Bile Spillage as a Prognostic Factor for Gall Bladder Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Biliary spillage (BS) is a common complication following initial cholecystectomy for gall bladder cancer (GBC). Few studies have explored the importance of BS as a long-term prognostic factor. We perform a meta-analysis of the association between BS and survival in GBC. METHODS: A systematic literature search was performed in February 2023. Studies evaluating the incidence of BS and its association with long-term outcomes in patients undergoing initial laparoscopic or open cholecystectomy for either incidental or resectable GBC were included. Overall survival (OS), disease-free survival (DFS), and rate of peritoneal carcinomatosis (RPC) were the primary end points. Forest plot analyses were used to calculate the pooled hazard ratios (HRs) of OS, DFS, and RPC. Metaregression was used to evaluate study-level association between BS and perioperative risk factors. RESULTS: Of 181 published articles, 11 met inclusion criteria with a sample size of 1116 patients. The rate of BS ranged between 9% and 67%. On pooled analysis, BS was associated with worse OS (HR = 1.68, 95% confidence interval [CI] = 1.32-2.14), DFS (pooled HR= 2.19, 95% CI = 1.30-3.68), and higher RPC (odds ratio = 9.37, 95% CI = 3.49-25.2). The rate of BS was not associated with higher T stage, lymph node metastasis, higher grade, positive margin status, reresection, or conversion rates. CONCLUSIONS: Our meta-analysis shows that BS is a predictor of higher peritoneal recurrence and poor survival in GBC. BS was not associated with tumor characteristics or conversion rates. Further research is needed to identify other potential risk factors for BS and investigate the ideal treatment schedule to improve survival.

Robotic fluorescence-guided anatomical segment IVb and V liver resection with radical lymphadenectomy for gall bladder cancer.

Radical surgery remains the primary treatment option for gall bladder cancer (GBC). Margin-negative liver resection is a critical component of radical cholecystectomy. Anatomical segment IVb and V resection is preferred in primary GBC with liver infiltration and incidental GBC patients with puckering of gall bladder (GB) bed. Despite the initial scepticism, minimally invasive radical cholecystectomy is recommended as a treatment option in selected GBC patients. However, anatomical Segment IVb and V resection using the minimally invasive approach is scarcely reported. The standardised technique of robotic (daVinci®XiTM) anatomical Segment IVb and V liver resection guided by indocyanine green fluorescence is described here. The systematic fluorescence-guided anatomical resection described in this report could facilitate minimally invasive Segment IVb and V resection with radical lymphadenectomy in selected patients with GBC.

Expression of Human epidermal growth factor receptor 2, Survivin, Enhancer of zeste homolog -2, Cyclooxygenase-2, p53 and p16 molecular markers in Gall bladder carcinoma.

INTRODUCTION: Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging. MATERIALS AND METHODS: This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry. RESULTS: Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 - 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ2 = 9.886, P = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ2 = 7.017, P = 0.037 and χ2 = 5.861, P = 0.033) respectively. CONCLUSIONS: The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.

Structural based screening of potential inhibitors of SMAD4: a step towards personalized medicine for gall bladder and other associated cancers.

Gall bladder cancer (GBC) is an aggressive and most common malignancy of biliary tract lacking effective treatment due to unavailability of suitable biomarkers and therapeutics. SMAD4 is an essential mediator of transforming growth factor-ß pathway involved in various cellular processes like growth, differentiation and apoptosis and also recognized as therapeutic target for GBC and other gastrointestinal tract cancers. In the present study, 3D structure of SMAD4 mutants was optimized through molecular dynamics simulation (MDS) along with wildtype. Furthermore, binding site of protein was predicted through hybrid approach and structural based virtual screening against two drug libraries was performed followed by docking. MDS of top docking score protein-ligand complexes were carried, and binding free energy was rescored. Two potential inhibitors, namely ZINC2098840 and ZINC8789167, were screened that displayed higher binding affinity towards mutant proteins compared with wildtype and both hydrophilic as well as hydrophobic interactions play a crucial role during protein-ligand binding. Current study identified novel and potent inhibitors of SMAD4 mutant that could be used as a drug candidate for the development of personalized medicine for gall bladder and other associated cancers.

The giant resectable carcinoma of gall bladder-a case report.

