 Sep 3;104(34):3171-3174. doi: 10.3760/cma.j.cn112137-20240415-00879.
ABSTRACT
Gallbladder polyp is a common disease of gallbladder, the incidence of gallbladder polyp in China is about 5%~10%, and the trend is increasing year by year. The patients with gallbladder polyps had no obvious clinical symptoms, which was more than that found by ultrasonography during physical examination. At present, the diameter of gallbladder polyps>10 mm is still used by clinicians as the main surgical indication for cholecystectomy. According to the data, about 80% to 90% of gallbladder polyps are cholesterol type polyps and benign gallbladder polyps. For these patients whose gallbladder is removed due to benign gallbladder polyps, we consider that we can continue to observe or retain the gallbladder, without having to bear the adverse consequences that may be caused by gallbladder removal. Based on the literature analysis at home and abroad, this paper discusses the surgical treatment of gallbladder polyps and the results of postoperative pathological diagnosis, and reminds the majority of clinicians to be careful when removing gallbladder polyps.
PMID:39193604 | DOI:10.3760/cma.j.cn112137-20240415-00879
BMC Gastroenterol. 2024 Aug 27;24(1):289. doi: 10.1186/s12876-024-03374-w.
ABSTRACT
PURPOSE: Systemic inflammation and nutrition are vital for tumor progression. This study aimed to identify prognostic inflammation nutrition markers and develop a predictive nomogram for gallbladder cancer (GBC).
METHODS: A total of 123 patients with GBC who underwent surgical resection at the First Affiliated Hospital of Soochow University and Suzhou Kowloon Hospital were included in our study. The final prognostic variables were identified using univariate and multivariate analyses. A nomogram model was then established, and the consistency index (C-index), calibration curves, and Kaplan-Meier analysis were performed to evaluate the accuracy and discrimination of the nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) suggested that our nomogram had better predictive ability and clinical feasibility than a published model.
RESULTS: The cox regression analysis showed that carcinoembryonic antigen (CEA) > 4.580, albumin-bilirubin (ALBI) > -2.091, geriatric nutritional risk index (GNRI) < 90.83, T3-T4, and N2 are independent prognostic factors. A predictive nomogram was constructed with a C-index of 0.793. In the calibration curves, the nomogram-predicted 1-, 3-, and 5-year survival matched well with the actual survival. Kaplan-Meier analysis showed that the high-risk group had worse survival than the low-risk group (P < 0.001). Finally, our nomogram achieved better 1-, 3- and 5-year AUCs than an established model (0.871, 0.844, and 0.781 vs. 0.753, 0.750, and 0.693). DCA also confirmed that our model outperformed the established model.
CONCLUSIONS: In conclusion, our study revealed that CEA > 4.580, GNRI < 90.83, ALBI > -2.091, T3-T4 stage, and N2 were related to clinical outcomes of patients with GBC after surgical resection. The constructed nomogram has superior predictive ability and clinical practicality.
PMID:39192242 | PMC:PMC11350988 | DOI:10.1186/s12876-024-03374-w
Gan To Kagaku Ryoho. 2024 Aug;51(8):843-845.
ABSTRACT
A 49-year-old man underwent an open cholecystectomy for advanced gallbladder cancer in 2021. Three months after surgery, the patient underwent an additional resection, which showed no malignant findings, but 12 months after surgery, contrast-enhanced CT and MRI showed a new mass lesion in segment 8 of the liver, and the patient was diagnosed with postoperative hepatic metastatic recurrence of gallbladder cancer. After referral to our institution, he received 1 course of gemcitabine+cisplatin(GC)therapy and 8 courses of gemcitabine+cisplatin+durvalumab(GCD)therapy. Contrast- enhanced CT and MRI showed that the metastases had shrunk, and PET scan showed no FDG accumulation. Two months after completion of chemotherapy, there was no evidence of metastatic enlargement and new metastasis including distant metastasis, and the patient was referred to our department. Since curative resection was expected, a laparoscopic partial hepatectomy of segment 8 of the liver was performed. Pathological diagnosis revealed no residual tumor. If the metastases could be well controlled by systemic chemotherapy, hepatectomy for hepatic metastases of biliary tract cancer could be a treatment option.
PMID:39191717
Cureus. 2024 Jul 27;16(7):e65490. doi: 10.7759/cureus.65490. eCollection 2024 Jul.
ABSTRACT
Gallbladder agenesis is a rare anatomical variant, and most cases are asymptomatic and diagnosed on autopsy. Few of them may present with features suggestive of biliary tract pathology. A 32-year-old male presented with complaints of intermittent epigastric pain for three months. Abdominal ultrasonography was suggestive of chronic calculous cholecystitis, and he was planned for laparoscopic cholecystectomy. However, no gallbladder was found during the surgery. Postoperative evaluation was suggestive of an absent gallbladder with a normal ductal system. A provisional diagnosis of sphincter of Oddi dysfunction was made based on his symptoms. Congenital absence of gallbladder is a rare anomaly and only a few of the affected individuals are symptomatic. Lack of specific features, coupled with the inability of standard abdominal ultrasonography to detect the absence of gallbladder, can put the treating surgeon in a dilemma intraoperatively. Agenesis of the gallbladder is often missed and this entity should be kept in mind while having difficulty in visualizing the gallbladder. An astute surgeon should be wary of this diagnosis during difficult dissection to avoid bile duct injuries.
PMID:39188464 | PMC:PMC11345654 | DOI:10.7759/cureus.65490
Int Rev Cell Mol Biol. 2024;387:195-213. doi: 10.1016/bs.ircmb.2024.03.007. Epub 2024 May 14.
ABSTRACT
Obesity and cancer are two major health issues all around the world due to their elevated prevalence. Several experimental and epidemiological studies have demonstrated the relationship between obesity and cancer, in which obesity is considered a risk factor for cancer development. The ultimate goal of knowing the epigenetic contribution to the relationship between obesity and cancer is to find the method of intervention or treatment of obesity and cancer. Therefore, providing the most general perspective on epigenetic contribution to the relationship between obesity and cancer is necessary. Obesity is closely related to some common cancers that are currently encountered, including breast, esophagus, liver, kidney, uterus, colorectal, pancreatic, and gallbladder. Obesity has a significant impact that increases the risk of cancer deaths and thereby indirectly affects the choice of treatment. It is estimated that about 4-8% of cancer cases are caused by obesity. In particular, the basic mechanism to understand the relationship between cancer is very complicated and has not been fully understood. This work is aimed at summarizing the current knowledge of the role of epigenetic regulation in the relationship between obesity, and potential applications.
PMID:39179347 | DOI:10.1016/bs.ircmb.2024.03.007
Biofabrication. 2024 Aug 22;16(4). doi: 10.1088/1758-5090/ad6d8c.
ABSTRACT
Gallbladder carcinoma (GBC) is a malignant hepatobiliary cancer characterized by an intricate tumor microenvironments (TME) and heterogeneity. The traditional GBC 2D culture models cannot faithfully recapitulate the characteristics of the TME. Three-dimensional (3D) bioprinting enables the establishment of high-throughput and high-fidelity multicellular GBC models. In this study, we designed a concentric cylindrical tetra-culture model to reconstitute the spatial distribution of cells in tumor tissue, with the inner portion containing GBC cells, and the outer ring containing a mixture of endothelial cells, fibroblasts, and macrophages. We confirmed the survival, proliferation, biomarker expression and gene expression profiles of GBC 3D tetra-culture models. Hematoxylin-eosin (HE) and immunofluorescence staining verified the morphology and robust expression of GBC/endothelial/fibroblast/macrophage biomarkers in GBC 3D tetra-culture models. Single-cell RNA sequencing revealed two distinct subtypes of GBC cells within the model, glandular epithelial and squamous epithelial cells, suggesting the mimicry of intratumoral heterogeneity. Comparative transcriptome profile analysis among variousin vitromodels revealed that cellular interactions and the TME in 3D tetra-culture models reshaped the biological processes of tumor cells to a more aggressive phenotype. GBC 3D tetra-culture models restored the characteristics of the TME as well as intratumoral heterogeneity. Therefore, this model is expected to have future applications in tumor biology research and antitumor drug development.
PMID:39121870 | DOI:10.1088/1758-5090/ad6d8c
BMC Gastroenterol. 2024 Aug 20;24(1):276. doi: 10.1186/s12876-024-03364-y.
ABSTRACT
BACKGROUND: The association between marital status and gallbladder cancer (GBC) remains uncertain. This study aimed to verify the relationship between marital status and GBC and construct a prognostic nomogram to predict the impact of marital status on GBC patients.
METHOD: GBC patients were divided into married and unmarried groups using data from the Surveillance, Epidemiology, and End Results (SEER) database. We employed competing risk analyses, propensity score matching (PSM), and Kaplan-Meier survival analyses. The relationship between marital status and GBC was then verified, and the predicted nomogram was constructed.
RESULTS: A total of 3913 GBC patients were obtained from the SEER database, and an additional 76 GBC patients from Hangzhou Traditional Chinese Medicine Hospital were selected as the external validation group. The competing risk analysis revealed a significant disparity in the 5-year cumulative incidence of cancer-specific death (CSD) between the two cohorts (59.1% vs. 65.2%, p = 0.003). Furthermore, the multivariate competing hazards regression analysis identified a significant association (HR, 1.17; 95% CI, 1.04-1.31; p = 0.007) between marital status and CSD. To assess the 1-, 3-, and 5-year risks of CSD, a comprehensive competing event nomogram was constructed using factors derived from the multivariate analysis. The area under the receiver operating characteristic curve (AUC) values for the 1-, 3-, and 5-year training cohorts were 0.806, 0.785, and 0.776, respectively. In the internal validation cohort, these values were 0.798, 0.790, and 0.790, while the external validation cohort exhibited AUC values of 0.748, 0.835, and 0.883 for the corresponding time intervals. Furthermore, calibration curves demonstrated a commendable level of concordance between the observed and predicted probabilities of CSD.
CONCLUSION: Marriage was a protective factor for GBC patients after taking competing risk into consideration. The proposed nomogram demonstrated exceptional predictive power.
PMID:39164628 | PMC:PMC11334324 | DOI:10.1186/s12876-024-03364-y
BMC Cancer. 2024 Aug 20;24(1):1025. doi: 10.1186/s12885-024-12770-0.
ABSTRACT
BACKGROUND: Most studies on tumour progression from precursor lesion toward gallbladder adenocarcinoma investigate lesions sampled from distinct patients, providing an overarching view of pathogenic cascades. Whether this reflects the tumourigenic process in individual patients remains insufficiently explored. Genomic and epigenomic studies suggest that a subset of gallbladder cancers originate from biliary intraepithelial neoplasia (BilIN) precursor lesions, whereas others form independently from BilINs. Spatial transcriptomic data supporting these conclusions are missing. Moreover, multiple areas with precursor or adenocarcinoma lesions can be detected within the same pathological sample. Yet, knowledge about intra-patient variability of such lesions is lacking.
METHODS: To characterise the spatial transcriptomics of gallbladder cancer tumourigenesis in individual patients, we selected two patients with distinct cancer aetiology and whose samples simultaneously displayed multiple areas of normal epithelium, BilINs and adenocarcinoma. Using GeoMx digital spatial profiling, we characterised the whole transcriptome of a high number of regions of interest (ROIs) per sample in the two patients (24 and 32 ROIs respectively), with each ROI covering approximately 200 cells of normal epithelium, low-grade BilIN, high-grade BilIN or adenocarcinoma. Human gallbladder organoids and cell line-derived tumours were used to investigate the tumour-promoting role of genes.
