Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Multicentre analysis of the learning curve for laparoscopic liver resection of the posterosuperior segments.

BACKGROUND: Laparoscopic liver resection demands expertise and a long learning curve. Resection of the posterosuperior segments is challenging, and there are no data on the learning curve. The aim of this study was to evaluate the learning curve for laparoscopic resection of the posterosuperior segments. METHODS: A cumulative sum (CUSUM) analysis of the difficulty score for resection was undertaken using patient data from four specialized centres. Risk-adjusted CUSUM analysis of duration of operation, blood loss and conversions was performed, adjusting for the difficulty score of the procedures. A receiver operating characteristic (ROC) curve was used to identify the completion of the learning curve. RESULTS: According to the CUSUM analysis of 464 patients, the learning curve showed an initial decrease in the difficulty score followed by an increase and, finally, stabilization. More patients with cirrhosis or previous surgery were operated in the latest phase of the learning curve. A smaller number of wedge resections and a larger number of anatomical resections were performed progressively. Dissection using a Cavitron ultrasonic surgical aspirator and the Pringle manoeuvre were used more frequently with time. Risk-adjusted CUSUM analysis showed a progressive decrease in operating time. Blood loss initially increased slightly, then stabilized and finally decreased over time. A similar trend was found for conversions. The learning curve was estimated to be 40 procedures for wedge and 65 for anatomical resections. CONCLUSION: The learning curve for laparoscopic liver resection of the posterosuperior segments consists of a stepwise process, during which accurate patient selection is key.

ANTECEDENTES: La resección hepática laparoscópica exige experiencia y una larga curva de aprendizaje. La resección de los segmentos posterosuperiores (PS) es un reto, y no hay datos acerca de la curva de aprendizaje (learning curve, LC). El objetivo de este estudio fue evaluar la LC de la resección laparoscópica de los segmentos PS. MÉTODOS: Se realizó un análisis CUSUM de la puntuación de dificultad (difficulty score, DS) de la resección en pacientes de 4 centros especializados. La técnica CUSUM se ajustó al riesgo (risk-adjusted CUSUM, RA-CUSUM) para el tiempo operatorio, la pérdida de sangre y las conversiones a cirugía abierta ajustando según la DS de los procedimientos. Se utilizó una curva ROC para identificar el momento en el que se consideró que la LC había sido completada. RESULTADOS: De acuerdo con el análisis CUSUM de los 464 pacientes incluidos, se observó una DS baja al inicio, que posteriormente se fue incrementando hasta llegar a una estabilización. En la última fase de la LC se operaron más pacientes con cirrosis o cirugía previa. De forma progresiva se fueron reduciendo el número de resecciones hepáticas en cuña y aumentando el de resecciones anatómicas. A lo largo del tiempo se introdujo el CUSA y la maniobra de Pringle con mayor frecuencia. El RA-CUSUM mostró una reducción progresiva del tiempo operatorio. La pérdida de sangre inicialmente aumentó ligeramente, luego se estabilizó y finalmente disminuyó con el tiempo. Una tendencia similar se observó para las conversiones. La LC se estimó en 40 casos para las resecciones en cuña y en 65 casos para las resecciones anatómicas. CONCLUSIÓN: La LC de la resección hepática laparoscópica de los segmentos PS es un proceso paso a paso durante el cual la selección del paciente es clave.

Multicentre propensity score-matched study of laparoscopic versus open repeat liver resection for colorectal liver metastases.

BACKGROUND: Repeat liver resection is often the best treatment option for patients with recurrent colorectal liver metastases (CRLM). Repeat resections can be complex, however, owing to adhesions and altered liver anatomy. It remains uncertain whether the advantages of a laparoscopic approach are upheld in this setting. The aim of this retrospective, propensity score-matched study was to compare the short-term outcome of laparoscopic (LRLR) and open (ORLR) repeat liver resection. METHODS: A multicentre retrospective propensity score-matched study was performed including all patients who underwent LRLRs and ORLRs for CRLM performed in nine high-volume centres from seven European countries between 2000 and 2016. Patients were matched based on propensity scores in a 1 : 1 ratio. Propensity scores were calculated based on 12 preoperative variables, including the approach to, and extent of, the previous liver resection. Operative outcomes were compared using paired tests. RESULTS: Overall, 425 repeat liver resections were included. Of 271 LRLRs, 105 were matched with an ORLR. Baseline characteristics were comparable after matching. LRLR was associated with a shorter duration of operation (median 200 (i.q.r. 123-273) versus 256 (199-320) min; P < 0·001), less intraoperative blood loss (200 (50-450) versus 300 (100-600) ml; P = 0·077) and a shorter postoperative hospital stay (5 (3-8) versus 6 (5-8) days; P = 0·028). Postoperative morbidity and mortality rates were similar after LRLR and ORLR. CONCLUSION: LRLR for CRLM is feasible in selected patients and may offer advantages over an open approach.

