Systemic therapy in metastatic renal cell carcinoma (mRCC): an evidence-based recommendation of the German interdisciplinary RCC guidelines group.

PURPOSE: The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations. METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate. RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated. CONCLUSION: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.

Histopathological features in fatal COVID-19 acute respiratory distress syndrome

Background COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. Objective To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. Design A prospective cohort study was carried out. Setting Intensive Care Unit of a tertiary hospital. Patients The first 22 consecutive COVID-19 deaths. Measurements Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated.Results The median patient age was 66 [63–74] years; 73% were males. The median duration of mechanical ventilation was 17 [8–24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. Limitation Limited sample size. Conclusions The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen. (AU)

Antecedentes El síndrome de dificultad respiratoria aguda (SDRA) asociado a la COVID-19 comparte características histológicas con otros tipos de SDRA. Sin embargo, no se ha establecido adecuadamente la cronología de las lesiones histológicas. Objetivo Describir las alteraciones histopatológicas cronológicas en los pulmones de los pacientes con síndrome de dificultad respiratoria aguda asociado a COVID-19. Diseño Estudio prospectivo de cohortes. Ámbito Unidad de cuidados intensivos de un hospital terciario. Pacientes Las primeras 22 muertes consecutivas por COVID-19. Intervenciones Se llevaron a cabo biopsias pulmonares y análisis histopatológicos en pacientes fallecidos por SDRA asociado a COVID-19. Se evaluaron los datos clínicos y la evolución médica. Resultados La mediana de edad de los pacientes fue de 66 (63-74) años y el 73% eran varones. La mediana de la duración de la ventilación mecánica fue de 17 (8-24) días. La lesión pulmonar inducida por COVID-19 se caracterizó por una fase exudativa durante la primera semana de la enfermedad, seguida de una fase proliferativa/organizativa en la segunda y tercera semana y, por último, una fase de fibrosis en fase terminal tras la tercera semana de evolución. Se detectaron proteínas y ARN vírico en neumocitos y macrófagos en una fase muy temprana de la enfermedad, pero estos ya no se volvieron a detectar a partir de la segunda semana. Limitación Tamaño limitado de la muestra. Conclusión La evolución cronológica de las lesiones histopatológicas pulmonares asociadas a la COVID-19 parece ser similar a la de otras formas de SDRA. En particular, se observan daños pulmonares coherentes con las lesiones potencialmente sensibles a los corticosteroides. (AU)

Histopathological features in fatal COVID-19 acute respiratory distress syndrome.

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. OBJECTIVE: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. DESIGN: A prospective cohort study was carried out. SETTING: Intensive Care Unit of a tertiary hospital. PATIENTS: The first 22 consecutive COVID-19 deaths. MEASUREMENTS: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. RESULTS: The median patient age was 66 [63-74] years; 73% were males. The median duration of mechanical ventilation was 17 [8-24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. LIMITATION: Limited sample size. CONCLUSIONS: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.

Histopathological features in fatal COVID-19 acute respiratory distress syndrome.

Background: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. Objective: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. Design: A prospective cohort study was carried out. Setting: Intensive Care Unit of a tertiary hospital. Patients: The first 22 consecutive COVID-19 deaths. Measurements: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. Results: The median patient age was 66 [63-74] years; 73% were males. The median duration of mechanical ventilation was 17 [8-24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. Limitation: Limited sample size. Conclusions: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.

