Gas Chromatography-Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies.

Thymoquinone (TQ) is the primary component of Nigella sativa L. (NS) oil, which is renowned for its potent hepatoprotective effects attributed to its antioxidant, anti-fibrotic, anti-inflammatory, anti-carcinogenic, and both anti- and pro-apoptotic properties. The aim of this work was to establish a method of measuring TQ in serum in order to investigate the pharmacokinetics of TQ prior to a targeted therapeutic application. In the first step, a gas chromatography-mass spectrometry method for the detection and quantification of TQ in an oily matrix was established and validated according to European Medicines Agency (EMA) criteria. For the assessment of the clinical application, TQ concentrations in 19 oil preparations were determined. Second, two serum samples were spiked with TQ to determine the TQ concentration after deproteinization using toluene. Third, one healthy volunteer ingested 1 g and another one 3 g of a highly concentrated NS oil 30 and 60 min prior to blood sampling for the determination of serum TQ level. After the successful establishment and validation of the measurement method, the highest concentration of TQ (36.56 g/L) was found for a bottled NS oil product (No. 1). Since a capsule is more suitable for oral administration, the product with the third highest TQ concentration (No. 3: 24.39 g/L) was used for all further tests. In the serum samples spiked with TQ, the TQ concentration was reliably detectable in a range between 5 and 10 µg/mL. After oral intake of NS oil (No. 3), however, TQ and/or its derivatives were not detectable in human serum. This discrepancy in detecting TQ after spiking serum or following oral ingestion may be attributed to the instability of TQ in biomatrices as well as its strong protein binding properties. A pharmacokinetics study was therefore not viable. Studies on isotopically labeled TQ in an animal model are necessary to study the pharmacokinetics of TQ using alternative modalities.

Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure.

PURPOSE: Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy. METHODS: In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses. RESULTS: Volumetric analysis showed a significant volume increase, especially for patients with colorectal metastases. Pre-existing liver parenchyma damage (odds ratio = 0.717, p = 0.017) and preoperative chemotherapy were found to be significant predictors (odds ratio = 0.803, p = 0.045) of higher morbidity and mortality. In addition, a survival benefit for maintenance of middle hepatic vein was shown. CONCLUSION: This technical modification of the ALPPS procedure can accentuate future liver remnant volume hypertrophy. The higher morbidity and mortality observed are most likely associated with pre-existing parenchymal damage within this group.

Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

[Benign liver tumors : Diagnostics and treatment]. / Benigne Lebertumoren : Diagnostik und Behandlung.

Benign liver tumors are often detected during routine ultrasound examinations or as an incidental finding in radiological imaging. Only very few benign liver tumors are at risk of becoming malignant. In the majority of cases the differentiation from malignant tumors is currently carried out using imaging procedures. In a few cases of diagnostic uncertainty, a transcutaneous liver biopsy can lead to clarification. If the suspicion of malignancy is substantiated or this cannot be excluded with absolute certainty, the tumor should be removed by partial liver resection.

[Application of the Objective Structured Clinical Examination (OSCE) in German Medical Schools: An Inventory]. / Objective Structured Clinical Examination (OSCE) an Medizinischen Fakultäten in Deutschland ­ eine Bestandsaufnahme.

INTRODUCTION: The German medical licensing regulations, as amended by the government in 2002, now require the assessment of clinical skills in undergraduate medical education. As a result, the Objective Structured Clinical Examination (OSCE) was introduced as an assessment tool in many medical schools. This article provides a detailed inventory of the current application of the OSCE assessment in Germany. METHODS: From June to September 2015, the implementation of the OSCE in all 36 German medical schools was investigated using semi-structured telephone interviews and email correspondence. The areas of focus comprised implementation of the OSCE, and number and type of performance records according to the medical licensing regulations or involved disciplines. Following collection, data were analysed quantitatively and qualitatively. RESULTS: All medical schools (100%) participated in the survey. Nearly every school (94%) has introduced the OSCE into its assessment portfolio, however, to varying extents. For each location, the numbers range between 0 and 18 (M=4.7) performance records of the clinical science section assessed by OSCEs. The implementation of this assessment format includes most of the clinical performance records, but more than half (51.4%) of these cover surgery, internal medicine, emergency medicine, anaesthesiology, and orthopaedics. CONCLUSION: The results reported in this paper confirm the widespread introduction of the OSCE assessment in German medical schools. However, the implementation remains heterogeneous with respect to the scope, schools and individual disciplines involved in the process. In order to ensure extensive clinical competence of prospective physicians the application of the OSCE should be broadened. For this purpose, further information to convince medical school staff is still required.

