Does powered stapler improve the mechanical integrity of gastrojejunal anastomosis compared to the current techniques? Experimental study in ex vivo porcine models.

BACKGROUND: Numerous techniques have been described for fashioning gastrojejunostomy (GJ) in a Roux-en-Y gastric bypass. These include hand-sewn anastomosis (HSA) and mechanical anastomosis; the latter includes circular stapled anastomosis (CSA) or manual linear stapled anastomosis (mLSA). More recently, this list also includes powered linear stapled anastomosis (pLSA). The aim of this study was to analyse if addition of power to stapling would improve the integrity of GJ anastomosis in ex vivo porcine models. SUBJECTS AND METHODS: The present study included five groups - mLSA1, mLSA2, HSA, CSA, and pLSA. Sequential infusions of methylene blue-coloured saline were performed into the GJ models. Pressure readings were recorded till the point of leak denoting burst pressure (BP). Total volume (TV) and site of leak were recorded. Compliance was calculated from the equation ΔTV/ΔBP. RESULTS: Differences in pouch and intestinal thickness were not statistically significant between the models. BPs were higher in the mechanical anastomosis groups, i.e., pLSA 21 ± 9.85 mmHg, CSA 20.33 ± 5.78 mmHg, mLSA1 18 ± 4.69 mmHg and mLSA2 11 ± 2.94 mmHg, when compared to HSA 9.67 ± 3.79 mm Hg, which was found to be statistically significant (Kruskal-Wallis test, P = 0.03). Overall, the highest BP was recorded for powered stapling followed by circular, and then, linear stapling; however, this difference was not statistically significant (P = 0.86). There was no statistically significant difference among groups with regard to compliance (Kruskal-Wallis test, P = 0.082). CONCLUSION: Despite the limited number of samples, mechanical anastomosis showed a statistically higher BP when compared to HSA, suggesting better anastomotic integrity. The pLSA group showed promising results with the highest BP recorded among all groups; however, this did not reach statistical significance.

Prevalence and Impact of Sarcopenia in Chronic Pancreatitis: A Review of the Literature.

INTRODUCTION: Malnutrition is a common sequela of chronic pancreatitis (CP). Alterations in body composition and the assessment of sarcopenia have gained the interest of clinicians in recent years. There is a scarcity of data currently available concerning sarcopenia in patients with CP. This review aims to investigate the prevalence and impact of sarcopenia in CP. METHODS: Embase and Medline databases were used to identify all studies that evaluated sarcopenia and outcomes in patients with chronic pancreatitis. Due to paucity of data, conference abstracts were included. PRISMA guidelines for systematic reviews were followed. RESULTS: Six studies, with a total of 450 individuals were reviewed. Three full-text studies and three conference abstracts met the predetermined eligibility criteria. The prevalence of sarcopenia in CP from all studies ranged from 17-62%. Pancreatic exocrine insufficiency was associated as an independent and significant risk factor for sarcopenia. Sarcopenia was found to be associated with a reduced quality of life, increased hospitalisation, and reduced survival. It was associated with significantly lower islet yield following total pancreatectomy with islet auto transplantation in CP. CONCLUSION: The review of these existing studies amalgamates the limited data on sarcopenia and its impact on CP. It has shown that sarcopenia is exceedingly prevalent and an important risk factor in CP patients. The data presented emphasises that sarcopenia has a significant prognostic value and should be included in future prospective analyses in the outcomes of CP.

Significance of indeterminate pulmonary nodules in resectable pancreatic adenocarcinoma-a review.

BACKGROUND: The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC. METHODS: A systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed. RESULTS: Five studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs. CONCLUSION: This is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.

Outcomes of peri-operative glucocorticosteroid use in major pancreatic resections: a systematic review.

BACKGROUND: There is increasing evidence that peri-operative glucocorticosteroid can ameliorate the systemic response following major surgery. Preliminary evidence suggests peri-operative usage of glucocorticosteroid may decrease post-operative complications. These positive associations have been observed in a range of different operations including intra-abdominal, thoracic, cardiac, and orthopaedic surgery. This review aims to investigate the impact of peri-operative glucocorticosteroid in major pancreatic resections. METHODS: A systematic review based on a search in Medline and Embase databases was performed. PRISMA guidelines for systematic reviews were followed. RESULTS: A total of five studies were analysed; three randomised controlled trials and two retrospective cohort studies. The total patient population was 1042. The glucocorticosteroids used were intravenous hydrocortisone or dexamethasone. Three studies reported significantly lower morbidity in the peri-operative glucocorticosteroid group. The number needed to treat to prevent one major complication with hydrocortisone is four patients. Two studies demonstrated that dexamethasone was associated with a statistically significantly improved median overall survival in pancreatic cancer. CONCLUSION: This is the first systematic review conducted to investigate the significance of peri-operative glucocorticosteroid in patients undergoing pancreatic resection. This review shows a correlation of positive outcomes with the administration of glucocorticosteroid in the peri-operative setting following a major pancreatic resection.. More randomised clinical trials are required to confirm if this is a true effect, as it would have significant implications.

