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Biomedical subjects

Elin R Sigurdson

Publications and source records attributed to Elin R Sigurdson.

12 recordsLinked to original sources

Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481).

PURPOSE: Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome. METHODS: In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers. RESULTS: Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade > or = 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or > or = 4, the median survival was 24 and 14 months, respectively (P = .17). CONCLUSION: HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.

Adult↗

Liver-directed therapies for patients with primary liver cancer and hepatic metastases.

Liver cancer, whether primary or metastatic, is a major cause of death throughout the world. The surgical management of these diseases varies according to the extent of disease and the overall health of the patient. Surgical resection of hepatic disease remains the only chance for cure. However, a large proportion of patients with liver cancer are unable to undergo a complete surgical resection. These patients are often treated with liver-directed therapies. Although not as effective as surgical resection, these approaches can help to improve the survival of patients. In patients with primary liver cancer, underlying liver disease often prohibits surgical intervention. However, survival advantages have been gained with the application of percutaneous alcohol injection and radiofrequency ablation (RFA). In patients with hepatic metastases, the number of metastases is often what prevents surgical resection. In these patients, RFA, cryoablation, and hepatic artery infusional therapy have all aided in prolonging survival. As chemotherapeutic agents improve and targeted therapies are developed, more patients will be able to undergo surgical management of their liver cancer, primary or metastatic.

Carcinoma, Hepatocellular↗

Liver-directed therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. This disease can be treated through several surgical and nonsurgical approaches. Although the only curative options for patients with HCC are surgical (resection or transplantation), most patients unfortunately present with advanced neoplastic disease or experience the effects of chronic liver disease, making surgical resection implausible. Several additional options are available for treating this population. Ablative therapies such as percutaneous ethanol injection, cryotherapy, radiofrequency ablation, laser ablation, and microwave hyperthermic ablation can be used with varying degrees of success. Transarterial chemoembolization can be used in patients with advanced disease or advanced chronic liver disease that cannot be treated with resection or ablation. This article explores the various liver-directed therapies, including surgical resection, and defines morbidity, mortality, and survival for each.

Carcinoma, Hepatocellular↗

Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes.

PURPOSE: Colorectal cancer is the second leading cause of cancer deaths in the United States, with poor survival predicted by regional lymph node (LN) metastasis. The impact of LN ratio (LNR) on survival is unknown in this disease. PATIENTS AND METHODS: We analyzed data from Intergroup trial 0089 of adjuvant chemotherapy for stage II and III patients with colon cancer, in which all patients received fluorouracil-based therapy. Survival was similar for all arms of the study, allowing us to evaluate all patients together. End points included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Multivariate analyses were performed on all patients and on groups according to LNR quartiles (LNR: < 0.05, 0.05 to 0.19, 0.2 to 0.39, and 0.4 to 1.0). Covariates included in the models were age, sex, tumor stage, grade, histology, number of positive LNs, number of LNs removed, and LNR. RESULTS: The median age was 63.7 years, and the median number of LNs removed was 11. In the multivariate analysis, LNR was a significant factor for OS, DFS, and CSS in patients with 10 to 15 LN and more than 15 LN removed but not for patients with less than 10 LN removed. Using quartiles, LNR maintained its significance for all three end points when patients were grouped by node status. CONCLUSION: After curative resection for colorectal cancer, the LNR is an important prognostic factor and should be used in stratification schemes for future clinical trials investigating adjuvant treatments.

Adenocarcinoma↗

The association of cytokeratin-only-positive sentinel lymph nodes and subsequent metastases in breast cancer.

INTRODUCTION: The purpose of this study was to better characterize the clinical significance of cytokeratin immunohistochemistry (IHC)-only-positive lymph node metastases among patients with breast cancer. METHODS: We performed a retrospective review of 334 patients who underwent sentinel lymph node (SLN) biopsy from 1 February 1997 through 31 July 2001. SLN biopsies were evaluated using standard hematoxylin and eosin (H&E) techniques. If H&E was negative, cytokeratin IHC was performed. We then evaluated the incidence of subsequent regional and distant metastatic disease. RESULTS: Cytokeratin IHC was performed on 183 sentinel node biopsies from 180 patients comprising a total of 427 sentinel lymph nodes. The procedures included lumpectomy and SLN biopsy (n = 83), mastectomy with SLN biopsy (n = 7), lumpectomy with SLN biopsy and completion axillary dissection (n = 80), and modified radical mastectomy with SLN biopsy and completion axillary dissection (n = 13). Cytokeratin IHC was negative in 175 axillary specimens and positive in 8 (4.4%) from 8 different patients. In these eight specimens, deeper sections with subsequent H&E staining additionally identified micrometastasis in four patients. Three of these 8 patients (37.5%) developed distant metastatic disease compared with 1 of the 172 patients (0.6%) with negative cytokeratin IHC (P < .001). Additionally, one of the cytokeratin-positive patients developed regional nodal metastasis compared with none of the 172 cytokeratin-negative patients. CONCLUSIONS: Cytokeratin IHC provides a clinically relevant adjunct to H&E staining for evaluating sentinel lymph nodes in breast cancer. These data suggest that patients with cytokeratin-positive sentinel nodes are at increased risk for development of regional and distant metastatic disease.

