Kiwao Ishimoto

Reconstruction with bilateral gluteus maximus myocutaneous rotation flap after wide local excision for perianal extramammary Paget's disease

PURPOSE: Extramammary Pagets disease is a rare dermatosis. Wide local excision is recommended in patients with perianal extramammary Pagets disease. After wide local excision, it is necessary to do reconstruction, with preservation of bowel function. We present here two cases of perianal Pagets disease, in which the patients were treated by reconstruction with bilateral gluteus maximus myocutaneous rotation flap after wide local excision. PATIENTS AND METHODS: A 55-year-old woman and 58-year-old man were admitted with anal pain and bleeding. Histologic examination of the perianal lesion revealed the presence of typical Pagets cells, and no underlying carcinoma and no distant metastasis was detected in either patient. Wide local excision, including the rectal mucosa, was performed, with reference to intraoperative frozen sections. Surgical defect was overlapped with bilateral gluteus maximus myocutaneous rotation flap, and the anus was reconstructed. RESULTS: Postoperative bowel function and quality of life were well preserved, and flaps healed satisfactorily. Patients have had no recurrence and have been able to return to work. CONCLUSION: Bilateral gluteus maximus rotation flap may be useful after wide local excision of perianal extramammary Pagets disease without underlying invasive carcinoma.

Clinical evaluation of chemosensitivity testing for patients with colorectal cancer using MTT assay

PURPOSE: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. The chemosensitivity test should be performed to individualize the chemotherapy for patients with colorectal cancer, which is less sensitive for anticancer drugs. The present study was designed to determine the chemosensitivity in fresh human colorectal cancer, using highly purified tumor cells, and the correlation of this sensitivity with clinical response. METHODS: We determined the chemosensitivity for cisplatin, mitomycin C, adriamycin, and 5-fluorouracilin vitroin 93 fresh human colorectal cancers using the MTT assay and performed chemotherapy according to results of the MTT assay. RESULTS: Inhibition rate of tumor cells for cisplatin was higher than those for other drugs. Fifteen patients who have evaluable lesions received chemotherapy according to results of the MTT assay. Clinical responses were obtained in 5 of 15 patients, and the inhibition rate for cisplatin was higher in responders than in nonresponders. CONCLUSIONS: It is suggested that the chemotherapy according to results of the MTT assay is effective in patients with colorectal cancer.

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.

Irinotecan hydrochloride (CPT‐11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT‐11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT‐11 and other antitumor agents were determined by a 3‐(4,5‐di‐methylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells.

Decreased expression of α2,8 sialyltransferase and increased expression of β1,4 N-acetylgalactosaminyltransferase in gastrointestinal cancers

Gangliosides such as GD3, GM2, and GD2 are abundantly expressed on the cell surfaces of various malignant cells, suggesting the potential for anti-ganglioside antibody therapy for tumors. Anti-ganglioside GD2 antibody treatment is currently undergoing clinical trials for melanoma and neuroblastoma. We previously reported high in vivo antitumor effects of anti-GM2 ganglioside antibody against lung cancer. To determine whether anti-GM2 antibody may be clinically indicated for gastrointestinal cancers, we evaluated the mRNA expression of α2,8 sialyltransferase, a GD3 synthase, and β1,4 N-acetylgalactosaminyltransferase (β1,4 GalNAc-T), a GM2/GD2 synthase, in gastrointestinal cancers. We performed modified semi-quantitative RT-PCR, which reduces complexity incidental to radiolabeling on samples taken from small surgically removed clinical specimens. Stomach (19/22) and colorectal (21/30) cancers showed decreased expression of α2,8 sialyltransferase as compared with respective normal tissues (P < 0.05). In contrast, increased expression of β1,4 GalNAc-T was detected in both types of tumors. Clinicopathological analysis revealed significantly higher expression level of α2,8 sialyltransferase in the poorly differentiated than in the well-differentiated stomach cancer group (P < 0.05). Furthermore, the expression level of α2,8 sialyltransferase was significantly decreased in male as compared with female colorectal cancer patients (P < 0.05). These results suggest that expression level of GM2 ganglioside is elevated in gastrointestinal cancer, and that anti-GM2 antibody may be applicable to its treatment.

Excretion of new quinolones and their glucuronide conjugates into human bile.

New oral quinolones, which are pyridone carboxylic acid derivatives, have antibacterial activity against Gram-positive cocci, Gram-negative bacilli, and anaerobic organisms. The efficacy rates of .these quinolones in patients with cholecystitis and cholangitis are high and range from 72.7 to 90.9%.[1-3] New quinolones are conjugated with glucuronic acid in the liver and lose their antibacterial activity. These conjugates are excreted into urine and bile. The ratios of glucuronide conjugates to unchanged drug in bile are different for each new quinolone and are affected by liver dysfunction and obstructive jaundice. This is an important consideration in antimicrobial drug selection in patients with biliary infections. In this study, we measured drug concentrations and determined the ratios of unchanged drug to glucuronide conjugates of 4 new quinolones (sparfloxacin, ofloxacin, levofloxacin, and NM441) in the bile of patients with indwelling biliary drainage tubes. All patients had obstructive jaundice caused by choledocholithiasis or malignant disease, such as cancer of the pancreas, lower bile duct or gallbladder. T-tube drainage and percutaneous transhepatic biliary drainage were performed.

