Isolation of porcine pancreatic islets for xenotransplantation.

This chapter deals with a technique for isolating intact islets of Langerhans from the pig pancreas based on our experience performing approximately 750 isolations. The procedure we describe involves identification of an optimal donor pancreas, purification and in vitro culture of islets, diabetes induction in recipients, and transplantation of islets and their immunomodulation. Besides the sophistication of the technical equipment employed, the major factors influencing the isolation outcome are the pig breed, the number and morphology of the islets in the donor pancreas, the quality of the collagenase/neutral protease, and the skill of the team members.

Tumor necrosis factor-α is associated with positive lymph node status in patients with recurrence of colorectal cancer-indications for anti-TNF-α agents in cancer treatment.

Introduction: The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis.

Methods: Expression of Tumor necrosis factor-alpha (TNF-α) was analyzed in colorectal cancer specimen and the cancer cell line HT-29 by immunohistochemistry and RT-PCR.

MMP-1 is a (pre-)invasive factor in Barrett-associated esophageal adenocarcinomas and is associated with positive lymph node status.

Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process.

Methods: Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33.

Pyoderma gangraenosum as rare complication of incisional hernia repair in a patient with Werlhof's disease.

On the 3rd day following surgery to repair an incisional hernia, a 67-year-old male patient with Werlhof's disease (idiopathic thrombocytopenic purpura) was diagnosed with a histologically confirmed pyoderma gangraenosum (PG), a rare complication of wound healing. Dexamethasone pulse therapy resulted in rapid remission of the skin lesions. Further improvement was slowed when the patient suffered multiple organ failure in the intensive care unit, delaying his transfer to rehabilitation for 8 weeks.

Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases.

Background: The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth.

Glucocorticoid-induced TNFR family-related receptor (GITR)-expression in tumor infiltrating leucocytes (TILs) is associated with the pathogenesis of esophageal adenocarcinomas with and without Barrett's mucosa.

Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Glucocorticoid-induced TNFR family-related Receptor (GITR)-mediated inflammation of tumor infiltrating leucocytes (TILs) in the tumor microenvironment might play a role during the multistep carcinogenetic process as either tumor promoting factor according to an inflammatory microenvironment or as a feature of anti-tumor activity.

Methods: Immunohistochemical analysis of GITR expression was analyzed in esophageal cancer (n=70: 41 EAC with BE, 19 EAC without BE, and n=10 esophageal squamous-cell carcinomas, ESCC), the adenocarcinoma cell line OE-33, and peripheral blood leucocytes (PBLs) of EAC patients, furthermore in biopsies of BE without intraepithelial neoplasia (IN) (n=18).

The intraportal injection model: a practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer.

Background: The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease.

Methods: We injected immunoincompetent nude mice intraportally with different numbers (1 x 10(5), 1 x 10(6) and 5 x 10(6) cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow.

Results: Only the injection of 1 x 10(6) cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals.

Laparoscopic Roux-en-Y gastric bypass surgery in the obesity center Wuerzburg--patient selection and results.

Background: The choice between different bariatric procedures for each patient is an important question in bariatric surgery. In this article, we explain criteria for patient selection for laparoscopic Roux-en-Y gastric bypass at the Obesity Center Wuerzburg and compare the corresponding outcomes for these selection criteria.

Methods: 60 consecutive patients underwent gastric bypass surgery (34 female, 26 male; mean age 45.

Predictability of outcome in laparoscopic gastric banding.

Background: The success rate of laparoscopic adjustable gastric banding (LAGB) in the treatment of morbid obesity is very variable.A reasonable preoperative selection of eligible patients seems to be important for a successful outcome of LAGB. In the present study, criteria were investigated to predict the outcome of LAGB.

Use of the continuous glucose monitoring system in Goettingen Minipigs, with a special focus on the evaluation of insulin-dependent diabetes.

Objectives: Adult pig islet isolation has greatly improved in the past few years. Islet grafts may now be tested in large animals. Continuous Glucose Monitoring System (CGMS) was applied to diabetic Goettingen Minipigs (GMP) to improve the management of hyperglycemia and hypoglycemia and their welfare before transplantation.

Exendin-4 improves the oral glucose tolerance in diabetic rats: pancreas regeneration, better function of pancreatic islets, or impaired glucose uptake?

One major obstacle for successful clinical transplantation of isolated pancreatic islets (PI) is their limited survival in vivo. The aim of this study was to analyze the functional and morphological regeneration of PI in diabetic rats by Exendin-4 (Ex4) treatment in vivo. Male Wistar rats (n = 3/group) received 20 nmol/kg Ex4 i.

The morphology of islets within the porcine donor pancreas determines the isolation result: successful isolation of pancreatic islets can now be achieved from young market pigs.

Clinical islet allotransplantation has become an increasingly efficient "routine" therapy in recent years. Shortage of human donor organs leads to porcine pancreatic islets as a potential source for islet xenotransplantation. Yet it is still very difficult to isolate sufficient numbers of intact porcine islets, particularly from young market pigs.

Highly efficient isolation of porcine islets of Langerhans for xenotransplantation: numbers, purity, yield and in vitro function.

Unlabelled: Xenogeneic transplantation of porcine islets of Langerhans is regarded as a potential future treatment for diabetes mellitus. Despite considerable biotechnological progress, however, it is still very difficult and often unreliable to isolate sufficient numbers of highly purified, intact islets from the porcine pancreas with good in vitro function.

Objective: Of this study was to describe an efficient and reliable method to isolate sufficient numbers of highly purified islets of Langerhans with good in vitro function from adult as well as from young hybrid pigs.