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Purpose: Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs., Methods: This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization-positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status., Results: From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001)., Conclusion: The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).

Purpose: To analyze diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder (GBC) and to establish its possible impact on post-recurrence survival., Method: FDG PET/CT studies of suspected recurrent GBC were retrospectively analyzed alongside tumor markers serum CEA and CA 19-9. Abnormal FDG-avid lesions and abnormal morphological lesions were considered positive for recurrence, and were categorized as isolated abdominal wall recurrence, loco-regional recurrence, and distant metastatic disease. Histopathology, definite progression on imaging and positive response to treatment was considered as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used as diagnostic performance parameters. Post-recurrence survival was calculated whenever appropriate follow-up was available, based on the abovementioned categories of sites of recurrence using survival curves and log-rank test., Results: Out of 117 PET/CT studies, 93 (79.5%) were positive and 24 (20.5%) were negative for recurrence. 86 out of 93 were true positive and 23 of 24 were true negative. PET/CT demonstrated sensitivity, specificity, PPV, NPV and accuracy of 98.8%, 76.7%, 92.5%, 95.8% and 93.1%, respectively. Diagnostic performance of PET/CT was significantly better than combination tumor markers. Of 66 cases with available follow-up, isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence demonstrated significantly higher post-recurrence survival as compared to distant metastasis; median survival being 39, 25 and 12 months, respectively., Conclusion: F-18 FDG PET/CT has better diagnostic performance than tumor markers combination. Isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence on PET/CT demonstrated better survival than non-regional metastatic disease. These results suggest a possible role of PET/CT as a surveillance modality, as well as a guide to therapeutic decision-making in cases of recurrent GBC., (© 2022. The Author(s) under exclusive licence to Japan Radiological Society.)

Background: Tata Memorial Centre (TMC) is a high-volume centre for pancreatic tumour resections. We found a continually increasing referral of pancreatic tumours for re-evaluation for surgery, after an initial unsuccessful attempt at resection., Aim: To evaluate reasons of initial in-operability, the feasibility of re-operative pancreatico-duodenectomy (R-PD) and short- and long-term outcomes after R-PD., Methods: Data was collected from a prospective database of GI and hepato-pancreato-biliary service, TMC, Mumbai from January 2008 to December 2016., Results: Forty patients with periampullary/pancreatic head tumours were referred to us after exploration. Thirty were planned for re-exploration, of whom 25 patients underwent successful R-PD, either upfront (n = 12) or after neo-adjuvant therapy (n = 13). Twenty were adenocarcinomas, 5 had other histologies. Majority of the patients were deemed inoperable in view of suspected vascular involvement at the time of initial surgery (68%). R0 resection was achieved in 90% of adenocarcinoma cases (n = 18). Postoperative major morbidity was 20% and mortality was 4% (n = 1). The estimated 1-, 2- and 5-year survival for those with adenocarcinoma was 83, 71.2, and 29.9% respectively., Conclusion: R-PD is safe and should be performed in experienced centres and can achieve long-term outcomes, comparable to conventional PD. The most common reason for denying resection at initial surgery was suspected or perceived vascular involvement., (© 2018 S. Karger AG, Basel.)

Purpose: Locally advanced (T3/T4) gallbladder cancers with large fixed portal nodes have a dismal prognosis. If undertaken, surgery entails extensive resections with high morbidity; therefore, in many centers, patients are offered palliative chemotherapy. In this prospective study, we used neoadjuvant concurrent chemoradiation with the intention of downstaging and facilitating R0 resection of these tumors., Patients and Methods: Twenty-eight patients with locally advanced carcinoma gallbladder (stage III, having deep liver infiltrations and/or large portal nodes) underwent prior positron emission tomography/computed tomography to rule out metastatic disease. All were treated with concomitant chemoradiation using helical tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor and 45 Gy over 25 fractions to the surrounding nodes) with injectable gemcitabine (300 mg/m(2)/week × 5 weeks)., Results: Of the 28 patients, 25 (89 %) successfully completed planned chemoradiation and 20 (71 %) achieved partial or complete radiologic response. Eighteen (64 %) patients were surgically explored, of whom 14 (56 %) achieved R0 resection. At the median follow-up of 37 months for the surviving patients, the median overall survival (OS) was 20 months for all patients. Only one patient recurred in the common bile duct postsurgery, whereas six patients had distant metastasis. The 5-year OS was 24 % for all patients and 47 % for patients with R0 resection. Biliary leak was seen in 6 (43 %) patients, of whom two required interventions., Conclusion: Locally advanced unresectable cancers may benefit from neoadjuvant chemoradiation to facilitate a curative resection with a good survival.

