Advanced Gallbladder Cancer Research Articles

Laparoscopic hepatopancreatoduodenectomy for locally advanced gall bladder cancer.

Hepatopancreatoduodenectomy (HPD) can offer a survival advantage in selected patients with locally advanced gall bladder cancer (GBC). While the safety and feasibility of minimally invasive radical cholecystectomy have been recently documented, laparoscopic HPD for GBC has not been previously reported. A 73-year-old male with GBC infiltrating the bile duct underwent laparoscopic HPD to achieve R0 resection. The patient had an uneventful post-operative course except for delayed gastric emptying that improved with conservative management. The feasibility of laparoscopic HPD for locally advanced GBC reported in the present case needs to be documented in a large case series.

Neoadjuvant Chemotherapy in Locally Advanced Unresectable Carcinoma Gall Bladder (ENACT Trial): A Novel Beginning in a Tertiary Centre in North India

Introduction: Locally advanced Gall Bladder Cancer (LAGBC) is usually unresectable and presents with dismal prognosis. The role of neoadjuvant chemotherapy (NACT) in LAGBC is still not fully established. In our study we look for effect of NACT in LAGBC in terms of response and survival.

A Study of Advanced Gallbladder Cancer to Evaluate Surgical Procedure and Poor Prognostic Factors

A Study of Advanced Gallbladder Cancer to Evaluate Surgical Procedure and Poor Prognostic Factors

Clinical Implication of PD-L1 Expression in Gallbladder Cancer

Introduction: Programmed death ligand-1 (PD-L1) expression has been established as a prognostic factor for various solid tumors, but is not well understood in gallbladder cancer (GBC). This study was designed to evaluate PD-L1 expression in GBC and investigate its association with clinicopathological factors, tumor-infiltrating immune cells and survival outcomes. Methods: The expression of PD-L1 was detected by immunohistochemistry from 94 GBC patients who underwent R0/R1 resection at our institution between 2003 and 2016. Tumor-infiltrating CD8+ T cells or CD163+ positive macrophages were assessed at invasive front of tumor, tumor stroma and intraepithelial, respectively. To evaluate the cytotoxic activity of CD8+ T cell, the expression of Perforin and Granzyme B was also assessed using immunohistochemistry. Results: The expression of PD-L1, Perforin and Granzyme B was identified in 38 patients (40.4%), 29 patients (30.9%) and 20 patients (21.3%), respectively. High PD-L1 expression was associated with male gender, high preoperative CA19-9 level, lymphatic invasion, venous invasion, lymph node metastasis and liver metastasis. High PD-L1 expression was related to poorer OS (p=0.0046) and DFS (p=0.0011). In addition, CD163+ macrophage infiltration of tumor was positively correlated with PD-L1 expression. Moreover, high CD8+ TIL group at invasive front of tumor had better OS (p=0.011) compared to low CD8+ TIL group. However, high PD-L1 was also related to poor prognosis in this subgroup. Conclusions: PD-L1 expression is a useful biomarker for advanced GBC. The subgroup of high PD-L1 with high CD8+ TIL at invasive front of tumor would be potential therapeutic target for PD-1/PD-L1 checkpoint inhibitors.

Microarray based gene expression profiling of advanced gall bladder cancer.

Gall bladder cancer (GBC) is an aggressive cancer with specific predilection like female gender and specific geographical areas, however the molecular mechanisms and factors contributing to the clinical or biological behavior are not understood. The aim of this study was to perform a comprehensive analysis of differentially expressed genes in advanced GBC and chronic cholecystitis(CC) cases. Microarray was planned on fresh specimens of advanced GBC and CC cases using single color cRNA based microarray technique (8X60K format; Agilent Technologies, USA). Twelve advanced GBC and four CC patients were included in the study. Of the total of 1307differentially expressed genes, 535genes were significantly upregulated, while 772genes were significantly downregulated in advanced GBC vs CC samples. Differentially expressed genes were associated with biological processes (55.03%), cellular components (31.48%), and molecular functions (13.49%) respectively. The important pathways or key processes affected were cell cycle, DNA replication, oxidative stress, gastric cancer pathway. Using in silico analysis tools, three differentially expressed genes i.e. TPX2, Cdc45and MCM4were selected (for their significant role in DNA replication and microtubule function) and were further validated in 20advanced GBC cohort by immunohistochemistry. Significant positive association of Cdc45and MCM4proteins was found in advanced GBC cases (p=0.043), suggesting the probable oncogenic role of Cdc45and MCM4proteins in advanced GBC. Our data demonstrate the potential regulation of Cdc45-MCM4axis in advanced GBC tumors. Additionally, our study also revealed a range of differentially expressed genes (e.g. TPX2, AKURA etc.) between GBC and CC, and further validation of these genes might provide a potential diagnostic or therapeutic target in future.