The role of pregnancy, perinatal factors and hormones in maternal cancer risk: a review of the evidence.

An understanding of the origin of cancer is critical for cancer prevention and treatment. Complex biological mechanisms promote carcinogenesis, and there is increasing evidence that pregnancy-related exposures influence foetal growth cell division and organ functioning and may have a long-lasting impact on health and disease susceptibility in the mothers and offspring. Nulliparity is an established risk factor for breast, ovarian, endometrial and possibly pancreatic cancer, whilst the risk of kidney cancer is elevated in parous compared with nulliparous women. For breast, endometrial and ovarian cancer, each pregnancy provides an additional risk reduction. The associations of parity with thyroid and colorectal cancers are uncertain. The timing of reproductive events is also recognized to be important. Older age at first birth is associated with an increased risk of breast cancer, and older age at last birth is associated with a reduced risk of endometrial cancer. The risks of breast and endometrial cancers increase with younger age at menarche and older age at menopause. The mechanisms, and hormone profiles, that underlie alterations in maternal cancer risk are not fully understood and may differ by malignancy. Linking health registries and pooling of data in the Nordic countries have provided opportunities to conduct epidemiologic research of pregnancy exposures and subsequent cancer. We review the maternal risk of several malignancies, including those with a well-known hormonal aetiology and those with less established relationships. The tendency for women to have fewer pregnancies and at later ages, together with the age-dependent increase in the incidence of most malignancies, is expected to affect the incidence of pregnancy-associated cancer.

Development and validation of a difficulty score to predict intraoperative complications during laparoscopic liver resection.

BACKGROUND: Previous studies have demonstrated that patient, surgical, tumour and operative variables affect the complexity of laparoscopic liver resections. However, current difficulty scoring systems address only tumour factors. The aim of this study was to develop and validate a predictive model for the risk of intraoperative complications during laparoscopic liver resections. METHODS: The prospectively maintained databases of seven European tertiary referral liver centres were compiled. Data from two-thirds of the patients were used for development and one-third for validation of the model. Intraoperative complications were based on a modified Satava classification. Using the methodology of the Framingham Heart Study, developed to identify risk factors that contribute to the development of cardiovascular disease, factors found to predict intraoperative complications independently were assigned points, and grouped into low-, moderate-, high- and extremely high-risk groups based on the likelihood of intraoperative complications. RESULTS: A total of 2856 patients were included. Neoadjuvant chemotherapy, lesion type and size, classification of resection and previous open liver resection were found to be independent predictors of intraoperative complications. Patients with intraoperative complications had a longer duration of hospital stay (5 versus 4 days; P < 0·001), higher complication rates (32·5 versus 15·5 per cent; P < 0·001), and higher 30-day (3·0 versus 0·3 per cent; P < 0·001) and 90-day (3·8 versus 0·8 per cent; P < 0·001) mortality rates than those who did not. The model was able to predict intraoperative complications (area under the receiver operating characteristic (ROC) curve (AUC) 0·677, 95 per cent c.i. 0·647 to 0·706) as well as postoperative 90-day mortality (AUC 0·769, 0·681 to 0·858). CONCLUSION: This comprehensive scoring system, based on patient, surgical and tumour factors, and developed and validated using a large multicentre European database, helped estimate the risk of intraoperative complications.

Outcome after laparoscopic and open resections of posterosuperior segments of the liver.

BACKGROUND: Laparoscopic resection of posterosuperior (PS) segments of the liver is hindered by limited visualization and curvilinear resection planes. The aim of this study was to compare outcomes after open and laparoscopic liver resections of PS segments. METHODS: Patients who underwent minor open liver resection (OLR) and laparoscopic liver resection (LLR) between 2006 and 2014 were identified from the institutional databases of seven tertiary referral European hepatobiliary surgical units. Propensity score-matched analysis was used to match groups for known confounders. Perioperative outcomes including complications were assessed using the Dindo-Clavien classification, and the comprehensive complication index was calculated. Survival was analysed with the Kaplan-Meier method. RESULTS: Some 170 patients underwent OLR and 148 had LLR. After propensity score-matched analysis, 86 patients remained in both groups. Overall postoperative complication rates were significantly higher after OLR compared with LLR: 28 versus 14 per cent respectively (P = 0·039). The mean(s.d.) comprehensive complication index was higher in the OLR group, although the difference was not statistically significant (26·7(16·6) versus 18·3(8·0) in the LLR group; P = 0·108). The mean(s.d.) duration of required analgesia and the median (range) duration of postoperative hospital stay were significantly shorter in the LLR group: 3·0(1·1) days versus 1·6(0·8) days in the OLR group (P < 0·001), and 6 (3-44) versus 4 (1-11) days (P < 0·001), respectively. The 3-year recurrence-free survival rates for patients with hepatocellular carcinoma (37 per cent for OLR versus 30 per cent for LLR; P = 0·534) and those with colorectal liver metastases (36 versus 36 per cent respectively; P = 0·440) were not significantly different between the groups. CONCLUSION: LLR of tumours in PS segments is feasible in selected patients. LLR is associated with fewer complications and does not compromise survival compared with OLR.

