Gallbladder Adenocarcinoma Research Articles

ASO Author Reflections: CTCs in Patients with Gallbladder Adenocarcinoma.

ASO Author Reflections: CTCs in Patients with Gallbladder Adenocarcinoma.

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma: A propensity score-matched study.

Gallbladder mucinous adenocarcinoma (GBMAC) is a rare subtype of gallbladder adenocarcinoma (GBAC), with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis. To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field. This study was conducted using data from the Surveillance, Epidemiology, and End Results database, including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017. The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts. In addition, propensity score matching (PSM) analysis was performed to balance the selection biases. Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). The Kaplan-Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients. The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC. They included a larger proportion of patients with unmarried status, advanced American Joint Committee on Cancer (AJCC) stage, higher T stage, higher N1 stage rate and lower N0 and N2 stage rates (P < 0.05). Multivariate analyses demonstrated that surgery [OS: Hazard ratio (HR) = 2.27, P = 0.0037; CSS: HR = 2.05, P = 0.0151], chemotherapy (OS: HR = 6.41, P < 0.001; CSS: HR = 5.24, P < 0.001) and advanced AJCC stage (OS: Stage IV: HR = 28.99, P = 0.0046; CSS: Stage III: HR = 12.31, P = 0.015; stage IV: HR = 32.69, P = 0.0015) were independent prognostic indicators for OS and CSS of GBMAC patients. Furthermore, after PSM analysis, there was no significant difference between GBMAC and matched typical GBAC patients regarding OS (P = 0.82) and CSS (P = 0.69). The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC. However, they show similar survival prognoses. Surgery, chemotherapy, and lower AJCC stage were associated with better survival outcomes. Further research is needed in the future to verify these results.

Comparison of carcinosarcoma and adenocarcinoma of the gallbladder: a study based on SEER population for propensity matching and nomogram analysis.

Carcinosarcoma of the gallbladder (CSGB) is an uncommon malignancy, and limited literature is available on its clinicopathological features, prognosis, and treatment options. Using the SEER database, we selected 7634 gallbladder adenocarcinoma patients (diagnosed from 2004 to 2015) and 58 carcinosarcoma of the gallbladder patients (diagnosed from 1988 to 2019) based on predetermined criteria. We compared the overall survival (OS) and cancer-specific survival (CSS) before and after propensity score matching in two groups. Cox univariate and multivariate analyses were performed, and a nomogram was further generated to investigate the impact of clinical and pathological variables on the survival of patients with CSGB. Finally, we evaluated the effect of different treatment modalities on the overall survival of CSGB patients. Notably, CSGB patients had larger tumors and underwent surgery more frequently than gallbladder adenocarcinoma patients, with lower rates of deeper tumor infiltrates, and lymph node infiltrates. Conversely, gallbladder adenocarcinoma patients had a higher proportion of AJCC staging (III-IV). Despite these differences, no significant differences were found in OS and CSS between the two groups before and after propensity score matching. For CSGB patients, AJCC staging, surgery and tumor size were significant prognostic factors, while treatment modalities such as surgery combined with chemotherapy, or combined radiochemotherapy, as well as radical resection, did not significantly prolong patient survival. No significant difference was found in survival rates between CSGB and gallbladder adenocarcinoma patients, while radical surgery and different combined treatment modalities did not provide significant survival benefits.

Role of Morphology and Immunohistochemistry in the Diagnosis of Incidental Cancers in Gallstone Disease

