[Awake ECMO therapy in airway stenosis. Bronchoscopic treatment using laser resection]. / Wach-ECMO-Therapie bei Atemwegsstenose. Bronchoskopische Behandlung mithilfe der Laserresektion.

This article presents the case of a 62-year-old patient with cancer in the left upper pulmonary lobe who underwent lobe resection with postoperative respiratory insufficiency. The right upper lobe had already been resected 5 years earlier because of an adenocarcinoma. Prior to the present surgery a computed tomography scan detected a narrow stenosis at the former resection site; however, both pulmonary lobes beyond this stenosis appeared to be sufficiently ventilated. After resection of the left upper lobe attempted extubation was unsuccessful due to insufficient global gas exchange as the stenosis prevented ventilation of the right lung. Bronchoscopy provided evidence of a normal diameter of the bronchus behind the stenosis so both lobes were to be recruited after possible correction of this section. A veno-venous extracorporeal membrane oxygenation device (ECMO) was established as bridging therapy to attain normal gas exchange. As the patient showed no muscle weakness and was cooperative, extubation was performed and spontaneous breathing occurred without any support while still under ECMO treatment. The stenosis was reduced by bronchoscopic laser resection within seven consecutive sessions. Each of these surgeries was conducted with the patient under general anesthesia with oral intubation and jet ventilation in combination with the ECMO. The patient was extubated after each treatment session and weaned from ECMO after the final resection within 2 days. This case demonstrates the use of ECMO in combination with surgical procedures in a spontaneously breathing patient as a causal therapy and option for selected patients to prevent complications from long-term ventilation.

[Video-assisted thoracoscopic (VATS) sublobar anatomic resections for lung cancer]. / Videoassistierte thorakoskopische (VATS) sublobäre anatomische Resektionen beim Lungenkarzinom.

Pulmonary segmentectomy implies the removal of one or more anatomic units of the lung. It requires dissection of the segmental bronchus and artery and identification of the intersegmental vein, which should be respected. Benign lesions, solitary pulmonary nodules, pulmonary adenocarcinoma in situ and T1a lung cancer are possible indications. The VATS approach for segmentectomies is technically challenging and differs slightly from the conventional open one. Its combination of minimal invasiveness with a maximum of lung parenchyma preservation provides a surgical treatment option for NSCLC patients with little pulmonary reserve. Data on the oncologic outcome after VATS segmentectomy are inconclusive as yet.

Genetic differences in Native Americans and tacrolimus dosing after kidney transplantation.

Tacrolimus pharmacokinetics vary due to single nucleotide polymorphisms (SNPs) in metabolizing enzymes and membrane transporters that alter drug elimination. Clinically we observed that Native Americans require lower dosages of tacrolimus to attain trough levels similar to Caucasians. We previously demonstrated that Native Americans have decreased oral clearance of tacrolimus, suggesting that Native Americans may have more variant SNPs and, therefore, altered tacrolimus pharmacokinetic parameters. We conducted 12-hour pharmacokinetic studies on 24 adult Native American kidney transplant recipients on stable doses of tacrolimus for at least 1 month posttransplantation. Twenty-four Caucasian kidney transplant recipients were compared as controls. SNPs encoding the genes for the enzymes (CYP3A4, CYP3A5) and transporters (ABCB1, BCRP, and MRP1) were typed using TaqMan. The mean daily tacrolimus dose in the Native Americans was 0.03 ± 0.02 compared with the Caucasians 0.5 ± 0.3 (mg/kg/d; P = .002), with no significant differences in trough levels, (6.7 ± 3.1 vs 7.4 ± 2.1 ng/dL; P = .4). Many Native Americans, but not Caucasians, demonstrated the 3/*3 - C3435T CC and the *3/*3 -G2677T GG genotype combination previously associated with low tacrolimus dosing. Native Americans required significantly lower tacrolimus doses than Caucasians to achieve similar tacrolimus trough levels, in part due to lower tacrolimus clearance from decreased drug metabolism and excretion.

Outcomes after simultaneous pancreas and kidney transplantation and the discriminative ability of the C-peptide measurement pretransplant among type 1 and type 2 diabetes mellitus.

BACKGROUND: Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease. METHODS: To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m(2) and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT. RESULTS: Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM. CONCLUSION: SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.

Laparoscopic partial posterior (Toupet) fundoplication improves esophageal bolus propagation on scintigraphy.

