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Seigo Kitano

Publications and source records attributed to Seigo Kitano.

At least 55 records · Page 3Linked to original sources

Heterotopic ossification of rectal adenocarcinoma: report of a case.

Heterotopic ossification of gastrointestinal tract tumors is rare. We report the case of a 67-year-old man with heterotopic ossification of a rectal adenocarcinoma. The patient presented with intermittent abdominal pain and frequent diarrhea, and colonoscopic examination showed a large polypoid tumor partially obstructing the rectal lumen. Abdominal computed tomography (CT) revealed a large tumor in the rectal lumen with calcified spots. We performed low anterior resection of the rectum, and histologic examination showed a well-differentiated adenocarcinoma with heterotopic ossification infiltrating the full thickness of the rectum. Local recurrence and liver metastases were found 2 months after surgery, and the patient died 3 months later. Such a rapidly progressive course of rectal adenocarcinoma with heterotopic ossification is very unusual.

Abdominal Pain↗

Outcome of paraaortic node-positive pancreatic head and bile duct adenocarcinoma.

BACKGROUND: This retrospective study aimed to identify the clinicopathologic features and surgical results of paraaortic node-positive periampullary adenocarcinoma. METHODS: Between 1995 and 1999, 101 patients underwent pancreatectomy with regional and paraaortic lymphadenectomy. Fifteen (15%) patients had histologically proven paraaortic lymph node disease. RESULTS: The 15 patients included 9 (26%) of 34 patients with pancreatic head carcinoma and 6 (17%) of 36 patients with bile duct adenocarcinoma. All 15 patients had locally advanced tumor invading adjacent structures. The 1-, 2-, and 3-year survival rates were 33%, 27%, and 0%, with median survival of 12 months (range 3 to 33). In patients with pancreatic head carcinoma or bile duct adenocarcinoma, survival curve for those without paraaortic lymph node metastasis was significantly better than that for those with involved paraaortic lymph nodes (P = 0.0033 or P = 0.0149). CONCLUSIONS: When the paraaortic lymph nodes obtained from sampling biopsy are histologically positive, radical pancreatectomy with extended lymphatic and soft tissue clearance should be abandoned owing to poor outcome.

Adenocarcinoma↗

Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers.

We evaluated the significance of aberrant DNA methyltransferase 1 (DNMT1) protein expression during gastric carcinogenesis. The protein expression of DNMT1, Muc2, human gastric mucin, E-cadherin, and proliferating cell nuclear antigen was examined immunohistochemically in gastric cancers and corresponding noncancerous mucosae from 134 patients. The DNA methylation status of the CpG islands of the p16, human MutL homologue 1 (hMLH1), E-cadherin, and thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT)-1, -2, -12, and -31 clones was examined by methylation-specific polymerase chain reaction and combined bisulfite restriction enzyme analysis. Epstein-Barr virus (EBV) infection was detected by in situ hybridization. Nuclear immunoreactivity for DNMT1 was not detected in any of the noncancerous epithelia, except in proliferative zones (positive internal control), but was found in 97 (72%) of the gastric cancers. DNMT1 overexpression correlated significantly with poorer tumor differentiation (P < 0.001), but not with the phenotype (gastric type versus intestinal type) of the cancer cells. It also correlated significantly with DNA hypermethylation of the CpG islands of the hMLH1 (P = 0.024) and THBS-1 genes (P = 0.043), and with the CpG island methylator phenotype in the gastric cancers (P = 0.007). Reduced E-cadherin expression correlated significantly with poorer tumor differentiation (P = 0.002), DNA hypermethylation of the E-cadherin gene (P < 0.001) and DNMT1 overexpression (P = 0.014). DNMT1 overexpression was also associated with EBV infection (a potential etiological factor in gastric carcinogenesis) but not with the proliferative activity of the cancer cells as indicated by the proliferating cell nuclear antigen-labeling index. These results suggest that DNMT1 overexpression may not be just a secondary effect of increased cancer cell proliferative activity, but may be associated with EBV infection and other etiological factors during gastric carcinogenesis. Furthermore, DNMT1 may play a significant role in the development of poorly differentiated gastric cancers by inducing frequent DNA hypermethylation of multiple CpG islands.

Adult↗

Hyaluronic acid stimulates tumor-cell proliferation at wound sites.

