Lamont G. Weide

Thymic carcinoma. A distinct clinical entity responsive to chemotherapy

Background. Thymic carcinomas are rare tumors of the anterior mediastinum. These tumors are distinct thymic neoplasms that differ from their more common counterpart, thymoma. As opposed to thymomas, thymic carcinomas are histologically malignant neoplasms with a clinical course that tends to be much more aggressive than that of patients with thymoma.

Surgical treatment of diabetes mellitus with pancreas transplantation.

ObjectiveThe authors compared results and morbidity in insulin-dependent diabetes mellitus (IDDM) patients undergoing preemptive pancreas transplantation (PTx) either before dialysis or before the need for a kidney transplant with IDDM patients undergoing conventional combined pancreas-kidney transplantation (PKT) after the initiation of dialysis therapy. Summary Background DataCombined PKT has become accepted generally as the best treatment option in carefully selected IDDM patients who either are dependent on dialysis or for whom dialysis is imminent. With improving results, the timing of PKT relative to the degree of nephropathy is evolving. However, it is not well established that the advantages of preemptive PTx can be achieved without incurring a detrimental effect on graft function or survival. MethodsOver a 4-year study period, data on the following 3 recipient groups were collected prospective and analyzed retrospectively: 1) 38 IDDM patients undergoing combined PKT while on dialysis (PKT:D);2) 44 IDDM patients undergoing preemptive PKT before dialysis (PKT:ND); and 3) 20 IDDM patients undergoing solitary PTx. All patients underwent whole organ PTx with bladder drainage and were treated with quadruple immunosuppression. ResultsActuarial 1-year patient survival is 100%, 98%, and 93%, respectively. One-year actuarial PTx survival (insulin-independence) is 92%, 95%, and 78%, respectively. The incidence of rejection, infection, operative complications, readmissions, and total hospital days was similar in the three groups. Long-term renal and pancreas allograft function and quality of life were similarly comparable. Rehabilitation potential favored the solitary PTx and PKT:ND groups. ConclusionsPreemptive PKT or solitary PTx performed earlier in the course of diabetes is associated with good results, facilitated rehabilitation, and may prevent further diabetic complications.

Recipient selection and evaluation for vascularized pancreas transplantation

Vascularized pancreas transplantation (PT) is becoming an accepted therapy for selected type I diabetic patients. However, selection and evaluation criteria remain uncertain. In the last 3.5 years, we have interviewed 205 and evaluated 151 diabetic patients for PT. The degree of renal dysfunction (creatinine clearance below 45 ml/min) was used to select patients for combined pancreas-kidney transplantation (PKT) or solitary pancreas transplantation (PTA) (clearance above 70 ml/min). The cardiovascular evaluation (stress thallium study with liberal use of coronary angiography) was used to determine operative risk and provided the other major selection criterion. A total of 104 patients were selected as candidates for PT; 70 have undergone PKT with 98.6% patient survival (1 cardiovascular death), 97.1% kidney graft survival, and 94.2% pancreas graft survival. Thirty-three evaluated patients (24.1%) were not accepted as candidates for PT; 13 have undergone cadaveric kidney transplantation, 5 were placed on the kidney waiting list, and 9 have died. Criteria for PTA include 2 or more diabetic complications or hyperlabile diabetes. Patient (n = 12) and pancreas graft survival after PTA is 83.3 and 50%, respectively. Our conclusion is that a multidisciplinary approach was used for recipient selection for PT based on degree of nephropathy, cardiovascular risk, and presence of diabetic complications. Nearly 75% of diabetic patients evaluated were acceptable candidates for PT. Only 4 (3.8%) of these selected patients died while awaiting or undergoing PT, thus optimizing the use of scarce allograft resources and providing evidence for appropriate patient selection.

Solitary Pancreas Transplantation: Experience with 62 consecutive cases

OBJECTIVE To determine the safety and efficacy of solitary pancreas transplantation in the treatment of IDDM. RESEARCH DESIGN AND METHODS A single-center retrospective case series of 62 consecutive solitary pancreas transplants (20 sequential pancreas after kidney, 42 pancreas transplants alone) performed in 57 adult IDDM patients was studied. Indications for solitary pancreas transplantation were 1) the presence of two or more overt diabetic complications and/or 2) glucose hyperlability with hypoglycemic unawareness and impaired quality of life. The recipient group consisted of 31 men and 26 women with a mean age of 38 years (range 25–62) and a mean duration of diabetes of 26 years (range 14–52). Mean pretransplant glycohemoglobin level was 9.9 ± 2.6%. Organ acceptance was restricted to ideal donors and man-dated a minimum of a two-antigen match (mean human leukocyte antigen ABDR match 2.7). The mean cold ischemia time was 16.6 h. Whole-organ pancreas transplantation was performed with bladder drainage by the duodenal segment technique. All patients were managed with either triple or quadruple immunosuppression. Monitoring included prospective urine cytology as well as cystoscopic transduodenal needle biopsies. RESULTS The mean length of initial hospital stay was 18 days, and mean hospital charges were

