Mitsuhiro Morikawa

Improvement of islet culture with sericin.

Islet transplantation is a promising treatment for diabetes. Serum is a necessary supplement in islet cultures, but it has various disadvantages including the risk of contamination by several pathogens. Results of this study suggest that sericin is a useful alternative supplement. Sericin accelerated the proliferation of the rat insulinoma cell line RIN-5F and improved the serum-free culture of rat islets.

Rat islet culture in serum-free medium containing silk protein sericin

BACKGROUND The development of islet cultures is desirable for successful clinical islet transplantation. Fetal bovine serum (FBS) has been used as a supplement in islet culture medium, but it may be an unsuitable supplement due recent animal health problems. We have evaluated the use of the silk protein, sericin, derived from Bombyx mori as a replacement for FBS in islet culture medium. METHODS Twenty rat islets were cultured in medium containing either sericin or FBS, or no supplement, for 14 days, during which time viable islets were counted in order to evaluate islet survival. Insulin secretion was measured in vitro by static incubation on days 3 and 7. In vivo function of cultured islets was tested by syngeneic transplantation. The islets were evaluated histologically and immunohistochemically after culture and transplantation. RESULTS Ninety-five percent of islets were viable after culture for 14 days in culture medium supplemented with either FBS or sericin, while no islets survived beyond 7 days in culture without supplement. No significant differences in stimulated insulin secretion were noted between two groups of islets grown on supplemented media. Following transplantation, islets cultured in FBS or sericin rapidly reversed hyperglycemia and maintained normal glycemic control. Histologically, islets cultured with sericin displayed a well-preserved structure and strong insulin staining before and after transplantation. CONCLUSION Serum-free medium containing sericin appears to be useful for islet culture.

Five-Year Survival of Alpha-Fetoprotein-Producing Gastric Cancer with Synchronous Liver Metastasis: A Case Report

Alpha-fetoprotein-Producing gastric cancer is associated with poor prognosis because of frequent liver and lymph node metastasis. We present a case with synchronous liver metastasis who survived for 5 years. A 69-year-old man with upper abdominal pain was referred to our hospital. Gastrointestinal endoscopy revealed a Borrmann II-like tumor in the lower part of the stomach. Computed tomography revealed a tumor in the left lobe of the liver. Serum alpha-fetoprotein levels were markedly increased. We performed distal gastrectomy after administering oral tegafur/gimeracil/oteracil potassium and administered hepatic intra-arterial cisplatin injection. Liver metastasis showed partial response on computed tomography. Despite left hepatic lobectomy, further metastases to the liver and mediastinal lymph nodes became difficult to control. After sorafenib tosylate administration, stabilization of the disease was observed for 4 months. We conclude that hepatic intra-arterial chemotherapy and oral administration of sorafenib tosylate may potentially improve the prognosis in such cases.

Sericin in the isolating solution improves the yield of islets isolated from the pancreas

Approximately half of the transplantable pancreatic islet tissue is lost during isolation, including the digestion and purification steps. Modifying the isolation method could increase the yield. This would enable the one donor-one recipient concept and improve the therapeutic effects of islet transplantation. This study aims to improve islet transplantation by increasing the yield of islets from the pancreas, both the number of islets and their size. Therefore, we used a sericin-containing isolating solution. Rat pancreatic islets were isolated by collagenase digestion and hand picking. We refer to islets isolated with or without sericin in the isolation solution as the sericin and control group, respectively. Volume yield, endocrine function, and islet morphology were compared between the groups. Histological distribution of sericin was evaluated by immunofluorescence staining to examine its mechanism of action in pancreatic islets. The pancreatic islet yield in the sericin group was significantly higher than that in the control group. The endocrine function of islets in the sericin group was comparable to that of islets isolated by conventional methods. Sericin adhered to the surface of isolated pancreatic islets and colocalized with E-cadherin, a cell membrane protein, which might explain the cytoprotective effects of sericin. The islet morphology tended to be better preserved in the sericin group. Sericin could prevent cytoarchitectural damage during the isolation and purification process, resulting in increased pancreatic islet yield. This suggests that sericin could contribute to islet therapy by enhancing the stability of islets.

