Rapid multiple immunocytochemical staining method using microwave irradiation for intraoperative cytology.

OBJECTIVE: To develop a more rapid and accurate staining procedure for intraoperative cytology through an assessment of a rapid multiple immunocytochemical staining method using microwave irradiation. STUDY DESIGN: A preliminary test of a triple immunostaining method using microwave irradiation was performed to determine optimal incubating conditions for primary antibodies against MOC-31, BerEP4 and carcinoembryonic antigen. The test samples were adenocarcinoma cells obtained by washings from 10 resected colorectal cancer specimens. Adenocarcinoma cells in peritoneal washings diagnosed by cytologic examination from 8 colorectal cancer patients were retrospectively examined using the previously determined optimal incubating conditions. RESULTS: High rates of positive cells (83-87%) with intense immunoreactions were obtained using a rapid process with primary antibody concentrations that were 2 times higher than those used for standard incubation at room temperature (82-86%). The staining under these conditions was completed within 19 minutes. Adenocarcinoma cells in the peritoneal washings were also intensely stained under these conditions. CONCLUSION: Using our microwave method, the processing time was dramatically shortened, and intense and sensitive immunoreactions were obtained. The present method is useful for the rapid and accurate diagnosis of intraoperative cytology.

Phase II trial of S-1 plus low-dose cisplatin for unresectable and recurrent gastric cancer (JFMC27-9902 Step2).

AIMS: The efficacy and the toxicity of oral fluorouracil derivative S-1 plus low-dose cisplatin in unresectable or recurrent gastric cancer were evaluated by a phase II study. METHODS: S-1 was administered orally for 28 days following 14 days' rest at 80-120 mg/body/day, depending on body surface area. During administration of S-1, cisplatin was given twice a week at the recommended dose (10 mg/m(2)), which was determined by a phase I study. Data from 34 patients in phase II and 8 patients treated with the recommended dose of cisplatin in phase I were analyzed. The primary endpoint was objective response. RESULTS: The response rate was 47.1%. The median survival time was 11.0 months and the median progression-free survival was 6.9 months. The grade 3/4 toxicities observed in 10% or more of the treated patients were neutropenia (16.7%), anemia (16.7%) and anorexia (11.9%). The serum concentration of cisplatin was 794 ± 341 ng/ml at day 25 of the first course. CONCLUSIONS: S-1 plus low-dose cisplatin may be a clinically useful regimen for unresectable or recurrent gastric cancer because of its infrequent adverse events in spite of considerable efficacy and its convenience of no hydration and no hospitalization.

Significance of fecal deoxycholic acid concentration for colorectal tumor enlargement.

Deoxycholic acid (DCA) has been shown to promote proliferation of colonic carcinoma cells in many fundamental studies. However, no large-scale prospective clinical study providing direct evidence for an association of DCA with progress of colorectal tumor development in humans has been reported to date. To address this question, we conducted a two-step epidemiological study applying enzyme-linked immunosorbent assays to measure fecal cholic acid (CA) and DCA concentrations. Firstly, we compared bile acid concentrations of fecal samples from 366 patients who had multiple colorectal tumors removed endoscopically (tumor group) with those from 24 controls without abnormality in their large intestine (control group). Secondly, the tumor group was followed-up to evaluate the association between fecal bile acid concentrations and recurrence of colorectal tumors four years later. Fecal DCA level in the tumor group were significantly higher than that in the controls, whereas there was no difference in CA levels between the two groups. In the tumor group, a subgroup with high DCA level had higher recurrence risk of large adenomas (> 3 mm) four years later than the low DCA subgroup (odds ratio:1.85, 95% confidence interval: 1.12-3.05). This trend was observed more strongly in the left side colon. In conclusion, a high fecal DCA concentration may be a promoter of colorectal tumor enlargement.

Malignant lymphoma in the ileum diagnosed by double-balloon enteroscopy.

