Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154

Reported effects of anti-CD154 treatment on autoimmunity, alloreactivity, and inflammatory events mediated by macrophages and endothelial cells indicated that it might be an ideal agent for the prevention of intrahepatic islet allograft failure. This hypothesis was tested in MHC-mismatched rhesus monkeys. Transplantation of an adequate number of viable islets resulted in engraftment and insulin independence in six of six recipients treated with anti-CD154 (hu5c8) induction plus monthly maintenance therapy (post-operative day >125, >246, >266, >405, >419, >476). Anti-CD154 (hu5c8) displayed no inhibitory effect on islet cell function. For monkeys followed for >100 days, continued improvement in graft function, as determined by first phase insulin release in response to intravenous glucose, was observed after the first 100 days post-transplant. No evidence of toxicity or infectious complications has been observed. All recipients treated with anti-CD154 became specifically nonresponsive to donor cells in mixed lymphocyte reactions. Furthermore, three monkeys are now off therapy (>113, >67, and >54 days off anti-CD154), with continued insulin independence and donor-specific mixed lymphocyte reaction hyporeactivity. In striking contrast to all previously tested strategies, transplantation of an adequate number of functional islets under the cover of anti-CD154 (hu5c8) monotherapy consistently allows for allogeneic islet engraftment and long-term insulin independence in this highly relevant preclinical model.     

Surgical treatment of cervical anastomotic leaks following esophageal reconstruction

Cervical anastomotic leaks occurring in the early postoperative period after esophageal reconstruction are life-threatening complications, with a mortality rate similar to that of intrathoracic leaks if the posterior wall of the anastomosis is affected. Prompt diagnosis and aggressive surgical treatment is vital. The surgical procedures commonly used are often inadequate or unsatisfactory because of the difficulties encountered in the subsequent reconstruction. Twelve patient with an early cervical anastomotic leak following elective esophageal surgery were treated using an original surgical technique which allows diversion and simple delayed reconstruction of the anastomosis without risk of late stricture. Uncontrolled mediastinal sepsis accounted for the three deaths of the series and occurred in patients with a leak of the posterior anastomotic wall in whom definitive surgical treatment was delayed.     

Islet cell transplantation: the future?

BACKGROUND: Islet of Langerhans' cell transplantation is a promising strategy for the treatment of type-1 diabetes mellitus. Results of this procedure have yet to match those of whole organ pancreas transplantation, but are rapidly improving, as witnessed by increasing rates of insulin independence and graft function (i.e., C-peptide production) after islet transplantation. DISCUSSION: Identification of obstacles to the success of islet transplantation, such as primary nonfunction, immunosuppression-related metabolic workload, or recurrence of autoimmunity, will allow the development of new strategies tailored to overcome them. In particular, novel immunosuppressive protocols, with or without the aim of inducing tolerance, and immunoisolation devices are reaching the stage of clinical applicability. Finally, several strategies, such as utilization of porcine xenogeneic islets or genetically engineered beta-cell lines, or in vitro expansion of cultured beta-cells could theoretically expand indefinitely the pool of islet tissue for transplantation.     

Phase II study of cisplatin, 5-FU, and allopurinol in advanced esophageal cancer

Forty patients with advanced squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, 5-FU (by continuous 5-day infusion), and allopurinol; 37 are evaluable for response. Thirteen remissions (35%) were obtained, including three complete and ten partial, with a median duration of 9 months. After chemotherapy, seven responding patients underwent a surgical procedure, which was radical in four. The most frequent side effects were nausea and vomiting. This regimen is effective and can be included in a multimodality approach.     

Cholesterol microlithiasis: bacteriology, gallbladder bile and stone composition

It is not known whether microcalculi possess structural differences compared with larger stones or whether they represent simply an earlier stage in stone disease. We carried out a controlled study on 10 patients affected by gallbladder cholesterol microlithiasis (CM). In all patients, samples from all parts of the stones were studied by X-ray diffraction and by infrared spectrophotometry. Bile analysis was carried out to determine cholesterol, phospholipid and total bile acid content. The cholesterol saturation indices (C.S.I.) were calculated. In all samples, bacterial bile culture was carried out. The results were compared with those of 10 patients who had undergone cholecystectomy for large cholesterol stones, and for 10 patients who had undergone abdominal surgery but without biliary pathology. Patients in these latter groups were matched with the first according to sex and age. Microcalculi proved to be layered (nucleus and external layer) in only 2 cases and larger stones in 9; cholesterol was seen to be the principal crystalline component in all cases. Traces of bilirubin were found in 7 CM and in the nuclei of 5 larger stones. These results show that the structural composition of microcalculi is similar to that of the nucleus of larger stones. No substantial differences exist, however, between the two groups of patients regarding the other parameters taken into consideration.