Sachio Fushida

Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma

BACKGROUND This study examined the clinical value of intraoperative peritoneal lavage for cytological examination in patients with gastric cancer. Peritoneal dissemination is the most frequent mode of recurrence for this tumor. METHODS A retrospective of lavage findings, other factors, and outcome was performed in 1,297 patients with gastric cancer who underwent intraoperative peritoneal lavage. RESULTS The 5-year survival rate of patients with positive lavage cytology was only 2%. Patients who underwent curative resection and had negative cytology had a significantly better 5-year survival rate (P < 0.001). Even among patients with macroscopic peritoneal dissemination, the survival rate was significantly better with negative cytology, which reflected fewer free cancer cells in the peritoneal cavity. Serum concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9 were significantly higher in patients with positive cytology. Multivariate analyses indicated that intraoperative cytological findings was an independent prognostic factor for survival, and was the most important factor for predicting peritoneal recurrence. CONCLUSIONS Intraoperative peritoneal lavage cytology is important in predicting survival and peritoneal recurrence in gastric cancer.

Outcome of ratio of lymph node metastasis in gastric carcinoma.

BackgroundThe purpose of this study was to clarify the outcome of the ratio of the metastatic lymph nodes (RML) in gastric cancer patients.MethodsThe postoperative survival of 650 patients with gastric cancer who underwent D2 curative gastrectomy was analyzed with regard to the RML. The location, number, and RML in the N1 station and in all (N1 and N2) stations were analyzed. These data were compared from the viewpoints of staging accuracy and patient survival.ResultsThe RML was classified as follows: RML 0, no involvement; RML 1, 0 to .1; RML 2, .1 to .25; and RML 3, ≥.25. The 5-year survival rates stratified by RML were RML 0, 86%; RML 1, 68%; RML 2, 35%; and RML 3, 16%. Cox model identified all methods of classifying lymph node metastases as independent prognostic indicators in each calculation. However, a second Cox regression revealed that RML was the only independent prognostic factor among the three methods (P<.001). Stage migration was present in 35 cases (15%) when the number was considered. However, only 15 cases (7%) were underdiagnosed when RML was used.ConclusionsRML is a useful classification of patients with gastric cancer. It may prevent the phenomenon of stage migration.

Mapping sentinel nodes in patients with early-stage gastric carcinoma†

Nodal status in gastric carcinoma is related not only to prognosis but also to the extent of nodal dissection. However, a method for accurate assessment of nodal status during operation has not been established. This study aimed to map the sentinel nodes of gastric carcinoma and to estimate the clinical usefulness of sentinel node biopsy.

Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination

BACKGROUND The most common cause of noncurative resection and recurrence is gastric cancer is peritoneal seeding. However, the results of treatment of peritoneal dissemination with chemotherapy have been poor with 5-year survival rates of 0%. METHODS A new in vitro thermochemosensitivity test was performed on gastric cancer cells obtained from 19 surgically resected specimens by using tetrazolium-based colorimetric assay (MTT assay). A novel treatment of the intraoperative chemohyperthermia was undertaken in 83 patients with gastric cancer with peritoneal dissemination. After aggressive resection of primary tumor, lymph nodes, and peritoneal metastases, warmed saline solution containing mitomycin C 30 mg, etoposide 150 mg, and cisplatin 300 mg was introduced into the peritoneal cavity via a closed circuit continuous hyperthermic peritoneal perfusion (CHPP) for 60 minutes to keep the abdominal temperature at 42 degree to 43 degrees C by means of a heat exchange mechanism. RESULTS The in vitro thermochemosensitivity test that 43 degrees C enhanced the cytotoxin effects on gastric cancer cells under clinically achievable drug concentrations. During CHPP, drug concentrations of cisplatin, mitomycin C, and etoposide in the perfusate remained statistically higher than in the peripheral venous circulation. Among 43 evaluable patients with residual peritoneal seeding, eight (19%) and nine (21%) exhibited complete response and partial response, respectively. The overall 1- and 5-year survival rates were 43% and 11%, respectively. Patients who underwent complete resection survived significantly longer than those with residual disease, and those with complete response had a significantly better prognosis than did those with partial response, and nonresponders. One-year survival rates with complete response, partial response or nonresponders were 88%, 27% and 22%, respectively. Five patients survived longer than 5 years. CONCLUSIONS Our triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation

A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes ⩽ 3000/mm3 and/or platelets ⩽ 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second‐look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two‐year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P < 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti‐cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO.

Expression of p53 protein in colorectal cancer and its relationship to short‐term prognosis

Background and Methods. The expression of p53 protein in 100 large bowel cancers was studied immuno‐histochemically by use of a monoclonal antibody (PAb1801).

