Mixed reality combined with ALPPS for colorectal liver metastases, a case report.

INTRODUCTION: Improvement of treatments for patients suffering from colorectal carcinoma and extended liver metastases has increased the overall survival and enables more patients to undergo surgical therapy. If the future liver remnant (FLR) is expected to be low, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a potential treatment with high feasibility and an increase in overall survival. The evolving mixed reality technology could support hepatobiliary surgery. This case report demonstrates for the first time the combination of mixed reality technology and ALPPS procedure for a patient with low expected FLR. PRESENTATION OF CASE: A 49-year-old patient is presented with adenocarcinoma of the caecum with bilateral liver metastasis. After colon resection, a palliative chemotherapy was administered with good response and partial remission, so curative liver resection was intended. Based on the low expected FLR, calculated from the 3D-model of the liver, we decided to perform an in-situ split resection supported by mixed reality intraoperatively. The total operation time was 6 + 2 h. During both steps no blood transfusion was required and no major complication occurred. The patient was discharged 15 days after the second step. Final pathology revealed multiple predominantly necrotic metastases of the pre-existing colon carcinoma (ypM1, R0). DISCUSSION: After the first step of ALPPS, an increase of the FLR up to 57 % was achieved, so the second step was performed on postoperative day (POD)11. The 3D-model and the intraoperative use of mixed reality supported our decision making and intraoperative navigation. This technique could be implemented on a larger scale to support complex liver resections. CONCLUSION: The combination of mixed reality with ALPPS resulted in a good surgical outcome and should be considered as a potential alternative for liver resections.

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis.

Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry.

BACKGROUND: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. METHODS: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. RESULTS: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). CONCLUSION: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

Women in surgery: a web-based survey on career strategies and career satisfaction.

Women represent the majority of medical students in several countries. In any surgical specialty and above all in surgical leadership positions, women still remain disproportionally underrepresented. The objective of this study was to investigate female surgeons' career advancement and satisfaction with training. A standardized questionnaire was devised and sent out via the web-based survey tool SurveyMonkey® to female surgeons in the German federal state of North Rhine-Westphalia. A total of 125 completed questionnaires were analyzed (response rate 40.8%). Female surgeons are at least largely (76%) satisfied with their surgical training. Increased time (>5 h/week) as the principal surgeon in the operating room significantly stimulates the satisfaction with the surgical training (86% vs. 68%, p = 0.0384). At the participants' current workplace, the heads of departments are predominantly male surgeons (91%). Respondents not satisfied with their surgical training prefer a female head of department more frequently (24% vs. 2%, p = 0.0085). The majority of the respondents themselves aspire to become a consultant surgeon (56%), while only 12% intend to become a head of a department. Female surgeons aiming at leadership positions work overtime (≥50 h/week) significantly more frequently (81% vs. 57%, p = 0.0041). Favoritism of male colleagues is perceived by 34%. Respondents who do not perceive any preferential treatment are significantly more satisfied with their surgical training (88% vs. 57%, p = 0.0004). In conclusion, female surgeons seem positive about their career choice, once in the surgical profession, and aptly fill upcoming positions. Women interested in surgery are likely to pursue a surgical career despite the alleged workload, demonstrating the importance of professional self-fulfillment among female surgeons.

Long-term outcome of third, fourth and fifth kidney transplantation: technical aspects and immunological challenges.

BACKGROUND: The number of patients on waiting lists for repeated kidney transplantation has increased. However, retransplanted patients have a greater surgical and immunological risk than first-time kidney recipients. METHODS: We retrospectively analysed all kidney recipients that underwent third, fourth or fifth kidney transplantation (Group 3+) at the University Hospital Essen, Essen, Germany from October 1973 to January 2017. A historical cohort of recipients retransplanted with a second kidney (Group 2) served as the control. Donor and recipient demographic data, cold ischaemia time (CIT), warm ischaemia time, overall operation time and methods, transplantectomy of previous kidney grafts, incidence of surgical and immunological complications as well as patient- and death-censored survival were analysed. RESULTS: We identified 108 recipients transplanted with the third, fourth or fifth renal allograft. Patients with more than one transplantation had significantly higher surgical risk due to atherosclerosis (P = 0.002) and higher immunological risk due to higher panel reactive antibody levels preoperatively (current panel reactive antibody P = 0.004; highest panel reactive antibody value P = 0.0001). Group 3+ patients had more often undergone previous transplant nephrectomy (P = 0.0001). There was a significant difference in CIT (P = 0.009), overall operative time (P = 0.0001) and post-transplantation thrombotic events (P = 0.02). We could not demonstrate any differences in graft and patient survival. CONCLUSION: Third, fourth and fifth transplant recipients are a high-risk patient cohort. Our results suggest that patient survival after more than three renal transplantations is similar to that of second graft recipients. This supports the concept of repeated kidney retransplantations.

