[Management of penile cancer patients: new aspects of a rare tumour entity]. / Das Management von Patienten mit Peniskarzinom ­ Neue Aspekte in der Therapie einer seltenen Tumorentität.

Over the past few decades, some principles in the treatment of penile cancer have changed fundamentally. While 15 years ago a negative surgical margin of at least 2 cm was considered mandatory, organ-sparing surgery permitting minimal negative surgical margins has a high priority nowadays. The current treatment principle requires as much organ preservation as possible and as much radicality as necessary. The implementation of organ-sparing and reconstructive surgical techniques has improved the quality of life of surviving patients. However, oncological and functional outcomes are still unsatisfactory. Alongside with adequate local treatment of the primary tumour, a consistent management of inguinal lymph nodes is of fundamental prognostic significance. In particular, clinically inconspicuous inguinal lymph nodes staged T1b and upwards need a surgical approach. Sentinel node biopsy, minimally-invasive surgical techniques and modified inguinal lymphadenectomy have reduced morbidity compared to conventional inguinal lymph node dissection. Multimodal treatment with surgery and chemotherapy is required in all patients with lymph node-positive disease; neoadjuvant chemotherapy has been established for patients with locally advanced lymph node disease, and adjuvant treatment after radical inguinal lymphadenectomy for lymph node-positive disease. An increasing understanding of the underlying tumour biology, in particular the role of the human papilloma virus (HPV) and epidermal growth factor receptor (EGFR) status, has led to a new pathological classification and may further enhance treatment options. This review summarises current aspects in the therapeutic management of penile cancer.

[What do prostate cancer patients know about smoking? : Results of a bicentric questionnaire study (KRAUT study)]. / Was wissen Patienten mit einem Prostatakarzinom über das Rauchen? : Ergebnisse einer bizentrischen Fragebogenstudie (KRAUT-Studie).

BACKGROUND: According to the results of a recent meta-analysis, cancer-specific mortality of prostate cancer (PCA) patients is enhanced by 24 % in case of a positive smoking history with a dose-dependent impact of smoking. Until now it is unknown whether this information actually reaches the patients and how extensively an informational discussion about this topic is pursued by physicians. OBJECTIVE: Three study hypotheses were defined: (1) the knowledge of PCA patients about the potential relationship between tumor progression and cigarette consumption is low, (2) only in rare cases has a clear statement been provided by treating physicians including the explicit advice to stop smoking, and (3) there was a direct association between tumor stage and the extent of cigarette consumption. MATERIALS AND METHODS: A questionnaire comprising 23 items was developed and validated with 25 uro-oncological patients prior to study start. Between September 2013 and December 2014 a total of 124 PCA patients (median age 65 years) from two urology departments were included in this questionnaire-based survey. RESULTS: The study population comprised 43 % (n = 54), 39 % (n = 48), and 18 % (n = 22) nonsmokers, former smokers and active smokers, respectively. Active and former smokers differed insignificantly in the number of pack-years only (24.8 vs. 23.7 years, p = 0.995). Of the patients, 56 % regarded an influence of cigarette consumption on the PCA-specific prognosis as possible. However, because a significant (p < 0.001) number of patients wrongly suspected smoking to be causative for PCA development, their knowledge about PCA prognosis is supposedly not based on adequate knowledge. Two of 22 active smokers (9.1 %), 5 of 48 former smokers (10.4 %), and 2 of 54 nonsmokers (3.7 %) had an informational discussion with their urologist about the association of cigarette consumption and PCA-related prognosis (a further 9.1, 4.2 and 3.7 %, respectively, received this information solely from other medical specialties). Only 1 of 22 active smokers (4.5 %) was offered medical aids for smoking cessation by the general practitioner; none of the patients received such support by an urologist. There was no association between a positive smoking history or number of pack-years and PCA tumor stage. CONCLUSIONS: Education of PCA patients about the relationship between cigarette consumption and cancer-related prognosis is currently inadequate. Following the latest findings on this topic, urologists should pursue informational discussions with their patients, thereby strengthening their position as the primary contact person for decision making in PCA management.

[Rates of prostate-specific antigen testing for early detection of prostate cancer: a first comparison of German results with current international data]. / PSA-basierte Früherkennung des Prostatakarzinoms durch den Hausarzt: Erste deutsche Ergebnisse im internationalen Vergleich.

