Desmoid tumors.
Explore the source record for details and available documents.
Diagnosis, Differential↗
Biomedical subjects
N J Petrelli
Publications and source records attributed to N J Petrelli.
Familial and nutritional risk factors for p53 overexpression in colorectal cancer.
Although familial and dietary factors are recognized as important risk determinants for colorectal tumorigenesis, the specific causes of colorectal cancer remain unclear. Studies of p53 genetic alterations have provided clues concerning the etiology of many cancers. This study was designed to determine whether overexpression of the p53 protein is associated with familial and dietary risk factors. Epidemiological data were obtained from 163 colorectal cancer cases and 326 healthy controls. Tumors of all patients were analyzed immunohistochemically for p53 overexpression using an avidin-biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM1. Of patient tumors, 44.8% showed p53 nuclear reactivity. Colorectal cases versus controls were three times more likely to report a family history of colorectal cancer [odds ratio (OR), 3.12; 95% confidence interval (CI), 1.77-5.52]. Only cruciferous vegetables exhibited a significant inverse association (OR, 0.59; 95% CI, 0.34-1.02; trend test, P = 0.03) for the highest versus lowest quartiles. Both meat and beef displayed an elevated increase in risk. When cases with p53 overexpression (p53 positive) were compared with cases without p53 overexpression (p53 negative), etiological heterogeneity was suggested for family history of colorectal cancer (OR, 0.39; 95% CI, 0.16-0.93), cruciferous vegetables (trend test, P = 0.12), and beef consumption (trend test, P = 0.08). To estimate the individual relative risks for p53-dependent and p53-independent pathways, each p53 subtype was compared with controls. Cruciferous vegetables exhibited a significant association (OR, 0.37; 95% CI, 0.17-0.82; trend test, P = 0.03) when p53 positive cases were compared with controls. When p53 negative cases were compared with controls, a significant increase in risk was observed for family history of cancer (OR, 4.46; 95% CI, 2.36-8.43) and beef (OR, 3.17; 95% CI, 1.83-11.28; trend test, P = 0.006). The p53 (positive) dependent pathway was characterized by an inverse association with cruciferous vegetables, and p53-independent tumors were characterized by family history and beef consumption. These data may indicate the significance of linking epidemiology and molecular biology in assessing specific etiological pathways.
Adenocarcinoma↗
The management of infectious and noninfectious anorectal complications in patients with leukemia.
BACKGROUND: Infectious and noninfectious anorectal complications may occur in patients undergoing therapy for leukemia. Controversy surrounds the treatment of this problem in immunocompromised patients. STUDY DESIGN: A retrospective review of the medical records of 83 patients with acute or chronic leukemia in whom anorectal disease developed during inpatient therapy for leukemia was performed to determine the initial signs and symptoms, treatment, and outcomes. RESULTS: During a 12-year period, 92 patients with anorectal complications were treated. This series included 25 patients with perirectal abscesses, 22 patients with anal fissures, 18 patients with symptomatic external hemorrhoids, 12 patients with perianal ulcerations, 12 patients with symptomatic internal hemorrhoids, and three patients with fistulas in ano. Overall, 79 (86 percent) of the 92 anorectal complications resolved in 68 of the 83 patients. Increasing periods of neutropenia did not adversely affect the resolution of anorectal disease. Thirteen patients (16 percent) required surgical intervention, most commonly secondary to a perirectal abscess. Incision and drainage was necessary in ten (40 percent) of 25 patients with perirectal abscess, which included five patients with fluctuation and five patients in whom infection failed to respond to medical therapy. CONCLUSIONS: Noninfectious anorectal complications in patients with leukemia respond to nonoperative intervention and rarely progress to a life-threatening infection. Nonoperative intervention in the form of systemic antibiotics and sitz baths is successful in the treatment of infectious anorectal complications. Incision and drainage should be performed when fluctuation is present and in patients whose complications fail to respond to medical therapy.
Abscess↗
An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer.
Fischer rat embryo fibroblasts subjected to temporary anoxia followed by an aerobic recovery period show genomic instability in the form of highly elevated CAD gene amplification rates. As revealed by flow cytometric analysis this is associated with DNA breakage in vivo, followed by repair during the recovery period. Such genomic instability parallels expression of a M(r) 29,000/31,000 endonuclease; this enzyme requires no added divalent metal ion and has a pH optimum of about 6.5. The same endonuclease was found to be expressed within healing wounds and in four of ten human colorectal cancers but was not seen in eight normal colorectal tissue samples. Our results indicate that DNA breakage resulting from endogenous endonuclease activity can have a substantial effect in modulating genomic instability.