Second-line Chemotherapy Prolongs Survival in Real World Patients With Advanced Biliary Tract and Gallbladder Cancers: A Multicenter Retrospective Population-based Cohort Study.

Limited evidence is available regarding the survival benefit of second-line therapy in real world patients with advanced biliary tract and gallbladder cancer. Until very recently, there was a lack of randomized clinical trials to address this important question. In this multicenter population-based cohort study, the authors evaluated whether second-line therapy improves the survival of real world patients with advanced biliary tract and gallbladder cancer. Patients with biopsy-proven advanced biliary tract and gallbladder cancer who were diagnosed during the period of 2006 to 2015 and had received first-line chemotherapy were assessed. Cox proportional multivariate analysis was performed to determine the survival benefit of second-line therapy. One hundred thirty-six eligible patients with a median age of 66 years and male:female ratio of 1:1.34 were identified. Sixty-eight percent of patients had metastatic disease. Primary tumor sites were as follows: gallbladder 31%, intrahepatic cholangiocarcinoma 36%, extrahepatic bile duct 23%, and ampullary cancer 10%. Overall, 37% of patients received second-line therapy. The median overall survival of the treatment group was 17 months (95% confidence interval [CI]: 12.5-21.5) compared with 7 months (95% CI: 5.3-8.7) in the control (P<0.0001). Patients who received combination chemotherapy had a median overall survival of 20 months (14.0-26.1) compared with 17 months (13.5-20.5) if they received single-agent second-line therapy (P=0.73). Multivariate analysis of second-line therapy, hazard ratio: 0.55 (95% CI: 0.36-0.83) and neutrophil to lymphocyte ratio >2, HR: 1.10 (1.05-1.15) showed a significant correlation with survival. This well-designed population-based retrospective cohort study suggests that second-line chemotherapy improves survival of real world patients with advanced biliary tract and gallbladder cancers and should be offered to the patients who are potential candidates for chemotherapy.

Gemcitabine＋Cisplatin併用化学療法後にConversion Surgeryを施行し，R0切除を達成した切除不能進行胆嚢癌の1例

Gemcitabine＋Cisplatin併用化学療法後にConversion Surgeryを施行し，R0切除を達成した切除不能進行胆嚢癌の1例

Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Gallbladder Cancer.

The aim of this study was to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil for patients with advanced gallbladder cancer (GBC). Twenty-six patients with advanced GBC, who underwent HAIC with oxaliplatin and 5-fluorouracil from January 2012 to July 2019, were enrolled in this retrospective study. The HAIC regimen consisted of infusions of oxaliplatin at 40mg/m2 for 2h, followed by 5-fluorouracil at 800mg/m2 for 22h on days 1-3 every 3-4weeks. A maximum of six cycles of HAIC were applied for tumor control patients followed by maintenance with oral capecitabine or S-1. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were investigated. Six of the 26 patients (23.1%) had failed systemic chemotherapy, 8/26 (30.8%) patients had failed various local therapies, and 9/26 (34.6%) patients had contraindications to systemic chemotherapy. The median OS was 13.5months, and the median PFS was 10.0months. The overall response rate was 69.2% (18/26), and disease control rate was 92.3% (24/26). Carcinoembryonic antigen (CEA) ≥ 10U/ml (p = 0.003) and carbohydrate antigen 19-9 (CA19-9) ≥ 200U/ml (p = 0.000) were independent risk factors for decreased survival. The most frequent Grade 3 or 4 treatment-related adverse event was liver dysfunction (4, 15.4%). HAIC with oxaliplatin and 5-fluorouracil is an acceptable and well-tolerated treatment for advanced gallbladder cancer even for patients in whom systemic chemotherapy had failed or is contraindicated. Level 2, Observation Study with Dramatic Effect.

Locally advanced gallbladder cancer: a review of the criteria and role of imaging.