Measures for preventing wound infections during elective open surgery for colorectal cancer: scrubbing with gauze.

In addition to the general surgical-site infection prevention measures in colorectal cancer surgery, we performed a simple subcutaneous scrubbing procedure with gauze at the time of abdominal closure, which reduced the incidence of wound infections. There are 289 patients whose primary colon cancer lesions were removed by elective surgeries. They were divided into Group A (74 patients with no wound infection prevention measures who were treated from 2002 to 2003), Group B (76 patients with wound infection prevention measures who were treated from 2007 to 2008), and Group C (139 patients with subcutaneous scrubbing with gauze plus the measures in Group B who were treated from 2009 to 2012). The incidence in Group A was 23%, while the corresponding values in Group B and Group C were 14.5% and 2.9%, respectively. The incidence of wound infections was substantially reduced by additional subcutaneous scrubbing with a saline solution and gauze during closure of a surgical incision. This very simple procedure was considered useful for surgical site infection prevention.

Revascularization And Function Of Pancreatic Islet Isografts In Diabetic Rats Following Transplantation.

In pancreatic islet transplantation, revascularization is crucial for the grafts survival and function. In this study, the endothelium of isolated islets and revascularization and function of islet isografts in diabetic rat were investigated. Islets were isolated from Lewis rats by collagenase digestion method and were examined using immunohistochemistry (CD31 stain) on days 0, 1, 3, and 7 after isolation. The number of CD31-positive cells in these isolated islets was counted (mean +/- SD %). Isografts (freshly isolated islets: group A, and islets cultured for 7 days: group B) transplanted in the renal subcapsule of streptozotocin-induced diabetic Lewis rats were examined using immunohistochemistry (CD31 stain) on days 3, 5, and 7 after transplantation. Intravenous glucose tolerance tests (IVGTT) were performed on days 3 and 7 after transplantation. The number of CD31-positive cells in the isolated islets on days 0, 1, 3, and 7 after isolation were: 17.3 +/- 4.1%, 8.2 +/- 0.7%, 2.1 +/- 0.8%, and 0.8 +/- 0.5%, respectively (p < 0.05). On day 5 after transplantation, CD31-positive cells were not detected in group A and B grafts, but were detected in both groups in periphery of the islets. On day 7, CD31-positive microvessels were present throughout the entire graft. IVGTT values in groups A and B on days 3 and 7 after transplantation did not show significant differences. In renal subcapsular isografts in diabetic rats, revascularization into islet grafts occurs from the surrounding host tissue 5 days after transplantation, but has no influence on the response to glucose during this period.

Prokineticin 2 expression as a novel prognostic biomarker for human colorectal cancer

Molecular tumor biomarkers hold considerable promise for accurately predicting colorectal cancer (CRC) recurrence and progression. Prokineticin 2 (PROK2) may be associated with angiogenesis and tumor formation in some malignant tumors. However, its prognostic value remains unknown. We focused on the association between PROK2 expression and clinical characteristics of CRC to assess value of PROK2 as a potential biomarker for stage I–III CRC patients prognosis. Between 1992 and 2006, 436 consecutive patients with stage I–III CRC treated with curative resection were included. PROK2 expression in primary tumors was investigated using immunohistochemistry. An animal model of liver metastasis was used to assess the role of PROK2. Positive PROK2 expression in primary tumors was found in 222 of 436 (50.9%) human CRC specimens and was significantly associated with lymphatic invasion, lymph node metastasis, clinical stage, and postoperative liver recurrence rate. Recurrence-free survival was significantly shorter in patients with positive PROK2 expression than in those with negative PROK2 expression. PROK2 expression was an independent unfavorable prognostic indicator for CRC [hazards ratio, 2.119; 95% confidence interval, 1.315–3.415; p = 0.002]. PROK2 overexpression promoted liver metastasis in vivo. We suggest that positive PROK2 expression is observed in CRC primary tissues; thus, PROK2 may be a useful predictor for liver recurrence and prognosis in CRC.

