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Biomedical subjects

Seigo Kitano

Publications and source records attributed to Seigo Kitano.

At least 91 records · Page 5Linked to original sources

Microwave coagulation therapy accelerates growth of cancer in rat liver.

BACKGROUND/AIMS: Although microwave coagulation therapy (MCT) has been performed for liver cancer, there has been no report examining the influence of this therapy on the growth of possible remnant cancer. METHODS: A solid cube of AH-130 cells (ascites hepatoma cell line) was implanted into the left lateral lobe of the rat liver. Five days later, MCT was applied to the middle liver lobe of these rats. Tumor growth and cytokine levels in plasma and the liver were compared between rats that underwent MCT and rats that did not. RESULTS: The mean tumor weight in the MCT group (222.6+/-51.5 mg, mean+/-SD) was significantly greater than that in the control group (126.7+/-19.7 mg, P<0.01) at postoperative day (POD) 5. Immunohistochemistry for anti-proliferating cell nuclear antigen showed the labeling index in the MCT group (90.4%) to be higher than that in the control group (76.7%, P<0.01). Liver basic fibroblast growth factor and transforming growth factor-beta 1 levels in the MCT group on POD 3 were significantly higher than levels in the control group. CONCLUSIONS: The present study suggests the clinically important finding that MCT accelerates the growth of small residual tumors in the liver.

Animals↗

Anti-tumor angiogenesis therapy using soluble receptors: enhanced inhibition of tumor growth when soluble fibroblast growth factor receptor-1 is used with soluble vascular endothelial growth factor receptor.

We have shown that a soluble receptor for vascular endothelial growth factor (sVEGFR), which adsorbs VEGF and may function as a dominant-negative receptor, suppresses tumor angiogenesis and enhances apoptosis of cancer cells, thereby inhibiting tumor growth [Cancer Res 60 (2000) 2169-2177]. In the present study, using as many as 11 cancer cell lines, we tested two hypotheses: (a) that a soluble fibroblast growth factor receptor-1 (sFGFR1) might inhibit tumor angiogenesis and growth in sVEGFR-resistant cancers, and (b) that combining sFGFR1 with sVEGFR might produce an enhanced inhibitory effect. In two cell lines derived from human lung cancer, H460 and A549, both of which produce a considerable amount of FGF-2, sVEGFR and a soluble receptor for angiopoietin-1 were both ineffective; however, sFGFR1 inhibited tumor angiogenesis and growth, demonstrating the critical role that FGFs play in some cancers. In three cell lines (QG56 from lung cancer, T3M4 and Panc1 from pancreatic cancer), which produced both VEGF and FGF-2 at detectable levels, combined sVEGFR and sFGFR1 produced an enhanced inhibitory effect compared to their individual effects. The combined usage of sVEGFR plus sFGFR1 suppressed tumor growth in all cancer cell lines tested, suggesting possible effectiveness of this strategy against a wide range of cancers.

Angiogenesis Inhibitors↗

Ethanol injection therapy of an isolated bile duct associated with a biliary-cutaneous fistula.

Bile leakage after hepatic resection often results in the formation of a biliary-cutaneous fistula. Such a fistula, when caused by an isolated bile duct in the remnant liver, can be intractable. We report a successful case of ethanol injection therapy of an isolated bile duct. A 73-year-old man underwent right hepatic resection for hepatocellular carcinoma. Bile leakage occurred after surgery, and the patient developed a biliary-cutaneous fistula. Fistulography revealed an isolated bile duct in the remnant portion of the caudate lobe without communication to the main biliary system. As conservative management with simple drainage was ineffective, injection therapy with ethanol was performed with a balloon occlusion catheter. After 11 therapy sessions, the bile duct was eradicated, and the biliary- cutaneous fistula was completely healed. The post-treatment course was uneventful. Ethanol injection therapy can be a choice for management of patients with a biliary fistula caused by an isolated bile duct.

Aged↗

Esophageal ulceration activates keratinocyte growth factor and its receptor in rats: implications for ulcer healing.

