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Biomedical subjects

Norifumi Tsutsumi

Publications and source records attributed to Norifumi Tsutsumi.

7 recordsLinked to original sources

Essential role of PDGFRalpha-p70S6K signaling in mesenchymal cells during therapeutic and tumor angiogenesis in vivo: role of PDGFRalpha during angiogenesis.

Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-alpha (PDGFRalpha)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor-free assay system, we demonstrated that p70S6K inhibitor rapamycin (RAPA) targets mesenchymal cells to shut down the sustained expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via silencing of the PDGFRalpha-p70S6K pathway. Irrespective of the varied expression profiles of angiogenic factors in each tumor tested, RAPA constantly led the tumors to dormancy and severe ischemia in the time course, even associated with upregulated expression of VEGF from tumors. Because RAPA showed only a minimal effect to hypoxia-related expression of VEGF in culture, these results suggest that RAPA targets the host-vasculature rather than tumor itself in vivo. Thus, our current study indicates that the PDGFRalpha-p70S6K pathway is an essential regulator for FGF-2-mediated therapeutic neovascularization, as well as for the host-derived vasculature but not tumors during tumor angiogenesis, via controlling continuity of expression of multiple angiogenic growth factors.

Animals↗

Propranolol alone may not be acceptable to prevent first esophageal variceal bleeding in Japanese cirrhotic patients: randomized controlled trial.

BACKGROUND AND AIM: In Japan, endoscopic injection sclerotherapy (EIS) is widely used to prevent first esophageal variceal bleeding, in contrast to pharmacological therapy which is the main treatment used in the rest of the world. The present study investigated if propranolol alone is acceptable to prevent first esophageal variceal bleeding in Japanese cirrhotic patients. This was compared with EIS. METHODS: Twenty-five Japanese cirrhotic patients with endoscopically proven, likely to bleed esophageal varices were randomly assigned for propranolol administration (12 patients; group A) and EIS (13 patients; group B) to prevent first esophageal variceal bleeding. Complications, non-recurrence rate, bleeding rate and probability of survival were compared between the two groups. RESULTS: One patient in group A had severe bradycardia with loss of consciousness that seriously worsened his quality of life. The cumulative non-recurrence rate of group A was significantly lower compared with that of group B (P < 0.05). In group A, 2 of the 12 patients requested to discontinue taking propranolol and were excluded from the trial. The EIS treatment (group B) showed excellent results. No patient in group A or group B bled from esophageal varices throughout this study. The two groups showed no statistically significant differences in probability of survival. CONCLUSIONS: Propranolol alone may not be acceptable to prevent first esophageal variceal bleeding in Japanese cirrhotic patients.

Adrenergic beta-Antagonists↗

Long-term results of endoscopic Histoacryl injection sclerotherapy for gastric variceal bleeding: a 10-year experience.

BACKGROUND: The long-term efficacy and safety of endoscopic injection of N-butyl-2-cyanoacrylate (Histoacryl) were evaluated as the initial treatment for bleeding gastric varices. PATIENTS AND METHODS: Fifty-two patients with bleeding gastric varices underwent endoscopic injections of Histoacryl for hemostasis over a 10-year period. Histoacryl was injected intravariceally. Among these 52 patients, 32 had active bleeding and 20 had recent bleeding. Most of the varices were large (F2 or F3, 48 cases). After Histoacryl injection, the patients were followed endoscopically with retreatment administered as necessary. The patients were followed for a mean 28.1 months. RESULTS: The rate of initial hemostasis (no bleeding occurred for 48 hours after sclerotherapy) was 96.2%. Cumulative nonbleeding rates were 64.7%, 52.7%, and 48.2% at 1, 5, and 10 years, respectively. When rebleeding occurred, 80.0% was within 1 year after initial injection. Recurrent bleeding was easily stopped with the reinjection of Histoacryl in most patients. The treatment failure-related mortality rate was 4.0% (2 of 52). The cumulative survival rates were 66.9%, 60.4%, and 55.5% at 1, 5, and 10 years, respectively. The mortality depended on either malignancy or liver function (Child-Pugh classification). CONCLUSIONS: These results suggest that Histoacryl injection sclerotherapy is highly effective for the treatment of bleeding gastric varices, with rare complications occurring both acutely and long-term. Therefore, Histoacryl injection sclerotherapy is considered to be the first choice of treatment for bleeding gastric varices, but the rate of recurrent bleeding is so high that further methods or devices still need to be developed in order to prevent gastric variceal rebleeding.