RESULTS: Spatial transcriptomics revealed that each type of lesion displayed limited intra-patient transcriptomic variability. Our data further suggest that adenocarcinoma derived from high-grade BilIN in one patient and from low-grade BilIN in the other patient, with co-existing high-grade BilIN evolving via a distinct process in the latter case. The two patients displayed distinct sequences of signalling pathway activation during tumour progression, but Semaphorin 4 A (SEMA4A) expression was repressed in both patients. Using human gallbladder-derived organoids and cell line-derived tumours, we provide evidence that repression of SEMA4A promotes pseudostratification of the epithelium and enhances cell migration and survival.
CONCLUSION: Gallbladder adenocarcinoma can develop according to patient-specific processes, and limited intra-patient variability of precursor and cancer lesions was noticed. Our data suggest that repression of SEMA4A can promote tumour progression. They also highlight the need to gain gene expression data in addition to histological information to avoid understimating the risk of low-grade preneoplastic lesions.
PMID:39164619 | PMC:PMC11334592 | DOI:10.1186/s12885-024-12770-0
Chin Med J (Engl). 2024 Aug 20;137(16):1957-1964. doi: 10.1097/CM9.0000000000003225. Epub 2024 Jul 3.
ABSTRACT
BACKGROUND: Digestive system cancers constitute a significant number of cancer cases, but their burden is not uniform. As Global Cancer Observatory (GLOBOCAN) 2022 has recently updated its estimates of cancer burden, we aimed to investigate the burden of six major digestive system cancers both worldwide and in China, along with geographical and temporal variations in cancer-specific incidence and mortality.
METHODS: We extracted data on primary cancers of the esophagus, stomach, colorectum, liver, pancreas, and gallbladder from the GLOBOCAN database for 2022. Age-standardized incidence and mortality rates were calculated and stratified by sex, country, region, and human development index (HDI). We used the 2022 revision of the World Population Prospects (United Nations) to obtain demographic data for various age groups in China from 1988 to 2012 and used the joinpoint model and the average annual percentage change (AAPC) to analyze cancer incidence trends in China.
RESULTS: In 2022, the estimated global incidence of digestive system cancers reached 4,905,882, with an estimated 3,324,774 cancer-related deaths. Colorectal cancer was most prevalent in terms of incidence and mortality. There was a significant correlation between the burden of gastrointestinal cancers and country HDI. From 1988 to 2012, the incidence of esophageal, gastric, and liver cancers declined in China, whereas colorectal and pancreatic cancer incidences continued to increase. By 2050, colorectal and liver cancers are projected to remain the leading cancer types in China in terms of incidence and mortality, respectively.
CONCLUSIONS: Digestive system cancers remain a significant public health challenge globally and in China. Although progress has been made in the prevention and control of some cancers, the burden of digestive system cancers persists. The implementation of tertiary prevention strategies must be intensified to reduce the incidence and mortality of digestive system cancers, mitigating their impact on public health.
PMID:38958046 | PMC:PMC11332782 | DOI:10.1097/CM9.0000000000003225
2024 Aug 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–.
ABSTRACT
Gallbladder carcinoma is a rare malignancy but represents almost 50% of all biliary tract cancer. Most tumors are adenocarcinomas, with squamous, adenosquamous, and neuroendocrine tumors being less common. Gallbladder neoplasms are more prevalent in women, with marked geographic variation in incidence. Most gallbladder tumors arise from the mucosal lining as the gallbladder lacks a submucosal layer and subsequently spread through the thin muscularis early in the disease course. Early symptoms may be similar to biliary colic or cholecystitis and might account for the late stage of diagnosis associated with this cancer. Consequently, tumors are often nonresectable at diagnosis.
Surgical resection is the treatment of choice, and not infrequently, a focus of early-stage carcinoma may be incidentally detected in patients undergoing cholecystectomy. In contrast to other biliary carcinomas, gallbladder carcinoma is associated with a higher rate of distant metastatic disease and may derive more benefit from chemotherapy. Chemotherapy is used in the adjuvant setting and palliative care. The overall prognosis is poor, with 5-year survival rates of <20%. Recent advances in studying the genetic drivers and molecular profile of these tumors have heralded the use of targeted agents, hopefully improving the prognosis of this disease.
Ann Hepatobiliary Pancreat Surg. 2024 Aug 20. doi: 10.14701/ahbps.24-117. Online ahead of print.
ABSTRACT
BACKGROUNDS/AIMS: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC.
METHODS: A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon-Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location.
RESULTS: Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location.
CONCLUSIONS: NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.
PMID:39160451 | DOI:10.14701/ahbps.24-117
Cureus. 2024 Jul 17;16(7):e64762. doi: 10.7759/cureus.64762. eCollection 2024 Jul.
ABSTRACT
Introduction Cholecystectomy, the surgical removal of the gallbladder, is a common procedure worldwide. Despite no visible anomalies, routine histopathological examination (HPE) of gallbladder specimens post-surgery is standard practice to exclude pathologies, notably gallbladder cancer (GBC). Incidence rates of GBC vary geographically and ethnically. Surgical intervention is recommended for advanced GBC stages, while early stages may require cholecystectomy alone. Although rare, GBC and bile duct cancers pose increased risks in certain demographics, such as women and individuals over 65. Routine HPE practices vary globally based on resource availability and GBC incidence. This study assesses the necessity of routine HPE by evaluating the selective processing of gallbladder specimens suspected of GBC, prioritizing patient safety. Materials and methods This retrospective cohort study conducted at Redland Hospital, a district general hospital in Australia, investigated the necessity of routine HPE for excised gallbladder specimens. Adhering to routine HPE policy, the study encompassed all elective and emergency cholecystectomies performed from January 2023 to December 2023, excluding pediatric cases, concurrent surgical procedures, and those with suspected malignancy. Demographic data, surgery indications, intraoperative findings, histopathological results, and incidental gallbladder cancer (IGC) outcomes were analyzed. Pathology reports and case documentation were reviewed for cancerous pathology indicators. Results Over the one-year study period from January 2023 to December 2023, a total of 266 gallbladder specimens were subjected to HPE post-cholecystectomy. Of these, 201 were female and 65 were male, yielding a male-to-female ratio of 3:1. Elective cholecystectomy was performed on 56.4% (150) of patients, while 43.6% (116) underwent emergency procedures. Laparoscopic cholecystectomy (LC) was the primary surgical approach, except for one case requiring conversion to an open procedure. None of the patients exhibited GBC; however, 3.3% (9) displayed premalignant histopathological features in their specimens. Conclusion In conclusion, adopting a selective approach, where only gallbladder specimens with macroscopic abnormalities undergo HPE, seems prudent, especially in regions with low GBC incidence. Our study, which revealed no cases of GBC, supports this approach. It not only reduces the risk of missing incidental carcinoma in clinically unsuspected cases but also proves cost-effective and reduces the histopathology department workload without compromising patient outcomes. Therefore, we advocate for routine macroscopic examination of gallbladder specimens for abnormalities before HPE submission, particularly in cholecystectomy patients with gallstone disease.
PMID:39156251 | PMC:PMC11329314 | DOI:10.7759/cureus.64762
JAMA Oncol. 2024 Aug 1;10(8):1116-1120. doi: 10.1001/jamaoncol.2024.1944.
ABSTRACT
IMPORTANCE: There is limited evidence with regard to the benefit of adjuvant chemotherapy chemoradiotherapy in resected gallbladder cancers (GBCs).
OBJECTIVE: To establish a baseline survival rate for operated GBCs in patients receiving either gemcitabine plus cisplatin (GC) or capecitabine and capecitabine concurrent with chemoradiation (CCRT).
DESIGN, SETTING, AND PARTICIPANTS: The GECCOR-GB study was a multicenter, open-label, randomized phase 2 noncomparator "pick the winner" design trial of adjuvant GC and CCRT in patients with resected histologically confirmed adenocarcinoma or adenosquamous carcinoma of the gallbladder, (stage II/III) with no local residual tumor (R0) or microscopic residual tumor (R1). The study was carried out in 3 tertiary cancer institutions in India. Patients 18 years or older with adequate end-organ functions, and Eastern Cooperative Oncology Group Performance Status of 1 or lower between May 2019 and February 2022 were enrolled. The cutoff date for data analysis was February 28, 2023.
INTERVENTIONS: Patients were randomized 1:1 to receive either GC every 3 weeks (maximum of 6 cycles) or CCRT comprising capecitabine with concurrent chemoradiation (capecitabine concurrent with radiotherapy) sandwiched between capecitabine chemotherapy.
MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival (DFS) at 1 year in randomized patients. This study was conducted as 2 parallel, single-stage phase 2 clinical trials. Within each treatment arm, a 1-year DFS rate of less than 59% was considered as insufficient activity, whereas a 1-year DFS rate of 77% or higher would be considered as sufficient activity.
RESULTS: With a median follow-up of 23 months, 90 patients were randomized, 45 in each arm. Overall, there were 31 women (69%) and 14 men (31%) in the GC arm with a mean (range) age of 56 (33-72) years and 34 women (76%) and 11 men (24%) in the CCRT group with a mean (range) age of 55 (26-69) years. In the GC and CCRT arms, 1-year DFS and estimated 2-year DFS was 88.9% (95% CI, 79.5-98.3) and 74.8% (95% CI, 60.4-89.2), and 77.8% (95% CI, 65.4-90.2) and 74.8% (95% CI, 59.9-86.3), respectively. Completion rates for planned treatment was 82% in the GC arm and 62% in the CCRT arm.
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, GC and CCRT crossed the prespecified trial end points of 1-year DFS in patients with resected stage II/III GBCs. The results set a baseline for a larger phase 3 trial evaluating both regimens in operated GBCs.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CTRI/2019/05/019323I.
PMID:38958997 | PMC:PMC11223048 | DOI:10.1001/jamaoncol.2024.1944
Cancer Lett. 2024 Aug 28;598:217067. doi: 10.1016/j.canlet.2024.217067. Epub 2024 Jun 26.
ABSTRACT
Aberrant expression of G protein-coupled receptor class C group 5 member A (GPRC5A) has been reported in multiple cancers and is closely related to patient prognosis. However, the mechanistic role of GPRC5A in gallbladder cancer (GBC) remains unclear. Here, we determined tumor expression levels of GPRC5A and the molecular mechanisms by which GPRC5A regulates gallbladder cancer metastasis. We found that GPRC5A was significantly upregulated in GBC, correlating with poorer patient survival. Knocking down GPRC5A inhibited GBC cell metastasis both in vitro and in vivo. GRPRC5A knockdown resulted in downregulation of TNS4 expression through the JAK2-STAT3 axis. Clinically, GPRC5A expression positively correlated with TNS4. Finally, STAT3 bound to TNS4's promoter region, inducing its expression. Overall, GPRC5A showed high expression in GBC tissues, associated with poor patient prognosis. Our findings first demonstrate that the GPRC5A-JAK2-STAT3-TNS4 pathway promotes GBC cell metastasis, suggesting potential therapy targets.
PMID:38942137 | DOI:10.1016/j.canlet.2024.217067
Genes Immun. 2024 Aug;25(4):307-316. doi: 10.1038/s41435-024-00280-9. Epub 2024 Jun 12.
ABSTRACT
Gallbladder cancer (GBC) is an aggressive cancer with poor prognosis. PARP inhibitors (PARPi) target PARP enzymes and have shown efficacy in patients with breast cancer gene (BRCA) mutations. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, the combined impact of PARPi and ICIs in GBC remains unclear. We present a groundbreaking case of a GBC patient with BRCA2 mutations who received combination therapy with PARPi and ICIs after failing multiple lines of treatment. Next-generation sequencing (NGS-Seq) identified BRCA gene mutations. To further investigate potential mechanisms, we developed a PARP1-BRCA1-BRCA2 pathway-related risk score (PBscore) system to evaluate the impact of PARPi on the tumor immune microenvironment via RNA-Seq data. Gene expression and functional analysis identified potential mechanisms associated with the PBscore. Experimental validation assessed the impact of the combination therapy on the tumor microenvironment using multiplexed immunofluorescence imaging and immunohistochemistry in patients with BRCA gene wild type or mutations. RNA-Seq analysis revealed correlations between PBscore, immune checkpoint levels, tumor-infiltrating immune cells (TIICs), and the cancer-immunity cycle. Multiplexed immunofluorescence imaging validated that low PBscore patients might have an active tumor microenvironment. Furthermore, upon drug resistance, we observed an upregulation of negative immune checkpoints such as CEACAM1, indicating that the tumor immune microenvironment becomes suppressed after resistance. Our study revealed that PBscore could serve as a biomarker to predict immunotherapy efficacy, offering a promising alternative for BRCA2-mutated GBC patients.