OBJECTIVE: Measurement of prostate-specific antigen (PSA) is not only used as a screening instrument by urologists, but also by general practitioners and internal specialists (GP-IS). Until now, there are neither data on the approach of German GP-IS in practicing this nor have data been classified in the context of available international literature on this topic. MATERIALS AND METHODS: Between May and December 2012, a questionnaire containing 16 items was sent to 600 GP-IS in Brandenburg and Berlin. The response rate was 65% (392/600). Six indicator questions (IQ1-6) were selected and results were set in the context of available international data. The quality of present studies was evaluated by the Harden criteria. RESULTS: Of the 392 responding physicians, 317 (81%) declared that they would use PSA testing for early detection of PCA (IQ1) and, thus, formed the study group. Of these GP-IS, 38% consider an age between 41 and 50 years as suitable for testing begin (IQ2), while 53% and 14% of the GP-IS perform early detection until the age of 80 and 90 years, respectively (IQ3). A rigid PSA cut-off of 4 ng/ml is considered to be reasonable by 47% of the involved GP-IS, whereas 16% prefer an age-adjusted PSA cut-off (IQ4). Patients with pathological PSA levels were immediately referred to a board-certified urologist by 69% of the GP-IS. On the other hand, 10% first would independently control elevated PSA levels themselves after 3-12 months (IQ5). Furthermore, 14% of the interviewed physicians consider a decrease of PCA-specific mortality by PSA screening as being proven (IQ6). Knowledge regarding PCA diagnostics is mainly based on continuous medical education for GP-IS (33%), personal contact with urologists (6%), and guideline studies (4%). While 53% indicated more than one education source, 4% did not obtain any PCA-specific training. The results provided by this questionnaire evaluating response of German GP-IS to six selected indicator questions fit well into the international context; however, further studies with sufficient methodical quality are required. CONCLUSIONS: Despite current findings and controversial recommendations of the two large PCA screening studies on this issue, German GP-IS still frequently use PCA screening by PSA measurement. Primary strategies of early detection as well as follow-up after assessment of pathologically elevated PSA levels poorly follow international recommendations. Thus, an intensification of specific education is justified.

Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients.

Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8(+) T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti-tumour response. In addition, lenalidomide-treated patients showed higher abundance of CD14(+) myeloid cells co-expressing CD15. This population was able to inhibit both CD4(+) and CD8(+) T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid-derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (T(regs)) and CD14(+) CD15(+) MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter-regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide.

[Anxiety and depression in cancer patients during the course of radiotherapy treatment]. / Angst und Depressivität bei Tumorpatienten im Verlauf der radioonkologischen Behandlung.

BACKGROUND: Undergoing radiotherapy is often associated with severe impairment of quality of life in cancer patients. Especially psychosocial aspects like anxiety and depression play a major role. The aim of this study was to closely analyze anxiety and depression during the course of radiotherapy treatment. METHODS: A total of 60 patients, who received radiotherapy because of a tumor disease between June 2005 and April 2006, were included in the prospective study; 57 (95%) patients were primarily treated with radiotherapy. In 72% of the cases the intention to treat was curable, in 18% palliative. Anxiety and depression (HADS-D) were assessed at three points in time: before (A) and after (B) radiotherapy treatment (RT), and 6 weeks after finishing RT at the follow-up appointment (C). RESULTS: Before therapy (A), 41% of the treated patients showed positive or marginally positive symptoms of anxiety and 33% symptoms of depression. The symptoms of anxiety significantly decreased during the course of therapy. The proportion of patients with a positive score of anxiety dropped from 16% at the beginning of RT (A) to 9% after the RT (B; p = 0.04). In addition, there was an increase in the number of patients who scored negatively with regard to anxiety from 59% (A) to 72% (B; p = 0.04). With regard to the median score of anxiety, no statistically significant change (p > 0.05) was observed during therapy, while for depression, the number of positively tested patients also decreased significantly during the course of therapy from the beginning of RT (A, 14%) to the first follow-up appointment (C, 9%; p = 0.02). Furthermore, the number of negatively tested patients rose by 8% (p = 0.02). During the whole course of the study, the median score of depression decreased from 6 (A) to 5 points (C; p = 0.01). CONCLUSION: More than one third of the treated patients suffered from positive or marginally positive symptoms of anxiety and depression. This present study showed a decrease of anxiety and depression symptoms during the course of radiotherapy.