Antecedentes: El síndrome de dificultad respiratoria aguda (SDRA) asociado a la COVID-19 comparte características histológicas con otros tipos de SDRA. Sin embargo, no se ha establecido adecuadamente la cronología de las lesiones histológicas. Objetivo: Describir las alteraciones histopatológicas cronológicas en los pulmones de los pacientes con síndrome de dificultad respiratoria aguda asociado a COVID-19. Diseño: Estudio prospectivo de cohortes. Ámbito: Unidad de cuidados intensivos de un hospital terciario. Pacientes: Las primeras 22 muertes consecutivas por COVID-19. Intervenciones: Se llevaron a cabo biopsias pulmonares y análisis histopatológicos en pacientes fallecidos por SDRA asociado a COVID-19. Se evaluaron los datos clínicos y la evolución médica. Resultados: La mediana de edad de los pacientes fue de 66 (63-74) años y el 73% eran varones. La mediana de la duración de la ventilación mecánica fue de 17 (8-24) días. La lesión pulmonar inducida por COVID-19 se caracterizó por una fase exudativa durante la primera semana de la enfermedad, seguida de una fase proliferativa/organizativa en la segunda y tercera semana y, por último, una fase de fibrosis en fase terminal tras la tercera semana de evolución. Se detectaron proteínas y ARN vírico en neumocitos y macrófagos en una fase muy temprana de la enfermedad, pero estos ya no se volvieron a detectar a partir de la segunda semana. Limitación: Tamaño limitado de la muestra. Conclusión: La evolución cronológica de las lesiones histopatológicas pulmonares asociadas a la COVID-19 parece ser similar a la de otras formas de SDRA. En particular, se observan daños pulmonares coherentes con las lesiones potencialmente sensibles a los corticosteroides.

[Narrow band imaging-assisted cystoscopy in bladder tumor follow-up: Can more tumors be identified?]. / "Narrow-band-imaging-assistierte" Zystoskopie in der Blasentumornachsorge : Sind mehr Tumoren erkennbar?

BACKGROUND: Narrow band imaging (NBI) is a new technique of urethrocystoscopy, in which only certain wavelengths [415 (blue) and 540 nm (green)] are used to detect urothelial carcinoma. The aim of the investigation was to analyze the potential benefit of NBI in the follow-up of patients with transitional cell carcinoma of the bladder. METHODS: Between August 2013 and July 2014, patients with a history of transitional cell carcinoma of the bladder, presenting for follow-up cystoscopy, were either examined via flexible white light endoscopy (WLE) plus second look WLE (n = 251, controls) or second look NBI cystoscopy alone (n = 251) in the same session. RESULTS: Rates of recurrences were similar in the two groups [NBI 68 (27.1 %); WLE 70 (27.9 %)]. NBI after WLE identified more tumors in 13 patients (5.69 vs. 3.92). In 8 patients NBI showed no vascularization in suspicious areas. In the control arm, in 8 cases more tumors (3.75 vs. 3.13) were identified in the second WLE. CONCLUSIONS: The additional use of NBI in the follow-up cystoscopy of patients after transurethral resection of nonmuscle invasive bladder cancer leads to an increased number of detected tumors; however, a part of the additionally detected tumors can be explained by the double examination. NBI appears to provide information in individual cases whether transurethral resection of bladder tumor is necessary.

Endothelial Caveolin-1 regulates the radiation response of epithelial prostate tumors.

The membrane protein caveolin-1 (Cav1) recently emerged as a novel oncogene involved in prostate cancer progression with opposed regulation in epithelial tumor cells and the tumor stroma. Here we examined the role of stromal Cav1 for growth and radiation response of MPR31-4 prostate cancer xenograft tumors using Cav1-deficient C57Bl/6 mice. Syngeneic MPR31-4 tumors grew faster when implanted into Cav1-deficient mice. Increased tumor growth on Cav1-deficient mice was linked to decreased integration of smooth muscle cells into the wall of newly formed blood vessels and thus with a less stabilized vessel phenotype compared with tumors from Cav1 wild-type animals. However, tumor growth delay of MPR31-4 tumors grown on Cav1 knockout mice to a single high-dose irradiation with 20 Gray was more pronounced compared with tumors grown on wild-type mice. Increased radiation-induced tumor growth delay in Cav1-deficient mice was associated with an increased endothelial cell apoptosis. In vitro studies using cultured endothelial cells (ECs) confirmed that the loss of Cav1 expression increases sensitivity of ECs to radiation-induced apoptosis and reduces their clonogenic survival after irradiation. Immunohistochemical analysis of human tissue specimen further revealed that although Cav1 expression is mostly reduced in the tumor stroma of advanced and metastatic prostate cancer, the vascular compartment still expresses high levels of Cav1. In conclusion, the radiation response of MPR31-4 prostate tumors is critically regulated by Cav1 expression in the tumor vasculature. Thus, Cav1 might be a promising therapeutic target for combinatorial therapies to counteract radiation resistance of prostate cancer at the level of the tumor vasculature.

[Superficial bladder cancer: Transurethral resection and instillation therapy]. / Oberflächliches Harnblasenkarzinom : Transurethrale Blasentumorchirurgie und Instillationstherapie.