PMID:38866965 | DOI:10.1038/s41435-024-00280-9
Clin Cancer Res. 2024 Aug 15;30(16):3499-3511. doi: 10.1158/1078-0432.CCR-24-0657.
ABSTRACT
PURPOSE: Intrahepatic cholangiocarcinoma (IHC) is a heterogeneous tumor. The hidden-genome classifier, a supervised machine learning-based algorithm, was used to quantify tumor heterogeneity and improve classification.
EXPERIMENTAL DESIGN: A retrospective review of 1,370 patients with IHC, extrahepatic cholangiocarcinoma (EHC), gallbladder cancer (GBC), hepatocellular carcinoma (HCC), or biphenotypic tumors was conducted. A hidden-genome model classified 527 IHC based on genetic similarity to EHC/GBC or HCC. Genetic, histologic, and clinical data were correlated.
RESULTS: In this study, 410 IHC (78%) had >50% genetic homology with EHC/GBC; 122 (23%) had >90% homology ("biliary class"), characterized by alterations of KRAS, SMAD4, and CDKN2A loss; 117 IHC (22%) had >50% genetic homology with HCC; and 30 (5.7%) had >90% homology ("HCC class"), characterized by TERT alterations. Patients with biliary- versus non-biliary-class IHC had median overall survival (OS) of 1 year (95% CI, 0.77, 1.5) versus 1.8 years (95% CI, 1.6, 2.0) for unresectable disease and 2.4 years (95% CI, 2.1, NR) versus 5.1 years (95% CI, 4.8, 6.9) for resectable disease. Large-duct IHC (n = 28) was more common in the biliary class (n = 27); the HCC class was composed mostly of small-duct IHC (64%, P = 0.02). The hidden genomic classifier predicted OS independent of FGFR2 and IDH1 alterations. By contrast, the histology subtype did not predict OS.
CONCLUSIONS: IHC genetics form a spectrum with worse OS for tumors genetically aligned with EHC/GBC. The classifier proved superior to histologic subtypes for predicting OS independent of FGFR2 and IDH1 alterations. These results may explain the differential treatment responses seen in IHC and may direct therapy by helping stratify patients in future clinical trials.
PMID:38864854 | PMC:PMC11326964 | DOI:10.1158/1078-0432.CCR-24-0657
BMC Health Serv Res. 2024 Aug 14;24(1):932. doi: 10.1186/s12913-024-11306-3.
ABSTRACT
BACKGROUND: Upper gastrointestinal cancers (UGICs) are increasingly prevalent. With a poor prognosis and significant longer-term effects, UGICs present significant adjustment challenges for individuals with cancer and their informal caregivers. However, the supportive care needs of these informal caregivers are largely unknown. This systematic review of qualitative studies synthesises and critically evaluates the current evidence base on the experience of informal caregivers of individuals with UGIC.
METHODS: A Joanna Briggs Institute systematic review was conducted. Searches were performed in four databases (MEDLINE, PsycINFO, Embase, CINAHL) from database inception to February 2021. Included studies explored experiences of informal caregivers of individuals diagnosed with primary cancer of the oesophagus, stomach, pancreas, bile duct, gallbladder, or liver. Studies were independently screened for eligibility and included studies were appraised for quality by two reviewers. Data were extracted and synthesised using meta-aggregation.
RESULTS: 19 papers were included in this review, and 328 findings were extracted. These were aggregated into 16 categories across three findings: (1) UGIC caregiver burden; UGIC caregivers undertake extensive responsibilities, especially around patient diet as digestion is severely impacted by UGICs. (2) Mediators of caregiver burden; The nature of UGICs, characterised by disruptive life changes for caregivers, was identified as a mediator for caregiver burden. (3) Consequences of caregiver burden: UGIC caregivers' experiences were shaped by unmet needs, a lack of information and a general decline in social interaction.
CONCLUSIONS: The findings of this review suggest the need for a cultural shift within health services. Caregiving for UGIC patients is suggested to adversely affect caregivers' quality of life, similarly to other cancer caregiving populations and therefore they should be better incorporated as co-clients in care-planning and execution by including them in discussions about the patient's diagnosis, treatment options, and potential side effects.
PMID:39143501 | PMC:PMC11325824 | DOI:10.1186/s12913-024-11306-3
J Ethnopharmacol. 2024 Nov 15;334:118583. doi: 10.1016/j.jep.2024.118583. Epub 2024 Jul 14.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Liver and breast cancers are the most dominant cancer types with high occurrence rates. Artichoke (Cynara scolymus L.) has been reputed for its traditional use in alleviating many liver and gallbladder ailments beside its anticancer activity against various types of cancer cells.
AIM OF THE STUDY: To demonstrate detailed chemical matrices of the different plant parts and evaluate their cytotoxic activities aiming to unveil the relationship between these activities and the intrinsic metabolites using metabolomic studies, in-vitro experiments and network pharmacology.
MATERIALS AND METHODS: Chemical profiling of extracts from the different plant parts (stems, leaves, bracts and receptacles) was performed using HPLC/QqQ/MS followed by unsupervised chemometric studies. In-vitro cytotoxic potentials of the extracts were evaluated on breast and liver cancer cell line then an OPLS study using linear regression was conducted. Consequently, a network pharmacology analysis on the most bioactive plant organ was applied.
RESULTS: Unsupervised chemometric analysis revealed that kaempferol-3-O-α-L-rhamnopyranoside-7-O-β-D-galacturonopyranoside, chrysoeriol-7-rutinoside and 1-caffeoylquinic acid were responsible for the segregation of the bract (CSB) segregated from the rest of the plant organs. Interestingly, CSB extract possessed the highest potential in-vitro cytotoxic activity against both liver and breast cancer cells (IC50 = 1.65 and 1.77 μg/mL). As expected, the aforementioned biomarkers were observed to be the discriminatory cytotoxic metabolites in the constructed supervised chemometric model. Network pharmacology analysis on CSB revealed 27 liver cancer-related metabolites of which, 1-caffeoylquinic acid was the most enriched one contributing to 13% of the total interactions. Furthermore, 38 target genes were involved, the most enriched of which were Aldo-keto reductase family 1 member B1 (AKR1B10) and interleukin-2 (IL-2). KEGG pathway analysis unveiled 23 significantly related pathways including metabolic pathways that possessed the lowest p-value (1.6E-5).
CONCLUSION: The findings demonstrated that CSB is a significant source of cytotoxic metabolites against breast cancer and liver cancer cell lines, hence, drawing attention to the pharmaceutical and medicinal value of this negligible plant organ and paving the route for insightful research into its exact pharmacological cytotoxic mechanisms.
PMID:39013541 | DOI:10.1016/j.jep.2024.118583
Medicine (Baltimore). 2024 Aug 9;103(32):e39208. doi: 10.1097/MD.0000000000039208.
ABSTRACT
RATIONALE: Malignant gastric glomus tumor (GGT) is an extremely rare malignant tumor of mesenchymal origin, it affects the patient's health and even threatens life. Malignant GGT with vascular invasion is even more rarely reported in the available literature without a prognostic study. So, in this case, we report a malignant GGT with vascular invasion and performed a 5-year postoperative follow-up. To the best of our knowledge, we report the first case of malignant GGT with vascular invasion without recurrence 5 years after surgery. This provides examples and lessons for the treatment of malignant GGT with vascular invasion.
PATIENT CONCERNS: A 49-year-old male was admitted to the hospital with gallbladder stones found on health check. After completing abdominal CT and ultrasound gastroscopy, a mass in the gastric antrum was found.
DIAGNOSES: The diagnosis of malignant GGT was confirmed by combination of postoperative pathology with positive immunohistochemistry for SMA, vimentin, synaptophysin, H-caldesmon, and calponin, mitosis > 10/50 HPF and moderate-to-severe nuclear atypia.
INTERVENTIONS: On the 6th day of hospitalization, the patient underwent laparoscopic distal gastrectomy and cholecystectomy.
OUTCOMES: The patient was discharged successfully 1 week after surgery and was followed up for 5 years without recurrence.
CONCLUSION: Malignant GGT can be asymptomatic. For malignant GGT without distant metastasis, despite the presence of vascular invasion, negative margin surgery can still be the standard surgical radical treatment.
PMID:39121329 | PMC:PMC11315574 | DOI:10.1097/MD.0000000000039208
J Dig Dis. 2024 Jun;25(6):404-408. doi: 10.1111/1751-2980.13298. Epub 2024 Jul 15.
NO ABSTRACT
PMID:39010258 | DOI:10.1111/1751-2980.13298
Cancer. 2024 Sep 1;130(17):2904-2906. doi: 10.1002/cncr.35352. Epub 2024 Jun 14.
NO ABSTRACT
PMID:38873826 | DOI:10.1002/cncr.35352
Cancer Control. 2024 Jan-Dec;31:10732748241271682. doi: 10.1177/10732748241271682.
ABSTRACT
BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis.
METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT.
RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups.
CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.
PMID:39105433 | PMC:PMC11312743 | DOI:10.1177/10732748241271682
Front Endocrinol (Lausanne). 2024 Jul 22;15:1217250. doi: 10.3389/fendo.2024.1217250. eCollection 2024.
ABSTRACT
BACKGROUND: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass.
METHODS: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS).
RESULTS: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor.
CONCLUSION: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.
PMID:39104815 | PMC:PMC11298461 | DOI:10.3389/fendo.2024.1217250
BMC Surg. 2024 Aug 6;24(1):223. doi: 10.1186/s12893-024-02503-2.
ABSTRACT
INTRODUCTION: The incidence of Pancreatic cancer is different in different parts of the world. It is a cancer with the worst prognosis of all malignancies. Pancreatic cancer is predominantly a disease of an older population. There are different environmental (modifiable) and non-modifiable risk factors associated with the development of pancreatic cancer. At present, surgical resection is the only potential cure for pancreatic cancer. However, as only 10-20% of the patients have resectable disease at the time of diagnosis. The morbidities associated with surgeries for pancreatic cancers remain high though the post-operative mortality has shown significant reduction in the past few decades. So far, no study has been conducted to investigate pancreatic cancer in Ethiopia.
OBJECTIVES: To assess the clinico-pathologic profile, associated factors, surgical management and short-term outcome of patients with pancreatic cancer in Tikur Anbessa Specialized hospital.
METHODS: A 5 years retrospective hospital-based cross-sectional study was conducted on 52 patients operated with the diagnosis of pancreatic cancer with either curative or palliative intents. The study period was from April 2016 to July 2021. The data collected includes demographic profile, associated risk factors and comorbidities, clinical presentations, biochemical parameters, pathologic features of the tumors as well as type of treatment offered and short term treatment outcome. The data was analyzed using SPSS version 25.
RESULT: The mean and median age of patients was 54.1 and 54.5% respectively. Males constitute about 52% the patients. 21% of the patients have potential risk factors; whereas only 10 (19.2%) of the patients had medical comorbidities. Median duration of symptoms at diagnosis was 12 weeks. Abdominal pain (88.5%) was the most common presenting symptom followed by anorexia (80.8%) and significant weight loss (78.8%), while 71.2% of the patients have jaundice. On clinical evaluation, 69.2% were jaundiced, while 34.6% had a palpable gallbladder. More than two third of patients presented with advanced disease. 76.9% of the tumors are located in the head of pancreas. More than three quarters (77%) of the surgeries performed were palliative. Postoperative morbidity and mortality were 19.2% and 3.8% respectively.