Association of visceral adipose tissue on the incidence and severity of acute pancreatitis: A systematic review.

BACKGROUND: With the rising prevalence of obesity, there is a plethora of literature discussing the relationship between obesity and acute pancreatitis (AP). Evidence has shown a possible correlation between visceral adipose tissue (VAT) and AP incidence and severity. This systematic review explores these associations. METHODS: Eligible articles were searched and retrieved using Medline and Embase databases. Clinical studies evaluating the impact of VAT as a risk factor for AP and the association of the severity of AP and VAT were included. RESULTS: Eleven studies, with a total of 2529 individuals were reviewed. Nine studies showed a statistically significant association between VAT and the severity of AP. Only four studies found VAT to be a risk factor for acute pancreatitis. Two studies showed VAT to be associated with an increased risk of local complications and two studies showed a correlation between VAT and mortality. CONCLUSION: This is the first systematic review conducted to study the association between VAT and AP. The existing body of evidence demonstrates that VAT has a clinically relevant impact and is an important prognostic indicator of the severity of AP. However, it has not shown to be an independent risk factor to the risk of developing AP. The impact of VAT on the course and outcome of AP needs to be profoundly explored to confirm these findings which may fuel earlier management and better define the prognosis of patients with AP. VAT may need to be incorporated into prognostic scores of AP to improve accuracy.

The role of total pancreatectomy with islet autotransplantation in the treatment of chronic pancreatitis: A report from the International Consensus Guidelines in chronic pancreatitis.

BACKGROUND: Advances in our understanding of total pancreatectomy with islet autotransplantation (TPIAT) have been made. We aimed to define indications and outcomes of TPIAT. METHODS: Expert physician-scientists from North America, Asia, and Europe reviewed the literature to address six questions selected by the writing group as high priority topics. A consensus was reached by voting on statements generated from the review. RESULTS: Consensus statements were voted upon with strong agreement reached that (Q1) TPIAT may improve quality of life, reduce pain and opioid use, and potentially reduce medical utilization; that (Q3) TPIAT offers glycemic benefit over TP alone; that (Q4) the main indication for TPIAT is disabling pain, in the absence of certain medical and psychological contraindications; and that (Q6) islet mass transplanted and other disease features may impact diabetes mellitus outcomes. Conditional agreement was reached that (Q2) the role of TPIAT for all forms of CP is not yet identified and that head-to-head comparative studies are lacking, and that (Q5) early surgery is likely to improve outcomes as compared to late surgery. CONCLUSIONS: Agreement on TPIAT indications and outcomes has been reached through this working group. Further studies are needed to answer the long-term outcomes and maximize efforts to optimize patient selection.

ZEB1 and IL-6/11-STAT3 signalling cooperate to define invasive potential of pancreatic cancer cells via differential regulation of the expression of S100 proteins.

BACKGROUND: S100 proteins have been implicated in various aspects of cancer, including epithelial-mesenchymal transitions (EMT), invasion and metastasis, and also in inflammatory disorders. Here we examined the impact of individual members of this family on the invasion of pancreatic ductal adenocarcinoma (PDAC) cells, and their regulation by EMT and inflammation. METHODS: Invasion of PDAC cells was analysed in zebrafish embryo xenografts and in transwell invasion assays. Expression and regulation of S100 proteins was studied in vitro by immunoblotting, quantitative PCR and immunofluorescence, and in pancreatic lesions by immunohistochemistry. RESULTS: Whereas the expression of most S100 proteins is characteristic for epithelial PDAC cell lines, S100A4 and S100A6 are strongly expressed in mesenchymal cells and upregulated by ZEB1. S100A4/A6 and epithelial protein S100A14 respectively promote and represses cell invasion. IL-6/11-STAT3 pathway stimulates expression of most S100 proteins. ZEB1 synergises with IL-6/11-STAT3 to upregulate S100A4/A6, but nullifies the effect of inflammation on S100A14 expression. CONCLUSION: EMT/ZEB1 and IL-6/11-STAT3 signalling act independently and congregate to establish the expression pattern of S100 proteins, which drives invasion. Although ZEB1 regulates expression of S100 family members, these effects are masked by IL-6/11-STAT3 signalling, and S100 proteins cannot be considered as bona fide EMT markers in PDAC.

