Developments in pancreatic cancer surgery.

Pancreatic cancer surgery, with one of the worst prognoses in oncology, is a challenge to the surgical community. Centralization of pancreatic surgery has led to the foundation of high-volume centers, thereby greatly facilitating the successful performance of more radical approaches. This review spotlights on recent advances in surgical approaches to pancreatic cancer and the risks and benefits of vascular reconstruction to improve resectability. Surgery being the only modality to achieve cure, multivisceral and vascular resections are being incorporated to improve dismal operability rates of < 10%. Great leaps have been made in neoadjuvant and adjuvant treatment, as targeted and specific chemotherapeutic agents are being continually added. The concept of borderline and locally advanced pancreatic tumors and the use of neoadjuvant chemorad has extended the indications of oncological resection in such tumors. Venous resections are being routinely performed so as to facilitate en bloc removal of tumors, while arterial resections, owing to the increased morbidity and mortality, are offered to highly selective cases. New techniques like the triangle operation and periarterial divestment have opened new viable surgical options. Although laparoscopic approach is time consuming, it offers reduced operative blood loss and a shortened hospital stay at specialized centers. Robotic surgery may produce better results in patients needing vascular resection and reconstruction, but the expenses involved and limited availability are major deterrents. Advanced techniques of surgical resection and vessel reconstruction provide a repository for curative-intent surgery in borderline resectable and locally advanced pancreatic cancer.

Impact of Covid-19 on gastrointestinal cancer surgery: A National Survey.

PURPOSE: To understand the actual impact of the Covid-19 pandemic and frame the future strategies, we conducted a pan India survey to study the impact on the surgical management of gastrointestinal cancers. METHODS: A national multicentre survey in the form of a questionnaire from 16 tertiary care gastrointestinal oncology centres across India was conducted from January 2019 to June 2021 that was divided into a 15-month pre-Covid era and a similar period of active Covid pandemic era. RESULTS: There was significant disruption of services; 13 (81%) centres worked as dedicated Covid care centres and 43% reported suspension of essential care for more than 6 months. In active Covid phase, there was a 14.5% decrease in registrations and proportion of decrease was highest in the centres from South zone (22%). There was decrease in resections across all organ systems; maximum reduction was noted in hepatic resections (33%) followed by oesophageal and gastric resections (31 and 25% respectively). There was minimal decrease in colorectal resections (5%). A total of 584 (7.1%) patients had either active Covid-19 infection or developed infection in the post-operative period or had recovered from Covid-19 infection. Only 3 (18%) centres reported higher morbidity, while the rest of the centres reported similar or lower morbidity rates when compared to pre-Covid phase; however, 6 (37%) centres reported slightly higher mortality in the active Covid phase. CONCLUSION: Covid-19 pandemic resulted in significant reduction in new cancer registrations and elective gastrointestinal cancer surgeries. Perioperative morbidity remained similar despite 7.1% perioperative Covid 19 exposure.

Evaluation of biomarkers, genetic mutations, and epigenetic modifications in early diagnosis of pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is one of the deadliest malignancies with an alarming mortality rate. Despite significant advancement in diagnostics and therapeutics, early diagnosis remains elusive causing poor prognosis, marred by mutations and epigenetic modifications in key genes which contribute to disease progression. AIM: To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley. METHODS: A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9 (CA 19-9), tissue polypeptide specific antigen (TPS), carcinoembryonic antigen (CEA), vascular endothelial growth factor-A (VEGF-A), and epidermal growth factor receptor (EGFR). Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma (KRAS), Breast cancer type 2 (BRCA-2), and deleted in pancreatic cancer-4 (DPC-4) genes. However, epigenetic modifications (methylation of CpG islands) were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A (p16; CDKN2A), MutL homolog 1 (hMLH1), and Ras association domain-containing protein 1(RASSF1A) genes. RESULTS: We found significantly elevated levels of biological markers CA 19-9 (P ≤ 0.05), TPS (P ≤ 0.05), CEA (P ≤ 0.001), and VEGF (P ≤ 0.001). Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12 (16 subjects, P ≤ 0.05), and 13 (12 subjects, P ≤ 0.05). However, we did not find a mutation in DPC-4 (1203G > T) and BRCA-2 (617delT) genes. Furthermore, epigenetic modification revealed that CpG methylation in 21 (P ≤ 0.05) and 4 subjects in the promoter regions of the p16 and hMLH1 gene, respectively. CONCLUSION: In conclusion, CA 19-9, TPS, CEA, and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC. Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC. Additionally, methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.