BACKGROUND: For EMR, the submucosal injection of sodium hyaluronate has become popular, because this substance creates a more prominent and longer-lasting mucosal protrusion than normal saline solution. However, the effects of sodium hyaluronate on tumor growth at wound sites remain unclear. METHODS: For these experiments, a murine model with artificial wounds was used. Forty mice were randomly divided into two groups according to the substance to be injected into a wound: a sodium hyaluronate group and a control group. Tumors were created by inoculation of transplantable adenocarcinoma cell line colon 26. Two weeks later, the size, weight, proliferating cell nuclear antigen-labeling index, and CD44 expression of the subcutaneous tumors were compared between the two groups of mice. RESULTS: There were significantly greater increases in the growth and the weight of subcutaneous tumors in the sodium hyaluronate group compared with the control group. The PCNA-labeling index of cancer cells also was higher in the sodium hyaluronate group. Immunohistochemistry and Western blot analysis demonstrated that the CD44 protein expression of cancer cells was higher in the sodium hyaluronate group vs. the control group. CONCLUSIONS: In this study, sodium hyaluronate enhanced both tumor growth and CD44 expression of cancer cells at wound sites, suggesting that the use of sodium hyaluronate for EMR might stimulate the growth of residual tumor cells.

Animals↗

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid].

Delivery of the interleukin-12 (IL-12) gene to solid tumors is a promising anticancer therapy. Vectors are currently being developed to achieve safe and effective intratumoral delivery of the IL-12 gene. Poly [D,L-2,4-diaminobutyric acid] (PDBA) is a novel gene carrier that was recently described. The goal of this study was to use this gene delivery system for treatment of solid tumors. To determine the optimal conditions for transfection, established B16F10-melanomas in C57BL/6 mice were treated with intratumoral injection of the PDBA/plasmid luciferase (pLuc) complex. We determined that the optimal complex composition was 50 microg/ml pLuc and 150 microg/ml PDBA. High levels of IL-12 protein were expressed in tumors after a single injection of PDBA/murine IL-12 (pmIL-12) complex, whereas serum levels of IL-12 in treated mice were below the limits of detection. IL-12 gene therapy with the PDBA system significantly inhibited tumor growth in comparison with the controls (P<.001). Moreover, both natural killer and cytotoxic T lymphocyte activities from draining lymph nodes of PDBA/pmIL-12-treated mice were increased substantially in comparison with those of controls (P<.05). These results suggest that PDBA-mediated IL-12 gene therapy is a potential strategy for treatment of patients with solid tumors.

Aminobutyrates↗

Expression of CD10 in basal cell carcinoma.

We investigated the expression of CD10 by an immunohistochemical method in 51 basal cell carcinomas (BCCs), eight pilomatricomas, five trichoblastomas, two trichofolliculomas, three sebaceomas, five sebaceous carcinomas, ten syringomas, two spiradenomas, ten poromas, four porocarcinomas, one eccrine duct carcinoma (not otherwise specified, NOS), six mixed tumors of apocrine origin, and nine squamous cell carcinomas (SCCs). We detected strong expression of CD10 in tumor cells of BCC (86%), and found that the smaller the number of positive tumor cells, the larger the number of positive stromal cells, in particular in sclerosing BCCs. Spearman's rank correlation test revealed a significant negative correlation in BCCs between the expression of CD10 in tumor cells and that in stromal cells (P = 0.001). In all pilomatricomas (100%) and in four trichoblastomas (80%), strong expression was also detected in tumor cells. There was no detectable expression in trichofolliculomas. One sebaceoma (33%) and two sebaceous carcinomas (40%) expressed CD10 in a similar fashion to BCCs. All tumors of eccrine gland origin, including syringoma, spiradenoma, poroma, porocarcinoma, and eccrine duct carcinoma (NOS), did not express CD10. Five mixed tumors (83%) were immunopositive. In SCC, CD10 was overexpressed only in the stromal cells. These findings support the hypothesis that BCC is derived from the folliculo-sebaceous apocrine unit, especially having the same origin as trichoblastoma and pilomatricoma. CD10 might be an indicator of tumor invasiveness if it is expressed in stromal cells, while it might be a marker of follicular differentiation if it is expressed in the actual tumor cells of cutaneous epithelial neoplasms.

Acrospiroma↗

Clinicopathologic characteristics of early-stage mucinous gastric carcinoma.

