[Molecular research methods in the detection of germinal mutations in hereditary colorectal cancer]. / Metodos de investigacion molecular en la deteccion de mutaciones germinativas en cancer colorrectal hereditario.

Colorectal cancer (CRC) is one of the main causes of death in South American countries. The hereditary forms of CRC are, familial adenomatous (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome (LS), which is the most common form. The detection of mutations in the DNA repair genes (MMR) and in the APC genes enables the development of prevention strategies. Some of these methods for molecular diagnosis are applied in research and the detection of mutations of these genes, such as the partial thromboplastin time test (PTT), the single strand conformational polymorphism test (SSCP), the Denaturing High Performance Liquid Chromatography test (DHPLC) and the Polymerase Chain Reaction (PCR) in real time (qPCR).

The use of silicone expander and cecal transposition after pelvic exenteration.

AIMS: Describe a new approach for pelvic floor treatment employing a temporary mechanical support device with silicone expander, with or without association to cecal transposition. METHODS: From January 2000 to June 2006, 106 patients were submitted to pelvic exenteration. A retrospective evaluation was done of the last 30 patients previously submitted to total pelvic exenteration without neither urinary nor faecal sphincter preservation who latter were submitted to a pelvic floor treatment with silicone expander with or without association to cecal rotation. RESULTS: Twenty-six patients were female and four male. The most common primary neoplasm site were of gynecological origin (20 cases). The median follow-up period was 12 months (0.36-38). Only one patient presented small intestine loops slipping after expander removal. No other patient had small intestine loops slippage into the pelvis, probably because of cecal transposition. All patients were submitted to a post-operative CT scan to confirm that intestinal loops remained out of the pelvis. Six patients presented pelvic hollow infection after device removal. All cases had complete resolution with local cleaning using physiological solution associated with systemic antibiotic therapy, except one who needed a trans-abdominal surgical approach. CONCLUSIONS: Pelvic floor treatment employing a temporary mechanical support device with silicone expander, associated or not to cecal transposition is a low-morbidity procedure. The most common complication is pelvic floor infection, but maintaining a cutaneous perineal hole allows easy access and treatment of possible pelvic abscesses as well as early recurrence diagnosis.

Prognostic and predictive value of the thymidylate synthase expression in patients with non-metastatic colorectal cancer.

AIMS: To assess the value of thymidylate synthase (TS) expression as a predictive factor in the efficacy of adjuvant chemotherapy in colorectal cancer, as well as its independent prognostic value for survival. METHODS: We studied 114 high risk colorectal carcinoma patients (high risk stage II and stage III), distributed in two treatment groups: surgery alone (61 patients) or surgery followed by 5-FU-based chemotherapy (53 patients). TS protein expression in the tumour tissue was assessed by immunohistochemistry. RESULTS: In the surgery alone subgroup, overall survival (OS) at 5 years were 77.5% for the patients with low TS expression, against 57.7% for the patients with high TS expression (p=0.006). Among patients with low TS, there was no difference in OS as a result of whether adjuvant chemotherapy was carried out or not (65.8 vs 77.5%, p=0.29). Among the patients with high TS, there was a significant gain in OS in favor of chemotherapy (87.8 vs 57.7%, p=0.04). Analyzing the complete sample, TS expression was not shown as an independent prognostic factor for survival in the multivariate analysis. CONCLUSIONS: The immunohistochemical TS expression may be used for selecting patients for better adjuvant chemotherapy protocols. In this sample, TS expression was not an independent prognostic factor for survival.

Pelvic exenteration and sphincter preservation in the treatment of soft tissue sarcomas.

