[Recommendations on treatment of acute appendicitis : Recommendations of an expert group based on the current literature]. / Empfehlungen zur Therapie der akuten Appendizitis : Empfehlungen einer Expertengruppe vor dem Hintergrund der aktuellen Literatur.

The paradigm shift in the treatment concept for acute appendicitis is currently the subject of intensive discussions. The diagnosis and differentiation of an uncomplicated from a complicated appendicitis as well as the selection of an adequate treatment is very challenging, especially since nonoperative treatment models have been published. The laparoscopic appendectomy is still the standard for most cases. Guidelines for the treatment of acute appendicitis do not exist in Germany. Therefore, a group of experts elaborated 21 recommendations on the treatment of acute appendicitis after 3 meetings. After initial definition of population, intervention, comparison and outcome (PICO) questions, recommendations have been finalized through the Delphi voting system. The results were evaluated according to the current literature. The aim of this initiative was to define a basic support for decision making in the clinical routine for treatment of acute appendicitis.

Screening of more than 2000 Hungarian healthcare workers' anti-measles antibody level: results and possible population-level consequences.

Due to the European measles epidemic and the increased number of imported cases, it can be theorised that the risk of exposure among Hungarian healthcare workers (HCWs) has increased. In 2017, the increased measles circulation in the region led to the emergence of smaller local and hospital epidemics. Therefore, our objective was to determine the herd immunity in the high-risk group of HCWs. A hospital-based study of detecting anti-measles IgG activity was performed in 2017 and included 2167 employees of the Military Medical Centre (Hungary). The screening of HCWs presented a good general seropositivity (90.6%). The highest seroprevalence value (99.1%) was found in the age group of 60 years or older. The lowest number of seropositive individuals was seen in the 41-45 years (86.2%) age group, indicating a significant herd immunity gap between groups. Regarding the Hungarian data, there might be gaps in the seroprevalence of the analysed HCWs, implying that susceptible HCWs may generate healthcare-associated infections. This study suggests that despite the extensive vaccination and high vaccine coverage, it is still important to monitor the level of protective antibodies in HCWs, or in a representative group of the whole population of Hungary, and possibly in other countries as well.

[3 D laparoscopy versus 2 D laparoscopy : An up to date evaluation]. / 3-D-Laparoskopie vs. 2­D­Laparoskopie : Eine aktuelle Bewertung.

BACKGROUND: The 3D laparoscopy is currently under intensive discussion. At the moment the majority of newly acquired laparoscopy systems include the 3D technique. New 4K systems, which will be offered in combination with 3D, are complicating the decision-making when buying new laparoscopic systems. The aim of the article is to show the advantages and possible limitations of 3D laparoscopy. Furthermore, the position of 3D laparoscopy in the current video market is evaluated. MATERIAL AND METHODS: This study was based on an up to date literature search in PubMed. Concerning the question whether the 3D is replacing the 2D laparoscopy, observations from the industry and a personal evaluation were included in the analysis. RESULTS: The current studies show clear advantages of 3D laparoscopy concerning operation time, efficiency and workload. A major proportion of the studies were conducted on simulation trainers; however, some clinical trials also confirmed these results. The learning curve in laparoscopic surgery is clearly improved with the 3D technique and 3D also seems be useful for operations by experts. The limitation is that not every surgeon can see three dimensionally. Furthermore, the set-up in the operation room needs to be optimized so that a 3D system can be successfully implemented with the nursing staff and side effects, such as exhaustion, dizziness or headache can be prevented. CONCLUSION: The choice of video system will depend on the personal interest of the surgeon and the ability to see 3D. It can be assumed that the majority of the systems will include 3D laparoscopy but 2D laparoscopy will not be completely replaced. A dynamic development of 3D in association with 4K and robotics can be expected.

Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia.

A child, 2 years with the 'hypercalprotectinaemia with hyperzincaemia' clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38°C, thrombocythaemia of > 700 × 109 /l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 2·0 array in blood on three occasions 3-5 months apart. Major up-regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors and activators, accounting for the febrile apathic state; and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Novel bocaparvoviruses in rabbits.