Introduction: The majority of gallbladder adenocarcinomas have been known to develop from dysplasia or carcinoma in situ, without pre-existing adenomas, hence observation of these non-neoplastic or preneoplastic lesions is important as it may underlie an occult malignancy. To study the role of morphology and immunohistochemistry in the diagnosis of incidental cancers in cases of gall stone disease by adopting a universal histopathological screening policy for all the gallstone disease cases operated at our tertiary care center. Material and Methods: The present study was designed as an observational cross sectional study completed over a time period of 14 months. A total of 176 cases were included in the study including all the patients of gall stone disease in the adult age group. All the indeterminate and frankly malignant cases were subjected to immunohistochemistry with a panel of antibody markers including p53, CEA and Ki-67 using Streptavidin Biotin immunoperoxidase method Fisher-exact test was used to compare the data taking‘p’ value less than 0.05 as statistically significant. Results: Mean age of patients was 40.55±13.25 years. Majority of patients (n=141; 80.1%) were females. The final diagnosis revealed a dominance of non-neoplastic inflammatory (n=168; 95.5%) pathology. There were 8 (4.5%) of malignancy, of these 7 were adenocarcinoma and 1 was adenosquamous carcinoma. Atypia was seen in 5 (2.8%) cases and 3 (1.7%) cases were of dysplasia. Histopathology detected carcinoma in 7 (4%) cases whereas addition of immunohistochemistry helped to find out one more unidentified case, thus the diagnostic yield increased to 8 (4.5%) cases. Out of three dysplasia cases, one (33.3%) was found positive on immunohistochemistry, which was later confirmed to be malignant. None of the cases of atypia were positive on p53, Ki-67 and CEA immunohistochemistry. On comparison between the three groups, the results were statistically significant (p=0.00062). Conclusion: Immunohistochemistry has a useful role in detection of incidental gallbladder carcinoma when morphology is limited by indeterminate results. A panel of immunohistochemical markers including p53, Ki-67 and CEA may prove very useful to pick up cases of malignancy in such cases of diagnostic dilemma.

Co-Expression of Immunohistochemical Markers MRP2, CXCR4, and PD-L1 in Gallbladder Tumors Is Associated with Prolonged Patient Survival.

Gallbladder cancer (GBC) is a rare pathology in Western countries. However, it constitutes a relevant health problem in Asia and Latin America, with a high mortality in middle-aged Chilean women. The limited therapeutic options for GBC require the identification of targetable proteins with prognostic value for improving clinical management support. We evaluated the expression of targetable proteins, including three epithelial tumor markers, four proteins associated with multidrug and apoptosis resistance, and eleven immunological markers in 241 primary gallbladder adenocarcinomas. We investigated correlations between tumor marker expression, the primary tumor staging, and GBC patients' survival using automated immunohistochemistry, a semi-automatic method for image analysis, univariate and multivariate statistical analyses, and machine learning algorithms. Our data show a significant association between the expression of MRP2 (p = 0.0028), CXCR4 (p = 0.0423), and PD-L1 (p = 0.0264), and a better prognosis for patients with late-stage primary tumors. The expression of the MRP2/CXCR4/PD-L1 cluster of markers discriminates among short-, medium-, and long-term patient survival, with an ROC of significant prognostic value (AUC = 0.85, p = 0.0012). Moreover, a high MRP2/CXCR4/PD-L1 co-expression is associated with increased survival time (30 vs. 6 months, p = 0.0025) in GBC patients, regardless of tumor stage. Hence, our results suggest that the MRP2/CXCR4/PD-L1 cluster could potentially be a prognostic marker for GBC.

Immunotherapy in Biliary Tract Cancers: Current Standard-of-Care and Emerging Strategies.

Biliary tract cancers (BTCs), comprising intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder adenocarcinoma, continue to be challenging to manage. Conventional chemotherapy regimens for advanced disease are limited in both options and benefits, and more effective perioperative regimens are also needed. Over the last decade, immunotherapy has had a profound impact on the management of many solid tumor types, particularly in using immune checkpoint inhibition to enable a tumor-directed T cell response. Immunotherapy administered on its own has had limited utility in BTCs, in part due to a hostile immune microenvironment and the relative infrequency of biomarker-based tumor-agnostic indications for immunotherapy. However, immunotherapy in conjunction with chemotherapy, molecularly targeted therapies, and/or anti-angiogenic therapies has gained traction, supported by evidence that these agents can impart favorable immunomodulatory effects on the tumor microenvironment. The TOPAZ-1 trial led to the first BTC-specific immunotherapy approval, establishing the combination of durvalumab with gemcitabine and cisplatin as the preferred first-line treatment for advanced or metastatic disease. Recently, the KEYNOTE-966 trial showed positive results for the combination of pembrolizumab with gemcitabine and cisplatin in the same setting, adding further evidence for the addition of immune checkpoint inhibition to the standard chemotherapy backbone. Meanwhile, advances in the molecular profiling of BTCs has contributed to the recent proliferation of molecularly targeted therapeutics for the subset of BTCs harboring alterations in IDH1, FGFR2, MAP kinase signaling, HER2, and beyond, and there has been great interest in investigating combinations of these agents with immunotherapy. Emerging immunotherapy strategies beyond immune checkpoint inhibition are also being studied in BTCs, and these include immunostimulatory receptor agonists, Wnt signaling modulators, adoptive cell therapy, and cancer vaccines. A large number of trials are underway to explore promising new combinations and immune-targeted strategies, offering opportunities to expand the role of immunotherapy in BTC management in the near future.

