佐田 尚宏

The growth, invasiveness and metastasis of human cancers are determined not only by cancer cells, but also by their microenvironment. Activated stromal fibroblasts promote tumor progression by secreting growth factors. In the present study, we focused on interrelations between cancer and fibroblasts, the main component of tumor stroma. We retrospectively analyzed the relations of mortality to clinical, pathological, and α-smooth muscle actin (α-SMA) characteristics in 97 consecutive patients with esophageal squamous cell carcinoma (ESCC). In vitro, we used TE-11, KYSE150 and KYSE220 ESCC cell lines and isolated esophageal stromal fibroblasts, some of which were immortalized. Migration assays were conducted to assess the effects of fibroblasts on cancer-cell migration and 3-dimensional organotypic cultures. In vivo, TE-11 and KYSE220 cells plus immortalized fibroblasts were co-transplanted subcutaneously in Nod/Scid mice to assess the effects of fibroblasts on tumorigenicity. Clinicopathologically, the α-SMA expression of cancer stroma was correlated with venous invasion (p<0.01), nodal involvement (p=0.02), recurrence (p=0.01), and was a predictor of survival in patients with stage I and II ESCC (p=0.04). In vitro, the presence of fibroblasts strongly promoted the migration of TE-11, KYSE150 and KYSE220 cells. On organotypic culture, stromal invasion was observed only in the presence of immortalized fibroblasts. In vivo, tumors developed or grew in a fibroblast‑dependent manner after implantation. Our findings provide evidence that stromal fibroblasts and tumor cells interact to promote tumor progression in ESCC. In patients with earlier stage ESCC, α-SMA may be a predictor of mortality. Inhibition of paracrine systems associated with tumor fibroblasts may slow or reverse tumor progression, potentially leading to the development of new targeted therapies.

A 41-year-old woman was admitted with upper abdominal pain, vomiting and fever. Abdominal CT scan showed a colo-duodenal fistula with inflammatory thickening of the transverse colon. The patient's general health was poor because of hypoalbuminemia and coagulopathy. Endoscopy showed a fistula at the lower duodenal angle and the stomach was filled with refluxed stool. Ileostomy and percutaneous endoscopic gastrostomy were performed at that time and a double lumen gastro-jejunostomy inserted through the gastrostomy to allow both gastric drainage and distal enteral feeding. Nutrition support was gradually converted from parenteral to enteral feeding. Colonoscopy showed stenosis of the transverse colon with a colo-colonic fistula near the stenosis. Two months later, right hemi-colectomy and closure of the colo-duodenal fistula were performed. The resected specimen showed stenosis and a fistula in the transverse colon due to Crohn's disease. The colo-colonic fistula was present and the colo-duodenal fistula had almost closed due to fibrosis. The postoperative course was uneventful and the patient was discharged after administration of infliximab. Use of a double lumen gastro-jejunostomy tube was effective in improving the patient's general condition. This therapeutic strategy allowed the safe conduct of major resection in a high-risk patient.

Rational treatment for neoplasms of the duodenal papilla (NDPs) is still controversial, especially for early stage lesions. Total papillectomies are indicated in patients expected to have adenomas, adenocarcinoma in an adenoma, or mucosal adenocarcinomas with no lymph node metastases. However, the preoperative pathological evaluation of NDPs is still challenging and often inaccurate, mainly because of the complicated anatomical structures involved and the possibility of an adenocarcinoma in an adenoma. Herein, we introduce a new method of total papillectomy, the extraduodenal papillectomy (ExDP). In this method, papillectomy is undertaken from outside of the duodenum, instead of resection from the inside through a wide incision of the duodenal wall as is done in conventional transduodenal papillectomy (TDP). The advantages of ExDP are precise and deeper cutting of the sphincter and shorter exploration time of the tumor compared to conventional TDP. We demonstrate three representative patients, all of whom had an uneventful postoperative course. One of them subsequently underwent a pylorus preserving pancreatoduodenectomy after detailed postoperative pathological evaluation. Including that patient, no recurrence has occurred with 37-46 months of follow-up. In conclusion, ExDP is regarded as a "total biopsy" for early stage borderline lesions and a feasible, less demanding alternative method for the treatment of NDPs.

症例は66歳の女性で，嘔吐と体重減少を主訴に当院を受診した．腹部CTにて十二指腸周囲，肝十二指腸間膜，小網に至る気腫像，胃十二指腸下行脚部の著明な拡張，水平脚部のcaliber changeを認めた．さらに，多量の腹腔内free airと十二指腸周囲の後腹膜ガス像も認めたため，上腸間膜動脈症候群による腸管気腫症および上部消化管穿孔の診断で緊急手術を施行した．術中所見では胃十二指腸の拡張，および十二指腸気腫を認めたが穿孔所見や腹水は認めなかった．経胃腸瘻造設のみ行い，術後経過は良好であった．腸管気腫症の原因は多岐にわたり，時にfree airを伴い消化管穿孔との鑑別が困難なことがある．患者の臨床所見と腸管気腫症の成因を詳細に検討し治療方針を決定することが重要で，審査腹腔鏡も選択肢の一つと考えられた．

Pancreatic islet transplantation has received widespread attention as a promising treatment for type 1 diabetes. However, islets for transplantation are subject to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here we found that protein fractions secreted by mesenchymal stem cells (MSCs) were capable of activating preserved islets. A conditioned medium from the supernatant obtained by culturing adipose tissue MSCs (derived from wild-type Lewis rats) was prepared for 2 days in serum-free medium. Luc-Tg rat islets to which an organ preservation solution was added were then incubated at 4°C with fractions of various molecular weights prepared from the conditioned medium. Under the treatment with some of the fractions, by 4 days the relative luminescence intensities (representative of the ATP levels of the cold-preserved islets) had increased to over 150% of their initial values. Our novel system may be able to restore isolated islets to the condition they were in before transport, culture, and transplantation.

INTRODUCTION: Laparoscopic splenectomy using pneumoperitoneum has been performed since 1992. The gasless abdominal wall-lifting method for laparoscopic splenectomy was introduced as an alternative. This retrospective study was undertaken to compare results using the two techniques. METHODS: Between 1995 and 2010, 54 patients underwent laparoscopic splenectomy at a single institution; 30 underwent the procedure using the gasless technique and 24 using pneumoperitoneum. There were no significant differences between the two groups regarding age, sex or BMI, but more patients underwent concurrent operations in the pneumoperitoneum group. The abdominal wall-lift system with subcutaneous K-wires was used for the gasless method. RESULTS: Intraoperative blood loss was similar in the two groups (193.0 ± 196.7 mL gasless, 217.3 ± 296.6 mL pneumoperitoneum; P > 0.05), but operative time (182.1 ± 92.1 min, 135.1 ± 46.1 min; P < 0.05), and resected spleen weight (306.1 ± 297.7 g, 138 ± 81.0 g; P < 0.05) were significantly different. In the gasless group, additional procedures included conversion (n = 1), mini-laparotomy (n = 2), and CO(2) insufflation (n = 2). Excluding the concurrent living-related kidney donor patients, hospital stay was similar (6.9 ± 2.5 days, 6.3 ± 2.0 days, P > 0.05). CONCLUSION: Although gasless laparoscopic splenectomy is feasible, there are disadvantages, particularly the restricted operative working space in some patients. These results suggest that either technique may be used on an individual basis in patients undergoing laparoscopic splenectomy.