Long-term Survival after resection for perihilar cholangiocarcinoma: Impact of UICC staging and surgical procedure.

BACKGROUND/AIMS: Perihilar cholangiocarcinoma is a rare disease with unfavorable prognosis resulting in low survival rates. This study aims to retrospectively assess the beneficial histopathological features and surgical procedures in long-term survivors (i.e., patients surviving perihilar cholangiocarcinoma for at least 2 y). MATERIAL AND METHODS: In total, 322 patients with perihilar cholangiocarcinoma underwent surgery at our center. The follow-up ended in 2017; 76 patients survived for >2 y. The type of resection, UICC stage, and histopathological features were compared between three survival groups (>2-3, >3-5, and >5 y). RESULTS: The >5-year-survival rate in our selected study cohort was 43.4% (>3-5 y,31.6% and >2-3 y, 25.0%), and 14.5% of the patients survived for >10 y after surgery. Patients with non-regional lymph node positive tumors and/or distant metastasis (i.e., UICC stage IVb; p=0.0112), R2 status (p=0.0288), and exploratory laparotomy only (p=0.0157) showed the poorest survival rates. Perineural invasion had no significant impact on the overall survival. However, 29.0% patients surviving for >5 y displayed the lowest perineural infiltration prevalence. Interestingly, Bismuth-Corlette stage IIIa (p=0.0467), especially caudate lobectomy (p=0.0034), was associated with disease-specific overall survival of >5y. CONCLUSION: Complete/extended tumor resection with additional caudate lobe resection is strongly associated with long-term survival. Perineural infiltration as a negative prognostic marker for prolonged survival needs to be evaluated in larger study cohorts.

Comparison of the sixth and the seventh editions of the UICC classification for intrahepatic cholangiocarcinoma.

BACKGROUND: The current seventh edition of the TNM classification for intrahepatic cholangiocarcinoma (ICC) includes tumor number, vascular invasion, lymph node involvement but no longer the tumor size as compared to the sixth edition. The impact of the seventh edition on stage-based prognostic prediction for patients with ICC was evaluated. METHODS: Between 03/2001 and 02/2013, 98 patients with the diagnosis of an ICC were surgically treated at our center. Median survival times were calculated for these patients after separate classification by both sixth and seventh editions. RESULTS: Median overall survival was increased in patients classified to the lower tumor stages I and II using the seventh as compared to the sixth edition: stage I (54.9 vs. 47.3 months), stage II (19.9 vs. 18.9 months), stage III (17.2 vs. 19.9 months), and stage IV (23.2 vs. 15.3 months), respectively. The seventh edition definition of the T category resulted in an increased median survival regarding the T1 (50.4 vs. 47.3 months) as well as the T2 category (19.9 vs. 15.6 months) and revealed a reduced median survival of patients within the T3 (21.6 vs. 24.8 months) as well as the T4 category (19.9 vs. 27.0 months). CONCLUSIONS: The UICC seventh edition TNM classification for ICC improves separation of patients with intermediate stage tumors as compared to the sixth edition. The prognostic value of the UICC staging system has been improved by the seventh edition. Trial registration The data for this study have been retrospectively registered and the study has been approved by the ethic committee of the medical faculty of the University Hospital of Essen, Germany (license number 15-6353-BO).

Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine-Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled, Multicenter Study.

BACKGROUND: Arterial ex situ back-table perfusion (BP) reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation. METHODS: Our prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP. The primary endpoint was the incidence of ischemic-type biliary lesions over a follow-up of 2 years after liver transplantation, whereas secondary endpoints included 2-year graft survival, initial graft damage as reflected by transaminase levels, and functional biliary parameters at 6 months after transplantation. RESULTS: A total of 75 livers preserved via standard aortic perfusion and 75 preserved via standard aortic perfusion plus arterial BP were treated using a standardized protocol. The incidence of clinically apparent biliary lesions after liver transplantation (n = 9 for both groups; P = 0.947), the 2-year graft survival rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP, 68%; P = 0.34), and incidence of initial graft injury did not differ between the 2 perfusion modes. Although 33 of the 77 patients with cholangiography workups exhibited injured bile ducts, only 10 had clinical symptoms. CONCLUSIONS: Contrary to previous findings, the present study indicated that additional ex situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion injury after liver transplantation. Moreover, there was considerable discrepancy between cholangiography findings regarding bile duct changes and clinically apparent cholangiopathy after transplantation, which should be considered when assessing ischemic-type biliary lesions.