Port-site Metastasis from Gall Bladder Adenocarcinoma with Squamous Differentiation Following Laparoscopic Cholecystectomy: A Rare Case Report

Port site cutaneous metastasis of gallbladder cancer is an exceedingly infrequent phenomenon with very few cases reported in the past. Herein, we report a case of port site cutaneous metastases of gallbladder adenocarcinoma in a 57 years old female. Physical examination revealed a non healing ulcer in the epigastric region. FNA was suggestive of poorly differentiated carcinoma. Biopsy demonstrated atypical cells. Immunohistochemical analysis showed diffuse cytoplasmic staining with CK 7 and p63 showed focal nuclear positivity in tumour cells. This confirmed the diagnosis of metastastatic gall bladder adenocarcinoma with squamous differentiation. Diagnosis in such a case can be very challenging as the differential of primary cutaneous malignancies should also be kept in mind.

Complete radiologic and pathologic response in a metastatic gallbladder adenocarcinoma patient treated with neoadjuvant checkpoint inhibitor/chemotherapy combination and extended cholecystectomy

Complete radiologic and pathologic response in a metastatic gallbladder adenocarcinoma patient treated with neoadjuvant checkpoint inhibitor/chemotherapy combination and extended cholecystectomy

A multicenter, open-label, randomized phase II study evaluating adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (CAPE-RT) in patients with operated gallbladder adenocarcinoma (GBC): The GECCOR-GB trial.

4017 Background: Adjuvant gemcitabine plus cisplatin (GC) and concurrent chemo-radiotherapy are commonly used treatment options for resected GBC. Methods: GB-GECCOR is a multicentre, open-label randomized non-comparative phase II study in patients of Gallbladder cancer (GBC), with R0 or R1 resection within 3 months of randomization. Patients were randomized 1:1 to GC arm (Gem 1000 mg/m2 and Cisplatin 25mg/m2 on day 1 and 8, q 3 weeks) for 6 cycles or CAPE-RT arm {Capecitabine 1000mg/m2 BD on days 1-14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825mg/m2 twice) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary end point was 1-year disease-free survival (DFS). With 80% power to detect the difference between a 59% (minimum sufficient activity of the regimen) and a 77% (sufficient activity for future larger studies with the regimen) 1-year DFS rate assuming an attrition of 10%, a total of 90 patients were required for the study. Results: Between May 2019 and February 2022, 90 patients (45 in each arm), were included. Stage II and stage III GBC were seen in 50 (56%) and 40 patients (44%) respectively, with R0 resection observed in 86 patients (96%). Patient characteristics were well balanced between the 2 arms except for R1 resections which were greater in the CAPE-RT arm (p=0.041). With a median follow-up duration of 23 months, the 1-year DFS rate was 88.9% (95% CI: 79.5-98.3) in the GC group and 77.8% (95% CI: 65.4 – 90.2) in the CAPE-RT group, respectively. The most common AEs were grade 3/4 neutropenia in 6 patients (13.3%) in the GC group and grade 2/3 HFS in 14 patients (31.1.%) in the CAPE-RT group. The distant metastases were seen in 12 patients (26.6 %) in each arm and loco-regional metastases in 3 patients (6.6 %) in the GC arm. Conclusions: In this study of operated GBC, GC and CAPE-RT successfully achieved the minimum pre-specified DFS rates. Within the confines of a non-comparative randomised study, GC had narrowed the gap in survivals of stage III vs. stage II GBCs, which was not noted in the CAPE-RT arm. This study results give credence to the use of both regimens as reasonable standards of care till evaluation in larger phase 3 studies. Clinical trial information: CTRI/2019/05/019323 . [Table: see text]

