Factors influencing local and distant recurrence following resection of periampullary cancer.

BACKGROUND: Recurrence of periampullary cancer after pancreatoduodenectomy is common. The aim of this study was to investigate patterns of recurrence, incidence, and factors associated with local and distant recurrences. METHODS: This retrospective, single-centre study included consecutive patients with periampullary cancer who underwent resection with curative intent from January 2012 to January 2018. Survival, patterns of recurrence, and factors associated with recurrences were analysed. RESULTS: Median overall survival (OS) and disease-free survival among 398 included patients was 58.4 and 49.5 months respectively. Twenty-three patients (5.8 per cent) developed isolated local recurrences (LR), 50 (12.6 per cent) developed LR along with distant metastasis (DM), and 103 (25.9 per cent) developed isolated DM. Median OS was 40.4 months for patients with isolated LR versus 23 months for those with DM (P < 0.001). Tumour subtype (distal common bile duct (CBD): odds ratio (OR) 6.18, 95 per cent c.i. 2.19 to 17.46) and node-positive status (OR 2.36, 1.26 to 4.43) were independently associated with higher rates of LR. The most common site for isolated LR was along the superior mesenteric artery (12 of 23 patients). Tumour subtype (distal CBD: OR 2.86, 1.09 to 7.52), nodal positivity (OR 2.46, 1.53 to 3.94), and presence of perineural invasion (OR 1.80, 1.02 to 3.18) were independently associated with DM. CONCLUSION: Isolated LR is associated with better survival than DM and occurs most commonly along the superior mesenteric artery.

Risk factors and outcomes of conversion in minimally invasive distal pancreatectomy: a systematic review.

PURPOSE: The reported conversion rates for minimally invasive distal pancreatectomy (MIDP) range widely from 2 to 38%. The identification of risk factors for conversion may help surgeons during preoperative planning and patient counseling. Moreover, the impact of conversion on outcomes of MIDP is unknown. METHODS: A systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR). The PubMed, Cochrane, and Embase databases were searched for studies concerning conversion to open surgery in MIDP. RESULTS: Of the 828 studies screened, eight met the eligibility criteria, resulting in a combined dataset including 2592 patients after MIDP. The overall conversion rate was 17.1% (range 13.0-32.7%) with heterogeneity between studies associated with the definition of conversion adopted. Only one study divided conversion into elective and emergency conversion. The main indications for conversion were vascular involvement (23.7%), concern for oncological radicality (21.9%), and bleeding (18.9%). The reported risk factors for conversion included a malignancy as an indication for surgery, the proximity of the tumor to vascular structures in preoperative imaging, higher BMI or visceral fat, and multi-organ resection or extended resection. Contrasting results were seen in terms of blood loss and length of stay in comparing converted MIDP and completed MIDP patients. CONCLUSION: The identified risk factors for conversion from this study can be used for patient selection and counseling. Surgeon experience should be considered when contemplating MIDP for a complex patient. Future studies should divide conversion into elective and emergency conversion.

The role of older age and obesity in minimally invasive and open pancreatic surgery: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The aim of this study was to assess the impact of older age (≥70 years) and obesity (BMI ≥30) on surgical outcomes of minimally invasive pancreatic resections (MIPR). Subsequently, open pancreatic resections or MIPR were compared for elderly and/or obese patients. METHODS: A systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on MIPR (IG-MIPR). Study quality assessment was according to The Scottish Intercollegiate Guidelines Network (SIGN). A meta-analysis was performed to assess the impact of MIPR or open pancreatic resections in elderly patients. RESULTS: After screening 682 studies, 13 observational studies with 4629 patients were included. Elderly patients undergoing laparoscopic distal pancreatectomy (LDP) had less blood loss (117 mL, p < 0.001) and a shorter hospital stay (3.5 days p < 0.001) than elderly patients undergoing open distal pancreatectomy (ODP). Postoperative pancreatic fistula (POPF) B/C, major complication and reoperation rate were not significantly different in elderly patients undergoing either laparoscopic or open pancreatoduodenectomy (OPD). One study compared robot PD with OPD in obese patients, indicating that patients with robotic surgery had less blood loss (mean 250 ml vs 500 ml, p = 0.001), shorter operative time (mean 381 min vs 428 min, p = 0.003), and lower rate of POPF B/C (13% vs 28%, p = 0.039). CONCLUSION: The current available limited evidence does not suggest that MIPR is contraindicated in elderly or obese patients. Additionally, outcomes in MIPR are equal or more beneficial compared to the open approach when applied in these patient groups.

