Resection status, age and nodal involvement determine survival among patients receiving adjuvant chemoradiotherapy in pancreatic adenocarcinoma.

CONTEXT: Pancreas cancer can potentially be cured by resection, but the role of adjuvant chemotherapy and/or chemoradiation has been controversial. OBJECTIVES: To better define clinicopathological factors that may serve as predictive and/or prognostic variables. PATIENTS: Between 1984 and 2006, we retrospectively analyzed 91 patients with pancreas cancer treated with pancreaticoduodenectomy or total pancreatectomy followed by adjuvant 5-fluorouracil-based chemoradiation at the University of Pennsylvania. Final pathological coding including margin status was confirmed by a pathologist. INTERVENTIONS: Patients were treated with 48.6 to 63.0 Gy, and 96.7% completed their prescribed radiation dose. MAIN OUTCOME MEASURES: The prognostic significance of demographic factors, stage, year of surgery, tumor location, grade, resection status, and number of positive lymph nodes on overall survival were examined. RESULTS: With a median follow-up of 6.5 years, the overall median survival was 2.3 years (95% CI 1.5-3.2 years), and the 5-year overall survival was 28.9%. In multivariate analysis, completeness of resection (P<0.001), fewer number of positive lymph nodes (0 vs. 1-2 vs. 3 or more) (P=0.004), and age less than, or equal to, 60 years (P=0.006) were all independently associated with improved overall survival. The overall survival reported in this study compares favorably with the results of other single-institution studies and with the RTOG 97-04 trial. CONCLUSIONS: Adjuvant 5-FU-based chemoradiation following radical pancreatectomy can be delivered safely and results in comparatively good overall survival. The results of this analysis underscore the importance of resection status, number of involved lymph nodes and patient age as prognostic characteristics. These factors may be considered stratification variables for future post-pancreatectomy adjuvant therapy trials.

Biopsy findings after breast conservation therapy for early-stage invasive breast cancer.

PURPOSE: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. METHODS AND MATERIALS: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. RESULTS: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if 180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p >or= 0.15). CONCLUSION: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.

Use of radiotracer for sentinel lymph node mapping in breast cancer optimizes staging independent of site of administration.

PURPOSE: In an effort to optimize sentinel lymph node (SLN) mapping for breast cancer, sites of mapping agent administration and types of mapping agents used continue to be evaluated. This study compares SLN mapping using peritumoral (PT) or subareolar (SA) injection of radiolabeled colloid and examines the relative contributions of radiotracer and blue dye to SLN identification. MATERIALS AND METHODS: A retrospective review was performed of 456 patients with breast cancer and clinically negative axillae who underwent SLN mapping. Sequential groups of patients were injected with filtered Tc-99m SC, 326 peritumorally (group 1) and 130 subareolarly (group 2). All patients had intraoperative SA injection of 1% isosulfan blue dye. RESULTS: The SLN identification and isotope success rates were 97% and 96% in group 1 and 98% and 98% in group 2, respectively. Eighty-one patients (25%) in group 1 and 44 patients (34%) in group 2 had positive SLNs. Of these patients, 15% from group 1 and 14% from group 2 had only positive nodes detected by radiotracer, and 9 of these patients (6 from group 1 and 3 from group 2) had other nodes identified by both radiotracer and blue dye that were negative for metastases. Six percent of patients with positive SLNs were upstaged because of use of radiotracer. CONCLUSIONS: PT and SA injection of radiotracer have comparable success rates for axillary SLN identification. Given that 15% of patients in group 1 and 14% in group 2 had only positive SLNs detected by radiotracer, independent of site of administration, radiotracer remains essential for optimizing breast SLN mapping.

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.

Psychiatric diagnoses and psychiatric treatment among bariatric surgery candidates.

BACKGROUND: This study investigated the psychiatric diagnoses and psychiatric treatment histories of 90 bariatric surgery candidates. METHODS: Prior to surgery, all participants completed the Weight and Lifestyle Inventory, the Questionnaire on Eating and Weight Patterns, and the Beck Depression Inventory-II. Participants also underwent a behavioral/psychological evaluation with a psychologist, which reviewed responses to the measures and provided further assessment of participants' psychiatric status. The evaluation also was used to produce a recommendation on the patients' psychological appropriateness for surgery. RESULTS: Almost two-thirds of patients received a psychiatric diagnosis, the most common of which was major depressive disorder. Nearly two-fifths of all participants, and more than half of those given a psychiatric diagnosis, were engaged in some form of psychiatric treatment at the time of the evaluation. Nevertheless, 64% of patients were unconditionally approved for surgery; 31% were recommended for additional psychiatric or nutritional counseling prior to surgery. Three patients were not recommended for surgery. CONCLUSION: Results of this study provide important information on the preoperative psychiatric status and treatment histories of bariatric surgery candidates. Given the increasing population of bariatric surgery patients, evaluation of patients' preoperative psychiatric status may play an important role in maximizing successful postoperative outcomes.