Effects of Omegaven®, EPA, DHA and oxaliplatin on oesophageal adenocarcinoma cell lines growth, cytokine and cell signal biomarkers expression.

BACKGROUND: There is limited evidence assessing the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oesophageal adenocarcinoma, both in vitro and in vivo. We evaluated the effects of the omega-3 PUFA and oxaliplatin on OE33 and OE19 cells. METHOD: The two oesophageal cells were treated with Omegaven® (fish oil emulsion), EPA, DHA and oxaliplatin and incubated for up to 144 h. RESULTS: The following inhibitory effects were observed on OE33 cells: EPA reduced cell growth by 39% (p = 0.001), DHA by 59% (p < 0.000) and Oxaliplatin by 77% (p < 0.000). For OE19 cells, the EPA reduced growth by 1% (p = 0.992), DHA by 26% (p = 0.019) and oxaliplatin by 76% (p < 0.000). For both cells, Omegaven® resulted in reduced cell growth at intermediate concentrations (20-40 µM) and increased cell growth at low (10 µM) and high (50 µM) concentrations. DHA, Omegaven® and oxaliplatin were associated with significant downregulation of VEGF and p53 protein, and upregulation of p21 protein. DHA, Omegaven® and Oxaliplatin also led to significant downregulation of the total ERK1/2 and Akt proteins. CONCLUSION: DHA, Omegaven® and oxaliplatin were associated with downregulation of p53 and VEGF in both cells. Of the PUFAs studied, DHA alone or in combination (Omegaven®) had greater in vitro anti-cancer effects than EPA alone.

Ex Vivo Porcine Organ Perfusion Models as a Suitable Platform for Translational Transplant Research.

In transplantation surgery, extending the criteria for organ donation to include organs that may have otherwise been previously discarded has provided the impetus to improve organ preservation. The traditional method of cold static storage (CS) has been tried and tested and is suitable for organs meeting standard criteria donation. Ex vivo machine perfusion is, however, associated with evidence suggesting that it may be better than CS alone and may allow for organ donation criteria to be extended. Much of our knowledge of organ preservation is derived from animal studies. We review ex vivo porcine organ perfusion models and discuss the relevance to the field of transplantation surgery. Following a systematic literature search, only articles that reported on experimental studies with focus on any aspect(s) of ex vivo and porcine perfusion of organs yet limited to the context of organ transplantation surgery were included. The database search and inclusion/exclusion criteria identified 22 journal articles. All 22 articles discussed ex vivo porcine organ perfusion within the context of transplant preservation surgery: 8 liver, 3 kidney, 3 lung, 2 pancreas/islet, 4 discussed a combined liver-kidney multiorgan model, 1 small bowel, and 1 cardiac perfusion model systems. The ex vivo porcine perfusion model is a suitable, reliable, and safe translational research model. It has advantages to investigate organ preservation techniques in a reproducible fashion in order to improve our understanding and has implications to extend the criteria for organ donation.

A Study of Normothermic Hemoperfusion of the Porcine Pancreas and Kidney.

Normothermic machine perfusion has enormous potential to improve organ preservation and expand the organ donor pool. It is well established in other organs but not the pancreas, which has especially strict organ acceptance criteria. We established a model of normothermic hemoperfusion of the porcine pancreas with and without addition of the kidney as a dialysis organ. Four pancreases were harvested and perfused for 120 min with autologous whole blood at body temperature, two with parallel perfusion of the kidney and two without. The organs and perfusion circuit were evaluated for gross appearance, pH, histology and perfusion parameters. The organs maintained steadily increasing flow rate and perfusion pressure. Gross appearance of the organs was stable but appeared grossly ischemic toward the end of the perfusion period. Histology demonstrated necrosis centered in acinar tissue but islet cells were preserved. pH was significantly alkalotic toward the end of the perfusion, likely due to pancreatic tissue damage. Addition of the kidney did not result in significant improvement of the acid-base environment in this small series. In conclusion, normothermic perfusion of the pancreas is still in the experimental stages but holds great potential. Further studies to optimize perfusion parameters will significantly improve results. Parallel perfusion of the kidney may facilitate improvement in the acid-base environment.