Michael Hartmann

Risk Factors for Relapse in Clinical Stage I Nonseminomatous Testicular Germ Cell Tumors: Results of the German Testicular Cancer Study Group Trial

PURPOSEnTo prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT).nnnPATIENTS AND METHODSnFrom September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.5 months) or had pathologic stage II.nnnRESULTSnPathologic stage II disease was found in 27.9% of patients. Only 0.6% of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease. With reference pathology, vascular invasion (VI) was most predictive of stage in multifactorial analysis (accuracy, 65.1%). However, the positive predictive value (PPV) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7%. With absent VI, low-risk patients had a negative predictive value (NPV) of 76.9%. With a combination of several risk factors, the PPV increased to 63.6% and the negative predictive value increased to 86.5%.nnnCONCLUSIONnEven with an optimal combination of prognostic factors and reference pathology, more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and, therefore, would be overtreated with adjuvant therapy. However, patients at low risk may be predicted at an 86.5% level, and thus, surveillance in highly compliant patients would be a valuable option. For high-risk patients, further reduction of adjuvant treatment is necessary.

Oral naloxone reverses opioid-associated constipation.

Abstract Opioid‐related constipation is one of the most frequent side effects of chronic pain treatment. Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first‐pass metabolism. The aim of this study was to examine the effects of oral naloxone on opioid‐associated constipation in an intraindividually controlled manner. Twenty‐two chronic pain patients with oral opioid treatment and constipation were enrolled in this study. Constipation was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention (‘control period’). Then, oral naloxone was started and titrated individually between 3×3 to 3×12 mg/day depending on laxation and withdrawal symptoms. After the 4‐day titration period, patients were observed for further 6 days (‘naloxone period’). The Wilcoxon signed rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patients did not reach the ‘naloxone period’ due to death, operation, systemic opioid withdrawal symptoms, or therapy‐resistant vomiting. In the 6 day ‘naloxone’ compared to the ‘control period’, the mean number of days with laxation increased from 2.1 to 3.5 (P<0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P<0.01). The mean naloxone dose in the ‘naloxone period’ was 17.5 mg/day. The mean pain intensity did not differ between these two periods. Moderate side effects of short duration were observed in four patients following naloxone single dose administrations between 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of the patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5–6 h. This controlled study demonstrates that orally administered naloxone improves symptoms of opioid associated constipation and reduces laxative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration.

[18F]Fluorodeoxyglucose Positron Emission Tomography in Nonseminomatous Germ Cell Tumors After Chemotherapy: The German Multicenter Positron Emission Tomography Study Group

PURPOSEnIn patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospective trial has evaluated the accuracy of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the prediction of histology compared with computed tomography (CT) and serum tumor markers (STM).nnnPATIENTS AND METHODSnA total of 121 patients with stage IIC or III NSGCT scheduled for secondary resection after cisplatin-based CTX were included. FDG-PET was performed after completion of CTX. All results were confirmed by histopathology and correlated to STM and CT.nnnRESULTSnPrediction of tumor viability with FDG-PET was correct in 56%, which did not reach the expected clinically relevant level of 70%, and was not better than the accuracy of CT (55%) or STM (56%). Sensitivity and specificity of FDG-PET were 70% and 48%. The positive predictive values were not significantly different (55%, 61%, and 59% for CT, STM, and PET, respectively). Judging only vital carcinoma as a true malignant finding, the negative predictive value increased to 83% for FDG-PET.nnnCONCLUSIONnThe presence of vital carcinoma and mature teratoma is common (55%) in residual masses in patients with NSGCT, and CT and STM cannot reliably predict absence of disease. In contrast to prior studies, this prospective trial, which is the only with histologic confirmation in all patients, demonstrated that FDG-PET is unable to give a clear additional clinical benefit to the standard diagnostic procedures, CT and STM, in the prediction of tumor viability in residual masses.

Biosurgery supports granulation and debridement in chronic wounds: clinical data and remittance spectroscopy measurement

Background Maggot therapy (biosurgery) has received increasing interest for the debridement of chronic wounds and for the improvement of wound healing. The purpose of this study was to investigate the clinical effects, side‐effects, and possible mechanisms of action of biosurgery.

Hospital Incidence and Mortality Rates of Sepsis: An Analysis of Hospital Episode (DRG) Statistics in Germany From 2007 to 2013

BACKGROUNDnSepsis, the most severe manifestation of acute infection, poses a major challenge to health care systems around the world. To date, adequate data on the incidence and mortality of sepsis in Germany have been lacking.nnnMETHODSnNationwide case-related hospital DRG statistics for the years 2007-2013 were used to determine the in-hospital incidence and mortality of sepsis. Cases were identified on the basis of the clinical and pathogen-based ICD-10 codes for sepsis. The statistical evaluation was standardized for age and sex and carried out separately for each age group.nnnRESULTSnThe number of cases of sepsis rose by an average of 5.7% per year, from 200 535 in 2007 to 279 530 in 2013, corresponding to an increase in the adjusted in-hospital incidence from 256 to 335 cases per 100 000 persons per year. The percentage of patients with severe sepsis rose from 27% to 41%. The in-hospital mortality of sepsis fell over the same period by 2.7%, to 24.3%. In 2013, 67 849 persons died of sepsis in German hospitals (or died of another disease, but also had sepsis). The incidence was highest in the youngest and oldest age groups, and the in-hospital mortality rose nearly linearly with age from age 40 onward.nnnCONCLUSIONnSepsis and death from sepsis are markedly more common in Germany than previously assumed, and they are on the rise. Sepsis statistics should become a standard component of federal statistical reports on public health, as well as of hospital statistics. Preventive measures and evidencebased treatment should be implemented across the nation.

