Expression patterns of cell cycle and apoptosis-related genes in a multidrug-resistant human colon carcinoma cell line.

BACKGROUND: An in vitro multidrug resistance (MDR) system from a human colonic cancer cell line (SW620-MDR) has been established. To further study the mechanisms at molecular level and prevention of multidrug resistance in clinical practice, it was demonstrated that the expressions of several apoptosis-related and cell cycle regulator genes were changed in the cells. METHODS: A multidrug-resistant colonic cell line (SW620-MDR) was established, and the Atlas human cDNA expression array was used for studying the pattern of gene expression in this cell line. Furthermore, Northern hybridization or real-time PCR analysis confirmed the pattern of gene expression. RESULTS: In the SW620-MDR cell line the pro-apoptosis genes, CASP4, BIK, PDCD2, and TACE were expressed with decreased levels, and the antiapoptosis genes CD27-L and IGFBP2 were over-expressed. Furthermore, the cell cycle regulator genes such as CDK6, CCND1, CDC27HS, CDC16HS, Wee1Hu, MAPKK1, and IGFBP6 were expressed with decreased levels in the drug-resistant cell line. CONCLUSIONS: It is worthwhile investigating whether the differentially expressed pattern of the aforementioned genes exists in the drug-resistant cancer specimens, and to further understand their functions in the cancer drug-resistance mechanism.

Identification of novel genes that are differentially expressed in human colorectal carcinoma.

By using mRNA differential display technology, we have identified three cDNA clones, myl 3, myl 4, and myl 6, to show significant changes in expression between human colorectal tumor and paired normal tissue. Northern blot analysis indicated that clone myl 3 expression was elevated in normal tissue, and clone myl 4 expression was elevated in tumor tissue. Nucleotide sequence analysis revealed that clones myl 3 and myl 4 have not been previously identified. However, clone myl 6 appears to be the human homolog of the 3' end region of tissue inhibitor of metalloproteinase 3 (TIMP-3). Northern blot analysis showed that a 2.5 kb TIMP-3 transcript was expressed at a much higher level in normal tissue than the colorectal tumor.

Perforated rectal lymphoma in a renal transplant recipient: report of a case.

PURPOSE: We report the case of a renal transplant recipient with rectal lymphoma manifested by sudden onset of abdominal pain from a perforated rectum who was treated successfully with prompt surgical resection and reduction of immunosuppressants. METHODS: An emergent anterior resection with Hartmann's procedure was done. Immunosuppressants were drastically reduced by discontinuation of cyclosporine. RESULTS: Pathologic examination showed diffusely infiltrated large-cell malignant lymphoma with an immunoblastic feature. The patient has been followed-up for four years, with no tumor recurrence or graft rejection. CONCLUSION: Rectal lymphoma, although rare, should be kept in the list of differential diagnoses for transplant recipients who exhibit lower gastrointestinal bleeding, intestinal obstruction, or abdominal pain.

Retrograde lymphatic spread: a likely route for metastatic ovarian cancers of gastrointestinal origin.

In order to outline the pathways of gastrointestinal malignancies metastasizing to the ovaries, we reviewed 103 cases of metastatic ovarian tumors, and also performed para-aortic lymph node sampling on 11 patients at operation for metastatic ovarian tumors. Of the 103 patients, 74% (26/35) with gastric cancer and 67% (45/67) with colorectal cancer had lymph node metastasis at or before the diagnosis of ovarian tumor. Intraperitoneal metastases presented in 49 and 42% of patients with gastric and with colorectal cancers, respectively. Twenty-three percent of gastric cancer patients and 25% of colorectal cancer patients presented with both lymph node and intraperitoneal metastases. The ovary was the first or among the early metastatic organs diagnosed in 51 of the 53 patients with metachronous ovarian metastases. Only 4 patients with colorectal cancer and none with gastric cancer showed parenchymal organ metastases. These 4 patients also showed intraperitoneal lesions, and 3 of these 4 patients had node metastasis. Among the 11 patients who underwent prospective para-aortic lymph node sampling during operation for the ovarian tumors, only 1 had enlarged para-aortic nodes depicted by computed tomography, 2 had grossly enlarged (>/=1.5 cm) para-aortic lymph nodes noted at surgery, and 6 of the 7 patients with gastric cancer and all 3 with colorectal cancer had metastatic nodes histologically. Among the 58 nodes taken from these patients, 67% showed metastatic foci. We concluded that lymph node metastasis is frequently seen in patients with metastatic ovarian tumors of gastrointestinal origin, and hypothesized that retrograde lymphatic spread is a likely route for the metastases.