Meta-analysis of an artery-first approach versus standard pancreatoduodenectomy on perioperative outcomes and survival.

BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate perioperative outcomes and survival in patients undergoing an artery-first approach to pancreatoduodenectomy in comparison with those having standard pancreatoduodenectomy. METHODS: A systematic search of PubMed, MEDLINE, Embase and the Cochrane Database of Systematic Reviews was performed in accordance with PRISMA guidelines. Comparative studies including patients who underwent artery-first pancreatoduodenectomy and standard pancreatoduodenectomy were analysed. RESULTS: Seventeen studies were included in the final analysis. There were 16 retrospective cohort or case-control studies and one RCT. A total of 1472 patients were included in the meta-analysis, of whom 771 underwent artery-first pancreatoduodenectomy and 701 had standard pancreatoduodenectomy. Intraoperative blood loss (mean difference -389 ml; P < 0·001) and the proportion of patients requiring intraoperative transfusion (10·6 per cent (54 of 508) versus 40·1 per cent (186 of 464); P < 0·001) were significantly lower in the artery-first group. Although rates of perioperative mortality were comparable between the two groups, perioperative morbidity (35·5 per cent (263 of 741) versus 44·3 per cent (277 of 625); P = 0·002), and the incidence of grade B/C pancreatic fistula (7·4 per cent (26 of 353) versus 12·8 per cent (42 of 327); P = 0·031) were significantly lower in the artery-first group. The R0 resection rate (75·8 per cent (269 of 355) versus 67·0 per cent (280 of 418); P < 0·001) and overall survival (hazard ratio 0·72, 95 per cent c.i. 0·60 to 0·87; P < 0·001) were significantly higher in the artery-first group. CONCLUSION: The artery-first approach to pancreatoduodenectomy may be associated with improved perioperative outcomes and survival.

Management of patients with pancreatic cystic lesions: A case-based survey.

BACKGROUND: Pancreatic cystic lesions (PCL), including intraductal papillary mucinous neoplasia (IPMN), harbor different malignant potential and the optimal management is often challenging. The present study aims to depict the compliance of experts with current consensus guidelines and the accuracy of treatment recommendations stratified by the medical specialty and hospital volume. METHODS: An international survey was conducted using a set of 10 selected cases of PCL that were presented to a cohort of international experts on pancreatology. All presented cases were surgically resected between 2004 and 2015 and histopathological examination was available. Accuracy of the treatment recommendations was based on the European and international consensus guideline algorithms, and the histopathological result. RESULTS: The response rate of the survey was 26% (46 of 177 contacted experts), consisting of 70% surgeons and 30% gastroenterologists/oncologists (GI/Onc). In the case of main-duct IPMN (MD-IPMN), surgeons preferred more often the surgical approach in comparison with the GI/Onc (55 versus 44%). The mean accuracy rate based on the European and international consensus guidelines, and the histopathological result, were 71/76/38% (surgeons), and 70/73/34% (GI/Onc), respectively. High-volume centers achieved insignificantly higher accuracy scores with regard to the histopathology. Small branch-duct IPMN with cysts <2 cm and malignant potential were not identified by the guideline algorithms. CONCLUSION: The survey underlines the complexity of treatment decisions for patients with PCL; less than 40% of the recommendations were in line with the final histopathology in this selected case panel. Experts and consensus guidelines may fail to predict malignant potential in small PCL.