Outcomes of parenchyma-preserving hepatectomy and right hepatectomy for solitary small colorectal liver metastasis: A LiverMetSurvey study.

BACKGROUND: Occasionally, right hepatectomy, rather than parenchyma-preserving hepatectomy, has been performed for solitary small colorectal liver metastasis. The relative oncologic benefits of parenchyma-preserving hepatectomy and right hepatectomy are unclear. This study compared the outcomes of patients with solitary small colorectal liver metastasis in the right liver who underwent parenchyma-preserving hepatectomy and those who underwent right hepatectomy. METHODS: The study population consisted of a multicentric cohort of 21,072 patients operated for colorectal liver metastasis between 2000 and 2015 whose data were collected in the LiverMetSurvey registry. Patients with a pathologically confirmed solitary tumor of less than 30 mm in size in the right liver were included. The short- and long-term outcomes of patients who underwent parenchyma-preserving hepatectomy were compared to those of patients who underwent right hepatectomy. RESULTS: Of the 1,720 patients who were eligible for the study, 1,478 (86%) underwent parenchyma-preserving hepatectomy and 242 (14%) underwent right hepatectomy. The parenchyma-preserving hepatectomy group was associated with lower rates of major complications (3% vs 10%; P < .001) and 90-day mortality (1% vs 3%; P = .008). Liver recurrence occurred similarly in both groups (20% vs 22%; P = .39). The 5-year recurrence-free survival and overall survival rates were similar in both groups. However, in patients with liver-only recurrence, repeat hepatectomy was more frequently performed in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (67% vs 31%; P < .001), and the overall 5-year survival rate was significantly higher in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (55% vs 23%; P < .001). CONCLUSION: Parenchyma-preserving hepatectomy should be considered the standard procedure for solitary small colorectal liver metastasis in the right liver when technically feasible.

Two and a Half Hours of Cardiopulmonary Resuscitation in a Deceased Brain Dead Donor before Liver Transplantation - A Good Idea to Accept?

The sequelae of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in organ donors potentially results in ischemic organ injury and graft dysfunction after transplantation. Thresholds of resuscitation times in brain dead liver donors have not been established so far. We report the case of a brain dead liver donor who experienced 2.5 hours of CPR whose liver was successfully transplanted. A 75-year-old male experienced CA and was treated by CPR with streptokinase application for 2.5 hours until stabilization of cardiac function. Brain death was diagnosed at the day of admission and organ donation carried out within 24 hours. The DRI was 2.2 with a CIT of 8.8 hours. The liver was transplanted into a 64-year-old recipient suffering from alcoholic liver cirrhosis and a MELD-score of 10 non representative for severity of disease. During follow up of 4 years ERCP and stenting was performed regularly for biliary anastomosis stenosis. The patient remained in a very good overall state of health without any signs of liver dysfunction. This case demonstrates that an extensive period of CPR is not an obligatory exclusion criterion for liver donation. Thresholds of CPR times as well as predictive factors in donors with CA should be established.

Feasibility, safety and efficacy of two-stage hepatectomy for bilobar liver metastases of colorectal cancer: a LiverMetSurvey analysis.

BACKGROUND: The combination of liver resection and chemotherapy has become the standard of care for colorectal liver metastases (LM). The objective of the present study was to evaluate the impact of two-stage hepatectomy (TSH) on the long-term survival of patients with bilobar LM. METHODS: We included adult (over-18) patients from the LiverMetSurvey registry with confirmed multiple colorectal LM and having undergone either one-stage hepatectomy or TSH with curative intent. The "TSH (2/2)" group (n = 625) comprised patients having completed both stages of TSH; the "TSH (1/2)" group (n = 244) comprised patients having undergone only the first stage of TSH; the "hepatectomy" group. The primary outcome criterion was the overall survival (OS). The secondary outcomes were the morbidity and mortality rates. RESULTS: The 30- and 90-day mortality rates were respectively 3.8% and 9.3% in the TSH (2/2) group, 9.4% and 16.4% in the TSH (1/2) group, and 5.4% and 9.1% in the "hepatectomy" group. The three-year OS rate was 45% in the TSH (2/2) group, 30% in the TSH (1/2) group and 50.7% in the hepatectomy group. CONCLUSION: The LiverMetSurvey registry's data indicate that TSH is associated with rather good long-term survival and acceptable morbidity and mortality rates.