CONCLUSION: Age at first diagnosis of pancreatic cancer is relatively earlier in our setup. Most patients present with advanced condition, only amenable for palliative measures. The post-operative morbidity and mortality are more or less comparable with similar studies. The need for adjuvant therapy in pancreatic cancer should be emphasized.
PMID:39103810 | PMC:PMC11302827 | DOI:10.1186/s12893-024-02503-2
Int J Surg Case Rep. 2024 Sep;122:110117. doi: 10.1016/j.ijscr.2024.110117. Epub 2024 Aug 3.
ABSTRACT
INTRODUCTION: Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by gastrointestinal hamartomatous polyps, due to mutation of the STK11/LKB1 gene located on chromosome 19p. The polyps are most commonly found in the small bowel followed by colon.
CASE PRESENTATION: Our case series includes 4 patients, three being male and one female. Each of them either presented with abdominal pain and other associated symptoms. Oral cavity and lip melanin pigmentation were common. CT abdomen revealed multiple large jejunal, ileal, gastric and colon polyps. Cancer was found in one patient. Different surgical approaches were adopted. All recovered well.
DISCUSSION: PJS is an autosomal dominant disorder with an estimated incidence of 1:50,000 to 1:200,000 cases with a significant family history. Mostly found in small bowel followed by colon, it can also occur in a rare organ like gall bladder as evident in our case. PJS carries a substantial risk for gastrointestinal cancer. The treatment modality depends on the site of polyp, mode of presentation and availability of the expertise.
CONCLUSION: PJS is a common disease in our part which is usually observed in teen age groups male. They have a varied presentation, from intestinal obstruction (due to intussusception) to GI bleeding. Colonic malignancy at young age may be the first presentation of the disease. Observation of melanin pigmentations on lips helps diagnose the disease; and one should always look at this findings in a young patient with pain abdomen or in intestinal obstruction to confirm/exclude the disease.
PMID:39098175 | PMC:PMC11345572 | DOI:10.1016/j.ijscr.2024.110117
Lancet Public Health. 2024 Aug;9(8):e583-e593. doi: 10.1016/S2468-2667(24)00156-7.
ABSTRACT
BACKGROUND: Trends in cancer incidence in recent birth cohorts largely reflect changes in exposures during early life and foreshadow the future disease burden. Herein, we examined cancer incidence and mortality trends, by birth cohort, for 34 types of cancer in the USA.
METHODS: In this analysis, we obtained incidence data for 34 types of cancer and mortality data for 25 types of cancer for individuals aged 25-84 years for the period Jan 1, 2000, to Dec 31, 2019 from the North American Association of Central Cancer Registries and the US National Center for Health Statistics, respectively. We calculated birth cohort-specific incidence rate ratios (IRRs) and mortality rate ratios (MRRs), adjusted for age and period effects, by nominal birth cohort, separated by 5 year intervals, from 1920 to 1990.
FINDINGS: We extracted data for 23 654 000 patients diagnosed with 34 types of cancer and 7 348 137 deaths from 25 cancers for the period Jan 1, 2000, to Dec 31, 2019. We found that IRRs increased with each successive birth cohort born since approximately 1920 for eight of 34 cancers (pcohort<0·050). Notably, the incidence rate was approximately two-to-three times higher in the 1990 birth cohort than in the 1955 birth cohort for small intestine (IRR 3·56 [95% CI 2·96-4·27]), kidney and renal pelvis (2·92 [2·50-3·42]), and pancreatic (2·61 [2·22-3·07]) cancers in both male and female individuals; and for liver and intrahepatic bile duct cancer in female individuals (2·05 [1·23-3·44]). Additionally, the IRRs increased in younger cohorts, after a decline in older birth cohorts, for nine of the remaining cancers (pcohort<0·050): oestrogen-receptor-positive breast cancer, uterine corpus cancer, colorectal cancer, non-cardia gastric cancer, gallbladder and other biliary cancer, ovarian cancer, testicular cancer, anal cancer in male individuals, and Kaposi sarcoma in male individuals. Across cancer types, the incidence rate in the 1990 birth cohort ranged from 12% (IRR1990 vs 1975 1·12 [95% CI 1·03-1·21] for ovarian cancer) to 169% (IRR1990 vs 1930 2·69 [2·34-3·08] for uterine corpus cancer) higher than the rate in the birth cohort with the lowest incidence rate. The MRRs increased in successively younger birth cohorts alongside IRRs for liver and intrahepatic bile duct cancer in female individuals, uterine corpus, gallbladder and other biliary, testicular, and colorectal cancers, while MRRs declined or stabilised in younger birth cohorts for most cancers types.
INTERPRETATION: 17 of 34 cancers had an increasing incidence in younger birth cohorts, including nine that previously had declining incidence in older birth cohorts. These findings add to growing evidence of increased cancer risk in younger generations, highlighting the need to identify and tackle underlying risk factors.
FUNDING: American Cancer Society.
PMID:39095135 | DOI:10.1016/S2468-2667(24)00156-7
Medicine (Baltimore). 2024 Aug 2;103(31):e39147. doi: 10.1097/MD.0000000000039147.
ABSTRACT
RATIONALE: Neuroendocrine neoplasms (NENs) originating from neuroendocrine cells occur in the thyroid, respiratory, and digestive systems, with Gallbladder Neuroendocrine Carcinoma (GB-NEC) accounting for only 0.5% of all NENs and 2.1% of gallbladder cancers. Due to its rarity, little is known about GB-NEC's clinical presentation and treatment.
PATIENT CONCERNS: We report a case of a 52-year-old male presenting with acute upper right abdominal pain, leading to further investigation.
DIAGNOSES: Initial diagnostic workup, including abdominal ultrasound and contrast-enhanced CT, suggested gallbladder malignancy. Post-surgical pathology confirmed GB-NEC, with immunohistochemistry supporting the diagnosis.
INTERVENTIONS: The patient underwent radical cholecystectomy, followed by etoposide plus cisplatin chemotherapy. After disease progression indicated by CT, the patient received additional cycles of chemotherapy with cisplatin and irinotecan, plus targeted therapy with anlotinib and immunotherapy with paimiplimab.
OUTCOMES: The patient showed a partial response to initial treatment. Subsequent liver biopsy confirmed NEC, consistent with small cell carcinoma. With continued treatment, the patient maintains a good survival status.
LESSONS: GB-NEC is associated with poor prognosis, emphasizing the importance of early detection and multimodal treatment strategies. Our case underlines the potential benefit of a comprehensive treatment plan, including aggressive surgery and chemotherapy, with further research needed to standardize treatment for this rare condition.
PMID:39093760 | PMC:PMC11296443 | DOI:10.1097/MD.0000000000039147
Radiat Oncol. 2024 Aug 1;19(1):102. doi: 10.1186/s13014-024-02481-y.
ABSTRACT
BACKGROUND: Biliary tract cancers (BTC) are rare and aggressive malignancies originating from intrahepatic and extrahepatic bile ducts and the gallbladder. Surgery is the only curative option, but due to late-stage diagnosis, is frequently not feasible, leaving chemotherapy as the primary treatment. Radiotherapy (RT) can be an effective alternative for patients with unresectable, non-metastatic BTC despite the generally poor prognosis and significant variability. To help manage patients with unresectable BTC who receive RT, we aimed to identify prognostic markers that could aid in predicting overall survival (OS).
METHODS: A retrospective cohort study was conducted at the University of Pennsylvania, involving seventy-eight patients with unresectable BTC treated with definitive intent RT. Comprehensive demographic, clinical, and treatment-related data were extracted from the electronic medical records. Univariate and multivariate Cox regressions were employed to identify predictors of OS after RT. A biomarker model was developed for refined survival prediction.
RESULTS: The cohort primarily comprised patients with good performance status without significant hepatic dysfunction at presentation. The predominant treatment approach involved hypofractionated RT or concurrent 5FU-based chemoRT. Median OS after RT was 12.3 months, and 20 patients (15.6%) experienced local progression with a median time of 30.1 months. Univariate and multivariate analyses identified CA19-9 (above median) and higher albumin-bilirubin (ALBI) grades at presentation as significant predictors of poor OS. Median OS after RT was 24 months for patients with no risk factors and 6.3 months for those with both.
CONCLUSIONS: Our study demonstrates generally poor but significantly heterogeneous OS in patients with unresectable BTC treated with RT. We have developed a biomarker model based on CA19-9 and ALBI grade at presentation that can distinguish sub-populations with markedly diverse prognoses. This model can aid the clinical management of this challenging disease.
PMID:39090660 | PMC:PMC11293151 | DOI:10.1186/s13014-024-02481-y
Front Biosci (Landmark Ed). 2024 Jul 25;29(7):269. doi: 10.31083/j.fbl2907269.
ABSTRACT
BACKGROUND: The TGF-β gene is a gemcitabine (GEM) resistance gene; however, the mechanism by which it regulates GEM resistance in pancreatic cancer remains unclear.
METHODS: The PANC-1 cell line was treated with GEM and then stimulated with TGF-β. Subsequently, we constructed GEM-resistant pancreatic cancer cell lines, knocked down TGF-β in these cell lines, and detected changes in the proliferation and apoptosis of drug-resistant cancer cells. In addition, the protein expression levels of KLF-4, GFI-1, and ZEB-1 were determined. The xenograft tumor models of nude mice were constructed by subcutaneously injecting GEM-resistant PANC-1 cells into mouse axilla. The tumors were removed, dissected, and weighed after 6 weeks. The protein levels of KLF-4, GFI-1, and ZEB-1 in tumor tissues were quantified. In addition, the percentage of M2 macrophages in tumor tissues was determined using flow cytometry.
RESULTS: The protein levels of TGF-β in pancreatic cancer cells were significantly decreased after GEM treatment. The protein expression of KLF-4 was downregulated, whereas the expressions of GFI-1 and ZEB-1 were upregulated after TGF-β stimulation. Apoptosis increased and proliferation decreased after TGF-β knockdown in GEM-resistant pancreatic cancer cells, moreover, silencing TGF-β promoted the expression of Caspase 3 and Cleaved caspase 3. In addition, the protein expression of KLF-4 was upregulated, whereas the expressions of GFI-1 and ZEB-1 were downregulated. Further, the volume and weight of the transplanted tumor decreased after TGF-β knockdown. The protein expression of KLF-4 was upregulated, whereas the expressions of GFI-1 and ZEB-1 were downregulated in tumor tissues. In addition, the percentage of M2 macrophages decreased in tumor tissues after TGF-β knockdown.
CONCLUSIONS: The knockdown of TGF-β inhibits epithelial-to-mesenchymal transition, suppresses the proliferation and promotes the apoptosis of drug-resistant cancer cells, and decreases the macrophage polarization to the M2 phenotype, consequently ameliorating GEM resistance in pancreatic cancer.
PMID:39082329 | DOI:10.31083/j.fbl2907269
World J Surg Oncol. 2024 Jul 30;22(1):201. doi: 10.1186/s12957-024-03492-5.
ABSTRACT
BACKGROUND: Cross-species horizontal gene transfer (HGT) involves the transfer of genetic material between different species of organisms. In recent years, mounting evidence has emerged that cross-species HGT does take place and may play a role in the development and progression of diseases.
METHODS: Transcriptomic data obtained from patients with gallbladder cancer (GBC) was assessed for the differential expression of antisense RNAs (asRNAs). The Basic Local Alignment Search Tool (BLAST) was used for cross-species analysis with viral, bacterial, fungal, and ancient human genomes to elucidate the evolutionary cross species origins of these differential asRNAs. Functional enrichment analysis and text mining were conducted and a network of asRNAs targeting mRNAs was constructed to understand the function of differential asRNAs better.
