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Biomedical subjects

Seigo Kitano

Publications and source records attributed to Seigo Kitano.

At least 37 records · Page 2Linked to original sources

Biotin-rich intranuclear inclusions in morule-lacking adenocarcinoma of the gallbladder: a new category of "neoplastic/non-morular" lesions.

Biotin-rich intranuclear inclusions, also called "optically clear nuclei," are observed in various neoplastic and non-neoplastic lesions, including pregnancy-related endometrium and benign and malignant neoplasms with morular structures. A recent study reported that lesions with biotin-rich intranuclear inclusions can be classified as "(non-neoplastic) pregnancy-related endometrial" and as "(neoplastic) morular" category. In the present report, we describe two cases of well-differentiated adenocarcinoma of the gallbladder in which biotin-rich intranuclear inclusions were found without morular structures. Immunohistochemically, as reported previously, the intranuclear inclusions were positive for biotin and two biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). Intranuclear expression of beta-catenin was also observed in neoplastic cells with and without intranuclear inclusion. We also detected a frame shift mutation of APC gene in one case but no mutation of beta-catenin gene in both cases. Although intranuclear expression of beta-catenin by mutation of APC gene might contribute to carcinogenesis in our cases, the relationships among intranuclear expressions of beta-catenin, biotin, biotin-binding enzymes and intranuclear inclusions remain unclear. Our cases are the first neoplastic lesions with biotin-rich intranuclear inclusions that lacked morular structures. We propose a new "neoplastic/non-morular" category for lesions with biotin-rich intranuclear inclusions.

Adenocarcinoma↗

Safety and efficacy of laparoscopic distal pancreatectomy for the treatment of pancreatic disease.

BACKGROUND/PURPOSE: There are a few reports of laparoscopic distal pancreatectomy in the literature. We describe our experience with laparoscopic distal pancreatectomy and evaluate the safety and efficacy of the procedure in light of other reported findings. METHODS: A retrospective study was performed of all patients who underwent laparoscopic distal pancreatectomy between April 1996 and December 2002 at Oita University Faculty of Medicine. RESULTS: Laparoscopic distal pancreatectomy was attempted in seven patients (three men and four women) with a mean age of 65 years. One patient was converted to open surgery, and two patients required a hand-assistance procedure. There were no complications in any patients. Median operation time for all seven patients was 300 min, and median blood loss was 330 ml. Median postoperative hospital stay was 12 days (range, 7 to 21 days). CONCLUSIONS: Our limited results, together with reported outcomes, suggest that laparoscopic distal pancreatectomy is safe and effective for selected patients. The potential advantages of this procedure include reduced morbidity and reduced hospital stay.

Aged↗

An extramural gastrointestinal stromal tumor of the duodenum mimicking a pancreatic head tumor.

We report the case of a 53-year-old woman with a gastrointestinal stromal tumor (GIST) of the duodenum that showed only extramural growth, mimicking a pancreatic tumor. Preoperatively, computed tomography (CT) and angiography revealed a hypervascular mass, 3.0 cm in diameter, in the pancreatic head. Hypotonic duodenography showed compression of the second and third portions of the duodenum by the pancreatic lesion. Endoscopic examination showed no specific mucosal abnormalities in the duodenal lumen. The pancreatic head tumor was diagnosed preoperatively as a nonfunctioning islet cell tumor of the pancreas, and the patient underwent pylorus-preserving pancreaticoduodenectomy. A hard mass was palpated intraoperatively in the pancreatic head region, and neither peritoneal dissemination nor metastasis was detected. Histologically, the tumor was composed of spindle-shaped cells with a fascicular growth pattern, and only a few mitotic features were seen. Immunohistochemically, most of the tumor cells were positive for c-kit oncoprotein and CD34, but negative for alpha-smooth muscle actin and S-100 protein. Therefore, this neoplasm was finally diagnosed as a duodenal GIST of the uncommitted type. This is a rare case of a duodenal GIST with exclusively extramural growth mimicking a pancreatic head tumor.

Diagnosis, Differential↗

Analysis of risk factors for massive intraoperative bleeding during laparoscopic splenectomy.