Bladder cancer is the fifth most common tumor in men with the incidence of bladder tumors continuing to rise in industrialized and developed countries. Because 80% of all bladder tumors grow on the surface, endoscopic transurethral resection (TUR-B) can be used for complete removal. Due to continuous technical developments and improvements of endoscopic equipment, video imaging and bipolar resection (TUR-IS) offers a high level of safety. Despite optimal equipment, intra- and postoperative complications in transurethral electrosurgery of bladder tumors may occur.

[Organ and kidney function preservation in renal cell carcinoma]. / Organ- und Funktionserhalt beim Nierenzellkarzinom.

BACKGROUND: The organ-preserving partial nephrectomy has increasingly established itself in small unilateral renal tumours (<4 cm) with contralateral healthy kidney and counter gained in recent years in importance. There was found a significantly increased cardiovascular mortality rate and deteriorated quality of life, the more intact kidney tissue has been removed. OBJECTIVES: In the present study, the influence of pre- and perioperative factors on direct postoperative course was examined, including 5-year survival rate and relapse behaviour after open organ-preserving partial nephrectomy in our own collective. MATERIALS AND METHODS: In this retrospective study of 1657 patients were collected, who underwent surgery between 2007 and 2013 in the Department of Urology at the University Hospital Essen because of a renal tumour. 38 % of these operations (n = 636) were performed organ-preserving. In this trial there are factors identified that have an impact on need of blood transfusion and length of hospitalization in organ-preserving operation method. RESULTS: No independent parameter can be determined for the need of blood transfusion. Tumour size and thus time of resection procedure does not affect the need of erythrocytes administration. In addition, the tumour size influences neither the postoperative serum-haemoglobin nor serum-creatinine. Increased patient age and female gender are identified as non-modifiable factors, which cause a longer hospitalisation. Postoperative pain therapy can be considered as a variable size, which does not affect the length of hospital stay. Modifiable factors that increase the overall length of stay, however, are the type of direct postoperative monitoring (ICU vs. anaesthetic recovery room) and the administration of blood transfusions. CONCLUSIONS: There are constant factors, which can be associated with a longer residence time in the framework of an organ-preserving partial nephrectomy. Further there is shown evidence of the independence of the tumour size - in addition to proven good oncological results - of an extension of indication of organ-preserving nephrectomy of tumours > 4 cm.

[Urological surgery with analogosedation and local anesthesia. What makes sense?]. / Urologische Operationen in Analgosedierung und Lokalanästhesie. Was ist sinnvoll?

OBJECTIVE: Analogosedation and local anesthesia, including regional nerve blocks are used for endoscopic diagnostic or radiological and ultrasound-guided procedures in which the patient should not move or has to be free of pain. We retrospectively analyzed patient satisfaction, complications and the risk of urological interventions with analgosedation and/or local anesthesia between 2008 and 2012. MATERIAL AND METHODS: In total 21,690 urological patients underwent surgical treatment at the Department of Urology of the University Hospital of Essen between 2008 and 2012 and 3,327 of these cases were performed by urologists with the patient under analogosedation (n=1484) and local anesthesia (n=1843). In total 13 surgical and endoscopic procedures were separately analyzed and evaluated for safety and practicability. RESULTS: In five cases (0.15%) the procedures with analgosedation or local anesthesia were interrupted because of agitation (n=3) and in one case the transurethal resection was stopped due to a large bladder tumor. One patient suffered anaphylactic shock after preoperative intravenous application of cefuroxim 1.5 g. After cardiopulmonary resuscitation and a short stay on the intensive care unit the patient was discharged after 2 days.Conclusions. Local anesthesia and analgosedation should be performed by urologists for minor surgery, endoscopic procedures and radiological or ultrasound-guided treatment. For safety reasons there should always be a second medical doctor present for assistance. Analgesia with deep sedation or loss of defensive reflexes should be administered by anesthesiologists.

[Surgical gender reassignment in the elderly]. / Operative Geschlechtsangleichung im Alter.