Gallbladder carcinoma (GBC) is among one of the gastrointestinal malignancies with extremely dismal prognosis. This is due to the advanced stage at presentation. Majority of the patients with GBC are not considered candidates for surgery because of the locally advanced disease or metastases. However, with the accumulating evidence regarding the role of neoadjuvant chemotherapy, there is a need to correctly identify a subset of patients with locally advanced GBC who will benefit maximally from neoadjuvant chemotherapy and will be successfully downstaged to receive curative (R0) surgery. In this context, there is a lack of consensus and different groups have resorted to criteria for locally advanced disease eligible for neoadjuvant chemotherapy based on personal or institutional experiences. Imaging plays a critical role in the evaluation of patients with GBC as it helps stratify patients into resectable and unresectable. Imaging also has the potential to identify patients with locally advanced GBC and hence facilitate neoadjuvant chemotherapy and improve outcomes. In this review, we evaluate the various criteria for locally advanced GBC and the role of imaging in this scenario.

50P Ultrasound guided screening of gallbladder cancer in healthy volunteers: A prospective study from Northern India

Screening leads to reduction in cancer specific mortality for breast, cervix and colon cancer. Advanced Gallbladder cancer (GBC) is the commonest malignancy in Northern India. Due to rarity in western world, it remains an orphan disease for research. It carries a dismal prognosis. We did a pilot work of screening of GBC in healthy volunteers. This is a prospective study conducted under Armed Forces Medical Research Project at Lucknow from Jun2011 till Oct2012 after ethical approval and among high risk individuals. High risk was defined as asymptomatic, age ≥50 years and residents in Uttar Pradesh or Bihar. Volunteers residing in this region for < 5 years excluded. Screening was done with Ultrasound. Volunteers with irregular or focal wall thickening were considered for radical cholecystectomy. Established cases were taken as control (C-GBC). Written informed consent was obtained for all participants. Demographics were studied and survival was compared with C-GBC patients. A total of 778 volunteers were screened for GBC. Four cases of GBC were detected (S-GBC). There were 3 females and 1 male among S-GBC patients (M: F:3: 1) and 87 males and 32 females (M: F:2.7 :1) in C-GBC cases. S-GBC patients had early stage of diagnosis (p= 0.001) as compared to C-GBC. All four cases underwent curative radical cholecystectomy compared to 18.8 % in C-GBC cases (p= 0.004). Median overall survival (mOS) not reached and 09 months in S-GBC and C-GBC (p= 0.0453), respectively. This pilot work established the proof of principle of screening for GBC, leading to early detection, ensures surgical resection and improved overall survival. This finding must be studied in future larger longitudinal studies.

Examination of Prognostic Factors Affecting Long-Term Survival of Patients with Stage 3/4 Gallbladder Cancer without Distant Metastasis.

In advanced gallbladder cancer (GBC) radical resection, if multiple prognostic factors are present, the outcome may be poor; however, the details remain unclear. To investigate the poor prognostic factors affecting long-term surgical outcome, we examined 157 cases of resected stage 3/4 GBC without distant metastasis between 1985 and 2017. Poor prognostic factors for overall survival and treatment outcomes of a number of predictable preoperative poor prognostic factors were evaluated. The surgical mortality was 4.5%. In multivariate analysis, blood loss, poor histology, liver invasion, and ≥4 regional lymph node metastases (LNMs) were independent prognostic factors for poor surgical outcomes; invasion of the left margin or the entire area of the hepatoduodenal ligament and a Clavien–Dindo classification ≥3 were marginal factors. The analysis identified outcomes of patients with factors that could be predicted preoperatively, such as liver invasion ≥5 mm, invasion of the left margin or the entire area of the hepatoduodenal ligament, and ≥4 regional LNMs. Thus, the five-year overall survival was 54% for zero factors, 34% for one factor, and 4% for two factors (p < 0.05). A poor surgical outcome was likely when two or more factors were predicted preoperatively; therefore, new treatment strategies are required for such patients.

Extended Resections for Advanced Gallbladder Cancer: Results from a Nationwide Cohort Study

BackgroundExtended resections (i.e., major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) because outcomes remain inconclusive. Data regarding extended resections from Western centers are sparse. This Dutch, multicenter cohort study analyzed the outcomes of patients who underwent extended resections for locally advanced GBC.MethodsPatients with GBC who underwent extended resection with curative intent between January 2000 and September 2018 were identified from the Netherlands Cancer Registry. Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments), a pancreatoduodenectomy, or both. Treatment and survival data were obtained. Postoperative morbidity, mortality, survival, and characteristics of short- and long-term survivors were assessed.ResultsThe study included 33 patients. For 16 of the patients, R0 resection margins were achieved. Major postoperative complications (Clavien Dindo ≥ 3A) occurred for 19 patients, and 4 patients experienced postoperative mortality within 90 days. Recurrence occurred for 24 patients. The median overall survival (OS) was 12.8 months (95% confidence interval, 6.5–19.0 months). A 2-year survival period was achieved for 10 patients (30%) and a 5-year survival period for 5 patients (15%). Common bile duct, liver, perineural and perivascular invasion and jaundice were associated with reduced survival. All three recurrence-free patients had R0 resection margins and no liver invasion.ConclusionThe median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although postoperative morbidity and mortality were significant, long-term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival, and a subgroup of patients benefit from surgery.

