Citations

Abstract Background Management of patients with bilateral adrenal masses and corticotropin (ACTH)‐independent Cushing syndrome (CS) or subclinical CS is problematic. We report our experience with adrenal venous sampling (AVS) in the evaluation of 10 patients with bilateral masses who had ACTH‐independent CS or subclinical CS. Patients and Methods Ten patients (9 women, 1 man, mean age 56.4 years) with bilateral adrenal masses and ACTH‐independent CS ( n = 3) or subclinical CS ( n = 7) underwent AVS. Autonomous cortisol secretion was documented in all cases with suppressed serum ACTH concentrations and lack of cortisol suppression with dexamethasone administration. Adrenal venous sampling was performed on the second day of dexamethasone administration. Cortisol and epinephrine levels were measured from each adrenal vein (AV) and from a peripheral vein (PV). Results Mean (± SD) maximal diameter of the adrenal masses on computed tomography was 3.3 ± 1.3 cm (range: 1.2–6.0 cm). Successful catheterization was confirmed with AV:PV epinephrine gradients. A cortisol AV:PV gradient >6.5 was consistent with a cortisol‐secreting adenoma in 11 adrenal glands; 5 patients had clinically important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol‐secreting adenomas, and 2 had ACTH‐independent macronodular adrenal hyperplasia. Adrenal venous sampling‐guided adrenalectomy was completed in all 10 patients—2 patients had total bilateral adrenalectomy and 2 others had subtotal bilateral adrenalectomy. During a mean follow‐up of 36.1 months (range: 0.7–123 months), CS or clinically important cortisol secretory autonomy did not recur. Conclusions Adrenal venous sampling contributed to the localization of autonomous hypercortisolism in the setting of ACTH‐independent CS or subclinical CS in patients with bilateral adrenal masses.

An international collaboration was set up to prospectively evaluate the role of allogeneic transplantation for adults with acute lymphoblastic leukemia (ALL) and compare autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.5 years versus an autologous transplantation. A donor versus no-donor analysis showed that Philadelphia chromosome–negative patients with a donor had a 5-year improved overall survival (OS), 53% versus 45% (P = .01), and the relapse rate was significantly lower (P ≤ .001). The survival difference was significant in standard-risk patients, but not in high-risk patients with a high nonrelapse mortality rate in the high-risk donor group. Patients randomized to chemotherapy had a higher 5-year OS (46%) than those randomized to autologous transplantation (37%; P = .03). Matched related allogeneic transplantations for ALL in first complete remission provide the most potent antileukemic therapy and considerable survival benefit for standard-risk patients. However, the transplantation-related mortality for high-risk older patients was unacceptably high and abrogated the reduction in relapse risk. There is no evidence that a single autologous transplantation can replace consolidation/maintenance in any risk group. This study is registered at http://clinicaltrials.gov as NCT00002514.

Medical and surgical emergencies occasionally present as ruptured abdominal aortic aneurysms (RAAA). To assess benefits of laparotomies and adverse effects of unnecessary operations, the authors reviewed their experience. Thirteen patients, 9 women, 4 men (mean age: 72 years, range: 41-85) underwent emergency laparotomy between 1988 and 1996 for presumed RAAA and were found to have other surgical or medical emergencies. All the patients presented with hypotension, 12 had abdominal or back pain, four had pulsatile abdominal mass. Rupture was not excluded by computed tomography scan in three or by ultrasonography in two patients. Laparotomy disclosed intact abdominal aorta in all, but seven patients had abdominal aortic aneurysm. Of five surgical emergencies, laparotomy was indicated in four: three for ruptured visceral artery aneurysms, one for perforated duodenal ulcer. The fifth patient required thoracotomy for ruptured thoracic aneurysm. Four of eight medical emergencies were myocardial infarctions. One iatro genic complication required reoperation for bleeding. Mean hospital stay was 18 days; mean hospital charges were $40,771. Seven (54%) early deaths occurred; none were caused directly by the operation. Laparotomy was indicated in one third of deceptive emergencies that present as RAAA. Although mortality, morbidity, and costs were high, iatrogenic surgical complica tions were rare and deaths were not caused by unnecessary operations.

To investigate the concerns of parents, questionnaires were given to the "first 100" parents waiting for their child's pediatric appointment in four different medical settings. They were asked to rate whether they worry "frequently," "occasionally," or "not at all" about 17 physical health issues, 16 psychosocial problems, 7 possible injuries, 4 instances of victimization, and 4 questions about parents' ability to provide discipline, affection, values and financial support. The response rate was 94% ; 89% were completed adequately for analysis. Parental concerns were compared to data from the National Center for Health Statistics about the statistical likelihood of the risks occurring. Ear infections (65%) were the most common health concern, followed by reaction to immunization (57%), common colds (51%), and cancer (50%). The greatest psychosocial concern was about children watching too much television (53%), followed by concerns about the quality of day care (50%). Three-quarters of parents worry about car accidents and 72% worry about abduction of their children. Parents worry significantly about their own contribution to their child's welfare: appropriate discipline (73%), affection (56%), values and being a role model (55%), and financial support (66%). Parents who had not completed high school worried more than parents who had more than a high school education (P < 0.03).

