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.

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.

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.

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.

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.

A German survey of the abdominal transplantation surgical work force.

This manuscript reports the results of a nationwide survey of transplant surgeons in Germany, including the demographics, training, position, individual case loads, center volumes, program structure, professional practice, grade of specialization, workload, work hours, salary, and career expectations. We contacted all 32 German transplant centers that perform liver, kidney, and pancreas transplantation. Surgeons engaged in transplantation were asked to reply to the survey. Eighty-five surgeons responded, with a mean age of 44 ± 8 years, 13% of whom were female. The median transplant frequency per active transplant surgeon was relatively low, with 16 liver transplants, 15 kidney transplants, and three pancreas transplants. The median reported center volumes were 45 liver transplants, 90 kidney transplants, and five pancreas transplants per year. Most of the surgeons reported a primary focus on hepato-pancreato-biliary surgery, and only 10% of effective work time was actually dedicated to perform transplant surgeries. The majority of respondents estimated their weekly work hours to be between 55 and 66 h. When asked about their career satisfaction and expectations, most respondents characterized their salaries as inappropriately low and their career prospects as inadequate. This survey provides a first impression of the transplant surgery work force in Germany.

Polo-like kinase 3 is associated with improved overall survival in cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo-like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology. METHODS: We employed CCA samples from 73 patients and human HUCCT-1/Mz-CHA1/KMCH-1 CCA cells. Immunohistochemistry for PLK1/2/3 was performed using tissue microarrays from representative tumour areas. RESULTS: PLK1/2/3-immunoreactive cancer cells were present in most of the CCA samples. However, only PLK1 and especially PLK3 were expressed in higher amounts within CCA cells as compared to normal liver. Given that fibroblast growth factor (FGF) can induce PLK3 expression and also is present in CCA, we examined the effect of FGF on PLK3 in vitro. Indeed, rhFGF rapidly increased PLK3 mRNA expression all three CCA cell lines giving an explanation for the abundant PLK3 presence in the tissue samples. Clinicopathologically, PLK3 expression was associated with decreased tumour cell migration and lymph/blood vessel infiltration whereas higher levels of PLK1 were correlated with larger tumour sizes. Moreover, strong PLK3 expression was associated with prolonged overall survival. CONCLUSIONS: The results suggest that PLK3 predominantly is expressed in CCA cells and that high PLK3 expression correlates with prolonged overall survival. These observations might have implications for prognosis prediction of human CCA as well as the potential therapeutic use of polo-like kinase inhibitors (i.e., PLK1/2 specifity).

Donor-Specific Anti-HLA Antibodies and Endothelial C4d Deposition-Association With Chronic Liver Allograft Failure.

BACKGROUND: The significance of humoral immune response for allograft survival after liver transplantation (LT) is still a matter of debate. The aim of this cross-sectional study was to assess immunological and clinical factors associated with advanced fibrosis (F3-F4) and chronic graft failure in LT recipients. METHODS: Serum samples from 174 patients prospectively enrolled and followed up for 12 months were tested for anti-HLA antibodies and compared against donor HLA types. Immunohistochemical C4d staining was performed on formalin-fixed, paraffin-embedded liver tissue. RESULTS: Mean time period from LT to enrollment was 66.9 ± 51.9 months. Independent predictive factors for graft failure included donor-positive cytomegalovirus serostatus (P = 0.02), donor-specific antibodies (DSA) against HLA class II (P = 0.03), donor age (P = 0.01), hepatitis C virus allograft reinfection (P = 0.0008), and biliary complications (P = 0.003). HLA class II DSA and HLA class I antibody positivity, hepatitis C virus reinfection, and mycophenolate mofetil-free regimens were significant risk factors for advanced fibrosis after LT. There was a significant association between C4d deposition on allograft endothelial cells and presence of class II DSA (P < 0.0001). Patients with C4d deposits had a 4.3 times higher risk of graft failure than those with negative staining and a significantly lower median time to graft failure (94.6 months [range, 3.6-158.9 months] vs 176.4 months [range, 9.4-217.8 months], P < 0.0001). CONCLUSIONS: Screening for HLA DSA might be useful for early identification of LT recipients at increased risk of graft failure who could benefit from closer surveillance and tailored immunosuppressive regimens.

