Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response

Introduction: Optimal preoperative treatment of stage IIB (Pancoast)/III non-small cell lung cancer (NSCLC) remains undetermined and a subject of controversy. The goal of our study is to confirm feasibility and pathological response rates after induction chemoradiation (CRT) in our community-based treatment center. Patients and methods: Patients were selected according to functional and resectability criteria. Induction treatment comprised 3D conformal 4500 cGy radiotherapy delivered to the primary tumor and pathologic hilar and/or mediastinal lymph nodes on CT scan with an extra-margin of 1–1.5 cm. Concurrent chemotherapy regimen was cisplatinum 20 mg/m² d1–d5 and etoposide 50 mg/m² d1–d5, d1–5 d29–33. Within 3–4 weeks after CRT completion, operability was re-assessed accordingly. Surgery was performed 4–6 weeks after CRT completion in patients (pts) deemed resectable. Inoperable pts were referred for a 20–25 Gy boost ±1 extra-cycle of cisplatinum + etoposide. Results: From 1996 to 2005, 107 pts were initially selected for treatment and received induction chemoradiation (stage IIB-Pancoast 18, IIIA 58 and IIIB 31, squamous cell carcinoma 48%, adenocarcinoma 44%, large-cell undifferentiated carcinoma 14%). After preoperative evaluation, 72 pts (67%) had a thoracotomy (pneumonectomy 21, lobectomy 45, bilobectomy 5) and all but one (unresectable tumor) had a macroscopic complete resection. During the 3-month postoperative time, five patients (6.9%) died, four after pneumonectomy (right 3, left 1). The analysis of tumoral samples showed a pathological complete response rate or microscopic residual foci of 39.5%. Median follow-up time was 22.3 months (survivors: 36.8 months), 2-year and 3-year overall survival rates were 55% and 40%, respectively (median = 26.7 months) for all the intention-to-treat population (n = 107), 62% and 51% (median = 36.5 months) for 71 resected pts, 41% and 16% for 36 non-resected pts (median = 19.1 months). On multivariate analysis, surgical resection and tumoral necrosis >50% (or pathological complete response) were the most pertinent predictive factors of the risk of death (hazard ratio = 0.50 and 0.48, p = 0.006 and 0.038, respectively). Conclusion: Surgery was feasible after induction chemoradiation, particularly lobectomy in PS 0–1, stage IIB (Pancoast)/III NSCLC pts but pneumonectomy carries a high risk of postoperative death (particularly, right pneumonectomy). Pathological response to induction chemoradiation was complete in 39.5% of patients and was a significant predictive factor of overall survival.     

Gas emission during laparoscopic colorectal surgery using a bipolar vessel sealing device: A pilot study on four patients

Background  

Dissection during laparoscopic surgery produces smoke containing potentially toxic substances. The aim of the present study was to analyze smoke samples produced during laparoscopic colon surgery using a bipolar vessel sealing device (LigaSure™).     

Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and insulin sensitivity

OBJECTIVE— To ascertain the importance and mechanisms underlying the role of brain glucagon-like peptide (GLP)-1 in the control of metabolic and cardiovascular function. GLP-1 is a gut hormone secreted in response to oral glucose absorption that regulates glucose metabolism and cardiovascular function. GLP-1 is also produced in the brain, where its contribution to central regulation of metabolic and cardiovascular homeostasis remains incompletely understood.RESEARCH DESIGN AND METHODS— Awake free-moving mice were infused with the GLP-1 receptor agonist exendin-4 (Ex4) into the lateral ventricle of the brain in the basal state or during hyperinsulinemic eu-/hyperglycemic clamps. Arterial femoral blood flow, whole-body insulin-stimulated glucose utilization, and heart rates were continuously recorded.RESULTS— A continuous 3-h brain infusion of Ex4 decreased femoral arterial blood flow and whole-body glucose utilization in the awake free-moving mouse clamped in a hyperinsulinemic-hyperglycemic condition, only demonstrating that this effect was strictly glucose dependent. However, the heart rate remained unchanged. The metabolic and vascular effects of Ex4 were markedly attenuated by central infusion of the GLP-1 receptor (GLP-1R) antagonist exendin-9 (Ex9) and totally abolished in GLP-1 receptor knockout mice. A correlation was observed between the metabolic rate and the vascular flow in control and Ex4-infused mice, which disappeared in Ex9 and GLP-1R knockout mice. Moreover, hypothalamic nitric oxide synthase activity and the concentration of reactive oxygen species (ROS) were also reduced in a GLP-1R–dependent manner, whereas the glutathione antioxidant capacity was increased. Central GLP-1 activated vagus nerve activity, and complementation with ROS donor dose-dependently reversed the effect of brain GLP-1 signaling on peripheral blood flow.CONCLUSIONS— Our data demonstrate that central GLP-1 signaling is an essential component of circuits integrating cardiovascular and metabolic responses to hyperglycemia.There is now compelling evidence supporting the interplay between metabolic and vascular diseases (1,2) in which neuronal circuits in the central nervous system seem to play a critical role in orchestrating the control of glucose homeostasis (3). We recently demonstrated that the central infusion of insulin decreased blood pressure and increased arterial blood flow and heart rate through a molecular mechanism depending on the synthesis of nitric oxide in the hypothalamus (4). Importantly, the central regulation of nitric oxide (NO) metabolism affected whole-body glucose utilization (5). This mechanism was impaired during high-fat diet–induced insulin resistance and diabetes and reverted upon central NO supplementation (4). These findings raise the possibility that signals from peripheral tissues, which act on the brain to control glucose metabolism, could also regulate vascular function.Enteroendocrine cells have important roles in regulating energy intake and glucose homeostasis through their actions on peripheral target organs, including the endocrine pancreas. Enteroendocrine cells secrete multiple hormones, including glucagon-like peptide (GLP)-1, which controls pancreatic endocrine secretion (6). GLP-1 is also a neuropeptide synthesized by neurons in the caudal regions of the nucleus of the solitary tract (NTS) (7,8). GLP-1 is released into the hypothalamus and controls food intake, blood pressure, and heart rate (9,10). Whereas most of the glucose-lowering actions of GLP-1 have been attributed to the direct effect of the hormone on the endocrine pancreas, i.e., to stimulation of insulin and inhibition of glucagon secretion, we demonstrated the importance of extra-pancreatic GLP-1 receptor–dependent control of insulin secretion (11) and whole-body glucose distribution (12). The infusion into the brain of the GLP-1 receptor antagonist exendin-9 (Ex9) inhibited insulin secretion induced by gut glucose (11). Conversely, central administration of the GLP-1 receptor agonist exendin-4 (Ex4) augmented intravenous glucose-stimulated insulin secretion to a level similar to that obtained during an intragastric glucose infusion (11). Our data suggested that the absorptive state was associated with the stimulation of the gut-to-brain axis leading to the activation of brain GLP-1 signaling and, consequently, to hyperinsulinemia. During the absorptive state, blood flow redistribution toward mesenteric organs is also observed, which has been proposed to favor nutrient redistribution into the liver (13). Importantly, stimulation of the central GLP-1 receptor increases blood pressure and heart rate and activates autonomic regulatory neurons (8,14,15). However, recently it has been shown that GLP-1 reduced islet blood flow after glucose administration (16). Therefore, the role of brain GLP-1 signaling also in the control of cardiovascular homeostasis remains incompletely understood.We have now pursued the importance of GLP-1 action in the central nervous system for control of cardiovascular function using studies in conscious free-moving mice. After central GLP-1 infusion, we simultaneously recorded femoral arterial blood flow, heart rate, and insulin and glucose sensitivity during hyperinsulinemic-euglycemic or hyperglycemic clamps. We now demonstrate that hypothalamic reactive oxygen and nitrogen species are controlled by brain GLP-1 and are essential for the coordinated regulation of metabolic and cardiovascular function.     

Effects of a suction laryngoscope in a model with simulated severe airway hemorrhage

In severe airway hemorrhage, simultaneous suction and laryngoscopy may render intubation difficult. We built a suction laryngoscope that consists of an adjustable stainless steel-guide tube fixed at the lingual surface of a standard Macintosh laryngoscope blade. Via this steel-guide tube, a large suction catheter can be inserted and positioned exactly to suction pharyngeal blood or vomitus, rendering simultaneous suctioning and laryngoscopy possible. In contrast to previous suction laryngoscopes, our suction catheter has a large lumen, which enables fast suctioning and exact placement by adjusting the steel-guide tube. To assess whether our suction laryngoscope could provide better intubation conditions in comparison to a standard Macintosh laryngoscope in a bleeding airway scenario, 44 medical students intubated a manikin with severe simulated airway hemorrhage using our suction laryngoscope and a standard Macintosh laryngoscope in random order. There was no significant difference in time needed for intubation when using the suction versus the Macintosh laryngoscope (mean +/- SD: 43 +/- 13 vs 52 +/- 31 s; P = 0.07), but the number of esophageal intubations was significantly lower when using the suction laryngoscope [6 of 44 (13.6%) vs 19 of 44 (43.2%); P = 0.004]. In conclusion, when compared with a standard Macintosh laryngoscope, using a suction laryngoscope did not result in more rapid intubation, but significantly decreased the likelihood of esophageal intubations.     

Long-term outcome of forearm flee-flap phalloplasty in the treatment of transsexualism

OBJECTIVE

To assess the long‐term outcome of forearm free‐flap phalloplasty in transsexuals, as obtaining a satisfying neophallus in female‐to‐male transsexuals is a surgical challenge.