AbstractBackgroundRepair of complex incisional hernias poses a major challenge.AimThe aim of this study was to review the outcomes of the modified Rives‐Stoppa repair of complex incisional hernias using a synthetic prosthesis.MethodsWe reviewed patients undergoing a modified Rives‐Stoppa repair of complex incisional hernias from 1990 to 2003. Patients were followed through clinic visits and mailed questionnaires. Follow‐up data were complete in all patients (mean 70 months, range 24–177 months), and 87% of patients completed a mailed questionnaire. Primary outcome included mortality, morbidity, and hernia recurrence. Secondary outcome measures were duration of hospital stay, long‐term abdominal wall pain, and self‐reported patient satisfaction.ResultsAltogether, 254 patients underwent a modified Rives‐Stoppa repair. Among them, 60% had a significant co‐morbidity, and 30% had one or more previously failed hernia repairs. Mortality was zero, and overall morbidity was 13% (wound infection 4%, prosthetic infection 3%, seroma/hematoma 4%). The overall hernia recurrence rate was 5%, including explantation of mesh because of infection. Wound/prosthetic infection was predictive for hernia recurrence (31% vs. 4%, p = 0.003). Among the respondents, 89% reported overall satisfaction with their repair.ConclusionThe Rives‐Stoppa repair of complex incisional hernias using synthetic prosthetic materials is safe with a low recurrence rate (5%) and high patient satisfaction. Postoperative wound infection is a risk factor for hernia recurrence.

Abstract Purpose: This phase I study was undertaken to define the maximum tolerated dose, safety, and pharmacokinetic profile of CP-751,871. Experimental Design: Using a rapid dose escalation design, patients with advanced nonhematologic malignancies were treated with CP-751,871 in four dose escalation cohorts. CP-751,871 was administered i.v. on day 1 of each 21-day cycle. Pharmacokinetic evaluation was done in all treatment cohorts during cycles 1 and 4. Results: Twenty-four patients received 110 cycles at four dose levels. The maximum tolerated dose exceeded the maximal feasible dose of 20 mg/kg and, thus, was not identified. Treatment-related toxicities were generally mild. The most common adverse events were hyperglycemia, anorexia, nausea, elevated aspartate aminotransferase, elevated γ-glutamyltransferase, diarrhea, hyperuracemia, and fatigue. At 20 mg/kg, 10 of 15 patients experienced stability of disease. Two of these patients experienced long-term stability. There were no objective responses. Pharmacokinetic analysis revealed a dose-dependent increase in CP-751,871 exposure and ∼2-fold accumulation on repeated dosing in 21-day cycles. Plasma concentrations of CP-751,871 attained were several log-fold greater than the biologically active concentration. Treatment with CP-751,871 increased serum insulin and human growth hormone levels, with modest increases in serum glucose levels. Conclusions: CP-751,871 has a favorable safety profile and was well tolerated when given in continuous cycles. At the maximal feasible dose of 20 mg/kg, there was a moderate accumulation in plasma exposure, and most of the treated patients experienced stability of disease.

Abstract Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of relapsed multiple myeloma patients showed significantly longer time to progression, higher response rate, and improved survival with single-agent bortezomib versus high-dose dexamethasone. In this updated analysis (median follow-up: 22 months), survival was assessed in both arms, and efficacy updated for the bortezomib arm. Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone, a 6-month benefit, despite substantial crossover from dexamethasone to bortezomib. Overall and complete response rates with bortezomib were 43% and 9%, respectively; among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response. Higher response quality (100% M-protein reduction) was associated with longer response duration; response duration was not associated with time to response. These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy. This study is registered at http://clinicaltrials.gov (Study ID NCT00048230).

Abstract The majority of candidates for breast cancer prevention have not accepted tamoxifen because of the perception of an unfavorable risk/benefit ratio and the acceptance of raloxifene remains to be determined. One means of improving this ratio is to identify women at very high risk of breast cancer. Family history, age, atypia in a benign biopsy, and reproductive factors are the main parameters currently used to determine risk. The most powerful risk factor, mammographic density, is not presently employed routinely. Other potentially important factors are plasma estrogen and androgen levels, bone density, weight gain, age of menopause, and fracture history, which are also not currently used in a comprehensive risk prediction model because of lack of prospective validation. The Breast Cancer Prevention Collaborative Group (BCPCG) met to critically examine and prioritize risk factors that might be selected for further testing by multivariate analysis using existing clinical material. The BCPCG reached a consensus that quantitative breast density, state of the art plasma estrogen and androgen measurements, history of fracture and height loss, BMI, and waist–hip ratio had sufficient priority for further testing. As a practical approach, these parameters could be added to the existing Tyrer–Cuzick model which encompasses factors included in both the Claus and Gail models. The BCPCG analyzed potentially available clinical material from previous prospective studies and determined that a large case/control study to evaluate these new factors might be feasible at this time.