Prehospital fluid management of abdominal organ trauma patients--a matched pair analysis.

PURPOSE: Severe bleeding after trauma frequently leads to a poor outcome. Prehospital fluid replacement therapy is considered an important primary treatment option. We conducted a retrospective matched pair analysis to assess the influence of prehospital fluid replacement volume on the clinical course of patients with solid abdominal organ trauma. METHODS: Data were analyzed from 51,425 patients in TraumaRegister DGU® of the German Trauma Society. Inclusion criteria were as follows: injury severity score ≥ 16 points, primary admission, age ≥ 16 years, no isolated brain injury, transfusion of at least one unit of packed red blood cells (pRBCs), and systolic blood pressure ≥ 20 mmHg at the accident site. The patients were divided into "low-volume" (0-1000 ml) and "high-volume" (≥ 1,500 ml) groups according to the matched pair criteria. In each group, 68 patients met the inclusion criteria. RESULTS: Higher volume in fluid replacement was associated with increased need for transfusion (pRBCs: low-volume: 7.71 units, high-volume: 9.16 units; p = 0.074) and with by trend reduced clotting ability (prothrombin time: low-volume: 71.47 %, high-volume: 66.47 %; p = 0.27). The percentage of patients in shock (systolic blood pressure <90 mmHg) upon admission was equal in the two groups (25.0 %; p = 1). The mortality rate was discretely higher in the high-volume group (low-volume: 11.8 %, high-volume: 19.1 %; p = 0.089). CONCLUSIONS: Excessive prehospital fluid replacement is able to lead in an increased mortality rate in patients with solid abdominal organ injury. Our results support the concept of restrained fluid replacement in the preclinical treatment of severe trauma patients.

TRAIL expression levels in human hepatocellular carcinoma have implications for tumor growth, recurrence and survival.

The proapoptotic molecule TNF-related apoptosis-inducing ligand (TRAIL) has earned attention because of its ability to induce apoptosis in liver cancer cells without damaging normal liver cells. It may play an important role in preventing the development and outgrowth of hepatocellular carcinoma (HCC). TRAIL expression was investigated in a large series of human HCCs. We analyzed liver tissue from 108 patients undergoing partial liver resection (PLR) or liver transplantation (LT) because of either HCC or other indications. TRAIL expression was correlated with the cause of liver disease, demographic and clinical variables and pathologic properties. Our analysis found that in 66% of HCCs TRAIL expression was significantly lower than in the surrounding non-cancerous liver tissue (p≤0.012). Separation by cause of disease showed that HCC TRAIL mRNA expression was lower in almost all groups than in non-cancerous tissue but most significantly lower in NASH-associated liver tumors. Interestingly, low HCC TRAIL expression was found to correlate with tumor size (p≤0.007) and stage, as well as with tumor recurrence after resection and poor survival rates. The results of this study suggest that low TRAIL mRNA levels may be both a dominant feature in HCC development and growth and a predictor of tumor recurrence and poorer survival rates.

Safely expanding the donor pool: brain dead donors with history of temporary cardiac arrest.