A comparison between meperidine, clonidine and urapidil in the treatment of postanesthetic shivering.

Postanesthetic shivering can be treated with many types of drugs. We compared the effects of meperidine, clonidine, and urapidil on postanesthetic shivering. Sixty patients shivering during recovery from general anesthesia were treated in a randomized, double-blinded fashion with 25 mg meperidine IV, 0.15 mg clonidine IV, or 25 mg urapidil IV in three separate groups of 20 patients each. If shivering did not stop within 5 min, the treatment was repeated once; clonidine was replaced with saline for the second dose. Rectal temperature, arterial blood pressure, heart rate, Sao2 and vigilance were monitored. Clonidine stopped shivering in all 20 patients. A single dose of meperidine stopped the shivering in 18 of 20 patients, with the other 2 patients needing a second dose. Urapidil was less effective: the first dose stopped the shivering in only six patients; the second dose was effective in another six; the drug was ineffective in 8 of 20 patients. Meperidine and clonidine were both nearly 100% effective in treating postanesthetic shivering without negative side effects. By comparison, urapidil was only effective in 60% of patients treated (P <0.01). Implications Patients shivering during recovery from general anesthesia were treated in a randomized double-blinded fashion with meperidine, clonidine, or urapidil. Meperidine and clonidine were both very effective, whereas urapidil was only effective in 60% of patients treated.

Medical and surgical therapy of inflammatory bowel disease in the elderly — Prospects and complications

Population ageing is a global phenomenon. People aged 65 years and older comprise approximately 16% of the population of Europe. The medical management of elderly patients with inflammatory bowel disease (IBD) is challenging with respect to diagnosis, pharmaceutical and surgical treatment, and complications. IBD has a late onset in 10%-15% of patients, with the first flare occurring at 60 to 70 years of age; others suffer from the disease for several decades. Even though the natural course of the disease in geriatric populations and the diagnostic options may not differ much from those in younger patients, distinct problems exist in the choice of medical therapy. Recommended clinical practise has been rapidly evolving towards an intensified initial treatment in IBD. However, in patients older than 65 years, a gentler approach should be used, and a combination of immunosuppressive agents should be avoided because of increased risk of infectious and neoplastic complications. Furthermore, elderly patients with severe IBD show prolonged, complicated post-operative clinical courses with worse hospital outcomes, so early surgical intervention for elderly patients is recommended. This article provides an overview of elderly IBD patient care, including medical and surgical therapeutic considerations and emphasises the necessity of close collaborations between gastroenterologists and surgeons.

Burden or Relief: Do Second-Opinion Centers Influence the Quality of Care Delivered to Patients with Testicular Germ Cell Cancer?

BACKGROUNDnTo improve the quality of care, the German Testicular Cancer Study Group (GTCSG) has been publishing a series of testicular germ cell cancer guidelines since 1996. These guidelines were updated in the 2008 publication, European Consensus on Diagnosis and Treatment of Germ Cell Cancer. Several studies have shown that published guidelines have a limited effect on clinical practice. For this reason, the GTCSG made a further effort in 2006 to improve the quality of care by establishing a national second-opinion system for therapy planning for patients who underwent orchiectomy and staging evaluations.nnnOBJECTIVEnThe primary aim was to analyze the influence of the second-opinion system on guideline implementation with a view to improving the quality of care.nnnDESIGN, SETTING, AND PARTICIPANTSnAn Internet data exchange was established between the urologist seeking advice and the second-opinion centers. Second-opinion centers were 18 clinics that had contributed toward developing treatment guidelines.nnnMEASUREMENTSnData sets included the primary clinical, radiologic, and pathohistologic data; the planned therapy; the therapy recommended by the second-opinion center; and the follow-up.nnnRESULTS AND LIMITATIONSnFrom February 2006 to September 2008, 642 second opinions were requested. The therapy planned by the urologist seeking advice differed from that recommended by the second-opinion center in 32.3% of the cases. The discrepancy was significantly higher for nonseminomas than for seminomas (p=0.045) and showed a tendency to increase with advancing tumor stage (p=0.067). In cases of discrepancy, the applied therapy coincided with the second opinion in 71.8% of the cases. A discrepant second opinion prevented overtreatment in 40.3% and undertreatment in 26.5%.nnnCONCLUSIONSnApproximately every sixth second opinion resulted in a relevant change in the scope of therapy. Published guidelines for germ cell cancer are applied only sporadically and should be supported by second-opinion systems.