BACKGROUND: Pelvic sarcomas are rare and there are very few effective therapeutic alternatives. A complete resection is considered the main factor associated to a good prognosis, which justifies the employment of a pelvic exenteration (PE) in selected cases. METHODS: Between 1980 and 2000, 96 PE were performed, nine of which were for sarcomas. The clinical characteristics, surgical and anatomopathological aspects and the patients' evolution were described. RESULTS: The median follow-up time was 24 months (ranging from 1 to 57 months). In relation to the sphincters preservation, at least one sphincter was preserved in five patients. There were two post-operative deaths. In the last follow-up, six patients were alive without any evidence of the disease. CONCLUSION: Pelvic exenterations should be performed for the treatment of selected cases of locally advanced pelvic sarcomas. Sphincter preservation may be performed, provided that oncological resection principles are obeyed.

Less DeltamtDNA4977 than normal in various types of tumors suggests that cancer cells are essentially free of this mutation

Levels of mtDNA(4977) deletions (DeltamtDNA(4977)) have been found to be lower in tumors than in adjacent non-tumoral tissues. In 87 cancer patients, DeltamtDNA(4977) was detected by multiplex polymerase chain reaction (PCR) amplification in 43 (49%) of the tumors and in 74 (85%) of the samples of non-tumoral tissues that were adjacent to the tumors. DeltamtDNA(4977) deletions were detected in 24% of the breast tumors, 52% of the colorectal tumors, 79% of the gastric tumors, and 40% of the head and neck tumors as compared with 77, 83, 100, and 90% of the adjacent respective non-tumoral tissues at the same DNA template dilution. Based on limiting dilution PCR of 16 tumors and their adjacent non-tumoral tissues, it was found that the amount of DeltamtDNA(4977) was 10- to 100-fold lower in the tumor than in the respective control non-tumoral tissues. Real-time PCR experiments were performed to quantify the number of DeltamtDNA(4977) deletions per cell, by determining the mitochondrial-to-nuclear DNA ratio. In all of the cases of breast, colorectal, gastric, and head and neck cancer the proportion of DeltamtDNA(4977) in tumors was lower than that of the respective non-tumoral tissue. Traces of DeltamtDNA(4977) in tumors were apparently due to contamination of tumor tissue with surrounding non-tumoral tissue, as evidenced by tumor microdissection and in situ PCR techniques, suggesting that tumors are essentially free of this mutation. Although the metabolic effect of DeltamtDNA(4977) may be minimal in normal (non-tumor) tissue, in tissue under stress, such as in tumors, even low levels of DeltamtDNA(4977) deletions may be intolerable.

Treatment of severe actinic rectitis.

BACKGROUND: The authors report the treatment of three female patients with severe actinic rectitis, with stenosis or perforation, submitted to anterior proctosigmoidectomy and transanal coloanal anastomosis. METHODS: In all cases surgery consisted of total proctosigmoidectomy, mucosectomy of the anal canal, lowering of the left colon through the pelvis and transanal anastomosis performed manually at the level of the pectineal line using separate absorbable sutures. A protective intestinal shunt was performed in all cases. RESULTS: The three patients did not present transoperative or immediate postoperative complications, but the first patient developed deep venous thrombosis of the leg that was submitted to successful clinical treatment. The intestinal shunts were later closed in all three cases. Sphicter function was considered very good in the first case and regular in the remaining two. CONCLUSION: The surgical technique utilized was considered to be adequate for the cases reported and is the first option for the maintenance of transit in patients with severe actinic rectitis since the anastomosis is performed using non-irradiated colon with the pectineal line, practically outside the pelvis.

Radiation and chemotherapy instead of surgery for low infiltrative rectal adenocarcinoma: a prospective trial.