Career intentions of female surgeons in German liver transplant centers considering family and lifestyle priorities.

PURPOSE: Women represent up to 60 % of students entering the medical profession in many countries in the world. However, the proportion of women to men is not accordingly balanced among surgical residents and especially in leadership positions in surgery. Therefore, we investigated the career goals as well as family and lifestyle priorities of female surgeons in German liver transplant centers. METHODS: A standardized questionnaire was developed using the web-based survey tool SurveyMonkey®. Questionnaires were distributed electronically to 180 female surgeons in 24 German liver transplant centers. A total of 81 completed questionnaires were analyzed. RESULTS: Female surgeons in German liver transplant centers are eager to assume leadership positions and do not wish to follow traditional role models. After finishing training, most female surgeons plan to continue working at a university hospital. About 80 % of the respondents intend to continue working full time and wish to combine career and family. CONCLUSIONS: This is the first survey on career intentions of female surgeons in Germany. In the face of gender changes in the medical profession, we were able to demonstrate that female surgeons are willing to fill leadership positions. Individual and institutional creative modifications are necessary if the advancement of women in surgery is to be promoted.

Training, work, and lifestyle of transplant physicians and surgeons in Germany.

BACKGROUND: International data on training, work, and lifestyle of transplant physicians and surgeons are scarce. Such data might help in development of uniform education paths and provide insights for young clinicians interested in this field. This study aimed at the evaluation of these data in all transplant-associated medical disciplines. METHODS: A survey on professional and academic training, workload, and lifestyle was generated. The questionnaire was distributed to all members of the German Transplant Association (DTG), utilizing the tool SurveyMonkey(®) . RESULTS: A total of 127 members of the DTG responded (male/female 66.1%/33.9%, 45.8±10.3 years). The majority had been working in transplant medicine for more than 10 years (61.9%). Fifteen respondents (11.8%) obtained an official European certification (European Union of Medical Specialists). A total of 57 (48.3%) respondents worked full time on research during training. The research focus was clinical for most respondents (n=72, 61.5%). An average working time of 62±1.5 h/wk was reported. Fifty-eight percent of all respondents complained of inadequate remuneration and 50% reported inadequate acknowledgment of their professional performance. CONCLUSION: This is the first study reporting characteristics of training, work, and lifestyle in an interdisciplinary cohort of German transplant physicians and surgeons. Enormous efforts in clinical and research work were reported, associated with high rates of professional and financial dissatisfaction.

Long-term follow-up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study.

BACKGROUND: The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data. METHODS: PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment. RESULTS: A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively. CONCLUSION: Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up.

Edema, Hyperpigmentation, Induration: 3 Skin Signs Heralding Danger in Patients on Maintenance Hemodialysis.

Skin changes are common in patients on dialysis. This study focused on putative associations of specific skin findings with comorbidities and mortality.We performed a retrospective analysis of data from 508 patients on maintenance hemodialysis therapy in 7 centers in the German State of North Rhine Westphalia. Data had been collected by interview, from patient files, and from targeted physical examination in an earlier prospective study screening hemodialysis patients for the presence of nephrogenic systemic fibrosis. While on dialysis, patients' extremities had been examined for any of the following: edematous skin at the lower extremities, hyperpigmentation, induration, and xerosis cutis. Our present data analyses focused on associated mortality and comorbidities.Five hundred eight patients (median age 71 years, range 20.0-95.9; n = 292 men) had agreed to participate in the initial study: 48% (n = 243) were diabetics and 46% (n = 232) had been diagnosed with coronary heart disease. On examination, 86% of patients (n = 439) presented with at least 1 of the prespecified skin changes. Skin edema (n = 89; 18%), hyperpigmentation (n = 74; 15%), and induration (n = 9; 2%) were independently associated with increased mortality over 24 months (P < 0.002, P < 0.030, and P < 0.020, respectively).In our study, prespecified skin changes indicated an increased mortality risk in patients on chronic hemodialysis. Routinely assessing the skin of dialysis patients represents a simple, reliable, and cost effective means of identifying those at greatest risk.