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

PURPOSE: This trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone. MATERIALS AND METHODS: Patients 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. RESULTS: A 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). CONCLUSION: Escalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

'Artery-first' approaches to pancreatoduodenectomy.

BACKGROUND: The technique of pancreatoduodenectomy (PD) has evolved. Previously, non-resectability was determined by involvement of the portal vein-superior mesenteric vein. Because venous resection can be achieved safely and with greater awareness of the prognostic significance of the status of the posteromedial resection margin, non-resectability is now determined by involvement of the superior mesenteric artery (SMA). This change, with a need for early determination of resectability before an irreversible step, has promoted the development of an 'artery-first' approach. The aim of this study was to review, and illustrate, this approach. METHODS: An electronic search was performed on MEDLINE, Embase and PubMed databases from 1960 to 2011 using both medical subject headings and truncated word searches to identify all published articles that related to this topic. RESULTS: The search revealed six different surgical approaches that can be considered as 'artery first'. These involved approaching the SMA from the retroperitoneum (posterior approach), the uncinate process (medial uncinate approach), the infracolic region medial to the duodenojejunal flexure (inferior infracolic or mesenteric approach), the infracolic retroperitoneum lateral to the duodenojenunal flexure (left posterior approach), the supracolic region (inferior supracolic approach) and through the lesser sac (superior approach). CONCLUSION: The six approaches described provide a range of options for the early determination of arterial involvement, depending on the location and size of the tumour, and before the 'point of no return'. Whether these approaches will achieve an increase in the proportion of patients with negative margins, improve locoregional control and increase long-term survival has yet to be determined.

Learning Curves in Open, Laparoscopic, and Robotic Pancreatic Surgery: A Systematic Review and Proposal of a Standardization.

Objective: To depict and analyze learning curves for open, laparoscopic, and robotic pancreatoduodenectomy (PD) and distal pancreatectomy (DP). Background: Formal training is recommended for safe introduction of pancreatic surgery but definitions of learning curves vary and have not been standardized. Methods: A systematic search on PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in pancreatic surgery. Primary outcome was the number needed to reach the learning curve as defined by the included studies. Secondary outcomes included endpoints defining learning curves, methods of analysis (statistical/arbitrary), and classification of learning phases. Results: Out of 1115 articles, 66 studies with 14,206 patients were included. Thirty-five studies (53%) based the learning curve analysis on statistical calculations. Most often used parameters to define learning curves were operative time (n = 51), blood loss (n = 17), and complications (n = 10). The number of procedures to surpass a first phase of learning curve was 30 (20-50) for open PD, 39 (11-60) for laparoscopic PD, 25 (8-100) for robotic PD (P = 0.521), 16 (3-17) for laparoscopic DP, and 15 (5-37) for robotic DP (P = 0.914). In a three-phase model, intraoperative parameters improved earlier (first to second phase: operating time -15%, blood loss -29%) whereas postoperative parameters improved later (second to third phase: complications -46%, postoperative pancreatic fistula -48%). Studies with higher sample sizes showed higher numbers of procedures needed to overcome the learning curve (rho = 0.64, P < 0.001). Conclusions: This study summarizes learning curves for open-, laparoscopic-, and robotic pancreatic surgery with different definitions, analysis methods, and confounding factors. A standardized reporting of learning curves and definition of phases (competency, proficiency, mastery) is desirable and proposed.

A cystic hepatic lesion: when to worry?

A 16-year old female presented to hospital with abdominal pain. Features on computed tomography raised the possibility of biliary cystadenoma or cystadenocarcinoma. She underwent a liver resection, and histopathology confirmed a serous biliary cystadenoma. This case is presented to highlight the radiological features of this uncommon pre-malignant condition as well as to summarize a management algorithm for cystic liver lesions.

Modification in the technique of pancreaticoduodenectomy: supracolic division of jejunum to facilitate uncinate process dissection.

