Tissue localization of TGFalpha and apoptosis are inversely related in colorectal tumors.

Expression of TGFalpha and the EGF receptor was studied in relation to apoptosis in human colorectal mucosa and premalignant and malignant tumors. In normal mucosa the proteins colocalized both in the proliferation compartment and at the luminal pole of the crypts in cells committed to undergo apoptosis. While staining for the EGF receptor was increased in premalignant and malignant lesions, TGFalpha was undetectable in aberrant crypt foci as well as large areas of adenomas. Incidence of apoptosis (AI) was high in these areas ranging from 8.83-24.59. Adenomas did, however, contain islands of high TGFalpha expression where AI was decreased to a range of 0.76-4.00 (decreased at P=0.0027). In carcinomas TGFalpha expression was increased above both normal and adenoma levels corresponding to the decrease in apoptosis in the malignant tumors. Tissue localization of TGFalpha and AI were still inversely related ( P=0.022), but interpatient variability was much larger than for adenomas. The data indicate that TGFalpha is the main survival factor in premalignant tumor cells of the colon, while additional factors moderate its effect in carcinomas. This suggests the possibility of targeting the EGF receptor pathway not only for treatment but also for the reversal of adenoma growth and the prevention of malignant colorectal tumors.

Adenocarcinoma of the lower third of the rectum surgically treated with a <10-MM distal clearance: preliminary results in 35 N0 patients.

BACKGROUND: Recent reports suggest that a distal clearance (DC) of 10 mm at the lower surgical margin may be considered adequate in the surgical treatment of rectal cancer, but there are no data on the possible adequacy of a < 10-mm DC in N0 patients in whom a good prognosis can otherwise be expected, that is, those with negative surgical margins and negative lymph nodes. METHODS: Between November 1991 and December 1998, 154 consecutive patients with adenocarcinoma of the lower third of the rectum had a total rectal resection with total mesorectal excision and coloendoanal anastomosis. Among 76 N0 patients, there were 35 with <10-mm DC and 41 with > or =10-mm DC. Each group was divided into two subgroups depending on whether the surgical margins were involved or not, and the rate of local recurrence in the various categories was compared. All B2 Astler-Coller stage patients in the series received postsurgical chemoradiotherapy. RESULTS: The local recurrence rate in the 35 patients with DC < 10 mm was 11.4% and that of the 41 patients with DC > or =10 mm was 7.3%. When only patients with negative surgical margins were considered, the local recurrence rate was 3.4% for those with < 10-mm DC and 5.1% for those with > or =10-mm DC. CONCLUSIONS: Our results suggest that a radical surgery with <10-mm DC followed by chemoradiotherapy may be adequate in N0 patients, provided that a careful pathologic examination of the surgical specimen excludes the presence of lymph node metastases and that the distal rectal and mesorectal resection margins fall in healthy tissue.

Adenocarcinoma of the lower third of the rectum: metastases in lymph nodes smaller than 5 mm and occult micrometastases; preliminary results on early tumor recurrence.

BACKGROUND: The number of examined lymph nodes and metastases in lymph nodes smaller than 5 mm (small lymph nodes) are a determining factor in the stage of rectal cancer although the clinical significance of occult micrometastases is controversial. We are reporting our preliminary results on the identification and prognostic utility of metastases in small lymph nodes and occult micrometastases. METHODS: We searched small metastatic lymph nodes in 101 cases of adenocarcinoma of the lower third of the rectum. We used the manual technique to dissect mesorectal fat and occult micrometastases in the lymph nodes of 52 Dukes' A and B patients, using a pool of anticytokeratin antibodies. RESULTS: Forty-five percent of the metastatic lymph nodes were smaller than 5 mm in diameter and determined the Dukes' stage in 15 (30.6%) of 49 Dukes' C patients. Occult micrometastases were found in 21 (40.4%) patients: five recurred but vascular invasion, positive distal margin of the rectum, and positive circumferential margin of the mesorectum were present. CONCLUSIONS: Small metastatic lymph nodes, vascular invasion, positive distal margin of the rectum, and positive circumferential margin of the mesorectum were found to be more important than occult micrometastases in predicting early recurrence of rectal cancer.

Total rectal resection and complete mesorectum excision followed by coloendoanal anastomosis as the optimal treatment for low rectal cancer: the experience of the National Cancer Institute of Milano.

BACKGROUND: At present, abdominoperineal resection remains the most diffuse method of treatment of very low rectal cancer. Today, we can avoid this method in some patients by using a sphincter-saving procedure. METHODS: From March 1990 to January 1999, 273 consecutive total rectal resections and coloendoanal anastomoses were performed at our Institute; this study concerns 141 consecutive patients treated for a primary adenocarcinoma of the distal rectum, from 3.5 to 8 cm from the anal verge. Patient stratification, based on definitive pathological report, was 31 Dukes' stage A (T2N0), 44 stage B (T3N0), and 66 stage C (T2N+-T3N+). RESULTS: Overall recurrence rate was 9.2%; postoperative morbidity attributable to the procedure was low. A perfect continence was documented in 61% of cases. The only pathological factor related to local recurrence rate is peritumoral lymphocytic reaction inside and around the tumor (P = .0005 and .031) independently from the number of metastatic lymph nodes, depth of fatty tissue infiltration, and lymphatic and venous neoplastic emboli. The minimum follow-up time is 12 months. CONCLUSIONS: Our data, in accordance with other authors, seem to highlight the relevant role that a well-practiced surgery, together with accurate information on the spreading of this disease, has in achieving an optimal local control of cancer.

Prognostic effects of lymph node micrometastases in patients undergoing curative gastrectomy for cancer.

AIMS & BACKGROUND: It is not known whether the presence of micrometastases in the regional lymph nodes has an impact on the oncologic outcome of patients undergoing a curative (R0) gastrectomy for cancer. The aim of the study was to assess the effects of the presence of micrometastases on survival. METHODS: We reviewed 29 patients operated on for curative (R0) gastrectomy, with a final diagnosis of pN0, 16 or more lymph nodes in the specimen, and a follow-up of at least 4 years. The original hemotoxylin and eosin slides were reviewed, and a new section was cut from the lymph nodes and immunostained with a pool of antibodies against different types of cytokeratins. Micrometastases were detected in 5 patients (27.5% of the series) and 11 lymph nodes (1.51% of all removed lymph nodes). RESULTS: Mortality due to cancer progression occurred in 3 patients from the pN0 group (14.2%) and 1 patient from the pN1 group (12.5%). CONCLUSIONS: There was no suggestion from the data that the presence of micrometastases carries an ominous prognosis in terms of survival.