[Recommendations for training courses in bronchoscopy]. / Empfehlungen zu Trainingskursen in der Bronchoskopie.

Bronchoscopic training courses are an essential part of the education in bronchoscopy for all kinds of specialisations and professions performing such investigations. All aspects of the application should be mentioned during a course. These recommendations are necessary because the number of bronchoscopies performed in the last years has increased due to the increasing number of patients, improved equipment and better availability. Courses should provide the basic knowledge including main points of indications, preconditions for the procedure and decisions of consequence after bronchoscopy. Participants should be trained in the skills of correct handling and performing flexible bronchoscopies in training dummies. Necessary competence requirements on the course instructor are adequate professional qualifications, paedagogic skills and the availability of appropriate teaching material. Quality assurance of the course should be achieved by consequent evaluation. A widely spread field of bronchoscopic applications can improve patient care in many medical specialisations.

EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration.

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular-pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARbeta genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes.

[Endobronchial ultrasound for diagnosis of the mediastinum]. / Endobronchialer Ultraschall zur Diagnostik im Mediastinum.

The development of endobronchial ultrasound (EBUS) is one of the most important advances in bronchoscopy in recent years. Two different techniques are available which improve sonographic diagnostics of the mediastinum and staging in patients with lung and non-lung cancer. Radial EBUS and the technique of ultrasound-controlled transbronchial needle aspiration (TBNA) are now routine practice in many pulmonary centers. Their clinical application and diagnostic benefit have been established in many studies comparing them with conventional radiologic methods and other diagnostic procedures. Endobronchial ultrasound as a diagnostic tool is expected to gain importance in the near future. Especially the method combining EBUS and TBNA may replace more invasive methods such as mediastinoscopy for evaluating patients with unknown mediastinal lesions or for staging patients with lung cancer.

Lactate down-regulates cellular poly(ADP-ribose) formation in cultured human skin fibroblasts.

BACKGROUND: Polyadenosine diphosphate-ribose (poly(ADP-ribose)) is a nuclear polymer which is derived from nicotinamide adenine dinucleotide (NAD(+)) catalysed by poly(ADP-ribose) polymerase 1 (PARP-1). Aside from the well known role of poly(ADP-ribosyl)ation (pADPR) in DNA repair, pADPR is also involved in other cellular processes such as apoptosis and gene expression. However, the factors that regulate the level of pADPR are not fully elucidated. In view of the fact that healing wounds contain high concentrations of lactate (10-15 mM) and exogenous lactate reduce the NAD(+) pool in cultured fibroblasts, we propose that high lactate lowers the level of nuclear pADPR. MATERIALS AND METHODS: Neonatal human dermal fibroblasts (NHDF) were plated to subconfluence and allowed to adhere. Cells were treated with 15 mM l-lactate and pADPR production was assessed by immunofluorescence analysis using 10H antibody. Difference in pADPR production was determined by calculation of positively stained cells compared to total cell numbers. Inhibition of PARP activity was tested by treatment with 100 microM 3-aminobenzamide (3-AB). Specificity of the lactate effect on pADPR synthesis was verified by using the analogue d-lactate. The contents of nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) in lactated and non-lactated cell cultures were quantified by the enzymatic cyclic assay. RESULTS: We found that exogenous l-lactate (15 mM) can significantly depress pADPR content in cultured fibroblasts. PARP-1 activity was inhibited by 3-AB and analogue d-lactate showed no effect on pADPR synthesis. NAD(+)/NADH ratio was significantly lowered in lactated compared to non-lactated cell culture. CONCLUSIONS: Exogenous l-lactate (15 mM) can depress pADPR content in cultured fibroblasts. In view of the fact that healing wounds contain such high concentrations of lactate, we propose that down regulation of pADPR is associated with elevated tissue repair via pADPR dependent gene expression. This observation is important in understanding the stimulation of lactate-mediated protein expression during wound healing.

Endobronchial ultrasound-guided transbronchial lung biopsy in fluoroscopically invisible solitary pulmonary nodules: a prospective trial.

