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M S Talamonti

Publications and source records attributed to M S Talamonti.

29 records · Page 2Linked to original sources

Expression of p68 in human colon cancer.

p68 is an interferon-inducible protein kinase which is a key factor in the regulation of both viral and cellular protein synthesis. Since p68 plays a central role in cellular protein synthesis, we hypothesized that it would parallel translational activity, and thereby correlate with cellular differentiation in both normal and neoplastic cell types. Using the anti-p68 monoclonal antibody, TJ4C4, we have previously noted a correlation of p68 expression with the degree of cellular differentiation in the human upper aerodigestive tract and lung. During normal human fetal development, p68 is abundantly expressed in the upper aerodigestive tract and lungs, but considerably less so in the colon. In order to determine if this fetal expression pattern correlated with the pattern seen in adult colon and colonic adenocarcinomas, we analyzed the expression pattern of p68 in 80 patients with adenocarcinoma of the colon. Using light microscopic evaluation of immunoperoxidase-stained tissue sections, a spectrum of p68 expression was noted among the tissue samples. Increased p68 levels were noted in the majority of tumors with increased cellular differentiation, and those tissues with decreased p68 were, in general, less differentiated. These data are consistent with the concept that the expression of p68 parallels the degree of cellular differentiation, and are consistent with previously reported studies using this antibody. The limited fetal expression pattern of p68 in the colon and the variable correlation of p68 with differentiation suggests that p68, as well as other translational regulators, can be important in assessing the biological potential of tumors arising in the colon.

Adenocarcinoma↗

Site-specific differences in pp60c-src activity in human colorectal metastases.

The c-src proto-oncogene has been implicated in the progression of primary human colorectal carcinoma to hepatic metastasis. To determine if increased pp60c-src tyrosine kinase activity is a colon-specific phenomenon present in colorectal metastases to all sites, the pp60c-src-specific kinase activity of noncolon tumor metastases to the liver was compared to that of colorectal liver metastases. Activity of extrahepatic colon carcinoma metastases was compared to that of colorectal liver metastases as well as that of normal colonic mucosa. The specific activity of pp60c-src in multiple synchronous metastases from colon carcinoma was also examined. Tyrosine kinase activity was determined by immune complex kinase assay; protein levels were determined by immunoblotting. Specific activity was calculated for each group by dividing the total activity by protein level. Colon carcinoma metastases to the liver had significantly (P < 0.04) increased pp60c-src activity with an average 2.2-fold increase over normal mucosa. In contrast, noncolon tumor metastases to the liver showed minimal pp60c-src kinase activity. Extrahepatic colorectal metastases demonstrated significantly increased (P < 0.005) pp60c-src activity with an average 12.7-fold increase over normal mucosa. When compared to colon liver metastases, extrahepatic colorectal tumor metastases show a significant difference in activity (P < 0.05) with an average 5.7-fold increase. Examination of multiple synchronous colon carcinoma metastases confirmed these results. In summary, we conclude that (1) the activation of pp60c-src between primary tumors and metastases is specific to colon metastases, and (2) although pp60c-src activity is significantly increased in colorectal metastases, site-specific differences in the magnitude of activity are evident.

Adenocarcinoma↗

Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer.

Activation of the tyrosine kinase of the c-src gene product, pp60c-src, has been shown to occur in nearly every primary colorectal carcinoma, and is found as early as in polyps of high malignant potential. However, no studies have addressed potential pp60c-src changes which occur during progression. To examine this question, we have studied kinase activity and protein levels in 7 colonic polyps, 19 primary lesions, and 19 liver metastases relative to normal colonic mucosa. Significant increases in tyrosine kinase activity were seen as early as in colonic polyps of high malignant potential. Further increases were observed in activity and level in primary tumors. However, the greatest increases in activity and protein levels were observed in liver metastases. Additionally, six metastatic lesions were obtained in which synchronous primary tumor was resected. In each of these liver metastases, pp60c-src activity and level were significantly increased relative to the corresponding primary tumor, as well as to normal colonic mucosa. Our results demonstrate that progression of colon primary tumors to liver metastases correlates with increased pp60c-src kinase activity and protein level.

Adenocarcinoma↗

Locally advanced carcinoma of the colon and rectum involving the urinary bladder.

We reviewed the records of 70 patients who underwent resection of a carcinoma of the colon and rectum with en bloc total cystectomy (36 patients) or partial cystectomy (34 patients) because of tumor directly extending into the urinary bladder. Preoperative genitourinary symptoms were present in 33 of the 70 patients (41.7 percent) and were highly predictive of malignant invasion of the bladder (97.0 percent). Duration of catheter drainage after partial cystectomy correlated with early postoperative bladder function; all 25 patients who had the catheter remain in place at least ten days had normal voiding after catheter removal, while five of nine patients whose catheter was removed before ten days had retention requiring catheter reinsertion (p < 0.01). Urologic complications occurred in two patients after total cystectomy and in three patients after partial cystectomy. There were three postoperative deaths in the total cystectomy group but none after partial cystectomy. Sixty-four patients with negative resection margins had a median survival period of 34 months and a five-year actuarial survival rate of 51.8 percent. In contrast, the median survival period for six patients who had positive margins was 11 months, with no survivors at five years.

