Laparoscopic Cholecystectomy for Gallbladder Polyps: Is It Overtreatment?

BACKGROUND: The gallbladder polyp (GP) is an accepted risk factor of gallbladder cancer and an indication for laparoscopic cholecystectomy (LC). Generally, the pathologic result of GPs is benign, but it is difficult to distinguish a potential malignancy or a stone without pathological evaluation. This study compared the indication and pathologic result of cholecystectomy performed due to GP in our clinic. MATERIALS AND METHODS: This study employed retrospective data analysis. Patients who underwent LC from August 2021 through August 2024 were included in the study. Demographic features, operation status, indications for surgery, hospital stay, concomitant surgery, pathologic outcomes, and complications were recorded from patients' data. Polyp sizes and number of polyps were taken from ultrasonography (USG) data. RESULTS: A total of 533 patients were included in the study. The mean age was 44.31 ± 12.14, and 64.35% (n = 343) were of female gender. Twenty patients (3.75%) underwent surgery for GP. The mean polyp size was 7.47 mm (2-15); 65% of the patients (n = 13) had multiple polyps, and 35% (n = 7) had a single polyp. The mean hospital stay was 1.59 ± 0.88 days. The pathologic result of GP was pseudopolyp in 55% (n = 11) of cases and non-polyp in 45% (n = 9). One patient (0.18%) who underwent an operation for gallstone had a malignancy. The sensitivity of USG in detecting polyps was found to be 64.7%. The complication rate was 1.5% (n = 8). CONCLUSION: The pathological result of many patients who undergo cholecystectomy due to GPs is pseudopolyp or adenoma. In our study, no carcinoma was observed in any patient who underwent surgery for polyps. Further studies are needed to determine the indication for surgery due to GP.

Different biliary tract cancers, same operation: Importance of cancer origin in patients with hilar-invading tumors.

BACKGROUND AND AIMS: For patients with biliary tract cancer involving the hepatic hilum, major hepatic resection with extrahepatic bile duct resection may be required. In addition to perihilar cholangiocarcinoma (PHCC), the same extent of surgery is used in advanced gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHCC) with hilar involvement. Few studies compare prognostic factors and long-term outcomes across tumor types. This study compared risk characteristics and outcomes after surgery in all subtypes of biliary tract cancer with hilar involvement. METHODS: Patients with biliary tract cancer with hilar involvement undergoing major liver resection and extrahepatic bile duct resection between 2011 and 2021 at a single center were retrospectively analyzed. The primary postoperative outcome was overall survival. Secondary outcomes were recurrence-free survival and postoperative complications. Survival analysis was performed with Cox regression analysis and Kaplan-Meier method. RESULTS: One-hundred and eight patients were included. Seventy-three (67%) had PHCC, 24 (22%) had GBC, and 11 (10%) had IHCC. Hilar-invading IHCC and GBC had more adverse histopathological factors like lymph node positivity (p = 0.021), higher number of positive nodes (p = 0.043), and larger tumor size (p < 0.001) compared with PHCC. Peritoneal invasion and lymph node positivity were significant independent predictors for survival (p = 0.011 and p = 0.004, respectively). Median overall survival was 29 months for PHCC, 22 months for GBC and 21 months for IHCC (p = 0.53). IHCC tended to recur earlier (p = 0.046) than GBC and PHCC (6, 15, and 18 months, respectively). CONCLUSION: Patients with biliary tract cancer with hilar involvement undergoing major liver resection and resection of extrahepatic bile ducts had similar overall survival regardless of subtype, while IHCC recurred earlier. Peritoneal cancer invasion was common in all subtypes, including PHCC, and was an independent prognostic factor. This finding may support routine reporting of peritoneal invasion-status in resected biliary tract cancer.