[Liver Transplantation as Treatment for Rare Diseases in Adults]. / Lebertransplantation als Therapie von seltenen Erkrankungen beim Erwachsenen.

In addition to the main indications pertaining to 95 % of all patients receiving liver transplantation in Germany, there are numerous other diseases that may become clinically evident in the adult age and may lead to the decision for liver transplantation. These may be metabolic diseases with their main defect located in the liver, malformations of liver cells, hepatic vascular diseases and rare tumours of the liver. Standard exceptions for the listing are in place only for a limited number of diseases. Exact diagnostics and the point in time for transplantation are crucial for the prognosis.

Effects of methylene-blue staining on the extent of pilonidal sinus excision.

OBJECTIVE: We aimed to examine the effects of methylene-blue staining (MBS) on the volume of specimens after excision of pilonidal sinuses. METHOD: This was a retrospective analysis of 135 excised specimens after pilonidal sinus (PS) surgery. All patients underwent procedures at the Department of Surgery of University Hospital Jena between 2000 and 2010. All specimens were measured in three dimensions. To calculate the volumes of excised specimens, we used a model of a hemi-ellipsoid. Demographic information (age, height, weight, body mass index, smoking status) were also obtained for all patients. RESULTS: Excised specimens with MBS had significantly larger volumes (p<0.001) as reflected in length (p=0.001), width (p=0.001), and depth (p=0.017) of the excised specimen compared with specimens that were not stained with methylene blue (MB). In addition, the volume was larger in subjects with a recurrent PS (p=0.021), which was predominantly the case in female subjects (p=0.025). CONCLUSION: These data suggest that excised specimens with MBS had significantly larger volumes of the excised specimen compared with specimens that were not stained with MB. MBS of a fistula system could enable such a system to be marked sufficiently, thereby facilitating complete resection of a PS.

[Vascular Problem Constellations and the Operational Tactical Approaches in Post-Mortem Liver Transplantations]. / Vaskuläre Problemkonstellationen und ihre operationstaktischen Lösungsansätze im Rahmen der postmortalen Lebertransplantation.

In liver transplantation, vascular problems may occur in the donor as well as in the recipient and during the donor operation as well as during the transplantation. They have a major influence on the outcome of the transplantation. In addition to anatomic variants, arteriosclerotic vascular diseases, complications from portal hypertension, vascular lesions from mistakes during the donor operation, complications from interventions and bridging procedures need to be identified and treated. In addition to duplex sonography and contrast enhanced computed tomography, invasive vascular diagnostics (digital subtraction angiography) are established for diagnostic purposes. Problem constellations should be identified prior to transplantation and the technique of the donor operation and the transplantation should be adjusted accordingly. Problems that are diagnosed after transplantation may be treated interventionally or with open surgery. In a number of cases, vascular complications lead to loss of the transplant or death of the recipient from post-operative organ failure.

[Extended Pathohistological Criteria for Assessment of the Long-Term Prognosis of Gastric Cancer]. / Erweiterte pathohistologische Kriterien zur Bewertung der Langzeitprognose des Magenkarzinoms.

