Yuichi Tomiki

Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice

Plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of a major fibrinolytic factor, tissue-type plasminogen activator, can both promote and inhibit angiogenesis. However, the physiologic role and the precise mechanisms underlying the angiogenic effects of PAI-1 remain unclear. In the present study, we report that pharmacologic inhibition of PAI-1 promoted angiogenesis and prevented tissue necrosis in a mouse model of hind-limb ischemia. Improved tissue regeneration was due to an expansion of circulating and tissue-resident granulocyte-1 marker (Gr-1(+)) neutrophils and to increased release of the angiogenic factor VEGF-A, the hematopoietic growth factor kit ligand, and G-CSF. Immunohistochemical analysis indicated increased amounts of fibroblast growth factor-2 (FGF-2) in ischemic gastrocnemius muscle tissues of PAI-1 inhibitor-treated animals. Ab neutralization and genetic knockout studies indicated that both the improved tissue regeneration and the increase in circulating and ischemic tissue-resident Gr-1(+) neutrophils depended on the activation of tissue-type plasminogen activator and matrix metalloproteinase-9 and on VEGF-A and FGF-2. These results suggest that pharmacologic PAI-1 inhibition activates the proangiogenic FGF-2 and VEGF-A pathways, which orchestrates neutrophil-driven angiogenesis and induces cell-driven revascularization and is therefore a potential therapy for ischemic diseases.

Influence of obesity on the short-term outcome of laparoscopic colectomy for colorectal cancer

Purpose: Obesity has been generally associated with increased surgical risk. However, data on the outcome of laparoscopic colectomy in obese and non-obese patients are controversial. The aim of this study is to assess the short-term outcome of laparoscopic colectomy for colorectal cancer (CRC) in obese patients as compared with non-obese patients. Materials and Methods: Sixty-nine patients who underwent laparoscopic anterior resection for CRC during the past six years were retrospectively evaluated. The patients with CRC involving the sigmoid or rectosigmoid colon and subjected to intracorporeal anastomosis were included in this study. They were divided into three groups according to body mass index (BMI): obese (BMI ≥ 28.0 kg/m2), pre-obese (BMI: 25.0-27.9 kg/m2) and non-obese (BMI < 25.0 kg/m2). Results: Nine patients (13.0%) were obese, 11 patients (15.9%) were pre-obese and 49 patients (71.1%) were non-obese. Patient characteristics, such as age, gender, tumor location, previous laparotomy, were similar among the three groups. There were no significant differences in operative time, blood loss, intraoperative complications and conversion rates. Postoperative complications and duration of postoperative hospital stay were also similar among the three groups. However, two of the three patients in the pre-obese group had to be operated on again due to incarceration of the small bowel into a port site. Conclusions: Laparoscopic colectomy can be safely performed in obese patients with short-term results similar to those obtained in non-obese and pre-obese patients.

Glasgow Prognostic Score as a Prognostic Factor in Patients Undergoing Curative Surgery for Colorectal Cancer

Background/Aims: Systemic inflammatory responses have been reported to be independent predictors of cancer-specific survival in colorectal cancer. The Glasgow Prognostic Score (GPS), which is an inflammation-based prognostic factor, is defined by the presence of elevated C-reactive protein and hypoalbuminemia. The purpose of this study was to estimate whether GPS can be a prognostic factor in patients undergoing curative surgery for colorectal cancers. Methods: We studied 166 patients with stage II (TNM classification) and 200 patients with stage III who had undergone curative surgery for colorectal cancer between 1999 and 2004. Univariate and multivariate analyses were performed to evaluate the relationship between clinicopathological factors and prognosis. Results: Among patients with stage II, location and GPS were independent factors on multivariate analysis. In particular, GPS was revealed to be the strongest factor in cancer-specific survival (HR: 7.43, 95% confidence interval, CI: 2.86–19.30, p < 0.0001). On the other hand, among patients with stage III, the number of metastatic lymph nodes was the only independent factor on multivariate analysis (HR: 1.14, 95% CI: 1.07–1.20, p < 0.0001). GPS was not a prognostic factor in cancer-specific survival in stage III. Conclusion: Among patients with stage II, GPS was predictive of cancer-specific survival.

A case of fibromatosis of the breast.

A 36-year-old woman presented with a 10 mm diameter mass in the right breast. Since the mass persisted for 3 months after detection and mammary carcinoma was suspected based on ultrasonographic findings, the mass was resected. Histologically, the mass demonstrated proliferative margins and consisted of spindle cells with bland cytologic features and abundant collagen. Immunohistochemically, the spindle cells were positive for vimentin and smooth muscle actin, and were negative for cytokeratins and desmin. Furthermore, the cells showed MIB-1 immunoreactivity with a MIB-1 labeling index of 4.1. Based on these findings, was diagnosed fibromatosis. Breast fibromatosis is rare and is usually misdiagnosed as breast carcinoma preoperatively. To date, only 10 cases of breast fibromatosis have been reported in Japan. Among the reported cases in Japan, our patient presented with the smallest mass, and ultrasonographic findings in this case were the same as those of other cases. Our experience and a review of the literature indicated that differentiation of fibromatosis from carcinoma is very dificult by ultrasonographic examination. In our case, despite involvement of the surgical margins, there was no recurrence. This may be attributed to the small size of the mass and focal exposure.

Colonic carcinoma resembling submucosal tumor: report of a case and review of the literature.