The impact of anti-EGFR therapy when added to first-line standard platinum-gemcitabine chemotherapy in advanced biliary tract cancers: A meta-analysis of randomized studies.

e16109 Background: Biliary tract cancers (BTCs) represent the second-most common primary liver cancers. They are a heterogeneous group of tumors that include Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, and ampullary carcinoma. BTCs are usually diagnosed in an advanced stage and carry a poor prognosis. A better understanding of cancer biology has led to advances in targeted treatments in other cancers but remains an unmet need in BTCs. We conducted this meta-analysis to evaluate the efficacy of anti-EGFR therapy when added to the standard platinum-gemcitabine chemotherapy as first-line in patients with advanced BTCs. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of biliary tract tumors, randomized studies of first-line platinum-gemcitabine with and without anti-EGFR therapies, and studies that reported overall (OS) and progression free survival (PFS). A meta-analysis using the fixed effects and random effects models was conducted. Results: Four randomized studies with a total of 569 patients were included. Three studies were randomized phase 2 and one was randomized phase 3. Three studies used oxaliplatin and one used cisplatin in addition to gemcitabine as the standard combination. Panitumumab was used in two studies while cetuximab and erlotinib were used in one study each. The addition of anti-EGFR agent to first-line platinum-gemcitabine in advanced BTC resulted in a superior OS (HR = 0.72, 95%CI 0.61-0.85) and PFS (HR = 0.76, 95%CI 0.63-0.92). When the analysis was restricted to anti-EGFR monoclonal antibodies, their PFS benefit persisted (HR = 0.72, 95%CI 0.55-0.95), but their OS benefit failed to reach statistical significance (HR = 0.83, 95%CI 0.65-1.07). Conclusions: This is the first meta-analysis to show the addition of anti-EGFR agents to the standard first-line platinum-gemcitabine chemotherapy improves OS and PFS in advanced BTC.

Development and validation of a prognostic nomogram for gallbladder papillary adenocarcinoma.

Gallbladder papillary adenocarcinoma (GBPA) is an uncharacteristically gallbladder cancer subtype. Although some studies have shown that the prognosis of GBPA patients is significantly better than that of gallbladder adenocarcinoma (GBA) and gallbladder mucinous adenocarcinoma (GBMA) due to its rarity, there is a lack of large sample studies necessary to confirm the clinical characteristics and survival rate of GBPA. Therefore, this study aimed to describe the clinicopathological characteristics affecting survival in GBPA. This data was then used to establish a prognostic nomogram for GBPA. The data of patients diagnosed with gallbladder cancer between 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The clinical features and survival of patients with GBPA were compared with those of GBA and GBMA after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for GBPA. Subsequently, the overall survival (OS) and cancer-specific survival (CSS) nomograms were established to predict GBPA prognosis. The performance and discrimination of the nomogram were measured using concordance index (C-index), calibration curves, receptor operating characteristic curves(ROC), and decision curve analysis (DCA) was applied to examine the net benefit of tients with GBPA, 5798 patients with GBA, and 223 patients with GBMA. The mean 1-, 3- and 5-year OS rates for GBPA were 81.3%, 58.8%, and 49.1%, respectively, while the mean 1-, 3- and 5-year CSS rates were 85.0%, 68.1%, and 61.0%, respectively. The median OS rates was 58 months (95% CI: 43-88), while the median CSS was not reached. The PSM analysis showed a differ statistically significantly in the OS between GBPA and GBA. However, there has no statistically difference in CSS. Conversely, the OS and CSS between GBPA and GBMA have statistically significant differences. Age, marital, T stage, and M stage were strongly linked to the prognosis for OS, while T-stage, M-stage, and surgery were significantly associated with the prognosis for CSS in GBPA patients. The AUC for the 1-, 3-, and 5-year OS were 0.722 (95%CI: 0.630-0.813), 0.728 (95%CI: 0.665-0.790), and 0.706 (95%CI: 0.641-0.771), respectively. The AUC for the 1-, 3-, and 5-year CSS were 0.749 (95%CI: 0.659-0.840), 0.698 (95%CI: 0.627-0.770), and 0.665 (95%CI: 0.594-0.735), respectively. The C-indices for the OS and CSS nomograms were 0.701 (95% CI: 0.634-0.744) and 0.651 (95% CI: 0.598-0.703), respectively. The calibration curves showed that the nomograms were well consistency. The DCA showed that compared with the TNM system, the nomogram models had a significant positive net benefit in survival prediction. GBPA has distinct clinicopathological characteristics and survival compared to other gallbladder carcinomas. The established nomogram provided a better prediction of survival for GBPA patients than the traditional TNM models.