The effectiveness of image-guided percutaneous catheter drainage in the management of acute pancreatitis-associated pancreatic collections.

PURPOSE: Acute pancreatitis is commonly complicated by the development of pancreatic collections (PCs). Symptomatic PCs warrant drainage, and the available options include percutaneous, endoscopic, and open surgical approaches. The study aimed to assess the therapeutic effectiveness and safety of image guided percutaneous catheter drainage (PCD) in the management of acute pancreatitis related PCs. MATERIAL AND METHODS: This was a single-centre prospective study covering a 4-year study period. Acute pancreatitisrelated PCs complicated by secondary infection or those producing symptoms due to pressure effect on surrounding structures were enrolled and underwent ultrasound or computed tomography (CT)-guided PCD. The patients were followed to assess the success of PCD (defined as clinical, radiological improvement, and the avoidance of surgery) and any PCD-related complications. RESULTS: The study included 60 patients (60% males) with a mean age of 43.1 ± 21.2 years. PCD recorded a success rate of 80% (16/20) for acute peripancreatic fluid collections (APFC) and pancreatic pseudocysts (PPs), 75% (12/16) for walled-off necrosis (WON), and 50% (12/24) for acute necrotic collections (ANCs). Post-PCD surgery (necrosectomy ± distal pancreatectomy) was needed in 50% of ANC and 25% of WON. Only 20% of APFCs/PPs patients required surgical/endoscopic treatment post-PCD. Minor procedure-related complications were seen in 4 (6.6%) patients. CONCLUSION: PCD is an effective, safe, and minimally invasive therapeutic modality with a good success rate in the management of infected/symptomatic PCs.

Sonic Hedgehog Protein is Frequently Up-Regulated in Pancreatic Cancer Compared to Colorectal Cancer.

Sonic hedgehog (SHH) is a secreted protein which functions in autocrine or paracrine fashion on target cells to activate hedgehog (HH) signalling cascade responsible for growth and proliferation. This study is an attempt to understand the expression dynamics of SHH protein in colon, rectal and pancreatic cancers. Protein expression of SHH was studied by Western Blotting in the histologically confirmed colon, rectum and pancreatic cancer tissue samples along with their adjacent normal tissues. Only 31.4% (11 of 35) and 26.9% (7 of 26) of colon and rectal cancer cases respectively showed an increase in SHH expression in tumours compared to 72.7% (24 of 33) of the pancreatic cancer cases when compared with their adjacent normal tissues. Our results suggest that SHH may have a strong role in the predisposition of Pancreatic cancer and could possibly be used as a diagnostic or prognostic biomarker.

Nuclear localization and Overexpression of Smoothened in Pancreatic and Colorectal Cancers.

Smoothened (SMO) is a significant signalling protein which functions as a key transducer for the hedgehog signalling pathway, an important signalling mechanism with key roles in development and oncogenesis. The correlation of expression dynamics of SMO with pancreatic and colorectal cancer genesis has been known but with ambiguity. Therefore, in this study, we investigated messenger RNA (mRNA) and protein expression of SMO in pancreatic and colorectal cancers in our population and assessed relationship with various clinicopathological parameters. Surgically resected tumour and adjacent histologically normal tissues from 33 and 61 pancreatic and colorectal cancer patients were investigated in the present study. Expression of SMO was analysed by quantitative real-time polymerase chain reaction and immunohistochemistry. At mRNA level, SMO was overexpressed in 72.72% (24 of 33) and 50.81% (31 of 61) of the pancreatic and colorectal cancer cases as compared with their adjacent normal tissues. SMO immunohistochemical analysis revealed nuclear localization and overexpression was observed in 51.51% (17 of 33) and 40.98% (25 of 61) of pancreatic and colorectal cancer tissues. SMO overexpression was significantly associated with smoking, late-stage disease and lymph node metastasis in patients with Colorectal cancer. Our results showed that SMO is dysregulated in pancreatic and colorectal cancers and may be considered as a target in cancer therapeutics.

Impact of centralization of pancreaticoduodenectomy coupled with fast track recovery protocol: a comparative study from India.