Bocaparvovirus is a newly established genus within the family Parvoviridae and has been identified as a possible cause of enteric, respiratory, reproductive/neonatal and neurological disease in humans and several animal species. In this study, metagenomic analysis was used to identify and characterise a novel bocaparvovirus in the faeces of rabbits with enteric disease. To assess the prevalence of the novel virus, rectal swabs and faecal samples obtained from rabbits with and without diarrhoea were screened with a specific PCR assay. The complete genome sequence of the novel parvovirus was reconstructed. The virus was distantly related to other bocaparvoviruses; the three ORFs shared 53%, 53% and 50% nucleotide identity, respectively, to homologous genes of porcine bocaparvoviruses. The virus was detected in 8/29 (28%) and 16/95 (17%) samples of rabbits with and without diarrhoea, respectively. Sequencing of the capsid protein fragment targeted by the diagnostic PCR identified two distinct bocaparvovirus populations/sub-types, with 91.7-94.5% nucleotide identity to each other. Including these novel parvoviruses in diagnostic algorithms of rabbit diseases might help inform their potential pathogenic role and impact on rabbit production and the virological profiles of laboratory rabbits.

Full-genome sequencing of a Hungarian canine G3P[3] Rotavirus A strain reveals high genetic relatedness with a historic Italian human strain.

A canine Rotavirus A strain was identified in the fecal specimen of a young dog during 2012 in Hungary. The strain RVA/Dog-wt/HUN/135/2012/G3P[3] shared complete genotype constellation (G3-P[3]-I3-R3-C3-M3-A15-N2-T3-E3-H6) and high genome sequence similarity (nt, 98.8 %) with a historic human strain, RVA/Human-tc/ITA/PA260-97/1997/G3P[3]. This study provides evidence for the canine origin of the unusual NSP1 genotype, A15, and reinforces the hypothesis of direct interspecies transmission of canine rotaviruses to humans.

Comparison of test specificities of commercial antigen-based assays and in-house PCR methods for detection of rotavirus in stool specimens.

Seven commercial rotavirus antigen assays were compared with in-house PCR methods for detecting rotavirus in stool specimens. The assay sensitivities were 80% to 100%, while the specificities were 54.3% for one commercial immunochromatographic (ICT) method and 99.4% to 100% for other assays. Thus, except for one commercial ICT, all the assays were generally reliable for rotavirus detection.

[Surgical technique for laparoscopic kidney donation]. / Die chirurgische Technik der laparoskopischen Nierenlebendspende.

OBJECTIVE: Dialysis cannot fully replace kidney function in patients diagnosed with end-stage renal disease. Patients undergoing dialysis therapy show a significantly reduced quality of life, morbidity and mortality compared to healthy individuals. Every patient diagnosed with end-stage renal disease should be evaluated for a potential kidney transplant, potentially by means of living-donor kidney donation. INDICATIONS: Via living-donor kidney donation, patients diagnosed with end-stage renal disease can receive a kidney transplant already before dialysis therapy needs to be initiated. Those patients show a significantly improved long-term graft and patient survival in comparison to patients transplanted after cadaveric organ donation. PROCEDURE: We here describe the evaluation process of living-donor kidney donation and the procedure of transperitoneal laparoscopic donor-nephrectomy. CONCLUSION: Although technically demanding, laparoscopic donor nephrectomy after careful donor evaluation is a safe procedure. An interdisciplinary medical-surgical management is important for both careful patient selection and life-long aftercare.

[Operative therapy of hepatocellular carcinoma]. / Operative Therapie des hepatozellulären Karzinoms.

BACKGROUND: Curative surgical strategies for hepatocellular carcinoma are liver resection and transplantation. METHODS: This overview is based on a selective literature search on therapeutic strategies for hepatocellular carcinoma. The new German S3 guidelines are outlined in detail but guidelines from other societies were also taken into consideration. RESULTS: The question of resectability is of utmost importance and should not only be evaluated in an interdisciplinary tumor board but also in an experienced liver center. Primary resectable hepatocellular carcinoma in patients without portal hypertension should be resected. Most patients without cirrhosis qualify for resection. In patients with Child grade A cirrhosis but without severe portal hypertension and a stable health status, a liver resection should be considered. At resection intraoperative ultrasound is standard. Intrahepatic tumor recurrences also can be re-resected or thermally ablated. New techniques for extended liver resections or minimally invasive liver resections are commonly used and have to be studied further. CONCLUSION: In addition to liver resection, liver transplantation now represents a standard therapy for hepatocellular carcinoma in cirrhosis. Observing the Milan selection criteria 5-year survival rates of 70-90 % can be achieved; however, increasing organ shortage leads to longer waiting times and thus higher risk of tumor progression. Therefore, patients on the waiting list should have follow-up imaging and bridging with surgical resection, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) by interventional radiology. Living donor liver transplantation should be considered in all these patients with expected longer waiting times.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