BACKGROUND & AIMS: Cellular and molecular mechanisms of esophageal ulcer healing remain unexplored. We studied the sequential cellular events and the expression of keratinocyte growth factor (KGF) and its receptor (KGF-R) during the healing of experimental esophageal ulcers. METHODS: Esophageal ulcers were produced in rats by local application of acetic acid. Studies included (1) ulcer size, (2) quantitative histology, and (3) KGF and KGF-R messenger RNA and protein expression by reverse-transcription polymerase chain reaction, Western blotting, and immunostaining. In separate groups, ulcer size and esophageal epithelial proliferation were evaluated after a single injection of recombinant human KGF (1 mg/kg) around the ulcer. RESULTS: Ulcers were fully developed 3 days after induction, and 58% of ulcers were re-epithelialized by 9 days. At 3 days, in esophageal tissue bordering the ulcers, KGF messenger RNA and protein were increased by 191% and 151%, respectively, and KGF-R messenger RNA and protein were increased by 357% and 237%, respectively. KGF was expressed in stromal cells, whereas KGF-R was expressed in epithelial cells. At 6 days, epithelial proliferation at the ulcer margin was increased by 216%, and treatment with KGF further enhanced cell proliferation and accelerated ulcer healing. CONCLUSIONS: KGF is a likely mediator of esophageal epithelial proliferation and ulcer healing.

Animals↗

Endoscopic injection sclerotherapy in the management of 2105 patients with esophageal varices.

BACKGROUND: The objective of this study is to examine the overall clinical results of endoscopic injection sclerotherapy (EIS) for patients with esophageal varices in our institution. METHODS: From January 1982 to May 2001, 2105 patients with esophageal varices were treated with EIS, which included prophylactic injections for patients with risky varices according to our criteria. Follow-up endoscopy was performed every 3 months, and recurrent varices were treated with additional EIS. RESULTS: Acute variceal bleeding was controlled in 468 of 473 patients (98.9%). Esophageal varices were completely eradicated in 1757 of 2105 patients (83.5%) with 3.8 +/- 1.6 sessions of EIS. The cumulative recurrence rates were 32.2% at 5 years, 36.5% at 10 years, and 37.8% at 15 years. The cumulative nonbleeding rates were 92.3% at 5 years, 90.1% at 10 years, and 89.5% at 15 years. The survival rate of acute bleeders was significantly lower than for both elective and prophylactic cases (P <.05). The overall cumulative survival rate was 28.2% at 10 years. CONCLUSIONS: EIS is the first choice of treatment for esophageal variceal bleeding, and rebleeding was shown to be well controlled in a long-term follow-up with endoscopy and additional EIS. The lower survival rate observed in acute bleeders may therefore justify the use of prophylactic EIS.

Acute Disease↗

A randomized controlled trial comparing open vs laparoscopy-assisted distal gastrectomy for the treatment of early gastric cancer: an interim report.

BACKGROUND: The application of laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer remains controversial among gastric surgeons. The purpose of this study was to compare LADG with open distal gastrectomy (ODG) regarding clinical outcome and postoperative parameters, including postoperative pain and pulmonary function. METHODS: From October 1998 to March 2001, 28 patients with early gastric cancer were randomly assigned to an LADG (n = 14) or ODG group (n = 14) with Billroth I reconstruction. Postoperative pain during resting, coughing, and walking were evaluated by a visual analog scale (VAS). Pulmonary functions such as forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) measured on the third postoperative day were compared with preoperative functions. RESULTS: Patients in the 2 groups were comparable for age, gender, height, weight, staging, and location of gastric cancer. The mean blood loss was significantly less in the LADG than in the ODG group (P <.05). Histologic examinations of resected specimens revealed that these 2 operations were identical from the standpoint of curability. Patients in the LADG group recovered both bowel movement and walking ability earlier than did patients in the ODG group (P <.05). The postoperative VAS pain score during rest was lower for 3 days after LADG than ODG (P <.05) and for 1 day during coughing or walking (P <.05). The pulmonary functions such as FVC and FEV1 values were reduced on the third day after LADG and ODG. However, the FVC value on the third day after LADG was lower than after ODG (P <.05). CONCLUSIONS: This study demonstrates that LADG has several advantages including an earlier recovery, less pain, and less impaired pulmonary function after gastric surgery when compared with ODG; furthermore, no reduction in curability was observed.