The risk of cholangiocarcinoma in patients with MASLD is not increased compared to the general population.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in prevalence globally. MASLD is associated with an increased rate of comorbidities, including cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma (HCC). While the link between MASLD and HCC is well known, the potential association with biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), is less certain. To evaluate whether individuals with MASLD are at increased risk of developing CCA compared to the general population, we performed a nationwide cohort study investigating the longitudinal association between MASLD and CCA. METHODS: A retrospective cohort study was performed including all patients ≥18 years of age, diagnosed with MASLD, from 1st of January 1987 to 31st of December 2020, through the Swedish National Patient Register. For each patient with MASLD, ten individuals, matched to the MASLD patient on year of diagnosis, age, sex, and municipality were selected as reference individuals. The international Classification of Diseases (ICD) codes were used to define MASLD and incident CCA. Incidence rates were calculated, and regression analyses were performed. RESULTS: Out of the 11,940 exposed patients with MASLD, 11 developed CCA (0.1%) out of whom three were diagnosed with iCCA (0.03%), during a median follow-up time of five years. Out of 112,537 reference individuals, 62 were diagnosed with CCA (0.3%), out of whom 15 were diagnosed with iCCA (0.01%). The rate of GBC was not higher compared to the reference population. CONCLUSION: This large cohort study found a low incidence of CCA in patients with MASLD, comparable to the general population which can reassure clinicians and patients that no specific vigilance for CCA should be considered in MASLD patients at present.

Gallbladder Cancer.

Gallbladder cancer is the most common biliary tract malignancy, often detected incidentally post-cholecystectomy or at an advanced stage, historically linked to a poor prognosis. Advances in minimally invasive surgery and systemic therapies have improved outcomes. Global incidence varies, with risk factors including gender, age, gallbladder disease history, and polyp size influencing malignancy risks. Management involves cross-sectional imaging, staging laparoscopy in select cases, and radical cholecystectomy with lymphadenectomy and adjuvant therapy, though its use is limited. Trials are ongoing assessing the role of neoadjuvant therapy. Prognosis depends on the tumor stage, with early detection crucial for long-term survival.

Gallbladder Burkitt's Lymphoma: A Literature Review Including a Case Report in a Child Living with HIV.

Malignant lymphoma is an unusual form of gallbladder neoplasm. Almost all these tumors are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas. Herein, we present a literature review of gallbladder Burkitt's lymphoma (BL) cases that includes also an unpublished case in an HIV-infected child, observed by our center. The patient (a five-year-old black female child) attended the Federal Hospital of Lagoa, Rio de Janeiro, Brazil, underwent cholecystectomy, and the postoperative pathological analysis of the gallbladder revealed a diagnosis of BL (EBV-positive). Also, HIV serology was performed and returned positive. She was transferred to the Martagão Gesteira Institute of Pediatrics and Childcare for oncological treatment, dying from sepsis and disease progression about 18 months later. The patient did not undergo ART/cART. Previous cases of gallbladder BL were herein described and analyzed to characterize the clinicopathological features and possible similarities. BL can occur in the gallbladder both in the context of HIV infection and in the pediatric population. A biopsy is mandatory in cases with suggestive findings of lymphoma, and an early diagnosis can change the course of the disease. Furthermore, the case highlights the importance of an early initiation of ART/cART in people living with HIV (PLWH), especially in children.

Effect of anesthetic technique on antitumor immunity in patients undergoing surgery for gall bladder cancer: A prospective randomized comparative study.

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-ß (TGF-ß), 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-ß (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-ß 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.

Novel multifactor predictive model for postoperative survival in gallbladder cancer: a multi-center study.

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.

SNORA71A Downregulation Enhances Gemcitabine Sensitivity in Gallbladder Cancer Cells by Inducing Ferroptosis Through Inhibiting the AKT/NRF2/GPX4 Pathway.

