[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.

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.

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.

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.

[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.

Arginase acts as an alternative pathway of L-arginine metabolism in experimental colon anastomosis.

L-Arginine is the substrate for the nitric oxide synthase (NOS) pathway that is essential for gastrointestinal wound healing. L-Arginine is also the substrate for the enzyme arginase which metabolizes L-arginine to ornithine and subsequently to proline and polyamines both known to interact in cell proliferation and collagen synthesis. Two distinct isoforms of arginase exist. The temporal expression of the L-arginine metabolism in experimental colon anastomosis was investigated. Male Lewis rats underwent laparotomy. A left-sided colotomy was performed and the colon reanastomosed using 6-0 prolene. Sham operation was performed in controls. On days 2, 5, 10, 14, and 28 after the surgery the anastomosis was excised. The tissue at the anastomosis (ANAST) as well as above and below the anastomosis (PDC) and from sham colon was harvested and analyzed for distinct arginase isoform I (AI) and arginase isoform II (AII) activity, protein and mRNA expression as well as immunohistochemistry. iNOS protein and mRNA expression were investigated in parallel. A mean of 3 to 4 separate rats were analyzed per time point. Statistical analysis was performed by student's t-test, significance was reached when P < 0.05. AI activity, protein, and mRNA expression were significantly upregulated at the anastomosis compared to sham controls and PDC colons at all time points. The maximum was achieved at days 10 to 14 after wounding, and decreased to baseline levels thereafter. Inflammatory cells stained positive for AI. AII protein was not detectable. However RT-PCR showed low baseline expression. iNOS expression was upregulated early but for a shorter time period after wounding and reverted quickly to undetectable levels. In anastomotic healing, AI upregulation suggests a prolonged metabolism of arginine via arginase to polyamines and proline to provide substrate for collagen synthesis and cell proliferation. The functional implication of this arginase pathway further needs to be elucidated.

Endobronchial ultrasound-guided transbronchial lung biopsy in solitary pulmonary nodules and peripheral lesions.

Transbronchial biopsy (TBBX) for peripheral lung lesions is usually performed with the help of fluoroscopy, but the yield varies widely. This feasibility study aimed to assess the ability of endobronchial ultrasound (EBUS) to provide imaging guidance for TBBX. In a prospective study, 50 consecutive patients referred for TBBX for peripheral lesions underwent fluoroscopy-guided and EBUS-guided TBBX in random order. Diagnostic yields were compared for both modalities and feasibility was assessed for EBUS. Diagnostic material was obtained in 80% of patients with EBUS and 76% of patients with fluoroscopy. There was a nonsignificant trend for EBUS to be better than fluoroscopy for lesions <3 cm in diameter. Four lesions could not be visualised with EBUS. There were no significant complications associated with the use of EBUS. Endobronchial ultrasound-guided transbronchial biopsy is feasible. It appears to be at least equivalent to fluoroscopy without the accompanying radiation exposure. Further large-scale studies are indicated to assess the possible role of endobronchial ultrasound as a potential imaging method of choice for the biopsy of peripheral lung lesions.

Aspirin does not increase bleeding complications after transbronchial biopsy.

STUDY OBJECTIVES: The present study was performed to determine whether the risk of bleeding after transbronchial lung biopsy is increased in patients taking aspirin. DESIGN: Prospective cohort study. PATIENTS AND INTERVENTIONS: After excluding patients with other coagulation problems, 1,217 patients who had undergone transbronchial lung biopsy during a prospective 1.5-year study period were included in this study. The use of aspirin was not discontinued before the procedure. Two hundred eighty-five patients (23%) had consumed aspirin within 24 h of the procedure, and most of them (82%) used aspirin on a daily basis. Transbronchial biopsies were performed, and the bleeding incidence was compared between the groups. RESULTS: A total of 57 patients (4.7%) experienced procedure-related bleeding. Minor bleeding occurred in 5 of 285 patients (1.8%) taking aspirin and in 27 of 932 control patients (2.9%; not significant). Moderate bleeding was seen in 3 of 285 patients (1.1%) in the aspirin group and in 13 of 932 patients (1.4%) in the control group (not significant). Major bleeding occurred in only 9 patients, 2 of 285 (0.9%) in the aspirin group and 7 of 932 (0.8%) in the control group (not significant). All bleeding was controlled by endoscopic means, and there were no fatalities and no need for blood transfusions. CONCLUSIONS: We conclude that the risk of severe bleeding after transbronchial lung biopsy is small (ie, < 1%) and that the use of aspirin is not associated with any increased risk of bleeding.