Pancreaticoduodenectomy remains the recommended procedure for periampullary and pancreatic head tumors. The dissection of the uncinate process from the superior mesenteric vessels is a key step in this surgery. We describe a modification in the existing practice of infracolic division of the jejunum in order to facilitate this step. In this modification, the duodenojejunal (DJ) flexure and the proximal jejunum are delivered into the supracolic compartment and then the jejunum is divided. This exposes the uncinate process completely and facilitates the separation from the Superior Mesenteric Artery (SMA) and the Superior Mesenteric Vein (SMV). We have successfully employed this modified technique for 33 resections since February 2004. This modification of dividing the jejunum in the supracolic compartment is based on sound anatomic and embryologic grounds. It helps in aligning the uncinate process with the jejunal mesentery thereby making the dissection of uncinate process from the superior mesenteric vessels safe and complete.

Laparoscopy in pancreatic tumors.

Recently, increasing number of manuscripts - original articles and case reports have attempted to provide evidence of the forays of minimal access surgery into pancreatic diseases. Many, based on the lack of Level I evidence, still believe that laparoscopy in pancreatic surgery is experimental. This article attempts to look into data exploring the existing use of minimally invasive surgery in pancreatic disease to answer a vital question - what does the evidence say on the current status of laparoscopic surgery in pancreatic tumors.

Neurolytic celiac plexus block: a better alternative to opioid treatment in upper abdominal malignancies: an Indian experience.

The majority of patients with advanced upper abdominal malignancies suffer from moderate to severe pain due to unavailability of morphine in developing world. This study was undertaken to evaluate the role of neurolytic celiac plexus block on pain and quality of life in this patient subpopulation. One hundred consecutive patients receiving opioids for their pain relief were divided in two groups. Group I (control) patients received oral morphine & NSAIDS and group II (study) patients underwent neurolytic celiac plexus block (NCPB) to compare their effects on pain relief, morphine consumption, quality of life (QOL), Karnofsky and performance scores up to one month. NCPB provided statistically significant better pain relief and reduced morphine consumption at one month (P = 0.000). Superior Karnofsky and performance scores also favored NCPB group (P = 0.000); however the difference in overall QOL was not statistically significant (P = 0.24). Patients in oral morphine group had more side effects (94% vs. 58%) as compared to NCPB (P = 0.000). NCPB is an effective tool to reduce opioid requirement and the drug-related adverse effects. It is a rewarding technique, especially when morphine availability and its easy accessibility to the deserving patient is poor.

Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center.

BACKGROUND: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. PATIENTS AND METHODS: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS) was computed using the Kaplan-Meir product limit method and compared across groups using the log-rank statistics. Cox proportional hazards model, adjusted for a number of patient and tumor characteristics, was then used to determine factors prognostic for OS. RESULTS: Median age at diagnosis was 55 years (range: 21-81 years). 57.4% (n = 58) of patients were male, 22% (n = 22) had performance status (PS) of <2 at diagnosis and 89% received first-line chemotherapy, while the rest received best supportive care. For the whole cohort, 6 month and 1-year OS was 57% (95% confidence interval [CI]: 46-66%) and 47% (95% CI: 35-57%), respectively. In a multivariable model, PS <2 and oligometastatic disease were associated with a significantly decreased risk of death. CONCLUSION: Results from our analysis indicate that the prognostic outcome among Indian patients with metastatic pancreatic cancer is poor with survival outcomes similar to those reported in North America and Europe.