A 73-year old man presented with abdominal pain. A tumor with central ulceration was observed in the ileum using double-balloon enteroscopy. Histological findings of the biopsy specimens were consistent with malignant lymphoma. Double-balloon enteroscopy confirmed the diagnosis of a malignant lymphoma tumor which was surgically resected. The patient is still in complete remission now.

Kinetic analysis of bile acids in the feces of colorectal cancer patients by gas chromatography-mass spectrometry (GC-MS).

PURPOSE: We used gas chromatography mass spectrometry (GC-MS) and reviewed dynamics of bile acids every colorectal cancer occupation part as contrast with a healthy adults after enforcement by all at once analysis of bile acids in feces of a healthy adults and the colorectal cancer patients so that we clarified the details of a possibility of colorectal cancer outbreak participation of allo type bile acids. SUBJECTS: The fecal bile acid measurements were made in a colorectal cancer group consisting of 89 patients and a control group consisting of 103 healthy adults. METHODS: All at once analyzed bile acid in feces of a control group and colorectal cancer group by GC-MS. Student's t-test was used to test for significant differences. RESULTS: As for allo cholic acid (allo CA), allo deoxycholic acid (allo DCA), allo lithocholic acid (allo LCA) and ursodeoxycholic acid (UDCA) which was 4 ingredients of 12 bile acid ingredients out of feces of colorectal cancer group, it showed a significant high level tendency in colorectal cancer group. The following ingredient showed a tendency to significant high level in every colorectal cancer occupation part. Ascending colon: allo DCA and allo LCA. Transverse colon: allo LCA. Descending colon: UDCA. Sigmoid colon: allo DCA and allo LCA. Rectum: allo CA, allo DCA, allo LCA and UDCA. CONCLUSION: The results suggested that the allo type secondary bile acids (allo DCA and allo LCA) are factors that are more strongly involved in colorectal carcinogenesis than DCA or LCA. It was particularly noteworthy that there was a tendency for the allo LCA values to be higher in both sexes (p<0.001-p< 0.005). The results suggested that allo LCA may be a factor involved in colorectal cancer at all sites, except cecum and descending colon. The results suggested that at high values UDCA may be a bodily defense reaction factor that is involved in suppression of carcinogenesis rather than a factor involved in carcinogenesis.

Clinicopathological features of nonpolypoid colorectal tumors as viewed from the patients' background.

BACKGROUND: This study was performed to characterize the clinicopathological features of colorectal tumors with flat-, depressed-, or protruded-type morphology (hereafter referred to simply as flat, depressed, or protruded lesions). METHODS: There are two major types of colorectal tumor: polypoid (protruded) and nonpolypoid (flat and depressed). A total of 130 lesions from 130 patients with colorectal submucosal invasive cancer were classified into three groups according to their macromorphology seen during endoscopy: flat (laterally spreading) and depressed nonpolypoid tumors and protruded polypoid tumors. The following factors in the patients' background were evaluated: indication for colonoscopy, age, and family history of colorectal cancer in first-degree relatives (i.e., parents, siblings, children). We also compared the following characteristics of the tumors: size, location, depth of submucosal invasion, vascular invasion, and frequency of synchronous and metachronous tumor lesions. RESULTS: The incidence of abnormal findings on follow-up studies after polypectomy as an indication for colonoscopy was significantly higher among patients with flat lesions (4/24, 16.7%) and depressed lesions (3/22, 13.6%) than among those with protruded lesions (1/84, 1.2%) (P < 0.01, P < 0.01). Patients with flat lesions (65.8 +/- 7.6 years old) were significantly older than those with protruded lesions (P < 0.05). The patients with flat tumors had a significantly higher rate of a family history of colorectal cancer (6/24, 25.0%) than patients with protruded or depressed lesions (P < 0.01, P < 0.05). The protruded lesions were significantly larger than the depressed lesions (size 13.3 +/- 6.7 mm) (P < 0.05), and the flat lesions (24.1 +/- 10.1 mm) were significantly larger than either the protruded or depressed lesions (P < 0.01, P < 0.01). Seventy-five percent (18/24) of the flat lesions were located in the right colon, and this proportion was significantly higher than that among the protruded or depressed lesions (P < 0.01, P < 0.01). The mean +/- SD depth of submucosal invasion was 1218 +/- 1034 microm in the flat lesions, 2392 +/- 1869 microm in the depressed lesions, and 2761 +/- 1929 microm in the protruded lesions, representing a significant difference (P < 0.05, P < 0.0001). Of the 24 patients with flat lesions, 9 (37.5%) showed vascular invasion; this proportion was significantly lower than that among patients with the depressed or protruded lesions (P < 0.01, P < 0.01). Patients with depressed lesions tended to have higher incidence of synchronous and metachronous malignant polyps than those with protruded or flat lesions. CONCLUSION: It is important to examine the morphology of colorectal tumors when diagnosing them and planning the treatment strategy, including follow-up, after resection of nonpolypoid tumors. It is useful to know the patient's family history so nonpolypoid tumors can be accurately diagnosed.

