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N J Petrelli

Publications and source records attributed to N J Petrelli.

At least 55 records · Page 3Linked to original sources
PubMed1998

Colonocyte differentiation is associated with increased expression and altered distribution of protein kinase C isozymes.

BACKGROUND & AIMS: Colon cancer cells express reduced levels of protein kinase C (PKC). This study examines the regulation of PKC isozymes in normal colonic epithelium, as a basis for understanding the significance of alterations in this enzyme system in colon carcinogenesis. METHODS: The expression and localization of PKC isozymes in mouse and rat colonocytes at different developmental stages were determined using a combined morphological and biochemical approach. PKC alpha expression was compared in colonic adenocarcinomas and adjacent normal mucosa by immunoblot analysis. RESULTS: Mouse and rat colonocytes express PKC alpha, beta II, delta, epsilon, and zeta. Relatively low levels of these isozymes were detected in proliferating cells of the crypt base, predominantly in the cytosolic compartment. Coincident with colonocyte growth arrest/differentiation, PKC isozyme expression markedly increased in both the cytosolic and, more significantly, in the membrane/cytoskeletal fraction. Colonic tumors express reduced levels of PKC alpha, an isozyme that has been implicated in negative control of intestinal cell growth. CONCLUSIONS: These findings are supportive of a role for certain PKC isozyme(s) in signaling pathways mediating postmitotic events in colonocytes in situ, and suggest that diminished activity of these pathway(s) may contribute to the alterations in growth control/differentiation associated with colonic neoplasia.

Animals↗
PubMed1998

Aspirin use and p53 expression in colorectal cancer.

p53 protein overexpression indicates loss of tumor suppressor activity and is the most common genetic alteration in colorectal neoplasms. Epidemiologic and experimental studies suggest that regular use of aspirin may reduce colorectal cancer risk. We set out to determine whether p53 overexpression of the colorectum was associated with a patient's history of aspirin use. Self-administered questionnaires, including information on aspirin use, were obtained from 163 patients with nonfamilial colorectal cancer and from 326 healthy controls. Nuclear p53 protein overexpression using anti-p53 CM-1 polyclonal antibody was observed in 44.8% (73/163) of patients' tumors. A nonsignificant inverse association was observed between use of aspirin and colorectal cancer. Compared with that for nonusers, the odds ratio (OR) for individuals who took aspirin at least twice weekly was 0.68 (95% confidence interval [95% CI]: 0.39-1.18). The odds ratio for those individuals who used aspirin for less than 5 years was 0.54 (95% CI: 0.24-1.23), and 0.80 (95% CI: 0.42-1.51) for those who used aspirin for 5 years or more, when compared with nonusers. An inverse association of regular aspirin use (two times per week or more) was found both for cases with p53 overexpression (OR: 0.79; 95% CI: 0.39-1.59), and for cases without p53 overexpression (OR: 0.56; 95% CI: 0.25-1.22). There was little evidence of a difference in the effect of aspirin use on cancer risk between cases with and without p53 overexpression, even after adjustment for potential confounders.

Adenocarcinoma↗
PubMed1998

Fundoplication wrap disruption: an experimental study in rats.

Antireflux surgery usually gives long lasting control of gastroesophageal reflux disease, but late failures can occur from fundoplication wrap disruption. Disruption presumably occurs when physiological mechanical stresses cause the sutures to pull out of the fundoplication wrap. We hypothesized that complete fundoplications (fundus sutured to fundus) would withstand disruptive forces better than partial fundoplications (fundus sutured to esophagus). Forty-eight rats underwent fundoplication (24 partial and 24 complete). Fundoplication wraps were disrupted by distending the stomach (bursting pressure technique) and by distracting the wrap in a tensiometer (breaking strength technique). Bursting pressures were similar in the partial (103.7 +/- 13.5 mmHg) and complete (100.5 +/- 13.1 mmHg) fundoplication wraps (P = 0.93, not significant). In both groups, all disruptions occurred by sutures tearing through the stomach wall. Breaking strength was also equivalent for the two types of wrap. Partial wraps disrupted at 6.69 +/- 1.49 N and complete wraps disrupted at 6.52 +/- 1.28 N (P = 0.77, not significant). Sutures tore out of the stomach side of the partial wrap in five rats and out of the esophagus in the other seven rats with partial wraps. Disruption occurred by sutures tearing through the stomach in all rats with complete fundoplications. This experimental study in the rat did not show any difference in the ability of partial and complete fundoplication wraps to withstand disruptive forces.

Animals↗
PubMed1998

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

PURPOSE: Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS: This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS: Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION: The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

Adult↗
PubMed1998

Intraoperative endoscopy in the management of patients with colorectal disease.