Primary diffusely infiltrative adenocarcinoma of the colon and rectum.

BACKGROUND: Primary diffusely infiltrative colorectal adenocarcinoma is rare. About 100 cases have been reported in the literature. The mucosal alterations in this type of tumor and their clinicopathological characteristics in relation to survival are not clear. METHODS: We retrospectively reviewed 30 cases of primary diffusely infiltrative colorectal adenocarcinoma operated upon in a single institution. RESULTS: Eighteen (60%) of these 30 patients were women. The average age at diagnosis was 47.4 (SD, 19.3) years. Eighteen tumors (60%) were located in the rectum. The tumors could be classified into two major types. A type 1 tumor had minimal mucosal alteration and no discrete ulcer. A type 2 tumor was associated with a discrete ulcer. The type 1 tumor was more frequently associated with intracellular or extracellular mucin production and stage IV disease. Hematogenous spread (including peritoneal carcinomatosis) was more frequently seen in type 1 than in the type 2 tumors (61% vs. 18%, p = 0.013). The overall median cancer-specific survival time was 15 (SE, 3; 95% confidence interval, 10-21) months. TNM stage is the only significant factor in predicting outcome (p = 0.016). When compared with stages II and III, the odds of death for stage IV was 2.9 (95% confidence interval: 1.1-7.4). CONCLUSION: Diffusely infiltrative colorectal cancer can be separated into two subtypes according to the presence of a discrete ulcer. The type 1 tumor (without a discrete ulcer) was associated with a higher frequency of hematogenous spread. TNM Stage was the only important clinicopathological factor in determining outcome.

Survival impact of lymph node metastasis in TNM stage III carcinoma of the colon and rectum.

BACKGROUND: Node-positive (TNM stage III) adenocarcinoma of the colon and rectum consists of tumors with a widely variable prognosis. To predict the outcome of patients with stage III carcinoma, we assessed the survival impact of the number and level of lymph node metastasis and other clinicopathological variables. STUDY DESIGN: A retrospective study was performed on 538 patients with stage III carcinoma of the colon and rectum who underwent curative resection at Chang Gung Memorial Hospital between 1980 and 1989. Ten or more lymph nodes in each resected specimen were identified microscopically. Multivariate analysis was used to determine the independent variables. RESULTS: The relative survival rates at five and ten years were 52 and 42 percent, respectively. Tumor morphology, depth or tumor penetration, histologic grade, and the status (number and level) of nodal involvement were significant in the univariate analyses. Only grade and nodal status remained significant in the multivariate analysis. Based on the nodal status, these patients were separated into three groups: stage IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more nodes or presence of pN3). The five-year survival rates for patients with stages IIIA, IIIB, and IIIC disease were 69, 44, and 29 percent, respectively. Compared with patients with stage IIIA disease, the odds of death for patients with stages IIIB and IIIC carcinoma were 2.1 (95 percent confidence interval: 1.5 to 2.8, p = 0.0001) and 3.3 (95 percent confidence interval 2.4 to 4.5, p = 0.001), respectively. CONCLUSIONS: We suggest that stage III adenocarcinoma of the colon and rectum be divided into three substages: IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more positive nodes or presence of pN3.

The association between perioperative blood transfusion and survival of patients with colorectal cancer.

