Effectivity of Palliative Care Bundle on Advanced Gallbladder Cancer: A Randomised Controlled Trial.

Objectives: The main aim of this study was to develop, test, and compare palliative care bundles to improve functional recovery, resilience, and quality of life among advanced gallbladder cancer patient with their routine palliative care. Material and Methods: This study was to test a palliative care bundle, a single-center, and two-arm randomised controlled trial done on a total of 116 participants (58 in each arm) from July 2019 to December 2021 at All India Institute of Medical Sciences, Rishikesh. Results: By the end of 4th month, the recruitment rate was 96.7%, retention rate acceptance rate was 95%, and adherence rate was 85%. The palliative care bundle showed that a significant difference in trial outcome index score (P = 0.014*) indicates the effectiveness of the palliative care bundle related to improvement in physical mobility, resilience, and quality of life of patients and reduced caregiver burden. Reported barriers faced by participants were physical exhaustion (65%), psychological factors (25%), social factors (15%) and unfamiliar surroundings (5%). Caregivers reported barriers that their job (40%), physical fatigue related to the care of their patient (40%), their education (10%), and lack of support for their other family members (10%) were some reasons forcing them not to practice palliative care bundle. Conclusion: The palliative care bundle did not interfere with the palliative treatment plan of any patients and significantly improved physical mobility, resilience, quality of life of patients, and reduced caregiver burden. Hence, a palliative care bundle can be considered in the palliative care of advanced cancer patients during their palliative treatment to provide holistic care.

Competing-risk nomogram for predicting survival in patients with advanced (stage III/IV) gallbladder cancer: A SEER population-based study.

OBJECTIVE: The primary aim of this study was to assess the cumulative incidence of cause-specific mortality (CSM) and other cause-specific mortality (OCSM) for patients with advanced gallbladder cancer (GBC), and then to develop a nomogram based on competing-risk analysis to forecast CSM. METHODS: We identified the patients with GBC with specific screening criteria and from the Surveillance Epidemiology and End Results (SEER) database. We calculated the cumulative incidence function for CSM and OCSM, and constructed a competing-risk nomogram based on the Fine and Gray's proportional subdistribution hazard regression model to forecast the probability of CSM of these patients. In addition, the concordance index and calibration plot were performed to validate the novel established model. RESULTS: A total of 1411 patients were included in this study. The 1-, 2-, and 3-year overall cumulative mortalities were 46.2, 62.2, and 69.6% for CSM, respectively, while they were 6.2, 8.7, and 10.4% for OCSM. Additionally, the 1-, 2-, and 3-year estimates of overall survival were 47.6, 29.1, and 19.9% for above these patients, respectively. We also developed a competing-risk nomogram to estimate the CSM. The concordance index was 0.775 (95% confidence interval (CI): 0.750-0.800) in the training set and that was 0.765 (95% CI: 0.730-0.800) in the internal validation set, which suggests the robustness of the novel established model. Furthermore, the calibration curves and concordance index demonstrated that the nomogram was well-calibrated and demonstrated good discriminative ability. CONCLUSIONS: The ample sample allowed us to develop a reliable model which demonstrated better calibration and discrimination for predicting the probability of CSM of patients with advanced GBC.

Symptom Palliation in Advanced GallBladder Cancer: An Institutional Experience.

AIM: Palliation of symptoms of patients with advanced carcinoma gallbladder (GB). MATERIALS AND METHODS: Sixty-two newly diagnosed patients of unresectable advanced and metastatic GB cancers were enrolled, and following clinicoradiological assessment patients were considered for palliative symptom management. RESULTS: The most common presenting symptom was pain in 57 (92%) patients. Obstructive jaundice was observed in 29 (46.7%) patients. Patients were considered for percutaneous biliary drainage/internal stenting, therapeutic ascitic tapping, and pain control. Patients with good performance status were considered for palliative chemotherapy. CONCLUSION: Patients with advanced carcinoma GB were managed with various palliative procedures with the aim to improve the quality of life of patients because of jaundice, loss of appetite, nausea, pain, etc. Symptoms are distressing for patients.

Comprehensive treatment of gallbladder cancer: a case report.