Previous findings have indicated a marked upregulation of SNORA71A in gallbladder cancer (GBC) tissues compared to normal samples. However, the precise role and molecular mechanisms of SNORA71A in GBC remain largely unknown. Moreover, gemcitabine (GEM) drug resistance has been found to lead to unfavorable outcomes and recurrence in GBC patients. Therefore, this study aims to investigate the impact of SNORA71A on GBC and explore its potential effects on the sensitivity of GBC cells to GEM. RT-qPCR was conducted to assess SNORA71A level in matched normal and GBC tissues. Cell proliferation was examined through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays. Additionally, the expression of proteins in GBC cells was analyzed using western blot assay. The level of SNORA71A was notably higher in GBC tissues relative to normal tissues. SNORA71A overexpression led to increased GBC cell proliferation and invasion. Conversely, SNORA71A deficiency strongly suppressed GBC cell proliferation and invasion and triggered cell apoptosis and ferroptosis. Additionally, downregulation of SNORA71A obviously enhanced the antiproliferative and anti-invasive effects of GEM on GBC cells, whereas these changes were reversed by inhibiting ferroptosis. Furthermore, deficiency of SNORA71A further augmented the GEM-induced downregulation of p-Akt, Nrf2, and GPX4 in NOZ cells; however, these effects were reversed by ferroptosis inhibition. Collectively, these findings suggested that downregulation of SNORA71A may increase the sensitivity of GBC cells to GEM by triggering ferroptosis through inhibiting the AKT/NRF2/GPX4 signaling pathway.

Practices in the Management of Incidental Gallbladder Cancer.

Peeyush VarshneyBackground Histopathology of gallbladder removed for stones may reveal incidental gallbladder cancer (iGBC). We conducted this online e-survey to document the knowledge and practices of management of iGBC among surgeons in India. Methods A 38-question online e-survey Results Two-hundred thirty responses were recorded. Ninety-eight out of two-hundred (49%) responses were general surgeons. Two-hundred ten out of two-hundred twenty-one (95%) saw at least one iGBC per year, but only 74/225 (32%) correctly defined true iGBC. One-hundred seventy-eight out of two hundred twenty-two (80%) did computed tomography/magnetic resonance imaging for thick-walled gallbladder (GB) detected on ultrasound, while 25/222 (11%) did laparoscopic cholecystectomy and 14/222 (6%) did open cholecystectomy. For GB mass on laparoscopy, 16/222 (7%) responses went ahead with simple cholecystectomy. Seventy-four out of two-hundred twenty-five (32%) responses routinely used bag while extracting GB. One-hundred ninety-one out of two-hundred twenty-five (86%) mentioned about stone/bile spill, 121/220 (55%) mentioned about use of bag for extraction while 137/220 62% mentioned port used for extraction of GB in operation notes. One-hundred sixty-six out of two-hundred twenty-seven (73%) always cut open GB after cholecystectomy. On encountering a mass/lesion on cut open GB, 111/225 (49%) sent it for frozen section, 89/225 (40%) sent for routine histopathology while 10% (22/225) directly proceeded for extended cholecystectomy. Ten out of two-hundred twenty-seven (4.4%) did not consider it important to send GB for histopathology. T stage on histopathology is most important factor for deciding reoperation by 205/223 (91%). Conclusion There are lacunae in understanding and deficiencies in management of iGBC in India-a high GBC incidence country. The situation is likely to be worse in low GBC incidence areas. There is need for more awareness and knowledge for proper management of iGBC among surgeons.

Prognostic utility of the modified albumin-bilirubin score among patients undergoing curative-intent surgery for gallbladder cancer.

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 albumin-bilirubin (mALBI) score among individuals undergoing curative-intent resection for GBC has not been determined. METHODS: Patients who underwent radical resection for GBC between 2000 and 2022 were identified from an international, multi-institutional database. Preoperative albumin and bilirubin levels were used to calculate the mALBI score. The relationship among mALBI score, overall survival (OS), and recurrence-free survival (RFS) was examined. RESULTS: Among 269 patients who underwent radical resection for GBC, 161 (59.9%) had mALBI grade 1, 48 (17.8%) had grade 2a, 47 (17.5%) had grade 2b, and 13 (4.8%) had mALBI grade 3. After surgery, compared with patients with a low mALBI grade (grade 1/2a), individuals with a high mALBI grade (grade 2b/3) had worse 5-year OS (54.4% vs 19.2%, respectively; P < .001) and RFS (42.0% vs 17.8%, respectively; P < .001). On multivariable analysis, after controlling for relevant clinicopathologic variables, individuals with a high mALBI score remained independently associated with higher risks of death and recurrence (OS: hazard ratio [HR], 2.38 [95% CI, 1.50-3.79]; RFS: HR, 2.12 [95% CI 1.41-3.20]) versus patients with a low mALBI score after curative-intent resection for GBC. Of note, mALBI score was associated with incrementally worse survival within T2, T3, and N+ categories, whereas classic American Joint Committee on Cancer subclassifications failed to distinguish patients with long-term survival. CONCLUSION: The mALBI score presents a simple, objective measure of hepatic functional reserve and may be a useful prognostic tool for patients undergoing curative-intent resection for GBC.

Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer.

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.

Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers.

Claudins, a family of tetraspan transmembrane proteins, are critical to the integrity of tight junctions in epithelia and endothelia, influencing cellular processes such as development, differentiation, and apoptosis. Abnormal claudin expression is associated with various malignancies, particularly affecting tissue architecture and potentially facilitating tumor invasion and metastasis. In this comprehensive review, we explore the multifaceted functions of claudins: their expression, specific roles in cancer with a focus on hepato-pancreato-biliary malignancies and highlight their potential as therapeutic targets. We discuss current claudin-targeted therapies, including monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engager and chimeric antigen receptor T-cell therapies. These approaches show promise in pre-clinical and clinical studies, particularly in hepato-pancreato-biliary cancers with large unmet needs. Despite these early signs of efficacy, challenges remain in effectively targeting these proteins due to their structural resemblance and overlapping functions.

Synchronous Primary Gallbladder and Colon Adenocarcinoma: A Case Report and Systematic Literature Review.

Synchronous primary malignancies, defined as two or more primary malignancies diagnosed simultaneously or within six months, are uncommon and present unique diagnostic and therapeutic challenges. Synchronous primary adenocarcinoma of the gallbladder and colon is particularly rare. We report a case of a 48-year-old female presenting with persistent right upper abdominal pain. Laboratory tests and imaging studies initially suggested xanthogranulomatous cholecystitis. However, subsequent laparoscopic cholecystectomy and pathological examination revealed a moderately differentiated adenocarcinoma of the gallbladder (pT2bN1M0). Further staging with CT and PET-CT scans identified a suspicious mass in the transverse colon, confirmed by colonoscopy and surgical resection as well-differentiated adenocarcinoma of the transverse colon (pT3N0M0). Immunohistochemistry and genetic profiling of both tumors indicated distinct primary origins without loss of mismatch repair (MMR) protein expression. The patient underwent additional liver resection, lymph node dissection, and right extended hemicolectomy. She is currently undergoing further staging and awaiting chemotherapy. A review of English-language literature revealed eight reported cases of synchronous primary gallbladder and colorectal cancer and a total of 13 with synchronous primary malignancy of other organs. Such cases are rare and diagnostically complex cases. Common factors contributing to multiple primary malignancies (MPM) include genetic predispositions, previous cancer treatments, and lifestyle factors such as smoking and alcohol consumption. This case underscores the importance of thorough investigation and prompt treatment in patients suspected of having MPM. Advances in diagnostic imaging and molecular profiling are crucial for early detection and tailored therapeutic strategies. Standardized guidelines for managing synchronous cancers are needed to improve patient outcomes.

Advances and current research status of early diagnosis for gallbladder cancer.

Gallbladder cancer (GBC) is the most common malignant tumor in the biliary system, characterized by high malignancy, aggressiveness, and poor prognosis. Early diagnosis holds paramount importance in ameliorating therapeutic outcomes. Presently, the clinical diagnosis of GBC primarily relies on clinical-radiological-pathological approach. However, there remains a potential for missed diagnosis and misdiagnose in the realm of clinical practice. We firstly analyzed the blood-based biomarkers, such as carcinoembryonic antigen and carbohydrate antigen 19-9. Subsequently, we evaluated the diagnostic performance of various imaging modalities, including ultrasound (US), endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT) and pathological examination, emphasizing their strengths and limitations in detecting early-stage GBC. Furthermore, we explored the potential of emerging technologies, particularly artificial intelligence (AI) and liquid biopsy, to revolutionize GBC diagnosis. AI algorithms have demonstrated improved image analysis capabilities, while liquid biopsy offers the promise of non-invasive and real-time monitoring. However, the translation of these advancements into clinical practice necessitates further validation and standardization. The review highlighted the advantages and limitations of current diagnostic approaches and underscored the need for innovative strategies to enhance diagnostic accuracy of GBC. In addition, we emphasized the importance of multidisciplinary collaboration to improve early diagnosis of GBC and ultimately patient outcomes. This review endeavoured to impart fresh perspectives and insights into the early diagnosis of GBC.