RESULTS: A total of 17 differentially expressed antisense RNAs (asRNAs) were identified in gallbladder cancer tissue compared to that of normal gallbladder. BLAST analysis of 15 of these asRNAs (AFAP1-AS1, HMGA2-AS1, MNX1-AS1, SLC2A1-AS1, BBOX1-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS) showed varying degree of similarities with bacterial and viral genomes, except for UNC5B-AS1 and SOX21-AS1, which were conserved during evolution. Two of these 15 asRNAs, (VPS9D1-AS1 and SLC2A1-AS1) exhibited a high degree of similarity with viral genomes (Chikungunya virus, Human immunodeficiency virus 1, Stealth virus 1, and Zika virus) and bacterial genomes including (Staphylococcus sp., Bradyrhizobium sp., Pasteurella multocida sp., and, Klebsiella pneumoniae sp.), indicating potential HGT during evolution.
CONCLUSION: The results provide novel evidence supporting the hypothesis that differentially expressed asRNAs in GBC exhibit varying sequence similarity with bacterial, viral, and ancient human genomes, indicating a potential shared evolutionary origin. These non-coding genes are enriched with methylation and were found to be associated with cancer-related pathways, including the P53 and PI3K-AKT signaling pathways, suggesting their possible involvement in tumor development.
PMID:39080678 | PMC:PMC11287962 | DOI:10.1186/s12957-024-03492-5
Sci Rep. 2024 Jul 30;14(1):17561. doi: 10.1038/s41598-024-63503-z.
ABSTRACT
The increased risk of liver malignancies was found in workers of the first Russian nuclear production facility, Mayak Production Association, who had been chronically exposed to gamma rays externally and to alpha particles internally due to plutonium inhalation. In the present study, we updated the radiogenic risk estimates of the hepatobiliary malignancies using the extended follow-up period (1948-2018) of the Mayak worker cohort and the improved «Mayak worker dosimetry system-2013». The cohort comprised 22,377 workers hired at the Mayak PA between 1948 and 1982. The analysis considered 62 liver malignancies (32 hepatocellular carcinomas, 13 intrahepatic cholangiocarcinomas, 16 angiosarcomas, and 1 anaplastic cancer) and 33 gallbladder adenocarcinomas. The analysis proved the positive significant association of the liver malignancy risk (the total of histological types, hepatocellular carcinoma) with the liver absorbed alpha dose from internal exposure. The excess relative risk per Gy (95% confidence interval) of alpha dose (the linear model) was 7.56 (3.44; 17.63) for the total of histological types and 3.85 (0.95; 13.30) for hepatocellular carcinoma. Indications of non-linearity were observed in the dose-response for internal exposure to alpha radiation. No impact of external gamma-ray exposure on the liver malignancy incidence was found. In the study cohort, the number of angiosarcomas among various types of liver malignancies was very high (25.8%), and most of these tumors (73.3%) were registered in individuals internally exposed to alpha radiation at doses ranging between 6.0 and 21.0 Gy. No association with chronic occupational radiation exposure was observed for the incidence of gallbladder malignancies.
PMID:39079951 | PMC:PMC11289462 | DOI:10.1038/s41598-024-63503-z
Cureus. 2024 Jun 27;16(6):e63286. doi: 10.7759/cureus.63286. eCollection 2024 Jun.
ABSTRACT
Introduction Gallbladder carcinoma is a rare but aggressive cancer of adults that affects females more than males. Its occurrence is more common in the regions of South America and Asia. Chronic inflammation and cholelithiasis are frequently associated risk factors of gallbladder carcinoma. The incidental discovery of a gallbladder carcinoma during cholecystectomy, gross or microscopic examination of the unsuspected gallbladder specimens is termed incidental gallbladder carcinoma (IGBC). Considering the lack of extensive studies on gallbladder carcinoma in the Eastern region of India, especially in Jharkhand, this study has been done to present the demographic and clinicopathological characteristics of gallbladder carcinoma in this region. Methods A retrospective and descriptive study was done at Rajendra Institute of Medical Sciences (RIMS), Ranchi, a tertiary care center in Jharkhand. The study sample comprised 2386 gall bladder cases received in the Department of Pathology over five years, from December 2018 to December 2023. Results Of 2368 specimens, 25 cases (n=25) were reported as primary gallbladder carcinoma. The female-to-male ratio was 4:1. Pain was the most common complaint by the patients. Of the 25 cases, 12 were suspected intra-operatively or diagnosed microscopically (IGBC). Most showed a mass at the neck. In six cases, no gross mass/lesion was seen. Cholelithiasis is present in 19/25 cases. Most cases showed adenocarcinoma (not otherwise specified). Out of the adenocarcinoma cases, most were well differentiated. At the time of diagnosis, most were at the pT2 stage. Twelve cases of IGBC were found. Eight out of 12 IGBC were early-stage carcinoma when diagnosed. Conclusion Twenty-five cases of gallbladder carcinoma were diagnosed in the last five years in our center, with 19 (76%) of them associated with cholelithiasis. Twelve (48%) of the cases were incidentally diagnosed either preoperatively or during gross/microscopic examination, and eight (66%) of those were discovered early, out of which five (62.5%) were observed to be in the T1b stage. At this stage, there is a diversion from the general surgical management of gallbladder carcinoma for a better prognosis. This underscores the significance of routine histopathological examination of gallbladder specimens, even if there is no preoperative suspicion of gallbladder carcinoma.
PMID:39070401 | PMC:PMC11283235 | DOI:10.7759/cureus.63286
Clin J Gastroenterol. 2024 Aug;17(4):724-730. doi: 10.1007/s12328-024-01986-z. Epub 2024 May 21.
ABSTRACT
A 52-year-old woman presented to our hospital with chief complaints of upper abdominal bloating and lower leg edema. Computed tomography (CT) revealed liver metastasis from a gallbladder tumor. This tumor was diagnosed as neuroendocrine carcinoma (NEC) on performing a biopsy. Physical examination revealed a moon face. Blood tests revealed hypokalemia and high levels of adrenocorticotropic hormone (ACTH) and cortisol. Dexamethasone suppression test revealed that cortisol secretion was not suppressed, and the patient was diagnosed with gallbladder NEC and ectopic ACTH syndrome (EAS). Metyrapone was administered to suppress cortisol production; however, she developed septic shock due to cellulitis in the lower leg and died on the 16th day of admission. A pathological autopsy was performed, which revealed disseminated intravascular coagulation and acute respiratory distress syndrome as the cause of death. Only a few cases of EAS due to NEC originating from the gallbladder have been reported. The patient reported here succumbed shortly after diagnosis, thereby highlighting the challenges in treating gallbladder NEC complicated by EAS.
PMID:38773001 | DOI:10.1007/s12328-024-01986-z
J Med Ultrason (2001). 2024 Jul;51(3):429-436. doi: 10.1007/s10396-024-01467-3. Epub 2024 Jun 16.
ABSTRACT
Gallbladder wall thickening is relatively common in clinical settings, and for appropriate diagnosis, the size, shape, internal structure, surface contour, and vascularity of the gallbladder wall must be evaluated. Morphological evaluation is the most important; however, some gallbladder lesions resemble gallbladder cancer in imaging studies, making differential diagnosis challenging. Vascular evaluation is indispensable for a precise diagnosis in these cases. In this review, we present the current status of vascular evaluation using US and diagnosis using vascular imaging for gallbladder lesions, including those presenting with wall thickening. To date, several ultrasound imaging techniques have been developed to assess vascularity, including Doppler imaging with high sensitivity, use of contrast agents, and microvascular imaging using a novel filter for Doppler imaging. Although conventional color Doppler imaging is rarely used for the diagnosis of gallbladder lesions, the efficacy of contrast-enhanced ultrasound in assessing the vascularity, enhancement pattern, or timing of enhancement/washout has been reported. Presence of multiple irregular microvessels has been speculated to indicate malignancy. However, few reports on microvessels have been published, and further studies are required for the precise diagnosis of gallbladder lesions with microvascular evaluation.
PMID:38879837 | DOI:10.1007/s10396-024-01467-3
Tomography. 2024 Jul 3;10(7):1031-1041. doi: 10.3390/tomography10070077.
ABSTRACT
BACKGROUND: There is little information regarding the size measurement differences in gallbladder (GB) polyps performed by different radiologists on abdominal ultrasonography (US).
AIM: To reveal the differences in GB polyp size measurements performed by different radiologists on abdominal US.
METHODS: From June to September 2022, the maximum diameter of 228 GB polyps was measured twice on abdominal US by one of three radiologists (a third-year radiology resident [reader A], a radiologist with 7 years of experience in abdominal US [reader B], and an abdominal radiologist with 8 years of experience in abdominal US [reader C]). Intra-reader agreements for polyp size measurements were assessed by intraclass correlation coefficient (ICC). A Bland-Altman plot was used to visualize the differences between the first and second size measurements in each reader.
RESULTS: Reader A, reader B, and reader C evaluated 65, 77, and 86 polyps, respectively. The mean size of measured 228 GB polyps was 5.0 ± 1.9 mm. Except for the case where reader A showed moderate intra-reader agreement (0.726) for polyps with size ≤ 5 mm, all readers showed an overall high intra-reader reliability (reader A, ICC = 0.859; reader B, ICC = 0.947, reader C, ICC = 0.948), indicative of good and excellent intra-reader agreements. The 95% limit of agreement of reader A, B, and C was 1.9 mm of the mean in all three readers.
CONCLUSIONS: GB polyp size measurement on abdominal US showed good or excellent intra-reader agreements. However, size changes of approximately less than 1.9 mm should be interpreted carefully because these may be within the measurement error.
PMID:39058049 | PMC:PMC11281002 | DOI:10.3390/tomography10070077
Comput Biol Med. 2024 Aug;178:108663. doi: 10.1016/j.compbiomed.2024.108663. Epub 2024 May 28.
ABSTRACT
BACKGROUND: Robust and practical prognosis prediction models for hepatocellular carcinoma (HCC) patients play crucial roles in personalized precision medicine.
MATERIAL AND METHODS: We recruited two independent HCC cohorts (discovery cohort and validation cohort), totally consisting of 222 HCC patients undergone surgical resection. We quantified the expressions of immune-related proteins (CD8, CD68, CD163, PD-1 and PD-L1) in paired HCC tissues and non-tumor liver tissues from these HCC patients using immunohistochemistry (mIHC) assays. We constructed the HCC prognosis prediction model using five different machine learning methods based on the patients in the discovery cohort, such as Cox proportional hazards (CoxPH).
RESULTS: We identified 19 features that were associated with overall survival of HCC patients in the discovery cohort (p < 0.1), such as immune-related features CD68+ and CD8+ cell infiltration. We constructed five HCC prognosis prediction models using five different machine learning methods. Among the five different machine learning models, the CoxPH model achieved the best performance (area under the curve [AUC], 0.839; C-index, 0.779). According to the risk score from CoxPH model, we divided HCC patients into high-risk group/low-risk group. In both discovery cohort and validation cohort, the patients in low-risk group showed longer overall survival compared with those in high-risk group (p = 1.8 × 10-7 and 3.4 × 10-5, respectively). Moreover, our novel scoring system efficiently predicted the 6, 12, and 18 months survival rate of HCC patients with AUC >0.75 in both discovery cohort and validation cohort. In addition, we found that the scoring system could also distinguish the patients with high/low risks of relapse in both discovery cohort and validation cohort (p = 0.00015 and 0.00012).
CONCLUSION: The novel CoxPH-based risk scoring model on clinical, laboratory-testing and immune-related features showed high prediction efficiencies for overall survival and recurrence of HCCs undergone surgical resection. Our results may be helpful to optimize clinical follow-up or therapeutic interventions.
