[S3 guidelines on the diagnosis and treatment of carcinoma of the endometrium : Requirements for pathology]. / S3-Leitlinie Diagnostik und Therapie des Endometriumkarzinoms : Anforderungen an die Pathologie.

The present article summarises the relevant aspects of the S3 guidelines on endometrioid carcinomas. The recommendations include the processing rules of fractional currettings as well as for hysterectomy specimens and lymph node resections (including sentinel lymph nodes). Besides practical aspects, the guidelines consider the needs of the clinicians for appropriate surgical and radiotherapeutic treatment of the patients. Carcinosarcomas are assigned to the endometrial carcinoma as a special variant. For the first time, an algorithmic approach for evaluation of the tumour tissue for Lynch syndrome is given. Prognostic factors based on morphologic findings are summarised.

[S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology]. / S3-Leitlinie Diagnostik und Therapie des Zervixkarzinoms.

Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.

A methodological protocol for the development of a national guideline on perioperative management of gastrointestinal tumors in Germany.

BACKGROUND: The success of abdominal cancer surgery depends not only on the surgery itself but is influenced by the overall perioperative management. Given the multitude of perioperative measures and the ever-increasing number of studies on perioperative management, it is difficult to keep track and provide evidence-based perioperative management. The planned guideline on perioperative management will review the existing evidence and derive treatment recommendations. METHODS: The processing of the evidence is carried out by 6 working groups according to an 8-step scheme: after drafting the guideline questions in PICO format (1), a systematic literature search is carried out (2), and the records found are screened by two independent reviewers from the coordination team. Subsequently, the full texts of the potentially relevant articles are made available to the working groups for full text screening (3). All articles to be included are reviewed for methodological quality (4) before summary of findings tables are generated (5). In line with the GRADE approach, confidence in the evidence is assessed (6) before a recommendation is derived from the evidence, using a modified GRADE Evidence to Decision Framework (7). Finally, all recommendations are compiled and agreed within the guideline group (8). DISCUSSION: Guidelines serve as foundation for therapy decisions in everyday clinical practice and should therefore be based on up-to-date research results. However, while primary studies and systematic reviews are critically reviewed for their methodological quality, the process of guideline development is often not comprehensible. A protocol with predefined methodology should therefore create transparency and strengthen confidence in the recommendations. TRIAL REGISTRATION: The guideline is registered in the AWMF (Association of the Scientific Medical Societies) Guideline Register (088-010OL).

The ecological impact of membrane-based extraction of phenolic compounds--a life cycle assessment study.

Many phenolic compounds show high boiling points, low molecular weights, moderate polarities or high toxicities. Therefore, conventional wastewater treatment is limited or expensive. Recycling of the separated compounds is often not possible. But, if liquid-liquid reactive extraction is linked to a non-porous membrane, some or all of the above mentioned limitations may be overcome. The key element is a composite membrane with a dense, hydrophobic top layer which avoids the mixing of the two aqueous fluid streams. The dilute phenol stream is one of them, the other is caustic soda as stripping solvent. Since the basics of this technology have been discussed before, the scope of this study is to facilitate process implementation and integration. To this end, a life cycle assessment framework is used to identify the optimal equipment size for the treatment of wastewater that may, for example, originate from the production of polycarbonate. Limiting for this application is not the environmental performance though, but most likely process economics.

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels.

