Short, Cool, and Well Oxygenated - HOPE for Kidney Transplantation in a Rodent Model.

OBJECTIVES: The aim of this study was to investigate novel and easily applicable preservation perfusion techniques in kidney grafts obtained from donors after circulatory death (DCD). BACKGROUND: A novel perfusion approach, hypothermic oxygenated perfusion (HOPE), used for DCD liver grafts, is based on cold perfusion for 1 hour by an oxygenated solution before implantation. Here, we aimed to test HOPE in a rodent model of kidney grafts associated with substantial warm ischemia. METHODS: Rat kidneys were exposed to 30 minutes in situ warm ischemia, without application of heparin. Kidneys were removed and cold stored for 4 and 18 hours, mimicking DCD organ procurement and conventional preservation. In additional experiments, kidneys were normothermically perfused with oxygenated blood for 1 hour after cold storage. In a third group, kidneys were perfused by HOPE for 1 hour after cold storage. In each group, orthotopic kidney transplantation was performed after recipient nephrectomy. RESULTS: HOPE-treated DCD kidneys showed dramatically better function after transplantation, than cold-stored grafts in terms of nuclear injury, macrophage activation, endothelium activation, tubulus damage, and graft function. A short period of warm oxygenated perfusion before implantation improved graft quality as compared with cold storage, but was significantly less effective in all endpoints compared with HOPE. The effect of HOPE was dependent on perfusate oxygenation in the cold. CONCLUSIONS: HOPE of DCD kidneys was superior to other clinically used preservation approaches, consistent to earlier results in livers. On the basis of this, we assume a strong and generalized effect on solid organ viability by HOPE before transplantation. These results justify a clinical trial.

Fibroblast matrix implants-a better alternative for incisional hernia repair?

The standard surgical procedure for abdominal hernia repair with conventional prosthetic mesh still results in a high recurrence rate. In the present study, we propose a fibroblast matrix implant (FMI), which is a three-dimensional (3D) poly-L-lactic acid scaffold coated with collagen (matrix) and seeded with fibroblasts, as an alternative mesh for hernia repair. The matrix was seeded with fibroblasts (cellularized) and treated with a conditioned medium (CM) of human Umbilical Cord Mesenchymal Stem Cells (hUC-MSC). Fibroblast proliferation and function were assessed and compared between treated with CM hUC-MSC and untreated group, 24 h after seeding onto the matrix (n= 3). To study the matricesin vivo,the hernia was surgically created on male Sprague Dawley rats and repaired with four different grafts (n= 3), including a commercial mesh (mesh group), a matrix without cells (cell-free group), a matrix seeded with fibroblasts (FMI group), and a matrix seeded with fibroblasts and cultured in medium treated with 1% CM hUC-MSC (FMI-CM group).In vitroexamination showed that the fibroblasts' proliferation on the matrices (treated group) did not differ significantly compared to the untreated group. CM hUC-MSC was able to promote the collagen synthesis of the fibroblasts, resulting in a higher collagen concentration compared to the untreated group. Furthermore, thein vivostudy showed that the matrices allowed fibroblast growth and supported cell functionality for at least 1 month after implantation. The highest number of fibroblasts was observed in the FMI group at the 14 d endpoint, but at the 28 d endpoint, the FMI-CM group had the highest. Collagen deposition area and neovascularization at the implantation site were observed in all groups without any significant difference between the groups. FMI combined with CM hUC-MSC may serve as a better option for hernia repair, providing additional reinforcement which in turn should reduce hernia recurrence.

MRI: the new reference standard in quantifying hepatic steatosis?

