[Persistent anemia after kidney transplantation in a 36-year-old male patient-an unusual cause]. / Persistierende Anämie nach Nierentransplantation bei einem 36-jährigen Patienten ­ eine ungewöhnliche Ursache.

An allogeneic kidney transplantation (match 1­1­0, cytomegalovirus, CMV, donor, D, +/recipient, R, - high risk) was performed in a 36-year-old patient. The patient was on dialysis due to a tubulointerstitial nephritis confirmed by biopsy 11 years previously. Posttransplantation there was a gradual decrease in the hemoglobin (Hb) level from 11.4 g/dl to 7.3 g/dl during the initial hospitalization period. Initially this was explained by the kidney transplantation and chronic fibrosing antral gastritis with erosions. Despite repeated transfusion of red cell concentrates, a refractory anemia persisted, which is why the patient presented several times at our clinic for further diagnosis and treatment. The presence of giant erythroblasts in the bone marrow and quantitative detection of parvovirus B19 (>900 million IU/ml DNA replications) was consistent with a virus-associated red cell aplasia. Intravenous immunoglobulin administration was established and showed long-term therapeutic success.

Complexity of PEComas : Diagnostic approach, molecular background, clinical management.

Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.

Increasing Operating Room Efficiency with Shop Floor Management: an Empirical, Code-Based, Retrospective Analysis.

With increasing economic pressure on health care, modern hospital management is focusing at industrial optimization techniques to improve efficiency while maintaining quality. Shop floor management, a technique of code-based, process-oriented guidance directly on site is a method of lean management intended to increase efficiency in the operating room. In the literature, there is only scant evidence that the introduction of this technique alone can increase efficiency. The aim of this retrospective study is to determine whether a single tool alone can significantly improve codes. We performed an empirical, retrospective analysis of a number of codes from 3800 operations during two periods of comparison: upon introduction of shop floor management, and one year thereafter. Data was extracted from the Hospital Information System and transferred to a database. There was no statistically significant change in the relevant codes chosen, whether specific to the operating room (turnover time, first patient in the room, waiting times for anesthesia and surgery (p = 0.637) or to planning stability (scheduled, cancelled (p = 0.505), unscheduled and total operations performed (p = 0.984)). There were absolute changes, such as a reduction in the turnover time from 17:37 min to 16:26 min, even though not statistically significant (p = 0.238). Implementation of shop floor management as a single intervention is not appropriate to achieve a significant, continuous improvement in codes. A combination with other techniques such as detailed process analyses is definitely required. This could be important additional information for units using Lean Health Care strategies.

[Complexity of PEComas : Diagnostic approach, molecular background, clinical management (German version)]. / Komplexität von PEComen : Diagnose, Molekulargenetik, klinisches Management.

Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.

Is the age of >65 years a risk factor for endoscopic treatment of primary inguinal hernia? Analysis of 24,571 patients from the Herniamed Registry.

INTRODUCTION: Several analyses of hernia registries have demonstrated that patients older than 65 years have significantly higher perioperative complication rates compared with patients up to the age of 65. To date, no special analyses of endoscopic/laparoscopic inguinal hernia surgery or of the relevant additional influence factors have been carried out. Besides, there is no definition to determine whether 65 years should really be considered to be the age limit. METHODS: In the Herniamed Hernia Registry, it was possible to identify 24,571 patients with a primary inguinal hernia and aged at least 16 years who had been operated on between September 1, 2009, and April 15, 2013, using either the TAPP technique (n = 17,214) or TEP technique (n = 7,357). Patients in the age group up to and including 65 years (≤65 years) were compared with those older than 65 years (>65 years) in terms of their perioperative outcome. That was done first using unadjusted analysis and then multivariable analysis. RESULTS: Unadjusted analysis revealed significantly different results for the intraoperative (1.19 vs 1.60%; p = 0,010), postoperative surgical (2.72 vs 4.59%; p < 0.001) and postoperative general complications (0.85 vs 1.98%; p < 0.001) as well as for complication-related reoperations (1.07 vs 1.37%; p = 0,044), which were more favorable in the ≤65 years age group. However, in multivariable analysis, it was not possible to confirm that for the intraoperative complications or the reoperations. Reoperations were needed more often for bilateral procedures (p < 0.001; OR 2.154 [1.699; 2.730]), higher ASA classification (IV vs I: p = 0.004; OR 6.001 [1.786; 20.167]), larger hernia defect and scrotal hernias. The impact of these factors, in addition to that of age >65 years, was also reflected in the postoperative complication rates. The age limit for increased onset of perioperative complication rates tends to be more than 80 rather than 65 years. CONCLUSION: The higher perioperative complication rate associated with endoscopic/laparoscopic inguinal hernia surgery in patients older than 65 years is of multifactorial genesis and is observed in particular as from the age of 80 years.