BACKGROUND: Fast track strategy in the management of patients undergoing intra-abdominal surgery of various types has emerged as a landmark approach to reduce surgical stress and accelerate recovery. This study was to evaluate the effect of fast track strategy on patients subjected to pancreaticoduodenectomy (PD) from an individual unit during transit from low to a high volume center. METHODS: A total of 142 PD patients who had been subjected to fast track strategy between June 2008 and September 2012 were compared with 46 patients who had received conventional surgery between January 2006 and May 2008. Comparative analysis was made of postoperative complications, postoperative recovery, length of hospital stay and patient readmission requirement. RESULTS: The patients subjected to fast track strategy had a faster recovery and a shorter hospital stay than those who were treated conventionally (7.8 vs 12.1 days). The intraoperative events like operative blood loss (417.9+/-83.8 vs 997.4+/-151.8 mL, P<0.001), blood transfused (a median of 0 vs 1 unit, P<0.001) and operative time taken (125 vs 245 minutes, P<0.001) were significantly lower in the fast track group. The frequency of pancreatic fistula (4.9% vs 13.0%) and delayed gastric emptying (7.0% vs 17.4%) was also significantly reduced with fast track treatment. Nevertheless, the readmission rate (11.3% vs 6.5%) was found relatively higher within the fast track group. However, increased readmission rates in this study seem to be independent of fast track protocol. CONCLUSIONS: This preliminary analysis suggests that the fast track approach might be beneficial to the well-being of the patients after PD, for it accelerates the immediate clinical recovery of patients and significantly shortens their length of hospital stay.

Pancreaticoduodenectomy: A study from India on the impact of evolution from a low to a high volume unit.

AIM: To analyse the impact of turning of our department from a low to a high volume provider of pancreaticoduodenectomy (PD) on surgical outcome. METHODS: A retrospective collection of data was done for patients who underwent PD. According to the number of PDs undertaken per year, we categorized the volume into low volume (< 10 PDs/year), medium volume (10-24 PDs/year) and high volume (> 25 PDs/year) groups. RESULTS: From 2002 to 2013, 200 patients underwent PD. The annual number of PD increased from 4 in 2002 to 34 in 2013. The mean operative time, operative blood loss and need for intraoperative blood transfusion decreased considerably over the volume categories (P < 0.001, P < 0.001 and P < 0.001, respectively). Increased procedural volume was associated with a lower morbidity (P = 0.021) and shorter length of hospital stay (P < 0.001). Similarly the rate of mortality dropped from 10% for the low volume group to 2.2% for the medium volume group and 0.0% for the high volume group (P = 0.007). CONCLUSION: The transformation from a low volume to a high volume provider of PD resulted in most favourable outcomes favouring the continued centralization of this high risk procedure.

Omental flaps reduces complications after pancreaticoduodenectomy.

BACKGROUND: Major complications after pancreaticoduodenectomy are usually caused by a leaking pancreaticojejunal anastomosis. Omental flaps around various anastomoses were used to prevent the formation of fistula. METHODS: We reviewed 147 patients who had undergone pancreaticoduodenectomy between March 2006 and March 2012. The patients were divided into 2 groups according to the application of omental flaps around various anastomoses: group A (101 patients) who underwent omental wrapping procedure; group B (46 patients) who did not undergo the omental wrapping procedure. Perioperative data of the two groups were reviewed to assess the effectiveness of omental flap procedure in the prevention of pancreatic fistula and other complications. RESULTS: No differences were observed in the clinical characteristics between the 2 groups. The incidences of pancreatic fistula (4.0% vs 17.4%), post-pancreatectomy hemorrhage (0 vs 6.5%), biliary fistula (1.0% vs 13.0%), and delayed gastric emptying (4.0% vs 17.4%) were significantly less frequent in group A. The overall morbidity (18.8% vs 47.8%) and hospital stay (8.3 vs 9.6 days) were also significantly lower in group A than in group B. CONCLUSIONS: Omental flaps around various anastomoses after pancreaticoduodenectomy can reduce the incidences of pancreatic fistula, biliary fistula, post-pancreatectomy hemorrhage and delayed gastric emptying. This procedure is simple and effective to reduce the overall morbidity after pancreaticoduodenectomy.

A selective approach to the surgical management of periampullary cancer patients and its outcome.