BACKGROUND: The objective of this prospective study was to determine the possibility of treatment based exclusively on chemotherapy and radiotherapy for patients with low infiltrative rectal tumors in an attempt to preserve sphincter function. METHODS: Sixteen patients with rectal adenocarcinoma up to 3 cm above the pectineal line with initial indications for abdominoperineal resection (APR) were submitted to a 5040-cGy (28 x 180 cGy) radiotherapy dose and chemotherapy during the first 3 and last 3 days of radiotherapy, using 425 mg/m2/day of 5-fluorouracil (5FU) and 20 mg/m2/day of folinic acid. Levamisole was used at 150 mg/day for 3 consecutive days at 2-week intervals throughout the period of therapy. Patients with a complete response were not submitted to APR, but received additional brachytherapy for curative purposes with doses from 2000 to 3000 cGy. Patients with recurrence after a complete response, with partial response, or with no response were submitted to APR. RESULTS: Six patients (37.5%) presented a complete response, five (31.25%) presented a partial response, and five (31.35%) did not respond. The disease-free interval ranged from 1 to 34 months (mean = 11 months) among the six patients with complete response, and only one patient not submitted to APR is currently asymptomatic. Among the 15 patients with an indication for APR, three refused surgery because of full improvement of clinical symptoms and currently have tumor activity in the rectum. Mean patient follow-up was 23.8 months (8 to 43 months), and ten patients (62.5%) showed no evidence of active disease at last follow-up. CONCLUSIONS: The therapeutic schedule used was not effective in preserving sphincter function in patients with low infiltrative rectal adenocarcinoma, because responses, although very frequent, were only temporary.

Internal hemipelvectomy in the treatment of recurrent carcinoma of the colon: report of a case.

PURPOSE: Although extended surgery has been established as an effective method for the treatment of advanced carcinoma of the colon, there are no reports in the literature of en bloc resection of the tumor together with the iliac bone. We report herein a 46-year-old woman with a second local recurrence after right colectomy, with the main objective of showing the possibility of indicating this type of surgery in selected cases. METHODS: In view of the lack of therapeutic options for the case and the absence of metastases, extended curative surgery for recurrent carcinoma of the colon was performed, with en bloc resection of the right iliac bone and of the crural nerve (Type I internal hemipelvectomy). RESULTS: After a 27-month follow-up, the patient is asymptomatic, with no signs of local recurrence or metastases. CONCLUSIONS: In selected cases, recurrent carcinoma of the colon can be treated by extended and aggressive surgery, including bone resection, to obtain an appropriate safety margins.

Prognostic factors in carcinoma of the penis: multivariate analysis of 145 patients treated with amputation and lymphadenectomy.

PURPOSE: The major issue in penile cancer is deciding who should or should not undergo lymph node dissection. Clinical and invasive methods are not reliable for staging. Clinical and pathological factors involved in lymph node metastases and prognosis were evaluated in 145 patients with penile carcinoma staged according to the 1978 TNM system, and treated with amputation and lymphadenectomy. MATERIALS AND METHODS: Clinical factors studied were patient age, race, disease evolution time, symptoms, and clinical T and N stages. Pathological factors of the primary tumor considered were tumor thickness, histological grade, lymphatic and venous embolization, infiltration of the corpora cavernosa, corpus spongiosum and urethra, mononuclear and eosinophilic infiltrates, and cell alterations suggestive of human papillomavirus. All slides were reviewed by 1 pathologist. The Cox regression hazards method for multifactorial analysis was used. RESULTS: Followup ranged from 0.7 to 453.2 months (mean 85.8, median 32.7). The 5-year disease-free and overall survival rates were 45.3 and 54.3%, respectively. Venous and lymphatic embolizations were the main factors affecting significantly the incidence of lymph node metastasis, which were the main risks factors for recurrence and death. Pathologically proved infiltration of the corpora cavernosa, urethra and adjacent structures, which corresponded to stages T2, T3 and T4 disease, respectively, of the current TNM classification, were not significant predictors for incidence of lymph node metastasis, disease-free and overall survival or risk factors for recurrence and death. CONCLUSIONS: Because venous and lymphatic embolizations were related to greatest risk of lymph node metastasis, we propose their evaluation in staging and therapeutic planning of patients with infiltrative tumors of the penis.

Chordoma: retrospective analysis of 24 cases.