BACKGROUND AND PURPOSE: The cation channel transient receptor potential canonical (TRPC) 6 has been associated with several pathologies including focal segmental glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate the therapeutic potential of these agents. EXPERIMENTAL APPROACH: A library of potential TRPC channel inhibitors was designed and synthesized. Activity of the compounds was assessed by measuring intracellular Ca(2+) levels. The lead compound SAR7334 was further characterized by whole-cell patch-clamp techniques. The effects of SAR7334 on acute hypoxic pulmonary vasoconstriction (HPV) and systemic BP were investigated. KEY RESULTS: SAR7334 inhibited TRPC6, TRPC3 and TRPC7-mediated Ca(2+) influx into cells with IC50 s of 9.5, 282 and 226 nM, whereas TRPC4 and TRPC5-mediated Ca(2+) entry was not affected. Patch-clamp experiments confirmed that the compound blocked TRPC6 currents with an IC50 of 7.9 nM. Furthermore, SAR7334 suppressed TRPC6-dependent acute HPV in isolated perfused lungs from mice. Pharmacokinetic studies of SAR7334 demonstrated that the compound was suitable for chronic oral administration. In an initial short-term study, SAR7334 did not change mean arterial pressure in spontaneously hypertensive rats (SHR). CONCLUSIONS AND IMPLICATIONS: Our results confirm the role of TRPC6 channels in hypoxic pulmonary vasoregulation and indicate that these channels are unlikely to play a major role in BP regulation in SHR. SAR7334 is a novel, highly potent and bioavailable inhibitor of TRPC6 channels that opens new opportunities for the investigation of TRPC channel function in vivo.

Treatment with potentially hepatotoxic drugs and the risk of hepatocellular carcinoma: results of a european case - control study.

Some toxicological data and case reports have suggested that patients taking potentially hepatotoxic drugs may have an increased risk of benign and malignant liver tumours. Pharmacoepidemiological studies on this issue are sparse, most of them focusing on the association between hepatocellular carcinoma (HCC) and the use of oral contraceptives (OC). The objectives of our study were to examine the risk of HCC in patients taking the drugs mentioned in these case reports and toxicological studies. We used data from an international case - control study which had investigated the risk of HCC in women taking OC including 317 cases of HCC and 1060 frequency age-matched hospital controls. We investigated the risk for oral antidiabetic and immunosuppressive drugs, methyldopa, nitrofurantoin and clofibrate using unconditional logistic regression analysis. The analysis was adjusted for age, hepatitis B, hepatitis C, alcohol abuse and other risk factors of HCC. The adjusted odds ratios for ever-use of the investigated drugs varied between 0.67 and 1.64, none of them being statistically significant. There was equally no significantly increased risk for long-term use of these drugs. Altogether there is no evidence for an increased risk of HCC in patients taking the drugs investigated, however, the relatively small statistical power for certain drugs with a low exposure prevalence has to be taken into account. Copyright (c) 2000 John Wiley & Sons, Ltd.

Complementary medicine in guidelines of the German Guideline Program in Oncology: comparison of the evidence base between complementary and conventional therapy. huebner@med.uni-frankfurt.de.

INTRODUCTION: The German Guideline Program in Oncology (GGPO) comprises guidelines aiming at epidemiology, prevention, diagnosis, treatment and aftercare of different types of cancer. As many patients in Germany use complementary and alternative medicine (CAM), the aim of our study was to assess the information on CAM presented in these guidelines compared to conventional, supportive and psychosocial therapy. METHODS: We assessed all recommendations and statements from guidelines published from 2010 to 2012 from the program according to level of evidence (LoE) as given in the guideline. We differentiated between conventional cancer treatment, conventional supportive treatment, psychosocial interventions and complementary treatment. RESULTS: A total of 9 guidelines (ovarian, colorectal, pancreatic, gastric, breast, prostate, oral cancer, melanoma and Hodgkin lymphoma) were included in our analysis. The total number of statements is highly diverse, ranging from 35 to 150. Only few statements and recommendations are given regarding supportive, psychosocial or complementary therapy. Regarding conventional treatments, only two guidelines (ovarian and oral cancer) have more than 50 % statements and recommendations on level 1. Considering supportive treatments, the LoE is lower, except the guideline on pancreatic cancer (40 % level 1). In breast cancer, all statements are based on expert consensus. Four guidelines do not include any statement at all. All guidelines beside that on Hodgkin lymphoma include at least one statement or recommendation on psychosocial therapy. Most recommendations are GCP.CAM is discussed in 8 guidelines; LoE is low with GCP statements dominating. DISCUSSION: There may be different reasons for the low number of statements and recommendations on supportive, psychosocial and CAM therapies. Often, these topics are considered less important, and evidence is assumed as being low. In the GGPO, guidelines focusing on psychosocial and supportive therapy are under development. Thus, cancer-specific guidelines will be able to refer to these guidelines and only include recommendations on psychosocial care and supportive therapy which are specific for the type of cancer. A national guideline on CAM would close the gap of information for physicians and patients. In case of missing or low evidence, a transparent description of this uncertainty would be valuable information to professionals and patients.