BACKGROUND: Impaired esophageal clearance is important in the pathogenesis of gastroesophageal reflux disease (GERD). It is unknown whether esophageal clearance improves following antireflux surgery. The aim of this study was to investigate the effect of laparoscopic Nissen fundoplication (NF), laparoscopic partial posterior (Toupet) fundoplication (PPF) or medical therapy on esophageal clearance. METHODS: This was a prospective nonrandomized crossover study. Sixty patients were evaluated with endoscopy, esophageal manometry, radionuclide scanning of esophageal emptying, and assessment of symptoms prior to surgery or medical therapy and 6 months after treatment. In 20 GERD patients with normal esophageal peristalsis an NF was performed, in 20 patients with impaired esophageal peristalsis a PPF was chosen, and 20 patients received proton-pump inhibitor (PPI) treatment. RESULTS: On endoscopy, esophagitis had resolved in all patients after surgery; two patients with medical therapy still had esophagitis. On manometry, a significant improvement of lower esophageal sphincter competence was seen in both surgical groups. LES relaxation was complete after PPF, but incomplete after NF. Esophageal peristalsis did not improve after medical therapy, was significantly improved after PPF, but had worsened after NF. On scintigraphic esophageal emptying for solid meals, there was no improvement after medical therapy but a significant improvement after PPF. A significant deterioration of esophageal emptying was observed after NF. There was a strong correlation between scintigraphic and manometric evaluation of peristalsis preoperatively (r(s) = -0.87, p < 0.05) and postoperatively (r(s) = -0.82, p < 0.05). There was no change in dysphagia after medical therapy and after NF but a significant improvement after PPF. Globus sensation was significantly improved after PPF but did not change after medical therapy or NF. Postprandial bloating and inability to belch were significantly more common after NF than after PPF. CONCLUSION: Laparoscopic partial posterior (Toupet) fundoplication can restore a preoperatively defective esophageal bolus propagation on scintigraphy with the same antireflux effect as the laparoscopic Nissen fundoplication, but with lower side-effects.

Neuropathic pain after femoropopliteal bypass surgery.

OBJECTIVE: This retrospective study was performed to investigate prolonged postoperative pain in the area of the proximal or distal scar or the bypass tunnel after femoropopliteal bypass surgery to treat symptomatic peripheral arterial disease. PATIENTS AND METHODS: Ninety-three patients with peripheral arterial disease who underwent femoropopliteal bypass surgery between January 2000 and December 2002 were included in the study. The short-form McGill Pain Questionnaire was used to score pain. Ultrasound examination of the soft tissue around the graft was performed to exclude other pathologic conditions responsible for pain, such as inflammatory processes, perigraft reactions, swollen lymph nodes, and hematomas. RESULTS: Pain in at least one scar existed in 22 patients on average 13.9 +/- 9.8 months after surgery. In 10 patients pain existed simultaneously along the inguinal scar and the above-knee or below-knee scar. Pain along the bypass tunnel was experienced by seven patients. Most patients had mild to moderate pain. The mean numeric ranking score of pain severity in patients with pain was 4.2 +/- 2.3. The occurrence of prolonged postoperative pain was not associated with age, gender, diabetes, indication for surgery, material or type of bypass, number of preceding operations, or postoperative wound complications. Only follow-up time after femoropopliteal bypass surgery tended to be lower in patients with pain compared with those without pain. CONCLUSION: Prolonged postoperative neuropathic pain along the distal and proximal incision or the bypass tunnel exists in one fourth of patients after femoropopliteal bypass surgery. Patients should be informed of this kind of complication before surgery. The results of our study justify further investigations of the origin and treatment of this pain, to find effective methods to reduce the incidence of prolonged postoperative pain after femoropopliteal bypass surgery.

First experiences with the da Vinci operating robot in thoracic surgery.