BACKGROUND & AIMS: Cardiac arrest (CA) in deceased organ donors can potentially be associated with ischaemic organ injury, resulting in allograft dysfunction after liver transplantation (LT). The aim of this study was to analyse the influence of cardiac arrest in liver donors. METHODS: We evaluated 884 consecutive adult patients undergoing LT at our Institution from September 2003 to December 2011. Uni- and multivariable analyses was performed to identify predictive factors of outcome and survival for organs from donors with (CA donor) and without (no CA donor) a history of cardiac arrest. RESULTS: We identified 77 (8.7%) CA donors. Median resuscitation time was 16.5 (1-150) minutes. Allografts from CA donors had prolonged CIT (p = 0.016), were obtained from younger individuals (p < 0.001), and had higher terminal preprocurement AST and ALT (p < 0.001) than those of no CA donors. 3-month, 1-year and 5-year survival for recipients of CA donor grafts was 79%, 76% and 57% and 72.1%, 65.1% and 53% for no CA donor grafts (log rank p = 0.435). Peak AST after LT was significantly lower in CA donor organs than in no CA donor ones (886U/l vs 1321U/l; p = 0.031). Multivariable analysis identified CIT as a risk factor for both patient and graft survival in CA donors. CONCLUSION: This analysis represents the largest cohort of liver donors with a history of cardiac arrest. Reasonable selection of these donors constitutes a safe approach to the expansion of the donor pool. Rapid allocation and implantation with diminution of CIT may further improve the outcomes of livers from CA donors.

MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity.

BACKGROUND & AIMS: Oncogene polycomb group protein enhancer of zeste homolog 2 (EZH2) has been proposed to be a target gene of putative tumor suppressor microRNA-101 (miR-101). The aim of our study was to investigate the functional role of both miR-101 and EZH2 in human hepatocellular carcinoma (HCC). METHODS: MiR-101 and EZH2 expressions were evaluated in tumor tissues of 99 HCC patients and 7 liver cancer cell lines by real-time PCR. Luciferase reporter assay was employed to validate whether EZH2 represents a target gene of miR-101. The effect of miR-101 on HCC growth as well as programmed cell death was studied in vitro and in vivo. RESULTS: MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH2. Luciferase assay results confirmed EZH2 as a direct target gene of miR-101, which negatively regulates EZH2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo. Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. CONCLUSION: Tumor suppressor miR-101 represses HCC progression through directly targeting EZH2 oncogene and sensitizes liver cancer cells to chemotherapeutic treatment. Our findings provide significant insights into molecular mechanisms of hepatocarcinogenesis and may have clinical relevance for the development of novel targeted therapies for HCC.

Oil Red O-assessed macrosteatosis in liver transplant donor biopsies predicts ischemia-reperfusion injury and clinical outcome.

Steatosis in donor livers is an accepted adverse prognostic factor after liver transplantation. While its semiquantitative assessment shows varying reproducibility, it is questioned as a standard method. Additionally, the influence of hepatic steatosis on ischemia/reperfusion injury (I/R injury) has not been evaluated in biopsies after reperfusion. We compared different staining and analyzing methods for the assessment of donor liver steatosis in order to predict I/R injury and clinical outcome after transplantation. To do this, 56 paired pre- and post-reperfusion liver biopsies were analyzed for macro- (MaS)/micro- (MiS) and total steatosis in cryo and permanent sections by special fat (Oil Red O or ORO) and standard stains. Computerized morphometrical analyses were compared to the semiquantitative assessment by a pathologist. I/R injury was determined histopathologically and by M30 immunohistochemistry. We found ORO to be more sensitive in detecting hepatic steatosis with higher reproducibility for MaS. Semiquantitative analyses were highly reproducible and not inferior to computerized morphometry. Categorized MaS as determined by ORO correlated with the extent of I/R injury, initial poor function, liver enzymes, and survival. Therefore fat stains like ORO are a reliable and easy method comprising significant advantages in the evaluation of hepatic steatosis and are thereby of prognostic value. Computerized analysis is a precise tool though not superior to semiquantitative analyses.

The effect of hepatic steatosis on survival following resection of colorectal liver metastases in patients without preoperative chemotherapy.