Introduction and importance: Gallbladder cancer is an extremely aggressive digestive system tumor. It is difficult to treat as early symptoms are insidious, and patients are usually diagnosed in advanced stages. The authors' case highlights the need for effective treatment strategies and underscores the critical role of an individualized approach in the management of complicated gallbladder cancer. Case presentation: The authors report a patient admitted to the hospital with back pain and discomfort who was diagnosed with advanced gallbladder cancer. The patient received two cycles of chemotherapy with gemcitabine and cisplatin (GC), but the response was unsatisfactory. The authors changed the treatment regimen to gemcitabine and oxaliplatin (GEMOX) combined with targeted therapy (lenvatinib) and immunotherapy (toripalimab), and achieved significant therapeutic effect. Subsequently, the patient underwent "extended right hemihepatectomy, cholecystectomy, lymph node dissection of the hepatoduodenal ligament " and continued to receive combined therapy after surgery, and no tumor recurrence has been observed so far. Clinical discussion: The authors delve into the challenges faced during treatment, exploring the subtle impact of modified regimens and the strategic integration of surgery and combination therapy. The focus of this study is on the intricate synergy between GEMOX, lenvatinib and teraplizumab, providing a holistic view of treatment effects and new insights into the clinical decision-making process. Conclusions: This case emphasizes the success of precision medicine in the treatment of advanced gallbladder cancer. The adjustment of strategy can not only improve the therapeutic effect but also promote the success of surgical intervention. This case provides a valuable lesson in the holistic management of gallbladder cancer patients and prompts further reflection on the nuances of individualized therapeutic approaches in cancer treatment.

Advanced gallbladder cancer with high tumor mutation burden: a case report and literature review.

Background: Gallbladder cancer (GBC) is a common malignant tumor of the biliary system. It is characterised by insidious onset, rapid progression and poor prognosis. Symptoms often indicate advanced or late-stage disease, with a 5-year survival rate of only 5-15%. Case Description: We present a case study of a patient with GBC who had a tumor mutation burden (TMB) of 32.5/MB (≥10 muts/MB). The patient received mFOLFIRINOX as first-line chemotherapy, which demonstrated significant efficacy. After stabilizing the disease, a sequential chemotherapy regimen was chosen. This regimen combined the immune checkpoint inhibitor (ICI) toripalimab (JS001), a humanised IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1), with S-1 therapy, an oral fluoropyrimidine derivative. However, this treatment did not provide any significant clinical benefit for the patient. Therefore, we hypothesise that combining immunotherapy with chemotherapy may be more effective as a first line treatment for high-TMB advanced GBC. This hypothesis needs to be validated in large-scale clinical studies. Conclusions: In summary, mFOLFIRINOX is a safe and effective first-line chemotherapy regimen for advanced GBC. The timing of combining immunotherapy with chemotherapy requires careful consideration. Further clinical trials involving immunotherapy in advanced GBC are necessary to identify biomarkers that can guide clinical decisions.

Anti-PD-1-based immunotherapy plus lenvatinib to treat advanced gallbladder cancer in the elderly: a case series and review of current literature.

BACKGROUND: Gallbladder cancer (GBC) is a rare malignant tumour of the bile duct. Due to the lack of typical clinical manifestations in the early stage, it is basically at an advanced stage when discovered. Radical resection remains the only curative therapy for patients with GBC. The resection rate is relatively low due to tumour invasion and metastasis, and the overall prognosis is poor. For most patients with unresectable lesions, chemotherapy has been the only recommended treatment for decades. Immunotherapy combined with TKIs (tyrosine kinase inhibitors) was proven to be effective in patients with hepatocellular carcinoma and cholangiocarcinoma. Some physicians have attempted to apply immunotherapy and TKIs combined with traditional chemotherapy in patients with advanced GBC. However, the outcomes were not clear because limited cases were reported. CASE PRESENTATION: We present a case series of four elderly patients with advanced GBC who received tislelizumab and lenvatinib combined with chemotherapy. All four patients responded to this treatment approach. Tumour responses were better in Patient 1 (TMB-H, MSS), Patient 2 (low TMB, MSS), and Patient 3 (low TMB, MSI-H) than in Patient 4 (low TMB, MSS), in whom metastasis occurred during the later stage of treatment. CONCLUSION: The combination of tislelizumab and lenvatinib may be a promising treatment for patients with advanced GBC. The efficacy and safety need further confirmation.