Nomenclature correction of "incidental gallbladder cancer" and its prevention strategies

Incidental gallbladder cancer(IGBC) originated in the West more than half a century ago.IGBC was translated and introduced into China afterwards with widespread clinical application.With the popularization of laparoscopic cholecystectomy, the trend of "abuse" of IGBC has become increasingly apparent worldwide.Many advanced gallbladder cancers have been categorized as IGBC which actually become the synonym of "missed diagnosis" . From the point of the pathology, the diagnosis of IGBC may cause delays in treatment and adversely affect the patient's prognosis.For country like China with relatively high incidences of chronic cholecystitis, cholelithiasis, and gallbladder cancer, the concept of IGBC, however, is no longer applicable to our diagnosis treat model.For improving the prognosis of gallbladder patients, it is necessary to update and rename the concept of IGBC and more attention should be paid to improve the diagnostic level of early stage tumor.

LBA-2 A two arm randomized prospective superiority phase II multicentric clinical trial to evaluate the efficacy of capecitabine-irinotecan (CAPIRI) versus irinotecan in advanced gall bladder cancer progressing on first line chemotherapy

There is limited data with regard to second line chemotherapeutic options (CT2) in advanced gallbladder cancer (GBC) post progression on gemcitabine-based1st line chemotherapy (CT1). Using a combination or monotherapy as CT2 is an important question in this context.

PD-1 Systematic review and meta-analysis of the efficacy of chemotherapeutic regimens in advanced gallbladder cancer: Assessing current practice and treatment benefit

Biliary tract cancers (BTC) are a heterogeneous group of malignancies, including gallbladder cancer (GBC). Treatment for GBC is based on studies recruiting patients with all BTC primary sites rather than GBC alone. GBC represents a different molecular entity to other BTCs, which may impact the response to treatment. The benefit of chemotherapeutic regimens specifically for the treatment of patients with GBC, including the current standard first- and second-line regimens for BTC, is poorly understood. This study explored the benefit derived from palliative cytotoxic chemotherapeutic regimens in GBC. A systematic review and meta-analysis were designed and registered with the PROSPERO database prior to commencement (CRD42019155745). A systematic search was conducted on MEDLINE; key bibliographies were reviewed and selected annual conferences were used to identify articles. Eligible studies reported data on patients with advanced GBC treated with systemic chemotherapeutic regimens. Phase II and III trials, case series, and cohort studies were eligible; phase I studies and small cohorts (< 10 in the first line, < 5 in second/third line) were excluded. Data were pooled using random effects models. 3,035 studies were identified; 58 studies with 66 study arms (n= 1,986 patients with GBC) were eligible for meta-analysis. In patients with GBC, estimated pooled radiological overall response rates (ORR), mean progression-free survival (PFS) and overall survival (OS) were 23.2% [95% confidence interval (CI), 20.0-26.5], 4.8 months (95% CI, 4.3-5.2) and 8.3 months (95% CI, 7.6-8.9), respectively. In patients with GBC, the use of ≥3 chemotherapy agents in combination was associated with increased ORR [35.8% (95% CI, 25.4-46.8)], mean PFS [5.9 months (95% CI 5.2-6.7)] and OS [9.9 months (95% CI, 8.5-11.3). There was a significant improvement in ORR, disease-free survival (DFS), mean PFS and OS with increasing numbers of chemotherapeutic agents (all spearman rho coefficients=1; P< 0.001). Patients with GBC had a lower ORR than non-GBC BTC [odds ratio (OR) 0.65 (95% CI, 0.50-0.84)]; specifically, patients with GBC have lower ORR when compared with the individual subgroups of BTC: cholangiocarcinoma (not otherwise specified) [OR 0.63 (95% CI, 0.48-0.83)], intrahepatic cholangiocarcinoma [OR 0.51 (95% CI 0.32-0.83)] and extrahepatic cholangiocarcinoma [OR 0.64 (95% CI, 0.40-1.00)]. Patients with GBC respond differently to systemic therapy compared with other BTC primary sites; they achieve lower ORR. In GBC, increasing numbers of chemotherapy agents are associated with better outcomes. Although differences may be due to selection bias, intensification of chemotherapy in fitter patients may be investigated either in a GBC-specific trial or (with a planned statistical and reporting approach) within a large randomised BTC trial.