When is mesh fixation in TAPP-repair of primary inguinal hernia repair necessary? The register-based analysis of 11,230 cases.

Whereas for TEP the guidelines do not recommend mesh fixation on the basis of meta-analyses regardless of the defect size, for TAPP mesh fixation can be omitted only up to a defect size of 3 cm because of the paucity of studies on this topic. Hence, this study now seeks to explore this subject on the basis of prospective data from the Herniamed Hernia Registry. In the period September 01, 2009, to January 31, 2014, 11,228 male patients were operated on with the TAPP technique for a primary unilateral inguinal hernia and were followed up for 1 year. Mesh fixation was used for 7422 (66.1 %) of these patients and no mesh fixation for 3806 patients (33.9 %). Unadjusted analysis did not find any significant difference in the recurrence rate (0.88 % with fixation vs. 1.1 % without fixation; p = 0.259). Multivariable analysis of all potential influence factors (age, ASA, BMI, risk factors, defect size, mesh fixation, localization of defect, mesh size) did not identify any factor that impacted recurrence on 1-year follow-up. Only for medial and combined defect localization versus lateral localization was a highly significant effect identified (p < 0.001). With mesh fixation and larger mesh size, it was possible to significantly reduce the recurrence rate for larger medial hernias in this series (p = 0.046). For TAPP repair of an inguinal hernia, mesh fixation is not necessary in a significant number of patients. Patients with a medial and combined hernia are at higher risk of recurrence. In the patient series analyzed, it was possible to significantly reduce the recurrence rate with mesh fixation and larger mesh size for medial defects.

Seasonal phenology and abundance of Leucopis argenticollis, Leucopis piniperda (Diptera: Chamaemyiidae), Laricobius nigrinus (Coleoptera: Deridontidae) and Adelges tsugae (Hemiptera: Adelgidae) in the Pacific Northwest USA.

Adelges tsugae infested western hemlock trees were sampled periodically for 1 year at two locations in Oregon and Washington to compare the phenology and abundance of three associated predators (Leucopis argenticollis, Leucopis piniperda, and Laricobius nigrinus) and their host. On each sample date, two 3-10 cm long terminal twigs were collected from each tree and brought to the laboratory to count all life stages of A. tsugae and the three predators. Peak larval abundance of Leucopis spp. and La. nigrinus coincided with the presence of A. tsugae adults and eggs. Leucopis spp. larvae were present for a much longer period of time than were La. nigrinus larvae. Furthermore, Leucopis spp. larvae were present during both the progrediens and sistens egg stages, while La. nigrinus larvae were only present during the progrediens egg stage. Overall, we collected 2.3-3.5 times more Leucopis spp. of all life stages than La. nigrinus. These results support the continued study of Leucopis spp. from the Pacific Northwest as biological control agents for A. tsugae in the Eastern USA.

[Component separation for closing large abdominal wall defects: evolution of a method from 1990 to present day]. / Die Komponentenseparation zum Verschluss komplexer Bauchwandhernien: Entwicklung einer Technik von 1990 bis heute.

BACKGROUND: The separation of autologous and functional active components of the lateral abdominal wall for closing large midline defects was introduced in 1990. The original components separation technique (CS) has undergone numerous modifications. The aim of this work is to summarise the essential steps of the development. METHODS: Based on a literature review, the original technique, the modifications and advancements are presented and evaluated regarding indication, techniques and results. RESULTS: The original technique still has a high status, because of the large extent of rectus complex medialisation. Numerous modifications of the anterior conventional component separation with different clinical results were described. The development of a minimally invasive technique with balloon dilatation trocars was an essential step and decreased wound morbidity. The modified posterior component separation by transverse abdominis release currently seems to be an encouraging alternative to be regarded as a widening of the sublay technique. All methods can be combined with implantation of prosthetic or biological implants in intraperitoneal, sublay or onlay technique, whereby the recurrence rate can be decreased. CONCLUSION: From where we stand today no single technique can generally be recommended. The latest methods aim for decreasing complications and recurrences by means of minimally invasive procedures. The surgical strategy still depends on the complexity and extent of abdominal wall defect and has to be determined according to individual aspects and sometimes requires an interdisciplinary approach.

