A phase II study of high-dose calcitriol combined with mitoxantrone and prednisone for androgen-independent prostate cancer

OBJECTIVE

To evaluate the preliminary efficacy, safety, and impact on quality of life (QoL) of high‐dose calcitriol (DN‐101) combined with mitoxantrone and glucocorticoids in androgen‐independent prostate cancer (AIPC).

PATIENTS AND METHODS

Nineteen patients with metastatic AIPC and no previous chemotherapy received DN‐101 180 µg orally on day 1 and mitoxantrone 12 mg/m² intravenously on day 2 every 21 days with continuous daily prednisone 10 mg orally for a maximum of 12 cycles. A confirmed decline in prostate‐specific antigen (PSA) levels by half was the primary endpoint. QoL was evaluated using the European Organization for Research and Treatment of Cancer QLQ‐C30 questionnaire, and pain and analgesic use were evaluated.

RESULTS

Five of 19 patients (26%; 95% confidence interval, CI, 9–51) achieved a ≥50% decline in PSA level. The median (95% CI) time to PSA progression was 16 (6–26) weeks. The overall median (95% CI) survival was 16 (6–26) months; 47 (21–73)% of patients achieved an analgesic response. Toxicity was similar to that expected with mitoxantrone and prednisone alone. The QoL analysis suggested a decrease in physical functioning and increase in fatigue, insomnia, and diarrhoea.

CONCLUSIONS

DN‐101 given every 3 weeks does not add significant activity to mitoxantrone and prednisone in AIPC, as measured by the PSA decline. The high rate of analgesic response is encouraging. The addition of DN‐101 does not appear to increase the toxicity of mitoxantrone.     

Risk analysis of deep sternal wound infections and their impact on long-term survival: a propensity analysis

The objectives of this study are to determine risk factors associated with deep sternal wound infections (DSWIs) following cardiac surgery, and to describe their impact on long-term survival. Data was obtained from a departmental database. Analysis included 7,978 consecutive patients who underwent cardiac surgery between 1997 and 2003. To identify risk factors for DSWI, regression analysis was performed. The probability scores obtained from logistic regression were used for propensity analysis of 2 groups. Kaplan-Meier analysis with log-rank test and Cox proportional hazard models were then used in survival analysis. DSWI developed in 123 of 7,978 patients (1.5%). Preoperative predictors of DSWI were body mass index >30 kg/m(2) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.4; P < 0.05), diabetes mellitus (OR, 2.4; 95% CI, 1.6 to 3.4; P < 0.001), urgent operation (OR, 1.7; 95% CI, 1.2 to 2.6; P < 0.05), smoking history within past year (OR, 2.7; 95% CI, 1.5 to 4.9; P < 0.001), smoking history within past 2 weeks (OR, 2.6; 95% CI, 1.5 to 4.5; P < 0.001), and a history of stroke (OR, 1.9; 95% CI, 1.1 to 3.1; P < 0.005). In addition, total length of hospital stay (OR, 1.01; 95% CI, 1.01 to 1.02; P < 0.05) and sepsis and/or endocarditis following surgery (OR, 5.1; 95% CI, 2.9 to 9.0; P < 0.001) were also predictive of DSWI. Patients with DSWI had a prolonged total length of hospital stay (40.3 days versus 16.1 days; P < 0.001), and higher 30-day mortality (1.6% versus 7.3% in DSWI group, P < 0.05). There were no differences between groups in 4-year and 8-year survival rates, with 77.2% and 61.8%, respectively, in patients with DSWI compared with 78.0% and 67.5% in patients without DSWI (P = 0.16). After adjustments for preoperative, intraoperative, and postoperative factors, the adjusted hazard ratio of long-term mortality for patients with DSWI was 0.9 (95% CI, 0.6 to 1.2, P = 0.39). Though DSWIs are associated with increased early mortality, patients undergoing cardiac surgery complicated by DSWI do not experience worse long-term survival.     