Aged↗

Laparoscopy-assisted Billroth-I gastrectomy (LADG) for cancer: our 10 years' experience.

To evaluate laparoscopy-assisted Billroth-I gastrectomy (LADG), we examined the outcome of its use over the last 10 years. From December 1991 to December 2001, 116 patients with early gastric cancer underwent LADG in the surgical department of Oita Medical University and Koga hospital by the same surgical staffs. An operation record and clinical sheets were reviewed to obtain the operative findings, clinical course, and pathologic findings of resected specimens to evaluate the usefulness of LADG in the management of early gastric cancer. In all LADG procedures, regional lymph nodes dissection (D1+alpha) was successfully performed using laparoscopy. The mean operative duration and blood loss were 234 minutes and 139 mL, respectively. There were only four major complications, including pneumonia, leakage of anastomosis, pancreatic injury, and anastomotic stenosis, but all these cases were successfully treated conservatively. The mean length of postoperative stay was 16.3 +/- 2.5 days. All patients except one, who died not of cancer but of cerebral bleeding, were alive without recurrence or port-site metastasis during mean follow-up period of 45 months. We successfully performed 116 LADG procedures over 10 years. This procedure is recommended for the treatment of patients with early gastric cancer because of the associated good prognosis and several benefits, including less invasiveness and early recovery.

Adult↗

Modern treatment of early gastric cancer: review of the Japanese experience.

BACKGROUND: Recently, detections of early gastric cancer (EGC) have been increasing, and the treatment strategies for gastric cancer have been changing. To demonstrate recent clinical experience of EGC in Japan and to assess modern strategies for the treatment of EGC, we investigated the English-language literature of the past 10 years through computer searches. METHODS: This article intends to provide gastric surgeons with recent Japanese experience of the treatment for EGC. In a search for modern treatments of EGC, we selected 100 papers published in well-known medical journals, and focused on the following items of EGC: (1) prognostic factors, (2) endoscopic treatment, (3) surgical procedures, and (4) Japanese guidelines. RESULTS: The most important factor influencing the survival of patients with EGC is the status of lymph node metastasis. The incidence of lymph node metastasis is 1-3% for mucosal cancers and 11-20% for submucosal cancers. Endoscopic mucosal resection (EMR) is a technique for the treatment of EGC, and the recent indication includes the tumors confined to the mucosa up to 3 cm in size or those invading the superficial submucosa. Surgical procedures include conventional Billroth I gastrectomy, limited resections, and laparoscopic surgery. Laparoscopic wedge resection using the lesion-lifting method and laparoscopy-assisted distal gastrectomy provide less pain, faster recovery and shorter hospital stay. Guidelines for the treatment of gastric cancer proposed by the Japanese Gastric Cancer Association show that patients with mucosal cancer can be managed by EMR or distal gastrectomy, whereas patients with submucosal cancer are candidates for distal gastrectomy with lymph node dissection. CONCLUSION: Although the prognosis of patients with EGC depends on the presence or absence of lymph node metastasis, most are successfully treated by modern endoscopic or surgical techniques. Laparoscopic surgery and limited resections will contribute to the better quality of life of patients with EGC.

Biopsy, Needle↗

[Laparoscopic surgery for gastroduodenal disease].

Since 1990, laparoscopic surgery for gastrointestinal disease has been accepted worldwide because it is minimally invasive, associated with less pain, and results in early recovery. For the surgical management of gastroesophageal reflux and perforated peptic ulcer, laparoscopic procedures are recognized as the standard. Laparoscopic gastrectomies for cancer have developed since 1991. Laparoscopic wedge resection and intragastric mucosal resection are performed for the treatment of early gastric cancer without the risk of lymph node metastasis. For early gastric cancer with the risk of perigastric lymph node metastasis, laparoscopy-assisted Billroth-I gastrectomy with D1 lymph node dissection has been successfully performed. Thus, laparoscopic approaches play an important role in the management of gastroduodenal disease.

Duodenal Diseases↗

Papillary adenocarcinoma of the stomach.

