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Biomedical subjects

Seigo Kitano

Publications and source records attributed to Seigo Kitano.

At least 73 records · Page 4Linked to original sources

Z-shaped anastomosis for the treatment of a benign rectosigmoid stricture.

A girl with malrotation underwent a Ladd's operation at 35 days of age and later had an adhesiotomy at 115 days of age. After the adhesiotomy, she suffered from sepsis and subsequent disseminated intravascular coagulation (DIC). At 178 days of age, she developed an intestinal obstruction because of a rectosigmoid stricture probably caused by DIC-associated ischemia. As a result, an ileostomy was performed. At one year, 4 months of age, she underwent a resection of the proximal part of the rectosigmoid stricture and a reconstruction by means of a Z-shaped anastomosis. Based on our experience, Z-shaped anastomosis appears to be an excellent treatment not only for Hirschsprung's disease but also for benign rectosigmoid stricture.

Anastomosis, Surgical↗

Potent stimuli combined with lipopolysaccaride and IFNgamma may improve immunotherapy against HCC by increasing the maturation and subsequent immune response of the dendritic cells.

Dendritic cells (DCs)-based immunotherapy is a new strategy for cancer treatment and has been used in some clinical trials against cancer, including melanoma, and has shown promising results. However, the conventional protocol of DC immunotherapy may not be effective for hepatocellular carcinoma (HCC) because of impaired DC maturation in HCC patients. In order to induce sufficient maturation on HCC derived DCs, we tested various stimuli such as tumor necrosis factor (TNF) alpha, lipopolysaccharide (LPS), interferon (IFN)gamma and CD40-ligand. In stimulating with LPS + IFNgamma, DCs of HCC patients expressed significantly high levels of CD86 (p < 0.05) and produced high levels of IL-12 as compared to DCs stimulated with TNFalpha alone. Moreover, it showed better ability to stimulate allogeneic mixed lymphocyte reaction. It concluded that LPS and IFNgamma was the best combination of stimuli for induction of sufficient maturation on DCs derived from HCC.

Carcinoma, Hepatocellular↗

Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: To determine the optimal management of the intraductal papillary mucinous neoplasms (IPMNs) according to the morphologic type based on distinguishing between benign and malignant diseases. BACKGROUNDS: IPMNs are increasingly recognized clinicopathologic entity. Extended pancreatic resection with radical lymph node dissection has been recommended for treatment. STUDY: A retrospective clinicopathologic study was carried out of the 57 cases with IPMNs who were treated between 1985 and 2001. Forty-three patients with IPMNs underwent resection, and 14 patients with small IPMNs were observed without resection. RESULTS: Among the 43 resected IPMNs, 25 were benign and 18 were malignant. Malignant tumors were significantly greater in diameter than benign tumors (52.9 vs. 30.2 mm, P< 0.05). All main duct type tumors with mural nodules were malignant. All branch duct type tumors less than 30 mm in diameter and without mural nodules were benign. Twelve branch duct type IPMNs size less than 30 mm were not resected and have not progressed. CONCLUSION: These results suggest that the branch duct type IPMNs less than 30 mm and without mural nodules is benign and might be treatable with limited resection or careful observation.

Adult↗

AFP-producing gastric carcinoma: multivariate analysis of prognostic factors in 270 patients.

Serum alpha-fetoprotein (AFP) is sometimes high in patients with primary gastric carcinoma, and there is no comprehensive study on the clinicopathologic characteristics and prognostic factors of AFP-producing gastric carcinoma (AGC). To clarify the variables associated with the survival after gastrectomy for AGC, we reviewed the data of patients with AGC and examined the independent prognostic factors. We studied 270 cases of AGC reported in the Japanese literature from June 1982 to March 2001, together with 1 patient of our own experience. The clinicopathologic findings, including serum AFP level, operative curability, and stage of the disease were examined, and factors associated with survival were determined by multivariate analysis. There were 15 stage I tumors (6%), 50 stage II tumors (19%), 51 stage III tumors (20%), and 145 stage IV tumors (55%). The tumors were characterized by frequent serosal invasion (75%), lymph node metastasis (83%), liver metastasis (33%), stage III or IV disease (75%), and noncurative operation (48%). The survival was influenced by the serum AFP level, tumor size, serosal invasion, lymph node metastasis, and liver metastasis, but the independent prognostic factors were operative curability (curative vs. noncurative) and stage of the disease (I, II vs. III, IV). Although the 5-year survival rate and median survival period in all patients were 22% and 14 months, respectively, those in patients with curative gastrectomy were 42% and 29 months, respectively. The results indicate that operative curability and stage of the disease are factors associated with the survival of patients with AGC. Although tumors are often advanced and complicated with liver metastases, long-term survival can be achieved when patients with stage I or II tumor undergo curative gastrectomy.