BACKGROUND/PURPOSE: Laparoscopic splenectomy is occasionally converted to open surgery due to massive intraoperative bleeding. The aim of this study was to identify the risk factors for massive bleeding during laparoscopic splenectomy. METHODS: Fifty-three patients underwent laparoscopic splenectomy. The indications were hematologic disease in 25 patients, liver cirrhosis in 17 patients, and other conditions in 11 patients. Univariate analysis was conducted with Fisher's exact test, and multivariate analysis was conducted with a stepwise logistic regression model. RESULTS: None of the patients required open surgery. Blood loss of more than 800 ml was defined as massive intraoperative bleeding. Univariate analysis showed significant risk factors for massive bleeding to be liver cirrhosis, portal hypertension, splenomegaly, Child class, and preoperative platelet count. Independent risk factors in the multivariate analysis were portal hypertension and Child class. CONCLUSIONS: Careful attention to intraoperative bleeding during laparoscopic splenectomy is necessary for patients with portal hypertension and/or deteriorated liver function.

Adult↗

Minimally invasive surgery for gastric cancer--toward a confluence of two major streams: a review.

The minimalization of therapeutic invasiveness in order to preserve quality of life (QOL) is a major topic in the management of early gastric cancer. After laparoscopic surgery for gastric cancer was introduced by Kitano et al. in 1991, an enthusiasm to develop laparoscopic procedures has grown steadily. In the initial phase, early gastric cancer limited to the mucosal layer with no risk of lymph node metastasis was treated by laparoscopic wedge resection or intragastric mucosal resection. Since technical and instrumental advances in endoscopic treatment were achieved by gastroenterologists, these cases can be managed by intraluminal endoscopic approaches. The attention of surgeons then shifted to more radical procedures such as laparoscopic gastrectomy with lymph node dissection, which is comparable to open surgery and can be indicated even in advanced cancer. Although this paradigm shift has already been realized in the field of colorectal surgery, we must pay attention to the particular biological nature of gastric cancer in terms of the potential of peritoneal dissemination. While early-phase recovery after surgery has been improved by laparoscopic surgery, preservation of late-phase QOL by function-preserving surgery is also essential in this regard; therefore, the sentinel node (SN) concept has been a much-discussed topic in gastric cancer surgery to approach this aspect. Recently, the validity of the SN concept has been demonstrated by a number of single institutional studies, and prospective multicenter trials are currently ongoing. Theoretically, various types of function-preserving surgery could be applied in cases of early gastric cancer with negative SNs as less invasive surgery to improve long-term QOL. Although we still have to solve several remaining issues in the treatment of gastric cancers, a confluence of these two major streams, laparoscopic surgery and sentinel node navigation surgery, would enable us to apply a novel individualized minimally invasive approach, both in terms of degree of incisional access and extent of function preservation.

Gastrectomy↗

Analysis of preoperative prognostic factors for long-term survival after hepatic resection of liver metastasis of colorectal carcinoma.

Hepatic resection is the most effective therapy for liver metastasis of colorectal carcinoma. To clarify indications for this therapy, the clinicopathologic and follow-up data of 103 consecutive patients who underwent hepatic resection for metastases of colorectal carcinoma were analyzed. Factors influencing overall survival rate were investigated by multivariate analysis. Thereafter, patients who underwent resection were stratified according to the number of independent risk factors present, and their outcomes were compared with those of 14 nonresection patients with fewer than six liver tumors and without extrahepatic metastasis. The overall survival rate of the 103 resection patients was 43.1%. The clinicopathologic factors shown to affect on long-term survival after hepatic resection were the interval between colorectal and hepatic surgery (<12 months), preoperative carcinoembryonic antigen level (> or =10 ng/ml), and number of hepatic metastases (four or more). The 5-year overall survival rates were 75.0% with no risk factors (n=16), 53.6% with one risk factor (n=46), 23.0% with two risk factors (n=36), and 0% with three risk factors (n=5). Survival rates did not differ between resection patients with three risk factors and nonresection patients. Therefore, hepatic resection may be appropriate for patients with fewer than three risk factors.

Adenocarcinoma↗

Minimally invasive surgery for gastric tumors.