GOALS: Early mucinous gastric carcinoma (MGC) is very rare, and the clinicopathologic features are not well understood. The aim of this study is to clarify the clinicopathologic characteristics of early MGC. STUDY: A total of 806 patients with gastric cancer underwent gastrectomy between 1983 and 2002 at our department. Of these patients, 7 were found to have early MGC. MGC was defined as a tumor in which more than 50% of the tumor area contained extracellular mucin pools. Microscopic examination was performed, and particular attention was paid to the mucin component of the tumor and histologic subtype (ie, well-differentiated or poorly-differentiated). RESULTS: The incidence of early MGC among all gastric carcinomas in our series was 0.9% (7/806). Tumors ranged in size from 1.0 cm to 7.2 cm, with a mean of 3.7 cm, and 4 appeared macroscopically elevated and 3 appeared depressed. Histologically, 3 tumors were considered well-differentiated type and 4 were considered poorly differentiated type. Microscopic features were thickening of the submucosal layer due to accumulation of abundant mucin and elevation of the surrounding normal mucosa. Tumor invaded the submucosa in 6 cases, and lymph node metastasis occurred in 1 case. However, no patient died of recurrence during follow-up periods ranging from 4 to 85 months. CONCLUSIONS: Early MGC is characterized as an elevated lesion resembling submucosal tumor due to abundant mucin pools in the submucosa. Cases of early MGC have a good outcome similar to that of early non-MGC.

Adenocarcinoma, Mucinous↗

Laparoscopic resection of a retroperitoneal schwannoma behind the lesser omental sac.

Most schwannomas occur in the head, neck, or limbs with a few cases occurring in the retroperitoneal space. In benign schwannoma occurring in the retroperitoneal space, tumors are most commonly located near the adrenal gland. Herein, we report on a 55-year-old Japanese man with benign schwannoma (6x4 cm) behind the lesser omental sac, which was removed under laparoscopy. Non-functioning neurogenic tumor was suspected as a differential diagnosis by computed tomography, ultrasonography, and magnetic resonance imaging, and the patient underwent laparoscopic resection of the tumor. Histologically, the resected tumor was diagnosed as benign schwannoma. The patient was discharged from our hospital on the tenth postoperative day without any complications. A laparoscopic surgical technique is safe and feasible for the diagnosis and treatment of retroperitoneal benign tumors such as schwannoma.

Humans↗

Immunoactivative role of indoleamine 2,3-dioxygenase in human hepatocellular carcinoma.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme. Recent studies have focused on the immunoregulatory role of IDO in mononuclear cells. The role of IDO in hepatocellular carcinoma (HCC) cell lines and HCC patients was examined. METHODS: The expression of IDO mRNA in peripheral blood mononuclear cells (PBMC) cocultured with HCC cell lines was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The cytotoxicity of PBMC against HCC cell lines cultured with and without IDO inhibitor was examined by sodium 51chromate release assay. In the tumor portion of 21 HCC patients, the expression of mRNA of IDO, tryptophan 2,3-dioxygenase and some cytokines was detected by RT-PCR. The expression and distribution of IDO protein in HCC specimens was analyzed by immunohistochemistry. RESULTS: The IDO mRNA was strongly induced in PBMC cocultured with HepG2 and PLC/PRF/5 and faintly induced in PBMC cocultured with Hep3B and HuH7. The cytotoxicity of PBMC against HCC cell lines was directly proportional to the level of expression of IDO mRNA and reduced by IDO inhibitor. The expression of IDO mRNA in the tumor portion was detected in 12 out of 21 HCC patients. Immunohistochemistry revealed that the IDO-positive cells were identified to be tumor-infiltrating cells, not tumor cells. The IDO mRNA correlated significantly with gene expression of interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta. The recurrence-free survival rate of IDO-positive HCC patients was significantly higher than that of IDO-negative HCC patients (P<0.05). CONCLUSIONS: These results suggest that IDO is a necessary enzyme for anticancer immune reactions of tumor-infiltrating cells.

Aged↗

Re-evaluation of mucin phenotypes of gastric minute well-differentiated-type adenocarcinomas using a series of HGM, MUC5AC, MUC6, M-GGMC, MUC2 and CD10 stains.

We examined which, and how many, mucin markers are necessary to define the phenotypes of gastric cancers, and re-evaluated the incidence of their mucin phenotypes and whether minute gastric carcinomas arise as unclassified type. Well-differentiated-type minute gastric carcinomas (n = 33) measuring 0%, and was 33%, 33%, 3%, 30%, and 0%, respectively, when the percentage of positive mucin phenotype was set at >or=10%. Thus, a panel of MUC5AC (or HGM), MUC6, MUC2 and CD10 stains is indispensable for accurately determining the mucin phenotypes of gastric carcinomas, and the above-mentioned classification is important for studying changes in the histological types of well-differentiated-type adenocarcinomas during change to the poorly differentiated type, as well as corresponding genetic abnormalities.

