Colon Cancer Screening in Concierge Practice.

OBJECTIVES: This study evaluated the effectiveness of the Center for Executive Medicine (CEM) concierge primary care practice on preventive colorectal cancer (CRC) screening rates relative to local and national comparator data. METHODS: We performed an electronic medical record search encompassing our entire patient population who are between the ages of 50 and 75 years to determine the rate of CRC screening. We compared this rate with the average rate of Medicare Advantage plans reported by our Independent Physician Association (IPA) in 2015 and national health plans reported by the National Committee for Quality Assurance in 2014. RESULTS: The CEM had a CRC screening rate of 90.2%, which was significantly higher than local IPA Medicare Advantage plans (63.3%) and National Committee for Quality Assurance national plans (57.7%-66.5%). CEM members were significantly more likely than were IPA members to undergo screening (odds ratio 1.425, 95% confidence interval 1.348-1.507, P < 0.0001). CONCLUSIONS: These results suggest that the CEM practice strategy and processes increase CRC screening rates.

[German national second-opinion network for testicular cancer and penile carcinoma : Two sources for evidence-based information]. / Nationale Zweitmeinungsnetzwerke Hodentumoren und Peniskarzinom : Zwei "Evidenz-Pipelines".

BACKGROUND: The second-opinion network for testicular cancer is an internet-based platform addressing physicians treating testicular cancer patients. They are offered a second-opinion before determining further therapy after orchiectomy and completion of staging. THEME: The high rate of discrepancies between the first and second opinion in more than 30 % supports the assumption of a deficit in the implementation of treatment guidelines. In 2015, approximately 22 % of the newly diagnosed cases with testicular cancer in Germany were covered by this system. According to the present interim analysis, the second-opinion platform helps to avoid overtreatment of testicular cancer patients. The high acceptance of the project and the encouraging results of this interim analysis gave rise to considerations to apply the second-opinion model to penile carcinoma. Data from the UK and the Netherlands show that the second-opinion network for penile cancer could help to improve treatment standards and results in Germany. Current data and the intended further development of the system are discussed.

Carbohydrate supplementation stabilises plasma sodium during training with high intensity.

BACKGROUND: Investigations of the effect of beverages containing carbohydrates, only, on the sodium and fluid balance during intermittent exercise of high intensity are rare. Therefore, we compared the effects of water and carbohydrate supplementation on plasma, blood volume, and electrolyte shifts during intermittent exercise. METHODS: Ten male subjects performed an intermittent exercise test twice. In one trial, tap water (4 ml/kg/15 min) was consumed (Plac trial). In the other trial, the same amount of water supplemented with maltodextrin to achieve a 9.1 % carbohydrate solution (CHO trial) was ingested. Training schedule: warm-up at 50 % for 15 min. Afterwards, power changed between 100 % of the maximum power from a previous incremental test minus 10 and 10 W for each 30 s. Venous blood was sampled to measure electrolytes, osmolality, [protein], hct, [Lactate], [glucose], [Hb] and catecholamines. Hydration status was evaluated by BIA before and after exercise. RESULTS: After beverage ingestion [glucose] was significantly higher in CHO until the end of the trial. Starting with similar resting values, osmolality increased significantly more during CHO (p = 0.002). PV decreased by 5 % under both conditions, but recovered partly during exercise under Plac (p = 0.002). [Na+] and [Cl(-)] decreased with Plac during exercise (both p < 0.001) but remained constant during exercise with CHO. CONCLUSIONS: Sole carbohydrate supplementation seems to stabilise plasma [Na+]. This cannot be explained simply by a cotransport of glucose and [Na+], because that should lead to a recovery of the blood and plasma volume under CHO. In contrast, this was found during exercise with Plac.

[Recent Therapy of Organ-confined Testis Cancer]. / Aktuelle Therapie organbegrenzter Hodentumoren.