Since 1991, laparoscopic surgery has been adopted for the treatment of gastric tumors, including gastric cancer and gastric gastro-intestinal submucosal tumor (GIST). Although laparoscopic gastric resection for gastric tumors has not been accepted worldwide, its use has definitively increased due to its reduced invasiveness. The most common procedures are laparoscopy-assisted distal gastrectomy (LADG) for cancer and laparoscopic gastric resection as a standard of care for gastric tumors, multicenter randomized controlled clinical trials are needed to evaluate its short- and long-term outcomes.

Gastrectomy↗

Malignant serous cystic neoplasm of the pancreas: report of a case and review of the literature.

BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical entity. CASE REPORT: We report the case of an 87-year-old woman with a serous microcystic neoplasm in the tail of the pancreas that behaved in a malignant fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum. The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm, and the patient underwent distal pancreatectomy with splenectomy and segmental colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which occupied the body and tail of the pancreas. Histologically, the tumor was indistinguishable from serous cystadenoma. However, the tumor had invaded surrounding tissues including the splenic vein, and there were splenic invasion and a regional lymph node metastasis. The postoperative course was uneventful. DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in which malignancy was histologically confirmed in the resected specimen. There are no reports of a negative outcome with complete resection of the tumor. Surgical treatment should be considered for serous cystic neoplasms, especially large ones, because of the malignant potential.

Aged↗

Factors predicting recurrence after resection of pancreatic ductal carcinoma.

OBJECTIVE: Pancreatic ductal carcinoma frequently recurs postoperatively, and we analyzed clinicopathological features of patients treated by surgical resection to find predictors of postoperative recurrence. METHODS: A retrospective cohort study was performed that included 69 patients between 1985 and 2003. Clinicopathologic factors were evaluated for tumor recurrences by univariate and multivariate analyses. RESULTS: Mean survival time and actuarial 5-year disease-specific survival were significantly lower in cases of hepatic metastasis (13 months, 0%) and in cases of peritoneal carcinomatosis (15 months, 6.8%) than in cases of local retroperitoneal recurrence (30 months, 21%). Univariate and logistic regression analyses showed undifferentiated adenocarcinoma to be independently associated with hepatic metastasis (odds ratio, 7.4; 95% confidence interval, 1.5-37.0) and invasion of the portal vein to be independently associated with peritoneal carcinomatosis (odds ratio, 4.0; 95% confidence interval, 1.2-12.8). Multivariate analysis showed undifferentiated adenocarcinoma, invasion of the anterior capsule, and invasion of the portal vein to be independent prognostic factors. CONCLUSION: Undifferentiated adenocarcinoma and invasion of the portal vein are predictors of poor outcome and are related to hepatic metastasis and peritoneal carcinomatosis, respectively. Postoperative adjuvant chemotherapy, including intra-arterial chemotherapy, should be selected according to prediction of the patterns of recurrence.

Aged↗

A case of sporadic gastric carcinoid tumor treated successfully by laparoscopy-assisted distal gastrectomy.

A 49-year-old man was referred to us for treatment of a gastric carcinoid tumor. Gastroscopy revealed a superficial elevated lesion with a central depression covered with nonspecific gastric mucosa located in the anterior wall of the gastric body. The lesion was diagnosed on biopsy as a gastric carcinoid tumor. Preoperative ultrasound and computed tomography examinations revealed a tumor confined to the gastric submucosa and without lymph node metastasis. Therefore, laparoscopy-assisted distal gastrectomy (LADG) was performed. Macroscopically, the resected specimen contained an elevated lesion measuring 0.9 x 0.8-cm with a central depression. The postoperative course was uneventful, and the patient remains free of recurrence 10 months after surgery. There are few cases of sporadic gastric carcinoid tumor successfully treated by LADG. LADG may be useful for treatment of patients with sporadic gastric carcinoid tumor and possible lymph node metastasis.

Biopsy↗

Laparoscopic cholecystectomy for a double gallbladder of the duodenal type.