Adenocarcinoma↗

[Laparoscopic surgery for perforated peptic ulcer].

Laparoscopic surgery has become the treatment of choice for the management of perforated peptic ulcer. The advantages of laparoscopic repair for perforated peptic ulcer include less pain, a short hospital stay, and an early return to normal activity. Although the operation time of laparoscopic surgery is significantly longer than that of open surgery, laparoscopic technique is safe, feasible, and with morbidity and mortality comparable to that of the conventional open technique. To benefit from the advantages offered by minimally invasive laparoscopic technique, further study will need to determine whether laparoscopic surgery is safe in patients with generalized peritonitis or sepsis.

Humans↗

A convenient murine model for the study of intra-abdominal lymph node metastasis.

Lymph node metastasis is one of the most important prognostic factors for cancer patients. There are few animal models of lymph node metastasis. The purpose of this study was to develop a simple animal model without surgical trauma. B16F10 melanoma (1 x 10(6) cells in 0.1 ml phosphate-buffered saline) were slowly injected into the retroperitoneal space followed by direct puncture at the position between the anus and tail of 50 female C57BL6 mice. At 1-week intervals for 4 weeks after the procedure, we examined the retroperitoneal tumor and intra-abdominal lymph nodes. There was no morbidity and no mortality. At 2 weeks after inoculation, the retroperitoneal tumor was visible macroscopically at the position between the rectum and the sacrum, and histological examination showed the occurrence of intra-abdominal lymph node metastasis in all mice. The number of positive nodules was increased and was affected by the amount of cancer cells inoculated and the interval from inoculation to lymph node metastasis. A convenient murine model for the study of lymph node metastasis has been developed. Our animal model does not involve surgical trauma and may be useful in the analysis of the association between surgical stress and lymph node metastasis and in the elucidation of the mechanism and prevention of lymph node metastasis.

Abdominal Neoplasms↗

[mRNA expression of chemokine receptors in hepatic and pancreatic tumor cell lines].

Chemokines represent a large family of polypeptide signaling molecules that are notable for their role in chemotaxis, leukocyte homing, and directional migration. Recent observations have indicated that the expression of chemokine receptors on cancer cells may play a role in tumor progression and metastasis. In this study, the expression of mRNA for chemokine receptors in various human tumor cell lines was analyzed by multiplex-polymerase chain reaction (M-PCR). Strong expression of CCR6 mRNA in 3 of 3 hepatoma cell lines was observed. In the 3 pancreatic cancer cell lines, no specific expression of chemokine receptors was observed. Raji (lymphoma cell line) strongly expressed CCR7 and CXCR4. We further investigated CCR6 mRNA expression in these cell lines by real-time quantitative-PCR. Similar results were obtained by both the PCR methods. Because human liver constitutively express liver and activation-regulated chemokine (specific ligand for CCR6), hepatoma cells may selectively root and spread in the liver. Strong CCR7 and CXCR4 expressions in the lymphoma cell may explain the organ specificity of lymphoma for lymphoid organs as well. These findings probably indicate that some cancer cells have organ specificity via expression of chemokine receptors.

Burkitt Lymphoma↗

Protease-activating-receptor-2 is frequently expressed in papillary adenocarcinoma of the gallbladder.

Gallbladder carcinoma is one of the most devastating malignant tumors in Japan. An important risk factor for gallbladder carcinoma is pancreaticobiliary maljunction (PBM), which allows reciprocal reflux of bile and pancreatic juice. Protease-activated-receptor-2 (PAR-2), which is activated by trypsin, may be a key molecule in the process of carcinogenesis in the gallbladder epithelium. We investigated the relation between the expression of PAR-2 and clinicopathological findings in gallbladder carcinoma. The study group comprised 58 patients with gallbladder carcinoma. PAR-2 expression was identified by immunohistochemical staining of all tumor specimens. PAR-2 was expressed in cancerous gallbladder epithelium in 37 of 58 patients (64%). PAR-2 expression occurred more frequently in papillary adenocarcinoma (15 of 16 patients, 94%) than in non-papillary types (20 of 42 patients, 48%, p=0.005). Neither lymphatic invasion (p=0.03) nor venous invasion (p=0.009) occurred more frequently in gallbladder carcinoma with PAR-2 than in that without PAR-2. PAR-2 expression was not directly related to PBM (p=0.46). Papillary adenocarcinoma was associated with polypoid growth (p=0.01), PBM (p=0.01), decreased invasion to lymphatic (p=0.007) and venous vessels (p=0.005), lower T-factor (p<0.001), and lower clinical stage (p=0.02). PAR-2 is frequently expressed in papillary adenocarcinoma of the gallbladder. Trypsin may play an important role for carcinogenesis of the gallbladder through PAR-2 signaling.