SIUMB recommendations on the use of ultrasound in neoplastic lesions of the gallbladder and extrahepatic biliary tract.

Extrahepatic biliary tract and gallbladder neoplastic lesions are relatively rare and hence are often underrepresented in the general clinical recommendations for the routine use of ultrasound (US). Dictated by the necessity of updated summarized review of current literature to guide clinicians, this paper represents an updated position of the Italian Society of Ultrasound in Medicine and Biology (SIUMB) on the use of US and contrast-enhanced ultrasound (CEUS) in extrahepatic biliary tract and gallbladder neoplastic lesions such as extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, gallbladder adenomyomatosis, dense bile with polypoid-like appearance and gallbladder polyps.

Comparison of clinicopathological characteristics and long-term survival between patients with gallbladder adenosquamous carcinoma and pure gallbladder adenocarcinoma after curative-intent surgery: a single-center experience in China and a meta-analysis.

The aim of the study was to evaluate the similarities and differences between gallbladder adenosquamous carcinoma (GBASC) and pure gallbladder adenocarcinoma (GBAC). Patients with GBASC and GBAC from 2010 to 2020 were analyzed in terms of clinicopathological features and long-term survival. Moreover, a meta-analysis was also performed for further validation. Our experience: A total of 304 patients with resected GBC were identified, including 34 patients with GBASC and 270 patients with GBAC. Patients with GBASC had a significantly higher preoperative CA199 level (P <0.0001), a significantly higher incidence of liver invasion (P <0.0001), a relatively larger tumor size (P = 0.060), and a significantly higher proportion of patients with T3-4 (P <0.0001) or III-IV disease (P = 0.003). A comparable R0 rate was obtained between two groups (P = 0.328). A significantly worse overall survival (OS) (P = 0.0002) or disease-free survival (DFS) (P = 0.0002) was observed in the GBASC. After propensity score matching, comparable OS (P = 0.9093) and DFS (P = 0.1494) were obtained. Clear margin (P = 0.001), node metastasis (P <0.0001), T stage (P <0.0001), and postoperative adjuvant chemoradiotherapy (P <0.0001) were independent prognostic factors for OS for the entire cohort. Adjuvant chemoradiotherapy had a survival benefit for patients with GBAC, while the survival benefit was still being validated in patients with GBASC. Meta-analysis: With our cohort incorporated, a total of seven studies involving 1,434 patients with GBASC/squamous carcinoma (SC) were identified. GBASC/SC shared a worse prognosis (P <0.00001) and more aggressive tumor biological features than GBAC. GBASC/SC shared more aggressive tumor biological features and a much worse prognosis than those with pure GBAC.

Lymph node metastatic status could predict the prognosis of intracholecystic papillary neoplasm of gallbladder

Intracholecystic papillary neoplasm (ICPN) is a non-invasive epithelial tumor that presents as a grossly identifiable mass arising in the mucosa and protruding into the lumen. ICPN is associated with invasive carcinoma. There are few studies on the clinicopathological features of ICPN, including that with invasive carcinoma. We evaluated the clinicopathological characteristics of 42 ICPNs and 41 conventional gallbladder adenocarcinomas (cGBAs). Subserosa or deeper (≥ss) invasion was significantly lower in ICPN (61.9%) than that in cGBA (90.2%) (P=0.004). Cox regression analysis revealed that lymph node metastasis (hazard ratio [HR] [95% confidence interval (CI)]: 2.610 [1.131, 6.024], P=0.025) and positive margin (HR [95% CI]: 5.143 [2.113, 12.516], P<0.001), but not ≥ss invasion (HR [95% CI]: 1.541 [0.479, 4.959], P=0.469), were independent prognostic factors. In addition, there was a significant interaction between histological type and lymph node metastasis (HR [95% CI]: 0.191 [0.042, 0.983], P=0.033). In cGBA, the presence or absence of lymph node metastasis did not affect prognosis; however, ICPN without lymph node metastasis had better prognosis. Therefore, the histological classification of ICPN and cGBA and the pathological evaluation of lymph node metastasis in ICPN are crucial for determining prognosis.