PMID:38905890 | DOI:10.1016/j.compbiomed.2024.108663
Cancer Invest. 2024 Jul;42(6):478-490. doi: 10.1080/07357907.2024.2361305. Epub 2024 Jun 7.
ABSTRACT
Biliary dysbiosis is associated with gallbladder cancer (GBC). We aimed to look for biliary bacteria specifically detected in GBC patients. We used 16S rRNA-based metagenomic analysis to elucidate biliary microbiota in 30 GBC and 30 gallstones-associated chronic cholecystitis patients. Relative abundance of five genera, Streptococcus, Enterococcus, Halomonas, Escherichia and Caulobacter was significantly associated with GBC. Of 15-species, 7 were detected significantly higher in GBC, Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius, Actinomyces bowdenii, Actinomyces israelii, Actinomyces gerencseriae, and Escherichia fergusonii were biosafety level-2 infectious bacteria; other 8 species were biosafety level-1 bacteria. These bacterial species may be involved in pathogenesis of GBC.
PMID:38845533 | DOI:10.1080/07357907.2024.2361305
Korean J Clin Oncol. 2024 May;20(1):1-5. doi: 10.14216/kjco.24001. Epub 2024 Jun 30.
ABSTRACT
PURPOSE: Gallbladder carcinoma (GBC) poses significant challenges in oncology due to its aggressive nature and limited treatment options. The lack of effective biomarkers for early detection and prognosis exacerbates the prognosis for GBC patients. Tumor budding (TB) and tumor infiltrating lymphocytes (TILs) have emerged as potential prognostic indicators in various cancers, reflecting tumor-host immune interactions and tumor aggressiveness. The study of TB and TILs in GBC is particularly important due to the limited literature available.
METHODS: This retrospective observational study aimed to evaluate the association of TB and TILs with clinicopathological parameters in GBC patients. Clinicopathological data were collected from patients with histologically confirmed GBC who underwent surgical resection. The sections were evaluated for TB and TILs using standardized methods. Statistical analysis was performed to assess associations between these parameters and clinicopathological variables.
RESULTS: Tumor stage and grade showed significant associations with TB and TILs, indicating their potential as prognostic markers. High TB correlated with advanced tumor stage and higher grade, while high TIL infiltration was associated with early tumor stage and lower grade. Additionally, TILs exhibited a significant association with lymphovascular invasion. Interestingly, an inverse association was observed between TB and TILs, highlighting the dynamic interplay between tumor aggressiveness and host immune response.
CONCLUSION: TB and TILs hold prognostic significance in GBC, offering insights into its pathogenesis and potential therapeutic targets. Future research exploring the mechanistic underpinnings of tumor-host immune interactions in GBC is crucial for translating these findings into clinical applications and improving outcomes for patients.
PMID:38988012 | PMC:PMC11261181 | DOI:10.14216/kjco.24001
World J Gastrointest Surg. 2024 Jun 27;16(6):1507-1512. doi: 10.4240/wjgs.v16.i6.1507.
ABSTRACT
Gallbladder adenomas are rare lesions (0.5%) associated with potential malignant transformation, particularly with gallbladder adenomas that are ≥ 1 cm in size. Early detection and management are crucial for preventing lethal carcinoma development. These polyps can often be distinguished from the more often nonneoplastic cholesterol pseudopolyps (5%-10%), which are benign. Ultrasonography is the first-line tool for initial diagnosis and follow-up when indicated. The question is whether cholecystectomy is always necessary for all adenomas. The management of gallbladder adenomas is determined according to the size of the tumor, the growth rate of the tumor, the patient's symptoms and whether risk factors for malignancy are present. Adenomas ≥ 1 cm in size, an age > 50 years and a familial history of gallbladder carcinoma are indications for immediate laparoscopic cholecystectomy. Otherwise, ultrasound follow-up is indicated. For adenomas 6-9 mm in size, the absence of ≥ 2 mm growth at 6 months, one year, and two years, as well as an adenoma sized < 5 mm without existing risk factors indicates that no further surveillance is required. However, it would be preferable to individualize the management in doubtful cases. Novel interventional modalities for preserving the gallbladder need further evaluation, especially to determine the long-term outcomes.
PMID:38983335 | PMC:PMC11229988 | DOI:10.4240/wjgs.v16.i6.1507
Eur J Gastroenterol Hepatol. 2024 Aug 1;36(8):1029-1037. doi: 10.1097/MEG.0000000000002799. Epub 2024 May 31.
ABSTRACT
PURPOSE: Extrahepatic bile duct cancer (EBDC) is a compound malignant tumor mainly consisting of extrahepatic cholangiocarcinoma and gallbladder carcinoma. Most EBDC patients are diagnosed at an advanced stage characterized by distant metastases, and the liver is one of the common sites of metastasis. Hence, the purpose of this study is to investigate the clinicopathological features, identify prognostic risk factors, and assess the long-term prognosis of extrahepatic bile duct cancer liver metastasis (EBDCLM).
METHODS: We identified 1922 eligible EBDCLM patients from the SEER database.Cox regression models were used to predict independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS),and Kaplan-Meier survival curves were drawn. A nomogram was constructed based on the results of multivariate Cox analysis, and the predictive effect of the nomogram was evaluated.
RESULTS: Age, surgery, chemotherapy, brain metastasis, and lung metastasis were common independent prognostic factors for OS and CSS, and radiotherapy and bone metastasis were independent prognostic factors for CSS. The Kaplan-Meier survival curves showed a significant increase in survival for patients aged less than or equal to 70 years, undergoing surgery and chemotherapy, and without lung metastases. The results showed that the nomogram constructed by us had good predictability and ha d strong clinical application value.
CONCLUSION: Our study identified age, surgery, chemotherapy, brain metastasis, and lung metastasis as independent prognostic factors for EBDCLM patients. The nomogram can accurately predict the survival probability, which is helpful for clinicians to assess the prognosis of patients with advanced EBDC and provide personalized clinical decisions.
PMID:38829959 | PMC:PMC11198951 | DOI:10.1097/MEG.0000000000002799
Hum Pathol. 2024 Aug;150:67-73. doi: 10.1016/j.humpath.2024.07.001. Epub 2024 Jul 5.
ABSTRACT
A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.
PMID:38972607 | DOI:10.1016/j.humpath.2024.07.001
Lancet Gastroenterol Hepatol. 2024 Aug;9(8):734-744. doi: 10.1016/S2468-1253(24)00119-5. Epub 2024 Jun 10.
ABSTRACT
BACKGROUND: There is an unmet need for effective therapies in pretreated advanced biliary tract cancer. We aimed to evaluate the efficacy of nanoliposomal irinotecan and fluorouracil plus leucovorin compared with fluorouracil plus leucovorin as second-line treatment for biliary tract cancer.
METHODS: NALIRICC was a multicentre, open-label, randomised, phase 2 trial done in 17 German centres for patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-1, metastatic biliary tract cancer, and progression on gemcitabine-based therapy. Patients were randomly assigned (1:1) to receive intravenous infusions of nanoliposomal irinotecan (70 mg/m2), fluorouracil (2400 mg/m2), and leucovorin (400 mg/m2) every 2 weeks (nanoliposomal irinotecan group) or fluorouracil (2400 mg/m2) plus leucovorin (400 mg/m2) every 2 weeks (control group). Randomisation was by permutated block randomisation in block sizes of four, stratified by primary tumour site. Investigator-assessed progression-free survival was the primary endpoint, which was evaluated in all randomly assigned patients. Secondary efficacy outcomes were overall survival, objective response rate, and quality of life. Safety was assessed in all randomly assigned patients who received at least one dose of the study treatment. Enrolment for this trial has been completed, and it is registered with ClinicalTrials.gov, NCT03043547.
FINDING: Between Dec 4, 2017, and Aug 2, 2021, 49 patients were randomly assigned to the nanoliposomal irinotecan group and 51 patients to the control group. Median age was 65 years (IQR 59-71); 45 (45%) of 100 patients were female. Median progression-free survival was 2·6 months (95% CI 1·7-3·6) in the nanoliposomal irinotecan group and 2·3 months (1·6-3·4) in the control group (hazard ratio [HR] 0·87 [0·56-1·35]). Median overall survival was 6·9 months (95% CI 5·3-10·6) in the nanoliposomal irinotecan group and 8·2 months (5·4-11·9) in the control group (HR 1·08 [0·68-1·72]). The objective response rate was 14% (95% CI 6-27; seven patients) in the nanoliposomal irinotecan group and 4% (1-14; two patients) in the control group. The most common grade 3 or worse adverse events in the nanoliposomal irinotecan group were neutropenia (eight [17%] of 48 vs none in the control group), diarrhoea (seven [15%] vs one [2%]), and nausea (four [8%] vs none). In the control group, the most common grade 3 or worse adverse events were cholangitis (four [8%] patients vs none in the nanoliposomal irinotecan group) and bile duct stenosis (four [8%] vs three [6%]). Treatment-related serious adverse events occurred in 16 (33%) patients in the nanoliposomal irinotecan group (grade 2-3 diarrhoea in five patients; one case each of abdominal infection, acute kidney injury, pancytopenia, increased blood bilirubin, colitis, dehydration, dyspnoea, infectious enterocolitis, ileus, oral mucositis, and nausea). One (2%) treatment-related serious adverse event occurred in the control group (worsening of general condition). Median duration until deterioration of global health status, characterised by the time from randomisation to the initial observation of a score decline exceeding 10 points, was 4·0 months (95% CI 2·2-not reached) in the nanoliposomal irinotecan group and 3·7 months (2·7-not reached) in the control group.
INTERPRETATION: The addition of nanoliposomal irinotecan to fluorouracil plus leucovorin did not improve progression-free survival or overall survival and was associated with higher toxicity compared with fluorouracil plus leucovorin. Further research is necessary to define the role of irinotecan-based combinations in second-line treatment of biliary tract cancer.
FUNDING: Servier and AIO-Studien.
PMID:38870977 | DOI:10.1016/S2468-1253(24)00119-5
Abdom Radiol (NY). 2024 Jul 5. doi: 10.1007/s00261-024-04444-z. Online ahead of print.
ABSTRACT
PURPOSE: To use preoperative MRI data to construct a nomogram to predict survival in patients who have undergone R0 resection for gallbladder cancer.
METHODS: The present retrospective study included 143 patients (M:F, 76:67; 67.15 years) with gallbladder cancer who underwent preoperative MRI and subsequent R0 resection between 2013 and 2021 at two tertiary institutions. Clinical and radiological features were analyzed using univariate and multivariate Cox regression analysis to identify independent prognostic factors. Based on the multivariate analysis, we developed an MRI-based nomogram for determining prognoses after curative resections of gallbladder cancer. We also obtained calibration curves for 1-,3-, and 5-year survival probabilities.
RESULTS: The multivariate model consisted of the following independent predictors of poor overall survival (OS), which were used for constructing the nomogram: age (years; hazard ratio [HR] = 1.04; 95% confidence interval [CI], 1.04-1.07; p = 0.033); tumor size (cm; HR = 1.40; 95% CI, 1.09-1.79; p = 0.008); bile duct invasion (HR = 3.54; 95% CI, 1.66-7.58; p = 0.001); regional lymph node metastasis (HR = 2.47; 95% CI, 1.10-5.57; p = 0.029); and hepatic artery invasion (HR = 2.66; 95% CI, 1.04-6.83; p = 0.042). The nomogram showed good probabilities of survival on the calibration curves, and the concordance index of the model for predicting overall survival (OS) was 0.779.
CONCLUSION: Preoperative MRI findings could be used to determine the prognosis of gallbladder cancer, and the MRI-based nomogram accurately predicted OS in patients with gallbladder cancer who underwent curative resection.
PMID:38969822 | DOI:10.1007/s00261-024-04444-z
Clin Nucl Med. 2024 Jul 3. doi: 10.1097/RLU.0000000000005352. Online ahead of print.