BACKGROUND: Gall bladder cancer (GBC) is the fifth most common malignancy in the gastrointestinal system and the most common malignancy of the biliary system. GBC is a very aggressive malignancy having a 5 year survival rate of 19%. Giant Gall Bladder (GGB) is an uncommon condition that can result from cholelithiasis or chronic cholecystitis and rarely with malignancy. CASE REPORT: A 65 year old lady presented with vague abdominal pain for 12 years and right abdominal lump of size 20 × 8 cms was found on examination. CT scan showed a circumferentially irregularly thickened wall (2.5 cm) of gall bladder indicative of malignancy. Per-operatively a GB of size 24 × 9 cm was noted and patient underwent radical cholecystectomy. It was surprise to find such a giant malignant GB with preserved planes. Histopathology, it was well differentiated adenocarcinoma of gall bladder of Stage II (T2a N0 M0). DISCUSSION: It is known that mucocoele of GB can attain large size, however chronic cholecystitis will lead to a shrunken gall bladder rather than an enlarged one. A malignant GB of such size and resectable is rare without any lymph node involvement or liver infiltration. Few cases of giant benign gall bladder have been reported in literature, however this appears to be the largest resectable gall bladder carcinoma reported till date as per indexed literature. CONCLUSION: Giant GB is an uncommon finding. They are mostly benign, however malignant cases can occur. Radiological findings may suggest features of malignancy and define extent of disease. Prognosis depends on stage of disease and resectability, irrespective of size.

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.

Raised CA19-9 and CEA have prognostic relevance in gallbladder carcinoma.

BACKGROUND: Role of tumor markers in gall bladder carcinoma (GBC) is not well established. We evaluated the prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoma embryonic antigen (CEA) in patients with GBC. METHODS: Of the 225 patients of GBC enrolled,176 patients were included in the study (excluded 49 patients with jaundice). Patients were divided into 3 groups; resectable n = 92, unresectable n = 17, metastatic n = 67. The clinico-pathological characteristics, tumor markers and survival data were analysed. The cutoff values of CA19-9 & CEA for predicting metastases were computed using receiver operating characteristic curve. Kaplan Meir survival and Cox regression analysis were done for factors predicting survival and recurrence. RESULTS: The median value of Ca19-9 was significantly higher in metastatic group [resectable: 21.3, unresectable: 53.9 and metastatic: 79; p < 0.001] but not for CEA [3.5, 7.8 and 5 ng/ml (p = 0.20)]. A cutoff value of 72 IU/ml for CA19-9, 5 ng/ml for CEA had a sensitivity and specificity of 52 and 80%, 51 and 72% respectively for detection of metastatic disease. Median, 3-year & 5-year survival were significantly lower in patients with CEA > 4 (p = 0.041), Ca19.9 > 37 (p = 0.019), T3/T4 (p = 0.001), node positive (p = 0.001) and presence of perineural invasion (p = 0.001). However, on multivariate analysis, only Ca19.9 > 37 predicted recurrence (p = 0.002, HR 5.8). CONCLUSIONS: Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19-9 was better than CEA in prediction of tumor burden and in predicting recurrence.

Role of carbohydrate antigen 19-9, carcinoembryonic antigen, and carbohydrate antigen 125 as the predictors of resectability and survival in the patients of Carcinoma Gall Bladder.

INTRODUCTION: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) have been reported in previous studies to assess the prognosis of gall bladder cancer (GBC) individually and in combination. However, the evidence of utility of preoperative CA 19-9, CEA and carbohydrate antigen 125 (CA 125) in determining the resectability and prognosis of GBC is still lacking. In the present study we correlated the serum levels of tumor markers CA 19-9, CEA and CA 125 individually and combined to determine the resectability and prognosis of the GBC. MATERIALS AND METHODS: Seventy one diagnosed patients of GBC between January 2018 and September 2019 were included in the present study. Serum CA 19-9, CEA and CA 125 were determined by chemiluminescence. Receiver operating characteristic (ROC) curve was used to evaluate the role of tumor markers in determining the resectability of GBC. The Kaplan Meier survival curves were made and log rank analysis was performed to assess the prognostic role of tumor markers in terms of overall median survival. RESULTS: All the three tumor markers CA19-9, CEA and CA 125 showed high discriminatory power in determining the resectability with respective area under curve of 0.76, 0.68 and 0.78 as determined by ROC. Median survival in patients with high serum CA 19-9, CA 125 was significantly lower than patients with normal serum CA 19-9, CA 125 whereas no significant difference was observed in case of CEA. CONCLUSION: The present study suggested that CA 19-9, CEA and CA 125 can predict resectability in GBC and raised levels of CA 19-9 and CA 125 can predict poor prognosis in patients with elevated levels.