STUDY OBJECTIVES: Transbronchial biopsy (TBBX) for solitary pulmonary nodules (SPNs) is usually performed under fluoroscopic guidance, but the diagnostic yield depends on lesion size and varies widely. Nodules < 3 cm frequently cannot be visualized fluoroscopically. An alternative guidance technique, endobronchial ultrasound (EBUS), also allows visualization of pulmonary nodules. This study assessed the diagnostic yield of EBUS-guided TBBX in fluoroscopically invisible SPNs. DESIGN: The study was a prospective trial using a crossover design. PATIENTS AND METHODS: All patients with SPNs and indications for bronchoscopy were included in the study. An EBUS-guided examination was performed in patients with fluoroscopically invisible nodules. The EBUS probe was introduced through a guide catheter into the presumed segment. If a typical ultrasonic picture of solid tissue could be seen, the probe was removed and the catheter left in place. The biopsy forceps were introduced and specimens taken. RESULTS: One hundred thirty-eight consecutive patients with SPNs were examined. Of those, 54 patients presented with SPNs that could not be visualized with fluoroscopy. The mean diameter of the nodules was 2.2 cm. In 48 patients (89%), the lesion was localized with EBUS, and in 38 patients (70%) the biopsy established the diagnosis. The 16 patients with undiagnosed SPNs were referred for surgical biopsy; 10 of those lesions were malignant and 6 were benign. The diagnosis in nine patients (17%) saved the patients from having to undergo a surgical procedure. The only complication was a pneumothorax in one patient. CONCLUSIONS: EBUS-guided TBBX is a safe and very effective method for SPNs that cannot be visualized by fluoroscopy. The procedure may increase the yield of endoscopic biopsy in patients with these nodules and avert the need for surgical procedures.

Long-term outcome of conservative treatment in patients with diverticulitis of the sigmoid colon.

INTRODUCTION: The indication for surgery after conservative treatment of acute diverticulitis is still under debate. This is partly as a result of limited data on the outcome of conservative management in the long run. We therefore aimed to determine the long-term results of conservative treatment for acute diverticulitis. METHODS: The records of all patients treated at our institution for diverticulitis between 1985 and 1991 were reviewed (n=363, median age 64 years, range 29-93). Patients who received conservative treatment were interviewed in 1996 and 2002 [follow-up time 7 years 2 months (range 58-127 months) and 13 years 4 months (range 130-196 months). RESULTS: A total of 252 patients (69%) were treated conservatively, whereas 111 (31%) were operated on. At the first follow-up, 85 patients treated conservatively had died, one of them from bleeding diverticula. A recurrence of symptoms was reported by 78 of the remaining 167 patients, and 13 underwent surgery. At the second follow-up, one patient had died from sepsis after perforation during another episode of diverticulitis. Thirty-one of the 85 patients interviewed reported symptoms and 12 had been operated on. In summary, at the second follow-up interview, 34% of patients treated initially had had a recurrence and 10% had undergone surgery. No predictive factors for the recurrence of symptoms or later surgery could be determined. CONCLUSION: Despite a high rate of recurrences after conservative treatment of acute diverticulitis, lethal complications are rare. Surgery should thus mainly be undertaken to achieve relief of symptoms rather than to prevent death from complications.

Encapsulation of islets in rough surface, hydroxymethylated polysulfone capillaries stimulates VEGF release and promotes vascularization after transplantation.