[Endobronchial ultrasound for local tumour and lymph node staging in patients with centrally growing lung cancer]. / Endobronchialer Ultraschall (EBUS) zum lokalen T-und Lymphknotenstaging bei zentralem Bronchialkarzinom.

AIM: Lung cancer is a common disease and exact staging is of extreme importance in order to plan therapy. A frequent problem in assessing the extent of tumour spread is the question of infiltration versus compression of central airways by central tumours and a correct lymph node staging. Chest CT as the general imaging procedure of choice is often not helpful with these questions. Endobronchial ultrasound (EBUS) has been available for several years, and we were interested to find out if the addition of EBUS to regular bronchoscopy can help to differentiate between airway infiltration and external compression and improves the yield of transbronchial needle aspiration (TBNA). METHOD: Patients with central tumour growth and enlarged lymph nodes were examined with EBUS and CT, classified according to local tumour invasion, and a needle biopsy of the lymph nodes was performed after EBUS detection. RESULTS: 50 patients were examined and subsequently operated. Relative to the local T-staging EBUS resulted in a sensitivity of 89 % and a specificity of 100 %. The results were highly improved statistically compared to the CT results (sensitivity 25 %, specificity 80 %). With EBUS-guided TBNA the results of correct N-staging could be improved to 86 %. CONCLUSION: Our study suggests that EBUS, if performed by experienced endoscopists for the detection of airway wall infiltration or compression is highly accurate and superior to chest CT in assessing potential airway infiltration by a malignant tumour. Furthermore, the results of the lymph node staging could be improved through the additional use of EBUS. It is easily performed within the context of a standard bronchoscopy and may spare many patients unnecessary surgical biopsies.

Endobronchial ultrasound in therapeutic bronchoscopy.

Endobronchial ultrasound (EBUS) has been introduced as an adjunct to diagnostic bronchoscopy as it allows evaluation of the submucosal and parabronchial structures. Its use in therapeutic bronchoscopy has not been assessed. A large observational study of the value of EBUS in therapeutic bronchoscopy is presented here. From January 1998-January 2001 all patients undergoing therapeutic bronchoscopy and EBUS were evaluated prospectively. Patient demographics, indication for bronchoscopy, interventional treatments used and changes in therapy as influenced by the use of EBUS were documented. A total 2,446 therapeutic bronchoscopies were performed. In 1,174 cases EBUS was used (29% mechanical tumour debridement, 20% airway stenting, 13% Neodymium:yttrium aluminium garnet (Nd:YAG) laser use, 23% argon plasma coagulation, 11% brachytherapy, 2% foreign body removal and 2% endoscopic abscess drainage). EBUS guided or changed therapy significantly in 43% of cases. Changes included adjustment of stent dimensions, termination of tumour debridement when nearing vessels, and referral for surgical interventions rather than endoscopic treatment. Complications associated with EBUS use were minimal. No patient undergoing EBUS guided tumour destruction experienced severe bleeding or fistula formation. In summary, endobronchial ultrasound was easily performed and changed or guided therapeutic decisions during therapeutic bronchoscopic procedures in a substantial number of cases. As this may result in better outcomes, it has become a standard adjunct in the authors practice.

Anorectal functional disorders in the absence of anorectal inflammation in patients with Crohn's disease.

BACKGROUND: Histological alterations in the enteric nervous system (ENS) have been described in patients suffering from Crohn's disease (CD). The aim of this study was to investigate whether patients with CD without rectal inflammation have abnormal anorectal function compared with healthy volunteers. METHODS: Fifty-four patients with CD and 26 healthy volunteers were examined by anorectal manometry and answered a standardized questionnaire. No patient had active CD in the rectum as determined by endoscopy. RESULTS: Maximum anal resting and squeeze pressures did not differ between patients and healthy volunteers. The rectoanal inhibitory reflex was absent in 24 of 54 patients and two of 26 healthy volunteers (P < 0.05). The first sensation to distension of the rectal balloon was reported at mean(s.e.m.) 57.9(4.4) ml by patients and 37.5(2.2) ml by healthy volunteers (P < 0.01). The standardized interview revealed additional disorders of anorectal function in patients with CD. CONCLUSION: Anorectal function appears to be altered in many patients with CD even in the absence of macroscopic anorectal disease. This may be due to a disorder of the ENS.