Pancreatic islet transplantation is a promising treatment for diabetes but still faces several challenges. Poor islet isolation efficiency and poor long-term insulin independence are currently two major issues, although donor shortage and the need for immunosuppressants also need to be addressed. We established the Kyoto islet isolation method (KIIM), which has enabled us to isolate and transplant islets even from non-heart-beating donors. KIIM involves 1) cooling the donor pancreas in situ, 2) preserving the ducts with modified Kyoto solution, 3) using a modified two-layer pancreas preservation method, and 4) adjusting the density of the density gradient centrifugation and using an iodixanol-based solution for purification. KIIM has enabled us to transplant 17 islet preparations out of 21 isolations (an 81% success rate). All transplanted islets functioned, and all transplanted patients had improved glycemic control without hypoglycemic unawareness. Recently, we used KIIM for islet isolation from a brain-dead donor at Baylor, which resulted in a very high islet yield (789,984 IE) with high viability (100% by fluorescein diacetate/propidium iodide staining and a stimulation index of 4.7). This preliminary evidence suggests that KIIM may also be promising for islet isolation from brain-dead donors. In addition, to assess engrafted islet mass, we developed a secretory unit of islet transplant objects (SUITO) index: fasting C-peptide (ng/dL) / [fasting blood glucose (mg/dL) - 63] x 1500. This simple index has enabled us to monitor the engrafted islet mass. This index should be useful when deciding whether to perform additional islet transplantations to maintain insulin independence. Poor islet isolation efficacy and poor long-term results could be resolved with ongoing research.

Abstract. The placement of a self-expanding metallic stent (SEMS) in obstructive colorectal cancer (OCRC) is acknowledged to be a safe and effective procedure for the relief of obstruction. However, there is concern that shear forces acting on the tumor during stent expansion may release cancer cells into the circulation, resulting in a poor prognosis. The aim of the present study was to determine whether colonic stent insertion increases viable circulating tumor cells (v-CTCs). A telomerase-specific replication-selective adenovirus-expressing GFP (TelomeScanF35) detection system was used to detect v-CTCs in 8 OCRC patients with a SEMS before and after stent insertion and after surgical resection. In 7 patients, a SEMS was inserted as a bridge to surgery (BTS), and in one patient, a SEMS was inserted for palliation. Surgical resection (R0) was performed in 7 patients. Four patients had no v-CTCs before SEMS placement, two of four measurable patients had an increased number of v-CTCs after SEMS placement (1-3 v-CTCs), and one of two patients with increased v-CTCs developed distant lymphatic metastasis despite curative resection. Four patients had v-CTCs (1-19 cells) before SEMS placement, and two of these four patients had an increase in the number of v-CTCs (20-21 cells) after SEMS placement, while one of the four patients died early with distant metastasis. The present study demonstrated that endoscopic stent insertion for OCRC may result in tumor cell dissemination into the peripheral circulation and may induce distant metastases. IntroductionAt the time of the initial diagnosis of colorectal cancer, 8-13% of patients have obstructive symptoms (1,2). The treatment of choice for these patients has traditionally been emergency surgery. However, most studies have found that the morbidity and mortality rates are higher for emergency colorectal surgery than for elective surgery, and a temporary colostomy, which decreases patients' quality of life, is needed in many patients, which, in 10-40% of cases, becomes permanent (3). The purpose of stenting as a bridge to surgery (BTS) is to relieve the acute situation without emergency surgery, allowing elective surgery to be performed and thus improve surgical outcomes, determine the correct tumor stage, detect synchronous lesions, stabilize comorbidities, and carry out laparoscopic surgery. Immediate results in higher surgical risk patients who were stented were better for primary anastomosis, permanent stoma, wound infection, and overall morbidity, resulting in greater benefit. However, stent insertion was recently reported to have a high risk of perforation, re-obstruction, or stent migration (4,5). Moreover, perforations can lead to peritoneal dissemination. Sabbagh et al (6) reported worse overall survival and higher 5-year cancer-specific mortality of left-sided obstructive colorectal cancer (OCRC) patients with self-expanding metallic stent (SEMS) insertion than emergency surgery due to perforation induced by stent insertion. Furthermore, SEMS insertion as a BTS is ...

The maximal removal rate of indocyanine green (ICG Rmax) is considered to be an important parameter of hepatic function. However, the method of analysis has some flaws, and an abnormal value is obtained for about 15% of patients. We developed a new method of measuring the ICG Rmax with a clearance meter (RK-1000) that continuously measured the ICG concentration using a fingertip optical sensor. Twenty patients were examined. The histologic diagnosis was as follows: normal for 10, cirrhosis in 6, hepatitis in 4. The ICG concentration was measured in vivo continuously with the RK-1000. To obtain the Rmax by the Michaelis-Menten model, the ICG concentration in the VLDL compartment was subtracted from the values obtained by the RK-1000 because ICG binds to various serum proteins and its rate of removal in the VLDL compartment differs from that in other protein compartments. The removal velocity was calculated and a Michaelis plot obtained. Then Rmax was calculated from the reciprocal of the y-intercept of a Lineweaver-Burk plot. The Rmax in subjects with liver disease was significantly lower than in those with normal liver. It is concluded that our new method of measuring ICG Rmax with the RK-1000 reflects liver function appropriately.

Evaluation of engrafted islets mass is important for clinical care of patients after islet transplantation. Recently, we developed the secretory unit of islet transplant objects (SUITO) index, which reflected engrafted islet mass. In this study, we evaluated the SUITO index for the prediction of clinical outcome after single islet transplantation. Single islet transplantations were performed into six type 1 diabetic patients. Isolated islets were quantitatively assessed at the time of transplantation. The SUITO index was calculated as follows: fasting C-peptide (ng/dl)/[fasting blood glucose (mg/dl) - 63] x 1500. Islet yield/recipient's body weight and SUITO index were evaluated, along with HbA(1C), relative insulin dose (insulin dose posttransplant/pretransplant), and M-values. HbA(1C) improved in all cases, irrespective of the SUITO index score or islet yield/body weight. The average SUITO index from postoperative days 3 to 30 (R(2) = 0.728, p < 0.04), but not islet yield/body weight (R(2) = 0.259, p = 0.303), correlated with relative insulin dose. The daily SUITO index strongly correlated with the daily relative insulin dose (R(2) = 0.558, p < 0.0001) and weakly correlated with the daily M-values (R(2) = 0.207, p < 0.02). A SUITO index score of less than 10 was associated with increasing insulin dose even after islet transplantation. The SUITO index seems to be a better predictor of success of islet transplantations than islet yield/body weight. SUITO index is recommended to assess clinical outcome of islet transplantation.

Females, patients aged 85-89 years, and patients with stage IB-IIIC cancer had significantly better OS with surgery than without. For males, patients aged ≥90 years, or stage IA patients, the decision to perform surgery should be carefully made, and BSC might be an optimal strategy.