BACKGROUND: Gastric cancer is one of the most frequent tumour diseases worldwide. Despite numerous innovations in the diagnostic procedures and treatment the prognosis remains poor as the detection of the disease depends on tumour-associated symptoms which develop rather late in the majority of cases. The treatment outcomes may be improved by a more differentiated and individualised evaluation of the tumour biology. We present a detailed analysis of potentially relevant factors. MATERIAL AND METHODS: From 1995 to 2011, data from 923 patients with gastric cancer have been collected in a prospective tumour database. We performed monovariate and multivariate analyses of factors. For the statistical analyses, SPSS software version 19.0 was used. The literature research was performed with Medline. RESULTS: 748 patients underwent surgical exploration. The resection rate was 87 % with a morbidity and mortality of 27 and 9 % (2004 to 2001: 13 and 5 %), respectively. 36 and 29 % of patients survived 5 years or 10 years, respectively. The 5-year and 10-year survival after curative resection was 58 and 46 %, respectively. TNM-associated criteria, tumour size, histological growth pattern, intestinal metaplasia, location of the tumour and classification according to Lauren were of significant influence in the monovariate analyses. In the multivariate analysis, tumour size, curative resection and lymph node involvement were independent prognostic factors. 90 % of the tumour recurrences developed within five years. The median recurrence-free interval was 16 months. Depending on the type of tumour, different survival times were identified. The 228 patients with node-negative curatively resected gastric cancer had a markedly better long-term prognosis. Diffuse type according to Lauren, tumour size, non-tubular histological growth pattern, female sex and proof of serosa infiltration from the primary tumour were prognostic factors in the monovariate analysis. In the multivariate analysis, tumour size was an independent significant prognostic factor (p = 0.05). CONCLUSION: The data analyses showed that the evaluation of gastric cancer may be extended in a sensitive way by factors that have not been previously established. The benefit of an individualised structured treatment and follow-up on the basis of extended criteria should be investigated in future studies.

[Living Donor Liver Transplantation - Past and Present]. / Lebertransplantation mit Lebendspende ­ Historie und Gegenwart.

Since the first living donor liver transplantations at the end of the 1980s, this transplantation technique has developed as an established tool within the modern transplantation medicine. Especially in Asia, the majority of liver transplantation is performed through living donation, mainly for religious reasons. Liver grafts for adult recipients are mainly the right liver lobe of the donor, for paediatric recipients mainly the left lateral lobe. In some cases, the living donor liver transplantation is realised from two different donors for one recipient, the so-called "dual graft" transplantation. This article summarises the history of living donor liver transplantation up to the current status of this transplantation procedure worldwide.

Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

UNLABELLED: DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). PRIMARY ENDPOINT: eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable.

MALDI imaging-based classification of hepatocellular carcinoma and non-malignant lesions in fibrotic liver tissue.

Histopathologic differentiation of nodular lesions in cirrhotic liver is difficult even for experienced hepatopathologists especially regarding diagnosis of hepatocellular carcinoma (HCC) in biopsies. For this reason, new tissue markers are needed to reinforce histopathologic decision-making. With advances in molecular techniques, proteomic analysis may help to confirm the diagnosis of HCC. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful technology which allows to determine and to localize proteins directly in tissue sections. Using MALDI IMS proteomic patterns of cryosections with lesions of HCC (n = 15) and non-malignant fibrotic liver tissue (n = 11) were investigated to establish a classification model of HCC, which was validated in an independent set of tissue to distinguish HCC (n = 10) from regenerative nodules (n = 8). By correlating generated mass spectrometric images with the histology of the tissue sections we found that the expression of 4 proteins as indicated by m/z 6274, m/z 6647, m/z 6222 and m/z 6853 was significantly higher in HCC tissue than in non-tumorous liver tissue. The generated classification model based on the most significant 3 differentially expressed proteins allowed a reliable prediction of benign and malignant lesions in fibrotic liver tissue with a sensitivity and specificity of 90 % in the validation set. The identified MALDI IMS proteomic signature can be diagnostically helpful to allow simplifying the diagnostic process and minimize the risks of delays in establishing the objective final diagnosis and initiating treatment of patients with HCC.

[Classic Limberg Flap Procedure for Treatment of a Sacrococcygeal Pilonidal Sinus Disease - Explanation of the Surgical Technique]. / Klassische Rautenplastik nach Limberg zur Behandlung einer sakrokokzygealen Pilonidalsinuserkrankung - Erklärung der OP-Technik.