Simultaneous laparoscopic treatment for rectosigmoid and ileal endometriosis.

Endometriosis is common in women of childbearing age, while severe intestinal endometriosis requiring bowel resection is relatively rare. Intestinal endometriosis has recently been managed laparoscopically. We report the case of a 38-year-old patient with rectosigmoid and ileal endometriosis who was successfully treated by laparoscopic bowel resections. The patient had first presented at age 34 years with a chief complaint of rectal bleeding and lower abdominal pain related to the menstrual cycle. She underwent laparoscopic surgery and was diagnosed with severe endometriosis involving the rectosigmoid colon. Although an additional laparoscopic surgery had been planned, she did not return to the hospital. When she was 38 years old, she presented again with the same symptoms. Magnetic resonance imaging revealed a low intensity mass between the uterus and the rectosigmoid colon. A barium enema showed a stenotic site in the rectosigmoid colon. After hormone therapy, she underwent laparoscopic surgery. The anterior wall of the rectosigmoid colon adhered firmly to the corpus of the uterus, and another stenotic site was identified at the terminal ileum. The rectosigmoid colon and ileum were partially resected under laparoscopy. The postoperative course was uneventful and she was freed of symptoms. Laparoscopic treatment for patients with severe endometriosis of the bowel has becomes feasible and safe.

Effect of gastrectomy on the pharmacokinetics of 5-fluorouracil and gimeracil after oral administration of S-1.

The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated in a total of 12 cases - nine in which partial gastrectomy was performed and three in which total gastrectomy was performed. A single oral dose of S-1, 50 mg as tegafur, was administered, serial peripheral blood samples were collected, and the concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured. The pre-operative S-1 dose was administered about 7 days before surgery and the post-operative dose was administered around post-operative hospital day 14. In the partial gastrectomy cases the maximum post-operative blood concentration (Cmax) of 5-FU and CDHP tended to be lower than before surgery, and the difference in 5-FU concentrations was significant. The area under the blood concentration-time curve (AUC0-8 h) for CDHP was significantly smaller post- than pre-operatively, but no significant difference was observed with regard to 5-FU. In the total gastrectomy cases the post-operative tmax of both 5-FU and CDHP was shorter than the pre-operative tmax, and no significant differences were observed between the pre- and post-operative AUC0-8 h values. Thus, the results of the present study showed that around post-operative hospital day 14, when total oral feeding had become possible after surgery for gastric cancer, the AUC0-8 h values of 5-FU and CDHP after S-1 administration were almost the same as before surgery and that gastrectomy had hardly any effect on the pharmacokinetics of S-1.

Studies of serum and feces bile acids determination by gas chromatography-mass spectrometry.