Preoperative colonoscopy is recommended in the evaluation of patients with lower gastrointestinal malignancies. The purpose of this study was to investigate the indications and impact on patient management in patients undergoing intraoperative endoscopy. This is a retrospective review of patient charts from February 1972 to July 1994 of 69 intraoperative endoscopic procedures performed in 54 patients during 54 operative sessions. The results of intraoperative endoscopy affected patient management in 29 of the 54 operative sessions (54%). This included 9 cases (17%) in which the planned surgical procedure was altered. There were no complications related to the endoscopies and 99% were completed successfully. Intraoperative endoscopy can provide important information that can alter the surgical management of patients with colorectal disease. This technique should be considered when intraoperative palpation fails to identify synchronous lesions identified on preoperative studies or in cases where the preoperative study is suboptimal.

Adult↗
PubMed1998

Local excision for rectal cancer: an uncertain future.

Adenocarcinoma of the rectum remains a significant public health challenge, with 39,000 new cases and 8,500 deaths predicted for 1998. Radical surgery, the current standard therapy, frequently necessitates the formation of a permanent colostomy and is associated with significant morbidity. For these reasons, alternatives to radical surgery have been sought. This review focuses on sphincter-sparing surgical modalities for distal rectal cancer. An extensive review of the literature on local excision alone, local excision plus postoperative radiation therapy (with or without chemotherapy), and local excision following preoperative chemoradiotherapy is presented. The design and interim results of the sole prospective multi-institution trial of local excision, Cancer and Leukemia Group B trial 8984, are also summarized. The literature on this subject, which is dominated by single-institution, retrospective reports, fails to support local excision as a superior or equal therapy to radical surgical excision for invasive distal rectal adenocarcinoma. The crucial question regarding the efficacy of radical surgical salvage for local recurrence following local excision also remains unanswered. We conclude that the role of local excision for invasive distal rectal adenocarcinoma remains undefined. If there is a future for this therapeutic modality, it will depend significantly on rigorous patient selection, provided that the efficacy of radical surgical salvage for local recurrence can be established.

Adenocarcinoma↗
PubMed1998

Colovaginal anastomosis: a unique complication of end-to-end anastomosis stapler use in low anterior resection.

Anastomotic staplers have been used in colorectal surgery for several years. End-to-end stapler use for low anterior resection, as well as for other procedures, is common in surgical practice. These staplers have allowed more extended, lower resections of the colorectum without loss of bowel continuity or sphincter function. There have been reported complications of stapler use, with anastomotic stricture and leakage being the most common. We report here a unique complication of direct colovaginal anastomosis using the end-to-end stapler during a low anterior resection of an early-stage rectal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Life-long screening of patients with intermediate-thickness cutaneous melanoma for asymptomatic pulmonary recurrences: a cost-effectiveness analysis.

BACKGROUND: Costs and potential benefits of an intensive chest X-ray (CXR) screening program to detect asymptomatic pulmonary metastases in patients with intermediate-thickness, local, cutaneous melanoma were assessed. METHODS: Cost-effectiveness analysis from a societal perspective was performed using data on recurrence detection from an historic cohort at Roswell Park Cancer Institute and other published studies, estimates of new cases of melanoma in 1996 from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, and estimates of cost and treatment benefits from published articles retrieved through MEDLINE. Net costs were calculated as the added cost of CXR screening to regular follow-up and the costs incurred in the surgical treatment of lung recurrences. Net benefits were calculated as potential savings in nonquality-adjusted life years (NQALY) and quality-adjusted life years (QALY) resulting from surgical treatment. Cost-effectiveness ratios were calculated as the present value of net costs divided by net benefits, with benefits presented in discounted and undiscounted forms. RESULTS: For the base case, cost of screening per NQALY was $150,000 and was $165,000 for QALY in 1996 dollars using undiscounted health benefits. Screening accounted for approximately 80% of program costs and treatment accounted for 20%. Annual cost-effectiveness ratios were lowest in Years 3-10 of screening. The total cost of a 20-year screening program for patients diagnosed in 1996 was estimated to be between $27-$32 million. CONCLUSIONS: Even in the absence of certain benefits, the model demonstrates that significant cost savings may be possible by decreasing screening frequency in the first 2 years and limiting screening to the first 5-10 years after diagnosis.