INTRODUCTION: Chordoma is a rare and slow-growing tumor, with local aggressiveness and preferential localization in the vertebral column. OBJECTIVE: The main objective of this study is to evaluate natural history and results of treatment of chordomas. METHODOLOGY: This is a retrospective study from 1953 to 1993. MATERIAL AND METHODS: The age ranged from 2 to 86 years (mean = 34.5). Twelve patients were male and 12 female. The localization of the tumor was: 20 in the sacral region, 3 in head and neck and one out of the spine. RESULTS: The treatment, alone or combined, was surgery, radiation therapy and chemotherapy. The survival rate for patients with lesions in the sacrum ranged from 4 to 119 months, since the date of the symptoms. The 5-year overall survival was 4.2%. CONCLUSION: Chordoma is a rare and slow growing tumor, with a very difficult approach by surgery due to its preferential location in the sacrum and poor therapeutic results with radiation therapy or chemotherapy, mainly in patients with advanced disease.

Unreliability of modified inguinal lymphadenectomy for clinical staging of penile carcinoma.

BACKGROUND: In 1988, Catalona proposed a modified bilateral inguinal lymphadenectomy for staging of lymph node metastasis from penile carcinoma. All three patients with penile carcinoma submitted to this procedure and without histologically confirmed metastases were free of disease within a mean follow-up time of 14.6 months. METHODS: In a prospective study, the authors evaluated thirteen patients staged by the TNM system and submitted to modified bilateral inguinal lymphadenectomy. RESULTS: None of the patients had histologic metastases in the medial quadrant lymph nodes. Two of these patients developed regional lymph node metastases within 13.2 months (mean follow-up time). CONCLUSIONS: Catalona's procedure was not reliable. We therefore recommend standard inguinal lymphadenectomy as the minimal treatment for patients with infiltrating carcinoma of the penis.

Surgical treatment of colon and rectum adenocarcinoma in elderly patients.

The results are presented of disease-free interval and overall survival in 53 elderly patients with colon or rectum adenocarcinoma treated with curative surgery. The average age was 75.3 years (median = 75.0); 21 patients were male and 32 were female. Tumor location was as follows: rectum 18 (34%), sigmoid 17 (32.1%), right colon 14 (26.4%), and transverse colon 4 (7.5%) All patients were surgically treated following the classical patterns for tumor resection. After pathological examination, which included the histological grade differentiation, the disease stage was reevaluated following the pTNM system. Overall and disease-free survival at 5 years, for all patients, independent of histological grade differentiation and disease stage, were 75.3% and 55.5%, respectively. Overall survival at 5 years for patients with grades I and II histological differentiation was 74.1% and 85.0%, respectively. None of the grade III patients (2 cases) survived more than 1 year. The 5 years disease-free survival for patients with histological grade differentiation I and II was 56.8% and 60%, respectively. There was no statistically significant difference in overall survival for patients with stages SI, SII, and SIII, but the disease-free survival at 5 years by stages was found to be significant with rates of 100%, 67.6%, and 22.6%. Postoperative mortality was 4 (7.5%). The postoperative mortality and survival rates obtained in this group of patients encourage us not to consider age as a limiting factor for curative surgical treatment.

Actinic rectitis--the role of colostomy.

From 4132 patients treated with radiation therapy due to gynecological malignancy from 1974 to 1988, 527 (12.75%) developed some grade of actinic rectitis with clinical manifestation. The authors analyzed the efficacy of colostomy in the management of 10 women with actinic rectitis grades I and II (Sherman classification) submitted to clinical treatment without response. Pelvic radiation therapy, clinical findings, proctoscopy and rectal biopsy were the basis for the diagnosis and staging of the actinic rectitis. All colostomies were made in the transverse colon and the median follow up from colostomy to last review was 53 months. Eight patients had complete remission of clinical findings after colostomy, but one had recurrence of symptoms 2 years later. One patient had incomplete remission but with clinical improvement and one patient had tumor recurrence. From 8 patients with complete clinical remission, 2 had the colostomies closed, but in 1 was restored 3 months later due to rectum-vaginal fistula.