Expression of C-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for C-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma

Correlations of c‐erbB‐2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c‐erbB‐2 protein in which the reaction was localized to the cell membrane. There was no significant association between c‐erbB‐2 staining and the macroscopic or histologic type of the carcinomas. c‐erbB‐2‐stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c‐erbB‐2‐unstained ones. In addition, c‐erbB‐2 was stained in none of early gastric carcinomas. The 5‐year survival rates of the c‐erbB‐2 protein‐positive and the protein‐negative group were 11% and 50%, respectively. When the c‐erbB‐2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c‐erbB‐2 tissue status emerged as independent prognostic variables. The results suggested that c‐erbB‐2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c‐erbB‐2 protein is an indicator of poor short‐term prognosis.

The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c‐met), autocrine motility factor receptor, and urokinase‐type plasminogen activator receptor

Hepatocyte growth factor receptor (c‐met), autocrine motility factor receptor (AMFR), and urokinase‐type plasminogen activator receptor (uPAR) are known to play important roles in tumor cell migration, invasion, and metastasis. The authors studied the relation between the expression patterns of these genes and the growth patterns of human gastric carcinoma.

Amplification of the c-met, c-erbB-2 and Epidermal Growth Factor Receptor Gene in Human Gastric Cancers: Correlation to Clinical Features

We examined amplification of the c-met, c-erbB-2, and epidermal growth factor receptor (EGFR) gene in the patients with primary gastric cancer, and compared the data with clinical features in order to clarify the relationship between oncogenic abnormality and clinical features. Oncogene amplifications were examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric cancers. Seven of the seventy cancers (10.0%) had c-met gene amplification, nine (12.9%) had c-erbB-2 gene amplification, and six (8.6%) had EGFR gene amplification, respectively. Eighteen cases (25.7%) exhibited one or multiple oncogene amplification, and two cases (2.9%) exhibited simultaneous amplification of the three genes. The cases with c-met gene amplification tend to show invasive character and were related to peritoneal dissemination. The cases with c-erbB-2 gene amplification were related to lymph node metastasis. The cases with EGFR gene amplification had large tumors and were in highly advanced stage. The survival rate in patients with oncogene amplification was significantly lower than that in patients without amplification. Our data indicated that these genes were related to growth and metastasis of gastric cancer. Furthermore, this study about the three genes suggested that the type of activated gene might decide on the type of metastasis and clinical features.

Impact of the Biliary Diversion Procedure on Carcinogenesis in Barrett's Esophagus Surgically Induced by Duodenoesophageal Reflux in Rats

Objective:To determine whether the elimination of bile reflux in the established esophagojejunostomy model of Barretts esophagus (BE) will reduce or eliminate the risk of developing esophageal adenocarcinoma. Summary Background Data:Reflux of duodenal juice as well as gastric acid plays an important role in the pathogenesis of BE and adenocarcinoma. Duodenoesophageal reflux (DER) per se induces these diseases without carcinogen. However, it is unclear whether antireflux surgery induces regression of BE and prevents adenocarcinoma. Methods:Two hundred F344 male rats underwent one of following 3 operations: (1) total gastrectomy and esophagojejunostomy to induce DER, followed by killing after 20 (n = 13), 30 (n = 12), and 50 weeks (n = 30); (2) biliary diversion procedure, converted to Roux-en-Y method, to avoid bile regurgitation into the esophagus at 20 (n = 29) and 30 weeks (n = 32) after the operation to induce DER, followed by killing 50 weeks after initial operation; or (3) total gastrectomy and Roux-en-Y esophagojejunostomy followed by killing after 50 weeks served as controls (n = 28). Results:BE developed in more than half of the animals exposed to DER for 20 weeks, in more than 90% of rats with DER for 30 weeks, and in 100% of animals exposed to DER for 50 weeks. In the incidence and the length of BE, there is no difference between the animals that underwent biliary diversion at 20 (62%) and 30 weeks (94%) and those that had DER for 20 (54%) and 30 weeks (92%), respectively. Incidence of adenocarcinoma was significantly lower in the rats that underwent the biliary diversion procedure after 30 (19%) and 20 weeks (3%) than in the rats that had DER for 50 weeks (60%) (P < 0.005). None of the control animals that underwent Roux-en-Y esophagojejunostomy developed BE and carcinoma. Conclusions:It is likely that the converting procedure from the esophagojejunostomy to induce DER to biliary diversion does not lead to regression of BE but prevents the development of esophageal adenocarcinoma in the rats.