Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease

OBJECTIVES: To test the hypothesis that patients with non-small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non-small cell lung cancer) by site of primary tumor and pattern of lymph node metastases. METHODS: Accurate staging was ensured by mandating either systematic sampling or complete dissection of the ipsilateral mediastinal lymph nodes. The overall survival of patients with left lung non-small cell lung cancer and metastases in only 1 of lymph node levels 5, 6, or 7 and right lung non-small cell lung cancer with metastases in only 1 of levels 4 or 7 was compared with that of patients with N1 disease originating in the same lobe. RESULTS: The median survival of the 172 patients with single-level N2 disease was 35 months (95% confidence interval: 27-40 months) versus 65 months (95% confidence interval: 45-84 months) for the 150 patients with N1 disease (median follow-up 84 months, P =.01). However, among patients with left upper lobe tumors, survival was not significantly different between patients with N1 disease and patients with single-level N2 disease (49 vs 51 months, P =.63). The median survival of the 71 patients with single-level N2 metastases without concomitant N1 disease (skip metastases) was 59 months (95% confidence interval: 36-107 months) versus 26 months (95% confidence interval: 16-36 months) for the 145 patients with both N1 and N2 metastases (P =.001). CONCLUSIONS: Survival of patients with left upper lobe non-small cell lung cancer and metastases to single-level N2 lymph nodes is not significantly different from that of patients with N1 disease. The presence of isolate N2 skip metastases is associated with improved survival when compared with patients with both N1 and N2 disease. Survival should be reported by the lobe of primary tumor and metastatic pattern to guide future clinical trial development, treatment strategies, and revisions of the TNM staging system.     

Aortic root replacement in patients with previous heart surgery

OBJECTIVE: The objective was to review the operative risk and outcomes of redo aortic root replacement. PATIENTS AND METHODS: From July 1990 to December 2001, aortic root replacement was performed in 165 patients who had at least one previous cardiac operation. Their mean age was 49 +/- 16 years and 78% were men. Twenty-eight patients had a previous aortic root replacement. The principal indication for surgery was prosthetic aortic valve dysfunction. All the patients had a dilated, calcified, ruptured, or some other abnormality of the aortic root. The follow-up was complete and extended from 0 to 12.5 years, mean of 3.8 years. RESULTS: There were 12 operative (7%) and 20 late deaths (12%). The survival at 8 years was 68%+/- 6%. The principal cause of death was cardiovascular related. Age at increments of 5 years (risk ratio: 1.2; CI: 95%; 1.1 to 1.4) and preoperative New York Heart Association functional class IV (risk ratio: 2.2; CI: 95%: 1.1 to 4.7) were the only two independent predictors of death. Two patients had a stroke and died; two patients developed three episodes of prosthetic valve endocarditis and died. Three patients were reoperated on because of endocarditis in one, bioprosthetic valve failure in one, and dehiscence of a prosthetic mitral valve in one. The freedom from reoperation at 8 years was 93%+/- 5%. CONCLUSIONS: Redo aortic root replacement can be done with low operative mortality in elective patients and the risk increases in those who need emergent surgery and are older. The long-term results are satisfactory and similar to those for patients who have aortic root replacement for the first time.     

Exercise training in obesity lowers blood pressure independent of weight change

PURPOSE: We used the rabbit model of obesity and exercise training to determine effects of exercise training during the development of obesity on resting blood pressure and heart rate, ventricular hypertrophy, blood volume, and hormonal profile. METHODS: Female New Zealand white rabbits were assigned to one of four groups: lean sedentary (L-S, N = 17), lean exercise-trained (L-EX, N = 16), obese sedentary (O-S, N = 18), and obese exercise-trained (O-EX, N = 15). Lean rabbits were fed a maintenance diet whereas obese rabbits were fed an ad libitum high fat (10% added fat) diet. Simultaneously, exercise-trained animals underwent a progressive treadmill exercise training protocol for 12 wk. After 12 wk of diet and exercise regimens, resting blood pressure and heart rate were measured from a central ear artery catheter. Ventricular hypertrophy was evaluated using wet ventricular weights. Blood volume was measured using the Evans blue dye procedure; hormonal profile was evaluated from arterial plasma/serum samples. RESULTS: After 12 wk, O-S and O-EX had similar body weights and similar percentage increases in body weight. Despite similar body weights, O-EX had an approximate 6-mm Hg lower mean blood pressure compared with the elevated pressure seen in O-S (P < or = 0.05). Obese rabbits had greater resting heart rate, plasma cholesterol and triglycerides, and plasma renin activity compared with lean rabbits, and these values were unaffected by exercise training. Plasma and blood volumes, as well as plasma insulin, cortisol, and aldosterone were unaffected by exercise training. CONCLUSION: These data suggest that exercise training, in the absence of differences in body weight, may be useful in the reduction of obesity-induced hypertension but that other therapies may be needed in order to control other cardiovascular risk factors.     