Biomarkers, Tumor↗

Oncolytic viral therapy for human pancreatic cancer cells by reovirus.

PURPOSE: Pancreatic cancer has a poor prognosis and few effective therapies are available. The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently found in pancreatic cancer. EXPERIMENTAL DESIGN: In this study, we examined the feasibility of using reovirus (serotype 3) as an antihuman pancreatic cancer agent. RESULTS: Reovirus was able to infect five human pancreatic cancer cell lines (Panc1, MIApaca-2, PK1, PK9, and BxPC3) in vitro. We also confirmed that the Ras activity in these cancer cell lines was elevated compared with that in the normal cell line and that susceptibility to reovirus was associated with the Ras activity of these cells. In a unilateral murine xenograft model using Panc1 and BxPC3 cell lines, each tumor growth was suppressed by intratumoral injection of reovirus. Furthermore, local injection of reovirus also had systemic antitumor effects in a bilateral xenograft model using Panc1 cell line. Immunohistochemical examination revealed that reovirus replication was observed within the tumor but not in surrounding normal tissue. CONCLUSIONS: These results suggest that reovirus can be considered for a novel therapy against pancreatic cancer.

3T3 Cells↗

[Laparoscopic and open splenectomy for idiopathic thrombocytopenic purpura].

Idiopathic thrombocytopenic purpura(ITP) is an immune disorder, which causes an acute or chronic thrombocytopenia, and may result in potentially life-threatening hemorrhage. Splenectomy is one of the treatment options that needs to be weighted in the treatment of ITP, particularly in cases that have shown response failure to medical modalities such as prednisone, or anti-D globulin therapy. However, because open splenectomy (OS) requires more surgical invasiveness, surgical treatment had not been accepted for many patients with ITP. Recently, laparoscopic splenectomy(LS) is being accepted as an effective alternative to OS in treating ITP. The most important parts of this method are, mobilization of the spleen by dissection of the splenic ligament, and the blocking of blood circulation to the spleen by division of the hilar arteries and veins. The procedure is as follows: (1) The patient is in a right lateral decubitus position. (2) The resection of the splenic ligament is made by an ultrasonic coagulating dissector. (3) The splenic hilum is dissected with an auto-stapler. (4) The freed spleen is contained in a nylon bag and extracted. Laparoscopic splenectomy is a feasible and safe for patients with ITP.

Humans↗

[Supporting system for regional medical liaison and role of a central hospital].

The current status and future development of the supporting system for regional medical liaison and a role of the central hospital in the network were outlined. One of such supportive systems for regional medical network would be tele-medicine or tele-mentoring that include radiological and pathological diagnoses in distance, tele-surgery, and tele-education. Most of these systems are facilitated in the universities and affiliated hospitals and generally need high-cost communication equipment. Another approach is the information sharing system through the modern telecommunication network. Electronic patient record (EPR) systems are the key to achieving this and currently active in several areas. Since the recent progress in information technology (IT) is astonishing, community-based EPR systems are practical with the capability of clinical information exchange between different institutions and even with patients. The role of a central hospital in these systems must be capacious. Management and continuous operation of the system would be the most important affairs. For extending these supporting systems to the ones working in a broader area, the establishment of a "one ID for one patient" system is crucial. Strict security management of the data base and legal institution for distant medical practice still remain as the future tasks.

Community Networks↗

Prognostic significance of intrahepatic lymphatic invasion in patients with hepatic resection due to metastases from colorectal carcinoma.

BACKGROUND: Intrahepatic spread from liver metastases of colorectal carcinoma has been well described; however, its prognostic value after hepatectomy is controversial. To clearly determine factors predicting survival after hepatectomy in such patients, the authors evaluated 14 clinicopathologic factors of liver metastasis from colorectal carcinoma with special reference to intrahepatic lymphatic invasion. METHODS: The authors retrospectively analyzed data obtained from 67 consecutive patients who underwent hepatectomy for liver metastasis from colorectal carcinoma. Intrahepatic spread was classified into discreet categories that were evaluated separately: invasion to the portal vein, hepatic vein, bile duct, and lymphatic or perineural space. Overall survival and disease free survival periods were examined as functions of clinicopathologic determinants by univariate and multivariate analyses. RESULTS: Intrahepatic spread was found in a total of 28 (43.1%) of the 65 evaluable cases. Portal vein invasion was found in 15 (23.1%) of these cases, hepatic vein invasion in 3 (4.6%), bile duct invasion in 10 (15.4%), and intrahepatic lymphatic invasion in 10 (15.4%). Five year overall and disease free survival rates after hepatectomy were 33.4% and 28.5%, respectively. A short interval (< 12 months) from treatment of primary colorectal carcinoma to liver metastasis and the presence of intrahepatic lymphatic invasion significantly and adversely affected the overall and disease free survival rates. CONCLUSIONS: Intrahepatic lymphatic invasion was shown statistically to be an independent predictor of recurrence and death after hepatectomy in patients with liver metastases from primary colorectal carcinoma.