INTRODUCTION: Sacrococcygeal pilonidal sinus disease is frequently encountered in surgical practice. Besides excision only, the current pilonidal sinus guideline of the Association of the Scientific Medical Societies in Germany (AWMF-S3) also recommends plastic surgical procedures such as the cleft-lift operation described by Bascom, the Karydakis flap procedure and, due to the low recurrence rates, the Limberg flap procedure, for the treatment of this disease. INDICATION: In our case we show the surgical procedure performed on a 23-year-old male patient, who was previously treated for an acute abscess-forming sacrococcygeal pilonidal sinus. METHOD: Our video shows the fasciocutaneous rhombic flap procedure described by Limberg step by step. CONCLUSION: The Limberg flap procedure is a simple operation for the treatment of sacrococcygeal pilonidal sinus disease.

[Assessment of bovine pericardium (tutomesh®) and coated polypropylene (proceed®) in the para-oesophageal position in a pig model]. / Untersuchung von bovinem Perikard (Tutomesh®) und beschichtetem Polypropylen (Proceed®) in paraösophagealer Position im Schweinemodell.

BACKGROUND: Hiatal hernias are nowadays increasingly treated with meshes. Often, biological implants are being used for this application. Oesophageal perforations have been reported as rare but serious complications from the application of synthetic meshes at the oesophageal hiatus. The role of the different mesh types has not been clearly established by experimental research so far. In the present large animal model, we investigated two implant types (Tutomesh® and Proceed®) with respect to their biocompatibility and mechanical stability. MATERIAL AND METHODS: We used 12 domestic pigs aged three months. Tutomesh® and Proceed® were implanted in 6 animals each for bridging at the oesophageal hiatus. After a follow-up of 3 months, the experiment was terminated. We performed endoscopy and intraoperative macroscopic evaluation of the situs. In representative histological sections, established histopathological and immunohistochemical parameters of biocompatibility were investigated and tensile strength testing was performed on standardised tissue samples. RESULTS: One animal of the Proceed® group had grade 2 oesophagitis. None of the animals had an oesophagus arrosion. The analysis of adhesions revealed slightly less adhesions in the Tutomesh® group. There was no significant difference with respect to the investigated inflammation response and immune response between both meshes. The most substantial finding of the mechanical analysis was a loss of tear strength of the Tutomesh®-tissue-complex of 30 % as compared to native tissue and more than 50 % compared to Tutomesh® prior to implantation, respectively. CONCLUSIONS: After 3 months, there was no significant difference between the two implant types with respect to the inflammatory response. The loss of tear strength of the Tutomesh®-tissue-complex at the oesophageal hiatus is probably clinically not relevant and may be explained by the so-called biological remodeling of biological materials. The remodeling depends on the extent of the cross-linking of the respective material. It is expected that biological hernia implants, such as Tutomesh®, may have a marked potential for avoiding complications at the oesophageal hiatus in the long run. This potential cannot be proven after 3 months from our data. Further experimental investigations are necessary to clarify this issue, in particular with respect to the long-term results.

[Preparation and in-vitro analysis of a polyethylenimine coating on hernia meshes]. / Herstellung und In-vitro-Analyse einer Polyethylenimin-Beschichtung auf Herniennetzen.

BACKGROUND: Certain coatings such as titanium may improve the biocompatibility of hernia meshes. The coating with biopolymers such as polyethylenimine (PEI) can also improve the material characteristics of implants. This approach has, however, not yet been explored. Thus, it was the aim of the present work to clarify if and how hernia meshes with their three-dimensional structure can be successfully coated with PEI and with which technique this coating can be best analysed. METHODS: Commercially available meshes made from polypropylene, polyester and ePTFE have been coated with PEI. The coating was analysed via cell proliferation test (mouse fibroblasts), electron microscopy, X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy. Cell viability and cytotoxicity were tested by the MTT test. RESULTS: With the PEI surface modification, mouse fibroblasts grow faster and in greater numbers on the mesh surface. XPS as well as fluorescence microscopy show weaknesses in their applicability and meaningfulness because of the three-dimensional mesh structure while XPS showed overall better results. Optical proof in the electron microscope after cell fixation was not unambiguously accomplished with the techniques used here. In the MTT test, no cellular damage from the PEI coating was detected after 24 hours. CONCLUSION: The present results show for the first time that PEI coating of hernia meshes is possible and effective. The PEI coating can be achieved in a fast and cost-efficient way. Further investigations are necessary with respect to coating quality and cytotoxicity before such a coating may be used in the clinical routine. In conclusion, PEI is a promising polymer that warrants further research as a coating for medical implants.