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells.

BACKGROUND & AIMS: Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. METHODS: Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. RESULTS: Cell preparation yielded the following cell counts per gram of liver tissue: 2.0 ± 0.4 × 10(7) hepatocytes, 1.8 ± 0.5 × 10(6 )Kupffer cells, 4.3 ± 1.9 × 10(5) liver sinusoidal endothelial cells, and 3.2 ± 0.5 × 10(5) stellate cells. Hepatocytes were identified by albumin (95.5 ± 1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5 ± 1.2%) and exhibited phagocytic activity, as determined with 1 µm latex beads. Endothelial cells were CD146(+) (97.8 ± 1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1 ± 1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. CONCLUSIONS: Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease.

Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study.

BACKGROUND: Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration. METHODS: In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control). RESULTS: Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24-month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, -3.2%; 95% confidence interval, -10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension. CONCLUSIONS: A clinically relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns.

Infectious complications in the era of MELD.

BACKGROUND: Infections are a major cause for morbidity and mortality in liver transplant recipients. So far there has been no study systematically investigating the correlation between the MELD (Model for End-Stage Liver Disease) scoring system and complications caused by infections. The aim of the present retrospective study was to evaluate the impact of the pretransplant MELD score on incidence and mortality of pneumonia and septicemia in liver transplant recipients. MATERIAL AND METHODS: The clinical courses of 201 liver transplant recipients between 12/2006 and 3/2009 were recorded and analyzed on the basis of chart review. Patients were stratified into three groups (pretransplant MELD score: group I 6-20, group II ≥ 21-30, group III ≥ 31-40) and compared in terms of incidence of infection and survival. RESULTS: The mean pretransplant MELD score was 22 ± 12. There were 81 patients in group I, 65 patients in group II, and 55 patients in group III. There was no difference in incidence of infections between the MELD groups. However, septicemia-associated mortality was significantly higher in group III. CONCLUSIONS: A high MELD score is not associated with higher incidence of infections but it is associated with a significantly higher mortality in the case of septicemia. Prevention of infections is of utmost importance, especially in liver transplant recipients with high MELD scores.

Medical students' education on organ donation and its evaluation during six consecutive years: results of a voluntary, anonymous educational intervention study.

BACKGROUND: One of the main reasons for organ shortage is insufficient education on organ donation. Knowledgeable medical students could share the information with friends and families resulting in a positive attitude to organ donation of the general public. METHODS: During six consecutive years (2009 to 2014), we conducted a voluntary, anonymous educational intervention study on organ donation among fourth year medical students in the course of the main surgery lecture at the University of Essen, Germany. RESULTS: Questionnaires of 383 students were analyzed. Prior to the specific lecture on organ donation, 64% of the students carried a signed organ donor card with the intention to donate. Further information regarding organ donation was required by 37% of the students. The request for further information was statistically significantly higher among students without a donor card compared to organ donor card carriers (P < 0.0001). After the lecture, the number of students requiring further information decreased statistically significantly to 19% (P < 0.0001). CONCLUSIONS: Already a 45-minute lecture for fourth year medical students significantly decreases their request for further information on organ donation and improves their attitude to organ donation. Continued training on organ donation will help medical students to become disseminators for this important topic in our society.

Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver metastasis; An international multi-center data analysis using LiverMetSurvey.

BACKGROUND AND OBJECTIVES: The use of neo-adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo-adjuvant chemotherapy on outcomes following liver resection for synchronous CLM. METHODS: An analysis of a multi-centric cohort from the LiverMetSurvey International Registry, who had undergone curative resections for synchronous CLM was undertaken. Patients who received neo-adjuvant chemotherapy prior to liver surgery (group NAS; n = 693) were compared with those treated by surgery alone (group SG; n = 608). Baseline clinicopathological variables were compared. Predictors of overall (OS) and disease free survival (DFS) were subsequently identified. RESULTS: Clinicopathological comparison of the groups revealed a greater proportion of solitary metastasis in the SG compared to the NAS group (58.8% versus 38.4%; P < 0.001) therefore a separate analysis of solitary versus multi-centric analysis was performed. N-stage (> N1), number of metastasis (> 3), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer OS, while N-stage (> N1), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer DFS. Neo-adjuvant chemotherapy did not independently affect outcome. CONCLUSION: We present an analysis of a large multi-center series of the role of neo-adjuvant chemotherapy in resectable CLM and demonstrate no survival advantage in this setting.