Development and Validation of Palliative Care Bundle for Advanced Gallbladder Cancer "PALLICR".

Kusum K. RohillaBackground The aim of this study was to develop and validate a comprehensive palliative care bundle "PALLICR" for advanced gallbladder cancer (GBC) patients. Materials and Methods The present study was an exploratory study with instrument validation design which was conducted at All India Institute of Medical Sciences, Rishikesh, India. A total of 25 advance cancer patients were selected using the purposive sampling technique. Results The newly developed PALLICR bundle consists of six items under three subfactors, that is, functional recovery, resilience, and quality of life. The final version of bundle with six items of PALLICR bundle was validated and showed a good fit to provide palliative care to advanced GBC patients. Standardized scales, that is, palliative care outcome scale, European Organization for Research and Treatment of Cancer quality-of-life scale for patients and caregiver strain index for caregivers were used for evaluation of PALLICR bundle effectiveness. Conclusion PALLICR bundle is valid and reliable methods to provide palliative care to advanced GBC patients.

Consolidation chemoradiation (cCTRT) improves survival in responders to first-line chemotherapy (CT) in locally advanced gallbladder cancer (LA-GBC): A new standard of care?

Introduction: Chemotherapy (CT) is the standard of care in advanced gallbladder cancer (GBC). Should locally advanced GBC (LA-GBC) with response to CT and good performance status (PS) be offered as consolidation chemoradiation (cCTRT) to delay progression and improve survival? There is a scarcity of literature on this approach in the English literature. We present our experience with this approach in LA-GBC. Materials and Methods: After obtaining ethics approval, we reviewed the records of consecutive GBC patients from 2014 to 2016. Out of 550 patients, 145 were LA-GBC who were initiated on chemotherapy. A contrast-enhanced computed tomography (CECT) abdomen was done to evaluate the response to treatment, according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. All responders to CT (PR and SD) with good PS but unresectable were treated with cCTRT. Radiotherapy was given to GB bed, periportal, common hepatic, coeliac, superior mesenteric, and para-aortic lymph nodes up to a dose of 45 to 54 Gy in 25 to 28 fractions along with concurrent capecitabine at the rate of 1,250 mg/m2. Treatment toxicity, overall survival (OS), and factors affecting OS were computed based on Kaplan-Meier and Cox regression analysis. Results: ">The median age of patients was 50 years (interquartile range [IQR] = 43-56 years), and men to women ratio was 1:3. A total of 65% and 35% patients received CT and CT followed by cCTRT, respectively. The incidence of Grade 3 gastritis and diarrhea was 10% and 5%, respectively. Responses were partial response (PR; 65%), stable disease (SD; 12%), progressive disease (PD; 10%), and nonevaluable (NE; 13%) because they did not complete six cycles of CT or were lost to follow-up. Among PR, 10 patients underwent radical surgery (six after CT and four after cCTRT). At a median follow-up of 8 months, the median OS was 7 months with CT and 14 months with cCTRT (P = 0.04). The median OS was 57 months, 12 months, 7 months, and 5 months for complete response (CR) (resected), PR/SD, PD, and NE (P = 0.008), respectively. OS was 10 months and 5 months for Karnofsky performance status (KPS) >80 and <80 (P = 0.008), respectively. PS (hazard ratio [HR] = 0.5), stage (HR = 0.41), and response to treatment (HR = 0.05) were retained as independent prognostic factors. Conclusions: CT followed by cCTRT appears to improve survival in responders with good PS.

PD-1 inhibitors plus nab-paclitaxel-containing chemotherapy for advanced gallbladder cancer in a second-line setting: A retrospective analysis of a case series.