FOXP3+ regulatory T-cells in renal allografts: correlation with long-term graft function and acute rejection.

BACKGROUND: The interpretation of a cellular infiltrate as cytotoxic or tolerogen represents an unsolved challenge in current transplantation. The so-called regulatory CD4+ CD25+ T-cells which express the FOXP3 gene have received increasing interest with respect to this question. The existing studies concerning the role of FOXP3+ Tregs for transplant tolerance yielded contradictory results. METHODS: We examined the numbers of the FOXP3+ Tregs in two groups of renal allograft biopsies both showing cellular infiltration, but either without (n=29) or with signs of acute cellular rejection (n=26), by means of immunofluorescence and correlated the amount of FOXP3+ Tregs to renal function at the time of biopsy and after 1 and 2 years of follow up. RESULTS: The number of FOXP3+ Tregs within infiltrates in non-rejecting biopsies did not correlate with renal function after 1 and 2 years. There were no significant differences in the numbers of FOXP3+ Tregs between biopsies with or without borderline infiltrates. Increased numbers of FOXP3+ Tregs were not associated with an ameliorated severity of graft rejection and did not correlate with outcome after the rejection episode and renal function after 1 and 2 years. CONCLUSIONS: The identification of the FOXP3+ regulatory cells within the allograft cannot be considered as an appropriate marker for the interpretation of infiltrates as cytotoxic or tolerogenic or as a prognostic marker for later transplant function.

Characterization of microvascularization of liver tumor lesions with high resolution linear ultrasound and contrast enhanced ultrasound (CEUS) during surgery: First results.

AIM: Evaluation of high resolution linear ultrasound and intra-operative linear contrast enhanced ultrasound (CEUS) and its benefit for the detection and characterization of tumor lesions. MATERIAL AND METHODS: Twenty patients were investigated preoperatively regarding tumor detection using CT (n = 8) or MRI (n = 12) and image fusion (VNav) (n = 3). All patients had surgery for their hepatic tumor (hepatocellular carcinoma (HCC), cholangiocellular carcinoma (CCC), metastasis, and adenoma). Ultrasound was performed intra-operatively first with B-scan using a convex probe. Than multifrequency linear transmitters (6-9 MHz, 6-15 MHz, LOGIQ E9, GE) were applied for B-scan, coulor coded Doppler sonography (CCDS) and Power Doppler followed by dynamic CEUS with Contrast Harmonic Imaging (CHI) after bolus injection of a maximum of 15 mL SonoVue®. RESULTS: In 9 cases with the use of intra-operative CEUS additional tumor lesions (diameter 4-15 mm) could be detected and were histologically confirmed after surgical resection (7 cases) or intra-operative biopsy (2 cases). Using intraoperative CEUS 64 tumor lesions could be detected compared to 51 tumor lesions detected by preoperative CT or MRI (p < 0.05). Using the 6-15 MHz multifrequency linear transducer with CHI, arterial perfusion of adenomas, neuroendocrine metastases and HCC lesions was detectable. In 3 cases a resection was not achievable. Two of these cases were treated with radio frequency ablation (RFA). The other case had no curable option due to multifocal tumor manifestation. CONCLUSION: The intra-operative use of high-resolution linear transducer techniques with CEUS offers new diagnostic perspectives for an effective liver surgery.

Giant cell hepatitis: an unusual cause of fulminant liver failure.