Aged↗
PubMed1997

Genomic DNA-based hMSH2 and hMLH1 mutation screening in 32 Eastern United States hereditary nonpolyposis colorectal cancer pedigrees.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early age of onset colorectal cancer (mean 45 years) as well as endometrial, urinary tract, and upper gastrointestinal adenocarcinomas. The HNPCC phenotype has been shown to segregate with germline mutations in the human homologues of the DNA mismatch repair genes MSH2, MLH1, PMS1, and PMS2. However, the majority of published DNA mismatch repair gene mutation surveys associated with HNPCC kindreds report multiple levels of preselection, including 2p and 3p chromosomal linkage analysis and the evaluation of microsatellite instability of proband colorectal cancers prior to mutation analysis. For this reason, the concise contribution of each of the known DNA mismatch repair genes to the HNPCC phenotype remains unknown. We report the results of a genomic DNA-based analysis of hMSH2 and hMLH1 germline mutations in 32 unrelated Eastern United States HNPCC kindreds. These families were selected for study on the basis of phenotype only. We identified three hMSH2 and six hMLH1 mutations in eight families, for a positive mutation rate of 25%. Two mutations were identified in one of the families. Four of the mutations detected have not been reported in the literature previously. One of the mutation-positive families is African American; the others were of European-American ancestry. These results provide a clarification of the contribution of hMSH2 and hMLH1 to the HNPCC phenotype and suggest that in the majority of Eastern United States HNPCC kindreds selected by phenotype alone, the molecular genetic basis for the disease remains unknown.

Adult↗
PubMed1997

Advanced cutaneous squamous cell carcinoma of the trunk and extremity: analysis of prognostic factors.

BACKGROUND: Patients with squamous cell carcinoma (SCC) of the skin may exhibit locally advanced or metastatic disease and present a challenging management problem. METHODS: A retrospective review of 40 patients with advanced SCC of the trunk or extremity managed at Roswell Park Cancer Institute from 1982 through 1992 was performed to identify clinical and pathologic factors that influenced outcome. RESULTS: There were 27 males and 13 females with a median age of 61 years. Median follow-up was 24 months. Surgical resection to control the primary tumor was often extensive. Amputation was required in nine patients, hemipelvectomy in three patients, and hemicorporectomy in one patient. Median survival was 28 months, and 5-year survival was 43%. Univariate analysis identified stage (P = 0.04), size (P = 0.0001), type of surgical procedure (P = 0.009), and margins of resection (P = 0.005) as having prognostic significance. On multivariate analysis, stage (P = 0.04) and size (P = 0.02) were found to be significant. CONCLUSIONS: Optimum treatment for advanced SCC of the trunk and extremity involves surgical resection with uninvolved margins. The role of elective node dissection remains undefined. Investigation is needed to define the role of neoadjuvant therapy that may improve functional and cosmetic results.

Adult↗
PubMed1997

Complications of absorbable pelvic mesh slings following surgery for rectal carcinoma.

PURPOSE: To evaluate the intraoperative, postoperative, and long-term complications of an absorbable pelvic mesh sling after surgery for rectal carcinoma. METHODS: A retrospective review of medical records from April 8, 1991, through April 8, 1996. RESULTS: Twenty patients with a mean age of 57 (range, 37-79) years underwent pelvic mesh sling placement. The tumor stages were as follows: Stage I, 5; Stage II, 2; Stage III, 11; and Stage IV, 1. A recurrent perianal basal cell carcinoma was not included in the staging group. Surgery consisted of 18 abdominoperineal resections, 1 total proctocolectomy, and one Hartmann's procedure. Mean follow-up was 18 (range, 2-49) months. There were no intraoperative complications related to mesh placement. Twenty-nine complications occurred in 14 patients during the immediate postoperative period. Five were possibly mesh-related and included a pelvic abscess, perineal seroma, toxic perineal wound, pulmonary embolus, and lower extremity deep venous thrombosis, respectively. A mild postoperative ileus developed in 17 patients (85 percent), and a diet was initiated at a mean of seven (range, 4-24) days. Fourteen patients received postoperative radiotherapy with a mean dose of 5,339 (range, 2,500-7,020) cGy delivered in 180-cGy fractions. There were 14 immediate complications caused by radiotherapy in 11 patients, but only two patients required delays in treatment. Two patients had diarrhea alone, six developed perineal dermatitis alone, and three patients had both diarrhea and perineal dermatitis. All patients with diarrhea had received chemoradiation. One patient developed a partial small-bowel obstruction following radiation. CONCLUSIONS: Absorbable pelvic mesh sling placement can be performed with minimum morbidity and is recommended following surgery for rectal cancer when radiation is anticipated as part of multimodality therapy.

Adenocarcinoma↗
PubMed1997

Anal canal and perianal epidermoid cancers.