BACKGROUND: Hepatic steatosis, a common condition associated with insulin resistance and excess body weight, is reported to be associated with an increased risk for perioperative mortality in patients undergoing resection of colorectal liver metastases (CLM), but its impact upon longterm survival is less well documented. METHODS: The effects of background liver pathology, categorized as 'normal', 'with steatosis' and 'other', on perioperative mortality, overall survival (OS) and cancer-specific survival (CSS) were assessed in patients undergoing resection for CLM according to data maintained in the LiverMetSurvey database. As preoperative chemotherapy may confound the effects of steatosis, patients who had been given preoperative chemotherapy were excluded. Survival analyses included log-rank tests for comparisons, and multivariate Cox models, including well-established prognosticators. RESULTS: Of 5853 patients who underwent first-time liver resection without preoperative chemotherapy, 1793 (30.6%) had background steatosis. Rates of 90-day perioperative mortality in patients with normal, steatosis and other pathologies were 2.8%, 2.1% and 4.9%, respectively. Steatosis was associated with improved 5-year OS (47.4% versus 43.0%; log rank, P = 0.0017) and CSS (56.1% versus 50.3%; P = 0.002) compared with normal background liver. After adjustments, the survival advantage associated with steatosis remained (hazard ratio = 0.806, 95% confidence interval 0.717-0.905 for CSS). DISCUSSION: The paradoxical survival advantage observed in patients with steatosis undergoing liver resection for CLM generates a hypothesis that peri-diagnosis of excess body adiposity has a survival protective effect that warrants further research.

Novel prognostic scoring system after surgery for Klatskin tumor.

Klatskin tumor is a rare hepatobiliary malignancy whose outcome and prognostic factors are not clearly documented. Between April 1998 and January 2007, 96 patients with hilar cholangiocarcinoma underwent resection. Data were collected prospectively. Thirty-one variables were evaluated for prognostic significance. There were 40 trisectionectomies, 40 hemihepatectomies, five central hepatectomies, and 11 biliary hilar resections. Thirty-seven (n = 37) patients required vascular reconstruction. There were 68 R0, 26 R1, and two R2 resections. Age (P = 0.048), pT status (P = 0.046), R class (P = 0.034), and adjuvant chemoradiation (P = 0.045) showed predictive significance by multivariate Cox proportional hazard regression analysis. A point scoring system was determined as follows: age younger than 62 years:age 62 years or older = 1:2 points; pT1:pT2 to 4 = 1:2 points; R0:R1/2 = 1:2 points; and chemoradiation yes:no = 1:2 points. The only model that reached statistical significance (P = 0.0332) described the following three groups: score 6 or less; score = 7; and score = 8. Median survival for score 6 or less, score = 7, and score = 8 was 26.5, 12, and 2.2 months, respectively (P = 0.032). The corresponding 1- and 3-year survival rates were 73 to 56 per cent, 52 to 38 per cent, and 17 to 0 per cent, respectively. We propose a scoring system predictive of long-term surgical outcome that could potentially improve patient selection for further postoperative oncologic treatment for Klatskin tumors.

Liver transplantation in nonalcoholic steatohepatitis is associated with high mortality and post-transplant complications: a single-center experience.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) with its progressive form nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in western countries which is associated with end-stage liver disease and hepatocellular carcinoma (HCC). This entity is a consistently increasing indication for transplantation. However, data about postsurgery outcome and complications are still limited. PATIENTS AND METHODS: Records of 432 consecutive transplanted patients between October 2007 and January 2011 were investigated retrospectively. Forty transplants were performed due to NASH-induced cirrhosis. Perioperative courses and short- and long-term outcomes were analyzed. RESULTS: The NAFLD population consisted of 16 women and 24 men with a mean age of 55 years. The median MELD score was 27 at the time of liver transplantion. BMI before surgery ranged from 21 to 45 (mean 31). Sixteen of the initial 40 patients are still alive. Patients with sustained obesity and features of the metabolic syndrome had a worse 1-year mortality rate of 42%. CONCLUSIONS: A significant number of liver transplantations in our center was performed due to NASH; transplantation in this cohort was associated with high mortality and postoperative complications, most likely due to associated obesity and diabetes. Weight reduction prior to surgery may lead to a better outcome.