[Transplantation for acute-on-chronic liver failure]. / Transplantation beim akut-auf-chronischen Leberversagen.

A review and discussion of the current literature on liver transplantation for acute-on-chronic liver failure (ACLF) was performed. The ACLF represents an acute deterioration of liver function with pre-existing liver disease and is associated with increasing multiorgan failure, depending on the stage. The 28-day mortality ranges to well over 70% in stage 3 and requires rapid intensive medical treatment involving an interdisciplinary team experienced in transplantation medicine. Under optimized conditions, liver transplantation provides long-term survival rates comparable to other indications. Achieving this requires a differentiated donor selection, choosing the appropriate time for transplantation in the context of a dynamic disease course and the use of appropriate surgical techniques.

Pancreatic Fistula and Biochemical Leak after Splenectomy: Incidence and Risk Factors-A Retrospective Single-Center Analysis.

PURPOSE: Postoperative pancreatic fistula (POPF) is a complication discussed in the context of pancreatic surgery, but may also result from splenectomy; a relationship that has not been investigated extensively yet. METHODS: This retrospective single-center study aimed to analyze incidence of and risk factors for POPF after splenectomy. Patient characteristics included demographic data, surgical procedure, and intra- and postoperative complications. POPF was defined according to the International Study Group on Pancreatic Surgery as POPF of grade B and C or biochemical leak (BL). RESULTS: Over ten years, 247 patients were identified, of whom 163 underwent primary (spleen-associated pathologies) and 84 secondary (extrasplenic oncological or technical reasons) splenectomy. Thirty-six patients (14.6%) developed POPF of grade B/C or BL, of which 13 occurred after primary (7.9%) and 23 after secondary splenectomy (27.3%). Of these, 25 (69.4%) were BL, 7 (19.4%) POPF of grade B and 4 (11.1%) POPF of grade C. BL were treated conservatively while three patients with POPF of grade B required interventional procedures and 4 with POPF of grade C required surgery. POPF and BL was noted significantly more often after secondary splenectomy and longer procedures. Multivariate analysis confirmed secondary splenectomy and use of energy-based devices as independent risk factors for development of POPF/BL after splenectomy. CONCLUSION: With an incidence of 4.5%, POPF is a relevant complication after splenectomy. The main risk factor identified was secondary splenectomy. Although POPF and BL can usually be treated conservatively, it should be emphasized when obtaining patients' informed consent and treated at centers with experience in pancreatic surgery.

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

[Machine perfusion for conditioning liver and kidneys before transplantation]. / Maschinenperfusion zur Konditionierung der Leber und Niere vor Transplantation.

Machine perfusion will become established as the standard of care for solid organ transplantation in the near future. Ongoing studies are investigating the appropriate perfusion algorithms for each specific organ. Although it is neither proven which perfusion principle nor type of device is superior, it has already been sufficiently shown that the increasing number of marginal organs that are currently transplanted in Germany would benefit from machine perfusion for conditioning before transplantation. The addition of hypothermic and normothermic perfusion sequences opens up the possibility of conditioning of previously damaged organs as well as viability testing. Overall, machine perfusion increases the safety for the recipient and can counteract the increasingly more difficult scenario of working hour restrictions because solid organ transplantations in the future will be plannable and carried out during the day.

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.

Gastric neuroendocrine neoplasias: manifestations and comparative outcomes.

Although gastric neuroendocrine neoplasias (gNEN) are an orphan disease, their incidence is rising. The heterogeneous clinical course powers the ongoing discussion of the most appropriate classification system and management. Prognostic relevance of proposed classifications was retrospectively analysed in 142 patients from a single tertiary referral centre. Baseline, management and survival data were acquired for statistical analyses. The distribution according to the clinicopathological typification was gNEN-1 (n = 86/60.6%), gNEN-2 (n = 7/4.9%), gNEN-3 (n = 24/16.9%) and gNEN-4 (n = 25/17.6%), while hypergastrinemia-associated gNEN-1 and -2 were all low-grade tumours (NET-G1/2), formerly termed sporadic gNEN-3 could be subdivided into gNEN-3 with grade 1 or 2 and gNEN-4 with grade 3 (NEC-G3). During follow-up 36 patients died (25%). The mean overall survival (OS) of all gNEN was 14.2 years. The OS differed statistically significant across all subgroups with either classification system. According to UICC 2017 TNM classification, OS differed for early and advanced stages, while WHO grading indicated poorer prognosis for NEC-G3. Cox regression analysis confirmed the independent prognostic validity of either classification system for survival. Particularly careful analysis of the clinical course of gNEN-1 (ECLomas, gastric carcinoids) confirmed their mostly benign, but recurrent and extremely slowly progressive behaviour with low risk of metastasis (7%) and an efficient long-term control by repetitive endoscopic procedures. Our study provides evidence for the validity of current classifications focusing on typing, grading and staging. These are crucial tools for risk stratification, especially to differentiate gNEN-1 as well as sporadic gNET and gNEC (gNEN-3 vs -4).