BACKGROUND: Gender reassignment surgery (GRS) from male to female is increasingly being requested by older female patients. RESULTS: To the best of our knowledge this study has for the first time investigated the correlation between the age of patients and perioperative and postoperative complications. The presented data show that an age-related limitation for this intervention due to perioperative and postoperative complications is not justified. CONCLUSION: Health status and capability for self-sufficiency as well as physical and psychological limitations must be individually considered in order to achieve a successful postoperative course and a subjective satisfaction of patients.

[Failure to attend appointments: data analysis of a urological group practice over 12 months]. / Terminausfälle in der Praxis : Analyse einer Praxisklinik über 12 Monate.

PURPOSE: A well-structured system of appointments is mandatory in urological practices to provide a perfect work flow. A huge problem is appointments which are not cancelled by non-attending patients and remain free during consultation hours. METHODS: An analysis of the electronic calendar of our group practice was performed from January 2010 to December 2010. RESULTS: In 2010, 24,764 appointments in consultation hours were scheduled and of those 1,348 (5.4%) were not cancelled but not attended by the patients. Out of 1,760 X-ray investigations 59 (3.3%) patients did not show up and of 3,828 cystoscopy appointments, 109 (2.8%) patients did not cancel although they did not attend. A total of 440 outpatient appointments for surgery were scheduled and 8 (1.8%) patients did not attend but did not cancel surgery. Out of 176 (11.4%) scheduled spermiogram appointments, 20 patients did not bring a sample for analysis. CONCLUSIONS: Due to the experiences of the authors, combined investigations, e.g. intravenous pyelogram (IVP) and cystoscopy on one day, should therefore be avoided in order to be able to cancel the second appointment when patients do not show up for the first appointment. In cases of surgical interventions, patients should be contacted by telephone 2-3 days prior to surgery for confirmation. Currently under German law there is no way to claim compensation for missed appointments from the patients. Thus, the only way to avoid large numbers of missed appointments is to keep those as low as possible, as soon as appointments are made and scheduled (e.g. no double appointments).

[Kidney injury and multiple trauma: outcome, course and treatment algorithm. An organ-specific evaluation of 835 patients from the trauma register of the DGU]. / Nierenverletzung und Polytrauma: Outcome, Verlauf und Behandlungsalgorithmus. Eine organspezifische Auswertung von 835 Patienten des TraumaRegisters der DGU.

BACKGROUND: The relevance of renal trauma in severely injured patients within a large collective has not yet been thoroughly reviewed. This study aimed at assessing the prevalence of renal trauma in relation to the outcome and the currently established method of treatment. PATIENTS AND METHODS: Altogether data of 35,664 patients of the TraumaRegister of the German Society of Trauma Surgery (DGU) (1996-2007) were interpreted retrospectively. All patients with an injury severity score (ISS) ≥16, direct admission to a trauma center and an age of ≥16 years were included. All patients with abdominal trauma (AIS(Abdomen) ≥2) were compared with patients with abdominal and renal trauma (AIS(Kidney) ≥2). RESULTS: A total of 18,416 patients fulfilled the inclusion criteria of which 6,218 (34.1%) had abdominal injuries. Of these patients with abdominal injury 835 (13.3%) additionally showed a kidney injury (AIS(Abdomen) ≥2, AIS(Kidney) 2-5) and were analyzed according to the classification of the American Association for the Surgery of Trauma (AAST) organ-severity-score. AAST kidney: II°: 45.5%, III°: 31.1%, IV°: 15.6%, V°: 7.8%. Patients with leading kidney injury (grade IV and V) thereby showed a significant increase in mortality (IV: 32.3% and V: 40.0%) and an increase in the need for surgical intervention (IV: 61.5 and V: 81.5%). With an increasing grade of renal injury, however, the ISS is also increased but mortality was not increased over the expected mortality rate (RISC score) due to the additional renal injury. Dialysis rate in the surviving patients showed an increased rate depending on the degree of the kidney injury (II: 5.5%, III: 7.6%, IV: 18.8%, V: 8.3%). CONCLUSION: The results presented here show the prevalence and the outcome of kidney injury in a large collective within the TraumaRegister of the DGU for the first time. Based on the current literature and the findings a treatment algorithm has been developed.

[How should urologists perform implantation of subcutaneous central venous port systems? A single center experience of 347 cases]. / Wie sollen Urologen venöse subkutane Portsysteme implantieren? : Erfahrungen an einem Zentrum bei 347 Patienten.