Adult↗

Sphincter-preserving extended resection for locally advanced rectosigmoid carcinoma involving the urinary bladder.

Radical en bloc resection has gained acceptance in the management of locally advanced colorectal carcinoma. Total pelvic exenteration has been advocated as treatment for rectosigmoid cancers involving adjacent genitourinary structures. We report a series of 10 patients who underwent total cystectomy with en bloc segmental colorectal resection and restoration of intestinal continuity. All margins, including the distal colorectal margin of resection, were pathologically uninvolved by tumor. The median follow-up on these patients was 44 months and the mean survival was 42.5 months. The local recurrence rate (20%) and survival rates are comparable to those in reports describing pelvic exenteration for colorectal cancer. Our patients had normal postoperative bowel function. An extended colorectal resection, including a total cystectomy with rectal sphincter preservation, is occasionally possible when tumor-negative resection margins can be achieved. By restoring intestinal continuity, such an operation provides an improved quality of life, and more importantly, fulfills the criteria for an oncologically sound operation.

Colorectal Neoplasms↗

Gastrointestinal lymphoma. A case for primary surgical resection.

The cases of 42 consecutive patients with primary gastrointestinal lymphoma were reviewed to compare the risks and outcomes of different primary treatment modalities. Among patients with localized disease (stages I and II), 12 underwent complete tumor resection and 6 underwent radiation therapy; 5-year survival was 82% and 50%, respectively. Among patients with disseminated disease (stages III and IV), 6 underwent resection of the primary tumor followed by chemotherapy and 18 were treated with radiation and chemotherapy; 5-year survival was 81% and 6%, respectively. Five patients who did not undergo surgical resection before radiation therapy or chemotherapy developed severe life-threatening complications from their primary tumor. Surgical resection before the administration of other therapy should be performed when the patient is considered to be a surgical candidate and resection of the primary tumor is deemed feasible.

Adolescent↗

Early reexploration for excessive postoperative bleeding lowers wound complication rates in open heart surgery.

Clinical reviews of sternal wound infections following open heart surgery indicate many predisposing factors including diabetes, low cardiac output, use of bilateral internal mammary grafts, and reoperation for excessive postoperative bleeding. This study was undertaken to determine the role of mediastinal re-exploration in the development of sternal wound complications. From a series of 2,271 patients undergoing median sternotomy for open-heart surgery between 1979 and 1984, 71 (3.1%) were re-explored for excessive bleeding. Nine of these patients died in the early postoperative period of noninfectious complications. The remaining patients were divided into two groups. Group 1 (54 patients) were re-explored without subsequent problems. Group 2 (8 patients) developed sternal and costochondral wound complications. Comparison of age, intercurrent and pre-existing disease, total bypass time, crossclamp time, and postoperative hemodynamic status showed no statistical difference. All patients bled an average rate of 247 ml/hr. However, the average time before re-exploration was 7.6 hours in group 1 compared to 13.8 hours in group 2 (P less than 0.001). Sternal wound complications may be minimized by a policy of early re-exploration for excessive postoperative bleeding (greater than 200 ml/hr for 4 hours).

Cardiac Surgical Procedures↗

Management of ductal carcinoma in situ.

The management of ductal carcinoma in situ (DCIS) is one of the most controversial topics in the treatment of breast cancer. With the introduction and utilization of screening mammography, clinically occult or microscopic DCIS has become the most frequent presentation of this disease. Recent advances in the characterization of DCIS according to histologic subgroupings, size and extent of disease, and nuclear grade have provided important information regarding the natural history of this heterogeneous group of lesions. Critical issues such as multicentricity, occult invasion, and potential for local recurrence and axillary metastases have been addressed in recent series. Prospective, single institution trials and data from the National Surgical Adjuvant Breast and Bowel Project (NSABP-B17) protocol have demonstrated that in many patients with mammographically detected DCIS, mastectomy may be over-treatment. Treatment issues for DCIS now focus on the clinical selection process to identify patients best suited for wide local excision alone vs. wide local excision and breast irradiation.

Biopsy↗

Screening for colorectal cancer: developing a preventive healthcare program utilizing nurse endoscopists.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. In 2000, approximately 130,200 new cases of colorectal cancer will be diagnosed, and 56,300 persons will die from the disease (Greenlee, Murray, Boldan, & Wingo, 2000). A survey conducted for the National Colorectal Cancer Roundtable by the Gallup Organization, found that 47% of people over 50 are not being screened. The National Colorectal Cancer Awareness Month, which began in March 2000, will educate Americans age 50 and older and prescribe physicians about the importance of colorectal cancer screening tests. The effect of increased education and directing physicians to include colorectal screening for their patients will create a need for non-physician endoscopists to meet the screening needs of the population. A colorectal cancer screening center was developed at a large Midwestern teaching hospital utilizing nurse endoscopists. The purpose of this article is to provide information for institutions to develop and implement a colorectal cancer screening center utilizing nurse endoscopists.

Aged↗