Ex vivo normothermic porcine pancreas: A physiological model for preservation and transplant study.

INTRODUCTION: An ex vivo normothermic porcine pancreas perfusion (ENPPP) model was established to investigate effects of machine perfusion pressures on graft preservation. METHODOLOGY: Nine porcine pancreata were perfused with autologous blood at 50 mmHg (control) pressure. Graft viability was compared against four ex-vivo porcine pancreata perfused at 20 mmHg ('low') pressure. Arterio-venous oxygen gas differentials, biochemistry, and graft insulin responses to glucose stimulation were compared. Immunohistochemistry stains compared the cellular viability. RESULTS: Control pancreata were perfused for a median of 3 h (range 2-4 h) with a mean pressure 50 mmHg and graft flow 141 mL min-1. In comparison, all of the 'low' pressure models were perfused for 4 h, with mean perfusion pressure 20 mmHg and graft flow 40 mL.min-1. All pancreata demonstrated cellular viability with evidence of oxygen consumption with preserved endocrine and exocrine function. However, following statistical analysis, the 'low' pressure perfusion of porcine pancreata compared favourably in important biochemical and immunohistochemistry cellular profiles; potentially arguing for an improved method for graft preservation. CONCLUSION: ENPPP will facilitate whole organ preservation to be studied in further detail and avoids use of expensive live animals. ENPPP is reproducible and mimics a "donation after circulatory death" scenario.

Recombinant human lubricin for prevention of postoperative intra-abdominal adhesions in a rat model.

BACKGROUND: Postoperative intra-abdominal adhesions are a major cause of morbidity and mortality and contribute to a heavy burden on health care resources. At present, numerous introduced adhesion prevention products have demonstrated some benefit but none are consistently effective. The aim of this study was to examine the effectiveness of recombinant human lubricin in preventing intra-abdominal adhesion formation. MATERIALS AND METHODS: A total of 62 male Wistar Albino rats were randomly assigned to the study. Six rats were used to the initial pilot study and 56 rats were randomized into four groups: (1) control cecal abrasion; (2) treatment cecal abrasion with 0.5 mg/mL lubricin solution; (3) control cecal enterotomy and primary closure; and (4) treatment cecal enterotomy and primary closure with 0.5 mg/mL lubricin solution. Rats were sacrificed at 3 d and 21 d postoperatively for the pilot and main studies, respectively. Macroscopic and microscopic adhesion severity was graded by blinded investigators. RESULTS: For the pilot study, all six rats successfully reached the end point indicating safety of the lubricin gel. In the main randomized study, adhesions in the treated cecal abrasion group were significantly reduced both macroscopically (P = 0.001) and microscopically (fibrosis P = 0.009, inflammation P < 0.0001), when compared with the control group. In the cecal enterotomy group, adhesions were reduced for the treatment group in macroscopic (P = 0.011) and microscopic grading (fibrosis P = 0.500, inflammation P = 0.206) compared with the control group. CONCLUSIONS: Recombinant human lubricin significantly reduced both macroscopic and microscopic intra-abdominal adhesions in the cecal abrasion group. The cecal enterotomy group showed modest macroscopic adhesion reduction. Future study using higher concentration of lubricin solution are needed to investigate its toxicity and more profound antiadhesion properties in significant operations.

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.

Extracorporeal machine perfusion of the pancreas: technical aspects and its clinical implications--a systematic review of experimental models.

Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications.

Gut symptoms in diabetics correlate with components of the rectoanal inhibitory reflex, but not with pudendal nerve motor latencies or systemic autonomic neuropathy.

OBJECTIVE: Fecal incontinence (FI) occurs in up to 20% of diabetes mellitus (DM) patients. Rectoanal inhibitory reflex (RAIR) is an enteric anorectal reflex that reflects the integrity of mechanisms in the physiology of FI. We aimed to investigate whether diabetic patients with FI, not constipation, had prolongation of RAIR and altered gut-specific autonomic tone. METHODS: In this prospective case-matched study 31 type I DM (19 FI and 12 constipation) and 42 type II DM (26 FI and 16 constipation). Another 21 participants were included as controls. Patients underwent the following assessments: cardiovagal autonomic tone (Modified Mayo Clinic composite autonomic severity score), rectal mucosal blood flow (RMBF) (assessment of gut-specific autonomic tone) and RAIR. Three phases of RAIR and the amplitude of maximal reflex relaxation were compared between groups. All participants completed symptom scores for FI and constipation. RESULTS: RAIR recovery time back to resting pressure was slower in diabetic patients with FI than controls (8.7 s vs 3.6 s, P < 0.05) and was an independent variable correlating with symptoms of FI (P < 0.05). RAIR recovery time was correlated with RMBF (r = 0.58, P = 0.04). CONCLUSION: RAIR is correlated with anorectal symptoms of FI and was associated with gut-specific autonomic neuropathy.

Prospective randomized assessment of acquisition and retention of SILS skills after simulation training.

BACKGROUND: Skills in single-incision laparoscopic surgery (SILS) are difficult to acquire. Simulation training leads to skill acquisition but circumstances about skill deterioration are unclear. The aim of this study was to evaluate skill acquisition and retention after single-incision laparoscopic simulation training. METHODS: From October 2013 to January 2014, 30 surgically naive participants underwent a SILS training curriculum and completed two validated tasks (peg transfer, precision cutting) with subsequent testing to assess acquisition of skills (baseline testing, BT). The participants were randomized into two groups and skill retention testing (RT) was measured after 4 weeks (group A) or 12 weeks (group B). Task completion was measured in time with penalties for inaccurate performance. RESULTS: A SILS training curriculum was established. 90 % of the participants completed the training successfully and reached the required levels of proficiency. Comparison of BT and RT revealed significantly better RT performances for peg transfer and precision cutting in group A (P < 0.05). These effects were not seen for RT in group B. Evaluating the RT performance of both groups, group A showed a non-significant trend for improved peg transfer and precision cutting compared to group B. CONCLUSION: A proficiency-based training curriculum for acquisition of basic SILS skills was successfully established in our department. The results of this study indicate that acquired SILS skills are well retained for a short period without training (4 weeks) but a longer non-training period (12 weeks) resulted in a significant loss of acquired skills. For enhancement of surgical skills, specialised SILS training curricula could be developed for novices and inexperienced surgeons; however, continuous training is essential to maintain these acquired skills.