BACKGROUND: The authors undertook this study to test the hypothesis that perioperative blood transfusion has an adverse effect on survival of patients with colorectal cancer. METHODS: A retrospective analysis was performed on 725 patients who underwent curative resection for Dukes Stage B and C colorectal cancers in our institution between 1981-1985 and who were followed for 5-11 years. RESULTS: Rectal cancers occurred more frequently in the transfused than in the nontransfused patients (64% versus 47%; P = 0.0001). In the patients with colon cancer, no significant effect of transfusion on recurrence-free survival was seen (P = 0.8, log-rank; P = 0.49, Cox regression analysis). The cumulative 5-year survival rate was 77% (95% confidence interval, 69-85%) for the nontransfused and 78% (72-83%) for the transfused patients. In patients with rectal cancer, the 5-year survival rate was 79% (67-87%) for the nontransfused and 67% (59-71%) for the transfused patients. A significant association was noted in patients with Stage B cancer (P = 0.002, log-rank; P = 0.02, Cox regression analysis), but not in those with Stage C cancer (P = 0.05, log-rank; P = 0.15, Cox regression analysis). In patients with Stage B rectal cancer, more frequent abdominoperineal resections (APR) were performed among the transfused patients (65% versus 32%; P = 0.0001). This subgroup was further stratified by operative procedure and reanalyzed using the same Cox regression model. Transfusion had no effect on survival of patients treated by APR (P = 0.31) or of those having a sphincter-saving procedure (P = 0.53). CONCLUSION: The seemingly adverse effect of perioperative blood transfusion on the survival of patients with colorectal cancer may be explained by other covariates.

An alternative treatment of anal squamous cell carcinoma: combined radiotherapy and chemotherapy.

The conventional surgical treatment of anal squamous cell carcinoma is abdominoperineal resection. A new approach of combined radiotherapy and chemotherapy has been proposed following the observation of excellent local control. In this retrospective study, 40 cases of primary anal squamous cell carcinoma without distant metastasis were collected between 1979 and 1986 and the individual prognosis of the above two methods of treatment was evaluated. Group I (20 cases) received abdominoperineal resection with or without postoperative radiotherapy. Postoperative radiation was given if regional lymph node biopsy was positive. Group II (20 cases) received combined radiotherapy and chemotherapy with or without wide local excision. Radiation was delivered to the anus, pelvis, and bilateral inguinal nodal areas to a total dose of 5,500 rads. A continuous infusion of 5-FU was started on day 2 of the irradiation at a dose of 1,000 mg/m2 body surface/day for 5 days and a bolus injection of mitomycin was given on day 2 at a dose of 10 mg/m2 body surface. The second course was given 1 month later to complete the chemotherapy. The wide local excision was performed if the disease still persisted after completion of combined radiotherapy and chemotherapy. All 40 cases were followed up for at least 5 years. All cases (100%) in group I survived 1 year, 18 cases (90%) 2 years, 14 cases (70%) 3 years, 10 cases (50%) 4 years, and 6 cases (30%) 5 years. Twenty cases (100%) in group II survived 1 year, 17 cases (85%) 2 years, 13 cases (65%) 3 years, 8 cases (40%) 4 years, and 5 cases (25%) survived 5 years. All the mortalities in both groups died of distant metastasis or abdominal carcinomatosis. From the above results, the overall survival rate of combined radiotherapy and chemotherapy was not significantly worse than that of conventional abdominoperineal resection. In conclusion, combined radiotherapy and chemotherapy may be chosen as an alternative management in treating anal squamous cell carcinoma.

Postoperative adjuvant radiotherapy in Astler-Coller stages B2 and C rectal cancer.

Between 1979 and 1983, 127 patients with Stages B2 or C rectal cancer treated with surgery plus postoperative adjuvant radiotherapy (RT group) and 122 patients treated with surgery alone (S group) were compared to evaluate the effect of postoperative radiotherapy on survival and disease recurrence. Each group was stratified into subgroups according to stage and tumor differentiation as follows: Subgroups BW (Stage B2 and well-differentiated tumor), BM (Stage B2 and moderately differentiated tumor), CW (Stage C and well-differentiated tumor), CM (Stage C and moderately differentiated tumor), and P (poorly differentiated tumor). Ninety-five percent of the patients were followed until death or, if alive, to five years after surgery. Postoperative radiotherapy was associated with a reduced five-year survival rate in Subgroup BW (67 vs. 87 percent; P = 0.02). In the remaining subgroups of the RT group, there was a statistically insignificant trend toward a worse survival rate (56 vs. 65 percent, 47 vs. 64 percent, 41 vs. 46 percent, and 50 vs. 36 percent for Subgroups BM, CW, CM, and P, respectively). The local failure rates for the S group and RT group were 10 vs. 23 percent (P = 0.15) in Subgroup BW, 32 vs. 21 percent (P = 0.4) in Subgroup BM, 24 vs. 25 percent (P = 0.6) in Subgroup CW, and 18 vs. 18 percent (P = 0.6) in Subgroup CM, respectively. Eight percent (9/127) had severe or life-threatening radiation-related complications. Postoperative adjuvant radiotherapy alone did not improve the survival of patients with Stages B2 or C rectal cancers. It may have led to worsened survival in the subgroup of patients with well-differentiated Stage B2 rectal cancer.