Everolimus and early calcineurin inhibitor withdrawal: 3-year results from a randomized trial in liver transplantation.

The feasibility of de novo everolimus without calcineurin inhibitor (CNI) therapy following liver transplantation was assessed in a multicenter, prospective, open-label trial. Liver transplant patients were randomized at 4 weeks to start everolimus and discontinue CNI, or continue their current CNI-based regimen. The primary endpoint was adjusted estimated GFR (eGFR; Cockcroft-Gault) at month 11 post randomization. A 24-month extension phase followed 81/114 (71.1%) of eligible patients to month 35 post randomization. The adjusted mean eGFR benefit from randomization to month 35 was 10.1 mL/min (95% confidence interval [CI] -1.3, 21.5 mL/min, p = 0.082) in favor of CNI-free versus CNI using Cockcroft-Gault, 9.4 mL/min/1.73 m(2) (95% CI -0.4, 18.9, p = 0.053) with Modification of Diet in Renal Disease (four-variable) and 9.5 mL/min/1.73 m(2) (95% CI -1.1, 17.9, p = 0.028) using Nankivell. The difference in favor of the CNI-free regimen increased gradually over time due to a small progressive decline in eGFR in the CNI cohort despite a reduction in CNI exposure. Biopsy-proven acute rejection, graft loss and death were similar between groups. Adverse events led to study drug discontinuation in five CNI-free patients and five CNI patients (12.2% vs. 12.5%, p = 1.000) during the extension phase. Everolimus-based CNI-free immunosuppression is feasible following liver transplantation and patients benefit from sustained preservation of renal function versus patients on CNI for at least 3 years.

[Diagnostic procedures and results in surgical therapy for cholangiocarcinoma]. / Diagnostisches Vorgehen und Ergebnisse in der chirurgischen Therapie von Gallenwegstumoren.

INTRODUCTION: Despite a rising incidence worldwide, cholangiocarcinoma (CCC) is one of the infrequent malignancies of the gastrointestinal tract. The surgical approach depends largely on the location of the tumour. PATIENTS AND METHODS: Since 1995, 425 consecutive patients with cholangiocarcinoma were seen at our hospital; their data were prospectively entered in our cancer registry. Tumour-specific data were now retrospectively analysed for prognostic value. RESULTS: Resection with primarily curative intent was performed in 183 of the 425 patients; resection rates were 36 % for intrahepatic (66 patients), 44 % for hilar (69 patients) and 56 % for distal cholangiocarcinoma (48 patients). R0-resection was achieved in 152 patients (83 %) and was found to be the most important factor determining survival. With respect to intrahepatic cholangiocarcinoma, clinical T3- and T4-categories, lymph node metastases as well as UICC stages III and IV had negative predictive value; in hilar carcinomas, this was only seen for the last two factors. In distal cholangiocarcinoma, a low degree of differentiation was associated with a poor prognosis. No differences in survival were seen in the presence of perineural infiltration, angioinvasion or elevation of tumour marker CA 19 - 9.  Regarding the surgical techniques, we found a survival benefit for limited liver resection in intrahepatic cholangiocarcinomas, which is explained by earlier tumour stages seen in these cases, as well as the performance of trisectionectomy or liver transplantation in hilar carcinomas. CONCLUSIONS: Comparable to other malignant gastrointestinal tumours, radical surgery represents the most important prognostic factor in cholangiocarcinomas; for hilar tumours, a survival advantage is seen after extended resections (trisectionectomy or liver transplantation) if compared to more limited resections. At the time of presentation, however, the stage of disease was incurable in most patients, thus accounting for the low overall resection rates.

Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP).