Animals↗
Seizures associated with leucovorin administration in cancer patients.
Explore the source record for details and available documents.
Adult↗
Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial.
BACKGROUND: Cancer is most common in older age groups, but little information is available with regard to the impact of age on chemotherapy toxicity. This study was undertaken to determine if age is an independent risk factor for 5-fluorouracil (5-FU) toxicity. METHODS: Toxicity data from a prospective, randomized, multiinstitution trial of 5-FU-based treatment for advanced colorectal cancer were analyzed. Toxicity for each organ system was graded. Individual organ toxicity proportions were compared using chi-square analysis. A logistic regression was performed using age (younger than 70 years vs. 70 years or older), sex, treatment arm, performance status, and length of therapy as model parameters to predict severe toxicity. Toxicity in 331 patients was analyzed. RESULTS: Advanced age was significantly associated with the occurrence of any severe toxicity (58 vs. 36%, P < 0.001), leukopenia (24 vs. 10%, P < 0.005), diarrhea (24 vs. 14%, P = 0.01), vomiting (15 vs. 5%, P = 0.01), severe toxicity in more than 2 organ systems (10 vs. 3%, P = 0.02), and treatment mortality (9 vs. 2%, P = 0.01). By univariate analysis, age (P < 0.001) and sex (P < 0.0001) were independent predictors of severe toxicity. Twenty-two of 27 women age 70 years or older had severe toxicity. CONCLUSIONS: Age 70 years or older and sex are risk factors for severe toxicity from 5-FU-based chemotherapy. Advanced age does not contraindicate the use of this type of chemotherapy, but close monitoring for multiple organ toxicities and vigorous supportive care of those with toxicity are required. Dosing decisions in older patients are difficult and must integrate assessments of organ function, comorbidities, overall physical status, and goals of treatment, in an effort to ensure the best possible outcome for these patients.
Age Factors↗
A phase II and pharmacokinetic study of 6S-leucovorin plus 5-fluorouracil in patient with colorectal carcinoma.
Leucovorin (LV) is commonly used as a modulator of 5-fluorouracil (5-FU) cytotoxicity. In patient with colon cancer, the addition of LV to 5-FU improves response rates, and in some trials has improved survival in advanced disease and in the adjuvant setting. Leucovorin is generally administered as a racemic mixture, but the isomers differ substantially in pharmacokinetics and biological activity, with 6S-LV the predominant active component. The current study was undertaken to determine the effect of 6R on the pharmacokinetics of 6S-LV, and to characterize the toxicity and antitumor effect of 5-FU when administered with 6S-LV to patients with advanced colorectal carcinoma. Thirty patients were treated with weekly 5-FU plus high dose 6S-LV. To determine the effects of 6R-LV on the pharmacokinetics of S6-LV, 20 patients were randomly assigned to receive either 250 mg/m2 6S-LV or 500 mg/m2 6R,S-LV as a 2 hour IV infusion on day -2, and the other preparation on day -1, with pharmacokinetics measured each day. The presence of 6R-LV had no effect on the AUC, Clp, Cmax, or terminal phase t1/2 of 6S-LV. The overall response rate was 40% (C.I. 23-60%). The most frequent toxicities were gastrointestinal. In this small cohort, scheduled and delivered dose intensity was positively associated with response (p = 0.05). These results show that there is no pharmacokinetic advantage to the use of 6S-LV rather than 6R,S-LV as a modulator of 5-FU.
Adult↗
Patterns of colorectal liver metastases according to Couinaud's segments.