Breast Neoplasms↗

Accuracy of determining nodal negativity in colorectal cancer on the basis of the number of nodes retrieved on resection.

BACKGROUND: Correct determination of nodal status is pivotal to accurate staging and predicting survival. METHODS: This is a secondary analysis of INT0089, an intergroup trial of adjuvant chemotherapy for high-risk stage II and III colon cancer. A subset of patients was studied who underwent right or left hemicolectomy and from whom at least 10 lymph nodes were examined. A mathematical model was created to estimate the probability of a true negative result on the basis of the number of nodes examined. The number of nodes needed to predict nodal negativity with 85%, 50%, and 25% probability on the basis of tumor stage was calculated. RESULTS: In this analysis, 1585 patients were studied. The average number of nodes removed at surgery was comparable between treatment groups at 18.5 (median of 16 in all groups). With this model, when 18 nodes are removed at resection, there is a <25% probability of true node negativity in T1/T2 tumors, whereas <10 nodes need to be examined in T3 and T4 tumors to achieve the same probability. CONCLUSIONS: Tumor stage and the number of nodes retrieved at resection influence the accuracy of determining nodal status in colon cancer. Most patients are understaged. Underestimating nodal stage may influence decisions regarding adjuvant therapy, as well as overall prognosis.

Adult↗

Locoregional strategies for colorectal hepatic metastases.

Hepatic colorectal metastases present a challenging problem in patients with recurrent colorectal cancer. Twenty percent of patients with recurrence will have liver metastases as a component of their disease, and only 10% of these patients will have isolated liver metastases that are resectable. Although systemic chemotherapy alone has not proven efficacious in the treatment of liver metastases, a number of options exist in managing these lesions. For those that are resectable, surgery remains the optimal treatment, with an expected 5-year survival rate of 33%-39% based on several large series. Hepatic artery chemotherapy is another adjunct treatment in patients undergoing resection and may further improve survival. This benefit may be even more pronounced when combined with systemic chemotherapy. Newer-generation agents are likely to further improve results. More recently, new therapeutic modalities have been used to treat unresectable lesions. These include hepatic artery chemotherapy and ablative techniques such as radiofrequency ablation and cryoablation. This article will highlight the data regarding hepatic resection for colorectal metastases, describe the rationale for and efficacy of hepatic arterial chemotherapy in the postoperative adjuvant setting and in unresectable liver disease, and review the current literature describing ablative techniques in the treatment of liver metastases.

Antineoplastic Agents↗

Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study.

PURPOSE: Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated. PATIENTS AND METHODS: Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival. RESULTS: The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19) CONCLUSION: These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.

Antimetabolites, Antineoplastic↗

Surgical treatment of liver metastases.

Approximately 50% to 60% of patients with colorectal cancer will develop hepatic metastases during the course of their illness, with 20% to 30% of patients having liver metastases at time of diagnosis. In nearly a quarter of these patients the liver is the only site of disease. Surgical resection of isolated hepatic metastases has been associated with a 27% to 37% 5-year survival and confers a survival advantage compared to patients not undergoing resection. Thorough preoperative and intraoperative evaluation is necessary to select appropriate surgical candidates who may benefit from resection. This article examines criteria useful in patient selection, and also reviews the management of recurrent hepatic metastases and the role of repeat hepatic resection.

Chemotherapy, Adjuvant↗

Pancreatic resection for locally advanced primary and metastatic nonpancreatic neoplasms.

We conducted a retrospective review of our single-institution experience with pancreas resection for locally advanced primary malignancy or metastases from other organs. From January 1989 through April 2001 35 patients underwent pancreatic resection for locally advanced primary (17) and recurrent nonpancreatic (18) tumors. Patient records were examined for recurrence and survival. Seventeen patients with locally advanced primary tumors presented with pancreatic extension either into the head/body (six) or tail (11). Pancreatic resections were completed as en bloc procedures with the primary disease of stomach (five), colon (four), sarcoma (five), adrenal gland (one), or spleen (one). Procedures performed included pancreaticoduodenectomy for proximal lesions and distal pancreatectomy for disease limited to the pancreatic tail. Median overall survival was 56 months. Fourteen of 17 patients remain alive: three with disease and 11 without evidence of recurrence. Eighteen patients presented with recurrent tumor from a previously resected right upper quadrant tumor (nine) or metastases from an intra-abdominal source (nine). The primary source was colon (eight), biliary (three), sarcoma (three), melanoma (two), ovary (one), and unknown primary (one). Patients underwent pancreaticoduodenectomy, distal pancreatectomy, or resection of residual pancreas. Overall median survival was 46 months. In this group of 18 patients there was no increased survival in those patients with a time to recurrence from their primary tumor resection greater than 2 years. We conclude that pancreatic resection for locally advanced nonpancreatic or recurrent intra-abdominal malignancies is possible in properly selected patients. The ability to obtain disease-free margins through en bloc resection is a key component of therapy.

Abdominal Neoplasms↗