Extended left colon interposition for esophageal replacement using arterial augmentation.

Gastric necrosis after esophagectomy is a difficult clinical problem. Remedial operations to reestablish gut continuity usually rely on the use of the left colon as the neo-esophagus. Previous resection of the necrotic stomach, adhesions associated with a multiple redo-laparotomy and the need to use a substernal route to reach the cervical esophagus all conspire to produce a requirement for increased conduit length. We present a case in which the "arterial supercharge technique" was used to provide a colonic interposition with extended length in such a clinical situation.

Dexon mesh splenorrhaphy for intraoperative splenic injuries.

The preferred management option for intraoperative splenic injuries is organ repair and preservation rather than splenectomy given the important immunologic function of the spleen. Wrapping the injured spleen with a Dexon mesh has been shown to be an effective alternative to splenectomy for significant splenic bleeding. However, this technique uses a foreign body that carries a theoretical infectious risk particularly in cases in which the alimentary tract has been opened. This study was undertaken to evaluate whether Dexon mesh splenorrhaphy when used for intraoperative splenic injuries was associated with significant infectious complications. The clinical courses of 23 patients who had Dexon mesh splenorrhaphy performed at a university teaching hospital for intraoperative splenic injury from 1991 to 1999 were reviewed. Eleven patients (48%) had their gastrointestinal tract opened during the surgery. No patients developed an intra-abdominal abscess or required reoperation for bleeding. The most common postoperative complications were left lower lobe atelectasis (18 patients, 78%), postoperative fever (13 patients, 56%), and left pleural effusion (12 patients, 52%). Dexon mesh splenorrhaphy effectively controls splenic bleeding due to intraoperative injury without significant infectious complications.

Repair of large complex recurrent incisional hernias with retromuscular mesh and panniculectomy.

BACKGROUND: Recurrent incisional hernia repair is associated with high recurrence and wound complication rates. METHODS: The clinical courses of patients who underwent recurrent incisional hernia repair via retromuscular mesh placement with concomitant panniculectomy at a university teaching hospital from 1999 to 2004 were reviewed retrospectively. Postoperative evaluation included a quality of life survey. RESULTS: Forty-seven patients (13 male, 34 female) with an average body mass index of 34.4 kg/m2, an average midline hernia defect of 31.4 cm, and at least 1 and on average 2.5 previous repair attempts underwent hernia repair. Wound infections occurred in 4 patients (8%) and seromas requiring aspiration occurred in 1 patient (2%). Four patients (8%) had re-recurrences of their hernias. All patients rated the postoperative appearance of their abdomen as at least satisfactory. CONCLUSIONS: Recurrent incisional hernia repair with a retromuscular mesh and panniculectomy has low recurrence and wound complication rates and excellent patient satisfaction.

Changes in the surgical management of patients with breast carcinoma based on preoperative magnetic resonance imaging.

BACKGROUND: Breast magnetic resonance imaging (MRI) is a developing technique for the evaluation of patients with primary breast carcinoma. The authors assessed the impact of preoperative breast MRI on surgical management. METHODS: The current study was a retrospective review of 267 patients with primary breast tumors who had MRI studies prior to undergoing definitive surgery. RESULTS: Two hundred sixty-seven patients with invasive breast carcinoma who had preoperative breast MRI studies and had complete clinical, radiologic, and pathologic data available were identified and formed the basis of this analysis. The overall sensitivity of MRI for detecting primary, intact breast tumors was 95%. Planned surgical management was altered in 69 of 267 patients (26%); and, in 49 of those patients (71%), there was pathologic verification of malignancy in the surgical specimen that confirmed the need for wider or separate excision or mastectomy. Forty-four of 267 patients (16.5%) had conversion of planned breast conservation to mastectomy. In a univariate analysis, change in management was associated significantly with histology; management was altered in 11 of 24 lobular tumors (46%) compared with 58 of 243 ductal tumors (24%; P = 0.02). CONCLUSIONS: Breast MRI was very sensitive for the detection of primary, intact, invasive breast carcinoma and improved local staging in almost 20% of patients. Preoperative breast MRI studies may be particularly useful in surgical planning for and management of patients with lobular carcinoma.