ABSTRACT
Paraneoplastic neurologic syndromes are a rare, heterogeneous group of complications associated with malignancy, unrelated to direct tumor invasion or metastasis. They are the remote effects of a malignancy owing to immune-mediated reaction toward the antigens that are common to both the malignant and normal cells. Few paraneoplastic syndromes are reported with gall bladder cancer. However, neurological symptoms are infrequent. Here we share an interesting case of adenocarcinoma of gall bladder with initial presentation as a paraneoplastic noncompressing myeloneuropathy.
PMID:38968557 | DOI:10.1097/RLU.0000000000005352
JAMA Netw Open. 2024 Jul 1;7(7):e2421305. doi: 10.1001/jamanetworkopen.2024.21305.
ABSTRACT
IMPORTANCE: Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear.
OBJECTIVE: To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024.
EXPOSURES: Prescription of GLP-1RAs, insulins, or metformin.
MAIN OUTCOMES AND MEASURES: Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates.
RESULTS: In the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87).
CONCLUSIONS AND RELEVANCE: In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.
PMID:38967919 | PMC:PMC11227080 | DOI:10.1001/jamanetworkopen.2024.21305
Cancer Med. 2024 Jul;13(13):e7457. doi: 10.1002/cam4.7457.
ABSTRACT
BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy that is usually diagnosed at a late stage. Prior data showed increasing incidence of GBC in the US. However, little is known about race/ethnic-specific incidence and mortality trends of GBC per stage at diagnosis. Therefore, we aimed to conduct a time-trend analysis of GBC incidence and mortality rates categorized by race/ethnicity and stage-at-diagnosis.
METHODS: Age-adjusted GBC incidence and mortality rates were calculated using SEER*Stat software from the United States Cancer Statistics database (covers ~98% of US population between 2001 and 2020) and NCHS (covers ~100% of the US population between 2000 and 2020) databases, respectively. Race/Ethnic groups were Non-Hispanic-White (NHW), Non-Hispanic-Black (NHB), Hispanic, Non-Hispanic-Asian/Pacific-Islander (NHAPI), and Non-Hispanic-American-Indian/Alaska-Native (NHAIAN). Stage-at-diagnoses were all stages, early, regional, and distant stages. Joinpoint regression was used to generate time-trends [annual percentage change (APC) and average APC (AAPC)] with parametric estimations and a two-sided t-test (p-value cut-off 0.05).
RESULTS: 76,873 patients were diagnosed with GBC with decreasing incidence rates in all races/ethnicities except NHB who experienced an increasing trend between 2001 and 2014 (APC = 2.08, p < 0.01) and plateauing afterward (APC = -1.21, p = 0.31); (AAPC = 1.03, p = 0.03). Among early-stage tumors (9927 patients), incidence rates were decreasing only in Hispanic (AAPC = -4.24, p = 0.006) while stable in other races/ethnicities (NHW: AAPC = -2.61, p = 0.39; NHB: AAPC = -1.73, p = 0.36). For regional-stage tumors (29,690 patients), GBC incidence rates were decreasing only in NHW (AAPC = -1.61, p < 0.001) while stable in other races/ethnicities (NHB: AAPC = 0.73, p = 0.34; Hispanic: AAPC = -1.58, p = 0.24; NHAPI: AAPC = -1.22, p = 0.07). For distant-stage tumors (31,735 patients), incidence rates were increasing in NHB (AAPC = 2.72, p < 0.001), decreasing in Hispanic (AAPC = -0.64, p = 0.04), and stable in NHW (AAPC = 0.07, p = 0.84) and NHAPI (AAPC = 0.79, p = 0.13). There were 43,411 deaths attributed to GBC with decreasing mortality rates in all races/ethnicities except NHB who experienced a stable trend (AAPC = 0.25, p = 0.25).
CONCLUSION: Nationwide data over the last two decades show that NHB patients experienced increasing GBC incidence between 2001 and 2014 followed by stabilization of the rates. This increase was driven by late-stage tumors and occurred in the first decade. NHB also experienced non-improving GBC mortality, compared to other race and ethnic groups who had decreasing mortality. This can be due to lack of timely-access to healthcare leading to delayed diagnosis and worse outcomes. Future studies are warranted to investigate contributions to the revealed racial and ethnic disparities, especially in NHB, to improve early detection.
PMID:38963040 | PMC:PMC11222964 | DOI:10.1002/cam4.7457
Aust J Gen Pract. 2024 Jul;53(7):480-484. doi: 10.31128/AJGP-03-23-6775.
ABSTRACT
BACKGROUND: Gallbladder polyps are increasingly being identified due to the widespread use of abdominal ultrasound imaging. They are concerning lesions due to their potential malignant risk. It is hoped that managing them correctly will play a role in improving poor survival rates of gallbladder cancer. Awareness of these lesions is lacking. Management continues to be guided by expert opinion and observational studies and a number of consensus statements exist.
OBJECTIVE: This paper reviews and summarises the current literature and provides an approach for general practitioners based on the available guidance.
DISCUSSION: Although minor variation exists between consensus statements, the risk of malignancy for gallbladder polyps is still largely dictated by size, with those ≤5 mm generally considered to pose little risk and not requiring follow-up, whereas those ≥10 mm considered at greater risk and requiring referral for cholecystectomy.
PMID:38957064 | DOI:10.31128/AJGP-03-23-6775
Abdom Radiol (NY). 2024 Jul 2. doi: 10.1007/s00261-024-04431-4. Online ahead of print.
ABSTRACT
This comprehensive review explores a wide range of imaging findings associated with the gallbladder (GB), from anatomic variants to rare diseases. Through an in-depth review of diagnostic modalities including ultrasound, magnetic resonance cholangiopancreatography, CT, and MRI, we aim to highlight the crucial role of imaging techniques in diagnosing GB disorders, as congenital anomalies, inflammatory diseases, neoplasms, and surgical complications. Employing a detailed analysis and comparison of imaging findings across various modalities, this review seeks to improve diagnostic accuracy for GB-related pathologies, facilitating optimal patient management.
PMID:38953999 | DOI:10.1007/s00261-024-04431-4
Eur J Surg Oncol. 2024 Jul;50(7):108372. doi: 10.1016/j.ejso.2024.108372. Epub 2024 Apr 26.
ABSTRACT
BACKGROUND: Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER).
METHODS: A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity.
RESULTS: Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER.
CONCLUSION: This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.
PMID:38718620 | DOI:10.1016/j.ejso.2024.108372
Eur J Surg Oncol. 2024 Jul;50(7):108397. doi: 10.1016/j.ejso.2024.108397. Epub 2024 May 25.
ABSTRACT
INTRODUCTION: Incidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection's role as a modifying factor in the natural history of IGBC.
METHODS: All patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD.
RESULTS: Among the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38-60) for IGBC patients with no evidence of RD, compared to 31 months (23-42) for those with RD (p < 0.001).
CONCLUSION: Re-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.
PMID:38815335 | DOI:10.1016/j.ejso.2024.108397
J Gastrointest Surg. 2024 Jun 26:S1091-255X(24)00513-4. doi: 10.1016/j.gassur.2024.06.021. Online ahead of print.
ABSTRACT
INTRODUCTION: Perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma (IHCC), and gall bladder cancer are difficult malignancies to treat and are characterized by a tendency for local recurrence and a generally unfavorable prognosis. Surgical resection offers the only potential cure, conventionally performed via the open approach. Although minimally invasive approaches show promise, data remain limited.
METHODS: With the institutional review board's approval, we prospectively followed 100 patients between 2013 and 2023 who underwent robotic surgical resection for perihilar, IHCC, and gallbladder cholangiocarcinoma. Data are presented as median (mean ± SD). Significance was accepted at P ≤ .05.
RESULTS: The median patient age was 70 years, and the median operative duration was 333 min, with an estimated blood loss of 200 mL. Importantly, no unplanned conversions occurred, and only 1 intraoperative complication occurred within the IHCC cohort. The median length of stay was 4 days. There were a total of 19 postoperative complications and 19 readmissions within 30 days. Additionally, there were 3 in-hospital mortalities and 5 90-day mortalities. R0 resection was achieved in 87% of patients and R1 resection in 13%. At a median follow-up of 36 months, 62% of patients demonstrated disease-free survival, whereas 6% continued to live with the disease, and 32% did not survive.
CONCLUSION: Our experience demonstrates the feasibility and safety of robotic resection for these complex malignancies, yielding promising short-term outcomes. Further investigation is required to ascertain the long-term oncologic outcomes.
PMID:38942191 | DOI:10.1016/j.gassur.2024.06.021
Int J Mol Sci. 2024 Jun 19;25(12):6740. doi: 10.3390/ijms25126740.
ABSTRACT
Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.
PMID:38928444 | PMC:PMC11204134 | DOI:10.3390/ijms25126740
Sci Rep. 2024 Jun 24;14(1):14570. doi: 10.1038/s41598-024-61762-4.
ABSTRACT
Gallbladder cancer (GBC) is a rare but very aggressive most common digestive tract cancer with a high mortality rate due to delayed diagnosis at the advanced stage. Moreover, GBC progression shows asymptomatic characteristics making it impossible to detect at an early stage. In these circumstances, conventional therapy like surgery, chemotherapy, and radiotherapy becomes refractive. However, few studies reported some molecular markers like KRAS (Kirsten Rat Sarcoma) mutation, upregulation of HER2/neu, EGFR (Epidermal Growth Factor Receptor), and microRNAs in GBC. However, the absence of some specific early diagnostic and prognostic markers is the biggest hurdle for the therapy of GBC to date. The present study has been designed to identify some specific molecular markers for precise diagnosis, and prognosis, for successful treatment of the GBC. By In Silico a network-centric analysis of two microarray datasets; (GSE202479) and (GSE13222) from the Gene Expression Omnibus (GEO) database, shows 50 differentially expressed genes (DEGs) associated with GBC. Further network analysis revealed that 12 genes are highly interconnected based on the highest MCODE (Molecular Complex Detection) value, among all three genes; TRIP13 (Thyroid Receptor Interacting Protein), NEK2 (Never in Mitosis gene-A related Kinase 2), and TPX2 (Targeting Protein for Xklp2) having highest network interaction with transcription factors and miRNA suggesting critically associated with GBC. Further survival analysis data corroborate the association of these genes; TRIP13, NEK2, and TPX2 with GBC. Thus, TRIP13, NEK2, and TPX2 genes are significantly correlated with a greater risk of mortality, transforming them from mere biomarkers of the GBC for early detections and may emerge as prognostic markers for treatment.
PMID:38914609 | PMC:PMC11196699 | DOI:10.1038/s41598-024-61762-4
Int J Surg Case Rep. 2024 Aug;121:109930. doi: 10.1016/j.ijscr.2024.109930. Epub 2024 Jun 21.
ABSTRACT
INTRODUCTION AND IMPORTANCE: Xanthomatous inflammation is a rare chronic inflammatory condition typically affecting organs such as the kidney and gallbladder. Its occurrence in the female genital tract, particularly in the ovaries and fallopian tubes, is exceptionally rare and sparsely documented.
CASE PRESENTATION: We report a unique case of xanthomatous inflammation involving the fallopian tube and ovary, characterized by the presence of hobnail cells and apocrine metaplasia. This represents the first documented instance in medical literature. A 55-year-old woman presented with pelvic masses, initially raising suspicion of more common conditions such as ovarian neoplasms or tuberculosis.
CLINICAL DISCUSSION: Xanthomatous salpingo-oophoritis (XSO) often presents with symptoms resembling ovarian tumors or infectious diseases, posing challenges in diagnosis. Accurate preoperative identification is essential to avoid unnecessary radical surgeries and optimize patient management.