The evidence for the use of growth factors and active skin substitutes for the treatment of non-infected diabetic foot ulcers (DFU): a health technology assessment (HTA).

AIMS: Assessment of the safety, efficacy and effectiveness of growth factors alone or in combination with other technologies in the treatment of DFU including medical, economical, social, ethical and juridical aspects. METHODS: We systematically searched relevant data bases limited to English and German language and publications since 1990. Review and assessment of the quality of publications followed methods conforming to widely accepted standards for evidence-based medicine and health economics. RESULTS: We identified 25 studies comparing becaplermin, rhEGF, bFGF and the metabolically active skin grafts Dermagraft and Apligraf with standard wound care (SWC) alone or extracellular wound matrix. Study duration ranged from 12 to 20 weeks and the study population comprised between 17 and 382 patients. Treatment with becaplermin, rhEGF, Dermagraft and Apligraf resulted in a higher incidence of complete wound closure and shorter time to complete wound healing with statistically significant differences. Regarding the proportion of adverse events there was no difference between treatment groups. The methodological quality of the studies was affected by significant deficiencies. Economic evaluations showed becaplermin being cost-effective. CONCLUSIONS: Add-on therapy with growth factors and active skin substitutes for treating uncomplicated DFU could be an alternative to SWC alone. For explicit recommendations further studies with stronger evidence are necessary.

Dynamic thermography of the knee joints in rheumatoid arthritis (RA) in the course of the first therapy of the patient with methylprednisolone.

Thermography in rheumatology is most often used in a static manner: after having fulfilled the conditions of standardized preparation of the patient in a cold examination room one or more thermograms are taken in standard positions for the respective joints. In our hospital the thermograms are more or less supplementary. The main examination result is a rewarming curve of the skin over the knee joints. The rewarming is provoked by dry cooling of the skin for one minute. Calculation of the slope of the rewarming curve and plotting the slope on a logarithmic scale shows two different rewarming processes in the skin overlying inflamed joints. The faster one is the rewarming by the arterial blood flow in the skin and the slower one is an additional rewarming by a pathological venous skin blood flow originating from deeper tissues under the skin. One has to suppose that the occurrence of excessive nitric oxide production in inflamed tissues is responsible for this pathological venous skin blood flow. Until now only nine patients receiving for the first time methylprednisolone could be included in a therapy study. Therefore only slight indications can be seen in the results. Whereas the erythrocyte sedimentation rate (ESR [mm/h] becomes more homogeneous (lower confidence interval CI 95) over the course of the treatment with decreasing drug dose, the thermal signs of inflammatory activity as measured by dynamic thermography have greater CI 95 values at the end than at the beginning of the treatment under study. This indicates that not all patients had sufficient antiinflammatory medication with the final 6 mg/d of methylprednisolone as measured by dynamic thermography but not by ESR or CRP.

Lyme disease in a 74-year-old forest owner with symptoms of dermatomyositis.

We describe a 73-year-old forest owner with widespread erythema, myalgia, and proximal muscle weakness. The clinical signs and the results of electromyography, magnetic resonance imaging, and a muscle biopsy were consistent with dermatomyositis. However, serology was positive for Borrelia burgdorferi. More importantly, B burgdorferi DNA was detected in skin by polymerase chain reaction techniques, and spirochete-like organisms were detected in the muscle by silver staining. Lyme disease with muscle involvement can mimic or trigger dermatomyositis and should be considered in the differential diagnosis of dermatomyositis.