Background: Gallbladder cancer (GBC) is a fatal cancer, and the efficacy of the current standard second-line chemotherapy for GBC is limited. Novel therapies need to be explored. This retrospective analysis was aimed to investigate the outcomes of patients treated at West China Hospital with PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy (nab-paclitaxel monotherapy or nab-paclitaxel plus other cytotoxic agents) in a second-line setting. Methods: Between April 2020 and May 2022, the patients with advanced GBC receiving PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy after resistance to first-line gemcitabine-based chemotherapy at West China Hospital were retrospectively screened. Results: Eleven patients were included, and all received gemcitabine-based chemotherapy as first-line therapy. Eight patients underwent next-generation sequencing (NGS), and all had microsatellite stability (MSS) and a low tumor mutation burden (TMB). Six patients were negative for PD-L1 expression and one patient was positive for PD-L1. Therapeutically relevant genetic alterations were not found. All patients received PD-1 inhibitors in combination with nab-paclitaxel-based chemotherapy as second-line therapy. Pembrolizumab was administered in 3 patients, and sintilimab was administered in eight patients. One patient had no measurable target lesion. Complete response (CR) was observed in one (10.0%) patient, partial response (PR) in four (40%) patients, and stable disease (SD) in four (40%) patients. The median progression-free survival (PFS) was 7.5 (95% CI: 2.5-12.5) months, and the median overall survival (OS) was 12.7 (95% CI: 5.5-19.9) months. The adverse events (AEs) were manageable. Conclusion: Our results suggest that PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy as second-line therapy for advanced GBC might be a potential treatment and deserves further evaluation.

Gallbladder Cancer With Jaundice: Surgery Versus No Surgery.

Background Patients with gallbladder carcinoma (GBC) and jaundice have a poor prognosis. The surgical management of these patients is controversial. There is a dearth of studies comparing curative surgical resection (CR) versus non-curative resection/palliation (NCR) in patients with GBC and jaundice. Hence, this study aimed to compare the outcomes between CR and NCR in these patients. Methodology This was a retrospective study on patients with GBC and jaundice managed by a single surgical unit at a tertiary care center in northern India from May 2009 to March 2021. These patients were grouped into CR or NCR. The clinical demographical profile and overall survival (OS) were compared between the groups. Results A total of 82 patients with GBC and jaundice were managed during the study period. The final study cohort included 59 patients (CR, n = 34; NCR, n = 25) after excluding patients with metastatic disease (n = 23). Common bile duct infiltration was seen in 61.7% and 84% of CR and NCR patients, respectively (p = 0.062). The overall tumor-node-metastasis staging between the two groups was similar (p = 0.296). The median OS of CR was significantly better in CR than NCR (20 months vs. six months; p = 0.001). The median OS was better in CR than NCR patients who received systemic chemotherapy (22 vs. 12 months; p = 0.001) or did not receive chemotherapy (14 months vs. three months; p = 0.001). Conclusions Patients with GBC and jaundice have better significant survival after CR than NCR alone.

Successful multimodality treatment of metastatic gallbladder cancer: A case report and review of literature.

BACKGROUND: Gallbladder cancer is the most common malignant tumor in the biliary system, and it is characterized by high aggressiveness and an extremely poor prognosis. Current treatment for advanced gallbladder cancer remains unsatisfactory. Here, we report a patient with advanced gallbladder cancer who was cured by multidisciplinary treatment. CASE SUMMARY: A 73-year-old male presented to our hospital with right abdominal pain for 3 d and was diagnosed with stage IVB gallbladder cancer with multiple liver metastases, peritoneum metastasis, diaphragm metastasis and lymph node metastases. The patient initially received chemotherapy, targeted therapy, 125I seed implantation and immunotherapy, as there were no specific indications for radical surgery. During these palliative therapies, the level of tumor markers gradually decreased but remained higher than the normal level, lymph node metastases gradually disappeared, and liver metastasis was gradually limited to the left liver. Finally, the patient received radical surgery with left hepatectomy, radical lymphadenectomy and partial diaphragmatic resection. To date, the patient has survived for more than six years posttreatment, the levels of tumor markers are normal, and imaging examinations show no signs of tumor recurrence. CONCLUSION: Currently, the prognosis of advanced gallbladder cancer remains unsatisfactory. A single treatment method is not sufficient for patients with advanced gallbladder cancer. Multidisciplinary individualized treatment is essential and should be utilized for advanced gallbladder cancer patients to further improve prognosis.

Preoperative skeletal muscle fat infiltration is a strong predictor of poorer survival in gallbladder cancer underwent surgery.

