Yoshirou Matsumoto

Improved quality of life with jejunal pouch reconstruction after total gastrectomy

BACKGROUND There is increasing evidence that the effect of jejunal pouch reconstruction is satisfactory for reservoir function in several randomized control studies. However, these studies were performed in patients with advanced gastric cancer, where significant numbers of the patients died of disease recurrence. In order to exclude the influence of disease recurrence, we performed jejunal pouch reconstruction after total gastrectomy in patients with early gastric cancer in a randomized controlled study and investigated whether or not an improved quality of life (QOL) was observed with jejunal pouch reconstruction. METHODS Fifty consecutive patients receiving total gastrectomy for early gastric cancer were prospectively divided into the Roux-en-Y reconstruction group without pouch (RY group) or the jejunal pouch reconstruction group (pouch group). Body weight, eating capacity, QOL assessment by gastrointestinal symptom rating scale (GSRS), nutritional parameters, endoscopical examination, 24-hour pH monitoring and Bilitec monitoring were evaluated at 3, 12, and 48 months after surgery. RESULTS Jejunal pouch reconstruction provided the better QOL than Roux-en-Y reconstruction without pouch both at short-term and long-term periods in a randomized control study. Moreover, as a new finding, pouch reconstruction provided less bile reflux into the esophagus compared with Roux-en-Y reconstruction. CONCLUSIONS Jejunal pouch reconstruction provided improvement of QOL in patients receiving total gastrectomy.

The Expression of a Type II Transmembrane Serine Protease (Seprase) in Human Gastric Carcinoma

Objective: The invasion and metastasis of carcinoma cells require the proteolytic degradation of the extracellular matrix by various cell surface proteases. Among these, seprase is a type II transmembrane serine protease absent in normal tissues and it has been implicated in the invasion of the extracellular matrix by both tumor and stromal cells in human breast carcinoma and melanoma. In the present study, the expression of seprase mRNA, protein and its gelatin-degrading activity in human gastric carcinoma were examined to substantiate the potential role of seprase in gastric carcinoma invasion. Methods: We have examined the seprase expression in human gastric carcinoma (n = 34) by RT-PCR, Western immunoblotting analysis, immunohistochemistry, and gelatin zymography. Results: Immunoblotting analysis using mAb D8 directed against seprase showed that the carcinoma tissues in 26 out of 34 cases of gastric cancer expressed a dimeric form of seprase but their normal counterparts did not. Gelatin zymography confirmed that the isolated seprase exhibited the gelatin-degrading activity and was active. Seprase-expressing carcinoma tissues were more often found in the scirrhous type than in other types of gastric carcinoma. RT-PCR analysis showed that seprase mRNA was present in carcinoma tissues but not in normal tissues. Immunohistochemically, seprase was mainly located in gastric carcinoma cells, weakly in stromal cells and microvessel endothelial cells in the tumor nest, and none in normal cells. Conclusions: Our studies showed the unique expression and localization of seprase in the tumor and stromal cells within human gastric carcinoma but not in normal tissues, suggesting a role of seprase in the invasive and metastatic progression of gastric carcinoma.

Selective inhibition of cancer cell invasion by a geranylgeranyltransferase-I inhibitor

A number of small GTPases are involved in cancer cell proliferation, migration and invasion. They need to be prenylated for full biological functions. We have recently reported that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, which block the biosynthesis of farnesylpyrophosphate and geranylgeranylpyrophosphate, inhibit in vitro invasion of human pancreatic cancer cells. In the present study, we examined the effects of two selective inhibitors of prenylation, a farnesyltransferase inhibitor (FTI-277) and a geranylgeranyltransferase type I inhibitor (GGTI-298), on in vitro invasion of cancer cells in a modified Boyden chamber assay. The invasion of COLO 320DM human colon cancer cells was inhibited potently by HMG-CoA reductase inhibitor lovastatin and GGTI-298 but weakly by FTI-277. The treatment of cancer cells with GGTI-298 markedly caused RhoA to decrease in the membrane fraction and accumulate in the cytosolic fraction, whereas it had almost no effect on the translocation of Ras. FTI-277 markedly inhibited membrane localization of Ras, but its inhibitory effect on cancer cell invasion occurred only at doses that affected membrane localization of RhoA. FTI-277 and GGTI-298 decreased the growth potential of COLO 320DM cells, but the inhibitory effect of GGTI-298 was rather selective toward invasion in association with changes in cell morphology and RhoA localization. These results suggest that geranylgeranylation of RhoA by geranylgeranyltransferase type I is critical for cancer cell invasion, and inhibition of geranylgeranyltransferase type I activity should offer a novel approach to the treatment of invasion and metastasis of cancer cells resistant to farnesyltransferase inhibitors.