Double gallbladder is a rare congenital malformation and generally considered a duplication of 1 primordium. We encountered an extremely rare case of double gallbladder of the duodenal type that was considered a duplication of 2 primordia. We were able to diagnose the anomaly preoperatively by endoscopic retrograde cholangiopancreatography and spiral computed tomography after intravenous infusion cholangiography, and laparoscopic removal was successfully performed. To our knowledge, this is the first reported case of double gallbladder of the duodenal type that was diagnosed preoperatively and treated successfully by laparoscopic removal.

Aged↗

Dendritic cell immunotherapy with poly(D,L-2,4-diaminobutyric acid)-mediated intratumoral delivery of the interleukin-12 gene suppresses tumor growth significantly.

A conventional DC-based immunotherapy has been tested clinically for treatment of patients with advanced cancer but requires modification to further improve the clinical results. In this study, we evaluated the in vivo antitumor effects of DC therapy, non-viral-mediated IL-12 gene therapy, and a combination of the two in a murine bilateral subcutaneous tumor model. DC therapy alone and IL-12 gene therapy alone suppressed tumor growth at the injected sites. However, the antitumor effect on the distant contralateral tumor was insufficient. When DC therapy and IL-12 gene therapy were carried out simultaneously, tumor growth was significantly suppressed bilaterally (P < 0.001). Cytolytic activity was augmented significantly in mice given the combination treatment compared to in mice treated with either DC or IL-12 gene therapy alone (P < 0.05). Microvessel density of both tumors was significantly lower in mice subjected to the combination therapy than in mice treated otherwise (P < 0.05). Furthermore, no side-effects were observed in the treated mice. DC therapy combined with non-viral-mediated intratumoral IL-12 gene delivery has a synergistic antitumor effect not only on targeted tumors but also on contralateral distant tumors and may be of great potential as a therapeutic treatment for patients with advanced cancer.

Aminobutyrates↗

Consensus interferon enhances the anti-proliferative effect of 5-fluorouracil on human hepatoma cells via downregulation of dihydropyrimidine dehydrogenase expression.

BACKGROUND/AIMS: The effectiveness of 5-fluorouracil (5-FU) treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate whether interferon (IFN)-alpha influences expression of 5-FU catabolic or target-related enzymes in human hepatoma cells. METHODS: HepG2 cells were treated with 0, 0.15, 1.5, 15, and 150 ng/ml of consensus interferon (C-IFN). Expression of mRNAs encoding dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase, and thymidylate synthase was examined by reverse transcription-polymerase chain reaction before and after C-IFN treatment. To determine the effect of pretreatment with C-IFN on 5-FU+C-IFN combination therapy, we performed WST-1 cell proliferation assays. RESULTS: A significant reduction in the level of DPD mRNA was observed when HepG2 cells were pretreated with C-IFN (P<0.05). This reduction occurred in a time-dependent manner. Cell proliferation was reduced most significantly when HepG2 cells were treated with 5-FU and C-IFN. Furthermore, when cells were pretreated with C-IFN for 3 days, the anti-proliferative effect of 5-FU+C-IFN combination therapy was augmented significantly (P<0.05). CONCLUSIONS: C-IFN likely improves the anti-tumor effect of 5-FU via downregulation of DPD enzyme in hepatoma cells. Pretreatment with C-IFN may increase the anti-cancer effect of 5-FU+C-IFN combination therapy.

Antimetabolites, Antineoplastic↗

Laparoscopic gastrectomy for cancer.

There are three procedures for the management of early gastric cancer (EGC): laparoscopic wedge resection (LWR), intragastric mucosal resection (IGMR), and laparoscopic gastrectomy. LWR or IGMR can be applied to treat EGC without the risk of lymph node metastasis. However, owing to the recent technical advances in endoscopic mucosal resection for EGC, the use of laparoscopic local resection for these lesions has gradually decreased. On the other hand, laparoscopic gastrectomy with lymph node dissection, such as laparoscopy-assisted distal gastrectomy, is widely accepted for the treatment of EGC with the risk of lymph node metastasis. To establish the acceptability of laparoscopic gastrectomy with D2 lymph node dissection against advanced gastric cancers, safe techniques and new instruments must be developed. The following advantages of laparoscopic surgery for the treatment of gastric cancer have been well demonstrated: clinical course after operation, pulmonary function, immune response. In the future, laparoscopic surgeons have to design and implement education and training systems for standard laparoscopic procedures, evaluate clinical outcomes by multicentric randomized control trial studies, and clarify the oncological aspects of laparoscopic surgery in basic studies.