Evaluation of platelet distribution width as novel biomarker in gall bladder cancer.

INTRODUCTION: Gall bladder cancer (GBC) tends to present in advanced stages, therefore, early diagnosis of GBC is necessary. There is no ideal single tumor marker available presently for the diagnosis and prognosis of GBC. Platelet distribution width (PDW) is an early marker for activated platelets and has been used in a variety of tumors to assess prognosis. This study was designed to evaluate the utility of PDW in identifying GBC patients and its association with tumor markers, staging and resectability of GBC. MATERIALS AND METHODS: This cross sectional study was done on 100 patients of GBC and 100 age- and sex- matched healthy controls. PDW was evaluated and compared between GBC and healthy controls. Receiver-operating characteristics was plotted to determine optimal cut-off for identifying GBC patients and to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PDW. Correlation between serum tumor markers (carbohydrate antigen 19-9, carcinoembryonic antigen, and carbohydrate antigen 125) and PDW were evaluated. Association of PDW with hyperbilirubinemia, staging and resectability of GBC was also studied. RESULTS: A significantly higher PDW with a median of 18.1 was observed in GBC as compared to healthy controls with median value of 13. PDW was found to have a very high sensitivity (90%), specificity (95%), PPV (94%) and NPV (90%) in identifying GBC at cut-off of 16 with area under the curve (AUC) of 0.97. An increase of PDW was observed with increasing stage and unresectable GBC. However, it was not statistically significant. Significant positive correlation was observed between PDW and all three serum tumor markers and good positive correlation with r = 0.61 was observed with CA 19-9. CONCLUSION: PDW was associated with GBC and may be considered as a cost- effective marker in adjunct to other investigations for the diagnosis of GBC.

New Treatment Options for Advanced Biliary Tract Cancer.

OPINION STATEMENT: The standard of care first-line therapy for patients with advanced biliary tract cancers eligible for treatment continues to be the combination of gemcitabine and cisplatin. Based on the promising results of a phase II study, an ongoing multi-institutional phase III study is assessing the benefit of adding nab-paclitaxel to the chemotherapy doublet, and appropriate patients should be considered for enrollment at participating centers. We would recommend early comprehensive genomic profiling of patients' tumors to identify potentially targetable aberrations with available therapies. Results with therapeutic implications include tumors with microsatellite instability/deficient mismatch repair, alterations in FGFR, IDH1/2, and HER-2, and potentially other molecular vulnerabilities. Patients in whom a targetable genomic abnormality is found should be matched with appropriate agent. If a targetable fusion or mutation is not detected, patients eligible for second-line therapy should be considered for either clinical trial enrollment or a second-line cytotoxic chemotherapy regimen such as modified FOLFOX. Strategies incorporating immunotherapy into the treatment of patients with microsatellite stable advanced biliary tract cancers have yielded largely disappointing results thus far, and routine use of checkpoint inhibitors outside of a clinical trial is not recommended.

Epigenetic downregulation of desmin in gall bladder cancer reveals its potential role in disease progression.

Background & objectives: Gall bladder cancer (GBC) is a fatal neoplasm, with a globally variable incidence rates. To improve the survival rate of patients, a newer set of biomarkers needs to be discovered for its early detection and better prognosis. Our earlier studies on GBC proteomics and whole-genome methylome data revealed expression of desmin to be significantly downregulated with correlated promoter hypermethylation during gall bladder carcinogenesis. Thus, to evaluate desmin as a potential biomarker for GBC, we carried out a detailed follow up study. Methods: Methylation-specific polymerase chain reaction (MS-PCR) (n=17, GBC and n=23, non-tumour control), real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) [n=14, GBC and n=14, adjacent non-tumour (ANT)], immunohistochemistry (n=27, GBC and n=14, non-tumour) and immunoblotting (n=13, GBC and n=13, ANT) were performed in surgically removed gall bladder tissue samples. Results: MS-PCR analysis showed methylation of desmin in 88.23 per cent (15/17) gall bladder tumour samples as compared to non-tumour tissues (39.13%, 9/23). Real-time qRT-PCR analysis revealed a significant downregulation of desmin expression in GBC as compared to ANT tissue. This was further confirmed by western blot, showing reduced expression of desmin protein in GBC, as compared to non-tumour tissue. Immunohistochemical analysis also showed a decreased level of desmin i.e., more than 95 per cent (26/27) in tumour cells compared to non-tumours (35.71%, 5/14). Interpretation & conclusions: The increased frequency of desmin promoter methylation which could be responsible for its significant downregulation, indicates its potential as a candidate biomarker for GBC. This requires further validation in a large group of patients to evaluate its clinical utility.

Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink.

OBJECTIVE: To evaluate the association between statin use and risk of biliary tract cancers (BTC). DESIGN: This is a nested case-control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders. RESULTS: We included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007). CONCLUSION: Compared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.

Screening high risk populations for cancer: Hepatobiliary.

Cancers of the hepatobiliary tract are highly fatal, prompting the need for early detection to provide treatment and decrease the mortality rate. Screening patients for hepatobiliary cancers can provide early detection, but it is not feasible or efficient to screen all patients. Therefore, it is important to consider the known risk factors for each hepatobiliary cancer which creates a smaller population that is amenable to screening.

Atypical frontal lobe seizure as the first manifestation of gall-bladder cancer: a case report.

BACKGROUND: Gall bladder cancer (GBC) is associated with abdominal pain, lump, nausea, vomiting, and jaundice due to either gall bladder mass or the involved adjacent peritoneal structures. Gall bladder cancer presenting as refractory epilepsy is rare. Here we report a young female GBC patient who presented with an atypical and refractory frontal lobe seizures as the first manifestation of gall bladder cancer. CASE PRESENTATION: A 46 years young female presented first time to the hospital with uncontrolled seizures and headache in 5 months duration. Seizures were very atypical in semiology with ptosis and mydriasis to either side along with ipsilateral ocular deviation. The episodes were bilateral but right eyelid ptosis, mydriasis and right horizontal conjugate deviation were frequent. MRI brain showed encephalomalacia in the left frontal region on axial T2 and coronal T1 weighted images without any enhancement on gadolinium contrast. CECT abdomen revealed a heterogeneously enhancing gall bladder mass with the evidence of lung metastasis from chest CT scan. CSF for malignant cytology was negative. Seizures were refractory to the treatment. CONCLUSION: Though CNS involvement is uncommon but it can be the only presentation in gall bladder cancer.

Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers.

Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients' survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared. Treatment was repeated every two weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was the progression-free survival (PFS). Results A quarter of patients (8/32) from Group A and a fifth of patients (13/25) from Group B had an objective response. The median PFS was 6.48 months and 3.72 months in Group A and B, respectively (p = 0.049). The median OS was 11.31 months and 10.34 months in Group A and B, respectively. Grade 3/4 sepsis was identified in 9.4% and 12% in Group A and B, respectively, (p = 0.64). Conclusion In mBTC, the addition of bevacizumab to GEMOX increased the progression-free survival and was associated with manageable toxicity. These data pave the way for further evaluation of antiangiogenic agents in mBTC.

Emerging role of multimodality treatment in gall bladder cancer: Outcomes following 510 consecutive resections in a tertiary referral center.

BACKGROUND AND OBJECTIVES: Gall bladder cancer (GBC) is a disease with high incidence in India. We analyzed the outcomes of patients with suspected GBC who underwent surgical exploration. METHODS: Analysis of a prospectively maintained database of patients undergoing surgical exploration for clinic-radiologically suspected GBC from January 2010 to August 2015. Outcomes as well as factors influencing survival were analyzed. RESULTS: Five hundred and ten patients underwent surgery for suspected GBC. Of these 400 had histologically proven malignancy. Eighty patients were deemed inoperable. Radical cholecystectomy was performed in 153 patients, revision surgery for incidental GBC in 160 and port site excision in seven patients. A total of 112 received peri-operative chemotherapy or chemoradiation. Majority were stage III (36%, n = 144) and stage II (31.8% n = 127). At a median follow up of 28.4 months, the median overall survival (OS) was not yet reached. Median disease free survival (DFS) was 33.4 months. Lymph node involvement, stage of the disease and resection status were the main factors influencing outcomes (P = 0.0001). CONCLUSION: Surgery alone is curative only for early GBC (Stage I). Combination of surgery and peri-operative systemic therapy results in favorable outcomes even in stage II/III disease. Potentially, multimodality treatment may add meaningful survival for this disease with inherently aggressive tumor biology.