[Preoperative bowel conditioning]. / Präoperative Konditionierung des Darms.

BACKGROUND: Gastrointestinal surgery is still associated with a relevant morbidity with the intestinal microbiome being of high importance in the pathogenesis of infectious complications. Various approaches, such as mechanical bowel preparation (MBP) with or without administration of oral antibiotics, fasting or dietary supplements aim at modulating the intestinal flora. OBJECTIVE: This review summarizes the current literature pertinent to the influence of preoperative bowel conditioning on postoperative morbidity. MATERIAL AND METHODS: A literature search was performed using the mentioned keywords with a focus on recent meta-analyses. RESULTS AND CONCLUSION: Bowel conditioning reduces postoperative infectious complications. Promising approaches are MBP plus administration of oral antibiotics, dietary supplements aiming at stabilization of the intestinal flora as well as the screening for and equilibration of malnutrition. The use of MBP as monotherapy without antibiotics should no longer be considered part of the clinical routine.

[Staff Satisfaction within Duty Hour Models: Longitudinal Survey on Suitability and Legal Conformity at a Surgical Maximum Care Department]. / Mitarbeiterzufriedenheit im Arbeitszeitmodell: Längsschnittstudie zu Praxistauglichkeit und Gesetzeskonformität in einer chirurgischen Klinik der Maximalversorgung.

Background Between the conflicting requirements of clinic organisation, the European Working Time Directive, patient safety, an increasing lack of junior staff, and competitiveness, the development of ideal duty hour models is vital to ensure maximum quality of care within the legal requirements. To achieve this, it is useful to evaluate the actual effects of duty hour models on staff satisfaction. Materials and Methods After the traditional 24-hour duty shift was given up in a surgical maximum care centre in 2007, an 18-hour duty shift was implemented, followed by a 12-hour shift in 2008, to improve handovers and reduce loss of information. The effects on work organisation, quality of life and salary were analysed in an anonymous survey in 2008. The staff survey was repeated in 2014. Results With a response rate of 95% of questionnaires in 2008 and a 93% response rate in 2014, the 12-hour duty model received negative ratings due to its high duty frequency and subsequent social strain. Also the physical strain and chronic tiredness were rated as most severe in the 12-hour rota. The 18-hour duty shift was the model of choice amongst staff. The 24-hour duty model was rated as the best compromise between the requirements of work organisation and staff satisfaction, and therefore this duty model was adapted accordingly in 2015. Conclusion The essential basis of a surgical department is a duty hour model suited to the requirements of work organisation, the Working Time Directive and the needs of the surgical staff. A 12-hour duty model can be ideal for work organisation, but only if augmented with an adequate number of staff members, the implementation of this model is possible without the frequency of 12-hour shifts being too high associated with strain on surgical staff and a perceived deterioration of quality of life. A staff survey should be performed on a regular basis to assess the actual effects of duty hour models and enable further optimisation. The much criticised 24-hour duty model seems to be much better than its reputation, if augmented by additional staff members in the evening hours.

[Endoscopic therapy for gastroduodenal neuroendocrine neoplasms]. / Endoskopische Therapie gastroduodenaler neuroendokriner Neoplasien.

Neuroendocrine neoplasms (NEN) represent a group of potentially malignant tumors, which can be located in every section of the gastrointestinal tract, the pancreas and the bronchopulmonary system. Gastroduodenal NENs have a relatively good prognosis in comparison to other subentities, e.g. pancreatic or ileojejunal NENs. In the stomach there are four different types of NENs, while in the duodenum there are five types and all vary in the malignant potential and the therapeutic approach. Due to the simple access endoscopic methods not only have diagnostic but also important therapeutic relevance in this subgroup. Lesions smaller than 1 cm can easily be resected with forceps or snare resection and for larger lesions up to 2 cm more invasive strategies, such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) are available. Important criteria in gastric NEN for the risk evaluation of endoscopic treatment alone are the size of the lesion, depth of invasion and the tumor biology, e.g. neuroendocrine tumor (NET) G1/G2 versus neuroendocrine carcinoma (NEC) G3. In duodenal NEN the aforementioned risk factors also apply and in addition only lesions outside the ampulla of Vater should be endoscopically resected whereas periampullary lesions need to be addressed surgically. As an individualized therapeutic approach the possibility of a combined endoscopic and laparoscopic resection technique exists. Follow-up endoscopic investigations are necessary, especially in gastric type 1 NENs, which have a tendency to relapse.

European Society of Coloproctology consensus on the surgical management of intestinal failure in adults.