Adult↗

Clinical outcome of proximal versus total gastrectomy for proximal gastric cancer.

Tumors in the upper one-third of the stomach has been increasing. Although the standard operation for proximal gastric cancer has been total gastrectomy, some have used proximal gastrectomy reconstructed by jejunum or gastric tube. The aim of this study was to evaluate the surgical results, hospital costs, and quality of life after gastrectomy for cancer. A consecutive series of 51 patients with stage I or II proximal gastric cancer was studied: 14 underwent proximal gastrectomy reconstructed by gastric tube (direct anastomosis between esophagus and remnant of tube-like stomach), 17 proximal gastrectomy reconstructed by jejunum, and 20 total gastrectomy in Roux-en-Y fashion. Quality of life was estimated by a 24-item questionnaire with a scoring system of 1 to 3, and hospital costs covered all charges during the hospital stay. Operating time, blood loss, and hospital stay for the gastric tube group were less than those for the jejunum group or the total gastrectomy group. Hospital charges for the gastric tube group were lower than those for the jejunum group or the total gastrectomy group (141 x 10 4 yen, 179 x 10 4 yen, 211 x 10 4 yen, respectively). Although the total score for quality of life was not significantly different among the three groups (35.9, 39.5, 37.6), the number of meals per day was less and the performance status was better in the gastric tube group. Jejunal interposition was less favorably accepted by the patients as a good operation they would recommend to others. The results indicate that, in patients with proximal gastric cancer, proximal gastrectomy reconstructed by gastric tube provides a shorter operating time, earlier recovery, lower hospital charge, and better performance status when compared with proximal gastrectomy reconstructed with jejunum or total gastrectomy.

Aged↗

Prognostic factors after pancreatoduodenectomy with extended lymphadenectomy for distal bile duct cancer.

BACKGROUND: Since 1995, we have been performing pancreatoduodenectomy with regional and para-aortic lymph node dissection for patients with distal bile duct cancer. Prognostic indicators after extended lymphadenectomy have not been fully understood. HYPOTHESIS: Pancreatoduodenectomy with extended lymphadenectomy and adjuvant chemotherapy is the treatment of choice for patients with distal bile duct cancer. DESIGN: In a retrospective study, univariate and multivariate models were used to analyze the effect of patient demographics, tumor characteristics, and treatment factors on long-term survival. SETTING: Oita Medical University and its affiliated hospitals in Japan. PATIENTS: From 1995 to 1999, 27 patients with distal bile duct cancer underwent pancreatoduodenectomy with extended lymphadenectomy. In 9 patients fluorouracil (500 mg/d) was infused continuously for 14 days after surgery as adjuvant chemotherapy. MAIN OUTCOME MEASURES: Clinicopathologic characteristics and long-term results. RESULTS: In 6 patients (22%) major surgical complications occurred including 1 in-hospital death (3.7%). For 26 patients, the survival rates were 65% for 1 year and 37% for 3 and 5 years. Univariate analysis found that the absence of lymph node metastasis, no more than 2 involved nodes, and negative resection margins were predictors of survival. Multivariate analysis with a Cox proportional hazards regression model revealed that favorable factors for survival included up to 2 positive nodes, negative resection margins, and the use of postoperative adjuvant chemotherapy. CONCLUSIONS: Patients with up to 2 positive lymph nodes had a more favorable prognosis than that of other patients. We recommend pancreatoduodenectomy with extended lymphadenectomy and adjuvant chemotherapy for the treatment of patients with distal bile duct cancer.

Antimetabolites, Antineoplastic↗

Superficially spreading cancer of the stomach.