Long-lasting complete response status of advanced stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine: two case reports.

BACKGROUND: The prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer. CASE PRESENTATION: Case 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years. Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years. CONCLUSION: We report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs.

How we do it: double in situ split for staged mesohepatectomy in patients with advanced gall bladder cancer and marginal future liver remnant.

PURPOSE: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has increased the rate of liver resections in patients with marginal future liver remnant. We here describe a modified ALPPS procedure with splitting-off the central liver segments for staged mesohepatectomy in patients with advanced gall bladder cancer. METHODS: A double in situ split for ALPPS (DALPPS) is performed with splitting-off the central liver segments (segments 1, 4, 5, and 8). This induces a rapid hypertrophy of the left lateral (segments 2/3) and right posterior sectors (segments 6/7). An intrahepatic right posterior approach during splitting-off the right posterior sector is introduced as a part of this new procedure. This approach facilitates the dissection and ligation of the right anterior branch of the portal vein (segments 5 and 8) while the liver hilum remains untouched during the first step of surgery. RESULTS: Two patients with advanced gall bladder cancer were treated with the DALPPS procedure till date. After a short interval (7-9 days), a rapid hypertrophy of the left lateral and right posterior sector was observed (hypertrophy up to 72.6 and 54.6 %, respectively). A staged mesohepatectomy including caudate lobectomy and resection of the extrahepatic bile duct was then performed safely. There was no surgical-technical morbidity. No signs of posthepatectomy liver failure according to the 50-50 criteria were seen. However, one patient died from severe ARDS attributed to the preoperative chemotherapy. Nevertheless, this complication is deemed to be surgery related. CONCLUSIONS: The DALPPS procedure is a new surgical technique for staged mesohepatectomy for patients with small future liver remnant in size or in function. However, appropriate patient selection is mandatory to avoid morbidity and mortality.

Use of gemcitabine-platinum in Indian patients with advanced gall bladder cancer.

BACKGROUND: Gemcitabine-platinum (Gem-P) is the current standard for patients with advanced gall bladder cancer. MATERIALS & METHODS: This is retrospective analysis of a prospectively maintained database of 210 patients with advanced gall bladder cancer treated with Gem-P between January 2012 and September 2013. RESULTS: Median age was 53 years, 65.2% females. In total,158 patients had metastatic and 52 had locoregional disease. Median number of cycles was 5 (1-12). At a median follow-up of 10 months, median overall survival/progression-free survival was 10/5 months, respectively. On multivariate analysis, patients who underwent prior surgery for primary and locoregional disease had a significantly better progression-free survival and those with locoregional disease had a significantly better overall survival. A total of 45.7% received second-line chemotherapy. CONCLUSION: Use of Gem-P in Indian patients leads to slightly worse outcomes suggesting an aggressive biology.

Association of tumor budding and tumor infiltrating lymphocytes with clinicopathological parameters in gallbladder carcinoma.

PURPOSE: Gallbladder carcinoma (GBC) poses significant challenges in oncology due to its aggressive nature and limited treatment options. The lack of effective biomarkers for early detection and prognosis exacerbates the prognosis for GBC patients. Tumor budding (TB) and tumor infiltrating lymphocytes (TILs) have emerged as potential prognostic indicators in various cancers, reflecting tumor-host immune interactions and tumor aggressiveness. The study of TB and TILs in GBC is particularly important due to the limited literature available. METHODS: This retrospective observational study aimed to evaluate the association of TB and TILs with clinicopathological parameters in GBC patients. Clinicopathological data were collected from patients with histologically confirmed GBC who underwent surgical resection. The sections were evaluated for TB and TILs using standardized methods. Statistical analysis was performed to assess associations between these parameters and clinicopathological variables. RESULTS: Tumor stage and grade showed significant associations with TB and TILs, indicating their potential as prognostic markers. High TB correlated with advanced tumor stage and higher grade, while high TIL infiltration was associated with early tumor stage and lower grade. Additionally, TILs exhibited a significant association with lymphovascular invasion. Interestingly, an inverse association was observed between TB and TILs, highlighting the dynamic interplay between tumor aggressiveness and host immune response. CONCLUSION: TB and TILs hold prognostic significance in GBC, offering insights into its pathogenesis and potential therapeutic targets. Future research exploring the mechanistic underpinnings of tumor-host immune interactions in GBC is crucial for translating these findings into clinical applications and improving outcomes for patients.