BACKGROUND: Pancreaticoduodenectomy is a high risk, complex, technically challenging operation associated with significant perioperative morbidity and mortality. This study on the surgical management of periampullary cancer patients is based on our experience in a period of nearly 13 years. METHODS: The study was conducted on two groups of patients: group A included 42 patients who were treated between January 2000 and September 2005 and group B included 134 patients who were treated between October 2005 to October 2012. Preoperative, intraoperative and postoperative details of all these patients were collected, tabulated and analyzed to assess the impact of the selective approach introduced in the department with effect from October 2005. RESULTS: Intraoperative details revealed highly significant differences in the management of the two groups of patients in respect of operative time (250.4 vs 126.6 minutes; P<0.001), operative blood loss (1070.2 vs 414.9 mL; P<0.001) and intraoperative blood transfusion (1.4 vs 0.2 units; P<0.001). Variations between the two groups in the frequency of complications were found to be statistically insignificant. However, the difference between the two groups in the overall morbidity of patients (47.6% vs 26.1%; P=0.009) and the length of their hospital stay (11.8 vs 7.8 days; P<0.001) were significant. CONCLUSION: A selective approach applied to the surgical management of periampullary cancer patients is a step in the right direction.

Comparative efficacy of 5flourouracil/calcium leucovorine versus 5flourouracil/calcium leucovorine plus oxaliplatin in the adjuvant treatment of colonic carcinoma in Kashmir.

AIM: This prospective, randomized comparative study conducted in Kashmir evaluated the clinical profile of colonic carcinoma and the efficacy, side effects and survival advantage of adjuvant treatment with 5FU/CLV versus FOLFOX7. MATERIALS AND METHODS: Between 2007 and 2009, the clinical profiles of 50 patients enrolled and randomized equally into Arm A receiving 5FU/CLV alone (Mayo Clinic Regimen) and Arm B receiving the FOLFOX7 regimen (including oxaliplatin) were evaluated. RESULTS: Majority of the patients were in the 5(th) and 6(th) decade of life (males 70% versus females 30%), and most were from urban dwellings. Consumption of red meat, obesity and physical inactivity were common risk factors. A family history of colonic carcinoma was reported in 12% of the patients. Event-free and disease-free survival for the two arms were: Arm A - 12.8 ± 5 months and 14.2 ± 6 months; Arm B - 13.0 ± 6.7 months and 13.1 ± 6 months, respectively. Treatment-related morbidity was significant in Arm B whereas general well being and surrogate laboratory markers including a hemogram, favored Arm A. CONCLUSION: The clinical profile, risk factors and familial predisposition of Kashmiri colonic carcinoma patients matches that of colon cancer patients elsewhere. There was no added survival advantage by adding oxaliplatin to 5FU and CLV. Although the interim results showed that the Mayo Clinic Regimen has a better total survival advantage compared with the FOLFOX7 regimen, the results were not statistically significant. The Mayo Clinic Regimen was better than the FOLFOX7 regimen in terms of the toxicity profile. However, this finding needs to be studied further. The main idea of conducting this study was to reveal that there is no added advantage of adding oxaliplatin to 5FU and CLV, thereby (a) reducing the toxicity (b) and lowering cost of therapy.

Concomitant Rupture of Hydatid Cyst of Liver in Hepatic Duct and Gallbladder: Case Report.

Hydatid cyst liver rupture into the biliary tree may involve the common hepatic duct, lobar biliary branches, the small intrahepatic bile ducts or rarely the gallbladder. Rupture can be occult or frank. A frank intrabiliary rupture of hepatic hydatid cyst is a rare but serious event. The authors are reporting a case of concomitant rupture of hydatid cyst of liver into right hepatic duct and the gallbladder. A 50-year-old female patient who presented with acute cholangitis was confirmed as a case of intrabilary rupture on ultrasonography, endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography. Rupture of hydatid cyst of liver in right hepatic and the gallbladder was confirmed on surgery. Suture repair of cystobiliary fistula, choledochoduodenostomy with cholecystectomy was done.

Choledochal cysts in children and adults with contrasting profiles: 11-year experience at a tertiary care center in Kashmir.