Pelvic peritoneal reconstruction to prevent radiation enteritis in rectal carcinoma.

Some patients with rectal cancer who undergo exenterative surgery may require radiation therapy as an adjuvant treatment for recurrent or residual disease. A common devastating side effect of this treatment modality is radiation enteritis, a radiation-induced small bowel injury. Hence, the prevention of such a complication is essential for both the surgeon and the radiation oncologist. A new surgical method using the posterior rectus sheath and peritoneum to partition the abdominal cavity at the level of the umbilicus to the sacral promontory seems to accomplish this purpose, keeping the small bowel away from the pelvic cavity. After removal of the rectal lesion [eight abdominoperineal resections (APRs), nine Hartmann's procedures, and one low anterior resection (LAR)] in 18 patients with rectal cancer, this new surgical procedure was performed. One of the patients had an early postoperative intestinal obstruction, and all but one of the patients received postoperative adjuvant radiation therapy. In addition, a small bowel series was performed before the radiation therapy and six months and one year after surgery. Upon examination, most of these patients still had their small bowel kept intact in the abdominal cavity. During the follow-up period of 10 months to 2 years with an average of 18 months, two late complications of intestinal obstruction were noted. Exploratory laparotomy of these two patients revealed radiation enteritis of the small bowel. Therefore, the failure rate of the following procedure is 12 percent, since 2 of the 17 patients received small bowel injury. Although the follow-up period for this surgical method is short, the results have encouraged us to continue the use of this procedure on advanced rectal cancer patients who require postoperative radiation therapy.

[Experience of surgical treatment for colorectal endometriosis: report of 6 cases].

Endometriosis is a common disease with 8-15% occurrence in women during their reproductive period. Involvement of the bowel wall occurs rather frequently and probably presents in 12-34% of patient with pelvic endometriosis. However, it is classically asymptomatic and difficult to find out. From 1977 to 1987, we had six patients of colorectal endometriosis with mainly bowel symptoms. Five of them were located at rectum and sigmoid colon, one at the hepatic flexure of colon. All of the cases developed constipation or diarrhea, and four of them had severe abdominal pain. Four cases developed rectal bleeding. Previous operation for pelvic endometriosis was noted in two cases. The detailed examination included digital examination, endoscopy, barium enema and CT scan. Suspected malignancy was the indication for surgery in 4 cases and one in rectal stenosis. Low diagnostic rate was due to the fact that endometrial tissue rarely infiltrates the mucosa. Therefore, pathology of biopsied specimen often reveals non-conclusive finding to prevent differential diagnosis. However bowel resection offers conclusive diagnosis and chances of cure. In our study, only one suspected endometriosis case received bilateral oophorectomy. The stenotic segment of rectum restored to normal caliber after operation.

Prognostic factors in management of traumatic perforation of colon and rectum.

A retrospective analysis was made of the prognostic factors and management of traumatic perforation of the colon and rectum in 80 patients during the period of 1980 to 1988 at Chang Gung Memorial Hospital. The total mortality was 11%. Morbidity was 18% among the survivors. The mortality was higher in patients with old age (50% for those over 60 years old), delayed operation (50% for a delay of more than 72 hours), poor nutrition (57%), shock condition before or during operation (50%), severe abdominal fecal contamination (35%) and associated abdominal injury. We conclude that the surgical procedures for traumatic perforation of colon and rectum performed depend upon the patient's condition. The prognostic factors in patients with traumatic perforation are patient's age, timing of operation, degree of abdominal fecal contamination, injury to other abdominal organs and general condition such as nutrition and shock.

[The clinic diagnostic value of the rigid sigmoidoscopy].