German second-opinion network for testicular cancer: Sealing the leaky pipe between evidence and clinical practice

In 2006, the German Testicular Cancer Study Group initiated an extensive evidence-based national second-opinion network to improve the care of testicular cancer patients. The primary aims were to reflect the current state of testicular cancer treatment in Germany and to analyze the project’s effect on the quality of care delivered to testicular cancer patients. A freely available internet-based platform was developed for the exchange of data between the urologists seeking advice and the 31 second-opinion givers. After providing all data relevant to the primary treatment decision, urologists received a second opinion on their therapy plan within <48 h. Endpoints were congruence between the first and second opinion, conformity of applied therapy with the corresponding recommendation and progression-free survival rate of the introduced patients. Significance was determined by two-sided Pearson’s χ2 test. A total of 1,284 second-opinion requests were submitted from November 2006 to October 2011, and 926 of these cases were eligible for further analysis. A discrepancy was found between first and second opinion in 39.5% of the cases. Discrepant second opinions led to less extensive treatment in 28.1% and to more extensive treatment in 15.6%. Patients treated within the framework of the second-opinion project had an overall 2-year progression-free survival rate of 90.4%. Approximately every 6th second opinion led to a relevant change in therapy. Despite the lack of financial incentives, data from every 8th testicular cancer patient in Germany were submitted to second-opinion centers. Second-opinion centers can help to improve the implementation of evidence into clinical practice.

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].

Hintergrund: 1996 war von der “Interdisziplinären Arbeitsgruppe Hodentumoren” (IAH), in der Vertreter aller an der Diagnostik und Therapie des germinalen Hodentumors beteiligten Disziplinen aus den jeweiligen Fachgesellschaften und Arbeitsgruppen der Deutschen Krebsgesellschaft zusammenarbeiten, ein “Interdisziplinärer Konsensus zur Diagnostik und Therapie von Hodentumoren” erarbeitet worden (Strahlenther Onkol 1997;173–406). Die seinerzeit in interdisziplinärer Abstimmung definierten Empfehlungen wurden aufgrund fortschreitender Entwicklungen und klinischer Erkenntnisse dem aktuellen Wissensstand angepasst und überarbeitet. Hierfür sind durch den 1998 erfolgten Zusammenschluss der IAH mit der “Organgruppe Hodentumoren” der Arbeitsgemeinschaft Urologische Onkologie (AUO) zur “German Testicular Cancer Study Group (GTCSG) die wissenschaftliche Basis erweitert und die Qualität der erabeiteten diagnostischen und therapeutischen Standards für Hodentumoren erhöht worden mit der Zielsetzung, eine breite Umsetzung der interdisziplinär erstelltn Empfehlungen zu ermöglichen.nn Methodik: In Erweiterung der Erarbeitung des Konsensus von 1996 erfolgte die Überarbeitung auf Grundlage aktueller Literaturdaten in Anlehnung an die Prinzipien der “Evidence-bases Medicine” (EBM). Aussagen und Empfehlungen zu den von interdisziplinär besetzten Arbeitsgruppen recherchierten Themenkomplexen wurden nach dem Grad ihrer Qualität und Sicherheit bewertet. Das methodische Vorgehen entsprach dabei dem der Cochrane Collaboration, deren Bewertungskriterien übernommen wurden.nn Ergebnisse: Der zu 21 Themenkomplexen anhand wissenschaftliche begründeter Entscheidungskriterien erarbeitete “Interdisziplinärer Update-Konsensus” präzisiert und definiert diagnostische und therapeutischen Standards entsprechend dem aktuellen Wissensstand über diese Tumorentität. Für Therapiesituationen, bei denen mehrere Optionen bestehen und kein Konsens über die favorisierte Strategie erzielt wurde wie beim Seminom in klinischen Stadium I oder beim Nichtseminom in den Stadien CS I bzw. CS IIA/B, wurden jeweilige Alternativen mit deren Vor- und Nachteilen dargestellt.Der “Interdisziplinäre Update-Konsensus” wurde beim 24. Deutschen Krebskongress am 21.3.2000 vorgestellt, nachfolgend von den daran beteiligten wissenschaftlichen Fachgesellschaften geprüft und gebilligt.Background: An “Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors” was prepared in 1996 by the “Interdisciplinary Testicular Tumor Working Group” (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397–406). In 1998 the IAH met again together with the “Testicular Tumor Working Party” of the Urooncology Working Group (AUO) and formed the “German Testicular Cancer Study Group (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increases the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular on a broader scientific basis.nn Methods: According to the principles of “evidence-based medicine” (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the “Cochrane Collaboration”.nn Results: An “Interdisciplinary Update Consensus Statement” summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented.This “Interdisciplinary Update Consensus” was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.BACKGROUNDnAn Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors was prepared in 1996 by the Interdisciplinary Testicular Tumor Working Group (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the Testicular Tumor Working Party of the Urooncology Working Group (AUO) and formed the German Testicular Cancer Study Group (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis.nnnMETHODSnAccording to the principles of evidence-based medicine (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the Cochrane Collaboration.nnnRESULTSnAn Interdisciplinary Update Consensus Statement summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This Interdisciplinary Update Consensus was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.