Protective effect of FUT-175 on pulmonary function of xenografts in a guinea pig-to-rat lung perfusion model

Background: FUT-175 (nafamostat mesilate) has a variety of pharmacological effects; in addition to its stable potent serine protease inhibitory activity, it exerts far stronger anti-complement activity than other protease inhibitors. Here, we evaluated the protective effect of FUT-175 on pulmonary function of xenografts in an ex vivo guinea pig-to-rat lung perfusion model, using a device for analyzing pulmonary function in small animals. Methods: Animals were divided into three groups (n = 6 each), Isograft (Group I), Xenograft (Group X), and Xenograft with FUT-175 (Group XF). In the latter, 10 mg of FUT-175 was added to the extracorporeal circuit before perfusion with xenogeneic blood was started. The following parameters were serially measured in these three groups: complement activity causing 50% hemolysis (CH50 units) in the perfusion blood either before or during perfusion, pulmonary arterial pressure, dynamic pulmonary compliance, and airway resistance. In addition, Hematoxylin and Eosin staining of the lungs and assays of rat IgM, IgG, and anti-C3 deposition were carried out after perfusion. Results: The duration of satisfactory pulmonary function after the start of perfusion was significantly increased in Group XF. CH50 in Group XF decreased significantly than in Group X. In addition, FUT-175 suppressed both the increase in pulmonary arterial pressure and airway resistance, and the decrease in dynamic pulmonary compliance. In Group XF, intraalveolar hemorrhage and the thickening of the arterial wall were not observed. Groups X and XF showed deposition of IgM, IgG, and C3 at the endothelium of the pulmonary arteries but less in Group I. Conclusions: This study suggests that FUT-175 inhibited complement activation including the alternative pathway and improved lung xenograft pulmonary function. FUT-175 ameliorates hyperacute rejection in a guinea pig-to-rat ex vivo xenogeneic lung perfusion model

Increased Expression of Proliferating Cell Nuclear Antigen in Rejecting Rat Lung Allografts

The aim of this study was to investigate the expression of proliferating cell nuclear antigen (PCNA) as an index of cell proliferation in the Brown Norway (BN) to Lewis (LEW) rat lung allograft model.Following transplantation of BN left lungs into LEW recipients, counts of PCNA-positive cells in the perivascular cellular infiltrate and bronchus-associated lymphoid tissue (BALT) were compared with the histological grade of rejection. Lungs were excised on postoperative days 3 and 5. LEW-to-LEW donor-recipient transplantation was performed as a control. Routinely processed, paraffinembedded sections were selected and stained with PCNA. The PCNA index (% of nuclei positive for PCNA) in the BALT was significantly higher in allograft (19.1%, p < 0.05) compared with isograft (4.2%) at 3 days following transplantation. Similarly, the PCNA index was also greater in the perivascular cellular infiltrates of rejecting lungs (23.9% at 3 days, 31.6% at 5 days). These findings indicate that the cells stimulated by the rejection reaction could be increase the expression of PCNA, and the increasing severity of rejection was paralleled by an increase in the number of PCNA-positive cells. In conclusion, PCNA may be a useful marker of acute cellular rejection in lung allografts

Colorectal Cancer Resection Via a Single Minimal Incision

Smaller incisions may be the major reason for reduced invasiveness of laparotomy. The aim of this study was to clarify the feasibility and safety of a minimal skin incision for colorectal cancer resection. Between April 2005 and February 2008, 122 consecutive patients (56 women, 66 men) were enrolled in this prospective study and scheduled to undergo resection for colorectal cancer using a single minimal skin incision. All of the operations were performed by a single surgeon. The patients were grouped into "small-incision" (?7 cm), "medium-incision" (>7 and ?14 cm), and "large-incision" (>14 cm) for comparison. The small-incision, medium-incision, and large-incision groups included 64 (52.5%), 38 (31.1%) and 20 (16.4%) patients, respectively. The median length of laparotomy incision in the small-incision and medium-incision groups (102 patients) was 7 (interquartile range 7-10) cm. There was no operative mortality. The group with larger length of skin incision had longer operation time, greater operative blood loss, higher rate of postoperative complications and longer postoperative stay. Failure of the small-incision was significantly associated with tumor location (splenic flexure/rectum) and tumor characteristics (adhesion/invasion of tumor into adjacent organs, and/or tumor diameter ?6.0 cm). This experience suggests that the majority of colorectal cancer resection can be safely accomplished via a median length of skin incision of 7 (interquartile range 7-10) cm

Minilaparotomy Approach Employing a K?stner Incision for Rectal Cancer Resection: Report of Three Cases

A minilaparotomy approach (? 7 cm) for colorectal cancer resection is feasible and safe. Such minilaparotomy generally employs a small vertical incision. A low transverse abdominal incision (a K?stner incision) has been shown to be associated with cosmetic advantage, less postoperative pain, and fewer wound-complications than the midline incision. We report three cases (75-year-old female, 64-year-old male, and 74-year-old female) who underwent anterior resection of rectal cancer via a minilaparotomy approach employing the K?stner incision. No hand-port or laparoscope was used. The median body mass index was 18.9 (range, 18.3-19.3) kg/m2. The rectal tumors were located in the rectosigmoid and the upper rectum. There were no intraoperative complications. The median operating time and operative blood loss were 160 (range, 159-162) min and 80 (range, 30-90) ml, respectively. All tumors were curatively resected. The patients quickly returned to normal function without morbidity or mortality. No patients developed wound-related complications. During a median follow-up period of 27.4 (range, 26.8-29.0) months, all patients are alive without tumor recurrence. In addition, neither incisional hernia nor nerve damage developed. We conclude that the minilaparotomy approach employing a K?stner incision is a less invasive and an attractive method with a cosmetic advantage for rectal cancer resection in selected patients