Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a cytokine working group randomized trial.

PURPOSE: This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC). PATIENTS AND METHODS: Eligibility requirements were resected locally advanced (LA; T3b-4 or N1-3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 40% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history. RESULTS: Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P =.73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P =.38). Analysis including metastasectomy patients made no difference in DFS or overall survival. CONCLUSION: One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC.

Analysis of c-kit protein expression in small-cell lung carcinoma and its implication for prognosis.

Recently, therapies targeting signaling pathways involved in the pathogenesis of different tumors have been developed. Studies have shown that the tyrosine kinase inhibitor STI-571 (Gleevec) is used successfully against tumors expressing the c-kit oncogene, such as gastrointestinal stromal tumors (GISTs). A recent in vitro study also demonstrated an antiproliferative effect of STI-571 on small-cell lung cancer (SCLC) cell lines. To determine the expression of c-kit in SCLC, we retrospectively analyzed presence of c-kit by immunohistochemistry in biopsy samples from patients with SCLCs. Formalin-fixed, paraffin-embedded archival tissue samples from 30 SCLCs were stained with an antibody directed against c-kit (CD117) by immunohistochemistry. Thirty cases of SCLCs, including 17 males (age 44 to 89) and 13 females (age 21 to 85), were examined. Sixteen of 30 (53.3%) SCLCs showed c-kit expression. Kaplan-Meier survival analysis with a log-rank test revealed that patients with c-kit expression had a tendency toward lower survival than c-kit-negative patients (median survival, 6 months versus 31 months, P =.062). Based on previously established anti-c-kit effects of STI-571 on SCLC cell lines and our findings, clinical trials may be considered for selected SCLC patients with c-kit expression. Furthermore, determination of c-kit in SCLC may have a prognostic value in SCLC patients.

Zero mortality after 152 consecutive pancreaticoduodenectomies with pancreaticogastrostomy.

BACKGROUND: Since 1968, there have been three published reports in the United States literature of 41, 118, and 145 consecutive patients undergoing pancreaticoduodenectomy without mortality. In all of these series, the pancreatic remnant was anastomosed to the jejunum. STUDY DESIGN: This study was designed to review 152 consecutive patients who underwent pancreaticoduodenectomy in whom the pancreatic remnant was anastomosed to the stomach (pancreaticogastrostomy). RESULTS: A total of 152 patients underwent pancreaticoduodenectomy with pancreaticogastrostomy between July 1992 and May 2002. There were 85 men and 67 women with a mean age of 65.7 years (range 31 to 90 years). Of the patients, 87 were less than 69 years of age and 65 were more than 69 years. A total of 114 patients had a malignant neoplasm and the remaining 38 had either cystic neoplasms or benign disease. When the two groups were compared, the patients who were more than 69 years of age had a significantly high incidence of hypertension, previous cancer, atrial fibrillation, and coronary artery disease. In addition, patients more than 69 years of age had a significantly high incidence of jaundice and placement of preoperative stents. Patients more than 69 years of age had significantly less operative time but there was no between-group difference in estimated blood loss, transfusion, number of units transfused, and postoperative length of stay. There was no postoperative mortality [corrected] in this series. Pancreatic leak and fistulae were the most common complications, followed by intraabdominal abscess, wound infection, and delayed gastric emptying. CONCLUSIONS: In this study, 152 consecutive patients underwent pancreaticoduodenectomy with pancreaticogastrostomy without postoperative mortality. Morbidity was mostly because of pancreatic leaks and fistulae, which were successfully treated nonoperatively. With proper selection, careful preoperative preparation, and proper intraoperative conduct of operation, the Whipple procedure can be performed without postoperative mortality.

A comparison of pancreaticogastrostomy and pancreaticojejunostomy following pancreaticoduodenectomy.