OBJECTIVES: The da Vinci surgical robotic system was purchased at our institution in June 2001. The aim of this trial was to evaluate the applicability of the da Vinci operation robot for general thoracic procedures. METHODS: The da Vinci surgical system consists of a console connected to a surgical arm cart, a manipulator unit with two instrument arms and a central arm to guide the endoscope. The surgical instruments are introduced via special ports and attached to the arms of the robot. The surgeon, sitting at the console, triggers highly sensitive motion sensors that transfer the surgeon's movements to the tip of the instruments. The so-called 'EndoWrist technology' offers seven degrees of movement, thus exceeding the capacity of a surgeon's hand in open surgery. We evaluated the role of the robot for several thoracic procedures such as thymectomies, fundoplications, esophageal dissections, resection of mediastinal masses and a pulmonary lobectomy. RESULTS: A total of 10 thymectomies, 16 fundoplications, 4 esophageal dissections, 5 extirpations of benign mediastinal masses and 1 right lower lobectomy was performed with the robot. One resection of a paravertebral neurogenic tumor had to be converted due to surgical problems. A lesion to a left recurrent laryngeal nerve caused transient hoarseness after the extirpation of an ectopic parathyroid in the aortopulmonary window in one patient. The postoperative courses were uneventful and patients were discharged between postoperative days 3 and 8 (with the exception of patients who underwent dissection for esophageal cancer and the patient with conversion to an open access). CONCLUSIONS: Advanced general thoracic procedures can be performed safely with the da Vinci robot allowing precise dissection in remote and difficult-to-reach areas. This benefit becomes evident most elegantly in thymectomies, which at our institution have become a routine procedure with the robot. The rigid anatomy of the chest seems to be an ideal condition for robotic surgery. A major limitation for robotic surgery is the lack of more appropriate instruments. This disadvantage becomes most evident in pulmonary lobectomies.

Robot-assisted mediastinal parathyroidectomy.

We report the first case of robot-assisted thoracoscopic resection of a mediastinal parathyroid adenoma in the aorto-pulmonary window. Intervention planning was based on preoperative CT-MIBI image fusion, a new imaging modality that enabled reliable and precise localization of the parathyroid. The technique consists of taking MIBI-SPECT and CT separately, using a fixation unit that provides reproducible positioning of the patients head and neck. The data sets are then superimposed upon each other using special software. After the localization process, a minimally invasive operation was performed using the DaVinci operating robot. The procedure proved not only to be feasible but also safe and not time-consuming. The postoperative course was uneventful, and the patient was discharged 4 days postoperatively. Compared to conventional thoracoscopic surgery, the robotic operating system provides better visualization of the operating field and facilitates the movement of the instruments. Precise preoperative imaging enables the careful planning of robot-assisted surgery for ectopic parathyroids located at relatively inaccessible regions such as the anterior mediastinum.

Robot-assisted laparoscopic partial posterior fundoplication with the DaVinci system: initial experiences and technical aspects.

BACKGROUND: This pilot study evaluated the role of the DaVinci operation robot for laparoscopic antireflux surgery. PATIENTS AND METHODS: A robot-assisted laparoscopic Toupet-fundoplication was performed on nine consecutive patients with severe gastroesophageal reflux disease using the DaVinci robot system. The operative procedure was performed in the same way as for the conventional laparoscopic procedure. Clinical assessment and endoscopic and manometric follow-up investigations were performed 6 months after surgery in six of the patients. RESULTS: The mean robotic operative time was 173 min (120-235). A mean of 25 min (12-45) was required to establish the pneumoperitoneum, to set the trocars, and to place the robot arms. There were no intraoperative complications. Six months after surgery none of the patients suffered from reflux symptoms and none of the patients had acute esophagitis. Postoperatively one patient complained of mild transient dysphagia. However, persistent dysphagia was not found in any of the patients. One further patient complained of mild bloating. No other side effects occurred. Manometrically there was a significant improvement in the function of the lower esophageal sphincter. CONCLUSIONS: The robot-assisted partial posterior fundoplication is a safe procedure and provides a high-quality three-dimensional camera image that is superior to that with the conventional laparoscopic device. The handling of the instruments is precise, and intracorporeal suturing and knot tying is much easier than without the robotic technique. The procedure allows for an accurate approximation of the hiatal crura and for precise construction of the fundic wrap. However, robotic surgery is expensive and the setup of the system is time consuming at present.

The role of surgery in the treatment of carcinoma of the pancreatic head.

Surgery in pancreatic carcinoma has changed within the last two decades. One of two patients nowadays can be treated without operation. Palliative surgical procedures rarely have to be done. Actually jaundice in patients with unresectable pancreatic cancer is treated by stenting instead of performing the classic biliodigestive anastomosis. In our department the rate of patients suitable for radical surgery lays constantly between 20 and 25% within the last decades. However, this high percentage of potentially curable patients may be due to a "positive patient selection" referred to a University hospital. In accordance with international publications it seems to be certain, that surgical therapy for pancreatic cancer has reached its limitations. Due to these open questions, working on pancreatic cancer will remain one of the most challenging but worthwhile features for generations of surgeons. (Tab. 4, Fig. 7, Ref. 16).

Flow-mediated, endothelium-dependent vasodilatation is impaired in male body builders taking anabolic-androgenic steroids.