CONCLUSION: This case highlights the importance of considering xanthomatous inflammation in the differential diagnosis of ovarian and tubal lesions, especially when typical symptoms of pelvic masses are present. Recognizing this rare inflammatory condition can prevent overtreatment and guide appropriate therapeutic strategies.
PMID:38908163 | PMC:PMC11252927 | DOI:10.1016/j.ijscr.2024.109930
Indian J Gastroenterol. 2024 Jun 22. doi: 10.1007/s12664-024-01567-5. Online ahead of print.
ABSTRACT
BACKGROUND: Among cancers, carcinoma gallbladder has one of the most dismal prognosis. Early lesions are difficult to biopsy because of proximity to luminal structures and risk of biliary peritonitis. However, early surgery offers the only chance of a complete cure. Utilizing a risk score would allow characterization of the risk of malignancy and early referral to an oncology centre thereby resulting in better outcomes for patients with carcinoma gallbladder.
METHODS: The aim of this study was to develop a risk score for carcinoma in patients with suspicious gallbladder lesions based on clinical presentation and imaging. All patients with suspicious gallbladder lesions on radiological imaging who underwent surgery were analyzed. Patients were considered for scoring if the ultrasound showed the gallbladder wall thickening (more than 4 mm) and computed tomography scan showed operable disease. Statistical analysis was done to derive a score for malignancy.
RESULTS: Total 175 patients underwent an operation for suspicious gallbladder lesions from January 2005 to December 2014. The factors analyzed were clinical biochemical and imaging findings. Of these, 71 were benign on the final histopathology and 104 were malignant. The score was constructed with the following variables: female sex, high total bilirubin (≥ 1 mg/dL), presence of a mass, focal location of the lesion, presence of gallbladder stones and nodal involvement in the hepatoduodenal region on imaging. A model score and modified score were obtained. In this modified score, score of more than 8 out of 20 predicted malignancy with a sensitivity of 78% and specificity of 70.4%. Receiver operating characteristic (ROC) curve constructed with these variables had an area under curve of 0.828. There was no statistically significant difference between the model score and the modified score.
CONCLUSIONS: A pre-operative risk score was obtained for carcinoma gallbladder, which needs to be validated prospectively in future.
PMID:38907807 | DOI:10.1007/s12664-024-01567-5
Front Mol Biosci. 2024 Jun 6;11:1388294. doi: 10.3389/fmolb.2024.1388294. eCollection 2024.
ABSTRACT
Primary Sclerosing Cholangitis (PSC) is a persistent inflammatory liver condition that affects the bile ducts and is commonly diagnosed in young individuals. Despite efforts to incorporate various clinical, biochemical and molecular parameters for diagnosing PSC, it remains challenging, and no biomarkers characteristic of the disease have been identified hitherto. PSC is linked with an uncertain prognosis, and there is a pressing need to explore multiomics databases to establish a new biomarker panel for the early detection of PSC's gradual progression into Cholangiocarcinoma (CCA) and for the development of effective therapeutic interventions. Apart from non-coding RNAs, other components of the Ribonucleoprotein (RNP) complex, such as RNA-Binding Proteins (RBPs), also hold great promise as biomarkers due to their versatile expression in pathological conditions. In the present review, an update on the RBP transcripts that show dysregulated expression in PSC and CCA is provided. Moreover, by utilizing a bioinformatic data mining approach, we give insight into those RBP transcripts that also exhibit differential expression in liver and gall bladder, as well as in body fluids, and are promising as biomarkers for diagnosing and predicting the prognosis of PSC. Expression data were bioinformatically extracted from public repositories usingTCGA Bile Duct Cancer dataset for CCA and specific NCBI GEO datasets for both PSC and CCA; more specifically, RBPs annotations were obtained from RBP World database. Interestingly, our comprehensive analysis shows an elevated expression of the non-canonical RBPs, FANCD2, as well as the microtubule dynamics regulator, ASPM, transcripts in the body fluids of patients with PSC and CCA compared with their respective controls, with the same trend in expression being observed in gall bladder and liver cancer tissues. Consequently, the manipulation of tissue expression of RBP transcripts might be considered as a strategy to mitigate the onset of CCA in PSC patients, and warrants further experimental investigation. The analysis performed herein may be helpful in the identification of non-invasive biomarkers for the early detection of PSC and for predicting its progression into CCA. In conclusion, future clinical research should investigate in more depth the full potential of RBP transcripts as biomarkers for human pathologies.
PMID:38903178 | PMC:PMC11187294 | DOI:10.3389/fmolb.2024.1388294
Acta Med Okayama. 2024 Jun;78(3):291-294. doi: 10.18926/AMO/67205.
ABSTRACT
In the clinical course of malignant melanoma, which can metastasize to multiple organs, gallbladder metastases are rarely detected. A 69-year-old man who underwent resection of a primary malignant melanoma was subsequently treated with nivolumab for lung metastases and achieved complete response. Seven years after surgery, multiple nodules were found in the gallbladder, and he underwent laparoscopic cholecystectomy. The postoperative diagnosis was metastases of malignant melanoma. He has been recurrence-free 8 months after surgery. If radical resection is possible, such surgery should be performed for gallbladder metastases found in patients with other controlled lesions of malignant melanoma.
PMID:38902218 | DOI:10.18926/AMO/67205
Ann Surg Oncol. 2024 Jun 19. doi: 10.1245/s10434-024-15625-x. Online ahead of print.
ABSTRACT
BACKGROUND: Surgical resection, the only potentially curative treatment for gallbladder cancer (GBC), entails an extended cholecystectomy with portal lymphadenectomy. Lymph node dissection is a key staging procedure, but its therapeutic value is unclear. Additionally, it is technically challenging and potentially harmful. Methods for better assessment of lymph node status are needed. This report presents a case of indocyanine green (ICG)-guided sentinel lymph node biopsy (SNLB) for a patient with a gallbladder mass suspicious for GBC.
METHODS: An 81-year-old woman consulted for abdominal discomfort. Abdominal ultrasound showed an intraluminal gallbladder mass suspicious for GBC. Staging imaging did not show liver invasion, lymphadenopathy, or distant metastasis. Given the woman's advanced age and limited extent of disease, a laparoscopic extended cholecystectomy with an ICG-guided SLNB was performed. Injection of 1 ml of ICG (0.125 mg/mL) into the gallbladder bed was performed using a 22-gauge needle, avoiding direct injection into the gallbladder wall.
RESULTS: A near-infrared camera was used to visualize real-time ICG flow through the lymphatic vessels of the gallbladder toward the cystic node. Then, a sentinel lymph node posterolateral to the bile duct (station 12b) was identified. The node was resected and sent for permanent section. The procedure continued with an extended cholecystectomy. Pathology showed an intracholecystic papillary neoplasm with high-grade dysplasia. Cystic and sentinel lymph nodes were negative for malignancy.
CONCLUSION: For patients with gallbladder neoplasms, ICG-guided SLNB is a feasible technique that could allow for treatment de-escalation. Further evaluation in clinical trials is needed.
PMID:38896224 | DOI:10.1245/s10434-024-15625-x
BMJ Case Rep. 2024 Jun 18;17(6):e260297. doi: 10.1136/bcr-2024-260297.
ABSTRACT
SummarySquamous cell carcinoma (SCC) is an uncommon and frequently aggressive subtype of gallbladder cancer known for its poor outcomes compared with other gallbladder tumours. Gallbladder SCC typically presents as higher grade and more advanced than adenocarcinoma, resulting in lower estimated survival. Early recognition of these tumours is ideal, but infrequently achieved. Herein is a case of a male patient in his 80s with new onset abdominal pain who was initially diagnosed with cholecystitis, but diagnostic imaging revealed a gallbladder mass. Surgical resection and pathology revealed pure SCC of the gallbladder without local organ invasion or metastatic disease. Pure SCC histology of the gallbladder is rare, with limited studies on clinical presentation, natural history, and optimal treatment.
PMID:38890111 | DOI:10.1136/bcr-2024-260297
BMC Gastroenterol. 2024 Jun 17;24(1):201. doi: 10.1186/s12876-024-03291-y.
ABSTRACT
BACKGROUND: Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS.
METHODS: A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts.
RESULTS: Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3-11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19-18.84), and age (OR 1, 95% CI 1.01-1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57-83.33, OR 16.3, 95% CI 3.02-88.08).
CONCLUSION: MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause.
PMID:38886637 | PMC:PMC11181604 | DOI:10.1186/s12876-024-03291-y
Cell Death Dis. 2024 Jun 17;15(6):422. doi: 10.1038/s41419-024-06800-9.
ABSTRACT
TGF-β1 plays a pivotal role in the metastatic cascade of malignant neoplasms. N6-methyladenosine (m6A) stands as one of the most abundant modifications on the mRNA transcriptome. However, in the metastasis of gallbladder carcinoma (GBC), the effect of TGF-β1 with mRNA m6A modification, especially the effect of mRNA translation efficiency associated with m6A modification, remains poorly elucidated. Here we demonstrated a negative correlation between FOXA1 and TGF-β1 expression in GBC. Overexpression of FOXA1 inhibited TGF-β1-induced migration and epithelial-mesenchymal transition (EMT) in GBC cells. Mechanistically, we confirmed that TGF-β1 suppressed the translation efficiency of FOXA1 mRNA through polysome profiling analysis. Importantly, both in vivo and in vitro experiments showed that TGF-β1 promoted m6A modification on the coding sequence (CDS) region of FOXA1 mRNA, which was responsible for the inhibition of FOXA1 mRNA translation by TGF-β1. We demonstrated through MeRIP and RIP assays, dual-luciferase reporter assays and site-directed mutagenesis that ALKBH5 promoted FOXA1 protein expression by inhibiting m6A modification on the CDS region of FOXA1 mRNA. Moreover, TGF-β1 inhibited the binding capacity of ALKBH5 to the FOXA1 CDS region. Lastly, our study confirmed that overexpression of FOXA1 suppressed lung metastasis and EMT in a nude mice lung metastasis model. In summary, our research findings underscore the role of TGF-β1 in regulating TGF-β1/FOXA1-induced GBC EMT and metastasis by inhibiting FOXA1 translation efficiency through m6A modification.
PMID:38886389 | PMC:PMC11183149 | DOI:10.1038/s41419-024-06800-9
Transl Oncol. 2024 Sep;47:102036. doi: 10.1016/j.tranon.2024.102036. Epub 2024 Jun 14.
ABSTRACT
INTRODUCTION: Hepatopancreatobiliary (HPB) cancers encompassing malignancies of the liver, pancreas, gall bladder, and bile ducts pose a significant health burden in Africa. While the association of certain occupational carcinogens in cancer is well established globally, their potential role in HPB cancers remains understudied, especially in an African context.
AIM: This systematic review delves into the association between occupational carcinogens and HPB cancer in Africa. It examines the current state of research on occupational carcinogens and HPB cancers in Africa, identifying key challenges and knowledge gaps.
METHODS: This systematic review examined publications (published between 01 January 2012 and 31 May 2023) that highlight occupational carcinogens and HBP cancers in Africa. The search was conducted on electronic databases namely PubMed, Web of Science, and Africa Wide Information.
RESULT: Due to the lack of information on the association between occupational carcinogens and HPB cancers in Africa, as a result of the paucity of published studies, only four articles were included in this study. Hepatocellular carcinoma (HCC) was the predominant cancer associated with the occupational carcinogen, aflatoxin. Agricultural workers, especially those involved in the production and processing of maize and peanuts, appear to be the most exposed to aflatoxin.
CONCLUSION: Despite the sample size limitations due to the paucity of research studies on occupational carcinogens and HPB cancers in Africa, this study provides a reasonable tool for subsequent epidemiological studies. There is a need for more research on the association of occupational carcinogens and HPB cancers in Africa, especially with the growing industrialization.
PMID:38878612 | PMC:PMC11225925 | DOI:10.1016/j.tranon.2024.102036