Venous thromboembolic disease.

Venous thromboembolism (VTE) remains a common and life-threatening complication among patients with cancer. Thromboprophylaxis can be used to prevent the occurrence of VTE in patients with cancer who are considered at high risk for developing this complication. Therefore, it is critical to recognize the various risk factors for VTE in patients with cancer. Risk assessment tools are available to help identify patients for whom discussions regarding the potential benefits and risks of thromboprophylaxis would be appropriate. The NCCN Clinical Practice Guidelines in Oncology for VTE provide recommendations on risk evaluation, diagnosis, prevention, and treatment of VTE in patients with cancer.

A Phase I study of weekly intravenous oxaliplatin in combination with oral daily capecitabine and radiation therapy in the neoadjuvant treatment of rectal adenocarcinoma.

PURPOSE: We conducted a Phase I study to determine the maximum tolerated dose (MTD) of neoadjuvant capecitabine, oxaliplatin, and radiation therapy (RT) in Stage II to III rectal adenocarcinoma. METHODS AND MATERIALS: Capecitabine was given orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given i.v. once weekly x 5 (for 5 weeks) starting the first day of RT. RT was given daily except on weekends and holidays at 1.8 Gy per fraction x 28. Escalation for capecitabine or oxaliplatin was to occur in cohorts of three patients until the maximum tolerated dose (MTD) was defined. Endorectal tumor biopsy samples were obtained before and on Day 3 of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, dihydropyrimidine dehydrogenase, DNA repair, and apoptosis. RESULTS: Twelve patients were enrolled on this study. Two of 6 patients at dose level (DL) 1 (capecitabine 825 mg/m2 orally (p.o.) given twice daily (b.i.d.); oxaliplatin 50 mg/m2/week) had a dose-limiting diarrhea. One of 6 patients at DL (-)1 (capecitabine 725 mg/m2 p.o., b.i.d.; oxaliplatin 50 mg/m2/week) experienced-dose-limiting diarrhea. Three of 11 patients who underwent resection had a complete pathologic response. No remarkable variations in rectal tumor biologic endpoints were noted on Day 3 of treatment in comparison to baseline. However, a higher apotosis index was observed at baseline and on Day 3 in complete pathologic responders (no statistical analysis performed). CONCLUSIONS: Capecitabine 725 mg/m2 p.o., twice daily in combination with oxaliplatin 50 mg/m2/week and RT 50.4 Gy in 28 fractions is the recommended dose for future studies.

Postoperative computed tomography scan surveillance for patients with stage II and III colorectal cancer: worthy of further study?

The use of computed tomography scan (CT) of the abdomen and pelvis for surveillance of colorectal cancer (CRC) after primary curative therapy (PCT) remains controversial. Surveillance guidelines at Roswell Park Cancer Institute have included annual CT for the first 2 years after PCT. Isolated metastases from CRC may be amenable to surgical resection, potentially leading to a survival advantage. To assess this, a retrospective chart review of all 203 patients diagnosed with stage II or III CRC between January 1, 1990, and December 31, 1995, was conducted. First-year surveillance CT (CT-1) was performed for 146 of 203 patients and 81 of 146 patients had second-year surveillance CT (CT-2). CT was considered "directed" when at least 1 of the following prompted evaluation: suspicious symptoms or signs, rising carcinoembryonic antigen, findings from colonoscopies, chest x-rays, or laboratory tests. Otherwise, CT was considered "nondirected." Of 121 of 146 CT-1 and 63 of 81 CT-2 with nondirected CT, 7 of 121(5.8%) and 4 of 63 (6.4%) had proven recurrence, respectively. During 2 years of follow up, the estimated lower bound for detection of recurrence by nondirected CT was 11 of 121(9.1%). There were no apparent differences between the 2 groups in demographics, clinical presentation, surgical margins, treatment, tumor site, grade, or TNM stage. Surgical resectability of the metastases for directed and nondirected groups was 10 of 28 (36%) and 6 of 11 (54%), respectively. The median survival for the patients with recurrence in the directed and nondirected groups was 35 and 50 months, respectively. In conclusion, this retrospective study generates the hypothesis that CT surveillance may be of value. A prospective study, properly sized for power, is needed to answer this question.

Risk factors associated with earlier age of onset in familial pancreatic carcinoma.

BACKGROUND: An estimated 5-10% of all pancreatic adenocarcinomas have a hereditary association. The objective of the current study was to characterize the clinical and pathologic features of familial pancreatic carcinoma and to determine potential differences in demographics, risk factors, and outcomes between familial and sporadic pancreatic carcinoma populations. METHODS: A retrospective review was performed to identify patients diagnosed with pancreatic carcinoma who had an associated familial disposition. Demographic analyses and assessment of clinical features and treatment outcomes were performed for the familial subgroup, and the results were compared with observations made in the nonfamilial, or 'sporadic', population. RESULTS: Thirty of 826 patients (3.6%) had familial pancreatic carcinoma. Baseline demographics, resectability, and metastases were similar in both the familial cohort and the sporadic cohort. The mean age of onset was slightly lower in the familial cohort (57.6 years, compared with 61 years in the sporadic cohort). However, the familial population had a significantly greater proportion of patients who were diagnosed at age <50 years compared with the sporadic population (36.7% vs. 18.3%; P=0.017). A positive smoking history was more commonly associated with familial pancreatic carcinoma (87% vs. 66%; P=0.06). The overall median survival durations were 7 months and 6 months for the familial group and the sporadic group, respectively. CONCLUSIONS: Patients with familial pancreatic carcinoma present at an earlier age compared with their counterparts who have nonfamilial disease. Smoking may play a significant role in the risk or promotion of pancreatic carcinoma in patients with an inherited predisposition.