Cancer-associated retinopathy secondary to gallbladder carcinoma.

Objective: To present a rare case of cancer-associated retinopathy secondary to gallbladder carcinoma. Methods: Retrospective case report. Drugs used in case report: methylprednisolone (Medrol), CAS number: 83-43-2, producer: Pfizer; carboplatin, CAS number: 41575-94-4, producer: Accor; etoposide, CAS number: 33419-42-0, producer: Teva; methotrexate (Ledertrexate), CAS number: 59-05-2, producer: Pfizer. Results: A 57-year-old Moroccan man was referred with bilateral progressive vision loss in the last 4 months. At presentation, best corrected visual acuity (BCVA) was counting fingers for the right eye and 20/500 for the left eye. Examination demonstrated signs of vitritis, an electronegative full-field electroretinography (FF-ERG), ocular coherence tomography (OCT) abnormalities and multiple hyperautofluorescent round lesions on fundus autofluorescence imaging (FAF). The diagnosis of cancer-associated retinopathy (CAR) was considered, thus a positron emission tomography-computed tomography (PET-CT) was performed and revealed the presence of a metastasized gallbladder carcinoma. Additional fluorescence in situ hybridization (FISH) showed seropositivity for anti-retinal autoantibodies. High-dose corticosteroids together with anti-tumoral medication (carboplatin-etoposide) gradually improved the BCVA to 20/66 for the right eye and 20/20 for the left eye. Conclusions: Consider the diagnosis of CAR in patients with progressive concentric visual field loss, uveitis and fundus abnormalities, especially if bilateral. If CAR is suspected, perform a full work-up: FF-ERG, OCT, and whole-body PET-CT. In the treatment of CAR, immunosuppressives are mostly used, combined with antitumoral therapy. However, in the long-term, progressive visual loss is expected in most cases.

Impact of Retroperitoneal Lymphadenopathy (RPLN) on the Outcomes of Locally Advanced Gall Bladder Cancer (GBC) Following Chemotherapy (CT) or Chemotherapy Followed by Consolidation Chemoradiotherapy (CTRT).