PURPOSE: It is commonly believed that the right lobe of the liver is the most frequent site of colorectal liver metastases. However, direct evidence for this is lacking in the literature. This study was designed to document and evaluate the pattern of liver metastases according to liver segments. METHODS: A retrospective medical records review of 270 patients with hepatic metastases from colorectal adenocarcinoma was performed to determine the pattern of metastases according to Couinaud's segments. There was operative confirmation of liver metastases in 202 patients (75 percent). A total of 1,166 segments were involved with liver metastases and were used in this analysis. Segment I was excluded from calculations because of its dual blood supply. When groups contained different numbers of Couinaud's segments an appropriate correction was made in the statistical comparison. RESULTS: There were 736 (63 percent) right lobe segments (V, VI, VII, VIII) and 430 (37 percent) left lobe segments (II, III, IV) involved with metastases (P < 0.001). Of 430 left lobe segments, 298 (69 percent) involved the left lateral segment (II, III) and 132 (31 percent) involved the medial segment (IV) of the left lobe (P = 0.25). When evaluating patients with 4 or less segments involved, there were 258 right lobe segments (75 percent) and 88 left lobe segments (25 percent) involved with metastases (P < 0.0001). Of 88 left lobe segments with 4 or less segments involved, there were 68 segments (77 percent) involving the left lateral segment and 20 segments (23 percent) involving the medial segment of the left lobe (P = 0.035). All of these relationships were statistically independent of the primary tumor site. CONCLUSIONS: We have documented an overall predominance of right hepatic lobe metastases independent of site of the primary colorectal carcinoma. However, when metastases occurred in the left lobe, the left lateral segment (II, III) was more commonly affected than the medial segment (IV), but this difference was statistically significant only when there were four or less segments involved with liver metastases.
Adenocarcinoma↗
Intraoperative photodynamic therapy as an adjunct to surgery for recurrent rectal cancer.
BACKGROUND: Locally recurrent rectal cancer is a difficult management problem for the surgical oncologist. Current therapies including radical surgery, radiation and chemotherapy have had little success in producing curative results for these patients. This study incorporated intraoperative photodynamic therapy (PDT) as an adjunct to radical surgery for the treatment of locally recurrent rectal cancer. METHODS: Twenty-two patients were enrolled in a prospective feasibility study and injected with Photofrin (Quadra Logic Technologies, Vancouver, British Columbia, Canada) before surgery. Eight patients were found to be candidates and received PDT after surgical exploration and resection. Seven patients had rectal adenocarcinoma and one had squamous cell carcinoma of the anal canal. RESULTS: Based on the indication for PDT, three patient groups were evaluated: group A, resection of all gross disease with negative pathologic margins in four patients; group B, resection of gross disease with positive pathologic margins in two; and group C, residual bulky tumor in two patients. There was one perioperative death (12.5%), not related to PDT, and one major morbidity due to PDT (12.5%). Local recurrence occurred in six patients (two in group A, two in group B, two in group C). Mean overall survival was 15.4 months for group A, 6.5 months for group B, and 24.5 months for group C. CONCLUSIONS: The results of this study suggest that intraoperative PDT may be administered safely in patients undergoing resection of recurrent rectal cancer. However, its use in the present state of technology appears to be inadequate for control of disease, particularly if bulky tumor or residual microscopic disease is left behind.
Adenocarcinoma↗
Colorectal cancer: prevention and early detection are the issues, not postoperative surveillance.
Explore the source record for details and available documents.
Colonic Neoplasms↗
Prognosis and recurrence patterns of anal adenocarcinoma.
BACKGROUND: Anal adenocarcinomas are rare cancers, constituting fewer than 10% of all anal cancers. This is a retrospective review of 10 patients with anal adenocarcinoma. PATIENTS AND METHODS: Seven men and 3 women with a median age of 59 years (range 38 to 82) participated in the study. Using the 1976 World Health Organization classification, 4 patients had the rectal type of cancer, 2 had the anal duct type, and 1 had the anorectal fistula type. The 3 remaining patients had unclassifiable tumors with solely extramucosal disease. Seven patients underwent abdominoperineal resection, 1 had a radical vulvectomy and proctectomy, and 2 had local excision. RESULTS: The median survival was 29 months (range 5 to 249). Seven patients developed a recurrence at the following sites: 2 perineal, 5 inguinal, and 5 distant metastases. Five patients died from their disease a median of 28 months after surgery, and 2 patients died of unrelated causes. Three patients are alive at a median of 54 months; 2 of these patients are free of disease and 1 has a perineal recurrence. CONCLUSION: Anal adenocarcinomas were found to be a rare, heterogeneous group of tumors with a poor prognosis despite radical surgery.
Adenocarcinoma↗
The clinical and genetic manifestations of hereditary nonpolyposis colorectal carcinoma.
BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome that affects a significant percentage of the total cancer population but is not easily recognized because of a lack of a distinctive clinical marker such as multiple polyps. DATA SOURCES: The present review discusses the clinical characteristics, pathology, genetics, management, and surveillance of HNPCC. The diagnosis of HNPCC is dependent upon family history. It is defined by the Amsterdam criteria consisting of: (1) 3 or more relatives with histologically verified colorectal carcinoma, 1 of whom is a first-degree relative of the other 2; (2) colorectal carcinoma involving at least two generations; and (3) one or more colorectal carcinoma cases diagnosed at less than 50 years of age. CONCLUSIONS: The diagnosis of HNPCC requires the demonstration of vertical transmission of the syndrome in the family pedigree. Attention should be focused on reports of cancer of all anatomic sites and the determination of site, histology, and age at diagnosis.