Study of PD-L1 Expression in Tumours Based on Site and Histology of Tumour – The Experience of a Tertiary Referral Laboratory

Background: PD-L1 IHC test is used as a predictive biomarker using FDA-approved assays to select patients likely to benefit from immunotherapy in several advanced-stage tumors. We aim to present our data regarding the prevalence and expression pattern of PD-L1 across various tumors based on site and histology and compare them with those of the reported literature. Material and Methods: A retrospective study of 301 cases of various tumors at different sites was done for PD-L1 IHC using the 22С3 pharmDx assay on the recommended platform.Results: Out of 237 non small cell lung carcinoma cases, 14.7% were squamous and 85.2% were of nonsquamous histotype, with adenocarcinomas comprising the majority (82.2%). Fifty-seven percent of non small cell lung carcinoma was PD-L1 positive, 28.6% showed high expression. Sixty percent of the squamous and 56.4% of the non-squamous histotypes showed positive immunoexpression. Amongst non-squamous types, 56.4% of adenocarcinomas and 66.6% of sarcomatoid carcinomas were positive. At metastatic sites, 54.3% of on small cell lung carcinoma were positive. In head and neck squamous cell carcinoma, the majority (10/11) of cases were from the oral cavity; 81.8% of total cases were positive, 27.2% were strong expressors. For other sites, the number of cases showing PD-L1 immunopositivity is as follows: oesophageal squamous cell carcinoma (2/6), gastric adenocarcinoma (2/6), triple negative breast carcinoma (0/3), urothelial carcinoma (2/5), gall bladder (2/5), pancreatico-biliary (2/11), and colorectal (2/17) adenocarcinomas. In these tumors, PD-L1 immunoexpression did not differ significantly by age or gender. Conclusion: Our study showed PD-L1 immunopositivity in 57% of non small cell lung carcinoma and 81.8% of head and neck squamous cell carcinoma, which is comparable to international studies. Further studies with larger sample sizes are needed to see their expression pattern in tumors at other sites and with different histologies.

Targeted molecular profiling of solid tumours-Indian tertiary cancer centre experience.

Molecular Profiling of solid tumours is extensively used for prognostic, theranostic, and risk prediction. Next generation sequencing (NGS) has emerged as powerful method for molecular profiling. The present study was performed to identify molecular alterations present in solid tumours in Indian tertiary cancer centre. Study included 1140 formalin Fixed paraffin embedded samples. NGS was performed using two targeted gene panels viz. Ampliseq Focus panel and Sophia Solid Tumor Plus Solution. Data was analyzed using Illumina's Local Run Manager and SOPHiA DDM software. Variant interpretation and annotations were done as per AMP/ACMG guidelines. Total 896 cases were subjected to NGS after excluding cases with suboptimal nucleic acid quality/quantity. DNA alterations were detected in 64.9% and RNA fusions in 6.9% cases. Among detected variants, 86.7% were clinically relevant aberrations. Mutation frequency among different solid tumours was 70.8%, 67.4%, 64.4% in non-small cell lung (NSCLC), lung squamous cell carcinomas and head neck tumours respectively. EGFR, KRAS, BRAF, ALK and ROS1were commonly altered in NSCLC. Gastrointestinal tumours showed mutations in 63.6% with predominant alterations in pancreatic (88.2%), GIST (87.5%), colorectal (78.7%), cholangiocarcinoma (52.9%), neuroendocrine (45.5%), gall bladder (36.7%) and gastric adenocarcinomas (16.7%). The key genes affected were KRAS, NRAS, BRAF and PIK3CA. NGS evaluation identified co-occurring alterations in 37.7% cases otherwise missed by conventional assays. Resistance mutations were detected in progressive lung tumours (39.5%) against EGFR TKIs and ALK/ROS inhibitors. This is the largest Indian study on molecular profiling of solid tumours providing extensive information about mutational signatures using NGS.