OBJECTIVE: The purpose of this study was to assess non-invasive imaging modalities including MRI and CT and compare the quantitative amount of fat with data provided by the pathologist and a chemical lipid assay in leptin-deficient mouse livers. METHODS: A liver/fat phantom was first used to assess the accuracy of small-animal MRI and human MRI and CT, followed by correlation analysis with ob/ob mouse liver fat quantified by an accurate chemical lipid assay. Similarly, the authors compared the pathologist's quantification and the automated software quantification of fat with the lipid assay. The authors then investigated whether hepatic steatosis assessed by MRI correlates with the degree of liver injury in a model of ischaemia/reperfusion in leptin-deficient mice as well as with serious postoperative complications in patients undergoing major liver resection (NCT01234714). RESULTS: The authors designed lipid/liver mixtures at various ratios to mimic a wide range of fat liver contents. Small-animal and human MRI detected this fat with a high correlation to the actual fat contents. Mouse livers assessed by human MRI correlated best with total intrahepatic fat by chemical lipid analysis (r=0.975). Human CT, the pathologist's assessment and the automated software were less reliable (r=-0.873, 0.512 and 0.873, respectively). There was a significant correlation of the MRI fat quantification with several parameters of liver injury, and MRI data could predict mouse survival after ischaemia/reperfusion injury. In patients undergoing major liver resection, higher liver fat content was associated with more serious postoperative complications, such as liver or multiorgan failure and sepsis, necessitating admission to the intensive care unit. CONCLUSIONS: With the use of a well-defined set of biological standards, MRI can predict intrahepatic fat with high accuracy. In contrast to biopsies, this method is non-invasive, giving a representative assessment of the whole liver.

A multicenter randomized clinical trial of primary anastomosis or Hartmann's procedure for perforated left colonic diverticulitis with purulent or fecal peritonitis.

OBJECTIVES: To evaluate the outcome after Hartmann's procedure (HP) versus primary anastomosis (PA) with diverting ileostomy for perforated left-sided diverticulitis. BACKGROUND: The surgical management of left-sided colonic perforation with purulent or fecal peritonitis remains controversial. PA with ileostomy seems to be superior to HP; however, results in the literature are affected by a significant selection bias. No randomized clinical trial has yet compared the 2 procedures. METHODS: Sixty-two patients with acute left-sided colonic perforation (Hinchey III and IV) from 4 centers were randomized to HP (n = 30) and to PA (with diverting ileostomy, n = 32), with a planned stoma reversal operation after 3 months in both groups. Data were analyzed on an intention-to-treat basis. The primary end point was the overall complication rate. The study was discontinued following an interim analysis that found significant differences of relevant secondary end points as well as a decreasing accrual rate (NCT01233713). RESULTS: Patient demographics were equally distributed in both groups (Hinchey III: 76% vs 75% and Hinchey IV: 24% vs 25%, for HP vs PA, respectively). The overall complication rate for both resection and stoma reversal operations was comparable (80% vs 84%, P = 0.813). Although the outcome after the initial colon resection did not show any significant differences (mortality 13% vs 9% and morbidity 67% vs 75% in HP vs PA), the stoma reversal rate after PA with diverting ileostomy was higher (90% vs 57%, P = 0.005) and serious complications (Grades IIIb-IV: 0% vs 20%, P = 0.046), operating time (73 minutes vs 183 minutes, P < 0.001), hospital stay (6 days vs 9 days, P = 0.016), and lower in-hospital costs (US $16,717 vs US $24,014) were significantly reduced in the PA group. CONCLUSIONS: This is the first randomized clinical trial favoring PA with diverting ileostomy over HP in patients with perforated diverticulitis.

Donor information for living donor liver transplantation: where can comprehensive information be found?

Recently published data show that a large number of candidates for living donor liver transplantation (LDLT) actively look for additional information on the Internet because today it represents the main source of information for many of them. However, little is known about the quality of the information on LDLT available on the Internet. Our aim was, therefore, to comprehensively evaluate the online information available for LDLT candidates with the expanded Ensuring Quality Information for Patients (EQIP) tool (0-36 items). One hundred Web sites on LDLT were initially found with the Google, Bing, and Yahoo search engines, and we identified 32 Web sites that provided specific information for such candidates in English. Only 9 Web sites addressed >20 items and the scores tended to be higher for educational (P = 0.13) and scientific sites (P = 0.07) compared to hospital sites. The median number of items from the EQIP tool was only 16 (interquartile range = 13-20), and quantitative postoperative morbidity and mortality risk estimates were available on only 19% and 44% of the Web sites, respectively, despite the idea of major complications being mentioned on most Web sites. This analysis demonstrated several significant shortcomings in the quality of the information provided to potential donors for LDLT according to the EQIP instrument. We conclude that there is an urgent need to produce a Web site compliant with international standards for the quality of donor information.

The value of pancreatic stone protein in predicting acute appendicitis in patients presenting at the emergency department with abdominal pain.