BACKGROUND: Superficially spreading cancer (SSC) of the stomach is rare and extends widely along the mucosa or submucosa of the stomach. This study was conducted to clarify the clinicopathologic characteristics and prognosis of patients with SSC. METHODS: SSC was defined as a tumor invading the mucosa or submucosa and measuring > or =5 cm in size. The clinicopathologic findings and outcomes of 36 patients with SSC were compared with those of 300 patients with early gastric cancer (EGC) measuring < or =5 cm and 271 with advanced gastric cancer measuring > or =5 cm. RESULTS: SSC was significantly different from ordinary EGC in tumor size, frequency of lymph node metastasis, lymphatic invasion, venous invasion, and stage II, III, and IV disease. The frequency of serosal invasion, lymph node metastasis, and lymphatic and venous invasions in cases of SSC was significantly lower than with advanced gastric cancer. Although tumor size of SSC evaluated before operation was smaller than that on the resected specimen, the 10-year survival rate was not different between SSC and ordinary EGC. CONCLUSIONS: SSC was characterized by high frequency of lymph node metastasis and preoperative underestimation of tumor size. SSC should be treated by a gastrectomy and lymphadenectomy with sufficient resection margin.

Aged↗

Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer.

BACKGROUND: There is no consensus as to the impact of lymph node micrometastasis on survival of patients with gastric cancer. The aim of this study was to clarify the prognostic significance of lymph node micrometastasis in patients with histologically node-negative gastric cancer. METHODS: Lymph nodes (n = 2039) from 64 patients with histologically node-negative gastric cancer (T2, T3) were evaluated for micrometastasis. Three serial 5- micro m sections of the resected lymph nodes were prepared for immunohistochemical staining with the anti-cytokeratin antibody CAM 5.2. RESULTS: Micrometastasis was found in 73 of 2039 nodes (4%) and 20 of 64 patients (32%). The 5-year survival rate was significantly lower for patients with lymph node micrometastasis than for those without lymph node micrometastasis (66% vs. 95%, P <.01). The 5-year survival rate was significantly lower when there were four or more positive micrometastatic nodes (94% vs. 29%, P <.01) and when there were extragastric micrometastatic nodes (89% vs. 53%, P <.01). CONCLUSIONS: Lymph node micrometastasis was associated with poor outcome in patients with histologically node-negative gastric cancer. The number and the level of lymph node micrometastases are useful prognostic markers for deciding treatment strategies for additional therapy and follow-up.

Adenocarcinoma↗

Prolonged survival after repeat resection of pulmonary metastasis from hepatocellular carcinoma.

We report a patient in whom two pulmonary resections were performed for lung metastasis after hepatic resection of hepatocellular carcinoma (HCC). A 56-year-old Japanese man with an 8-year history of chronic liver disease was admitted with elevated serum alpha-fetoprotein (AFP) and a liver tumor that had been detected by ultrasonography. Computed tomography showed a 6-cm tumor in the medial segment of the liver, and partial resection of the medial segment was performed. Thirty-six months after the first operation, pulmonary resection was performed for a solitary metastasis in the left lung. Fifty-one months after the second operation, a solitary metastatic tumor was detected in the right lung, without any evidence of recurrence or other metastatic foci, and thoracoscopic partial resection of the right lung was performed as the third operation. The patient is alive 36 months after the second pulmonary resection, has a normal AFP value, and shows no signs of recurrent or metastatic foci. Repeat pulmonary resection for metastasis from HCC resulted in long-term survival in this patient.

Carcinoma, Hepatocellular↗

Laparoscopic cholecystectomy for acute cholecystitis.

The application of laparoscopic cholecystectomy (Lap. C) for acute cholecystitis (AC) remains controversial from the viewpoint of its higher rate of morbidity, and conversion to open surgery, in spite of the worldwide acceptance of Lap. C as the gold standard for the treatment of patients with symptomatic gallbladder diseases. The conversion rate has been reported to decrease with experience. Local and overall complication rates were shown to correlate with the time delay between the onset of acute symptoms and the operation. Although percutaneous gallbladder drainage (PGBD) has been reported to be a safe and effective procedure for the treatment of AC, it should be limited to high-risk groups such as elderly or critically ill patients. Early cholecystectomy within 4 days from the onset is strongly recommended to minimize surgical complications and to increase the chance of a successful laparoscopic approach.

Acute Disease↗

Antitumor and antivascular effects of AC-7700, a combretastatin A-4 derivative, against rat liver cancer.