Self-administration of anabolic-androgenic steroids to increase muscular strength and lean body mass has been used widely among athletes. Flow mediated dilatation (FMD) determined by ultrasound of the brachial artery is accepted as both an in vivo index of endothelial function and an indicator for future atherosclerosis. FMD was calculated in 20 male non-smoking body builders in different phases of their training cycle and in six male non-smoking control athletes. Ultrasound studies of the brachial artery were performed according to the protocol of Celermajer et al. Of the entire training cycle, work-out phase was training phase without actual intake of anabolic-androgenic steroids over 8 weeks; build-up phase included actual intake of anabolic-androgenic steroids; and competition phase consisted of 8 weeks post intake of anabolic-androgenic steroids. Baseline characteristics did not differ between body builder groups except for a higher weight in competition phase body builders. Hormonal analysis revealed suppressed luteinizing hormone and follicle stimulating hormone levels in build-up phase body builders. The lipid profiles showed a marked reduction of HDL-C in build-up phase body builders. FMD was reduced in body builders of all phases when compared to control athletes (work-out phase: 2.5+/-2.7%; build-up phase: 2.1+/-3.0%; competition phase: 0.4+/-2.9% vs. 10.9+/-4.4%, P<0.05 by pairwise comparison using Scheffe's test for work-out phase, build-up phase and competition phase vs. control athletes). The glyceryl trinitrate-induced vasodilatation was diminished, though not statistically significantly, in body builders when compared with control athletes. The differences in FMD persisted after adjustment for vessel size. Our data indicate that intake of anabolic-androgenic steroids is associated with both an atherogenic blood lipid profile and endothelial dysfunction and thus may pose an increased risk of atherosclerosis.

Hyperhomocysteinemia in bodybuilders taking anabolic steroids.

Background: Hyperhomocysteinemia has been accepted as an independent risk factor for atherosclerosis and atherothrombosis. In recent years, several reports have appeared in the literature linking the use of anabolic steroids with acute vascular events in bodybuilders. In this study, we investigated whether hyperhomocysteinemia could contribute to the high vascular risk in bodybuilders taking anabolic steroids. Methods and results: Twenty-three bodybuilders in different phases of their training cycle and six control athletes participated in our study. Anthropomorphic measures displayed a higher body mass index for bodybuilders in the competition phase than for bodybuilders in the work-out and build-up phases, and for control athletes. Homocysteine levels were 8.7+/-1.6 µmol/l (mean+/-S.D.) in control athletes, 8.5+/-2.8 µmol/l in work-out phase bodybuilders, and 8.3+/-1.5 µmol/l in competition phase bodybuilders, but 11.9+/-3.1 µmol/l in build-up phase bodybuilders (P<0.05 for build-up phase bodybuilders vs. control athletes, work-out phase bodybuilders, and competition phase bodybuilders, respectively). Vitamin B12 and folate levels did not differ significantly between the four groups. Conclusion: Our study shows that intake of anabolic steroids, as used typically by bodybuilders in the build-up phase, induces acute hyperhomocysteinemia and is likely to initiate an additional, potentially atherothrombotic mechanism in this group of athletes.

Fetal leptin and insulin levels only correlate inlarge-for-gestational age infants.

OBJECTIVE: To determine whether fetal leptin levels correlate with fetal weight and whether such correlation is direct or indirect via insulin or human placental lactogen (hPL), respectively. DESIGN: Cross-sectional study of offspring at term (n=175) with over-representation of large-for-gestational age (LGA; n=70) and small-for-gestational age (SGA; n=23) cases in a population of Caucasian women with no pregnancy pathology. METHODS: Fetal cord blood was collected after delivery. In several cases (n=62) paired mother-fetus blood samples were obtained. Leptin, insulin and hPL levels were measured by RIA. Anthropometric data (birth weight, body mass index, placental weight) were recorded. RESULTS AND CONCLUSIONS: Maternal insulin, hPL and leptin levels were higher than fetal concentrations. Cord blood leptin levels positively correlated with the anthropometric data with stronger correlations in female (0.54

Leptin receptor in human term placenta: in situ hybridization and immunohistochemical localization.