This retrospective study compares the results of pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ) in our institution, which has extensive experience in both techniques. Between the years of June 1995 and June 2001, 214 patients underwent pancreaticoduodenectomy (PD) at our institution. Of these 177 had PG and 97 had pancreatojejunostomy (PJ). There were 117 (54.6%) males and 97 (45.3%) females with a mean age of 64.2 +/- 12.4 years. Indications for surgery were pancreatic adenocarcinoma in 101 (47.2%), ampullary adenocarcinoma in 36 (16.9%), distal bile duct adenocarcinoma in 22 (10.2%), duodenal adenocarcinoma in 9 (4.2%), and miscellaneous causes in 46 (21.4%) of patients. Preoperatively, significant differences in the groups were that the patients undergoing PJ were significantly younger than those undergoing PG. Also noted preoperatively, was that the patients undergoing PG had a significantly lower direct bilirubin than those undergoing PJ. With regard to intraoperative parameters, operative time was significantly shorter in the PJ group when compared to the PG group. When the patients who did not develop fistula (N = 186) were compared to those who developed fistula (N = 28) the significant differences were that the patients who developed fistula were more likely to have hypertension preoperatively and a higher alkaline phosphatase. They also showed a significantly higher drain amylase and were likely to have surgery for ampullary, distal bile duct or duodenal carcinoma rather than pancreatic adenocarcinoma. In addition, those patients who developed fistula had a significantly longer postoperative stay, a larger number of intraabdominal abscesses and leaks at the biliary anastomosis. Thirty-day mortality was significantly higher in the PJ group compared to the PG (4 vs. 0, P = 0.041). There was a significantly larger number of bile leaks in the PJ group when compared to the PG (6 vs. 1, P = 0.048). In addition, the PJ group required a significantly larger number of new CT guided drains to control infection (8 vs. 2, P = 0.046) and the PJ group required a larger number of re-explorations to control infection or bleeding (5 vs. 0, P = 0.018). However, the pancreatic fistula rate was not different between the two groups (12% [PG] vs. 14% [PJ]). This retrospective analysis shows that safety of PG can be performed safely and is associated with less complications than PJ and proposes PG as a suitable and safe alternative to PJ for the management of the pancreatic remnant following PD.

Medical student electives in general surgical subspecialties.

BACKGROUND: The purpose of the study was to evaluate how well the burn, trauma, and peripheral vascular third-year medical school electives meet the objectives of the six ACGME core competencies. METHODS: Medical school graduates from 1999 to 2002 completed a survey that consisted of 13 demographic/miscellaneous questions, and 28 core competency questions. RESULTS: In all, 168 of 500 students responded for a 34% response rate. All three general surgical electives ranked above average in meeting objectives in the areas of: basic science, performing complete histories and physicals, writing logical and legible notes, creating complete assessments and plan, making decisions with evidence based medicine, performing basic procedures, interpreting test results, and maintaining professional attitudes. The burn elective ranked significantly higher in 16 of 28 objectives (P < 0.05) and the trauma elective ranked significantly higher in two of 28 objectives (P < 0.05). CONCLUSIONS: Despite a narrower professional focus, three general surgical subspecialty electives meet objectives in five of the six competencies set forth by the ACGME (and adopted by our medical school as objectives for the ideal graduate). The highly organized and structured burn elective can be used as a template for improving all surgical rotations to meet the six core competencies for third-year students.

The influence of reconstructive modality on cost of care in head and neck oncologic surgery.

OBJECTIVE: To determine the differential costs of 3 reconstructive modalities in patients undergoing head and neck oncologic surgery. DESIGN: Cost-identification analysis. SETTING: Academic tertiary care medical center. METHODS: Retrospective review of 104 major head and neck resections involving primary tumors of the upper aerodigestive tract requiring a tracheotomy (primary hospital discharge, diagnosis related group 482 from the International Classification of Diseases, Ninth Revision, Clinical Modification) from July 2, 1999, through June 30, 2000. Patients were stratified by reconstruction modality: (1) microvascular free tissue transfer (MFFT), (2) pedicle myocutaneous flaps (PMF), and (3) primary reconstruction and/or skin graft (PR). Dependent variables included length of hospitalization, direct and indirect hospital costs, total hospital costs, the percentage of total costs attributable to direct costs, and the percentage of total costs attributable to indirect costs. RESULTS: No significant age differences existed among the 3 patient groups. Significant differences (Kruskal-Wallis) were observed for all variables. The PR group was compared with the PMF and MFFT groups. Total patient charges were greatest in the MFFT group (mean, $22 821.04) and least for the PR group (mean, $13 125.70). Length of stay was greatest in the PMF group (mean, 7.53 days) and shortest in the PR group (mean, 5.53 days). CONCLUSIONS: Intricate reconstructions are frequently more times consuming than primary closure, and the additional surgical procedures are more likely to use more hospital resources. Efforts at providing superior functional outcomes must be balanced against increasing restrictions on the use of health care dollars. Careful evaluation of functional outcomes and quality of life will be required to justify the increased expenditure incurred when providing complex reconstructions.