Nodular Lymphoid Hyperplasia of the Terminal Ileum : Report of a Case and the Findings of an Immunological Analysis

The immunological and immunohistochemical characteristics of a patient with nodular lymphoid hyperplasia (NLH) of the terminal ileum were investigated pre- and post-operatively. The patient presented with diarrhea, lower abdominal pain, and weight loss, and an abdominal X-ray following barium enema revealed multiple small nodules in the terminal ileum which were subsequently confirmed to be NLH by histological examination. Preoperatively, although the serum immunoglobulin levels were normal, the T-cell responses in the peripheral blood, including the phytohemagglutinin (PHA)-blastogenesis and the T4/T8 ratio, were impaired. However, following an ileocecal resection, the PHA-blastogenesis became augmented and the T4/T8 ratio recovered to within the normal range. The immunohistochemical findings revealed a more marked accumulation of T cells in the interstitium around the hyperplastic follicles than in the interstitium of the normal intestine.

Diagnostic Significance of Serum CEA and CA19-9 Levels in Colorectal Cancers

We investigated the clinical significance of measuring serum CEA and CA19-9 levels for the early diagnosis of colorectal cancer in 157 cases. In the present study, the preoperative positive rate of serum CEA and CA19-9 levels in patients with curatively resected primary cancer was only 14.5% (11/76), 12.1% (4/33) of Dukes A, B, and 22.0% (11/50), 27.6% (8/29) of Dukes C, respectively, however, we found that serum CEA or CA19-9 levels were positive in 82.4% (14 cases) of 17 recurrent colorectal cancers after curative resection and that the elevation of these tumor markers was the first diagnostic method of recurrence in 38.1% of 21 cases. Thus, we conclude that the measurement of serum CEA and CA19-9 levels is not useful for the diagnosis of primary colorectal cancers, but is very useful for the early detection of recurrent colorectal cancers.

Effect of Short Chain Fatty Acids on Histopathological Type of Colon Cancer Induced by 1,2-Dimethylhydrazine in Rat

Short chain fatty acids (SCFAs) in cecal contents and feces were assessed in relation to the histological type of colon cancer induced by 1,2-dimethyl-hydrazine. When the amounts of SCFAs were changed by the ingestion of different types of dietary fibers, colon cancers showed differences in the distribution and differentiation. The incidence of the well differentiated type in large intestine containing a large amount of SCFAs and that of poorly differentiated type in large intestine containing a small amount of SCFAs were particularly high. SCFAs, butyric acid in particular, are considered to be closely involved in the histological type of colon cancer.

A Clinicopathological Study of Surgically Treated Colorectal Cancer

One hundred ninety three patients with colorectal cancer surgically treated at our department were reviewed from 1987 to 1992. The age of patients receiving surgical treatment ranged 33 to 86 years, with an average of 61.6 years. Location of colorectal cancers was as the following, rectum; 76 (39.4%), sigmoid colon; 56 (29.0%), descending colon; 10 (5.2%), transverse colon; 12 (6.2%), ascending colon; 23 (11.9%), cecum; 16 (8.3%). Curative operations were performed for 152 cases (78.8%). Thirty two cases (16.6%) were done with noncurative operations. Non-curative operations were performed more frequently for right-sided colon cancers than for left-sided colon and rectal cancers. Patients of Dukes’ A, B and C were 77 (39.9%), 24 (12.4%) and 92 (47.7%) cases. Furthermore, lesions of Dukes’ A and B cancers were found more frequently in left-sided colon and rectal than in right-sided colon. Thus, it is important for the total colonoscopy to be done for not only symptomatic but also asymptomatic patients because of the discovery of early or curative colorectal cancers, especially right-sided colon cancers.

Evaluation of surgical treatment for advanced gastric cancer based on long term results.

進行胃癌のうち, R2以上のリンパ節郭清を施行しえたA領域癌150例, M領域癌178例およびC領域癌100例を対象に, 組織学的リンパ節転移率を検討し, 手術時のリンパ節郭清の差が遠隔成績に及ぼす影響を, R1と比較して検討した. リンパ節郭清の意義が5年生存率に最もよく反映されるのはA, M領域のstage IIとM領域のstage III症例であることが判明した. C, CMにMCを含めた進行癌に対する胃全摘時の脾摘または膵脾合併切除の是非については, 5生率からは差は得られなかったが, 膵脾合併切除例で10, 11番リンパ節転移率が高率なこと, stage IVの全摘の5年生存例4例全例が膵合併切除例であったことより, 積極的な合併切除によるリンパ節郭清が重要であるといえる.