BACKGROUND & AIMS: Recently, a decrease in skeletal muscle, termed sarcopenia, has been reported to be associated with poorer survival of patients in several types of cancer. However, few studies have investigated the association between sarcopenia and the survival of patients with gallbladder cancer. METHODS: A total of 88 patients undergoing curative resection for advanced gallbladder cancer were included in this study. The quality of skeletal muscle was assessed by the intramuscular adipose tissue content (IMAC), and the quantity of skeletal muscle was assessed by the psoas muscle index (PMI), measured on preoperative computed tomography. The optimum cutoff values for IMAC and PMI for predicting the overall survival in each sex were determined using a minimum p value approach. Clinicopathological factors, IMAC and PMI were retrospectively analyzed to identify the predictors of overall survival (OS). RESULTS: The cutoff values for IMAC were -0.3 in males and 0.04 in females. The numbers of patients with low IMAC and high IMAC were 42 and 46, respectively. The cutoff values for PMI were 7.3 cm2/m2 in males and 5.0 cm2/m2 in females. The numbers of patients with low PMI and high PMI were 22 and 66, respectively. A multivariate analysis revealed that pT stage (pT3/4, hazard ratio [HR] = 6.72, p = 0.004), high IMAC (HR = 4.12, p < 0.001), Bile duct infiltration (present, HR = 2.82, p = 0.046), high age (≥72 years old, HR = 2.64, p = 0.010), major hepatectomy (performed, HR = 2.50, p = 0.031) and pN1/2 (HR = 2.17, p = 0.010) as independent prognostic factors. CONCLUSION: IMAC was independent prognostic factor for resected advanced gallbladder cancer, so the quality of skeletal muscle more strongly predicted survival than the quantity of skeletal muscle.

Insights From the Analysis of Clinicopathological and Prognostic Factors in Patients With Gallbladder Cancer.

Aims: To investigate the clinical efficacy and prognostic factors of primary gallbladder cancer (GBC) treated by radical surgery. Methods: The clinical and pathological data of 168 patients with primary gallbladder cancer admitted and treated in the Third Affiliated Hospital of Soochow University from January 1st, 2010 to December 31st, 2018 were analyzed retrospectively. Kaplan Meier method was used to draw the survival curve and evaluate the survival rate. Chi-square test was used for univariate analysis and binary logistic regression was used for multivariate analysis. Results: 94 cases showed symptoms of abdominal pain and abdominal distension. 7 cases showed symptoms of fatigue and weight loss. Jaundice occurred in 10 patients. Fever occurred in 6 patients. 51 patients had no symptoms at all. The median survival time of 168 patients was 35.0 (1.0 ~ 142.0) months. The overall 1-, 2- and 3-year cumulative survival rates were 69.6%, 55.4% and 48.8% respectively. The univariate analysis indicated that preoperative bilirubin, tumor size, tumor location, pathological type, degree of differentiation, liver invasion, nerve invasion, vascular invasion, surgical margin, filtration depth and N staging were significant factors influencing prognosis of patients with primary GBC (P<0.05). The results of multivariate analysis demonstrated that degree of differentiation, nerve invasion, filtration depth and N staging were independent risk factors for prognosis of patients with primary GBC (P<0.05). Conclusion: Patients with risk factors of gallbladder cancer should be more active in early cholecystectomy to avoid the malignant transformation of benign diseases. Degree of differentiation, nerve invasion, filtration depth and N staging were important factors for poor prognosis of patients with primary GBC. For T4 staging patients, preoperative evaluation should be more comprehensive, and patients and surgeons should be more prudent in adopting appropriate clinical treatment. The primary purpose should be prolonging the survival time and improving the quality of life.

Neoadjuvant Chemotherapy for Advanced Gallbladder Cancer: Do We have Enough Evidence? A Systematic Review.