SWOG 1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers.

LBA490 Background: Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Gemcitabine-based regimens are the standard of care in advanced disease, but median overall survival (OS) is roughly 12 months. The addition of albumin-bound paclitaxel to gemcitabine and cisplatin (GAP) demonstrated promising efficacy in a 60 patient, single-arm phase II study (Shroff et al, JAMA Oncol 2019), with observed median OS of 19.2 months. Methods: SWOG 1815 is a randomized, open-label, phase III trial comparing GAP to gemcitabine/cisplatin (GC). The study included newly diagnosed advanced BTC patients (pts), randomized 2:1 to GAP vs. GC. GAP included gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2 and albumin-bound paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. GC included standard dosing of gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of a 21-day cycle. Pts were treated until progression. The primary endpoint was overall survival (OS) with a target hazard ratio of 0.7 with 90% power and a 1-sided alpha of 0.025; randomization was stratified by disease site (intrahepatic cholangiocarcinoma [CCA] vs gallbladder adenocarcinoma [GBC] vs extrahepatic CCA), disease stage (locally advanced vs metastatic), and Zubrod PS 0 vs 1. Results: Of 441 eligible pts randomized, 55% were female. 67% of patients had intrahepatic CCA, 16% had GBC and 17% had extrahepatic CCA. Most pts had metastases (73%). Median OS with GAP vs. GC was 14 vs. 12.7 mo respectively (HR 0.93, 95% CI 0.74-1.19, p=0.58), ORR (confirmed and unconfirmed) 34% vs 25% (p=0.11) and median PFS 8.2 vs 6.4 mo (HR 0.92, 95% CI 0.72-1.16, p=0.47), respectively. Grade 3 and 4 treatment related adverse events (TRAEs) in ≥10% of pts for GAP and GC were anemia, neutropenia, and thrombocytopenia. GAP had more ≥ grade 3 hematologic AEs compared to the GC arm (60% vs. 45%, p=0.003). Discontinuation due to toxicity was at 24% vs 19% (p=0.26) with GAP vs GC. In exploratory subset analyses, GAP vs GC improved OS in pts with locally advanced disease (medians 19.2 vs 13.7 mo; HR 0.67, 95% CI 0.42-1.06, p=0.09) and in GBC pts (medians 17.0 vs 9.3 mo; HR 0.74, 95% CI 0.41-1.35, p=0.33). ORR for GAP vs GC in GBC was 50% vs 24% (p=0.09) and for locally advanced disease 28 vs 21% p=0.74. Conclusions: SWOG 1815 did not result in a statistically significant improvement in median OS with GAP vs. GC. The GAP regimen had higher rates of TRAEs without a statistically significant difference in discontinuation rates. Pts with locally advanced disease and GBC may benefit from the use of GAP. Further analyses are ongoing to understand potential benefit of GAP in subsets of BTC pts. Funding: NIH/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, and CA180868; and in part by Celgene Corporation, Summit, NJ (subsidiary of Bristol Myer Squibb). Clinical trial information: NCT#03768414 .

