Deborah L. Driscoll

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.

Rectal cancer risk in hereditary nonpolyposis colorectal cancer after abdominal colectomy

OBJECTIVE The authors analyzed the incidence of rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC) after an abdominal colectomy. SUMMARY BACKGROUND DATA The treatment of choice for a newly diagnosed patient with HNPCC with colon cancer is an abdominal colectomy. The incidence of rectal cancer after abdominal colectomy in HNPCC is not known. MATERIALS AND METHODS A questionnaire was mailed to all International Collaborative Group on HNPCC members to identify patients in whom rectal cancer developed after total, subtotal or completion colectomy. Statistics were performed using the log-rank test, Kaplan-Meier method, and Coxs proportional hazards model. RESULTS Rectal cancer developed in 8 (11%) of 71 patients a median of 158 months (range, 38-282 months) from their primary procedure. Of these eight patients, adenomas in the rectal mucosa developed in five at risk either before (4) or synchronous (1) with the diagnosis of rectal cancer. At the time of diagnosis of rectal cancer, six of eight patients were being observed. Age at first procedure and whether the patient was under surveillance were the only significant variables (p < 0.05) in the multivariate analysis in terms of rectal cancer risk. The risk of developing rectal cancer was estimated to be 3% every 3 years after abdominal colectomy for the first 12 years. CONCLUSIONS The risk of rectal cancer in patients with HNPCC after an abdominal colectomy is approximately 12% at 12 years. Age at first surgical procedure and surveillance correlated with rectal cancer risk. Aggressive endoscopic surveillance of the rectum should be performed after abdominal colectomy.

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

BackgroundNeuroendocrine tumors of the pancreas are rare tumors. We identified predictive factors that are associated with long-term survival (≥5 years).MethodsFifty 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.ResultsTwenty-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.ConclusionsDefinitive 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.

Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up

BACKGROUND Conventional therapy for pleural mesothelioma has met with disappointing results. METHODS From 1991 to 1996, 40 patients with malignant pleural mesothelioma were treated with surgical resection followed by immediate intracavitary photodynamic therapy. RESULTS The series included 9 women and 31 men with a mean age of 60 years. Morbidity and treatment-related mortality rates for the entire series, pleurectomy, and extrapleural pneumonectomy were 45% and 7.5%, 39% and 3.6%, and 71% and 28.6%, respectively. Median survival and the estimated 2-year survival rate for the entire series, stages I and II patients (n = 13), and stages III and IV patients (n = 24) were 15 months and 23%, 36 months and 61%, and 10 months and 0%, respectively. Multivariate analysis identified stage, length of hospital stay, photodynamic therapy dose, and nodal status as independent prognostic indicators for survival. CONCLUSIONS Surgical intervention and photodynamic therapy offer good survival results in patients with stage I or II pleural mesothelioma. For patients in stage III or IV, better treatment modalities need to be developed. Improvements in early detection and preoperative staging are necessary for proper patient selection for treatment.

Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma

Activation of the epidermal growth factor receptor (EGFR) has a role in oncogenesis and may correlate with prognosis. The aim of this study was to examine EGFR expression in esophageal adenocarcinoma and correlate EGFR status with pathologic and clinical prognostic features. An exploratory retrospective review of 38 patients with surgically resected esophageal adenocarcinoma was performed. All patients underwent an esophagogastrectomy with regional lymphadenectomy; 24 patients underwent primary resection and 14 patients had surgery after preoperative chemoradiation therapy. Immunohistochemical analysis was performed on paraffin-embedded tissue samples using an EGFR monoclonal antibody. Low- and moderate-grade tumors were positive for EGFR expression in 2 of 15 patients; poorly differentiated tumors were positive for EGFR expression in 13 of 23 patients (p = 0.02). The median survival was 35 months (confidence interval [CI]: 29–40) for EGFR negative patients (n = 23) and 16 months (CI: 10–22) for EGFR positive patients (n = 13) (p = 0.10). Disease recurred in 3 of 21 EGFR negative patients and 6 of 13 EGFR positive patients (p = 0.06). Poorly differentiated adenocarcinomas of the esophagus demonstrated higher EGFR expression compared to low-grade tumors based upon immunohistochemical analysis. A trend toward improved disease-free and overall survival was seen in EGFR negative patients.

Downregulated gelsolin expression in hyperplastic and neoplastic lesions of the prostate.

Because of its role in cell motility and growth regulation, gelsolin, an actin‐binding protein, has been considered a tumor suppressor and a potential prognostic marker in some neoplasias, such as breast and bladder cancer. Little is known about its immunoexpression in prostatic adenocarcinoma (PCA).