Both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) methods are utilized in the clinical laboratory to measure bile acids in human body fluids. For a more detailed analysis, we attempted simultaneous analysis of serum and feces bile acids using gas chromatography-mass spectrometry (GC-MS) and also investigated the dynamics of bile acids. Serum bile acid composition was examined in 22 healthy adults (79.9 +/- 6.0 years) and 20 colon cancer patients (65.1 +/- 9.5 years). Feces bile acid composition was examined in 20 healthy adults (50.7 +/- 7.6 years) and 20 colon cancer patients (63.6 +/- 8.5 years). The significance of differences was examined by Student's t-test. In both healthy adults and colon cancer patients, the bile acids detected in serum were cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and hyocholic acid (HCA). The following 12 bile acids were detected in feces: CA, allo CA, CDCA, allo CDCA, DCA, allo DCA, LCA, allo LCA, UDCA, HCA, UCA, and CA-6alpha-ol. For allo CA and allo CDCA, no significant differences were observed between the control group and the colon cancer patients. On the other hand, the concentration of allo LCA tended to be higher in the patients (p < 0.05), and the concentration of allo DCA was distinctly higher (p < 0.001) in the colon cancer group, particularly in men. The GC-MS method demonstrated bile acids undetectable by conventional RIA and ELISA. The dynamics suggested association of allo bile acids (DCA and LCA) with colon cancer.

The relationship between 5-fluorouracil sensitivity and single nucleotide polymorphisms of the orotate phosphoribosyl transferase gene in colorectal cancer.

Orotate phosphoribosyl transferase (OPRT) is an enzyme playing an important role in exertion of the effect of 5-fluorouracil (5-FU). A type of gene polymorphism, single nucleotide polymorphism (SNP), is considered to be a factor affecting individual differences in exertion of drug effects, and its analysis has recently made progress. We investigated the correlation between SNP of OPRT and 5-FU sensitivity in colon and rectal cancers. The subjects were 31 patients with colorectal cancer who underwent surgical excision between December 2003 and July 2004 at our department. Of SNP of OPRT, 638G/C, 1050T/A, and 1336A/G located in the coding region were analyzed by invader assay. The growth inhibition rate (% IR) of colorectal cancer by 5-FU was obtained by the CDDST method, and 5-FU sensitivity was compared among strains (wild-, homo-, and hetero-types) of each polymorphism. There was no relationship between the strains and 5-FU sensitivity in any of the SNPs. The investigated SNPs of OPRT may have no major influence on 5-FU sensitivity. However, there are many unknown factors in the relationship between SNP of OPRT and 5-FU sensitivity, and SNP analysis of other regions is necessary.

Comparison of characteristics and survival of colorectal cancer between Japanese-Americans in Hawaii and native Japanese in Japan.

PURPOSE: This study was designed to investigate whether characteristics, prognostic risk factors, and survival of colorectal cancer of Japanese-Americans in Hawaii are different from those of native Japanese in Japan. METHODS: A retrospective review of patients with colorectal cancer surgically resected in single institutions in Hawaii and Japan from 1996 to 2002. RESULTS: A total of 410 Japanese-American patients (218 males; median age, 73 years) and 621 native Japanese patients (382 males; median age, 65 years) were included. There were significant differences in age (P < 0.001), age distribution (P < 0.001), gender (P = 0.008), preoperative carcinoembryonic antigen (P < 0.001), and anatomic site distribution (P < 0.001). The tumor characteristics of Japanese-American patients were close to the general American population compared with the Surveillance, Epidemiology, and End Results data. There were no differences in tumor size, histologic grade, each of T, N, M status and TNM stage between the two groups. The overall five-year survival rates (Japanese-Americans, 75.5 percent; native Japanese, 76.2 percent; P = 0.55) and survival rates in each of four stratified stages were similar. Risk factors associated with survival were not different, except for carcinoembryonic antigen (P = 0.036). CONCLUSIONS: In patients with colorectal cancer in Japanese-Americans in Hawaii, some of tumor characteristics have changed from those of native Japanese in Japan. However, there are no remarkable differences in prognostic factors and survival between the two groups. The present study suggests that certain changes of colorectal cancer characteristics that were seen in Japanese-American may occur in native Japanese in Japan in the near future, although the survival outcome of colorectal cancer may remain the same.