BACKGROUND: Since 1999 urologists at the University of Essen in Germany have performed subcutaneous implantation of venous port systems, controlled by intravasal ECG. METHODS: Between December 1999 and June 2011 implantation of venous port systems was performed in 241 male (69.5%) and 106 (30.5%) female patients. The port systems were implanted subcutaneously above the pectoralis major muscle under local anesthesia. If it was not possible to isolate the cephalic vein or safe catheter implantation was not feasible, puncture of the subclavian vein was performed. RESULTS: The median follow-up was 491.6 days (2-2568), and 163.254 catheter days (mean 239 days, range 2-2604) were documented. During the follow-up period 191 (55.1%) patients died. The mean surgical implantation and explantation time was 36.5 min (14-85 min) and 25.4 min (10-46 min), respectively; 79.7% were implanted and controlled by ECG. Altogether, 390 devices were used in 379 surgical procedures, 355 implantations (91.1%) and 35 explantations (8.9%). Implanted vessels were the cephalic vein in 303 patients (85.6%) and the subclavian vein in 51 (14.4%) patients. Of 35 explanted devices, the explantation was necessary due to complications in 28 (8.0%) cases: infection n=6 (1.7%, 0.036 per 1,000 catheter days), occlusion n=8 (2.3%, 0.049 per 1,000 catheter days), dislocation n=7 (2.0%, 0.042 per 1,000 catheter days), deep vein thrombosis of the upper extremity n=6 (1.7%, 0.037 per 1,000 catheter days), and clotting n=1(0.3%, 0.006 per 1,000 catheter days). Premature catheter removal (<30 days post-op) was required in six cases (1.9%, 0.036 per 1,000 catheter days) due to complications: three catheter dislocations/malfunctions (0.9%, 0.019 per 1,000 catheter days), one port-related infection, one pocket port infection, and one deep vein thrombosis of the upper extremity (0.3%, 0.006 per 1,000 catheter days). Other problems described in the literature like pneumothorax, vein perforation, or pinch-off syndrome did not occur. CONCLUSIONS: Implantation of port systems with ECG control of the catheter tip position is related to a few cases of adverse events and good surgical outcomes. Furthermore, it has also shown great advantages in offering immediate support and early therapy initiation with a fast learning curve for the training urologists. The results of the presented analysis are comparable to those of surgical or radiological departments reported in the literature and provide good evidence that this procedure should be extended to urological centers with a high volume of chemotherapy patients.

[Perioperative antibiotic prophylaxis in radical retropubic prostatectomy: a randomised pilot study of perioperative and postoperative administration]. / Antibiotikaprophylaxe bei der radikalen retropubischen Prostatektomie: Eine randomisierte Pilotstudie zur perioperativen und postoperativen Gabe.

PURPOSE: A standard protocol for perioperative antibiotic prophylaxis in radical retropubic prostatectomy has not been established until now. The present pilot study compared the perioperative single-dose of piperacillin/tazobactam to the administration of ciprofloxacin or cotrimoxazol for 5 days with regard to postoperative infections. For the first time these antibiotic regimes were described in radical retropubic prostatectomy. MATERIAL AND METHODS: The patients were divided into three groups, each consisting of 17 patients: group 1: a single-dose of piperacillin / tazobactam 4.5 g i. v., group 2: ciprofloxacin 500 mg or cotrimoxazol 960 mg i. v. / p. o. and group 3: varying administration and duration of different kinds of antibiotics as control group. The basic characteristics of the patients such as age, body-mass-index, risk factors, diseases, former surgeries and medication were similar between all three groups. Also there were no significant differences in intraoperative parameters such as operation time, blood loss and other postoperative complications. RESULTS: The piperacillin / tazobactam group showed a significantly lower body temperature on postoperative days (POD) 1-3. The laboratory values were not significantly different among the groups, except the piperacillin / tazobactam group showed a significantly lower CRP level on POD 1-3 than group 3. All antibiotic regimes could afford an efficient protection: None of the patients died and there were no cases of serious consequences such as pneumonia, urosepsis or bacteriuria. Although not statistically significant, the piperacillin / tazobactam group showed better clinical outcomes: here the length of hospitalisation was two days less than in the other groups, no cases of wound infection occurred, the antimicrobial resistance rates were lower and fewer patients were treated with antibiotics in the postoperative course. CONCLUSIONS: Comparable to similar studies with a larger number of patients our pilot study demonstrated, although statistically not significant, better clinical results overall. We therefore conclude that a single-dose of piperacillin / tazobactam appears to be an efficient antibiotic prophylaxis in radical retropubic prostatectomy and even in some clinical parameters piperacillin / tazobactam seems to be equivalent or better than the usual 5-day administration of antimicrobial prophylaxis.