The transplantation of encapsulated islets of Langerhans is one approach to treat type 1 diabetes without the need of lifelong immunosuppression. Capillaries have been used for macroencapsulation because they have a favorable surface-to-volume ratio and because they can be refilled. It is unclear at present whether the outer surface of such capillaries should be smooth to prevent, or rough to promote, cell adhesions. In this study we tested a new capillary made of modified polysulfone (MWCO: 50 kDa) with a rough, open-porous outer surface for islet transplantation. Compared with free-floating islets, encapsulation of freshly isolated rat islets affected neither the kinetics nor the efficiency of glucose-induced insulin release in perifusion experiments. Free-floating islets maintained insulin secretion during cell culture but encapsulated islets gradually lost their glucose responsiveness and released VEGF. This indicated hypoxia in the capillary lumen. Transplantation of encapsulated rat islets into diabetic rats significantly reduced blood glucose concentrations from the first week of implantation. This hypoglycaemic effect persisted until explantation 4 weeks later. Transplantation of encapsulated porcine islets into diabetic rats reduced blood glucose concentrations depending on the islet purity. With semipurified islets a transient reduction of blood glucose concentrations was observed (2, 8, 18, 18 days) whereas with highly purified islets a sustained normoglycaemia was achieved (more than 28 days). Explanted capillaries containing rat islets were covered with blood vessels. Vascularization was also observed on capillaries containing porcine islets that were explanted from normoglycaemic rats. In contrast, on capillaries containing porcine islets that were explanted from hyperglycemic rats a fibrous capsule and lymphocyte accumulations were observed. No vascularization on the surface of transplanted capillaries was observed in the absence of islets. In conclusion, encapsulated islets can release VEGF, which appears to be an important signal for the vascularization of the capillary material. The rough, open-porous outer surface of the polysulfone capillary provides a site well suited for vascular tissue formation and may allow a prolonged islet function after transplantation.

Encapsulation of Islets in Rough Surface, Hydroxymethylated Polysulfone Capillaries Stimulates VEGF Release and Promotes Vascularization after Transplantation.

The transplantation of encapsulated islets of Langerhans is one approach to treat type 1 diabetes without the need of lifelong immunosuppression. Capillaries have been used for macroencapsulation because they have a favorable surface-to-volume ratio and because they can be refilled. It is unclear at present whether the outer surface of such capillaries should be smooth to prevent, or rough to promote, cell adhesions. In this study we tested a new capillary made of modified polysulfone (MWCO: 50 kDa) with a rough, open-porous outer surface for islet transplantation. Compared with free-floating islets, encapsulation of freshly isolated rat islets affected neither the kinetics nor the efficiency of glucose-induced insulin release in perifusion experiments. Free-floating islets maintained insulin secretion during cell culture but encapsulated islets gradually lost their glucose responsiveness and released VEGF. This indicated hypoxia in the capillary lumen. Transplantation of encapsulated rat islets into diabetic rats significantly reduced blood glucose concentrations from the first week of implantation. This hypoglycaemic effect persisted until explantation 4 weeks later. Transplantation of encapsulated porcine islets into diabetic rats reduced blood glucose concentrations depending on the islet purity. With semipurified islets a transient reduction of blood glucose concentrations was observed (2, 8, 18, 18 days) whereas with highly purified islets a sustained normoglycaemia was achieved (more than 28 days). Explanted capillaries containing rat islets were covered with blood vessels. Vascularization was also observed on capillaries containing porcine islets that were explanted from normoglycaemic rats. In contrast, on capillaries containing porcine islets that were explanted from hyperglycemic rats a fibrous capsule and lymphocyte accumulations were observed. No vascularization on the surface of transplanted capillaries was observed in the absence of islets. In conclusion, encapsulated islets can release VEGF, which appears to be an important signal for the vascularization of the capillary material. The rough, open-porous outer surface of the polysulfone capillary provides a site well suited for vascular tissue formation and may allow a prolonged islet function after transplantation.

[Design and use of patient pathways in general surgery]. / Entwicklung und Einsatz von Patientenpfaden in der Allgemeinchirurgie.

BACKGROUND: Clinical pathways are a new initiative intended to reduce costs while maintaining or even improving the quality of care. Based on treatment guidelines, patient pathways display an optimal sequence of staff actions in the preoperative, operative, and postoperative in- and outpatient treatment. METHODS: In this study, patient pathways were developed for selected elective general surgical disease entities following a new modular approach. All elements of care and their direct costs to the hospital were identified. Multidisciplinary teams of physicians, nurses, and administrative staff constructed and implemented the patient pathways. RESULTS: In the 1-year pilot phase, we developed and implemented 7 pathways with 16 subpathways: open herniorrhaphy, laparoscopic cholecystectomy and fundoplication, thyroidectomy, surgical treatment of diverticulitis and colon carcinoma and kidney transplantation. CONCLUSIONS: Patient pathways combine the management of care, hospital processes, and costs in a new integrated concept. Patient pathways streamline and standardize care, facilitate communication, and contribute to cost control efforts.