Squamous cell carcinoma of the anal canal serves as a paradigm for the successful application of multimodality treatment of solid tumors. Since 1974, multimodality treatment with combined radiation and chemotherapy has become the standard. The compelling advantage of sphincter preservation and the substantial survival benefit compared with surgery alone prompted investigators to adopt chemoradiation treatment. Several questions regarding the optimal radiation dose and chemotherapy in initial as well as salvage therapy remain, and only recently have results of several prospective randomized studies become available to address some of these unresolved issues. We reviewed the clinical aspects and historical treatment results of anal canal and perianal epidermoid cancers in light of the results of these modern trials. Current management strategies are redefined, and future directions of clinical studies are outlined.

Anus Neoplasms↗
PubMed1997

Basic science research in postgraduate surgical training: difficulties encountered by clinical scientists.

BACKGROUND: Clinical training of physicians and surgeons involves teaching students and residents both the science and the art of medicine. The science of medicine involves clinical skills honed through reading textbooks and journals and experience in diagnosing and treating myriad diseases. The art of medicine involves the important communication skills necessary for a good doctor-patient relationship. A third aspect of training, basic science research, is frequently de-emphasized or omitted entirely. In general, training programs frequently do not allow protected time in a laboratory setting for the resident. The few weeks to months that some programs allow is insufficient to establish a thorough understanding of scientific method. METHODS, RESULTS: The article describes the introduction of one of the authors from a clinically oriented training background into the laboratory and outlines the pitfalls frequently encountered when a clinician embarks on basic science research training. CONCLUSION: The necessity for sufficient protected time in the laboratory away from clinical responsibilities is recognized.

Clinical Competence↗
PubMed1997

Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer.

Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over-expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer.

Aged↗
PubMed1997

Use of carcinoembryonic antigen radioimmunodetection and computed tomography for predicting the resectability of recurrent colorectal cancer.

OBJECTIVE: The objective was to determine the role of arcitumomab (CEA-Scan; Immunomedics, Morris Plains, NJ), an anticarcinoembryonic antigen (CEA) Fab' labeled with technetium-99m, in the presurgical evaluation of patients with recurrent or metastatic colorectal carcinoma. SUMMARY BACKGROUND DATA: Surgical resection is the only method known to cure recurrent or metastatic colorectal carcinoma. The location and extent of disease must be determined before surgery. The role of antibody imaging, a new cancer detection modality, in preoperative evaluation for resection of locally recurrent or metastatic colorectal cancer has not been established, either alone or in combination with standard diagnostic modalities. METHODS: In a blinded analysis of 209 patients with known or suspected colorectal cancer, the accuracy of arcitumomab, alone and combined with computed tomography (CT), was compared to that of CT for predicting abdominopelvic tumor resectability by correlating the results with surgical and histopathologic findings. RESULTS: Arcitumomab alone or combined with CT was found to be significantly more accurate for predicting surgical outcome than CT alone. When the results of CT and arcitumomab were concordant for abdominopelvic resectability, nonresectability, or absence of disease, the prediction was accurate in 67%, 100%, and 64%, respectively. Thus, the concordance for nonresectability (100% correct) may obviate the need for other diagnostic modalities or exploratory surgery. When the two tests were discordant, arcitumomab was correct substantially more often than CT. Because the liver is the most common site of distant metastasis in colorectal cancer, a subset of patients with hepatic disease was also analyzed; findings were similar to the overall resectability results. The product's safety profile was excellent: the incidence of induction of an immune response against arcitumomab was <1% and that of potentially adverse events was 1.2%. CONCLUSIONS: The accuracy of arcitumomab for assessing resectability status is greater than that of CT, both in all patients undergoing evaluation for curative abdominopelvic resection of colorectal cancer and in the subset of patients with suspected or proven liver metastases. The additional use of arcitumomab with CT potentially doubles the number of patients who could be saved the cost, morbidity, and mortality of unnecessary abdominopelvic surgery and increases those who are potentially resectable for cure by 40%.

Adult↗
PubMed1997

Genomic instability in sporadic colorectal cancer quantitated by inter-simple sequence repeat PCR analysis.

Genomic instability plays a major role in cancer by facilitating tumor progression and tumor heterogeneity. Inter-simple sequence repeat (inter-SSR) PCR has been developed to provide a rapid and reproducible technique for quantitation of the major type of genomic instability observed in sporadic tumors, namely, that manifesting itself as amplifications, deletions, translocations, and insertions. Evaluation of 59 sporadic colorectal cancers by inter-SSR PCR has demonstrated a wide range of instability, independent of tumor stage at diagnosis. Comparison of these data and the results of microsatellite PCR analysis reveals an association of high genomic instability with loss of heterozygosity but no association with the replication error phenomenon arising from defects in mismatch repair.

Adult↗