Giant cell hepatitis is a very rare disease of unknown origin. It has been hypothesized that drugs, viral infections, or autoimmune reactions may play a pathogenetic role. Here, we describe a 33 year old patient with bacterial bronchitis who was treated with doxycycline (100 mg/d) for one week. Furthermore the patient complained of malaise and a distinct jaundice. Liver parameters increased dramatically (AST 4670 U/l, ALT 5350 U/l, bilirubin 226 µmol/l) and liver function was impaired (INR = 1,45). The ultrasound scan showed a hepatomegaly with no signs of cirrhosis, normal spleen size and normal bile ducts; liver perfusion was normal. No evidence of Wilson's disease, hemochromatosis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis A, B, C and E, HIV, CMV, VZV, adenoviral infections, or paracetamol intoxication was found. Subsequently, the patient developed acute liver failure (AST 2134 U/l, ALT 2820 U/l, bilirubin 380 µmol/l, INR 3.0) and a beginning renal failure. Therefore, he was transferred to our transplant center. Due to increasing confusion and somnolence due to cerebral edema mechanical ventilation was needed. Because of an acute renal failure and severe hepatic encephalopathia MARS-hemodialysis was performed. Three weeks after the appearance of the jaundice he underwent liver transplantation (MELD 40). Surprisingly, in the explanted liver the diagnosis of giant cell hepatitis was made. Today--2 years after successful liver transplantation--the patient is in very good condition with normal liver function. In conclusion, giant cell hepatitis is a rare cause of acute liver failure that is often recognized only histologically.

[Surgical treatment of liver metastases]. / Chirurgische Therapie von Lebermetastasen.

The treatment of liver metastases has become more and more complex in recent years. More individualized therapeutic concepts have become feasible by the increase in different treatment options (surgical, interventional and oncological). In the field of surgery the definition of resectability could be broadened. More extensive liver resections are being performed, which are partly carried out as staged resections after neoadjuvant chemotherapy in combination with portal vein embolization (PVE), radio frequency ablation (RFA) or other procedures in order to increase complete resection rates and patient survival. Consequently the overall 5 year survival rate of patients with resected colorectal liver metastases has doubled from 30% to nearly 60% in the past decade. Due to the complexity of the different treatment approaches an interdisciplinary assessment of the individual patient in experienced centers is necessary.

The impact of "high-producer" interleukin-6 haplotypes on cardiovascular morbidity and mortality in a kidney transplant population.

BACKGROUND: At present, inflammation is considered to be one of the key players in the development and maintenance of atherosclerosis, with ample impact on renal transplant outcomes. Interleukin-6 (IL-6) levels and the underlying genetically determined "high-producer" status impact cardiovascular morbidity and mortality. In end-stage renal disease (ESRD) patients, the role of genetically determined IL-6 differences in cardiovascular and renal outcomes of kidney transplantation is controversial. In this study, we sought to clarify the influence of IL-6 haplotypes on cardiovascular and renal outcomes among kidney transplant recipients. METHODS: Three hundred fifty-two first kidney transplant patients were genotyped for the two "clade" IL-6 polymorphisms ((-174)G/C and (1888)G/T) and two missense polymorphisms (Pro32Ser, Asp162Val), which are known to influence IL-6 levels and outcome. RESULTS: We observed four IL-6 haplotypes among our population: CCAG: 57.0%, CCAT: 2.8%, GCAT: 39.2%, GCTT: 1.0%. After stratifying the haplotypes into diplotypes in three different models, we failed to observe associations with early or late graft outcomes, or with all-cause or cardiovascular mortality. These findings were also confirmed when we separately analyzed each polymorphism. CONCLUSION: Despite evidence of associations in other transplant and ESRD cohorts, we could not confirm any association between IL-6 haplotypes/diplotypes and cardiovascular or graft-related outcomes among our population at high risk for inflammatory diseases.

New real-time image fusion technique for characterization of tumor vascularisation and tumor perfusion of liver tumors with contrast-enhanced ultrasound, spiral CT or MRI: first results.

