Mahesh Goel

Evolution of pancreatoduodenectomy in a tertiary cancer center in India: Improved results from service reconfiguration

BACKGROUND Pancreatic cancer incidence in India is low. Over the years, refinements in technique of pancreatoduodenectomy (PD) may have improved outcomes. No data is available from India, South-Central, or South West Asia to assess the impact of these refinements. PURPOSE To assess the impact of service reconfiguration and standardized protocols on outcomes of PD in a tertiary cancer center in India. METHODS Three specific time periods marking major shifts in practice and performance of PD were identified, viz. periods A (1992-2001; pancreaticogastrostomy predominantly performed), B (2003-July 2009; standardization of pancreaticojejunal anastomosis), and C (August 2009-December 2011; introduction of neoadjuvant chemo-radiotherapy and increased surgical volume). RESULTS 500 PDs were performed with a morbidity and mortality rate of 33% and 5.4%, respectively. Over the three periods, volume of cases/year significantly increased from 16 to 60 (p < 0.0001). Overall incidence of post-operative pancreatic anastomotic leak/fistula (POPF), hemorrhage, delayed gastric emptying (DGE), and bile leak was 11%, 6%, 3.4%, and 3.2%, respectively. The overall morbidity rates, as well as, the above individual complications significantly reduced from period A to B (p < 0.01) with no statistical difference between periods B and C. CONCLUSION Evolution of practice and perioperative management of PD for pancreatic cancer at our center improved perioperative outcomes and helped sustain the improvements despite increasing surgical volume. By adopting standardized practices and gradually improving experience, countries with low incidence of pancreatic cancer and resource constraints can achieve outcomes comparable to high-incidence, developed nations. SYNOPSIS The manuscript represents the largest series on perioperative outcomes for pancreatoduodenectomy from South West and South-Central Asia - a region with a low incidence of pancreatic cancer and a disproportionate distribution of resources highlighting the impact of high volumes, standardization and service reconfiguration.

IL17 producing γδT cells induce angiogenesis and are associated with poor survival in gallbladder cancer patients

Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCRγδ+ (Tγδ17), CD4+ (Th17), CD8+ (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC. Analysis by multi‐color flow cytometry revealed that compared to healthy individuals (HI), Tγδ17, Th17 and Tc17 cells were increased in peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of GBC patients. Tregs were decreased in PBMCs but increased in TILs of GBC patients. The suppressive potential of Tregs from GBC patients and HI were comparable. Serum cytokines profile of GBC patients showed elevated levels of cytokines (IL6, IL23 and IL1β) required for polarization and/or stabilization of IL17 producing cells. We demonstrated that Tγδ17 cells migrate toward tumor bed using CXCL9‐CXCR3 axis. IL17 secreted by Tγδ17 induced productions of vascular endothelial growth factor and other angiogenesis related factors in GBC cells. Tγδ17 cells promote vasculogenesis as studied by chick chorioallantoic membrane assay. Survival analysis showed that Tγδ17, Th17 and Treg cells in peripheral blood were associated with poor survival of GBC patients. Our findings suggest that Tγδ17 is a protumorigenic subtype of γδT cells which induces angiogenesis. Tγδ17 may be considered as a predictive biomarker in GBC thus opening avenues for targeted therapies.

D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

BackgroundPatients 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.MethodsAnalysis 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.ResultsIn 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).ConclusionsPerioperative 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.

Post-operative abdominal drainage following major upper gastrointestinal surgery: Single drain versus two drains

BACKGROUND Traditionally, surgeons have resorted to placing drains following major gastrointestinal surgery. In recent years, the value of routine drainage has been questioned, especially in the light of their role in post-operative pain, infection, and prolonged hospital stay. The aim of this study was to compare the peri-operative outcomes following the use of a single versus two drains for gastric and pancreatic resections. MATERIALS AND METHODS Patients undergoing resections for gastric and pancreatic malignancies were included in the study. Patients were subdivided into two groups depending on the number of drains placed, viz. one drain (Group 1) or two drains (Group 2). Clinico-pathologic outcomes were recorded and compared. RESULTS Of the 285 patients included in the analysis, group 1 consisted of 226 patients while group 2 included 59 patients. Overall, drains alerted the surgeon to existence of complications in 62% of patients - 70% in group 1 and 44.4% in group 2 (P < 0.19). The morbidity and mortality rates in groups 1 and 2 were 25.2% and 3.9%, and 23.7% and 0%, respectively (P < 0.61 and P < 0.12). There were no drain-related complications. Median hospital stay was significantly lower in group 1 (11 vs. 14 days) (P < 0.001). CONCLUSION The insertion of drains did aid in the detection of complications following gastric and pancreatic surgery. Two drains offer no further advantage over one drain in terms of detection of complications. While the number of drains did not contribute to, or reduce, the morbidity and mortality in the two groups, the use of one drain significantly reduced hospital stay. Taken together, these findings support the prophylactic insertion of a single intra-abdominal drain following gastric and pancreatic resections.