Intestinal failure (IF) is a debilitating condition of inadequate nutrition due to an anatomical and/or physiological deficit of the intestine. Surgical management of patients with acute and chronic IF requires expertise to deal with technical challenges and make correct decisions. Dedicated IF units have expertise in patient selection, operative risk assessment and multidisciplinary support such as nutritional input and interventional radiology, which dramatically improve the morbidity and mortality of this complex condition and can beneficially affect the continuing dependence on parenteral nutritional support. Currently there is little guidance to bridge the gap between general surgeons and specialist IF surgeons. Fifteen European experts took part in a consensus process to develop guidance to support surgeons in the management of patients with IF. Based on a systematic literature review, statements were prepared for a modified Delphi process. The evidence for each statement was graded using Oxford Centre for Evidence-Based Medicine Levels of Evidence. The current paper contains the statements reflecting the position and practice of leading European experts in IF encompassing the general definition of IF surgery and organization of an IF unit, strategies to prevent IF, management of acute IF, management of wound, fistula and stoma, rehabilitation, intestinal and abdominal reconstruction, criteria for referral to a specialist unit and intestinal transplantation.

Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial.

Efficacy and safety of protein kinase C inhibitor sotrastaurin (STN) with tacrolimus (TAC) was assessed in a 24-month, multicenter, phase II study in de novo liver transplant recipients. A total of 204 patients were randomized (1:1:1:1) to STN 200 mg b.i.d. + standard-exposure TAC (n = 50) or reduced-exposure TAC (n = 52), STN 300 mg b.i.d. + reduced-exposure TAC (n = 50), or mycophenolate mofetil (MMF) 1 g b.i.d. + standard-exposure TAC (control, n = 52); all with steroids. Owing to premature study termination, treatment comparisons were only conducted for Month 6. At Month 6, composite efficacy failure rates (treated biopsy-proven acute rejection episodes of Banff grade ≥1, graft loss, or death) were 25.0%, 16.5%, 20.9% and 15.9% for STN 200 mg + standard TAC, STN 200 mg + reduced TAC, STN 300 mg + reduced TAC and control groups, respectively. Median estimated glomerular filtration rates were 84.0, 83.3, 81.1 and 75.3 mL/min/1.73 m(2), respectively. Gastrointestinal events (constipation, diarrhea, and nausea), infection, and tachycardia were more frequent in STN groups. More patients in STN groups experienced serious adverse events compared with the control group (62.3-70.8% vs. 51.9%). STN-based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups.

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.

[Short bowel syndrome in Germany. Estimated prevalence and standard of care]. / Das Kurzdarmsyndrom in Deutschland. Geschätzte Prävalenz und Versorgungssituation.

OBJECTIVE: As data about prevalence and standard of care in short bowel syndrome (SBS) are not available for Germany, this study estimated the prevalence and assessed the medical infrastructure to potentially improve care of SBS patients. METHODS: In a validated approach for prevalence estimation in rare diseases, a randomized census of 478 size-stratified hospitals with surgical, internal medicine and pediatric departments was conducted to estimate SBS prevalence. The number of SBS patients, specialized outpatient clinics and caregiver expertise were assessed. RESULTS: The response rate was 85 % of randomized hospitals (405/478). Strata-derived estimation yielded a total of 2,808 SBS patients in Germany for 2011/2012 (95 % CI: 1750.3865), translating into a prevalence estimation for 34/million inhabitants (95 % CI: 21.47). Overall expertise in SBS treatment was only rated "satisfactory" by most caregivers. While 86 specialized outpatient clinics were identified, there was no central registry to access these resources. CONCLUSION: Short bowel syndrome, with a newly estimated prevalence of 34/million inhabitants is not a very rare medical condition in Germany. The interdisciplinary approach needed for optimal care for SBS patients would be greatly facilitated by a central registry.

[Surgery and organ transplantation]. / Chirurgie und Organtransplantation.

Liver and kidney transplantations have been performed for almost 50 years and is nowadays a routine procedure for the treatment of terminal liver failure and terminal-stage renal failure. Under given optimal conditions and increasing experience good results can be achieved. Improvements in surgical techniques have led to a decrease in the incidence of surgical complications after transplantation. Nevertheless after liver and kidney transplantation complications can occur and increase the morbidity and mortality. There are a number of possible complications which range from harmless wound healing disorders to severe vascular, biliary or urinary complications that can be associated with graft dysfunction and lead to graft loss. In order to identify risk factors preoperatively and achieve good outcome after transplantation a good preparation of the recipients is necessary. Furthermore, a good interdisciplinary cooperation is necessary both to recognize complications early and to treat these adequately.

A randomized, controlled study to assess the conversion from calcineurin-inhibitors to everolimus after liver transplantation--PROTECT.

Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal-sparing alternative. In this randomized 1-year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post-LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft-Gault formula (-2.9 mL/min in favor of EVR, 95%-CI: [-10.659; 4.814], p = 0.46), whereas use of the MDRD formula showed superiority for EVR (-7.8 mL/min, 95%-CI: [-14.366; -1.191], p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy-proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI-based to EVR-based immunosuppression proved to be a safe alternative post-LTx that deserves further investigation in terms of nephroprotection.

Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial.

A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.