BACKGROUND: In Germany, testicular cancer accounts for about 1-2% of all malignant tumours. Although, therefore, this is a rare tumour, it assumes an exceptional position among malignant tumours in several respects. In male patients aged 20-35 years it is the most common tumour, which directly affects the family and life planning of young men, a matter of prime importance at this age. Another aspect of testicular cancer is its excellent prognosis since the introduction of platinum-based chemotherapy into the armamentarium of testicular cancer therapy. Therefore, therapeutic innovations increasingly focus on reducing the radicality of treatment, even more so since this therapy, in addition to acute toxicity, can cause severe long-term consequences up to and including secondary malignancies. OBJECTIVES: This article gives an overview of the present therapeutic standard of stage I testicular cancer treatment. MATERIAL AND METHODS: Selective PubMed research Results and Discussion: Besides potential implications for organ-sparing surgery, the article elucidates the benefits of a risk-adapted therapeutic approach and indications for a surveillance strategy for patients with localised testicular cancer.

[National second opinion network for testicular cancer patients - transferring guidelines into practice!]. / Nationales Zweitmeinungsnetzwerk Hodentumoren - ein System zum Evidenztransfer!

The second opinion network for testicular cancer is an internet-based platform addressed to physicians treating testicular cancer patients. They are offered a second opinion before determining further therapy after orchiectomy and completion of staging procedures. The platform has been used in more than 3,000 cases of testicular cancer to date. The rate of discrepancies between first and second opinions is higher than 30%. This suggests a deficit in the implementation of published therapy guidelines. According to our present interim analysis, the second opinion platform helps in avoiding overtreatment of testicular cancer. The high acceptance of the project and the encouraging results of this interim analysis open the door for expansion of the second opinion model to other diseases, e. g., penile carcinoma.

[Organ-sparing therapy for testicular cancer]. / Organerhaltende Hodentumortherapie.

BACKGROUND: The therapy of malignant testicular neoplasms has always been characterized by a high degree of radicality. Thanks to a number of medical achievements the cure rate of testicular cancer has notably increased through the last decades. In the meanwhile the main focus is on reducing therapy load, scrutinizing radical orchiectomy as the only adequate therapy for the primary tumour. OBJECTIVES: This article discusses the question, if and under which conditions an organ-sparing approach can be used appropriately in clinical practice. MATERIALS AND METHODS: A selective literature search was performed in PubMed. RESULTS: A set of data suggest that endocrine and exocrine function of the testis can be preserved using an organ-sparing approach and many patients could benefit regarding their quality of life, e.g., preserving the ability to father a child at least temporarily and avoiding the need for hormone substitution. Different from kidney tumors, precancerous lesions (testicular intraepithelia neoplasia, TIN) can almost inevitably be found in the surrounding tissue of testicular tumors. This has to be considered when making a decision in favor of an organ-sparing approach, because radiation therapy on the affected testis has to be performed after tumor resection. Despite the absence of prospective data, organ-sparing surgical tumor resection can be recommended in carefully selected patients. CONCLUSION: After careful selection of patients, particularly young men can profit from an organ-sparing therapy regimen. Therefore, organ preservation should always be considered in the surgical treatment of testicular masses.

[Diagnostics and treatment of seminomatous germ cell tumors]. / Diagnostik und Therapie seminomatöser Hodentumoren.

Currently, seminomas account for about 60% of newly diagnosed testicular cancers in Germany, with an increasing trend. In lower tumor stages the main focus is on the avoidance of over therapy. This is of special interest in stage I where radiotherapy, carboplatin monotherapy and surveillance are available therapies as well as in stage IIA/B. Due to high late toxicity, radiotherapy of the retroperitoneal space is obsolete for young patients with clinical stage I and, in its present form, discussed controversially for patients with clinical stage IIA/B. The cause for this paradigm shift is the high percentage of secondary malignancies resulting after radiotherapy of the retroperitoneal space. Furthermore, 10-25% of the patients receiving radiotherapy alone for clinical stage IIA/B seminoma suffer from a relapse of the disease due to tumor recurrence in extraregional lymph nodes. Therefore, an ongoing study is investigating if a combined treatment with neoadjuvant carboplatin and radiotherapy with a limited target volume can reduce toxicity without jeopardizing the cure rate. Patients with residual tumors >3 cm should undergo 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) computed tomography scanning after a minimum interval of 6 weeks after chemotherapy. In the case of a positive FDG-PET-CT result, the further therapeutic strategy should be the subject of interdisciplinary discussions.