High-Temperature Hyperthermic Intraperitoneal Chemotherapy (H-HIPEC) with Cytoreductive Surgery for Patients with Peritoneal Metastases of Colorectal Cancer and Appendiceal Pseudomyxoma

Procedures of our H-HIPEC and cytoreductive surgery (CRS) for patients with peritoneal metastases from colorectal cancer and appendiceal pseudomyxoma (PMP) are reported.

Response to Modified TEGAFIRI in a Patient with Synchronous Multiple Liver Metastases of Colon Cancer

We report the case of a patient with colon cancer accompanied by multiple unresectable liver metastases who showed complete response (CR) to modified TEGAFIRI (mTEGAFIRI) (tegafur-uracil/leucovorin+irinotecan) chemotherapy. The patient was a 58-year-old Japanese male with cancer of the descending colon accompanied by multiple unresectable liver metastases. Following resection of the sigmoid colon cancer, mTEGAFIRI chemotherapy was administered. Abdominal computed tomography performed upon completion of 12 courses of chemotherapy showed that the unresectable liver metastatic lesions had disappeared, indicating CR. The only adverse drug reactions (ADRs) experienced to date have been stomatitis (grade 1) and neutropenia (grade 1). Anticancer therapy has thus been continued, and CR has been maintained for 15 months. The present patient achieved CR in response to mTEGAFIRI chemotherapy, a regimen that has not previously been reported, while experiencing only mild ADRs and maintaining a good quality of life. mTEGAFIRI chemotherapy is convenient to administer and is thought to be a potentially useful treatment option for patients with unresectable, recurrent colon cancer.We report the case of a patient with colon cancer accompanied by multiple unresectable liver metastases who showed complete response (CR) to modified TEGAFIRI (mTEGAFIRI) (tegafur-uracil/leucovorin+irinotecan) chemotherapy. The patient was a 58-year-old Japanese male with cancer of the descending colon accompanied by multiple unresectable liver metastases. Following resection of the sigmoid colon cancer, mTEGAFIRI chemotherapy was administered. Abdominal computed tomography performed upon completion of 12 courses of chemotherapy showed that the unresectable liver metastatic lesions had disappeared, indicating CR. The only adverse drug reactions (ADRs) experienced to date have been stomatitis (grade 1) and neutropenia (grade 1). Anticancer therapy has thus been continued, and CR has been maintained for 15 months. The present patient achieved CR in response to mTEGAFIRI chemotherapy, a regimen that has not previously been reported, while experiencing only mild ADRs and maintaining a good quality of life. mTEGAFIRI chemotherapy is convenient to administer and is thought to be a potentially useful treatment option for patients with unresectable, recurrent colon cancer.

A CASE OF REGIONAL ENTERITIS SUSPECTED TO BE CAUSED BY INGESTION OF HYPEROSMOLAR SALINE SOLUTION THROUGH JEJUNOSTOMY FEEDING TUBE

症例は79歳, 男性. 脳梗塞による嚥下障害のため空腸瘻を造設し, ラコール®1,200kcal/24hr, 食塩3g/分3の投与にて管理されていた. 経腸栄養開始2カ月後, 腹痛が出現し, CTにて空腸瘻カテーテル周囲の腸管の壁肥厚と壁内ガス像, 多量の腹水を認めた. 腹腔穿刺を施行すると, 腹水は混濁しグラム陰性桿菌を認めたため緊急手術となった. 空腸瘻カテーテル周囲の腸管に限局性の腸炎を認めるも穿孔は認められなかった. 腸炎の原因として, 空腸瘻のカテーテル自体による影響は考えにくく, 食塩の投与方法が疑われた. 食塩1gを20mlに溶解すると浸透圧は1540mOsm/mlであり, 腸管内が高浸透圧となり腸炎を引き起こしたのではないかと考えられた. 空腸瘻より食塩を投与する際は, 食塩を多くの水分で希釈し浸透圧を下げて投与するか, あるいは経静脈的に投与するような工夫が必要であると考えられた.