Gastrectomy↗

[EBM for surgeons].

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Evidence-Based Medicine↗

Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model.

New modalities are necessary for the treatment of patients with unresectable gastric cancer. The aim of this study was to investigate whether or not anti-HER2 antibody could suppress the growth of human gastric cancer cells with HER2 overexpression in vitro and in vivo. Four human gastric cancer cell lines, NCI-N87, MKN-45P, Kato-III, and MKN-1, were used in this study. The suppression of cell proliferation in vitro and of subcutaneous tumor growth in a nude mouse model after treatment with trastuzumab was examined. The expression of HER2 protein was investigated by Western blot analysis. The effect of trastuzumab on the survival rate of nude mice with peritoneal dissemination was examined. Trastuzumab significantly reduced proliferative activity in NCI-N87, a HER2-overexpressing human gastric cancer cell line, in vitro. In the nude mouse model with transplanted subcutaneous tumor, trastuzumab significantly suppressed the tumor growth of NCI-N87 cells, and then HER2 expression was reduced. Trastuzumab improved the survival rate of mice with peritoneal dissemination of MKN-45P cells. Trastuzumab therapy is a potential candidate for a novel treatment of HER2-overexpressing gastric cancer.

Animals↗

Efficacy of oncolytic reovirus against liver metastasis from pancreatic cancer in immunocompetent models.

Liver metastasis is common in pancreatic cancer patients, and the current treatments are insufficient to improve the clinical outcome. Recently, tumor-targeted replication-competent viruses have been developed as cancer therapy. The aim of this study was to clarify the efficacy of oncolytic reovirus against liver metastases from pancreatic cancer in immunocompetent models. Reovirus serotype 3 and three hamster pancreatic cancer cell lines (HPD1NR, HPD2NR, and HaP-T1) were used in this study. The susceptibility of reovirus to these cell lines was examined. The effect of intraportal administration of reovirus against metastatic liver tumors was evaluated in vivo. Reovirus infected all cell lines and propagated via an activated Ras signalling pathway in vitro. In syngeneic hamster models using the HPD2NR cell line, intraportal administration of reovirus significantly decreased the number and size of treated tumors in comparison with non-treated tumors. Immunohistochemical examination revealed reovirus replication within the tumor cells but not in the surrounding normal tissue and organs. There were no reovirus-related toxicities and deaths. Our results indicate that intraportal administration of reovirus is effective and safe in immunocompetent and syngeneic hamster models of liver metastases from pancreatic cancer, suggesting that reovirus can be developed into an effective therapeutic modality in future.

Animals↗

Clear cell carcinoma of the pancreas: an adenocarcinoma with unusual phenotype of duct cell origin.

Although clear cell carcinoma has been found in various organs, only six cases have been reported in the pancreas. Moreover, the histogenesis of clear cell carcinoma of the pancreas remains controversial. We report a case of clear cell carcinoma of the pancreas in a 61-year-old woman, with an unusual pheno- or genotype detected by histochemical, immunohistochemical, and K- ras oncogene analyses. Histologically, the pancreatic tumor was predominantly composed of clear cell nests with scanty fibrous stroma and scattered duct-like structures. Neither clear cell nor duct-like components of the tumor showed mucin production. Immunohistochemical analysis of neoplastic cells showed a positive reaction to antibodies against cytokeratins 8 and 19, carbohydrate antigen 19-9, and alpha-1-antitrypsin, and showed no reaction to antibodies against carcinoembryonic antigen, neuroendocrine markers, trypsin, amylase, and HMB45. K- ras analysis revealed no mutation at codon 12 in either clear cell or duct-like components. The patient has had no recurrence as yet. The pancreatic carcinoma in our patient may be of duct cell origin, but the results of histochemical, immunohistochemical, and gene analyses and patient's outcome were unusual compared with those of previous cases.

Adenocarcinoma, Clear Cell↗