AIM: Evaluation and characterization of the vascularisation and perfusion of liver tumors by means of image fusion of dynamic contrast-enhanced ultrasound (CEUS), multidetector-CT (MD-CT) or magnetic resonance imaging (MRI) with the ultrasound navigation technique. MATERIAL: For interventional planning a real-time image fusion involving CEUS (LOGIQ E9, GE) was performed in 20 patients (12 men, 8 women, age 43-69 years, median 54) with histologically confirmed malignant liver tumors (9 x hepatocellular carcinoma (HCC), 5 x metastases, 2 x hemangiomas, 1 x cholangiocellular carcinoma (CCC), 1 x lymphoma, 1 x neuroendocrine tumor, 1 x focal nodular hypoplasia (FNH)). In 17 patients the real-time CEUS was fused with contrast-enhanced MD-CT and in three patients with contrast-enhanced MRI (Gd-DTPA and liver-specific contrast medium Resovist. All of the ultrasound examinations were performed by an experienced examiner with a multi-frequency probe (2-5 MHz, LOGIQ E9, GE); dynamic image sequences up to 3 minutes in true agent detection mode of contrast harmonic imaging (CHI) were documented. An evaluation of the tumor was performed by the characterization of the dynamics of the contrast medium and microperfusion with CEUS, fused with MD-CT or MRI. RESULTS: In 18/20 cases there was an accurate agreement with respect to the segmental localization of the tumor lesion. In 2/20 cases the localization was comparable with the image fusion of CEUS and reference imaging (a total of at least 65 lesions: 3 x 1 lesion, 5 x 2 lesions, 8 x 3 lesions, 2 x 5 lesions, 1 x 8 lesions, 1 x at least 10 lesions (multifocal)). With image fusion a certain characterization was attained in 17/20 cases. In 3/20 cases (lymphoma after liver transplantation, multifocal CCC, metastases of a neuroendocrine tumor) the diagnosis was at first doubtful and had to be confirmed histologically. In patients with HCC an evaluation of the tumor perfusion was feasible in all 9 cases (8/9 after local trans-arterial chemoembolization (TACE), 1/9 after radio frequency ablation (RFA)). A tendency toward the identification of more lesions with image fusion of CEUS and CT than with contrast-enhanced CT alone could be recognized (p=0.059). CONCLUSION: Applying a new real-time fusion technique of MD-CT or MRI with CEUS new possibilities for the evaluation, intervention and monitoring of the therapy of liver lesions were made possible, since the method also comprised the dynamic microperfusion.

Percutaneous transluminal angioplasty as first-line treatment of transplant renal artery stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a frequent complication after renal transplantation, however long-term follow-up data after interventional treatment are rare. PATIENTS: In our transplant center 11 of 264 consecutive renal transplant recipients (4.17%) were diagnosed with TRAS. In addition, TRAS occurred in 2 renal transplant recipients that had been transplanted at other centers but who had their follow-up examinations in our center. Either a rise of the serum creatinine level and/or worsened systemic hypertension or routine examination with color Doppler sonography were indications for further diagnostic workup. METHODS: Direct angiography of the transplant renal artery was performed followed by percutaneous transluminal angioplasty (PTA) after the diagnosis of TRAS was confirmed in all of these patients. RESULTS: The immediate success rate for PTA was 92.3% (12/13). Only 1 patient with a severe kinking of the transplant renal artery had to undergo surgery to restore renal function. No complications occurred after the interventions. Thereafter the patients were monitored for a mean observation period of 33.15 months. Serum creatinine levels were significantly lower after the intervention, and estimated glomerular filtration rate (eGFR) increased accordingly. With regard to blood pressure there was only a trend for lower blood pressure levels and less antihypertensive use, whereas the dose of the prescribed drugs decreased significantly with time after interventional treatment of TRAS. In addition, a long-lasting rise of the hemoglobin levels could also be demonstrated. CONCLUSION: In summary, the beneficial effect of PTA of TRAS on renal function is long-lasting. Therefore, PTA, usually combined with stent placement, should be first-line treatment in TRAS in all patients. Surgical revascularization is only warranted, if PTA fails.

Severe renal vein stenosis of a kidney transplant with beneficial clinical course after successful percutaneous stenting.

A 51-year-old renal transplant recipient presented with marked renal function deterioration 13 months after renal transplantation. After exclusion of ureteral obstruction, transplant artery stenosis and acute rejection, the diagnosis of a severe renal vein stenosis was made by an MR scan. After angiographic confirmation of the stenosis, treatment was attempted with percutaneous stent angioplasty. The long-term clinical course was favorable, with marked improvement in renal function. Transplant renal vein stenosis is a rare, but potentially curable, cause of renal allograft functional deterioration.