Anti-Her2neu directed therapy in advanced gall bladder cancer: A prospective, multicenter experience from India.

e16682 Background: Prognosis of Gallbladder cancer (GBC) remains unchanged over the last 20 years. Her2neu amplification is present in 17% of cases of advanced GBC. We present our experience of anti Her2 targeted therapy. Methods: This is a multicenter, prospective, observational study conducted in northern India from Sept2017-Sept2019. All consecutive patients were tested for Her2neu by standard techniques or next-generation sequencing (NGS). Trastuzumab or Lapatinib was used as the anti Her2 therapy along with chemotherapy. Outcome measures were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) and compared to historical controls. Data were censored on 31Dec2019. Results: A total of 181 patients were screened; 38 (20.9%) patients were positive for Her2neu or Her3neu. Demographic details are depicted in the table. Her2 was detected by IHC 18 (47%), FISH 6(15.7%) or NGS 14(36.8%). Five patients were positive for Her3 mutation and/or amplification. Twenty-one patients received anti Her2 therapy upfront with chemotherapy. At a median follow-up of 6.8 months, median PFS was 4.1 months for chemotherapy only (n = 85) and 9.7 months for trastuzumab with chemotherapy (n = 21) (HR 0.22; P &lt; 0.05). The median OS was 14 and 6 months in patients with or without trastuzumab-based therapy (HR 0.08 P = 0.001), respectively. Trastuzumab with chemotherapy was well tolerated. Conclusions: Her2neu directed therapy significantly improve ORR, PFS, and OS in GBC with no added toxicities in the first line. It must be evaluated in a randomized phase 3 clinical trials. [Table: see text]

Patient-derived organoids as a potential tool for clinical decision in advanced gallbladder cancer.

e16717 Background: Human gallbladder cancer research lacks in vitro models that can recapitulate the pathophysiology of the original tumor and normal epithelia. Organoids cultures emulate the tumor heterogeneity and have been successively used as translational models to evaluate clinical response to anticancer drug. Here, we established and characterized patients derived organoids culture (PDOs) from human gallbladder cancer patients. Methods: Fresh tissues obtained from gallbladder cancer patients who underwent cholecystectomy were digested with Collagenase/Dispase, filtered and then suspension cells were mixed with Matrigel (1:1) for organoids establishment. Cultures were maintained at 37°C and 5% CO2. The organoids were characterized through histopathology evaluation, immunohistochemistry, and ultra-deed targeted sequencing (TruSeq protocol, Illumina, TSACP; 25 genes). In addition, we evaluated the response of organoids to gemcitabine, cisplatin and Fluorouracil (5-FU), using the CellTiter-Glo 3D luminescence assay. Results: We have successfully established PDOs cultures from six patients with gallbladder adenocarcinoma with a 60% efficiency (6/10). The PDOs recapitulated the histological features and maintained the expression of CK19, Ki67, P53 as compared with the epithelia of primary tumors. Moreover, the PDOs maintained the mutational status of major driver genes, including TP53 and PIK3CA. Finally, tumor organoids showed differential response to standard chemotherapy treatment. GBC-PDO2 and GBC-PDO4 showed high resistant to gemcitabine (IC50 &gt; 10μM), which suggests that the personalized treatment is necessary for generate better response. Conclusions: the established gallbladder tumor organoids exhibited similar histological and genomic features in relation to their original epithelia. PDOs can be considered a valuable tool for future research aimed to understand gallbladder cancer biology and for developing personalized-medicine approaches for advanced gallbladder cancer patients. (Funding Source: FONDECYT #1171463, FONDECYT #1170893 and Fondef IT16I10051).