Management of muscle-invasive bladder cancer.

The incidence of muscle-invasive bladder cancer (MIBC) is increasing. Many different and multimodal novel treatment options were brought on the way since the beginning of a new era in the early 1980s, when the neobladder as a common option for urinary diversion had been induced. In addition to open radical cystectomy and urinary diversion, recently, minimal invasive surgery has been implemented in experienced centers and led to promising results in short term follow-up, awaiting confirmation in larger cohorts. Pelvic lymphnode dissection can cure patients with low metastatic load. Expansion of pelvic lymphonodal dissection and its influence on survival was discussed intensively with trends to a moderate enlargement of the standard field. Outcome in nodal positive disease is remaining poor, while 90% of patients with multiple lymphnode metastases will suffer from systemic progress 5 years after diagnosis. In the last decade, treatment regimens based on neoajuvant or adjuvant chemotherapy were published with different results on efficiency. To decide whether to treat with surgery alone, or to offer perioperative systemic cytostatic therapy, is one of the unanswered questions. Furthermore, bladder preserving techniques are still optional for patients with small unifocal lesions or the medically unfit cohort. This review summarizes current data and aims to help guiding through several available recommendations on therapy and management of MIBC.

[National second-opinion network for testicular cancer patients. Results of a user survey]. / Nationales Zweitmeinungsnetzwerk testikuläre Keimzelltumoren. Ergebnisse einer Nutzerbefragung.

BACKGROUND: The national second opinion project of the German Testicular Cancer Study Group (GTCSG) has served to improve the quality of care provided to testicular cancer patients since 2006. AIM: A recent online survey was carried out to characterize the users of the second opinion offer and clarify their motivation for participating in the project. Furthermore, the aim was to identify weaknesses of the project which could be improved. A total of 440 users of the second opinion project were contacted of whom 192 participated in the survey. RESULTS: In summary, the data collected showed a high degree of satisfaction among the participants who appreciated the second opinions received. Some issues with a need for improvement, predominantly in the structural organisational area, were disclosed. These served as a basis for a recently completed revision of the project immanent internet-based communication platform with a new data mask facilitating the introduction of patients with relapsed tumors. Interestingly, a high proportion of survey participants expressed the desire for establishment of a similar second opinion project for patients with penile cancer (77.1% of the participants).

[Clinical stage I seminoma. Is surveillance a new therapy standard?]. / Seminom klinisches Stadium I. Neuer Therapiestandard Surveillance?

BACKGROUND: The therapy of stage I seminoma is under constant change. While surveillance, adjuvant radiotherapy and adjuvant chemotherapy were seen as equal therapeutic alternatives up to a few years ago, recently published studies make it necessary to adopt a more differentiated approach. DISCUSSION: In this review, recent data on the long-term effects of adjuvant radiotherapy and chemotherapy, the question of risk stratification as well as the advantages and limitations of a surveillance strategy are discussed.

Characterisation of novel uveal melanoma cell lines under serum-free conditions.

BACKGROUND: The establishment of long-term uveal melanoma (UM) cell lines is difficult. However, studying living cells and their behaviour in the presence of other cells and the extracellular matrix is important in terms of understanding tumour biology and malignant behaviour. We have established three UM cell lines and report a first characterisation of these cell lines. METHODS: Three established UM cell lines (UMT2, UMT26 and UMT33) were analysed according to their morphologic characteristics, melanocytic differentiation, adhesion on different extracellular matrices and proliferative activity. Copy number changes of chromosomes 1, 3, 6 and 8 were studied by multiplex ligation-dependent probe amplification (MLPA). Oncogenic mutations in UM involving exons 4 and 5 of GNAQ and GNA11, respectively, were analysed by sequencing. RESULTS: All cell lines grew in suspension. UMT2 cells were homogeneous, UMT26 and UMT33 cells heterogeneous with regard to cell size and pigmentation. All UM cell lines revealed a melanocytic differentiation. UMT2 and 33 adhered on various extracellular matrices, while UMT26 only adhered to basal membrane extract (BME). This difference corresponded to the different expression of various integrins. Ki67 was expressed by 89% of UMT2 and 95% of UMT33 cells, which thus were in a proliferative stage, while only 2% of UMT26 cells revealed immunostaining for this proliferation marker. The doubling time of UMT2 was 3 days, 12 days for UMT33, and circa 3-4 months for UMT26. MLPA revealed disomy 3 in UMT2 and monosomy 3 in UMT33. The same point mutation was found in UMT2, 26 and 33, in exon 5 of GNA11 at codon 209 (p.Q209L). CONCLUSIONS: The establishment of UM cell lines under serum-free conditions is possible. Characterisation of UMT2, 26, and 33 revealed obvious differences in cytomorphology, melanocytic differentiation, adhesion on extracellular matrices, and proliferative activity. UMT2, 26 and 33 showed the same oncogenic mutation in exon 5 of GNA11.