Duct epithelial cells cultured from human pancreas processed for transplantation retain differentiated ductal characteristics

106,341. The incidences of rejection, infection, and surgical complications were 70, 55, and 47%, respectively. Overall patient and graft survival rates were 86 and 52%, respectively, with a mean follow-up of 28 months. All patients with functioning grafts had excellent metabolic control (mean glycohemoglobin level 5.1%) and achieved good rehabilitation. CONCLUSIONS Despite morbidity, solitary pancreas transplantation can be performed with improving success, can enhance quality of life, and can offer an opportunity to arrest secondary diabetic complications.

Submandibular gland as a site for islet transplantation

A procedure is described for the isolation and growth in vitro of epithelial cells from the duct network of human pancreas, referred to as DEC. A significant advantage of our procedure over previously published procedures is that it enables the isolation of DEC from small pieces of pancreas tissue (<5 g) and, also, from the digest remaining after the isolation of islet cells from human pancreas, material that would normally be discarded. These were the only reliable sources for pancreas tissue available to us. This procedure shows that some of the techniques that have been successfully used for the isolation of rodent DEC are also valuable in the isolation of human DEC. In particular, the use of cholera toxin to prevent fibroblast growth and contamination obviates the need for the time-consuming procedure of physically removing fibroblasts or the use of expensive fibroblast-specific monoclenal antibodies. The use of sieving to separate the digest immediately achieves a partial purification, which, coupled with that of allowing duct cysts to form, adds to the purity of the final preparation. The ductal system of the intact pancreas tissue and the DEC derived from it expressed cytokeratins 7, 8/18, and 19 and markers for the presence of MUCl, CFTR, and carbonic anhydrase II, which are specific for ductal epithelial cells or for pancreatic ductal functions. This study showed that it is possible to obtain selectively viable DEC from small ducts in otherwise waste pieces of human pancreas. It showed that these cells retained all of the epithelial characteristics that were examined and, in combination with data from an earlier study, showed that the cultured DEC retain the metabolic functions of duct epithelial cells in vivo.

Desensitization of the adipocyte A1 adenosine receptor during untreated experimental diabetes mellitus

Homologous transplantation of islets of Langerhans into the submandibular glands of Syrian hamsters was successful in 8 out of 10 recipients. The technique was simple and led to formation of islets of various sizes within the parenchyma of the gland. The morphology and endocrine cell patterns of this islets were identical to pancreatic islets. The advantage of this model for islet transplantation is discussed.

FK 506 induction and rescue therapy in pancreas transplant recipients

We examined the changes that occur in the adenosine receptor system during diabetes mellitus. Experimental diabetes mellitus was induced in male Lewis rats with streptozocin (65 mg/kg), and A1 adenosine receptor binding was characterized with [125I]N6-2-(4-aminophenyl) ethyladenosine. In adipocytes, high-affinity A1 adenosine receptor binding decreased from 1466±228 of protein to 312±123 fmol/mg of protein (p<0.01) following 14 d of untreated diabetes mellitus. Neither the dissociation constant (Kd=1.3±0.2 nM) nor the basal level of adenylate cyclase activity (2.8±1.1 pmol cAMP/mg of protein/min) was altered by diabetes mellitus. The dose-response curve for the inhibition of adenylate cyclase byN6-R-phenylisopropyladenosine (R-PIA), however, did show a rightward shift, indicating that diabetic adipocyte membranes were less sensitive to the effects of adenosine than nondiabetic adipocyte membranes. In contrast, the A1 adenosine receptor-binding characteristics and adenylate cyclase dose-response curve for cerebral cortical tissue were unchanged by diabetes. These findings suggest that diabetes has tissue-specific effects on the A1 adenosine receptor system. Furthermore, the decreased sensitivity to adenosine potentially worsens the hyperlipidemia associated with diabetes mellitus. Such alterations in the adenosine receptor system may play a previously undescribed role in the pathophysiology of diabetes mellitus and may help explain why some organs are severely affected by diabetes, but others are relatively spared. Understanding these alterations in adenosine receptor function may lead tonovel therapies of this common metabolic disease.