Psychiatric and Cognitive Effects of Deep Brain Stimulation for Parkinson’s Disease

Deep brain stimulation (DBS) is effective for Parkinson’s disease (PD), dystonia, and essential tremor (ET). While motor benefits are well documented, cognitive and psychiatric side effects from the subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS for PD are increasingly recognized. Underlying disease, medications, microlesions, and post-surgical stimulation likely all contribute to non-motor symptoms (NMS).     

Bone material properties in premenopausal women with idiopathic osteoporosis

Idiopathic osteoporosis (IOP) in premenopausal women is characterized by fragility fractures at low or normal bone mineral density (BMD) in otherwise healthy women with normal gonadal function. Histomorphometric analysis of transiliac bone biopsy samples has revealed microarchitectural deterioration of cancellous bone and thinner cortices. To examine bone material quality, we measured the bone mineralization density distribution (BMDD) in biopsy samples by quantitative backscattered electron imaging (qBEI), and mineral/matrix ratio, mineral crystallinity/maturity, relative proteoglycan content, and collagen cross‐link ratio at actively bone forming trabecular surfaces by Raman microspectroscopy and Fourier transform infrared microspectroscopy (FTIRM) techniques. The study groups included: premenopausal women with idiopathic fractures (IOP, n = 45), or idiopathic low BMD (Z‐score ≤ ?2.0 at spine and/or hip) but no fractures (ILBMD, n = 19), and healthy controls (CONTROL, n = 38). BMDD of cancellous bone showed slightly lower mineral content in IOP (both the average degree of mineralization of cancellous bone [Cn.Ca_Mean] and mode calcium concentration [Cn.Ca_Peak] are 1.4% lower) and in ILBMD (both are 1.6% lower, p < 0.05) versus CONTROL, but no difference between IOP and ILBMD. Similar differences were found when affected groups were combined versus CONTROL. The differences remained significant after adjustment for cancellous mineralizing surface (MS/BS), suggesting that the reduced mineralization of bone matrix cannot be completely accounted for by differences in bone turnover. Raman microspectroscopy and FTIRM analysis at forming bone surfaces showed no differences between combined IOP/ILBMD groups versus CONTROL, with the exceptions of increased proteoglycan content per mineral content and increased collagen cross‐link ratio. When the two affected subgroups were considered individually, mineral/matrix ratio and collagen cross‐link ratio were higher in IOP than ILBMD. In conclusion, our findings suggest that bone material properties differ between premenopausal women with IOP/ILBMD and normal controls. In particular, the altered collagen properties at sites of active bone formation support the hypothesis that affected women have osteoblast dysfunction that may play a role in bone fragility. © 2012 American Society for Bone and Mineral Research.     

Alloplastic bladder substitution: are we making progress?

Radical cystectomy with lymphadenectomy and urinary diversion is the gold standard treatment for bladder cancer in organ-confined muscle-invasive disease and selected patients who have high-grade non-muscle-invasive disease or are non-responders to BCG. The main and most morbid complications of this challenging surgery are related to the use of bowel for urinary tract reconstruction. For this reason, many past projects were devoted to finding an alternative to the use of bowel. The aim of this review is to provide a summary of the evolution of alloplastic bladder substitution. A comprehensive review of the literature was performed using the Medline National Library of Medicine database and Google Scholar. Keywords used were cystectomy and intestine/bowel, replacement, bladder substitution, organ replacement, artificial bladder, alloplastic material, biomaterial, and tissue engineering. Various prostheses have been proposed for replacement of the urinary bladder, silicone being the most frequently used material. The first published model of an alloplastic bladder was described by Bogash et al. in late 1959, while the last, in 1996, was suggested by Rohrmann. Interprofessional collaboration, recent advances in technology, and tissue engineering may help in developing suitable bladder prostheses. Urologists as well as engineers and the industry need to give this matter serious attention.     

Gender-related differences in morbidity and mortality during combined valve and coronary surgery