SEVERE RADIATION MORBIDITY IN CARCINOMA OF THE CERVIX: IMPACT OF PRETHERAPY SURGICAL STAGING AND PREVIOUS SURGERY

PURPOSE The purpose of this study is to delineate the factors which (a) contribute to an increase in the severe, radiation induced complication rate and (b) have a significant effect on survival in patients with International Federation of Gynecologists and Obstetricians (FIGO) Stage I-IVA cervical cancer undergoing pretherapy surgical staging. METHODS AND MATERIALS From 1971-1991, 189 patients underwent pretherapy surgical staging via a retroperitoneal approach (67) or transperitoneal approach (122). Seventy-nine patients had previously experienced a laparotomy. Patients subsequently received a median of 85 Gy to point A. In patients receiving paraaortic radiation, a median of 45 Gy was administered. One hundred and thirty-two (69.8%) patients received hydroxyurea as a radiation sensitizer. RESULTS Pretherapy surgical evaluation revealed that 21 of 89 (23.6%) Stage II patients and 32 of 85 (37.6%) Stage III patients had paraaortic lymph node metastases. Multivariate logistic regression analysis detailed the significant factors favorably influencing the radiation-induced complication rate to be a retroperitoneal approach of pretherapy surgical staging and no previous laparotomy. Survival was significantly prolonged in patients receiving hydroxyurea, evaluated via a retroperitoneal incision, with negative paraaortic lymph nodes, and with an early stage of disease. CONCLUSION A retroperitoneal approach to pretherapy surgical staging and absence of previous surgery reduced the incidence of subsequent radiation-induced complications. Despite improvements in the detection of occult disease, prolonged survival is impaired when the therapeutic measures currently available are used.

Complications and outcome of external hemipelvectomy in the management of pelvic tumors.

AbstractBackground: Although the technique of external hemipelvectomy has been adequately described, little is known about its complications and late results. Design: Retrospective review of 68 external hemipelvectomies performed at our Institute between 1973 and 1994. Materials and methods: Eleven patients had bone tumor; 39 patients, soft-tissue sarcoma; seven patients, melanoma; 10 patients, squamous cell carcinoma; and one patient, giant neurofibroma. In 48 (71%) patients, the intent was curative. In 17 cases, the hemipelvectomy was extended. Results: Postoperative complications occurred in 36 (53%) patients, including flap necrosis in 11 (16%), wound infection in 24 (35%), and other complications in 12 (18%). Four (6%) patients died postoperatively. The average hospital stay after curative versus palliative resection was 39 versus 24 days. Only three (5%) patients were able to use a prosthesis, whereas 55 (81%) used crutches, six (9%) remained wheelchair bound, and four patients (6%) spent most of the time in bed. Local recurrence occurred in 35% of the patients. The estimated 5-year survival for curatively resected patients was 21%. Conclusions: External hemipelvectomy is a procedure with considerable morbidity and is indicated for only a minority of far-advanced tumors. It offers a chance of palliation and possibly cure when lesser surgical options have been exhausted.

Malignant fibrous histiocytoma: an institutional review.

Background: A thorough understanding of malignant fibrous histiocytoma (MFH), the most common subtype of soft tissue sarcoma, will lead to improved histologic-specific protocols. Methods: 126 patients with histologically confirmed MFH were analyzed. The median follow-up was 42 months (range 1–233 months). Results: Overall survival was 58% at 5 years and 38% at 10 years. Grade significantly influenced prognosis, with 10-year survival of 90%, 60%, and 20% for low, intermediate, and high grade tumors, respectively (p = 0.0007). Distant metastases at initial presentation (p = 0.0002) and size of the primary tumor (p = 0.0007) influenced outcome. Neither anatomic site nor depth of the primary tumor were significant prognostic factors. Positive microscopic margins were associated with a decreased disease-free survival (p = 0.006). Conclusions: Tumor grade, size, and distant metastases at initial presentation remain the most important prognostic factors for MFH. Resection with negative microscopic margins decreased the incidence of local recurrence.

Resectability and survival in retroperitoneal sarcomas

AbstractBackground: Retroperitoneal sarcomas historically have presented difficulties in their management due to a high rate of unresectability, which affects the survival of these patients. Methods: We retrospectively reviewed the charts of 87 consecutive patients with retroperitoneal sarcomas treated in the period 1977–1994. Results: The resectability rate was 100% for the primary tumors (n=55) and 87% for the locally recurrent tumors (n=32). The 5-year survival rate was 63% (66% for the primary tumors and 57% for those with local recurrence). The 10-year survival rate was 46% (57% for primary tumors and 26% for those referred with locally recurrent tumor). The overall local recurrence rate was 31% (25% for the primary tumors and 41% for those referred with local recurrence); it was 56% after local excision and 15% after wide resection (p=0.0003). The 10-year disease-free survival of patients with local excision (n=25) was 7%, and that of patients with wide resection (n=54) 59% (p=0.0001). Conclusions: The overall resectability rate of retroperitoneal sarcomas was 95%. Wide resection produced a significantly higher survival rate compared with that of local excision. The survival rate for the primary tumors, varying significantly with the histologic grade, approached the rate reported for primary soft-tissue sarcomas of the extremity.