Enhancement of the anti-tumor activity of S-1 by low-dose cisplatin in mice bearing the sarcoma-180 model.

The combination of S-1, consisting of 1 mol/l tegafur, 0.4 mol/l 5-chloro-2,4-dihydroxypyridine and 1 mol/l potassium oxonate, plus low-dose cisplatin has showed promising anti-tumor activities in experimental and clinical studies. The aim of this study was to investigate the mechanism of this combination chemotherapy. Mice bearing sarcoma-180 cells were divided into groups of seven animals each - Group A: no treatment; Group B: 5-fluorouracil (5-FU) 10 mg/kg continuous i.p. infusion; Group C: S-1 10 mg/kg p.o.; Group D: cisplatin 0.2 mg/kg i.p.; Group E: B+D; Group F: C+D. Treatments were given for 5 consecutive days, and then anti-tumor activity, the concentration of 5-FU, the thymidylate synthase inhibition rate (TSIR) and the level of 5-FU incorporated into RNA (F-RNA) in tumor tissue were evaluated. Anti-tumor activity in Group F was higher than in any other group. A significantly higher concentration of 5-FU in tumor was detected in the S-1-treated groups (C and F) than in the 5-FU-treated groups (B and E). No differences in TSIR were observed between the groups treated with 5-FU or S-1 with or without cisplatin; however, the F-RNA level in Group F was about 1.24 times significantly higher than that in Group C. Group F showed the highest anti-tumor activity, with increasing intratumoral levels of 5-FU and F-RNA, but not that of TSIR. These results suggested that the superior anti-tumor activity obtained by S-1+cisplatin might be associated with an incorporation of 5-FU into RNA.

Correlation between expression of orotate phosphoribosyl transferase and 5-fluorouracil sensitivity, as measured by apoptosis index in colorectal cancer tissue.

BACKGROUND: 5-Fluorouracil remains a key drug in the treatment of colorectal cancer, and the development of a simple and effective test for selecting patients likely to benefit from postoperative adjuvant chemotherapy is an important objective. AIM OF THE STUDY: This study aimed to clarify the feasibility of measuring apoptotic cell rate (AI%) in tumor after short-term oral 5-fluorouracil administration prior to surgery with the objective of establishing a simpler method to test for sensitivity. METHODS: Forty-five colorectal cancer patients were allocated to two groups, and 21 patients were given oral 5-FU for 3 d prior to surgery. The AI% in surgical specimen, detected by TUNEL staining, was compared in the 5-FU-loaded and control groups. The correlation of AI% with 5-FU metabolic enzyme mRNA levels in tumor was also evaluated. RESULTS: The AI% was significantly higher in the tumor tissue of patients receiving 5-FU than in the control group (p < 0.0005). Although insignificant, thymidylate synthase mRNA level and orotate phosphoribosyl transferase mRNA demonstrated a weak positive correlation with AI%. CONCLUSIONS: The AI% measurement in tumor tissue following a 5-FU oral load for 3 d prior to surgery was feasible. It remains to be elucidated if this measurement as a new 5-FU sensitivity test reflects the prognosis with 5-FU-based postoperative adjuvant chemotherapy.

Histopathologic changes in serum bile acid fractions in pressure ulcer patients.

BACKGROUND/AIMS: Bile acids are synthesized in the liver and released into the intestinal tract to aid in digestion and absorption by increasing permeability via alteration of the cell membrane. Bedridden elderly patients typically have pressure ulcers that may be due to both physical local pressure as well as skin cell changes induced by the physiologic effects of bile acids. METHODOLOGY: This study investigated 31 elderly bedridden patients with pressure ulcers (mean age, 81.7 years) and 19 healthy elderly (mean age, 79.7 years). Five serum bile acid fractions were summed to determine total bile acid, and transaminase and cholesterol levels were also measured. RESULTS: Total cholesterol levels were significantly lower (p<0.05) in pressure ulcer patients and transaminase levels were not significantly different between the two groups. The primary bile acids were generally higher and the secondary and tertiary bile acids lower in pressure ulcer patients. In particular, the secondary bile acid deoxycholic acid was significantly higher in all pressure ulcer patients. When analyzed by grade of pressure ulcer, the primary bile acids were significantly lower in pressure ulcer patients. CONCLUSIONS: Secondary bile acid fraction deoxycholic acid measurements may indicate bedridden patients at higher risk for pressure ulcers.