The Basis of Racial Differences in the Incidence of Thyroid Cancer

Background The incidence of thyroid cancer in black Americans is half that in white Americans. It is unknown whether this gap represents a population difference in disease or is attributable to inferior cancer screening in the black population. Methods A population-based cohort study of 53,990 patients (1973–2003) was performed using the National Cancer Institute’s Surveillance Epidemiology End Results database. Socioeconomic variables were explored using the Healthcare Cost and Utilization Project database and macroeconomic data. Results Since 1973, thyroid cancer incidence among whites has increased 150.2% (4.0 to 9.9 of 100,000), while incidence among blacks has increased 73.2% (3.0 to 5.1 of 100,000). Across 17 regions, the incidence correlated with the percentage of the population with health insurance (r = 0.56, P = .02). Regression analysis suggested that half of the black-white incidence gap might be attributable to differences in health insurance status. Patients with thyroid cancer were more likely to be insured or reside in wealthier ZIP codes. Black patients were more likely to present at advanced age (RR 1.08, P < .0001) and with tumors >4 cm in size (RR 1.13, P <.0001). Black patients were slightly less likely to present with advanced disease (RR 0.96, P = .0008). Cancer-specific mortality was identical in the two populations. Discussion Sociodemographic data and differences at presentation support a small detection disparity in thyroid cancer, which may contribute to part of the incidence gap. However, this effect is not sufficiently strong to fully explain the incidence gap. A population difference in the incidence of disease may be coexistent.     

Sedation in the neurologic intensive care unit

Opinion statement Providing adequate sedation in the neurologic intensive care unit (ICU) depends on determination of proper goals for sedation, adequate assessment of the level of sedation, and appropriate choice of drug based on the patient’s physiology. The management of sedation in the ICU will influence long-term outcome. Delirium, anxiety, and pain must be identified and treated separately. The use of protocols can improve compliance with published evidence-based recommendations. Propofol and dexmedetomidine may be used for rapidly titratable sedation, benzodiazepines for anxiolysis, neuroleptics for treatment of delirium, and opiates for analgesia. Unique aspects of patients with acute brain disease, such as elevated intracranial pressure or status epilepticus, require adaptation of sedative regimens. Processed EEG monitoring and volatile anesthetic agents have not yet proven beneficial or practical for use in the ICU.     

Posttraumatic stress symptoms, PTSD, and risk factors among lower Manhattan residents 2-3 years after the September 11, 2001 terrorist attacks

Manhattan residents living near the World Trade Center may have been particularly vulnerable to posttraumatic stress disorder (PTSD) after the September 11, 2001 (9/11) terrorist attacks. In 2003-2004, the authors administered the PTSD Checklist to 11,037 adults who lived south of Canal Street in New York City on 9/11. The prevalence of probable PTSD was 12.6% and associated with older age, female gender, Hispanic ethnicity, low education and income, and divorce. Injury, witnessing horror, and dust cloud exposure on 9/11 increased risk for chronic PTSD. Postdisaster risk factors included evacuation and rescue and recovery work. The results indicate that PTSD is a continued health problem in the local community. The relationship between socioeconomic status and PTSD suggests services must target marginalized populations. Followup is necessary on the course and long-term consequences of PTSD.     

The effect of warm ischemic time on renal function and injury in the isolated hemoperfused kidney

BACKGROUND: The precise effect of warm ischemia on renal allograft function remains unclear and leads to variable warm ischemic time (WIT) limits advocated by transplant programs. This study aims to investigate the relationship between WIT, renal ischemia reperfusion injury, and graft function using a hemoperfused kidney model. METHODS: Porcine kidneys were perfused with normothermic blood on an isolated organ perfusion system. Kidneys were divided into four groups (n=6) and subjected to 7, 15, 25, and 40 min WIT. Physiological parameters were measured throughout the 6 hr perfusion period. Serum, tissue, and urine samples were analyzed for histological and biochemical markers of ischemia reperfusion injury. RESULTS: Creatinine clearance, urine output, renal hemodynamics, and oxygen consumption deteriorated proportionally with increasing WIT. A significant increase in plasma carbonyl levels during perfusion was seen after 25 and 40 min WIT only. Plasma 8-isoprostane levels were higher after 40 min WIT (2.5+/-1.6) vs. 7, 15, and 25 min WIT (0.65+/-0.43, 0.25+/-0.12, and 0.62+/-0.21, respectively; P<0.05). A negative correlation was shown between urine output and plasma carbonyls (r=-0.415, P<0.05) and between 8-isoprostane levels and creatinine clearance (r=-0.649, P<0.005). Caspase-3 activity was significantly higher after 7 min WIT compared with the other groups, correlating positively with creatinine clearance, urine output, and renal blood flow. CONCLUSION: The isolated organ perfusion system successfully delineated a clear WIT-dependent variation in renal function which correlated accurately with oxidative injury markers. This model may represent a clinically applicable tool for assessing graft viability.     