BACKGROUND: Recently for advanced gallbladder carcinoma, neoadjuvant chemotherapy has emerged as an important strategy in place of adjuvant chemotherapy with the hope that it will help to improve the resectability and survival. AIM AND OBJECTIVE: The goal was to conduct a systematic review of published publications on the benefits of neoadjuvant chemotherapy for advanced gallbladder cancer treatment. MATERIALS AND METHODS: This systematic review followed the Meta-analysis Of Observational Studies in Epidemiology standards. The clinical benefit rate of neoadjuvant chemotherapy, curative resectability rate, and R0 resection were the major outcomes of interest. The secondary outcomes of interest were overall and disease-free survival. RESULTS: Six published papers were included (n = 420). One-hundred and twenty-eight cases (30.47%) despite receiving neoadjuvant chemotherapy had disease progression. Although 67.38% of patients (283 of 420) in this systematic review showed good response to the neoadjuvant chemotherapy, just 51.66% (217 of 420 cases) were operated, out of which only 171 cases were deemed to be feasible for surgical resection and had curative resection. Out of the cases that underwent curative surgery, 91.81% had R0 resection (157 out of 171 patients). The overall survival rate was found to be 18.5-50.1 months for patients in whom curative surgery was done and 5.0-10.8 months for nonsurgery patients. CONCLUSION: No sufficient data exist to advocate the regular use of neoadjuvant chemotherapy in advanced gallbladder carcinoma, as data showed that only 1/3 of patients benefited and had a R0 resection. Further research should be the randomized controlled trials to further quantify the benefit of neoadjuvant chemotherapy in advanced gallbladder carcinoma. HOW TO CITE THIS ARTICLE: Naveed S, Qari H, Thau CM, et al. Neoadjuvant Chemotherapy for Advanced Gallbladder Cancer: Do We have Enough Evidence? A Systematic Review. Euroasian J Hepato-Gastroenterol 2021;11(2):87-94.

Molecular Targets and Emerging Therapies for Advanced Gallbladder Cancer.

Biliary tract cancers (BTCs), for their low incidence, have been often considered together. Gallbladder cancer (GBC) is the most common biliary tract malignancy, characterized by late diagnosis and poor prognosis, and although it is considered a rare tumor in western countries, other areas of the world show considerable incidence rates. In 2010, results from the large phase III ABC-02 clinical trial on GBC identified the gemcitabine and cisplatin combination as the most effective first-line regimen for both GBC and other BTCs. Since then, various systemic therapies have proven active in BTCs in both first- and second-line settings. Molecular profiling has highlighted important genetic differences between GBC and other BTCs, opening new ways for targeted therapy in advanced disease where standard chemotherapies show marginal benefit. Genome-wide data analysis have shown that GBC molecular landscape offer possible strategies for precision medicine approaches, and a better molecular understanding of the GBC is needed to better stratify patients for treatment. In this review, we discuss the molecular targetable agents for GBC, including the results that emerged by clinical trials exploring new treatment strategies.

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

PURPOSE: 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). MATERIALS AND METHODS: 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 40 mg/m2 for 2 h, followed by 5-fluorouracil at 800 mg/m2 for 22 h on days 1-3 every 3-4 weeks. 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. RESULTS: 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 13.5 months, and the median PFS was 10.0 months. The overall response rate was 69.2% (18/26), and disease control rate was 92.3% (24/26). Carcinoembryonic antigen (CEA) ≥ 10 U/ml (p = 0.003) and carbohydrate antigen 19-9 (CA19-9) ≥ 200 U/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%). CONCLUSION: 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 OF EVIDENCE: Level 2, Observation Study with Dramatic Effect.

Combination of portal vein embolization and neoadjuvant chemotherapy for locally advanced gallbladder cancer requiring extended hepatectomy - A novel approach.

BACKGROUND: Locally advanced gallbladder cancer (GBC) may require extended hepatectomy. Portal vein embolization (PVE) can lead to hypertrophy of future liver remnant (FLR), and neoadjuvant chemotherapy (NACT) can be used in this cohort, with additional advantage of downstaging tumors as well as preventing progression while waiting for liver regeneration. Here, we share our experience of combining NACT along with PVE in locally advanced GBC requiring major hepatectomy. METHODS: Retrospective analysis of prospectively maintained database was conducted for patients with locally advanced GBC who underwent PVE and received NACT between 2012 and 2018. RESULTS: Fourteen patients with locally advanced GBC underwent PVE and NACT. Median baseline FLR volume was 25.09% with a median degree of hypertrophy of 8.8% after PVE. Out of 14 patients, 7 (50%) underwent curative resection. Median overall survival in resectable and unresectable patients was 27 months and 15 months respectively. CONCLUSION: PVE along with NACT made curative surgery feasible in half of the patients who were deemed unresectable initially.

Treatment of advanced gallbladder cancer: A SEER-based study.