Surgical site infection rates in six cities of India: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Surgical site infections are a threat to patient safety. However, in India, data on their rates stratified by surgical procedure are not available. METHODS: From January 2005 to December 2011, the International Nosocomial Infection Control Consortium (INICC) conducted a cohort prospective surveillance study on surgical site infections in 10 hospitals in 6 Indian cities. CDC National Healthcare Safety Network (CDC-NHSN) methods were applied and surgical procedures were classified into 11 types, according to the ninth edition of the International Classification of Diseases. RESULTS: We documented 1189 surgical site infections, associated with 28 340 surgical procedures (4.2%; 95% CI: 4.0-4.4). Surgical site infections rates were compared with INICC and CDC-NHSN reports, respectively: 4.3% for coronary bypass with chest and donor incision (4.5% vs 2.9%); 8.3% for breast surgery (1.7% vs 2.3%); 6.5% for cardiac surgery (5.6% vs 1.3%); 6.0% for exploratory abdominal surgery (4.1% vs 2.0%), among others. CONCLUSIONS: In most types of surgical procedures, surgical site infections rates were higher than those reported by the CDC-NHSN, but similar to INICC. This study is an important advancement towards the knowledge of surgical site infections epidemiology in the participating Indian hospitals that will allow us to introduce targeted interventions.

Are we achieving the benchmark of retrieving 12 lymph nodes in colorectal carcinoma specimens? Experience from a tertiary referral center in India and review of literature.

INTRODUCTION: The number of lymph nodes (LNs) retrieved from a specimen of colorectal carcinoma may vary. Factors that can possibly affect LN yield are age of the patient, obesity, location of the tumor, neoadjuvant therapy, surgical technique and pathologist's handling of the specimen. AIM: The aim of our study is to look at lymph node retrieval from colorectal cancer (CRC) specimens in our hands and review the literature. MATERIALS AND METHODS: From May 2010 to January 2011, a total of 170 colorectal carcinoma cases were operated in our institute. Type of the surgeries, lymph node yield was looked at. RESULTS: There were 103 (60.6%) males and 67 (39.4%) females. The commonest age group was 50-59 years (30.6%). The surgeries included 107 surgeries for rectal carcinoma (63%) and 63 surgeries for colonic carcinoma (37%). Sixty six (38.8%) cases had received preoperative chemoradiotherapy, whereas 104 (61.2%) cases were without adjuvant therapy. The total lymph node positivity (metastatic disease) was 44.7% .The overall mean lymph node yield was 12.68 (range 0-63; median 11). The mean lymph node harvest in the age group < 39 was 15.76 whereas, the lymph node harvest in the group more than 39 years old was 11.90. ( statistically significant; P=0.03). The mean lymph node yield from specimens of rectal cancers (10.30) was lower than the mean lymph node yield from specimens for colonic cancers (16.71);( statistically significant, P<0.01). There was also statistically significant difference between the mean LN yield in chemoradionaiive cases (14.63) and in the cases where neoadjuvant therapy was received, (9.59); P<0.01. CONCLUSION: Pathologist while assessing a specimen of CRC should aim to retrieve a minimum of 12 LN. Surgical expertise and diligence of the pathologists remain two main alterable factors that can improve this yield. Neoadjuvant or preoperative radiotherapy can yield in less number of nodes.

Preoperative assessment and optimization in periampullary and pancreatic cancer.

Perioperative management of pancreatic and periampullary cancer poses a considerable challenge to the pancreatic surgeon, anesthesiologist, and the intensive care team. The preoperative surgical evaluation of a pancreatic lesion aims to define the nature of the lesion (malignant or benign), stage the tumor, and to determine resectability or other non-surgical treatment options. Patients are often elderly and may have significant comorbidities and malnutrition. Obstructive jaundice may lead to coagulopathy, infection, renal dysfunction, and adverse outcomes. Routine preoperative biliary drainage can result in higher complication rates, and metal stents may be preferred over plastic stents in selected patients with resectable disease. Judicious use of antibiotics and maintaining fluid volume preoperatively can reduce the incidence of infection and renal dysfunction, respectively. Perioperative fluid therapy with hemodynamic optimization using minimally invasive monitoring may help improve outcomes. Careful patient selection, appropriate preoperative evaluation and optimization can greatly contribute to a favorable outcome after major pancreatic resections.