BACKGROUND: Pancreatic Stone Protein (PSP) is a protein naturally produced mainly in the pancreas and the gut. There is evidence from experimental and clinical trials that blood PSP levels rise in the presence of inflammation or infection. However, it is not known whether PSP is superior to other established blood tests (e.g. White Blood Count, Neutrophils or C - reactive protein) in predicting appendicitis in patients presenting with abdominal pain and a clinical suspicion of appendicitis at the emergency room. METHODS/DESIGN: The PSP Appendix Trial is a prospective, multi-center, cohort study to assess the value of PSP in the diagnostic workup of acute appendicitis. 245 patients will be prospectively recruited. Interim analysis will be performed once 123 patients are recruited. The primary endpoint of the study concerns the diagnostic accuracy of PSP in predicting acute appendicitis and therefore the evidence of appendicitis on the histopathological specimen after appendectomy. DISCUSSION: The PSP Appendix Trial is a prospective, multi-center, cohort study to assess the value of PSP in the diagnostic workup of acute appendicitis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01610193; Institution Ethical Board Approval ID: KEKZH- Nr. 2011-0501.

Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP): a protocol of a cohort study on the diagnostic efficacy and prognostic value of PSP and PAP as postoperative markers of septic complications in patients undergoing abdominal surgery (PSP study).

INTRODUCTION: Major abdominal surgery leads to a postoperative systemic inflammatory response, making it difficult to discriminate patients with systemic inflammatory response syndrome from those with a beginning postoperative infectious complication. At present, physicians have to rely on their clinical experience to differentiate between the two. Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP), both secretory proteins produced by the pancreas, are dramatically increased during pancreatic disease and have been shown to act as acute-phase proteins. Increased levels of PSP have been detected in polytrauma patients developing sepsis and PSP has shown a high diagnostic accuracy in discriminating the severity of peritonitis and in predicting death in intensive care unit patients. However, the prognostic value of PSP/PAP for infectious complications among patients undergoing major abdominal surgery is unknown. METHODS AND ANALYSIS: 160 patients undergoing major abdominal surgery will be recruited preoperatively. On the day before surgery, baseline blood values are attained. Following surgery, daily blood samples for measuring regular inflammatory markers (c-reactive protein, procalcitonin, interleukin-6, tumour necrosis factor-α and leucocyte counts) and PSP/PAP will be acquired. PSP/PAP will be measured using a validated ELISA developed in our research laboratory. Patient's discharge marks the end of his/her trial participation. Complication grade including mortality and occurrence of infectious postoperative complications according to validated diagnostic criteria will be correlated with PSP/PAP values. Total intensive care unit days and total length of stay will be recorded as further outcome parameters. ETHICS AND DISSEMINATION: The PSP trial is a prospective monocentric cohort study evaluating the prognostic value of PSP and PAP for postoperative infectious complications. In addition, a comparison with established inflammatory markers in patients undergoing major abdominal surgery will be performed to help evaluate the role of these proteins in predicting and diagnosing infectious and other postoperative complications. INSTITUTION ETHICS BOARD APPROVAL ID: KEKZH-Nr. STV 11-2009. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01258179.

Expression of serotonin receptors in human hepatocellular cancer.

PURPOSE: Serotonin is a well-known neurotransmitter and vasoactive substance. Recent research indicates that serotonin contributes to liver regeneration and promotes tumor growth of human hepatocellular cancer. The aim of this study is to investigate the expression of serotonin receptors in hepatocellular cancer and analyze their potential as a cytotoxic target. EXPERIMENTAL DESIGN: Using a tissue microarray and immunohistochemistry, we analyzed the expression of serotonin receptors in the liver from 176 patients with hepatocellular carcinoma, of which nontumor tissue was available in 109 patients. Relevant clinicopathologic parameters were compared with serotonin receptor expression. Two human hepatocellular cancer cell lines, Huh7 and HepG2, were used to test serotonin antagonists as a possible cytotoxic drug. RESULTS: The serotonin receptors 1B and 2B were expressed, respectively, in 32% and 35% of the patients with hepatocellular cancer. Both receptors were associated with an increased proliferation index, and receptor 1B correlated with the size of the tumor. Serotonin antagonists of receptors 1B and 2B consistently decreased viability and proliferation in Huh7 and HepG2 cell lines. CONCLUSION: We identified two serotonin receptors that are often overexpressed in human hepatocellular cancer and may serve as a new cytotoxic target.