BACKGROUND: Papillary gastric carcinoma (PGC) is a rare histologic entity among gastric adenocarcinomas. The aim of this study was to clarify the clinicopathologic characteristics of PGC, including the survival rate, recurrence pattern, and factors influencing the prognosis of patients with PGC.METHODS: The clinicopathologic findings of 65 patients with PGC and 566 patients with non-papillary gastric carcinoma (NGC) were examined and compared. The tumor was classified as PGC when more than 50% of the tumor area contained papillary structures. Survival rates were calculated using the Kaplan-Meier method and were assessed by the generalized Wilcoxon test. Prognostic factors were evaluated by univariate analysis, using the chi(2) test and Student's t-test, and confirmed by multivariate analysis, using the Cox proportional hazards model.RESULTS: PGC was characteristically found in patients over 65 years of age (68%), was located in the upper one-third of the stomach (37%), was of grossly localized type (85%), was negative for serosal invasion (86%), and was associated with liver metastasis (14%). The overall 5-year survival rate for patients with PGC was significantly lower than the rate for those with NGC (63% vs 76%) ( P < 0.05). Although the 5-year survival rate for each stage of PGC and NGC did not differ significantly, the death of PGC patients was more frequently associated with liver metastasis (62%) than with peritoneal dissemination (5%). Independent prognostic factors of PGC were liver metastasis, serosal invasion, and lymph node metastasis.CONCLUSION: These results suggest that PGC is characterized by advanced patient age, proximal tumor location, grossly localized type, negative serosal invasion, and frequent liver metastasis. A poor prognosis for patients with PGC is associated with the presence or recurrence of liver metastasis.

Journal Article↗

Gastric cancer with extragastric lymph node metastasis: multivariate prognostic study.

BACKGROUND: Although many authors have investigated the prognostic factors of gastric cancer, there are few comprehensive studies on the prognosis of patients with extensive lymph node metastasis. The aim of this study was to clarify the prognostic factors of gastric cancer with extragastric lymph node metastasis, using multivariate analysis.METHODS: The study population consisted of 121 patients who had undergone radical gastrectomy and extended lymph node dissection (D2, D3) for gastric cancer with extragastric lymph node metastasis. We examined 18 clinicopathologic factors, including the type of gastrectomy, tumor size, depth of wall invasion, status of lymph node metastasis, and stage of disease. Survival rates were analyzed by the Kaplan-Meier and Mantel-Cox methods, and multivariate analysis was done using the Cox proportional hazards model.RESULTS: The overall 5-year survival rate was 32%, and the 5-year survival rate after curative gastrectomy was 37%. Overall survival rate was associated with the type of gastrectomy, stage of disease, operative curability, tumor size, depth of wall invasion, and anatomical distribution of positive nodes, whereas the survival rate after curative gastrectomy was correlated with the type of gastrectomy, stage of disease, tumor size, gross type, and depth of wall invasion. Independent prognostic factors were operative curability and depth of wall invasion, and survival after curative gastrectomy was influenced only by the depth of wall invasion (mucosa and submucosa [T1], muscularis and subserosa [T2] vs serosa [T3]).CONCLUSION: In patients with gastric cancer with extragastric lymph node metastasis, independent prognostic factors after gastrectomy were operative curability and depth of wall invasion. Long-term survival can be achieved when the patients have no serosal invasion (T1, T2) and are treated by curative gastrectomy.

Journal Article↗

Surgical results of proximal gastrectomy for early-stage gastric cancer: jejunal interposition and gastric tube reconstruction.