Adolescent↗

A new era of robotic surgery assisted by a computer-enhanced surgical system.

Computer-enhanced robotic surgery has now been introduced into general surgical practice. The robotic system enables us to manipulate endoscopic instruments, as well as instruments during open surgical intervention, regarding both the operative field and operation techniques. This technologic innovation should therefore help surgeons overcome various difficulties and allow them to perform more precise, safer, and more minimally invasive surgery in the coming era.

General Surgery↗

Laparoscopic splenectomy for hematologic diseases.

BACKGROUND: Laparoscopic splenectomy has been demonstrated to be technically feasible and safe for the treatment of hematologic diseases. METHODS: The study comprised 64 consecutive patients with chronic immune thrombocytopenia purpura (ITP) who were admitted to our hospital from 1992 to 2000 and underwent laparoscopic splenectomy. Forty-one consecutive patients with ITP who underwent open splenectomy performed at the same hospital by the same surgical team between 1986 and 2000 were selected as the control group. RESULTS: We performed laparoscopic splenectomies for ITP, hereditary spherocytosis (HS), malignant lymphoma, autoimmune hemolytic anemia, and cryoglobulinemia. Laparoscopic surgery as compared with open surgery in ITP revealed a significantly lower pain medication requirement, an earlier resumption of oral intake, and a shorter hospital stay, but a longer operative time. During the present study (range: 3.8-80 months), the cumulative rate of nonrecurrence was 67.9% at 5 years after surgery, which was similar to the rate for the previous open splenectomy. CONCLUSIONS: Laparoscopic splenectomy is considered to be a suitable alternative therapeutic modality in the treatment of hematologic diseases.

Anemia, Hemolytic↗

Pulmonary embolism following laparoscopic surgery: a report of two cases.

Laparoscopic abdominal surgery is considered a low-risk procedure for postoperative complications because of reduced surgical stress and earlier mobilization. We report two patients who experienced pulmonary embolism following laparoscopic surgery; one patient underwent umbilical hernia repair and the other cholecystectomy. Although pulmonary embolism is indeed rare after laparoscopic surgery, early detection and early treatment are determinative factors for a good prognosis. Therefore, medical caregivers must remember that pulmonary embolism can be a critical complication after laparoscopic surgery and preventive measures should be employed for high-risk subjects.

Adult↗

Laparoscopic splenectomy for portal hypertension.

BACKGROUND/AIMS: Laparoscopic splenectomy is now increasingly being performed. However, controversy remains regarding the effectiveness of a laparoscopic splenectomy for patients with portal hypertension. METHODOLOGY: Seventy-three patients with portal hypertension who underwent a laparoscopic splenectomy from February 1992 until October 2000 were reviewed and the effectiveness of the procedures for portal hypertension was evaluated. Forty-two patients had esophagogastric varices and twenty had a concomitant hepatocellular carcinoma. The indications for surgery were bleeding tendency due to thrombocytopenia (n = 40), difficulty in receiving treatment for hepatocellular carcinoma due to thrombocytopenia (n = 18), and sclerotherapy-resistant esophagogastric varices (n = 15). RESULTS: A laparoscopic splenectomy was successfully performed in all the patients. The rate of conversion to conventional open surgery was 9.6% (7/73). The mean operative time was 210.1 +/- 101.9 minutes, and the estimated blood loss was 374.7 +/- 352.4 mL. There were no cases of mortality, and morbidity was encountered in 11.0% of patients. The increase in the platelet count correlated significantly to the spleen weight (P < 0.001). The platelet count had been maintained at over 10 x 10(4)/mm3 for over three years. Eighteen patients with hepatocellular carcinoma successfully underwent treatment for hepatocellular carcinoma after surgery and no recurrence of esophagogastric varices was encountered. CONCLUSIONS: A laparoscopic splenectomy resulted in the successful secondary treatment of hepatocellular carcinoma and esophagogastric varices. Portal hypertension was not a contraindication. A laparoscopic approach is therefore the procedure of choice for a splenectomy in portal hypertension.

Aged↗