INTRODUCTION: Retroperitoneal lymphadenopathy is considered a metastatic disease in GBC; however, some surgical series of radical surgery with enlarged RPLN who underwent RPLN dissection have shown results marginally inferior to those without enlarged RPLN. Radiological RPLN comprises a major proportion of advanced non-metastatic GBC. There is dilemma in the intent of treatment to be offered in such cases. We are reporting our series of outcome of GBC with RPLN treated with first-line CT followed by consolidation CTRT. MATERIALS AND METHODS: Non-metastatic locally advanced GBC with good performance status (KPS ≥ 80) were initiated on first-line CT (cisplatin-gemcitabine), and thereafter, responders were evaluated by CECT-angiography and PET-CT scan for resectability. If found unresectable, they were offered consolidation CTRT to a dose of 45 Gy by conventional fractionation (3D-CRT technique) along with concurrent capecitabine at 1250 mg/m2 to GBC and regional lymphatics including RPLN. Thereafter, boost dose of 9 Gy/5# was given to GBC only. Response assessment was done using CECT abdomen by RECIST criteria v 1.1. Outcomes (overall survival) of the two groups (RPLN vs non-RPLN) were computed with Kaplan-Meier survival curves and chi-square tests using SPSS v 20. RESULTS: Among 189 patients of advanced non-metastatic GBC recruited from 2011 to 2022, 80 had RPLN. The demographic features of both groups were comparable. Overall, 68% of the patients were women, 30% underwent upfront stenting for obstructive jaundice, and 90% had T3 and T4 disease. Only 10% had undergone upfront laparoscopic staging and had pathologically proven RPLN. Forty percent of the patients received four cycles of CT only and 50% of the patients received six cycles or more and 33% received CTRT. By RECIST criteria, 10% vs 16% achieved complete response (CR), 39% vs 41% achieved partial response (PR), 16% vs 15% achieved stable disease (SD), 2.7% vs 6% had disease progression (PD), and 14.5% vs 3.7% were non-evaluable in non-RPLN group vs RPLN group, respectively. 12% vs 6% could undergo radical surgery in non-RPLN group vs RPLN group (p = 0.03). The median OS was 9 months (95% CI 7.6-10.3 months) vs 10 months (95% CI 8-9.8 months) (p = NS) in non-RPLN group vs RPLN group, respectively. In those who received CT only, the median OS was 7 months vs 8 months, while in those who received CT followed by CTRT, the median OS was 14 months vs 13 months (p = 0.65) in non-RPLN group vs RPLN group, respectively. CONCLUSIONS: Based on this analysis, we conclude that RPLN constitutes a major proportion of advanced non-metastatic GBC and has outcomes similar to those without RPLN if treated with radical intent. RPLN should not be considered a metastatic disease and should be treated with radical intent.

A case of successful conversion surgery for unresectable gallbladder cancer treated with durvalumab in combination with gemcitabine plus cisplatin.

We report a rare case of a patient with initially unresectable gallbladder cancer who underwent conversion surgery with durvalumab in combination with gemcitabine plus cisplatin and achieved an R0 resection. A 68 year-old woman was found to have gallbladder cancer and multiple enlarged lymph nodes around the suprapancreatic rim and hepatic hilum invading the proper hepatic artery on computed tomography. The diagnosis was cT3cN2cM0, cStage IVB. After eight cycles of durvalumab in combination with gemcitabine plus cisplatin, all tumor markers became negative, and lymph node invasion of the hepatic artery disappeared. The patient underwent conversion surgery with gallbladder bed resection and regional lymph node dissection. There was no need for hepatic artery reconstruction. Pathology revealed ypT2aypN0ycM0, ypStage IIA, and radical resection was considered. Immunostaining of tissue collected at the time of endoscopic ultrasound-guided tissue acquisition revealed less than 1% programmed death ligand-1 expression. The patient continued adjuvant chemotherapy with single-agent durvalumab every 4 weeks and maintained a relapse-free survival of 8 months postoperatively. The utility of durvalumab in combination with gemcitabine plus cisplatin in unresectable gallbladder cancer independent of programmed death ligand-1 expression has been confirmed and may be an important option in future multimodal treatment, including conversion surgery.

Interplay of Cardiometabolic Syndrome and Biliary Tract Cancer: A Comprehensive Analysis with Gender-Specific Insights.

BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC.

Radical cholecystectomy without liver resection for peritoneal side early incidental gallbladder cancer.

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.

Safety of pressurized intraperitoneal aerosolized chemotherapy in biliary cancer patients with peritoneal metastases.

Biliary tract cancers are a rare diagnosis with a rising incidence. Up to 20% of patients have peritoneal metastases, resulting in symptoms of ascites, abdominal pain and potential bowel obstruction. A standard of care systemic treatment comprises gemcitabine, cisplatin and durvalumab (gem/cis/durva). However, the clinical benefit among patients with peritoneal metastases remains unknown. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivers chemotherapy directly to the peritoneal space, which could potentially improve efficacy with minimal systemic toxicity. We describe the design of a Phase I study investigating PIPAC with nab-paclitaxel plus systemic gem/cis/durva among biliary tract cancer patients with peritoneal metastases who have not received prior systemic treatment. The primary end point is safety of PIPAC with nab-paclitaxel in combination with systemic gem/cis/durva.Clinical Trial Registration: NCT05285358 (ClinicalTrials.gov).

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