Adenocarcinoma, Papillary↗

A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer.

BACKGROUND/AIMS: To evaluate the safety and feasibility of immunotherapy based on autologous dendritic cells (DC) for patients with unresectable primary liver cancer (PLC). METHODS: A total of ten patients were enrolled and immunized with DCs. Autologous DCs were generated ex vivo in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Cells were then pulsed with tumor lysate (TL), tumor necrosis factor-alpha (TNF-alpha) and keyhole limpet hemocyanin (KLH). Non-adherent cells were collected on day 9 and cells were administered into the inguinal lymph node. Each patient received 1-10 x 10(6) cells four times at weekly intervals. RESULTS: Immunization was well tolerated in all patients without significant toxicity. DC vaccination induced delayed-type hypersensitivity (DTH) against KLH in seven out of ten patients. In one patient, one of the two liver tumors (tumor in segment 7, 13 mm in diameter) decreased in size to 7 mm and showed necrotic change on computed tomography examination after eight immunizations. In two patients, serum levels of tumor markers decreased after vaccination. CONCLUSION: The present clinical trial suggested that immunization by TL-pulsed DCs is feasible in patients with unresectable PLC without any toxicity. Further improvement in the clinical results of immunotherapy might be expected by modifying the therapeutic protocol.

Aged↗

Laparoscopic resection for nonfunctioning small glucagon-producing tumor: report of a case and review of the literature.

Glucagonoma is a relatively rare type of pancreatic endocrine tumor, and is often well-developed and malignant at detection. We report a case of nonfunctioning small glucagon-producing tumor that was successfully resected by laparoscopic surgery. A 63-year-old woman was admitted to our hospital for further examination of a pancreatic tumor that had been detected incidentally. Hematological data and hormone concentrations were within normal ranges. Abdominal ultrasonography and computed tomography showed a small mass in the body of the pancreas. Laparoscopic distal pancreatectomy was done. Macroscopically, the resected tumor was a yellowish-white, solid mass measuring 8 x 8 x 7 mm. The tumor cells showed positive immunohistochemical staining for chromogranin A and glucagon. The postoperative course was uneventful. To the best of our knowledge, this is the first report of laparoscopic surgery for a nonfunctioning small glucagon-producing tumor. Because of recent improvements in laparoscopic surgery technique, use of this approach for resection of pancreatic benign small endocrine tumors will likely increase in the future.

Female↗

Less impaired cell-mediated immune response in the murine peritoneal cavity after CO(2) pneumoperitoneum.

PURPOSE: We compared changes in the populations of peritoneal T lymphocytes and natural killer (NK) cells after CO(2) pneumoperitoneum and laparotomy to clarify whether pneumoperitoneum affects cell-mediated immune responses in the peritoneal cavity. METHODS: We analyzed and compared populations of T lymphocytes and NK cells among peritoneal exudative cells (PECs) collected from 185 female mice subjected to pneumoperitoneum, laparotomy, or anesthesia only. PECs were collected postoperatively, and the populations of T lymphocytes and NK cell subsets were analyzed by flow cytometry. The NK cell cytotoxicity (NKCC) of PECs and splenocytes was measured. RESULTS: The populations of CD3(+), CD4(+), and CD8(+) lymphocytes in the PECs continued to increase up until postoperative day (POD) 7 after laparotomy. The CD4/8 ratio on POD 3 was significantly lower after laparotomy than after pneumoperitoneum. The percentages of NK cells in the pneumoperitoneum group were significantly lower than those in the laparotomy group. On POD 1, the NKCC of splenocytes was less impaired in the pneumoperitoneum group than in the laparotomy group (10.3% vs 5.0%, P << 0.05). CONCLUSION: Laparoscopic surgery is preferable to open surgery because it results in less impairment of systemic and intraperitoneal cell-mediated immune responses.

Animals↗