Immunohistochemical analysis on potential new molecular targets for esophageal cancer.

Despite multimodal therapeutic options, esophageal cancer is still among the most deadly malignancies. In the past decade, targeted therapy has shown great potential in other cancers, but data on esophageal carcinoma are still rare. Five potential new molecular targets in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) were investigated for their expression characteristics: vascular endothelial growth factor receptor (VEGFR)-3, human epidermal growth factor receptor-2, stem cell growth factor receptor, tissue inhibitors of metalloproteinase (TIMP)-4 and TIMP-3. One hundred seventy-one EAC and ESCC tissue samples obtained from patients undergoing esophagectomy from 2000 to 2008 were included. Clinical data were evaluated retrospectively. Immunohistochemical staining was performed using tumor tissue with and without neoadjuvant treatment and healthy tissue. For samples without neoadjuvant treatment, expression of all targets was higher in tumor tissue than in healthy tissue except for VEGFR-3 (>98% expression in both tissues). For TIMP-4, TIMP-3 and stem cell growth factor receptor, trends to higher expression in tumor tissue were also found in EAC and ESCC that had received neoadjuvant treatment. Using Matched-pair analysis, we compared target expression in tumor tissue with and without neoadjuvant treatment. Only TIMP-3 had significantly lower expression in neoadjuvant treated tumor tissue (EAC: P = 0.059, ESCC: P = 0.006). TIMP-4, TIMP-3 and VEGFR-3 appear to qualify for targeted therapy in esophageal cancer because of their high expression in neoplastic tissue. TIMP-3 appears to be downregulated in neoadjuvantly treated esophageal cancer, and VEGFR-3 shows high expression in healthy mucosa leading to severe side effects by molecular targeting. Thus, TIMP-4 seems the most promising target.

Routine versus no drain placement after elective laparoscopic cholecystectomy: meta-analysis of randomized controlled trials.

Routine drainage of the subhepatic space has been a surgical trend of open cholecystectomy, carried on to the era of laparoscopic surgery without substantial evidence. Avoiding the potentially devastating sequelae of an undetected bile leakage is the main rationale behind this practice. Aim of this meta-analysis was to compare evidence on routine drain placement after laparoscopic cholecystectomy versus no drainage. A meta-analysis of randomized controlled trials was conducted; outcome variables included postoperative pain, subhepatic collection, 30-day morbidity, wound-related complications, and drainage interventions. The fixed- and random effects models were used in order to calculate combined overall effect sizes of pooled data. Data are presented as the odds ratio (OR) or difference in means with 95% confidence interval (CI). Six randomized trials including 1167 patients were identified. Pain scores were significantly higher in the drainage group both at 6-12h (mean difference 1.12, 95% CI 1.01-1.24, P<0.0001) and at 12-24h after surgery (mean difference 1.12, 95% CI 0.86-1.39, P<0.0001). No difference was found with regard to the incidence of subhepatic collection and drainage procedures. A trend in favor of the no drain approach with regard to 30-day morbidity and wound infection was registered, although this was less pronounced after sensitivity analysis. The possible clinical benefit of routine use of abdominal drainage in uncomplicated laparoscopic cholecystectomies requires larger study populations. The approach is however not encouraged on the basis of the present analysis, as it results in increased postoperative pain and overall morbidity.

[Diagnosis and surgical therapy of hiatal hernia]. / Diagnose und chirurgische Therapie der Hiatushernie.

Using the usual diagnostic tools like barium swallow examination, endoscopy, and manometry, we are able to diagnose a hiatal hernia, but it is not possible to predict the size of the hernia opening or, respectively, the size of the hiatal defect. At least a correlation can be expected if the gastroesophageal junction is endoscopically assessed in a retroflexed position, and graded according to Hill. So far, it is not possible to come to a clear conclusion how the hiatal closure during hiatal hernia repair should be performed. There is no consensus on using a mesh, and when using a mesh which type or shape should be used. Further studies including long-term results on this issue are necessary. However, it seems obvious to make the decision depending on certain conditions found during operation, and not on preoperative findings.

[Inguinal hernia operations-Always outpatient?] / Leistenhernienoperationen ­ immer ambulant?