Early colon cancer detected by 18F-FDG PET.

Positron emission tomography (PET) is a noninvasive functional imaging modality that can disclose the presence of a malignant disease. It has recently been reported that PET may be useful to detect primary colorectal cancer (CRC). We present the case of a 47-yr-old man with early colon cancer detected by 18F-fluorodeoxyglucose (FDG) PET. The patient consulted us because of a positive fecal occult blood test and focal FDG uptake in the pelvic cavity detected at a physical check-up. After the usual work up, he was diagnosed as having a sigmoid polyp, 16 mm in diameter. Subsequently, colonoscopic polypectomy was carried out. The surgical specimen was histologically diagnosed as a well-differentiated adenocarcinoma, invading the submucosal layer with lymphatic invasion. Therefore, the involved portion of the sigmoid colon was laparoscopically resected. The FDG PET carried out 1 yr after the operation, showed no abnormal FDG uptake. PET can noninvasively detect an early colon cancer as small as in our patient, as well as other cancers in the whole body. Therefore, we consider it suitable as a screening examination.

Development of an enzyme-linked immunosorbent assay for fecal bile acid.

It has been suggested that the bile acids in the feces act as a promoter of colon cancer. Among the bile acids, deoxycholic acid (DCA), which is one kind of the secondary bile acid, is said to have strong influence. DCA/cholic acid (CA) ratio in feces is also said to have a diagnostic significance in colon cancer. With this in mind, we created a CA and DCA's monoclonal antibody (MoAb) to measure them through the enzyme linked immunosorbent assay (ELISA) method. Using these MoAb, we were able to measure CA and DCA concentrations with low cross-reaction to other bile acids compared with the method with polyclonal antibody (PoAb). We measured CA and DCA concentrations and calculated the DCA/CA ratios in healthy subjects and patients with colon cancer. All subjects had been screened for colon cancer. We then compared the healthy subjects, the cancer patients before surgery and the same cancer patients after surgery. Cancer patients after surgery had significantly low DCA/CA ratios compared to before surgery, whereas there was no significant difference between healthy subjects and the pre-operative colon cancer patients.

Advanced colorectal carcinomas measuring 20 mm or less exhibit markedly higher invasiveness despite their size.

To analyze the biology of small (20 mm or less) advanced colorectal carcinomas (SAC), 24 cases, 22 small early colorectal carcinomas (SEC) of similar size, and 52 advanced colorectal carcinomas (AC) were studied. The proliferative (Ki-67) labeling index for SAC was 65.9+/-17.1%, significantly higher than those for SEC (30.9+/-13.7%) or AC (43.0+/-17.1%) (P < 0.01). Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-2 expressions for SAC were 62.5 and 79.2%, respectively, significantly higher than those for SEC (4.5, 13.6%) or AC (21, 33%) (P < 0.01). Small advanced carcinomas have higher invasiveness than SEC or AC and may represent a different type of cancer.

Effect of combination of TS-1 and low-dose cisplatin on sarcoma-180 mouse sarcoma.

