Vikram Chaudhari

Re-Operative Pancreaticoduodenectomy: Challenges and Outcomes

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.

ERBB2 and KRAS Alterations Mediate Response to EGFR Inhibitors in early stage Gallbladder Cancer

The uncommonness of gallbladder cancer has contributed to the generally poor understanding of the disease, with scant reports restricted to advance-stage tumors. Here, using an integrated analysis of whole exome and phospho-proteome, we show recurrent activating ERBB2 and KRAS somatic mutations are present in 6 and 3 of 44 early-stage rare gallbladder tumors, respectively. In vitro and in vivo cell-based and biochemical assays reveal an essential role of ErbB pathway activation for the survival of gallbladder cells. Interestingly, the genetic and pharmacological dependencies of gallbladder cells are dependent on the KRAS mutant allele status, reminiscent of the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer. In overall, we present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, leading to an early adoption of an approved treatment regimen for gallbladder cancer patients.

ERBB2 and KRAS Alterations Mediate Response to EGFR Inhibitors in Early Stage Gallbladder Cancer: A Promising Targeted Therapy in Gallbladder Cancer

The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho‐proteome array profiling indicates ERBB2 alterations in 40% early‐stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n = 25) and recurrent mutations in 14% tumors (n = 44); along with co‐occurring KRAS mutation in 7% tumors (n = 44). We demonstrate that ERBB2 heterodimerizes with EGFR to constitutively activate the ErbB signaling pathway in gallbladder cells. Consistent with this, treatment with ERBB2‐specific, EGFR‐specific shRNA or with a covalent EGFR family inhibitor Afatinib inhibits tumor‐associated characteristics of the gallbladder cancer cells. Furthermore, we observe an in vivo reduction in tumor size of gallbladder xenografts in response to Afatinib is paralleled by a reduction in the amounts of phospho‐ERK, in tumors harboring KRAS (G13D) mutation but not in KRAS (G12V) mutation, supporting an essential role of the ErbB pathway. In overall, besides implicating ERBB2 as an important therapeutic target under neo‐adjuvant or adjuvant settings, we present the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti‐EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti‐EGFR treatment in colorectal cancer.

Analysis of 50 cases of solid pseudopapillary tumor of pancreas: Aggressive surgical resection provides excellent outcomes

INTRODUCTION This study reports the clinicopathological characteristics and the perioperative and long-term treatment outcomes after aggressive surgical resection in solid pseudopapillary tumor (SPT) of the pancreas performed at a high volume center for pancreatic surgery in India. MATERIALS AND METHODS We analyzed a prospectively maintained database of the patients operated for SPT at Tata Memorial Hospital, India over a period of 11 years from February 2007 to February 2018. RESULTS Fifty consecutive patients operated for SPT, during the study period were included. The median age at presentation was 24 years. Majority of the patients (43/50) were female (86%). Disease was predominantly localized in the head and uncinate process of pancreas (66%). Median tumor size was 7.7 cm (Range 1.6-15 cm). Tumor extent was radiologically defined as borderline resectable or locally advanced in 48% (n = 24) patients. Forty-six major pancreatic resections were performed, which included 10 (21%) vascular resections, 2 synchronous liver metastasectomies, 1 multi visceral resection and 5 total pancreaticosplenectomies. Five of these resections were reoperations in patients deemed inoperable on exploration at other centers. R0 resection was achieved in 47 patients (98%). Postoperative major morbidity was 19% and there was no mortality. At a median follow-up of 29 months (Range, 1-121 months), all patients were alive without any recurrence. CONCLUSION Aggressive complete surgical resection of SPT achieves excellent long-term survival. Surgery, especially for large and borderline resectable tumors, can be potentially complex and should be performed at high-volume centers to provide the best chance of cure.

Extended anterolateral thigh pedicled flap for reconstruction of trochanteric and gluteal defects: A new & innovative approach for reconstruction

Descending branch of the lateral circumflex femoral artery (LCFA) is commonly used pedicle for anterolateral thigh (ALT) flap. Oblique branch of LCFA is an alternative pedicle that can be used in micro-vascular surgery. According to review of literature and to the best of our knowledge we could not find the use of oblique branch of LCFA as a pedicle of the ALT flap in regional soft tissue reconstruction. Here we presented a case of a 55-year-old man sustaining soft tissue injury and wound over the left trochanteric and gluteal region following a road traffic accident, who was treated by the use of extended ALT pedicle flap with oblique branch of LCFA as the pedicle for reconstruction of soft tissue defect in trochanteric and gluteal regions with successful outcome.