Inguinal hernia operations represent the most frequent operations overall with 300,000 interventions annually in Germany, Austria and Switzerland (DACH region). Despite the announced political willingness and the increasing pressure from the legislator to avoid costly inpatient treatment by carrying out as many outpatient operations as possible, outpatient treatment has so far played a subordinate role in the DACH region. The Boards of the specialist societies the German Hernia Society (DHG), the Surgical Working Group Hernia (CAH of the DHG), the Austrian Hernia Society (ÖHG) and the Swiss Working Group Hernia Surgery (SAHC) make inroads into this problem, describe the initial position and assess the current situation.

Human placental transthyretin in fetal growth restriction in combination with preeclampsia and the HELLP syndrome.

Fetal growth restriction is a serious, still poorly understood pregnancy-related pathology often associated with preeclampsia. Recent studies speculate on the role of human transthyretin, a carrier protein for thyroxin and retinol binding protein, in the etiology of both pregnancy pathologies. Objective was to investigate the localization and abundance of transthyretin (TTR) in placentas of pregnancies suffering from fetal growth restriction with and without preeclampsia and HELLP. This was a retrospective case control study on human paraffin-embedded placentas from pregnancies with a gestational age at delivery between the 24th and 34th week of gestation. 16 placentas were included in this study, 11 cases and 5 from normotensive pregnancies as controls. Cases were divided into three groups: four from early onset idiopathic intrauterine growth restriction (IUGR), four from early-onset severe preeclampsia (PE), and three from early-onset IUGR with preeclampsia plus HELLP syndrome. Distribution and abundance of TTR were investigated by means of immunohistochemistry. Semi quantitative analysis of TTR staining of placental sections revealed that TTR was mostly expressed in the villous trophoblast covering placental villi. Only weak staining of TTR in villous stroma could be detected. The comparison of placentas revealed that in pure IUGR and severe PE there is a much stronger TTR reactivity compared to controls and cases with IUGR + PE + HELLP. Concluding, the study showed that TTR is dysregulated in cases of IUGR and severe early onset preeclampsia. Interestingly, TTR expression is not affected in cases with HELLP syndrome that reveal the same staining intensities as age-matched controls.

Regulation of electrolyte and fluid metabolism in multi-stage ultra-marathoners.

The purposes of this study were (i) to determine the prevalence of exercise-associated hyponatremia (EAH) in multi-stage ultra-marathoners and (ii) to gain more insight into fluid and electrolyte regulation during a multi-stage race. Body mass, sodium concentration ([Na⁺]), potassium concentration ([K⁺]), creatinine, urea, specific gravity, and osmolality in urine were measured in 25 male ultra-marathoners in the 'Swiss Jura Marathon' 2008 with 11,000 m gain of altitude over 7 stages covering 350 km, before and after each stage. Haemoglobin, haematocrit, creatinine, urea, [Na⁺], [K⁺], and osmolality were measured in plasma before stage 1 and after stages 1, 3, 5, and 7. Two athletes (8%) showed plasma [Na⁺] <135 mmol/l. Body mass, plasma [Na⁺], and plasma [K⁺] remained unchanged (p>0.05). Urine specific gravity (p<0.001) and osmolality in both plasma (p<0.01) and urine (p<0.001) were increased and haematocrit (p<0.0001), haemoglobin (p<0.0001) and plasma albumin were decreased (p<0.001). Plasma volume (p<0.01) and plasma urea (p<0.001) were increased. The K⁺/Na⁺ ratio in urine increased >1.0 after each stage and returned to <1.0 the morning of the next stage (p<0.001). To summarize, more sodium than potassium was excreted during rest. The increased urinary sodium losses during rest are compatible with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or the cerebral salt-wasting syndrome (CSWS). Further studies are needed to determine the antidiuretic hormone (ADH) and both the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) during multi-stage races.

Effect of a multistage ultraendurance triathlon on aldosterone, vasopressin, extracellular water and urine electrolytes.

Prolonged endurance exercise over several days induces increase in extracellular water (ECW). We aimed to investigate an association between the increase in ECW and the change in aldosterone and vasopressin in a multistage ultraendurance triathlon, the 'World Challenge Deca Iron Triathlon' with 10 Ironman triathlons within 10 days. Before and after each Ironman, body mass, ECW, urinary [Na(+)], urinary [K(+)], urinary specific gravity, urinary osmolality and aldosterone and vasopressin in plasma were measured. The 11 finishers completed the total distance of 38 km swimming, 1800 km cycling and 422 km running within 145.5 (18.8) hours and 25 (22) minutes. ECW increased by 0.9 (1.1) L from 14.6 (1.5) L prerace to 15.5 (1.9) L postrace (P < 0.0001). Aldosterone increased from 70.8 (104.5) pg/mL to 102.6 (104.6) pg/mL (P = 0.033); vasopressin remained unchanged. The increase in ECW was related neither to postrace aldosterone nor to postrace vasopressin. In conclusion, ECW and aldosterone increased after this multistage ultraendurance triathlon, but vasopressin did not. The increase in ECW and the increase in aldosterone were not associated.