Octreotide does not prevent postoperative pancreatic fistula or mortality following Pancreaticoduodenectomy.

The role of octreotide in preventing pancreatic fistula following pancreaticoduodenectomy (PD) remains controversial. The purpose of our study was to report our experience with octreotide in 266 patients undergoing PD from 1995 to 2002. There were 150 males and 116 females. Patients were divided into two groups. Group 1 did not receive octreotide (N = 61). Group 2 received octreotide (N = 205). The average patient age was 66.2 years in the control group and 63.6 years in the octreotide group. One hundred fifty patients were male and 116 were female. Thirty-day mortality for both groups was 1.9 per cent. The incidence of pancreatic fistula was 12 per cent. Fistula occurrence in the octreotide group was 13 per cent and in the no-octreotide group 8 per cent (P = 0.34). Common complications in the no-octreotide group were pancreatic leak (10%), pancreatic fistula (8%), and delayed gastric emptying (8%). Common complications in the octreotide group were pancreatic leak (18%), pancreatic fistula (13%), intra-abdominal abscess (7%), and arrhythmia or myocardial infarction (7%). The only statistically different variable was the incidence of arrhythmia or myocardial infarction (P = 0.026). Octreotide did not reduce pancreatic fistula, other complications, or mortality. Octreotide may contribute cardiac morbidity. Octreotide cannot be recommended to prevent mortality or postoperative complications after PD.

Response to treatment of hepatitis C in individuals with a recent history of intravenous drug abuse.

OBJECTIVE: The aim of this study was to determine the rate of sustained response (SR) to high-dose daily interferon (IFN) therapy in prior drug abusers with chronic hepatitis C. This was a retrospective matched cohort study conducted at a tertiary care university hospital in a large urban area. METHODS: The 120 individuals in each cohort were treated by the same physicians at the same facility, using the same treatment protocol and management procedures. Each patient received 5 million units of IFN daily for at least 1 yr and usually longer. RESULTS: Both groups achieved a similar rate of SR (no i.v. drug abuse, 37% vs i.v. drug abuse, 33%). The end of treatment (ET) response rate was unexpectedly higher in the drug-abusing population as compared to that non-drug-abusing control subjects but fell during the follow-up period to achieve an SR similar to that of the non-drug-abusing controls. The side effects of IFN therapy were no greater in the prior drug abusing population than in the controls, although many in the drug-abusing group increased their dose of methadone to counteract IFN side effects. CONCLUSIONS: The SR rate achieved by intravenous drug abusers to high-dose, daily IFN is similar to that in a non-drug-abusing HCV positive population. Recent use of illicit drugs within a 6-month period of starting IFN therapy or continued methadone use during treatment does not seem to impair the response to IFN when the results are compared with those of a matched cohort of non-drug-abusing controls.

Do mothers remember key events during labor?

OBJECTIVE: The purpose of this study was to assess the accuracy of maternal recall of key events during their most recent delivery. STUDY DESIGN: After institutional review board approval, women who were delivered at Loyola University Medical Center were recruited. Patients were asked a maximum of 13 questions about major labor management events that were applicable to the course of their delivery. Patient responses were compared with the delivery records. RESULTS: We interviewed 277 ethnically diverse women with a median interval since delivery of 10 weeks and a mean age at delivery of 26 years. Forty percent of the women answered all questions correctly. Mothers with better recollection were more likely to be white, older, to have had more recent deliveries and were more likely to have had cesarean delivery. CONCLUSION: Sixty percent of mothers cannot recall accurately at least one major labor management event. Studies that rely on patient recall of obstetric variables are likely to have high error rates.