PURPOSE: The treatment of advanced gallbladder cancer (GBC) remains controversial. Therefore, the purpose of this study was to explore treatment choices for advanced GBC. METHODS: We identified four different treatments from the surveillance, epidemiology, and end results (SEER) database: surgery, chemotherapy (CT), surgery and chemotherapy (Surgery + CT), and no surgery/no chemotherapy (No surgery/No CT). Kaplan-Meier method and Cox proportional hazards regression method were used to determine the risk factors for overall survival (OS) and cancer-specific survival (CSS). In addition, patients in AJCC stages III and IV stage were matched with 1:1 propensity score matching (PSM) for diagnosis age, race, marital status, histological type, tumor grade, and treatment pattern to decrease the possibility of selection bias. RESULTS: A total of 288 AJCC stage III patients and 4239 AJCC stage IV patients with advanced GBC were identified from the SEER database between 2004 and 2015. Treatment pattern was an independent risk factor for patients with advanced GBC. For all patient, AJCC stage III patients and AJCC stage IV patients, "Surgery + CT" treatment minimized the OS and CSS in advanced GBC patients. In addition, after the PSM analysis, the "Surgery + CT" treatment still significantly decreased patient OS and CSS. CONCLUSIONS: "Surgery + CT" treatment can provide survival benefits for patients with advanced GBC. In addition, "Surgery + CT" treatment was not fully utilized and may further improve the survival rate of GBC patients.

Role of positron emission tomography-contrast enhanced computed tomography in locally advanced gallbladder cancer.

INTRODUCTION: This study aims to define the role of flurodeoxyglucose (18F -FDG) positron emission tomography-contrast enhanced computed tomography (PETCECT) scan in upstaging disease in patients with locally advanced gallbladder cancer (LAGBC). METHODS: An analysis of a prospectively maintained database of gallbladder cancer (GBC) patients was performed. Patients found to have locally advanced (T3 and/or T4 or N+) but non-metastatic disease on initial imaging, either a contrast enhanced computed tomography (CECT) or a magnetic resonance imaging (MRI) scan, underwent an additional PETCECT for staging and the results impacting treatment decision were recorded. RESULTS: One hundred and three patients of LAGBC underwent CECT/MRI and PETCECT. 48/103 (46.6%) were found to be upstaged to stage IV after PETCECT. The most common metastatic site was non-regional retroperitoneal lymph nodes (12 patients, 11.7%) followed by satellite lesions in liver (11, 10.7%). Fourteen (13.6%) patients had equivocal findings on PET scan that required confirmation by tissue sampling out of which 10 (71.4%) were subsequently found to have metastatic disease. The only statistically significant factor predicting distant spread on PETCECT was the presence of loco-regional nodes on CT scan (odds ratio 6.15, P = .006). CONCLUSION: PETCECT is a valuable tool to rule out metastatic disease in patients presenting with LAGBC.

Complete response to immunotherapy combined with an antiangiogenic agent in multiple hepatic metastases after radical surgery for advanced gallbladder cancer: a case report.

Most advanced gallbladder cancers (GBCa) are unresectable or metastatic once diagnosed, and even patients who undergo surgery have a high risk of recurrence and metastasis. Immunotherapy, especially immune checkpoint inhibitors (ICIs), combined with an antiangiogenic agent, is an emerging prospective treatment for GBCa. However, the efficacy and safety of this combination therapy have not yet been investigated. We report the case of a 70-year-old female patient with recurrent metastatic GBCa (stage IVB) after radical surgery. Immunohistochemical examination revealed that 10% of the tumor cells expressed programmed cell death protein-1 (PD-1) and programmed cell death receptor ligand 1 (PD-L1). Whole-exome sequencing showed cancer tissues with a low tumor mutational burden (TMB) and microsatellite stability (MSS). The patient received Camrelizumab (200 mg, every three weeks) and Apatinib (40 mg/d). The clinical and immunological responses were observed, and the patient achieved a complete response after five cycles. This is the first case describing the efficacy and safety of Camrelizumab plus Apatinib in a GBCa patient with weak PD-1 and PD-L1 expression, and low TMB and MSS. The treatment had a tolerable safety profile and a complete response in the patient. Also, we found that the cluster of differentiation (CD)16+CD56+natural killer (NK) cell ratio in peripheral blood was increased after the combined treatment. Immunotherapy with antiangiogenic drugs may be a potential treatment option for patients with recurrent GBC or GBCa.