Background: The appropriate extent of gastric resection for patients with proximal third gastric cancer is controversial. This study addresses whether the choice of surgical strategy (proximal gastrectomy [PG] versus total gastrectomy [TG]) influences the outcomes for proximal third gastric adenocarcinoma., Materials and Methods: Review of prospective database at Tata Memorial Hospital from January 2010 to December 2012 identified 343 patients diagnosed and treated for gastric cancer. Of these, 75 underwent curative resections with D2 lymphadenectomy for proximal third gastric adenocarcinoma, which entailed proximal gastrectomy in 43 and total gastrectomy in 32 patients, depending on the epicenter of the primary and its relation with the mid-body of the stomach. Morbidity, lymph node yield, resection margins, patterns of recurrence, and survival were compared between these two groups., Results: 41/75 tumors were pT3 (23 cases [53.4 %] in the PG and 18 cases [56.3 %] in the TG group). Thirty-six patients [83.7 %] in PG and 29 patients [90.6 %] in TG group received neoadjuvant chemotherapy (NACT). There were no significant differences with regard to median blood loss, general complication rates and length of hospitalization between the two groups. The lymph node yield was comparable between the two procedures [PG = 14; TG = 15]. Positive proximal resection margin rates were comparable between the two groups [PG = 4.7 %; TG = 9.4 %], and there was no statistical difference observed in the distal resection margin positivity rates [PG = 4.7 %; TG = 3.1 %]. Regarding the patterns of recurrence, local recurrence in PG was 4.7 % and there was no local recurrence in the TG group (p = 0.08). Distant recurrence rates was dominant in TG [PG = 30.2 % versus TG = 53.1 %]. The overall 2-year survival following PG and TG was 73.8 and 49.9 %, respectively, and not statistically different (p = 0.10)., Conclusions: The extent of resection for proximal third gastric cancer does not influence the clinical outcome. PG and TG have similar survival rates. Both procedures can be accomplished safely. Therefore, PG should be an alternative to TG, even in locally advanced proximal gastric cancers treated by NACT, provided that the tumor size and location permit preservation of adequate remnant of stomach without compromising oncological resection margins. Future QOL studies would further lend credence to the concept of PG for proximal third gastric cancer.

Background: The perioperative use of epirubicin, cisplatin, and fluorouracil (ECF) significantly improves outcomes in patients with gastric and gastro-oesophageal (GO) cancers but is cumbersome to administer. Given the equivalence of epirubicin, oxaliplatin, and capectabine (EOX) with ECF in advanced setting, we analyzed the compliance, efficacy, and toxicity of perioperative EOX in resectable but locally advanced cancers., Methods: This is a retrospective analysis of prospectively maintained database of patients treated between January 2012 and September 2013 at Tata Memorial Centre. Patients were planned to receive 3# of neoadjuvant (NA) and 3# of adjuvant EOX (intravenous epirubicin 50 mg/m 2 D1, oxaliplatin 130 mg/m 2 , on D1, capecitabiine 1250 mg/m 2 D1-21) every 21 days. On completion of NA therapy, patients were planned to undergo gastrectomy and D2 lymphadenectomy., Results: A total of 99 patients (76% males, median age 51 years) were treated with perioperative EOX. Preoperatively, 93% patients completed EOX. Post-NA chemotherapy, 4 patients progressed, 1 patient died and 94 were taken up for surgery. Of these, 9 were inoperable and 85 patients underwent radical surgery. Of these, 71% (60/85) were able to complete three cycles of adjuvant EOX. The compliance to complete all 6 cycles of perioperative chemotherapy was 64%. Grade 3 and 4 toxicities were comparable to the MAGIC dataset apart from higher number of diarrhea in our patients., Conclusions: In patients with resectable GO adenocarcinoma, it is possible to deliver the MAGIC-type perioperative chemotherapy with EOX with better compliance, toxicity, and efficacy rates.