Neoadjuvant chemotherapy in patients with locally advanced gallbladder cancer

AIM Surgery is the only curative option for patients with gallbladder cancer (GBC). This study looks at the outcome of patients treated with neoadjuvant chemotherapy (NACT). PATIENTS & METHODS This is retrospective analysis of the prospectively maintained database of patients with locally advanced GBC treated between February 2009 and September 2013 with NACT. Patients received gemcitabine-platinum based regimen. RESULTS A total of 37 patients (median age: 54 years, 64.9% females) received NACT. Overall response rate was 67.5%. In total, 17 patients (46%) underwent R0 resection. Median overall survival/progression-free survival of the whole group was 13.4/8.1 months, respectively. Patients who underwent surgery had a significantly better overall survival (median not reached vs 9.5 months) and progression-free survival (25.8 vs 5.6 months), respectively. CONCLUSION NACT increases resectability and survival in patients with locally advanced GBC.

Epirubicin, oxaliplatin, and capectabine is just as "MAGIC"al as epirubicin, cisplatin, and fluorouracil perioperative chemotherapy for resectable locally advanced gastro-oesophageal 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.

Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study.

PurposeThis trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone.Materials and methodsPatients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery.ResultsA total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03).ConclusionEscalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

Down-staging following neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: Does timing of surgery really matter?

Background: Neoadjuvant chemoradiotherapy (NACTRT) improves local recurrence rate in locally advanced (LA) rectal cancer with no survival benefit. Pathological complete response (pCR) post-NACTRT is associated with improved outcome. Debate is ongoing as to when would be the opportune time to operate. Aim: To determine if greater down-staging can be achieved by a longer time interval from NACTRT to surgery (tumor regression score [TRS]) and whether this would impact sphincter saving surgery rates and early relapse rates. Materials and Methods: A retrospective analysis of a prospectively maintained database of patients with LA rectal adenocarcinoma treated from January 2012 to August 2013 was carried out. One hundred and ten patients who completed NACTRT (50 Gy/25 fractions with capecitabine 825 mg/m2 twice daily) followed by surgical resection were included. For response evaluation patients were divided into two groups, Group 1 (TRS ≤60 days, n = 42) and 2 (TRS >60 days, n = 68). Tumor down-staging, pCR rate, tumor regression grade (TRG) post-NACTRT and relapse rates were correlated with TRS. Results: Of 110 patients (median age: 49 years (21-73), 71% males; 18 (16.5%) with signet ring histology) 96% patients underwent an R0 resection. Post-NACTRT, CR was attained in 5 (4.5%), partial response in 98 (89%) and stable disease in 7 (6.4%) patients. Median time from completion of NACTRT to surgery was 64.5 days (6-474). Median lymph nodes harvested were 10 (1-50). Overall, 22 (20%) patients achieved pCR. 26 (62%) patients in Group 1 compared to 36 (53%) in Group 2 underwent sphincter sparing surgery (SSS) (P = 0.357). Six patients (14%) in Group 1 and 16 (24%) in Group 2 achieved pCR (P = 0.24). Median TRG in both groups was three. Conclusion: Timing of surgery following NACTRT for LA rectal cancer does not influence pathological response, ability to perform SSS or disease-free survival. There is no incremental benefit of delaying the surgery though this needs to be confirmed in a prospective randomized trial.

Pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (pancreatic NETs) are rare, low- to intermediate-grade neoplasms thought to arise from the pancreatic islets. Recent advances in pathology and our understanding of the biological behavior of this group of tumors has resulted in changes in their nomenclature and how we treat them. This review puts into perspective our current understanding of pancreatic NETs in terms of their incidence, pathology, and management.

Complications as indicators of quality assurance after 401 consecutive colorectal cancer resections: the importance of surgeon volume in developing colorectal cancer units in India

BackgroundThe low incidence of colorectal cancer in India, coupled with absence of specialized units, contribute to lack of relevant data arising from the subcontinent. We evaluated the data of the senior author to better define the requirements that would enable development of specialized units in a country where colorectal cancer burden is increasing.MethodsWe retrospectively analyzed data of 401 consecutive colorectal resections from a prospective database of the senior author. In addition to patient demographics and types of resections, perioperative data like intraoperative blood loss, duration of surgery, complications, re-operation rates and hospital stay were recorded and analyzed.ResultsThe median age was 52 years (10-86 years). 279 were males and 122 were females. The average duration of surgery was 220.32 minutes (range 50 - 480 min). The overall complication rate was 12.2% (49/401) with a 1.2% (5/401) mortality rate. The patients having complications had an increase in their median hospital stay (from 10.5 days to 23.4 days) and the re-operation rate in them was 51%. The major complications were anastomotic leaks (2.5%) and stoma related complications (2.7%).ConclusionsThis largest ever series from India compares favorably with global standards. In a nation where colorectal cancer is on the rise, it is imperative that high volume centers develop specialized units to train future specialist colorectal surgeons. This would ensure improved quality assurance and delivery of health care even to outreach, low volume centers.