[Plasma E-cadherin levels in urinary bladder cancer: does it improve risk stratification?]. / Plasmakonzentrationen von E-Cadherin bei Tumorerkrankungen der Harnblase : Kann die Prognoseabschätzung hiermit verbessert werden?

BACKGROUND: Urinary bladder cancer represents a heterogeneous group of cancers regarding their clinical behaviour. For patients with muscle-invasive bladder cancer the 5-year disease-specific survival rate is only 50%. The main cause of death in this patient group is rapid metastatic progression following surgery. Clinicopathological features provide only limited information to predict disease progression in these patients. E-cadherin is a transmembrane glycoprotein critically involved in epithelial cell adhesion. Elevated circulating E-cadherin levels were shown to be correlated with progression of bladder cancer. MATERIAL AND METHODS: Plasma E-cadherin levels of 97 patients and 17 controls were analysed using an enzyme-linked immunosorbent assay, and results were compared with the clinical follow-up data. RESULTS: Plasma E-cadherin concentrations were significantly higher in patients than in controls (p<0.001). E-cadherin levels were not significantly correlated with clinicopathological parameters such as tumour stage (p=0.196), grade (p=0.570) and lymph node status (p=0.581). In a subgroup of patients treated by radical cystectomy, E-cadherin concentrations were higher in lymph node-positive cases; however, this correlation (p=0.100) failed to reach statistical significance. Furthermore, plasma E-cadherin levels were not able to predict disease-specific survival or metastasis-free survival (p=0.512 and p=0.197). CONCLUSIONS: Our results suggest that soluble E-cadherin levels are not able to predict patients' prognosis and underline the importance of external validation in prognostic marker research. Molecular markers predicting disease progression after radical cystectomy to identify high-risk patients and improve therapy decisions are still needed.

Global Functional Disconnections in Post-anoxic Coma Patient.

Disorders of consciousness have been related to different disconnection patterns as assessed by neuroimaging tools such as PET or fMRI. In this report, we use resting-state functional MRI acquisition and a functional connectivity analysis by graph of brain networks, to investigate the global residual connection pattern in a patient with consciousness disorders following post-anoxic injury. We then compare this pattern with those of a group of twenty controls. We observed that the patient's graph presents multiple disconnections in primary areas and in high-order associative areas. This pattern is consistent with a vegetative state, as reported by other groups. Further, the informations conveyed by this approach are consistent with those provided by PET, fMRI and EP. This new approach presents a very strong potential for diagnosis for consciousness disorder patients since it is applicable very early after the insult.

[Treatment of vesico-enteric fistulae in men. Pedicled bladder flap]. / Behandlung enterovesikaler Fisteln beim Mann: Gestielte Blasenlappenplastik.

Genitourinary fistulae represent a rare condition for patients submitted to salvage radiotherapy due to local tumour relapse after radical prostatectomy. Nevertheless, it is associated with great morbidity and in many cases with repetitive surgeries limiting their quality of life. Many techniques have been proposed to reduce the incidence of early and late postsurgical complications, but up to now a safe and unique method to treat this disease has not been reported in the literature. Here we report on three cases of male patients who developed a vesicoenteric fistula after radiation salvage therapy following radical prostatectomy. A rotation bladder flap was used to cover the pelvic floor attempting to reduce the common complications. All of the patients underwent a urinary diversion and a protective colostomy. The 1-year follow-up showed good postsurgical outcomes with minor early complications and no signs of intestinal obstruction or recurrent fistula. Furthermore, perineal and pelvic pain improvement was also achieved.The small number of cases is a limiting factor in defining standard techniques for the treatment of actinic vesicoenteric fistulae. Nevertheless, the use of a rotational bladder flap for repair of the pelvic floor defect has shown promising results and should be indicated in special situations.