Background: The incidence of rectal cancer in young Indians is increasing. Recent evidence suggests a probable existence of noncanonical tumorigenesis pathways in early-onset colorectal cancer patients in India. The aim of the study was to evaluate rectal cancer outcomes in patients ≤40 years with those >40 years., Methods: An analysis of a prospective database of surgically treated rectal cancer patients ≤40 years (group 1) and those >40 years (group 2) over 2 years was performed. Clinicopathological features, perioperative outcomes, and disease-free survival (DFS) were analyzed., Results: Of the 512 patients with colorectal cancer treated surgically, 237 patients (group 1-57 patients; group 2-180 patients) were diagnosed with nonmetastatic rectal adenocarcinoma. Patients in group 1 were more likely to present with locally advanced (stage III) disease (p < 0.005) resulting in a higher proportion of them receiving neoadjuvant chemoradiotherapy (NACT-RT). There was no difference in morbidity and mortality between the two groups. Younger patients had a significantly higher median total and positive lymph node yield (p < 0.003). Patients in group 1 had a significantly lower overall DFS (p < 0.005). Stage-specific DFS also demonstrated a significantly lower trend in stage III patients in group 1., Conclusions: Young rectal cancer patients in India tended to present more frequently with locally advanced tumors resulting in a higher proportion being treated with NACT-RT. Stapled rectal anastomoses could be performed safely in young patients even after NACT-RT. The significantly poorer DFS in young Indian patients with stage III disease was a novel finding and merits further investigation into tumor biology.

Background: Patients with locally advanced resectable gastric cancers are increasingly offered neoadjuvant chemotherapy (NACT) following the MAGIC and REAL-2 trials. However, information on the toxicity of NACT, its effects on perioperative surgical outcomes and tumor response is not widely reported in literature., Methods: Analysis of a prospective database of gastric cancer patients undergoing radical D2 gastrectomy over 2 years was performed. Chemotherapy-related toxicity, perioperative outcomes and histopathological responses to NACT were analyzed. The data is presented and compared to a cohort of patients undergoing upfront surgery in the same time period., Results: In this study, 139 patients (42 female and 97 male patients, median age 53 years) with gastric adenocarcinoma received NACT. Chemotherapy-related toxicity was noted in 32% of patients. Of the 139 patients, 129 underwent gastrectomy with D2 lymphadenectomy, with 12% morbidity and no mortality. Major pathological response of primary tumor was noted in 22 patients (17%). Of these 22 patients, lymph node metastases were noted in 12 patients. The median blood loss and lymph node yield was not significantly different to the 62 patients who underwent upfront surgery. Patients who underwent upfront surgery were older (58 vs. 52 years, P <0.02), had a higher number of distal cancers (63% vs. 82%, P <0.015) and a longer hospital stay (11 vs. 9 days, P <0.001)., Conclusions: Perioperative outcomes of gastrectomy with D2 lymphadenectomy for locally advanced, resectable gastric cancer were not influenced by NACT. The number of lymph nodes harvested was unaltered by NACT but, more pertinently, metastases to lymph nodes were noted even in patients with a major pathological response of the primary tumor. D2 lymphadenectomy should be performed in all patients irrespective of the degree of response to NACT.

Laparoscopic cholecystectomy may result in spillage of gall bladder contents during dissection or delivery of gall bladder through the umbilical port. We report a 50-year-old man who underwent laparoscopic cholecystectomy for suspected calculous cholecystitis. Histology showed a single focus of adenocarcinoma in the gall bladder. There was spillage of gall bladder contents at the umbilical port during delivery. Six months later, he developed adenocarcinoma at the port site. This was treated by wide excision.