TS-1 contains tegaful (FT), 5-chloro-2,4-dihydroxypyridine (CDHP; an inhibitor of 5-fluorouracil (5-FU) degradation) and potassium oxonate (Oxo; an inhibitor of 5-FU assimilation mainly in the digestive tract) in a molar ratio of 1:0.4:1. We evaluated the combination of TS-1 and low-dose cisplatin on mouse sarcoma. Male ddy strain mice at 6 weeks of age were s.c. transplanted with 5 x 106 sarcoma-180 (S-1800) cells and divided into groups of seven animals each: Group A, no treatment; Group B, 5-FU alone by continuous i.p. infusion of 10 mg/kg with a minipump (Alzet); Group C, TS-1 10 mg/kg p.o. alone; Group D, cisplatin 0.2 mg/kg i.p. alone; Group E, B+D; Group F, C+D. Treatment was given for 5 days. Antitumor activity was evaluated on the basis of the tumor weight on day 8, and white blood cell count, red blood cell count, platelet count, BUN, GOT and GPT were determined to detect adverse effects. Tumor weights (g, mean+/-SD) were 0.54+/-0.15 in Group A, 0.52+/-0.17 in Group B, 0.34+/-0.05 in Group C, 0.46+/-0.12 in Group D, 0.34+/-0.07 in Group E and 0.16+/-0.03 in Group F. There were no noticeable adverse effects. The combined TS-1+cisplatin regimen showed considerably enhanced antitumor activities since sarcomas were significantly (p<0.05) decreased as compared with tissue. Mean AUC(0-12) (ng/ml.h) estimated in the groups receiving 5-FU+cisplatin or TS-1 alone was measured to calculate AUC(0-12) by the trapezoidal rule. 5-FU concentrations in blood and tumor from blood concentration data were 435 in Group B, 2651 in Group C, 343 in Group E and 1538 in Group F, while mean AUC(0-12) (ng/g.h) estimated from tumor tissue concentration data were 345 in Group B, 3548 in Group C, 324 in Group E and 2020 in Group F. Cisplatin acted as a modulator of 5-FU, suggesting clinical benefits of the combination of TS-1 and low-dose daily cisplatin.

Laparoscopic cholecystectomy after coronary artery bypass grafting using the right gastroepiploic artery: report of a case.

A laparoscopic cholecystectomy (LC) was successfully performed on a 61-year-old man who had undergone coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). He complained of right hypochondralgia 20 days after CABG. Gallstones were diagnosed and a cholecystectomy was performed 9 months after CABG. Under general anesthesia, the operation was performed using a pneumoperitonium. When a laparoscope was inserted, the RGEA pedicle could be clearly recognized. The pedicle obstructed the operating field and made the working space narrower than usual. No ST changes on the electrocardiogram were seen during LC, especially during the initiation of pneumoperitonium, the insertion of the ports, or when retracting the gallbladder. The postoperative course was uneventful. To avoid complications, care should be taken not to stretch the RGEA pedicle during LC, and careful monitoring of the electrocardiogram is also necessary. It is difficult to view the operating field and the RGEA pedicle together. It is therefore better to insert another laparoscope for concomitant monitoring of the RGEA pedicle.

T-cell malignant lymphoma of the ileum causing ileac fistulas: report of a case.

We herein present a rare case of three fistulas caused by a recurrence of T-cell lymphoma of the ileum. A 67-year-old man presented at a local hospital with left lower abdominal pain in May 1997. Upper and lower gastrointestinal examinations did not reveal any abnormal findings, but an abdominal aortic aneurysm was diagnosed by computed tomography, and thus was determined to be the source of the pain. The patient was referred to our hospital to undergo a grafting operation; however, a laparotomy performed in July 1997 revealed an unexpected small intestinal tumor, and therefore a partial ileectomy between 15 and 70cm in an oral direction from the terminal ileum was carried out instead. Histopathological and genetic examinations demonstrated diffuse small malignant lymphocytic T-cell lymphomas of the ileum invading all layers. Metastasis of the facial skin and local recurrence were recognized 5 months later, and chemotherapy with THP-COP and ESHAP only resulted in progressive disease. An ileac fistula was found to have formed between the intestine and abdominal wall in March 1998, and the patient died in May 1998. An autopsy revealed three fistulas caused by metastatic tumors, one of which communicated with the duodenum from the ileum, one with the skin from the ileum, and one to the transverse colon from the ileum.