Submucosal tumor-like colorectal carcinoma, most of whose surface is covered with normal mucosa, is very rare. We report a case of colonic carcinoma resembling submucosal tumor. A 54-yr-old man visited our institution for an evaluation of a positive fecal occult blood test. Colonoscopic examination revealed a small, mainly red polypoid lesion with a central deep ulceration and many white spots in the sigmoid colon. Indigocarmine staining demonstrated that the white spots were faint shallow depressions. Magnifying colonoscopic examination showed that the lesion surface, except for the ulceration and the depressions, was covered with normal mucosa. Although the tumor was small, we strongly suspected its malignancy due to a deep ulceration. As we could not excise it endoscopically, we performed sigmoidectomy. The lesion was 12 mm in size. Histologic examination revealed that the lesion was a moderately differentiated adenocarcinoma that was mainly covered with normal mucosa, that carcinoma was exposed only at the ulceration and the depressions on the surface, and that it had expanded to the muscularis propria. Together with considerations from the literature, this type of colorectal carcinoma is supposed to be invasive and surgical resection should be considered, no matter how small it may be.

Treatment of Internal Hemorrhoids by Endoscopic Sclerotherapy with Aluminum Potassium Sulfate and Tannic Acid

Objective. A new sclerosing agent for hemorrhoids, aluminum potassium sulfate and tannic acid (ALTA), is attracting attention as a curative treatment for internal hemorrhoids without resection. The outcome and safety of ALTA sclerotherapy using an endoscope were investigated in the present study. Materials and Methods. Subjects comprised 83 internal hemorrhoid patients (61 males and 22 females). An endoscope was inserted and retroflexed in the rectum, and a 1st-step injection was applied to the upper parts of the hemorrhoids. The retroflexed scope was returned to the normal position, and 2nd–4th-step injections were applied to the middle and lower parts of the hemorrhoids under direct vision. The effects of endoscopic ALTA sclerotherapy were determined by evaluating the condition of the hemorrhoids using an anoscope and interviewing the patient 28 days after the treatment. Results. A cure, improvement, and failure were observed in 54 (65.1%), 27 (32.5%), and 2 (2.4%) patients, respectively, treated with ALTA. Complications developed in 4 patients (mild fever in 3 and hematuria in 1). Recurrence occurred in 9.6%. Conclusions. The results of the present study suggest that endoscopic ALTA has the potential to become a useful and minimally invasive approach for ALTA sclerotherapy.

Laparoscopic cholecystectomy after coronary artery bypass grafting using the right gastroepiploic artery: Report of a case

Abstract.A laparoscopic cholecystectomy (LC) was successfully performed on a 61-year-old man who had undergone coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). He complained of right hypochondralgia 20 days after CABG. Gallstones were diagnosed and a cholecystectomy was performed 9 months after CABG. Under general anesthesia, the operation was performed using a pneumoperitonium. When a laparoscope was inserted, the RGEA pedicle could be clearly recognized. The pedicle obstructed the operating field and made the working space narrower than usual. No ST changes on the electrocardiogram were seen during LC, especially during the initiation of pneumoperitonium, the insertion of the ports, or when retracting the gallbladder. The postoperative course was uneventful. To avoid complications, care should be taken not to stretch the RGEA pedicle during LC, and careful monitoring of the electrocardiogram is also necessary. It is difficult to view the operating field and the RGEA pedicle together. It is therefore better to insert another laparoscope for concomitant monitoring of the RGEA pedicle.

Clinical pathway to discharge 3 days after colorectal endoscopic submucosal dissection

Colorectal endoscopic submucosal dissection (ESD) is a useful treatment method; however, no index has been established for time for patient to start food ingestion or be discharged after ESD. We investigated the potential of a clinical pathway in which patients started food ingestion on day 2 after ESD and were discharged on day 3.

A case of clear cell adenocarcinoma arising from endometriosis of the rectum treated by laparoscopic surgery.

Highlights • Clear cell adenocarcinoma arising from endometriosis is very rare.• Preoperative diagnosis of the malignant transformation in endometriosis is very difficult.• The patient was undergone low anterior resection under the diagnosis of rectal carcinoma.• Sampsons criteria are useful for diagnosis of the malignant transformation in endometriosis.• The prognosis of malignant transformation in endometriosis is poor.

The Validity of Predicting Prognosis by the Lymph Node Ratio in Node-Positive Colon Cancer

Background/Aims: Because the TNM system disregards the number of lymph nodes dissected and inter-individual differences exist in the number of regional lymph nodes, the lymph node ratio (LNR), which is estimated by dividing the number of metastatic lymph nodes by the number of dissected lymph nodes, has been proposed as a prognostic factor in recent years. The purpose of the present study is to examine the validity of predicting prognosis using the LNR in node-positive colon cancer. Methods: Three hundred and eleven patients with lymph node metastases who underwent curative surgery for colon cancer at our department between 1992 and 2005 were enrolled. Univariate and multivariate analyses were performed to evaluate the relationship between clinicopathological factors and prognosis. Results: Among the patients with ≥12 dissected lymph nodes, differentiation, invasion depth and TNM N category were found to be significant independent prognostic factors. On the other hand, among the patients with ≤11 dissected lymph nodes, differentiation and the LNR were found to be significant independent prognostic factors. Conclusion: Among the patients with ≤11 dissected lymph nodes, LNR was a significant independent prognostic factor.