In the present study, we investigated the expression and localization of leptin receptors in human term placentae. On human term placenta tissue slices, digoxigenin-UTP labelled RNA-probe detected the long form of the leptin receptor ObR(L)mRNA in syncytiotrophoblasts of the villi, whereas the haematological subtype of the leptin receptor ObR/B219.1 was detected in blood cells of the intervillous space and fetal vessels. Immunohistochemistry, with two polyclonal antibodies to the N-terminus recognizing ObR(L)and ObR(S)of the leptin receptors and one to the C-terminus recognizing the long form of the leptin receptor ObR(L), localized leptin receptor protein at the apical membrane of the syncytiotrophoblasts. Our results show that the long form of the leptin receptor ObR(L)is expressed in human term placentae. We localized the long form of leptin receptor mRNA to the cytoplasm of syncytiotrophoblasts and leptin receptor proteins in human term placentae to the apical membrane of syncytiotrophoblasts. We conclude that in term placentae, leptin could mediate a growth promoting effect in the fetoplacental unit through the long form of the leptin receptor localized in the syncytiotrophoblasts. In contrast, the haematological subtype of the leptin receptor is not expressed in placental cells, but solely by blood cells in the intervillous space and fetal vessels.

Cholesteryl ester transfer protein gene expression is not specifically regulated by CCAAT/enhancer-binding protein in HepG2-cells.

Cholesteryl ester transfer protein (CETP) mediates the exchange of neutral lipids among plasma lipoproteins and is expressed predominantly in liver and intestine. In band shift assays employing nuclear extracts of HepG2 cells we identified C/EBPbeta as the predominant C/EBP isoform involved in binding to the C/EBP consensus sequence within the 5' upstream region of the CETP gene. This was demonstrated by supershift experiments using antibodies specific for C/EBPalpha, C/EBPbeta and C/EBPdelta and an oligonucleotide containing a single point mutation (CAAT-->CTAT) in this site. Expression of a CETP promoter-fragment/luciferase construct in transiently transfected HepG2 and CaCo-2 cells and enhancement of promoter activity by co-transfection with human C/EBPalpha in HepG2 cells could be influenced neither by the mutation in the consensus sequence nor by elimination of this site together with a second potential binding site for C/EBP. Furthermore, transfection of HepG2 with human C/EBPalpha did not influence the synthesis of CETP by these cells. Our results indicate that the expression of C/EBP in HepG2 cells is not able (1) to influence specifically the expression of a transfected CETP promoter dependent reporter through binding to C/EBP sites in the promoter region and (2) to significantly enhance expression of the endogenous CETP gene.

[Leptin--an interim evaluation]. / Leptin--eine Zwischenbilanz.

The discovery of leptin, the product of the obese (ob)-gene, has broadened the horizons of research on energy balance. This hormone, produced and secreted by adipose tissue and some placental cells, finds its way to the hypothalamus, where it binds to the leptin receptors and signals satiety through the neuroendocrine axis. The fact that adipose tissue is not merely a storage depot, but also an important endocrine tissue, has revived the interest in the "lipostatic" theory of body fat regulation and has initiated many research efforts in the field of obesity, anorexia nervosa, bulimia, reproduction and haematology.

Detection of Chlamydia trachomatis antigens in male urethral swabs and urines with a microparticle enzyme immunoassay.

BACKGROUND AND OBJECTIVES: More information is needed on the natural history of Chlamydia trachomatis urethral infections in men. Newer assays for detecting antigens in male first void urine and urethral swabs identify patients for control programs. A new microparticle enzyme immunoassay from Abbott Laboratories called IMX Select Chlamydia was evaluated and compared with culture and an expanded gold standard for sensitivity and specificity. STUDY DESIGN: Paired samples of first void urine and two urethral swabs were tested from 230 men, 73% of whom had symptoms of urethritis. Both specimen types were tested with IMX Select, the other swab was cultured, and a part of the first void urine was tested by Chlamydiazyme enzyme immunoassay. Performance calculations were made against urethral culture and an expanded gold standard that included direct fluorescent staining of discordant specimens by Microtrak. RESULTS: Compared with urethral swab culture, the IMX Select test performed on urethral swabs and first void urine had sensitivities of 93.8% and 81.3%, and specificities of 95.2% and 95.7%, respectively. Calculations of sensitivity and specificity based on the expanded gold standard were: IMX Select on urethral swabs, 88.5% and 99.4%; IMX Select on first void urine, 80.8% and 100%; Chlamydiazyme after blocking confirmation on first void urine, 73.1% and 100%; culture on urethral swabs, 61.5% and 100%. CONCLUSION: This IMX Select Chlamydia enzyme immunoassay, which generates laboratory results within 2 hours, performed better than culture and an established enzyme immunoassay on male urethral swabs. The experimental first void urine protocol showed promise for noninvasive male testing.