BACKGROUND: The frequency of tumors in the upper one-third of the stomach has been increasing. The standard operation for proximal gastric cancer has been total or proximal gastrectomy. The aim of this study was to present the pathologic and surgical results of 30 patients with early-stage proximal gastric cancer managed by proximal gastrectomy.METHODS: A consecutive series of 30 patients who underwent proximal gastrectomy for early-stage proximal gastric cancer was studied. Sixteen patients underwent jejunal interposition, while 14 underwent gastric tube reconstruction, which consisted of a direct anastomosis between the esophagus and the remnant of the tube-like stomach.RESULTS: Twenty patients (67%) had no abdominal symptoms and the lesions were detected by screening gastric fiberscopy. The tumors were mostly located along the lesser curvature (73%), were grossly depressed type (IIc) (70%), and histologically well differentiated type (63%). The depth of wall invasion was the mucosa in 12 patients, submucosa in 15, and muscularis propria in 3; lymph node metastasis was absent in 28 patients (93%). When compared with patients with jejunal interposition, patients with gastric tube reconstruction had a shorter operation time (327 vs 165 min), less blood loss (508 vs 151 g), and shorter hospital stay after operation (31 vs 17 days). Endoscopy and 24-h pH monitoring showed no evidence of reflux esophagitis, except in 1 patient with gastric tube reconstruction, and no patient died of recurrence.CONCLUSIONS: Early-stage proximal gastric cancer can be successfully treated by proximal gastrectomy. Since gastric tube reconstruction is a simple, easy, and safe procedure, proximal gastrectomy followed by gastric tube reconstruction is recommended for patients with early-stage proximal gastric cancer.

Journal Article↗

Gastric cancer presenting with obstructive jaundice.

Gastric cancer is rarely associated with obstructive jaundice, which is associated with poor survival. We describe five patients with gastric cancer who presented with jaundice. Two patients had primary gastric cancer and three had recurrent disease. The patients were treated by operation, chemotherapy, and percutaneous transhepatic biliary drainage (PTBD) according to the stage of the cancers. Although these treatments often fail to prolong survival, chemotherapy and PTBD can improve patient's quality of life.

Journal Article↗

Laparoscopy in the management of scirrhous gastric cancer.

BACKGROUND: Scirrhous gastric cancer frequently shows extensive tumor spread, and gastrectomy for cure of the disease is not possible in the presence of peritoneal dissemination, which is often overlooked by conventional computed tomography. The aim of this study was to evaluate our experience of 16 patients who underwent laparoscopy in the management of scirrhous gastric cancer, and to examine whether peritoneal dissemination could be diagnosed accurately by laparoscopy.METHODS: All patients had nonobstructed, nonbleeding scirrhous gastric cancer and had no evidence of metastatic disease by ultrasonography and computed tomography. Laparoscopy was performed under general anesthesia with CO(2) pneumoperitoneum. A Hasson trocar and two manipulating forceps were inserted, and the surfaces of the peritoneum, omentum, stomach, spleen, pancreas, liver, and diaphragm were examined.RESULTS: The mean time for laparoscopy was 20 min. Peritoneal dissemination was disclosed in 4 patients (25%), and systemic and intraperitoneal chemotherapy was done without laparotomy. In 12 patients, subsequent gastrectomy with a curative intent was successfully performed. Pathology revealed that the tumor diffusely invaded the whole thickness of the gastric wall; the mean size of resected tumors was 12 cm, and the mean number of positive nodes was 17. Nine patients died of the disease with a mean survival period of 10 months, and 7 patients were alive without recurrence during a mean follow-up period of 11 months.CONCLUSIONS: Laparoscopy is useful for the evaluation of peritoneal spreads of advanced gastric cancer, can avoid unnecessary laparotomy because of peritoneal dissemination, and is important for the choice of treatments in patients with scirrhous gastric cancer.

Journal Article↗

Long-term survival after perforation of advanced gastric cancer: Case report and review of the literature.

Although the standard operation for early cancer of gastric cardia is proximal gastrectomy followed by jejunal interposition, we recently reported a simple and useful technique for proximal gastrectomy with gastric tube reconstruction. The operative procedures included resection of the proximal two-thirds of the stomach, followed by anastomosis between the esophagus and gastric tube, using a circular stapler (Proximate ILS 25; Ethicon, Cincinnati, OH, USA). The gastric tube was about 20 cm long and 4 cm wide. The patient a 76-year-old man had no reflux symptoms such as heartburn, retrosternal pain, and regurgitation. Endoscopy showed no evidence of reflux esophagitis, including mucosal redness, erosion, and ulceration. Ambulatory 24-h pH monitoring indicated that the pH of the lower esophagus was between 6 and 8 when the patient was upright and between 5 and 7 when he was in the supine position. There were nine reflux episodes during the day, and no reflux episode while he was asleep. The duration of each reflux episode was less than 1 min, and the total reflux time was 1 min in the 12-h day (0.1%). These data indicate that reconstruction by gastric tube may prevent esophageal reflux in patients who have undergone proximal gastrectomy for early cancer of the gastric cardia.