Evaluation of VEGF and VEGF-C expression in gastric cancer cells producing α-fetoprotein

Background. Gastric cancers producing α-fetoprotein (AFP) are known to have a poor prognosis and to show a high incidence of liver metastasis. Vascular endothelial growth factor (VEGF) and its isoform VEGF-C are reported to be associated with tumor progression through an angiogenic or lymphangiogenic function. In the present study, to clarify the cellular characteristics of AFP-producing gastric cancers, the expression of VEGF and that of VEGF-C in AFP-producing gastric cancer was compared with their expression in gastric cancers that do not produce AFP. Methods. Twenty-six patients with AFP-producing gastric cancers [AFP(+)] and 26 patients with stage-matched gastric cancers that did not produce AFP [AFP(−)] were evaluated for VEGF and VEGF-C expression and vessel density, using immunohistochemical analysis. Results. The survival rate of the AFP(+) group was significantly worse than that of the stage-matched AFP(−) group (P < 0.05). The frequency of VEGF-C expression was significantly higher in the AFP(+) group than in the AFP(−) group (P < 0.01). There was no significant difference in VEGF expression between the AFP(+) and AFP(+) groups. The microvessel density was higher in the AFP(+) group than in the AFP(−) group (P < 0.05). Conclusions. A higher expression of VEGF-C might be one explanation for the poorer prognosis of AFP-producing gastric cancers.

Differences in the recognition of tumor-specific CD8+ T cells derived from solid tumor, metastatic lymph nodes and ascites in patients with gastric cancer

We established gastric cancer‐specific CD8+ T‐cell (TCD8+) lines derived from different lymphocyte sources in the same patients by repeated stimulation with mitomycin‐C‐treated autologous tumor cells with low‐dose interleukin‐2, and we compared recognition patterns among the TCD8+ derived from solid tumor, lymph node metastasis and ascites in the same patient (n = 3) to determine their similarities and differences for therapeutic purposes. We confirmed that gastric cancer‐specific TCD8+ lines can be isolated, in a MHC class I‐restricted manner, from solid tumors, metastatic lymph nodes and malignant ascites. TCD8+ lines derived from tumor‐infiltrating lymphocytes (TIL) in solid tumor recognized autologous tumor cells derived from solid tumor, but not autologous tumor cells derived from ascites or metastatic lymph node, while TCD8+ lines derived from tumor‐associated lymphocytes (TAL) in malignant ascites recognized autologous tumor cells derived from ascites, but not tumor cells from solid tumor or metastatic lymph node. Furthermore, TCD8+ lines derived from regional lymph node lymphocytes (RLNL) recognized autologous tumor cells derived from metastatic lymph nodes, but not tumor cells derived from ascites. No significant differences were seen in MHC class I expression among the tumors derived from solid tumor, lymph node metastasis or ascites in the same patient. This suggests that there are differences of recognition patterns among the TILs, TALs and RLNLs in the same patient and that it is important to consider the source of lymphocytes, e.g., a combination of TILs, TALs and RLNLs, for adoptive immunotherapy in gastric cancer patients. Int. J. Cancer 71: 978‐981, 1997.

A case of arteriovenous malformation in the submucosal layer of the stomach

Arteriovenous malformation (AVM) of the stomach is extremely rare. We report a patient with asymptomatic gastric AVM detected during mass screening of the upper gastrointestinal tract. The patient, a 69-year-old female, had no history of gastro-intestinal bleeding. Endoscopy revealed a gastric submucosal tumor (3 cm in diameter) at the posterior wall below the esophago-cardiac junction. Endoscopic ultrasonography (EUS) showed a hypoechoic structure in the third layer of the stomach, suggesting gastric AVM in the submucosal layer. Complete resection of the AVM tissue was performed by strip biopsy with surgical resection. Histological examination showed AVM in the submucosal layer. EUS examination was useful for the diagnosis of gastric AVM in this case.

A CASE OF VON RECKLINGHAUSEN'S DISEASE WITH BREAST CANCER

A case of von Recklinghausens disease with breast cancer is reported. 45-year-old woman was admitted to our hospital 7 months after she noted a tumor in her left breast. The preoperative classification was T2N1bM0, Stage II. Standard radical mastectomy was carried out. Postoperative adjuvant chemotherapy could hardly be performed. The patient complained of lumbago 6 months after the operation, and a bone scintigram showed multiple bone metastasis. The reasons for the advanced stage and poor postoperative course were thought to be the patients breast tumor resembled a skin tumor and she could not understand the methods of treating her breast cancer because of her mental retardation.

A Case of Primary Intrahepatic Pure Cholesterol Stone Accompanied with Black Stone in the Gallbladder.

症例は50歳男性で, 右季肋部痛を主訴とし, 腹部超音波検査にて胆嚢, 肝内結石症を指摘された. ERCPでは肝外側区域胆管に狭窄を伴わない限局性の紡錐状拡張を認めた.胆摘, 肝外側区域切除術を施行した.摘出標本で, 胆嚢内には黒色で割面が無構造な小結石を認めた.肝臓には萎縮はなく, 拡張胆管内に黒色泥状の結石が充満し, 組織学的には軽度の胆管壁の肥厚を認めるのみで, 慢性増殖性胆管炎の像を認めなかった.結石分析の結果では胆嚢結石は炭酸カルシウム, ビリルビンカルシウム, リン酸カルシウムを含有し黒色石と診断した.肝内結石はコレステロールのみを含有しており純コレステロール結石と診断した.両結石形成の機序およびその関連性については不明であるが, われわれの文献検索の範囲内ではこのような症例は見られず, きわめてまれな1例と考えられる.