Bone mineral density among cirrhotic patients awaiting liver transplantation.

Osteoporosis is an important and common complication in patients with chronic liver disease. The goal of this study was to determine the bone mineral density (BMD) in different subgroups among pretransplant cirrhotic patients. BMD of the lumbar vertebrae (L) and femoral neck (F) were obtained in 104 consecutive cirrhotic patients. Descriptive and inferential statistics were used to compare the BMD among various groups. The mean BMD in males (n = 54) and females (n = 50) at L were 1.28 +/- 0.25 g/cm(2) and 1.13 +/- 0.20 g/cm(2), respectively (P =.001); at F they were 1.03 +/- 0.14 and 0.91 +/- 0.17, respectively (P <.0001). Among males, BMD at L in Child-Turcotte-Pugh class B and C were 1.40 +/- 0.21 and 1.13 +/- 0.20, respectively (P =.001); at F they were 1.11 +/- 0.10 and 0.93 +/- 0.13, respectively (P <.0001). Among females, BMD at L in Child-Turcotte-Pugh class B and C were 1.27 +/- 0.18 and 1.05 +/- 0.16, respectively (P =.0003); at F they were 1.02 +/- 0.16 and 0.83 +/- 0.12, respectively (P =.001). The BMD in premenopausal females (n = 15) and postmenopausal females (n = 35) at L were 1.20 +/- 0.19 and 1.11 +/- 0.20, respectively (P =.15); at F they were 0.97 +/- 0.17 and 0.88 +/- 0.16, respectively (P =.12). The BMD in postmenopausal females on hormone replacement therapy (n = 19) and on no hormone replacement therapy (n = 16) at L were 1.07 +/- 0.17 and 1.14 +/- 0.23, respectively (P =.29); at F they were 0.85 +/- 0.15 and 0.91 +/- 0.18, respectively (P =.33). The BMD values between etiologic groups were not significantly different. The overall prevalence of osteopenia and osteoporosis were 34.6% and 11.5%, respectively, being significantly higher in females than in males. In conclusion, significant difference in BMD values exists between males and females, as well as between Child-Turcotte-Pugh class B and C patients with cirrhosis. In addition, there is no significant influence of menopausal status, hormone replacement therapy, and etiology of cirrhosis on BMD.

Subjective and objective analysis of the prevalence of Peyronie's disease in a population of men presenting for prostate cancer screening.

PURPOSE: In this study we defined the prevalence of Peyronie's disease in a cohort of men being screened for prostate cancer in the United States. The association between Peyronie's disease, and medical comorbidities and patient self-reported erectile dysfunction was also defined. MATERIALS AND METHODS: A total of 534 men presenting to 1 of 3 prostate cancer screening centers provided a complete medical history, underwent physical examination performed in all by a urologist and completed the Sexual Health Inventory for Men (SHIM) questionnaire. This population was chosen because of the access to a large number of subjects combined with the fact that subjects were not presenting with a specific urological complaint. The diagnosis of Peyronie's disease was based on a palpable penile plaque. Data were assessed using univariate analysis, multivariate logistic regression and Pearson chi-square analysis. RESULTS: A total of 48 patients were found to have a palpable penile plaque on physical examination for a prevalence rate of 8.9%. The mean age of men with Peyronie's disease was 68.2 years compared to a mean of 61.8 years in men without Peyronie's disease (p <0.0001). On univariate analysis hypertension (p = 0.02) and diabetes (p = 0.007) were present with significantly increased frequency in patients with Peyronie's disease. Patients diagnosed with Peyronie's disease had significantly lower values for responses to each of the 5 questions on the SHIM survey. An increase in age and decrease in total SHIM score remained significantly associated with a greater probability of Peyronie's disease on multivariate analysis. CONCLUSIONS: We found the prevalence of Peyronie's disease to be greater than in most previously reported series. We also noted a significant association between Peyronie's disease aging, hypertension, diabetes and self-reported erectile dysfunction.