Journal Article↗

Gastric tube reconstruction prevented esophageal reflux after proximal gastrectomy.

Although the standard operation for early cancer of gastric cardia is proximal gastrectomy followed by jejunal interposition, we recently reported a simple and useful technique for proximal gastrectomy with gastric tube reconstruction. The operative procedures included resection of the proximal two-thirds of the stomach, followed by anastomosis between the esophagus and gastric tube, using a circular stapler (Proximate ILS 25; Ethicon, Cincinnati, OH, USA). The gastric tube was about 20 cm long and 4 cm wide. The patient a 76-year-old man had no reflux symptoms such as heartburn, retrosternal pain, and regurgitation. Endoscopy showed no evidence of reflux esophagitis, including mucosal redness, erosion, and ulceration. Ambulatory 24-h pH monitoring indicated that the pH of the lower esophagus was between 6 and 8 when the patient was upright and between 5 and 7 when he was in the supine position. There were nine reflux episodes during the day, and no reflux episode while he was asleep. The duration of each reflux episode was less than 1 min, and the total reflux time was 1 min in the 12-h day (0.1%). These data indicate that reconstruction by gastric tube may prevent esophageal reflux in patients who have undergone proximal gastrectomy for early cancer of the gastric cardia.

Journal Article↗

Prolongation of heart allograft survival of rats treated by a Th2 inhibitor.

In terms of Th1/Th2 balance in response to signals given during donor antigen presentation, induction of tolerance is more often correlated with Th2-type than with Th1-type reactions. However, in our study, heart allograft survival was prolonged by treatment of rats with a Th2 inhibitor. Suplatast tosilate (IPD; Taiho; Tokyo, Japan) is a novel immunoregulator that suppresses IgE production and eosinophil infiltration through selective inhibition of interleukin (IL)-4 and IL-5 synthesis by Th2-like cells but not IFN-gamma production in Th1 cells. Five LEW rats of DA heart grafts were treated with IPD (100 microg/day, p.o.) for 10 days. Heart allograft survival of all IPD-treated cases was prolonged more than 14 days while the beating of heart grafts in control groups was stopped within 9 days. In an in vitro study, the cell proliferation both in Con A blast and in mixed lymphocyte reaction assay was suppressed by IPD in dose-dependent manner. We could at least in part conclude that Th2 inhibition might temporarily suppress heart allograft rejection.

Animals↗

Inhibition of indoleamine 2,3-dioxygenase suppresses NK cell activity and accelerates tumor growth.

Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, is induced under various pathological conditions, including viral and bacterial infection, allograft rejection, cerebral ischemia, and tumor growth. We have previously reported that the expression of IDO mRNA was increased in some clinical cases of hepatocellular carcinoma in which the recurrence-free survival rate in these IDO-positive patients was significantly higher than that in patients without IDO mRNA induction in tumors. Additionally, IDO expressed in tumors was localized not to the tumor cells but instead to tumor-infiltrating cells by immunohistochemistry. In this study, in order to elucidate the mechanisms underlying anti-tumor effect of IDO, we investigated whether IDO inhibitor (1-methyl-dl-tryptophan, 1MT) affects the growth of subcutaneous B16 tumors in mice. Subsequently, the activity of natural killer (NK) cells was investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA expression of B16 cells, B16 subcutaneous tumor, sprenocytes of mice, and human NK cells were studied by reverse transcription-polymerase chain reaction. B16 subcutaneous tumor growth with or without IDO inhibition was observed and cytotoxic activity of NK cells were investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA was expressed in B16 subcutaneous tumor, splenocytes of tumor bearing mice, co-cultured splenocytes with B16, and human NK cells. On day 14, after injection of B16 melanoma cells, the sizes of tumors in IDO-inhibited mice were significantly larger than those in control mice. The cytotoxic activity of mice NK cells was reduced by IDO inhibition in vivo. In vitro inhibition of IDO, NK activity was reduced in dose-dependent manner of 1MT. In conclusion, these results indicated that IDO plays an important role in anti-tumor immunity by regulating cytotoxic activity of NK cells.

Animals↗