[Possible interventions in impaired wound healing]. / Korrekturmöglichkeiten der gestörten Wundheilung.

Chronic wounds are long-term results of various diseases. Evaluation and therapy of the underlying disorder must be the first goal of a comprehensive wound care protocol. Treatment of local (i.e. wound infection, necrosis, or foreign body) or systemic (i.e. diabetes, immunosuppression, or patient compliance) disturbing factors is the second major step for appropriate wound care. The third major point is wound bed preparation (i.e. debridement, moist wound dressings, or VAC therapy), and wound stimulation. After appropriate wound bed preparation, wounds can be closed by plastic surgery or wound stimulation through various agents (i.e. protease inhibitors, growth factors, or tissue engineering).

[Endobronchial ultrasound in bronchial carcinoma]. / Endobronchialer Ultraschall beim Bronchialkarzinom.

Conventional imaging procedures proved to be insufficient for staging of lung cancer especially with respect of N-stage, infiltration of mediastinal structures and early lung cancer. As also the view of the endoscopist is restricted we developed the new method of endobronchial ultrasonography (EBUS) as adjunct to conventional bronchoscopy. The initial technical problems were solved by development of a balloon catheter for application of miniaturized 20 MHz probes. EBUS is a new technology that can be easily applied and is well tolerated. It improves the results of bronchoscopy in addition to conventional diagnostic procedures. Further developments will be made in future to improve the application of ultrasound in chest medicine.

Treatment of advanced rectal cancer in a patient after combined pancreas-kidney transplantation.

BACKGROUND: Organ transplantation is a standard procedure today. Due to immunosuppressive drugs and increasing survival after organ transplantation, patients with transplanted organs carry an increased risk of developing malignant tumours. Accordingly, more patients with malignant tumours after transplantation will be faced by general or oncology surgeons. We report the case of a 48-year-old patient with advanced rectal cancer 6.5 years after pancreas-kidney-transplantation for type I diabetes. METHOD: The patient was treated with neo-adjuvant radio-chemotherapy, followed by low anterior rectal resection with total mesorectal excision. Consecutively, a solitary hepatic metastasis, a solitary pulmonary metastasis and a chest wall metastasis were resected over the course of 13 months. RESULT: The patient eventually died of metastasized cancer 32 months after therapy had been initiated, his organ grafts functioning well until his death. CONCLUSION: Our case report provides evidence that transplantation patients should receive standard oncology treatment, including neo-adjuvant treatment, so long as their general condition and organ graft functions allow us to do so, although a higher degree of morbidity might be encountered.

Autofluorescence bronchoscopy--a comparison of two systems (LIFE and D-Light).

BACKGROUND: Autofluorescense (AF) bronchoscopy is an established method to detect dysplasia and carcinoma in situ (CIS). Several different systems are currently available. OBJECTIVES: This study aimed to directly compare the LIFE system (Xillix Technologies, Vancouver, Canada) and the D-light system (Storz, Tuttlingen, Germany). METHODS: In a prospective study performed between May 1999 and October 2000, we examined patients with risk factors for lung cancer that underwent bronchoscopy with both (LIFE and D-light) systems in a crossover design. The findings were classified into normal, abnormal and suspicious lesions by independent investigators and then compared. RESULTS: This study comprised 332 patients (220 males, 112 females, mean age 62.7 years, range 40-85); 1,117 biopsies were studied (mean biopsy rate 3.4/patient). In 817 biopsies, mucosal areas were classified as normal with respect to control biopsy specimens, 113 as abnormal and 187 as suspicious using AF bronchoscopy. The histological examination showed normal tissue in 850 cases, in 55 cases scarring or inflammation, in 62 meta- or dysplasias, in 11 carcinomas in situ and in 127 invasive tumors. In only 5 cases, classifications were found to be different between the two systems (2 normal, 2 dysplasias, 1 invasive tumor). The mean time for the LIFE system examination amounted to 11.7 min (range 6.2-19.5) and for the D-light system to 7.4 min (range 4.3-11.9). This difference was statistically significant (p < 0.001). CONCLUSION: Both systems yielded comparable results. The examination time was significantly shorter with the D-light system, which may be explained by the more comfortable handling and the direct switch between white light and AF imaging. Different trials using either methodology could be compared directly.