PATIENTS AND METHODS

We analysed retrospectively 56 transsexuals who had a phalloplasty using a radial forearm free‐flap in our department from 1986 to 2002. The complication rate was assessed by regular examination. Patient satisfaction was evaluated by a questionnaire about cosmetic aspects, sexual life and overall satisfaction.

RESULTS

The mean follow up was 110 months; 53 of the 56 patients (95%) currently have a neophallus, after a mean of six surgical procedures. Satisfaction was assessed in 53 patients using a specific questionnaire: 51 (93%) of the patients reported that the phalloplasty allowed them to accord their physical appearance with their feeling of masculinity. There were flap complications in 14 patients (25%); three (5%) flaps were lost, with one each due to early haematoma, cellulitis and late arterial thrombosis. The other 11 flap complications were all transitory, e.g. infection, haematomas and vascular thrombosis. There were prosthesis complications in 11 of 38 patients (29%). Moreover, seven of 19 patients (37%) who had a urethroplasty presented with complex strictures and fistulae that led to perineal urethrostomy.

CONCLUSION

Our study shows that phalloplasty with a forearm free‐flap leads to good results in term of flap survival and patient satisfaction. However, there was a high rate of complications. Patients must be clearly informed that the procedure can seldom be achieved in one stage.     

Staged bilateral carotid stenting, an effective strategy in high-risk patients - insights from a prospective multicenter trial

OBJECTIVE: To prospectively evaluate outcomes of high-risk patients undergoing bilateral carotid artery stenting (CAS). METHODS: A total of 747 patients at increased risk for carotid endarterectomy (CEA) were enrolled in a prospective registry at 47 US sites of the Boston Scientific EPI: A Carotid Stenting Trial for Risk Surgical Patients (BEACH) trial. Among them, 78 (10.4%) patients underwent contralateral CAS > 30 days after the primary CAS procedure. Patients were followed at 1, 6, and 12 months, and annually thereafter for 3 years. The primary endpoint was the cumulative incidence of non Q-wave myocardial infarction within 24 hours, periprocedural (相似文献   

Laparoscopic cholecystectomy in cirrhotic patients

Since 1992, laparoscopic cholecystectomy has been the treatment of choice for symptomatic gallstones. The advantages of laparoscopic cholecystectomy for most patients have been extensively published. However, its benefits and successful use in patients with cirrhosis are less well documented. The aim of this study was to determine the efficacy and safety of laparoscopic cholecystectomy in cirrhotic patients. We did a retrospective review of the records of 26 consecutive laparoscopic cholecystectomy procedures performed on cirrhotic patients between January 1992 and September 2000. Twenty-two patients were classified as having Child's class A cirrhosis, and 4 patients were classified as having Child's class B. No patients were classified as having Child's class C cirrhosis. There were 20 men and 6 women, with a mean age of 57 years (range, 37-76). All procedures were completed laparoscopically. There was histologic confirmation of cirrhosis in all patients. The mean operative time was 126 minutes (range, 60-184). The mean estimated blood loss was 110 mL (range, 40-380). Complications occurred in 7 patients (27%). No operative mortality occurred in this study. The mean length of hospital stay was 5 days (range, 3-14). Our results and the results of others show that laparoscopic cholecystectomy in cirrhotic patients seems to be safe in selected Child-Pugh class A and B patients with compensated cirrhosis. Cholecystectomy remains a high-risk procedure in cirrhotic patients, and indications for cholecystectomy should be evaluated carefully. Controlled trials are required to confirm the safety of this procedure, and further studies are also required to evaluate the management of gallbladder disease in patients with Child-Pugh class C cirrhosis.     

Varus and valgus flexion laxity of total knee alignment methods in loaded cadaveric knees.

Both total knee alignment methods, the anatomic and classic, seek to achieve stability in flexion and extension. However, posterior femoral condyle referencing (anatomic alignment) combined with perpendicular tibial resection (classic alignment) results in a 3 degree relative internal rotation of the femoral component with lateral joint opening. The current cadaver study investigated the influence of total knee alignment methods and femoral component malrotation (3 degrees and 6 degrees internal and external malrotation) on femorotibial laxity. Varus and valgus excursion tests were done at 0 degrees, 30 degrees, 60 degrees, and 90 degrees knee flexion under vertical loading conditions of 150 N. None of the alignments produced increased laxity in extension. The largest laxity was found on the varus test at 60 degrees flexion with the femoral component at 6 degrees internal rotation. A 3 degree internal rotation of the femoral component showed increased varus laxity only for the combined alignment method. This finding shows that the femoral component position of the combined alignment method is a 3 degree relative internal malrotation and that an additional internal malrotation may compromise varus stability. Posterior femoral condyle referencing did not provide proper femoral component rotation. A ligament tensor may be helpful in determining femoral component rotation after soft tissue release in extension is performed.