BACKGROUND: Choledochal cyst is a surgical problem usually related to infancy and childhood. Despite advancements in management, a large number of cases still present during adulthood. The clinical course and outcome in children varies from that in adults. This study focuses on these variations in terms of presentation, management, histopathology, and outcome. METHODS: An in-depth retrospective analysis was carried out on 79 patients presenting with choledochal cysts between December 2007 and January 1997. The patients were segregated into two groups: group A comprising 32 children and group B with 47 adults. The presentation, clinical evaluation, radiologic, and biochemical findings; operative details; pathologic findings; and early and long-term complications in the two groups were studied on a comparative basis. RESULTS: The male/female ratios were 1:3 and 1.0:2.3 in groups A and B, respectively. A history of previous biliary surgery, pancreatitis, cholangitis, peroperative difficulties, and early and late postoperative complications were 5.1, 5.4, 6.4, 5.4, 2.0, and 3.3 times more common in group B than in group A. However, the classic triad of jaundice, abdominal pain, and a mass was 6.7 times more common in group A than in group B. The classic triad and cholangitis were the only parameters that were statistically significant. Rare presentations of spontaneous perforation of the cyst or cachexia manifested only in group A patients. The methods of detection and operative treatment were identical for both groups. Histologically, fibrosis of the cyst wall was a feature peculiar to group A, whereas signs of inflammation and hyperplasia were predominantly seen in group B. In the group B series, one patient had cholangiocarcinoma and another gallbladder carcinoma; one more patient developed malignancy during follow-up. Long-term complications were seen in 29.7% of patients in group B versus 9.3% in group A; the most rampant complication was a type IVa cyst, seen in 68.7% of patients. CONCLUSIONS: Choledochal cysts present differently in adults and children; whereas children present with the classic triad, adults present with common biliary or infective complications. Although the methods of detection and surgical treatment are similar for the two groups, the type IVa cyst typically seen in the adult group creates a marked deviation with respect to long-term complications such as ascending cholangitis, anastomotic strictures, stone formation, and development of cholangiocarcinoma. These are areas of grave concern that can be addressed to a large extent by providing an access loop during the initial surgery especially for type IVa cysts. The glaring differences in terms of presentation, histologic picture, and outcome urges us to consider choledochal cysts in children as a separate entity.

Central pancreatectomy: a new technique for resection of selected pancreatic tumors.

BACKGROUND: Pancreatic tumors located in the neck region usually require pancreaticoduodenectomy or splenopancreatectomy. For small benign tumors enucleation is not usually feasible due to their size and localization; then pancreatectomy is often needed. Central pancreatectomy consists of a limited resection of the midportion of the pancreas and can be offered in benign and low-grade malignant tumors of the neck of the pancreas. The study aimed to evaluate whether central pancreatectomy has a place in pancreatic surgery. METHODS: In this study, which covered a period of 14 months, we performed central pancreatectomy in four selected patients. Preoperative evaluation and operative frozen section biopsy in indicated cases allowed proper selection for the procedure. Operative details, complications and follow-up were recorded. RESULTS: Four patients, two with serous cystadenoma, and one with an islet cell tumor, and one with a hydatid cyst, were identified for the procedure. The mean tumor size was 3 cm, the mean operative time was 217.5 minutes, and the mean blood loss was 382.5 ml. There was no morbidity or mortality in this series. No endocrine or exocrine deficiency was observed in any patient during a mean follow-up of 22.7 months. CONCLUSIONS: Central pancreatectomy is a procedure that offers excellent results in benign and low-grade malignant tumors. It preserves functional elements (endocrine and exocrine) of the pancreas and also eliminates the infective and hematological effects of splenectomy. Thus, central pancreatectomy should be included in the armamentarium of pancreatic surgery, and in order to obtain good results, proper indications and adequate experience are recommended.

Preduodenal portal vein with preduodenal common bile duct: an extremely rare anomaly.

Preduodenal portal vein (PDPV) may occur as an isolated event and result in no symptoms, or it may found at autopsy as an incidental finding; associated preduodenal common bile duct (PDCBD) is an extremely rare event. To the 8 reported cases of PDPV with PDCBD, we add this rare case. Such a discovery is often incidental and of little import; however, it takes on major importance for hepatobiliary surgeons because the accidental damage of PDPV with PDCBD can lead to serious consequences. In addition to describing and illustrating this case, we discuss its relevant anatomy, embryology and associated malformations.