[The role of a radical surgical debridement and mesh graft tissue transfer for treatment of venous ulcers]. / Uber die Bedeutung des radikalen chirurgischen Debridements mit nachfolgender Spalthauttransplantation bei der Behandlung des venösen Ulkusleidens.

Many studies are published demonstrating remarkable results of skin grafting in venous ulcers, but only a few controlled randomised trials including a low number of patients are available. A review based on two controlled randomised trials concludes that there is no significant benefit for mesh graft tissue transfer compared to standard treatment. However, in all studies no adequate initial radical surgical debridement including fasciectomy for wound bed preparation has been performed. In a prospective study on 57 patients with venous ulceration we found significant lower recurrence rates after mesh graft tissue transfer and radical surgical debridement. In clinical practice the results of mesh graft tissue transfer following surgical debridement in the management of larger chronic venous ulcers have been encouraging, although the evidence-based recommendation is lacking. It may not be the treatment of first choice and should be preserved for large ulcers of long duration or history of recurrence. There is need for more randomised controlled studies comparing also cost effectiveness while ensuring baseline comparability.

Areal density measurement is a convenient method for the determination of porcine islet equivalents without counting and sizing individual islets.

The determination of islet mass is important for the normalization of islet experiments in the laboratory and for the precise dosing of islets for transplantation. The common microscopical analysis is based on individual islet sizing, calculation of the frequency distribution, and conversion into islet equivalents (IEQ), which is the volume of a spherical islet with a diameter of 150 microm. However, islets are of irregular form, which makes this determination user dependent, and the analysis is irreproducible once the original sample is discarded. This routine technique of islet quantification was compared with the analysis of areal density measurements. It was assumed that the entire area occupied by islets can be expressed in IEQ without sizing and counting individual islets. Porcine islets were isolated by continuous digestion/filtration and purified by gradient centrifugation. Purified islets were stained with dithizone and were repeatedly pictured under the microscope with random area selection. A total of 51 pictures was taken from 11 different purifications and stained islets were detected by digital image analysis. The correlation coefficient (r) between bothanalyses was 0.977 with an underestimation of islet yield by areal density detection (slope: 0.75 +/- 0.03). Areal density analysis per picture took about 1 min, which is about 10 times faster than the traditional method without increasing the method error (CV 2.1% vs. 2.7%). In summary, areal density measurements allow a rapid and reproducible estimation of IEQ without counting individual islets. It can be performed in a single step analysis without computer programming and is valuable for online determinations of islet yield preceding transplantation.

[Postoperative ileus: part II (Clinical therapy)]. / Postoperativer Ileus: Teil II (Klinische Therapie).

To avoid or reduce postoperative ileus, the operative trauma should be minimized and epidural anesthesia for spinal inhibition of the sympathetic nervous system or i. v. lidocaine should be used, all of which probably act by reducing visceral afferent nerve fiber activity. Recent data suggest that perioperative fluid restriction might reduce postoperative ileus. Epidural anesthesia with local anesthetics and replacing opioids by non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative pain treatment improve the recovery of gastrointestinal motility disturbances. Prior to the operation, the patient should be informed regarding postoperative motility disorders, its length and the presumed resumption of oral food intake, which has been shown to shorten hospital stay. Early postoperative food intake stimulates small and large bowel motility via interenteric reflex arches, avoids i. v. lines and renders discharge acceptable for the patient. Treatment of postoperative ileus includes osmotic laxatives and prokinetic drugs like erythromycine and acetylcholinesterase inhibitors. By combining epidural anesthesia and the sparse use of i. v. opioids with early food intake and, if necessary, laxatives or prokinetics, postoperative ileus should be coped adequately. Nevertheless, the development of new specific prokinetic drugs with minimal or no side effects should remain a target for drug companies to further improve treatment of postoperative ileus.