Rigid sigmoidoscopy is beneficial as it detects rectal or distal sigmoidal lesions very efficiently and precisely. But it also has some complications, e. g. rectal injury, rectal perforation or transient bacteremia. In this prospective study, 800 cases were collected and divided into two groups. In group I, 400 O.P.D. symptomatic cases were chosen randomly and in group II 400 cases registered for routine physical examination were picked up. The positive detection rate was 7% in group I versus 2% in group II. The lesions detected in group I are 15 cases of cancer, 7 cases of polyp, 4 cases of irradiation proctitis, 2 cases of ulcerative colitis and 1 case of pseudomembranous colitis. Only 8 polyps are found in group II. The routine sigmoidoscopy is mandatory for symptomatic patients but it is not cost-effective for routine check-ups. The stool occult blood is the best screening test for detecting colorectal lesions. For routine physical examination, stool occult blood test is safe and easy to perform. If the stool occult blood test is positive, then further examinations will be necessary.

Perianal Paget's disease--report of 4 cases.

Over the past nine years (from 1981 to 1989), four patients with perianal Paget's disease were treated. All were male with an average age of 58.5 years. Clinically, perianal Paget's disease manifests as a slowly enlarging eczematous, and sharply demarcated perianal skin rash that may be oozing or itching. In the characteristic pathology finding, Paget's cells appear as large, rounded signet-ring cells with abundant mucin stain positive cytoplasm in the basal layer of the acanthotic epidermis. All but one, who suffered from primary sweat gland carcinoma, had underlying rectal adenocarcinoma. The first two cases expired soon after a delayed diagnosis of terminal underlying malignancy. Only in the later two cases was there a preoperative suspicion of perianal Paget's disease. There is often a delay in diagnosis due to clinical ignorance. Patients with persisting perianal skin rash should be biopsied frequently. If perianal Paget's disease is diagnosed, the underlying malignancy should be surveyed and managed thoroughly.

[Removal of the ortho isomer of 4,4-bis(4-fluoro phenyl) butanoic acid by sulfonation].

4,4-Bis(4-fluorophenyl) butanoic acid is an important pharmaceutical intermediate. It is usually prepared by Friedel-Crafts reaction of 4-(4-fluorophenyl) butyrolactone with fluorobenzene. But the ratio of products is often affected by reaction conditions. By applying sulfonation, the undesired isomer can be successfully removed.

Non-traumatic perforation of colon and rectum.

Free perforation of the colon and rectum is an acute surgical condition. Possible factors affecting the prognosis include age, sex, underlying disease, surgical procedures, duration from onset to surgical treatment, general condition before surgery and degree of contamination. A series of 50 cases with acute, nontraumatic perforation of the colon and rectum treated at Chang Gung Memorial Hospital from 1979 to 1986 were reviewed and studied retrospectively according to these prognostic factors. The mortality rate was highest in the group with colo-rectal cancer (45%). The mortality rate was 50% in the group who underwent primary closure with proximal diversion and 40% in the group who underwent resection without anastomosis. The mortality may not be related to the surgical procedure: the selection of the procedure was based on the seriousness of the illness. The mortality rate was 87% in patients with septic shock, 62% when treatment was delayed for more than 72 hours, 72% with severe contamination and 56% with poor nutritional status. Age, sex and underlying diseases were not significant contributing factors.

Urodynamic studies before and/or after abdominoperineal resection of the rectum for carcinoma.

Urodynamic studies were performed on 62 patients who underwent abdominoperineal resection of the rectum during the last 14 months. Of these patients 20 were evaluated preoperatively and postoperatively, and 42 were studied postoperatively only. Urodynamic studies consisted of cystometry, urethral sphincter electromyography and uroflowmetry. The results of these studies revealed a significant decrease in effective bladder capacity, and increases in first sensation to void and residual urine postoperatively. The peak and average urinary flow rates also were decreased significantly. No significant changes could be found in urethral sphincter electromyography. The incidence of complete denervation of the bladder in our study was 11.3 per cent. More severe voiding dysfunction was found in patients with stage C2 anorectal tumors than in those with stage B2 disease and in patients with tumors 4 to 8 cm. from the anal verge. Urodynamic evaluation, especially cystometry, is necessary after abdominoperineal resection to detect voiding dysfunction.