Association of neoadjuvant chemotherapy on survival in locally advanced gallbladder cancer.

e16716 Background: Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy. Surgery remains the only potentially curative treatment for GBC. The role of neoadjuvant chemotherapy in patients with locally advanced GBC undergoing surgery is unknown. We studied the association of neoadjuvant chemotherapy on survival in locally advanced GBC patients who underwent resection. Methods: We identified adult patients with locally advanced (stage III-IV) GBC who underwent definitive surgery between 2004 and 2016 using the National Cancer Database. Treatment was categorized as neoadjuvant chemotherapy plus surgery (NAT), surgery plus adjuvant therapy (AT), and surgery alone (SA). Categorical variables were compared using the chi-square test with Bonferroni correction. Kaplan-Meier and Cox regression were used for survival analyses. We used 1:3 nearest neighbor propensity score matching based on NAT for each group. Results: Out of a total of 5,962 patients, 122 (2.2%) received NAT, 2934 (53.6%) AT, and 2421 (44.2%) SA. NAT was associated with private insurance and treatment at an academic/research facility (all p &lt; .001) while SA patients were older, Hispanic, had government insurance, and higher comorbidities (all p &lt; .001). Although all groups had similar lymph node assessment (NAT: 45%, AT: 46%, SA: 37%, p &lt; .001), NAT was associated with lymph node negative disease (NAT 23%, AT 13.2%, SA 13.2%, p &lt; .001). Median overall survival was higher in NAT compared to AT or SA (21 vs. 14 vs. 6 months, p &lt; .001) which persisted after propensity score matching (21 vs. 15 vs. 9 months, p &lt; .001) and multivariable regression analysis (Table). In node positive GBC, NAT was associated with improved median overall survival (NAT 24, AT 18, SA 8 months, p &lt; .001). Conclusions: NAT is infrequently used in patients with locally advanced GBC. NAT is associated with improved median overall survival compared to AT and SA, and appears to be most beneficial in node positive disease. Prospective studies are needed to evaluate the role of neoadjuvant chemotherapy in locally advanced GB. [Table: see text]

PD-L1 for gallbladder cancer: case report

The clinical outcome of the advanced biliary tract cancer (BTC) is unfavorable, and the mortality rate is high. With local advance and metastasis, the median survival time is less than 1 year. But this patient survived 14 months with no signs of progress under treatment in our hospital. And the patient situation is stable recently. This case report can provide a treatment template for clinicians. This patient was appeared dull pain in the upper abdomen, occasionally poor defaecating. After a series of medical tests, the patient was diagnosed with advanced gallbladder cancer (GBC). This patient received chemotherapy (oxaliplatin 220 mg d1 + capecitabine 1,500 mg bid d1–14; capecitabine 1,500 mg bid d1–14; gemcitabine 1.4 g d1, 8 + capecitabine 1,500 mg bid d1–14) combined with immunotherapy (pembrolizumab 200 mg). The patient is still alive.. And there were no signs of progress. The researches on the treatment of GBC are rare, and only standard first-line treatment, lack of second-line treatment of GBC. This patient of advanced GBC received standard first-line treatment (oxaliplatin 220 mg d1 + capecitabine 1,500 mg bid d1–14; capecitabine 1,500 mg bid d1–14; gemcitabine 1.4 g d1, 8 + capecitabine 1,500 mg bid d1–14) combined with immunotherapy (pembrolizumab 200 mg), the effect is fine and is expected to contribute to the treatment of BTC.

Surgical Indication for Advanced Gallbladder Cancer Considering the Optimal Preoperative Carbohydrate Antigen 19-9 Cutoff Value

Background: Selecting patients who will benefit from resection among those with advanced gallbladder cancer (GBCa) having poor prognostic factors is difficult. Methods: One hundred twenty-one patients who underwent resection for stage II–IV GBCa and 19 unresected patients (unresectable group) were enrolled. The clinical impact of carbohydrate antigen 19-9 (CA19-9) and advanced surgical procedures for GBCa was evaluated. Results: The optimal CA19-9 cutoff value (based on the greatest difference in overall survival) was 250 U/mL. CA19-9 ≥250 U/mL was found to be an independent prognostic factor. Patients with CA19-9 <250 U/mL who developed jaundice (median survival time [MST], 49.1 months) or who required major hepatectomy (MST, 21.5 months) or pancreatoduodenectomy (PD; MST, 50.3 months) had a better prognosis than those with CA19-9 ≥250 U/mL who developed jaundice (MST, 16.1 months; p = 0.061) or who required major hepatectomy (MST, 9.2 months; p = 0.066) or PD (MST, 8.6 months; p = 0.025); their prognosis was comparable to that of the unresectable group (jaundice: p = 0.145, major hepatectomy: p = 0.292, PD: p = 0.756). Conclusions: Even if GBCa patients develop jaundice or require major hepatectomy, or combined PD, resection can be considered for those with CA19-9 <250 U/mL. However, surgical indication should be carefully determined in patients with CA19-9 ≥250 U/mL.