[The use of Surgisis® optimizes and simplifies partial nephrectomy for large renal tumors]. / Anwendung von Surgisis® zur Optimierung und Vereinfachung der Nierenteilresektion bei größeren renalen Neoplasmen.

BACKGROUND: With lower rates of postoperative renal failure, diabetes and cardiovascular disease, partial nephrectomy achieves longer overall survival and equally long tumor-specific survival. It is thus the current gold standard treatment for renal tumors and now also for those ≥ 4 cm in size. The main complications of nephron-sparing surgery, particularly for large and centrally located tumors, are postoperative parenchymal bleeding and urinary fistulas after opening the urinary collecting system (UCS). MATERIAL AND METHODS: Between August 2003 and April 2012, 76 partial nephrectomies for tumors ≥ 4 cm in size were performed using porcine small intestinal submucosa (SIS, Surgisis®) to close the capsular, renal and in some cases, UCS defects. RESULTS: The median tumor size was 5.0 cm (range 4.0-13.0 cm) and the intervention was performed with warm ischemia in 25 cases (32.8 %), with cold perfusion in 16 cases (21.2 %) and without ischemia in 35 cases (46.0 %). A total of 4 patients (5.5 %) developed postoperative urinary fistulas and 4 (5.5 %) required revision surgery because of significant postoperative bleeding. There were no local infections or allergic reactions to the foreign material. CONCLUSIONS: Surgisis® enables a quick and technically uncomplicated closure of the renal defect after partial nephrectomy for tumors. It has the potential to further minimize postoperative bleeding and urinary fistulas and to facilitate the intervention to the extent that nephron-sparing surgery will gain broader acceptance even in patients with tumors ≥4 cm in size.

[Palliative care and medicamentous therapy during the final episode of life]. / Palliativmedizin und medikamentöse Therapie in der Sterbephase.

The idea of modern palliative care goes back to the times of Dame Cicely Mary Strode Saunders in 1967, a British nurse and physician. Modern palliative care is a multimodal therapeutic and supportive concept for the patient, when curative care has failed or seems to be not reasonable. In this article we review the basics of current palliative care and focus in particular on specific medicamentous therapy during the final episode of life.

Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer.

BACKGROUND: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo. METHODS AND RESULTS: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes. CONCLUSION: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin.

Radiotherapy after radical prostatectomy: immediate or early delayed?

BACKGROUND: Biochemical recurrence after radical prostatectomy (RP) is associated with risk indicators, including Gleason score, preoperative PSA level, tumor stage, seminal vesicle invasion, and positive surgical margins. The 5-year biochemical progression rate among predisposed patients is as high as 50-70%. Post-RP treatment options include adjuvant radiotherapy (ART, for men with undetectable PSA) or salvage radiotherapy (SRT, for PSA persisting or re-rising above detection threshold). Presently, there are no published randomized trials evaluating ART vs. SRT directly. METHODS: Published data on ART and SRT were reviewed to allow a comparison of the two treatment approaches. RESULTS: Three randomized phase III trials demonstrated an almost 20% absolute benefit for biochemical progression-free survival after ART (60-64 Gy) compared to a "wait and see" policy. The greatest benefit was achieved in patients with positive margins and pT3 tumors. SRT can be offered to patients with elevated PSA after RP. In 30-70% of SRT patients, PSA will decrease to an undetectable level, thus giving a second curative chance. The rate of side effects for both treatments is comparably low. The role of irradiation of pelvic lymph nodes and the additional use of hormone therapy and radiation dose are discussed. CONCLUSION: It remains unclear whether early SRT initiated after PSA failure is equivalent to ART. Where SRT is indicated, it should be started as early as possible.