HISTOMORPHOLOGICAL STUDY OF CHOLECYSTECTOMIES IN A TERITIARY CARE CENTER

Introduction: Cholecystectomy is the most common surgical procedure performed for cholelithiasis (gall stones). Cholelithiasis is one of the most common gastro intestinal disorder worldwide. Usually asymptomatic, but commonly encountered symptoms may be right upper quadrant pain, dyspepsia and belching. The incidence of cholelithiasis is 2-4 times more in women than in men. The aim of the present study is to identify various morphological patterns and frequency of gall bladder lesions in cholecystectomy specimens. The Materials And Methods: present study was a cross sectional descriptive study of all cholecystectomy specimens received in the department of pathology, NRI Institute of Medical Sciences, Sangivalasa, Visakhapatnam, Andhra Pradesh; conducted over a period of 12 months from September 2021 to August 2022. The relevant and detailed clinical history were taken and processing was done in these specimens for histopathological examination. A total of 80 cholecystectomy specimens were rece Results: ived in the department. Out of which, 79 were inammatory gall bladder lesions and only one case was reported as malignancy. The most common age group affected were in 4th to 5th decade with female preponderance comprising of 47cases (58.75%) while the gall bladder carcinoma was reported in 72 years of age. Among the inammatory lesions, most common one was chronic cholecystitis comprising of 64 cases, 80.5% (63.6% associated with gall stones) were chronic cholecystitis, followed by 10 cases (12.5%) of acute cholecystitis (100% associated with gall stones), 2cases (2.5%) of polyps &amp; Adenomyomatosis each. Only one case (1.25%) of each Cholesterolosis &amp; gall bladder adenocarcinoma was reported. Chronic cholecystit Conclusion: is is the most common gall bladder disease for which cholecystectomies are being done. The present had reported various morphological patterns encountered in the cholecystectomy specimens received in the department.

Laparoscopic versus open oncological extended re-resection for incidental gallbladder adenocarcinoma: we can do more than T1/2.

The laparoscopic and open approaches have comparable safety and oncological efficacy to treat early (T1b or T2) stage incidental gallbladder cancer (IGBC). However, their effects on T3 stage or above tumors unclear. Data of IGBC patients who underwent radical re-resection were retrospectively analyzed. Demographic characteristics, surgical variables, and tumor characteristics were evaluated for association with survival. We analyzed retrospectively 201 patients (72 men, 129 women; median age 63years; range, 36-85years). 84 underwent laparoscopic re-resection and 117 underwent open surgery. The 5-year OS post-resection was 74.7%, with a median survival of 74.52months. The median OS (73.92months vs. 77.04months, P = 0.67), and disease-free survival (72.60months vs. 71.09months, P = 0.18) were comparable between the laparoscopic re-resection and open surgery groups. The survival of patients with T1/T2 (median: 85.50months vs. 80.14months; P = 0.67) and T3 (median: 68.56months vs. 58.85months; P = 0.36) disease were comparable between the open re-resection and laparoscopic re-resection groups even after PS matching. Open surgery group lost significantly more blood, while laparoscopic surgery took longer. The postsurgical stay in the laparoscopic re-resection group was significantly shorter. Combined extrahepatic bile duct resection, gallbladder perforation, pT, pStage, histological grade, microscopic liver invasion, status of the resected margin, and adjuvant therapy comprised significant independent prognostic indicators for IGBC. Laparoscopic and open surgery can achieve similar short and long-term outcomes for T3 IGBC; however, careful surgical manipulation is necessary to avoid secondary injuries.

Multiple Cutaneous Nodules as Clinical Harbinger of Gallbladder Adenocarcinoma: A Case Report

Introduction: Cutaneous metastasis is defined as invasion of the skin by malignant cells originating elsewhere in the body. Cutaneous metastasis of Adenocarcinoma gall bladder is extremely rare. The skin can be involved simultaneously or metachronously with the primary tumour. Cutaneous metastases may present as a clinical harbinger to an otherwise difficult to diagnose primary Adenocarcinoma gallbladder. Case presentation: A young male presented with multiple nodules on scalp, trunk and limbs along with fever, weight loss and lymphadenopathy. Histopathologic examination of the nodule revealed a malignant infiltrating glandular neoplasm in dermis, consistent with metastatic adenocarcinoma with intestinal metaplasia on immunohistochemistry. Radiological investigations further confirmed the primary tumour in gall bladder with metastases in liver and lymph nodes. Unfortunately, the patient succumbed to his disease. Discussion: Gallbladder adenocarcinoma is the most commonly seen tumour of the biliary tract. Skin involvement in malignancy helps determine the treatment course and has inevitable prognostic significance. Conclusion: We herein report multiple cutaneous nodules as a remote manifestation of gallbladder adenocarcinoma. Biopsy of the skin lesion was easy to perform and quite reliably guided us towards the diagnosis of the primary tumour which would have been very difficult to diagnose otherwise.