Aged↗
Intraoperative small bowel enteroscopy in familial adenomatous and familial juvenile polyposis.
BACKGROUND: In familial adenomatous polyposis and juvenile polyposis, polyps can occur throughout the gastrointestinal tract. METHODS: We report seven patients with familial adenomatous polyposis and two patients with juvenile polyposis who underwent small bowel enteroscopy at the time of exploratory celiotomy either for colectomy or other pathology. RESULTS: Polyps in the jejunum and/or ileum were noted in five of nine (56%) patients at enteroscopy. In three of nine (33%) patients these polys were adenomatous. Two of these patients had polyps in the jejunum and in the ileum, whereas one patient had jejunal adenomas alone. These polyps were from 3 mm to 30 mm in size. The remaining two patients with polyps had lymphoid hyperplasia in the ileum. All three patients who had adenomas at intraoperative small bowel enteroscopy had duodenal adenomas at esophagogastroduodenoscopy. At the age of 14 years, one patient had an intramucosal carcinoma in a small bowel juvenile polyp. CONCLUSION: Baseline small bowel enteroscopy should be considered at the time of surgical exploration in patients with asymptomatic familial adenomatous polyposis and juvenile polyposis. In patients with duodenal polyps, enteroscopy should be performed at the time of surgery. Biopsy and/or excision of larger polyps should be performed because these polyps may harbor a carcinoma.
Adenomatous Polyposis Coli↗
Detection of pelvic recurrence of colorectal carcinoma: prospective, blinded comparison of Tc-99m-IMMU-4 monoclonal antibody scanning and CT.
PURPOSE: To prospectively compare the accuracy of imaging with technetium-99m-labeled Fab' fragment of the anti-carcinoembryonic antigen antibody (CEA) IMMU-4 with that of computed tomography (CT) for the detection of pelvic recurrence of colorectal carcinoma. MATERIALS AND METHODS: In 61 patients, blinded interpretations of both modalities were correlated with surgical-pathologic (n = 23) or clinical and CT follow-up findings (n = 38). RESULTS: Sensitivity and specificity with antibody scanning alone and combined with CT (79% and 84% vs 83% and 81%, respectively) were not significantly different from those values for CT alone (66% and 97%, respectively). Sensitivity of antibody scanning was greater for recurrences larger than 2 cm (94% vs 55% [P = .02]), serum CEA more than 2.5 ng/mL (91% vs 40% [P = .03]), and combined planar and single photon emission CT antibody scanning compared with planar alone (79% vs 48% [P = .03]), without a significant decrease in specificity. CONCLUSION: Antibody scanning does not improve on findings at CT alone for recurrent colorectal carcinoma but can help differentiate recurrent tumor from fibrosis.
Adult↗
It is time to stratify with prognostic factors for hepatic metastases.
Explore the source record for details and available documents.
Adenocarcinoma↗
Metastatic colorectal cancer: advances in biochemical modulation and new drug development.
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
Desmoid tumors in patients with familial adenomatous polyposis.
BACKGROUND: Sporadic desmoid tumors occur mainly in the abdominal wall and in extraabdominal sites. Desmoid tumors in patients with familial adenomatous polyposis (FAP) usually occur in the abdominal wall and in the bowel mesentery. Surgical resection of desmoids in patients with FAP has been controversial. METHODS: A retrospective review of patients with FAP and desmoid tumors treated from 1950 to 1991 was performed. Patients were evaluated for gender, age, site of desmoid tumors, treatment, recurrence, and survival. RESULTS: Twenty-one of 24 patients underwent 60 surgical procedures related to the desmoid tumors. Seven of nine patients who underwent potentially curative surgery had recurrences; three were reresected. Major morbidity after palliative or curative surgery was 47%. Five patients were alive with no evidence of disease at a median of 198 months, 10 patients were alive with disease at a median of 102 months, and 5 patients died with disease at a median of 31 months after diagnosis. CONCLUSIONS: Desmoid tumors are common in patients with FAP. Unresectability and recurrence are more common than cure. Palliative and curative resections have a high morbidity. Surgery should be reserved for those patients with symptomatic mesenteric desmoids.
Abdominal Neoplasms↗
Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.
A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.
Adult↗