[Verumontanum mucosal hyperplasia as a differential diagnosis of a local recurrence following radical prostatectomy]. / Verumontanum-Mukosahyperplasie als Differenzialdiagnose eines Lokalrezidivs nach radikaler Prostatektomie.

Verumontanum mucosal gland hyperplasia (VMGH) is a benign microacinar proliferative lesion, which occurs exclusively in the verumontanum and the posterior urethra and is one of the lesions that may be confused with a low-risk adenocarcinoma of the prostate gland.We present the case of a 72-year-old male patient who underwent radical prostatectomy due to an adenocarcinoma of the prostate gland (pT2c pN0 cM0 R0, Gleason Score: 3 + 3 = 6). Five years after the operation, we sonographically detected a 3x2 cm large tumour in the prostate bed. While our first assumption was a PSA-negative local recurrence following radical prostatectomy, a comprehensive histological examination along with the clinical evaluation led us to the diagnosis of a VMGH. VMGH is a less well-known differential diagnosis of PSA-negative local recurrence following radical prostatectomy, whose clinical manifestation should be presented.

[Accreditation in pathology and neuropathology : Paths and pitfalls]. / Akkreditierung in der Pathologie und Neuropathologie : Wege und Pitfalls.

There are many good reasons for accreditation in pathology or neuropathology as per DIN EN ISO/IEC 17020, regardless of the size and range of services of the facility. Only accreditation - in contrast to certification - also confirms professional competence. This article describes how to establish a quality management system that conforms to standards as effectively as possible and how to maintain it, involve staff, and avoid common pitfalls. Adequate resources and active management support are essential. In this way, not only can accreditation succeed, but the facility itself and its employees can benefit from quality management in their daily work.

Negative regulation of airway responsiveness that is dependent on gammadelta T cells and independent of alphabeta T cells.

The mechanisms regulating airway function are complex and still poorly understood. In diseases such as asthma, involvement of immune-dependent mechanisms has been suggested in causing changes in airway responsiveness to bronchoconstrictors. We now demonstrate that gammadelta T cells can regulate airway function in an alphabeta T cell-independent manner, identifying them as important cells in pulmonary homeostasis. This function of gammadelta T cells differs from previously described immune-dependent mechanisms and may reflect their interaction with innate systems of host defense.

Transitional B cells are the target of negative selection in the B cell compartment.

B lymphocytes recognize antigen through membrane-bound antigen-receptors, membrane IgM and IgD (mIgM and mIgD). Binding to foreign antigens initiates a cascade of biochemical events that lead to activation and differentiation. In contrast, binding to self-antigens leads to death or to inactivation. It is commonly believed that the B cells acquire the ability to discriminate between self and nonself in the early phases of development. We report here that immature B cells, which have just emerged from the mIgMneg, B220pos pool, are not deleted upon binding of self-antigen. In vivo, developing B cells become sensitive to tolerance induction in a relatively late window of differentiation, when they are in transition from the immature (HSAbright, B220dull) to the mature (HSAdull, B220bright) stage. In the transitional B cells, early markers of differentiation such as Pgp1 (CD44) and ThB reach the highest level of expression, while the expression of CD23 and mIgD, late markers of differentiation, and expression of class II MHC, progressively increases. Most of the transitional B cells, but only few of the mature and of the immature B cells, express the fas antigen, while mature B cells, but not immature and transitional B cells, express bcl-2 protein. mIgM is present in low amounts in immature B cells, reaches the highest level of expression in transitional B cells and is down-regulated in mature resting B cells, where it is coexpressed with mIgD. The high expression of mIgM, the presence of the fas antigen and the absence of bcl-2 protein is compatible with the high sensitivity of transitional B cells to negative selection. In vitro, immature B cells die rapidly by apoptosis after cross-linking of mIgM. This result, combined with the resistance of immature B cells to elimination in vivo, suggests that early in development the stroma cell microenvironment modulates signals transduced through mIgM. The functional and phenotypic division of IgMpos bone marrow B cells in three compartments not only allows to define the target population of physiological processes like negative selection, but will also be a helpful tool for an accurate description of possible developmental blocks in mutant mice.