BACKGROUND: To investigate whether addition of cetuximab to standard adjuvant chemotherapy with gemcitabine improves outcome in pancreatic cancer, specifically whether the rate of disease-free survival (DFS) at 18 months (primary end point) exceeds the previously reported 35% of gemcitabine alone. PATIENTS AND METHODS: Prospective, open-label, multicenter, nonrandomized phase II study in 76 patients with R0- or R1-resected ductal adenocarcinoma of the pancreas included between October 2006 and November 2008. Gemcitabine and cetuximab were administered for 24 weeks. Secondary end points included overall survival (OS) and toxic effect. RESULTS: Seventy-three patients received cetuximab. Median DFS was 10.0 [95% confidence interval (CI) 8.9-13.6] months and the DFS rate at month 18 of 27.1% (16.7%-37.6%) was inferior to 35%. Median OS was 22.4 (18.2-27.9) months. Subgroup analyses revealed a nonsignificant increase in DFS for patients with versus without skin toxic effect ≥ grade 2 (median 14.7 versus 8.3 months, P = 0.073) and wild-type versus mutated K-Ras (median 11.5 versus 9.3 months, P = 0.57). Grade 3/4 toxic effects included neutropenia (11.0%), thrombopenia (7%), skin toxic effect (7%) and allergic reactions (7%). CONCLUSION: Addition of cetuximab to adjuvant gemcitabine does not seem to improve DFS or OS of unstratified pancreatic cancer patients. Trends for improved DFS in patients with wild-type K-Ras and skin toxic effect remain to be confirmed.

[Liver transplantation - current aspects of allocation, indication and donor pool expansion]. / Lebertransplantation - aktuelle Aspekte der Allokation, Indikation und Strategien zur Erweiterung des Spenderpools.

Liver transplantation is nowadays an established treatment option for end-stage liver disease and the associated complications. In this article, we summarise the actual aspects of allocation, indication for transplantation as well as approaches for donor pool expansion in the field of liver transplantation in Germany. Beside the maintenance of long-term survival and quality of life, the actual donor organ shortage is the most important issue worldwide. While trying to control this shortage, there is a lot of discussion about the transplantation for malignant liver disease. In our opinion, the focus in this topic should be the utilisation and expansion of the donor pool. There are many logistic and medical aspects which could be optimised. Furthermore, there are open questions in public and political discussions (up to the revision of the transplantation law) which should be improved for the purpose of the waiting list patients.

[Hybrid NOS appendectomy (NA): clinical assessment of a new surgical technique]. / Hybrid-NOS-Appendektomie (NA), eine neue Operationsmethode - eine klinische Evaluation.

UNLABELLED: INTRODUCTION, AIM AND METHOD: Consecutive female patients undergoing hybrid NOS appendectomy (NA - with prospectively collected data) and laparoscopic appendectomy (LA - with retrospectively registered data) were compared by means of a matched-pair analysis according to selected criteria such as patient age, BMI, ASA and previous operations showing a near-perfect congruence with the following aims to: 1) demonstrate the feasibility of NA and to estimate its general costs, and 2) elucidate the outcome of the two techniques using available perioperative parameters from daily clinical practice. In particular, operating time, complications, histopathological findings, postoperative hospital stay and analgesic scores were used for comparison. A gynaecological follow-up investigation was carried out on the day of discharge and after a medium-term time period of 4 weeks in the NA group, and 6 months postoperatively, patients of both groups were interviewed using a standardised questionnaire. RESULTS: From 05/01/2008 to 02/28/2010, transvaginal NA (n = 30) was compared with the results of the conventional LA (n = 30) in 60 female patients with regard to the operative outcome. Overall, matched-pair analysis of LA with NA, the novel technique resulted in the assessment of basically comparable surgical procedures with regard to perioperative routine parameters and outcome. There were no intraoperative complications in either of the two approaches; conversion was not required in both techniques. In addition, there were no significant differences in operating time (p = 0.099), postoperative complications (p = 0.72) and analgesic scores (p = 0.33/0.46). Postoperative hospital stay was even slightly shorter in the NA group (p = 0.02). The costs of the two methods are almost identical if the same instruments are used. Patient interviews suggested a slightly faster recovery, greater satisfaction with the better cosmetic outcome as well as a reduced pain intensity in favour of transvaginal NA. CONCLUSION: Provided that a well developed laparoscopic expertise exists, it turned out i) that there are no serious reasons to resist a quick inauguration and establishment of NA for selected cases as well as ii) even to facilitate further clinical distribution of NA. Further systematic data collection appears to be indicated to analyse long-term outcome as parameters of an appropriate quality assurance.