Effect of concurrent radiation therapy and chemotherapy on pulmonary function in patients with esophageal cancer: dose-volume histogram analysis.

PURPOSE: The pulmonary effects of concurrent radiation therapy and chemotherapy were studied in patients enrolled in a phase I trial for esophageal cancer. MATERIALS AND METHODS: Pulmonary function tests were performed prospectively before and after combined-modality therapy (oxaliplatin, 5-fluorouracil, and radiation therapy) in 20 patients with esophageal cancer. Cumulative and differential lung DVH analysis from 0 to 5400 cGy in 25-cGy intervals was performed for the last 15 patients. Correlation between radiation exposure in various dose ranges and percent reduction in pulmonary function tests was calculated as an exploratory analysis. RESULTS: Significant reductions in carbon monoxide diffusion capacity corrected for hemoglobin (12.3%) and total lung capacity (2.5%) were evident at a median of 15.5 days after radiation therapy. DVH analysis revealed that the single dose of maximum correlation between lung volume radiation exposure and lung function reduction was less than 1000 cGy for all pulmonary functions. The percent lung volume that received a total dose between 700 and 1000 cGy maximally correlated with the percent reductions in total lung capacity and vital capacity, and the absolute lung volume that received a total dose between 700 and 1000 cGy maximally correlated with the percent reductions in total lung capacity, vital capacity, and carbon monoxide diffusion capacity. DISCUSSION: Significant declines in carbon monoxide diffusion capacity and total lung capacity are evident immediately after the administration of conformal radiation therapy, oxaliplatin, and 5-fluorouracil for esophageal cancer. Other lung functions remain statistically unchanged. The percent or absolute lung volume that received a total dose between 700 and 1000 cGy may be significantly correlated with the percent decline of carbon monoxide diffusion capacity, total lung capacity, and vital capacity. These associations will be evaluated further in a follow-up study.

Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas.

BACKGROUND: Neuroendocrine tumors of the pancreas are rare tumors. We identified predictive factors that are associated with long-term survival (> or=5 years). METHODS: Fifty patients with a diagnosis of neuroendocrine tumors of the pancreas were retrospectively evaluated. The following factors were evaluated for disease-specific mortality: age, sex, primary tumor location, functional status, type of primary tumor treatment, presence or absence of liver metastases, timing of liver metastases occurrence, and type of liver metastases treatment. Aggressive treatment of the liver metastases included surgery, chemoembolization, or intrahepatic arterial infusion chemotherapy. RESULTS: Twenty-three patients (47%) had tumor located in the head of the pancreas, and 29 patients (58%) had nonfunctioning tumor. Thirty-nine patients (78%) had liver metastases. The median follow-up for the entire group was 35 months (range,.76-206 months). The median survival for the entire group was 40 months, and the overall 1-, 2-, and 5-year survival rates were 84%, 69%, and 36%, respectively. Factors that had a significant favorable effect on survival included curative resection of the primary tumor, metachronous liver metastases, absence of liver metastases, and aggressive treatment of the liver metastases. CONCLUSIONS: Definitive surgical resection of the primary tumor, absence of liver metastases, metachronous liver metastases, and aggressive treatment of the liver metastases were predictors of long-term survival in patients with neuroendocrine tumors of the pancreas.

High-grade dysplasia within Barrett's esophagus: controversies regarding clinical opinions and approaches.

Barrett's esophagus with high-grade dysplasia is a well-known risk factor for the development of esophageal adenocarcinoma, which has become the predominant form of esophageal cancer in the United States. This review addresses four major fundamental issues that shape our treatment decisions regarding high-grade dysplasia within Barrett's esophagus: (1) the poorly defined natural history of high-grade dysplasia in its progression to adenocarcinoma, (2) the potentially high morbidity and mortality of esophageal resection for high-grade dysplasia, (3) the difficulty in detecting cancer among dysplastic cells during endoscopy, and (4) the controversial role of endoscopic mucosal ablative therapy for high-grade dysplasia. Until there are more accurate surveillance methods, better biochemical or molecular markers in predicting cancerous progression, or more effective minimally invasive methods of treatment, esophagogastrectomy must be considered the standard means of managing patients with Barrett's esophagus and high-grade dysplasia. Regular rigorous systematic surveillance and endoscopic mucosal ablation are alternative treatment options that are available but should be used only under strict conditions. The decision to proceed in a certain direction is quite complex and challenging and ideally requires the feedback of patients who are properly educated about the controversies surrounding this disease.

Esophageal resection for carcinoma in patients older than 70 years.

BACKGROUND: A larger number of older patients are presenting as candidates for esophageal resection. An aggressive surgical approach in this population is controversial. METHODS: Four hundred thirteen patients with esophageal cancer who presented to Roswell Park Cancer Institute from 1991 to 1998 were retrospectively reviewed. Clinical data, perioperative details, and postoperative courses were compared for patients older and younger than 70 years. RESULTS: One hundred forty-seven patients (36%) were older than 70 years. Risk factors, clinical symptoms, histology, and stage at presentation were equivalent for both age groups. A higher percentage of patients <70 years were candidates for curative resection. There were no significant differences between groups for estimated blood loss, intraoperative transfusions, length of stay, overall morbidity, or mortality. Only postoperative myocardial infarction and atrial fibrillation were increased in the older group. Excluding stage IV disease, there was a significant and similar improvement in median survival after resection for patients both <70 years and >70 years. CONCLUSIONS: In conclusion, esophageal cancer in older patients warrants surgical resection because the benefit to the patient is the same as it is for younger patients, without a significant increase in operative morbidity or mortality.