[Radical cystectomy and ileal neobladder reconstruction in elderly female patients over 70 years old: morbidity, functional and oncological long-term results]. / Zystektomie mit Anlage einer Ileumneoblase bei der über 70-jährigen Frau : Morbidität, funktionelle und onkologische Ergebnisse.

BACKGROUND: As life expectancy is increasing the incidence and therefore the number of elderly female patients with bladder cancer is also increasing. The aim of this study was to assess long-term clinical, functional and oncological outcome in elderly women (≥70 years) who were treated by radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer. MATERIAL AND METHODS: A total of 121 women with clinically organ-confined invasive urothelial carcinoma underwent radical cystecomy with an orthotopic ileal neobladder in Ulm between 1995 and 2010. The clinical course, functional, pathological, and oncological outcome of these women were analyzed retrospectively and compared between patients ≥70 (n=24) and <70 years of age (n=97). All complications which occurred during the first 90 days after surgery were analyzed in detail, defined and classified according to the modified Clavien system. RESULTS: The overall 90 day complication rates were 66.7 % and 62.5 % for patients ≥70 and <70 years, respectively. Of these 54.2% and 44.8% were minor complications and 12.5 % and 17.7 % were major complications, respectively. Infections were the most frequent cause of complications with 36.7 %. Univariate analyses revealed that neither age nor comorbidity (ASA score) were significant predictors of perioperative complications. The daytime continence rates were comparable in both age groups (71% versus 82%, p=0.64); however, younger patients showed significantly higher night time urinary continence rates (43% versus 89%, p=0.013). Neither univariable nor multivariable analyses indicated that age ≥70 years had a significant impact on tumor-specific survival. CONCLUSIONS: Chronological age per se does not seem to be a contraindication for the creation of an orthotopic ileal neobladder; however, the risk of postoperative incontinence seems to increase with age.

[Guidelines: reality and quality]. / Leitlinien: Realität und Qualität.

The aim of guidelines is to increase the quality of care in clinical practice. Any influence or financial support by the pharmaceutical industry must be excluded. In urology only two S3 guidelines have been published in German and all others are more or less recommendations (S1). The example of the second opinion project on testicular germ cell tumors shows that a reduction of recurrence, morbidity and mortality can be achieved by the consistent application of guidelines. Oncological guidelines are often focused on the unidirectional parameter overall survival but do not include other important aspects, such as long-term morbidity or quality of life.

Peroxisome morphology in pathology.

Peroxisomes are remarkably dynamic and versatile organelles that are essential for human health and development. They respond to physiological changes in the cellular environment by adapting their morphology, number, enzyme content and metabolic functions accordingly. With the discovery of the first key peroxisomal morphology proteins, the investigation of peroxisomal shape, distribution and dynamics has become an exciting new field in cell biology and biomedical sciences because of its relation to organelle functionality and its impact on developmental and physiological processes. In this review, we summarize recent findings on peroxisome biology, dynamics and the modulation of peroxisome morphology, especially in mammals. Furthermore, we discuss the roles of peroxisome dynamics and morphology in cell pathology and present recent examples for alterations in peroxisome morphology under disease conditions. Besides defects in the peroxisomal morphology machinery, we also address peroxisome biogenesis disorders, alterations of peroxisome number during carcinogenesis and liver cirrhosis, and morphological alterations of peroxisomes during viral infection.

[Value of positron emission tomography in urological neoplasms: more form than substance?]. / Stellenwert der Positronenemissionstomographie bei urologischen Tumoren : Mehr Schein als Sein?

Positron emission tomography/computed tomography (PET/CT) is widely used for imaging urological neoplasms. This overview should help the urologist actively involved in oncology to assess the value of PET or PET/CT in each tumor entity. Besides prostate, testicular, renal, and bladder cancer less common urological malignancies like penile carcinoma and retroperitoneal masses are discussed. Differences in using PET/CT for primary diagnosis, staging, or restaging are outlined separately. Appropriate indications for the use in clinical practice are cited.