Parental divorce and young adult children's romantic relationships: resolution of the divorce experience.

Fifty-one romantically involved young Israeli adults, whose parents were divorced, were questioned about their romantic relationship, parents' conflict, and current feelings about and reconstruction of the divorce. An integrative perception of the divorce was found to be related to fewer problems and to higher levels of friendship, enjoyment, and intimacy in the relationship. Implications for research and intervention with young adults are discussed.

Six-month overnight administration of intraperitoneal amino acids does not improve lean mass.

UNLABELLED: Intraperitoneal administration of 1% amino acid dialysis solution in patients on continuous peritoneal dialysis (CAPD) is associated with improvement in plasma amino acid concentrations and inconsistent results with respect to nitrogen balance. Whether alteration(s) in lean mass and body fat distribution also occur remains controversial. Therefore 18 patients (P), on CAPD for at least 6 months, were assigned in a prospective and controlled fashion to receive overnight either a 1% amino acid (AA-P) or a 1.36% glucose (Glu-P) containing dialysis solution. Body composition was investigated using whole body dual energy X-ray absorptiometry (Hologic QDR 1000/W). In P receiving glucose (n = 9), total body fat mass increased (+1.0 +/- 0.4 kg, mean +/- SEM, p < 0.03), whereas in patients on amino acids (n = 9), it decreased (-0.6 +/- 0.3, p < 0.02). This decrease in fat mass in AA-P was attributable to a decrease in upper body fat (-0.6 +/- 0.2, p < 0.02), whereas in Glu-P, it increased (+0.9 +/- 0.03, p < 0.03). No change in lower body fat was observed in either group. Total body lean mass remained similar in both groups during the six months of study (AA-P: 46.6 +/- 2.9 kg vs 47.0 +/- 3.0 kg, Glu-P 50.8 +/- 3.2 vs 50.1 +/- 2.2 kg baseline vs 6 months, respectively). In AA-P plasma urea concentrations increased from 25 +/- 2 to 34 +/- 3 mmol/l (p < 0.05), whereas plasma bicarbonate concentrations were similar before and after 6 months of therapy in either group. Plasma albumin and transferrin concentrations did not change in either group. Protein catabolic rate increased in AA-P (p < 0.01), whereas K x t/V did not change as a consequence of either therapy. CONCLUSION: Reduction in the amount of glucose in the peritoneal dialysate and the addition of amino acids decreases, whereas continuous dialysis with overnight glucose increases upper body fat over a 6-month period. However, no changes in protein stores were observed with the addition of amino acids. Therefore overnight peritoneal dialysis with amino acids offers minor advantages to protein-malnourished patients on CAPD, but may be of benefit in overweight CAPD patients.

High haemodialysis clearance of ornidazole in the presence of a negligible renal clearance.

The pharmacokinetics of ornidazole was studied in 6 patients treated by haemodialysis and in 8 subjects with a creatinine clearance between 4 and 99 ml/min x 1.73 m2. Blood and urine collections were performed for 72 h after i.v. and oral administration of 1.0 g ornidazole. Total body clearance, half-life, volume of distribution and systemic availability were independent of renal function and did not differ from previously reported values in normal volunteers. The haemodialysis clearance of ornidazole was greater than 100% higher than the total body clearance. The renal clearance of ornidazole accounted for less than 7% of the total body clearance. The percentage of the dose of ornidazole recovered in urine as parent compound or as the biologically active metabolites [alpha-(chloromethyl)-2 hydroxymethyl-5 nitroimidazole-1 ethanol and 3-(2 methyl-5 nitroimidazole-1-yl)1,2 propanediol] decreased linearly with decreasing renal function. Although the sum of those three compounds recovered in urine accounted for less than 10% of the total dose of ornidazole administered, they yielded therapeutic concentrations (greater than 4 micrograms/ml) in urine over 24 h after dosing. Due to the peculiar pharmacokinetic behaviour of ornidazole, i.e. high haemodialysis clearance in the absence of significant renal clearance, no dosage adjustment is necessary while renal function declines, but an increased dose is mandatory while patients are on dialysis.