BACKGROUND: Unlike the many chemotherapeutic agents that do not effectively stop blood flow or induce necrosis in hepatocellular carcinoma, AC-7700 has been shown to inhibit tubulin polymerization and selectively stop tumor blood flow. The aim of this study was to elucidate the antivascular and antitumor effects of AC-7700 on rat hepatoma. METHODS: AH-130 cells, a rat hepatoma cell line, were solidified and implanted into the liver of Donryu rats. Vascularity of the liver tumor was directly identified by in-vivo fluorescence microscopy from 0 to 60 min after the injection of 10 mg/kg AC-7700. To observe the antivascular effect of AC-7700, the vascular density of the tumor was measured and assessed as the ratio of preinjection to postinjection values. The antitumor effects were evaluated with histopathologic findings and analysis of animal survival. RESULTS: In-vivo microscopic observation showed that tumor perfusion diminished within 30 min after AC-7700 administration. Vascular density in the AC-7700 group was significantly less than that in the control group at 60 min (AC-7700, 26.3 +/- 16.4%; control, 88.5 +/- 9.2%; P < 0.001). After AC-7700 injection, marked necrosis of tumor cells was observed histologically, and tumor area was decreased significantly (AC-7700, 11.5 +/- 15.4 mm2; control, 43.5 +/- 18.3 mm2; P < 0.05). The survival rate (50%) of the AC-7700 group animals was better than that of the control group (0%; P < 0.01). CONCLUSION: Markedly decreased tumor perfusion was induced by AC-7700 within 30 min, and this decrease may have contributed to the tumor necrosis and favorable outcome in the treatment group. AC-7700 appears to be a promising agent for the treatment of hepatocellular carcinoma.

Angiogenesis Inhibitors↗

Esophageal ulceration triggers expression of hypoxia-inducible factor-1 alpha and activates vascular endothelial growth factor gene: implications for angiogenesis and ulcer healing.

Our previous studies demonstrated that enhanced epithelial cell proliferation is important for healing of experimental esophageal ulcers. However, the roles of angiogenesis, its major mediator, vascular endothelial growth factor (VEGF), and the mechanism(s) regulating VEGF expression during esophageal ulcer healing remain unknown. Esophageal ulcers were induced in rats by focal application of acetic acid. We studied expressions of hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha), an activator of the VEGF gene, and VEGF by reverse transcriptase-polymerase chain reaction, Western blotting, and immunostaining. To determine the efficacy of VEGF gene therapy in esophageal ulcer healing, we studied whether a single local injection of plasmid cDNA encoding recombinant human VEGF(165) affects ulcer healing and angiogenesis. Esophageal ulceration induced HIF-1 alpha protein expression and VEGF gene activation reflected by increased VEGF mRNA (240%) and VEGF protein (310%) levels. HIF-1 alpha protein was expressed in microvessels bordering necrosis where it co-localized with VEGF. Injection of cDNA encoding VEGF(165) significantly enhanced angiogenesis and accelerated esophageal ulcer healing. These results: 1) suggest that HIF-1 alpha may mediate esophageal ulceration-triggered VEGF gene activation, 2) indicate an essential role of VEGF and angiogenesis in esophageal ulcer healing, and 3) demonstrate the feasibility of gene therapy for the treatment of esophageal ulcers.

Animals↗

Selective cyclooxygenase-2 blocker delays healing of esophageal ulcers in rats and inhibits ulceration-triggered c-Met/hepatocyte growth factor receptor induction and extracellular signal-regulated kinase 2 activation.

Nonsteroidal anti-inflammatory drugs, both nonselective and cyclooxygenase-2 (COX-2) selective, delay gastric ulcer healing. Whether they affect esophageal ulcer healing remains unexplored. We studied the effects of the COX-2 selective inhibitor, celecoxib, on esophageal ulcer healing as well as on the cellular and molecular events involved in the healing process. Esophageal ulcers were induced in rats by focal application of acetic acid. Rats with esophageal ulcers were treated intragastrically with either celecoxib (10 mg/kg, once daily) or vehicle for 2 or 4 days. Esophageal ulceration triggered increases in: esophageal epithelial cell proliferation; expression of COX-2 (but not COX-1); hepatocyte growth factor (HGF) and its receptor, c-Met; and activation of extracellular signal-regulated kinase 2 (ERK2). Treatment with celecoxib significantly delayed esophageal ulcer healing and suppressed ulceration-triggered increases in esophageal epithelial cell proliferation, c-Met mRNA and protein expression, and ERK2 activity. In an ex vivo organ-culture system, exogenous HGF significantly increased ERK2 phosphorylation levels in esophageal mucosa. A structural analog of celecoxib, SC-236, completely prevented this effect. These findings indicate that celecoxib delays esophageal ulcer healing by reducing ulceration-induced esophageal epithelial cell proliferation. These actions are associated with, and likely mediated by, down-regulation of the HGF/c-Met-ERK2 signaling pathway.

Animals↗