BACKGROUND: Gender-related differences in morbidity and mortality are well described for coronary artery bypass grafting but are not well understood for combined valve and bypass surgery. METHODS: We reviewed retrospectively the morbidity and mortality of 1570 consecutive patients who underwent combined valve and bypass procedures at the Toronto General Hospital between January 1990 and October 2000. RESULTS: There were 1073 men (68%) and 497 women (32%). The mean ages (+/- 1 SD) of women and men were 69 +/- 9 and 68 +/- 9 years, respectively (P =.02). Of the 1570 total patients, 973 patients (62%) underwent aortic valve and coronary bypass surgery, 481 patients (31%) had mitral valve and coronary bypass operations, and 116 (7%) patients had double or triple valve and coronary bypass operations. Preoperative hypertension (P =.002), diabetes (P =.001), and atrial fibrillation (P =.001) were seen more frequently in women. Body surface area was significantly lower in women (P =.0001). At presentation, more women were in congestive heart failure (69% vs 58%, P =.001) and in New York Heart Association functional class III or IV (25% vs 19%, P =.001). Although there was no difference in the number of women with three or more diseased vessels (32% vs 38%), only 35% of women received three or more grafts compared with 44% of men (P =.001). The use of left internal thoracic grafts, although uncommon in the whole study population (36%), was less common in women than in men (26% vs 41%, P =.001). Multivariable logistic analyses for morbidity and mortality showed female gender to be an independent risk factor. Mitral valve replacement, age, left ventricular dysfunction, New York Heart Association classes III and IV, and association of tricuspid valve disease, diabetes, peripheral vascular disease, and preoperative renal failure were found to be independent risk factors for mortality. CONCLUSION: Female gender is an independent risk factor for combined morbidity and mortality during and after combined valve and coronary bypass surgery. As with isolated coronary artery bypass grafting, women undergoing combined procedures have more premorbid conditions, are more often in heart failure, had an equal incidence of triple vessel disease but received fewer grafts than men, and, therefore, were more frequently incompletely revascularized.     

Transcranial Doppler monitoring during laparoscopic anterior lumbar interbody fusion

We studied the consequences on cerebral hemodynamics of lengthy laparoscopic procedures requiring pneumoperitoneum and head-down positioning. From October 1995 to April 1999, 17 ASA status I or II patients (16 women and 1 man; mean age, 38 yr) were treated with laparoscopic anterior lumbar fusion. Besides standard perioperative monitoring for laparoscopic surgery, the mean blood-flow velocity of both middle cerebral arteries and the pulsatility index were determined by transcranial Doppler ultrasound. Adequate acoustic windows were encountered in 11 of the 17 patients, and the remaining 6 were excluded from the analysis. PaCO(2) and end-tidal CO(2) were maintained within normal limits (<40 mm Hg); ventilation was optimized in all cases. There was a significant increase (P < 0.05) in heart rate and central venous pressure with the change from supine to head-down position in all patients. Transcranial Doppler results for mean middle cerebral artery blood-flow velocity and pulsatility index showed no significant variations at any of the four time points studied during the procedure. There were no technique-related complications, except for moderate postoperative headache in eight patients that resolved with rest and oxygen therapy. We conclude that lengthy laparoscopic procedures in the head-down position performed in otherwise healthy patients do not significantly affect intracranial circulation. IMPLICATIONS: This study assessed the consequences of lengthy laparoscopic surgery with head-down (Trendelenburg) positioning on cerebral blood circulation by transcranial Doppler ultrasound, a noninvasive technique. It is important to investigate whether there are cerebral hemodynamic changes because these may be detrimental to some patients for whom this surgery is considered.     

Functional mu opioid receptors are reduced in the spinal cord dorsal horn of diabetic rats

BACKGROUND: The mechanisms of decreased spinal analgesic potency of morphine in neuropathic pain are not fully known. Agonist-stimulated [35S]GTPgammaS receptor autoradiography has been used to measure receptor activation of G proteins in vitro. Using this technique, we determined changes in the functional mu opioid receptors in the spinal dorsal horn in diabetic rats. METHODS: Rats were rendered diabetic with an intraperitoneal injection of streptozotocin. The lumbar spinal cord was obtained from age-matched normal and diabetic rats 4 weeks after streptozotocin treatment. [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAMGO, 10 microm)-stimulated [35S]GTPgammaS binding was performed in both tissue sections and isolated membranes. RESULTS: The DAMGO-stimulated [35S]GTPgammaS binding in the spinal dorsal horn was significantly reduced (approximately 37%) in diabetic rats compared with normal rats. However, [35S]GTPgammaS bindings in the spinal dorsal horn stimulated by other G protein-coupled receptor agonists, including [D-Pen2,D-Pen5]-enkephalin, R(-)N6-(2-phenylisopropyl)-adenosine, and WIN-55212, were not significantly altered in diabetic rats. The basal [35S]GTPgammaS binding in the spinal dorsal horn was slightly (approximately 13%) but significantly increased in diabetic rats. Western blot analysis revealed no significant difference in the expression of the alpha subunits of G(i) and G(o) proteins in the dorsal spinal cord between normal and diabetic rats. CONCLUSIONS: These data suggest that the functional mu opioid receptors in the spinal cord dorsal horn of diabetic rats are reduced. The impaired functional mu opioid receptors in the spinal cord may constitute one of the mechanisms underlying the reduced spinal analgesic effect of mu opioids in diabetic neuropathic pain.