Adenocarcinoma of the gastroesophageal junction after bariatric surgery

BACKGROUND: The development of upper gastrointestinal malignancies after bariatric surgery has not been well characterized. Our objective was to review the experience of patients with distal esophageal cancer that was diagnosed after bariatric surgery. METHODS: A retrospective review was conducted to identify patients who had undergone bariatric surgery (1999 to 2006) and who later developed high-grade dysplasia or adenocarcinoma of the distal esophagus. RESULTS: Three patients (of 2,875 [0.1%]) developed esophageal cancer: 2 after Roux-en-Y gastric bypass and 1 after vertical banded gastroplasty. All three patients had complaints of reflux, and two were treated with esophagectomy. The third patient presented with invasive carcinoma and died 2 years after diagnosis. CONCLUSIONS: Our findings emphasize the importance of precise endoscopic evaluation before bariatric surgery in patients with gastroesophageal reflux disease (GERD), of the necessity for continuing postsurgical surveillance in patients with known Barrett's esophagitis, and of early evaluation in patients who develop new symptoms of GERD after bariatric surgery.     

Use of perioperative cardiac medical therapy among patients undergoing coronary artery bypass graft surgery

BACKGROUND: Previous studies have demonstrated that cardiac medical therapy is associated with improved clinical outcomes in noncardiac surgery. However, the use of these agents among patients undergoing coronary artery bypass graft (CABG) remains poorly understood. METHODS: We described the in-hospital medication use among 2,389 consecutive patients who underwent CABG at three North American hospitals. Demographic, clinical, and medication use information was extracted from resource and cost accounting systems at each hospital. We examined use of aspirin, angiotensin-converting-enzyme (ACE) inhibitors, beta blockers, and statins during the following seven in-hospital periods: admission, presurgery, the day before surgery, the day of surgery, the day after surgery, postsurgery, and discharge. RESULTS: Medication use throughout hospitalization was low among patients undergoing CABG. Use of ACE inhibitors and statins on the day of surgery was <10%, while aspirin and beta blocker use on the day of surgery was 43.0% and 42.9%, respectively. The use of cardiac medical therapy at hospital discharge was also low (ACE inhibitors: 23.0%; aspirin: 74.9%; beta blockers: 58.9%; and statins: 28.2%). The use of cardiac medical therapy at discharge appeared to increase over time. CONCLUSION: In-hospital cardiac medical therapies are underused among patients undergoing CABG. This is particularly true at discharge, where the benefits of these agents for secondary prevention are well established.     

Dissecting aneurysms of the posterior inferior cerebellar artery: retrospective evaluation of management and extended follow-up review in 6 patients

OBJECT: The authors report the management protocol and successful outcomes in 6 patients with dissecting aneurysms of the posterior inferior cerebellar artery (PICA). METHODS: Medical records and neuroimaging studies of 6 patients who underwent surgical treatment of dissecting PICA aneurysms were reviewed. The mean follow-up duration was 1.8 years. No patient was lost to follow-up review. RESULTS: Four patients presented with acute subarachnoid hemorrhage and 2 with PICA ischemia. All patients underwent surgery, which entailed proximal occlusion with distal revascularization in 3 cases and circumferential wrap/clip reconstruction in 3 cases. The revascularization techniques used were occipital artery-PICA bypass and PICA-PICA anastomosis. Delayed follow-up angiography was performed in all cases. In patients treated with proximal occlusion, delayed angiography showed minimal retrograde opacification of the dissected segments. The 3 patients treated with wrap/clip reconstruction showed unexpectedly significant normalization of their lesions on angiographic studies. Outcome was good in all cases. CONCLUSIONS: Dissecting PICA aneurysms are rare lesions with an apparent propensity for bleeding. Individualized management including distal revascularization with PICA sacrifice or circumferential wrap/clip reconstruction to reinforce the dissected segment produced good outcomes. Patients treated with aneurysm wrapping may show dramatic angiographic improvement of the dissected segment.