Indocyanine Green Near-Infrared Fluorescence in Pure Laparoscopic Living Donor Hepatectomy: a Reliable Road Map for Intra-Hepatic Ducts ?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Indocyanine green near-infrared fluorescence in pure laparoscopic living donor hepatectomy: a reliable road map for intra-hepatic ducts?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet ; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Simultaneous Parenchyma-Preserving Liver Resection, Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stage IV Colorectal Cancer.

BACKGROUND: The outcome of stage IV colorectal cancer (CRC) has improved with modern systemic therapy. However, the concomitant presence of liver metastases (LM) and peritoneal carcinomatosis (PC) remains associated with a dismal prognosis and surgery in this context remains exceptional. METHODS: Stage IV CRC patients with LM and PC undergoing simultaneous cytoreductive surgery, intraperitoneal chemotherapy (IPC) and liver resection/ablation were identified from prospectively collected databases. We assessed response to neoadjuvant chemotherapy (NACT), postoperative complications, progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-one patients with resectable disease were treated between 2007 and 2014. In 16 patients (76%), NACT was administered and tumour response defined their selection. The remaining 5 (24%) were selected according to the pattern of recurrence. Median peritoneal cancer index was 5 (range: 3-10.5). Liver surgery included 34 wedge resections, 5 ablations and one bisectionectomy to treat a total of 45 hepatic lesions with a median of 2 per patient (range: 1-2) and a median size of 1.35 cm (range: 0.8-2). Tumour regression grade 4 (fibrosis but residual cancer cells predominate) was seen in 50% of the resected metastases after NACT. Median hospital stay was 17 days (range: 14-24); severe morbidity (Clavien-Dindo grade 3-4) occurred in 24% and no perioperative mortality (0-90 days) was recorded. The median OS was 44 months (range: 31-57) while the median PFS was 10 months (range: 8-12). CONCLUSIONS: Combined parenchyma-preserving liver resection, cytoreductive surgery and IPC in patients with LM and PC from CRC can be performed safely and results in promising mid-term overall survival.

Pure laparoscopic full-left living donor hepatectomy for calculated small-for-size LDLT in adults: proof of concept.

Adult-to-adult living donor liver transplantation (A2ALDLT) is an accepted mode of treatment for end-stage liver disease. Right-lobe grafts have usually been preferred in view of the higher graft volume, which lowers the risk of a small-for-size syndrome. However, donor left hepatectomy is associated with less morbidity than when it is compared to right hepatectomy. Laparoscopic donor hepatectomy (LDH) has been considered almost exclusively in pediatric transplantation. The results of laparoscopic left-liver graft procurement for calculated small-for-size A2ALDLT in four donors are presented. The graft-to-recipient body weight ratio was <0.8 in all recipients. The mean portal vein flow and the pressure and hepatic artery flows were measured at 190 ± 56 mL/min/100 g, 13 ± 1.4 mm/Hg and 109 ± 19 mL/min, respectively. No early postoperative donor complications were recorded. One graft was lost due to intrahepatic abscesses. Asymptomatic stenosis of a right posterior duct was treated with a Roux-en-Y loop 4 months later in one donor. We show that LDH of the full-left lobe is feasible. LDH is a very demanding operation, potentially decreasing donor morbidity. Standardization of this procedure, making it accessible to the growing number of experienced laparoscopic liver surgeons, could help renewing the interest for A2ALDLT in the Western world.

Standardized added metabolic activity (SAM) IN ¹8F-FDG PET assessment of treatment response in colorectal liver metastases.

PURPOSE: Standardized added metabolic activity (SAM) is a PET parameter for assessing the total metabolic load of malignant processes, avoiding partial volume effects and lesion segmentation. The potential role of this parameter in the assessment of response to chemotherapy and bevacizumab was tested in patients with metastatic colorectal cancer with potentially resectable liver metastases (mCRC). METHODS: (18)F-FDG PET/CT was performed in 18 mCRC patients with liver metastases before treatment and after five cycles of FOLFOX/FOLFIRI and bevacizumab. Of the 18 patients, 16 subsequently underwent resection of liver metastases. Baseline and follow-up SUVmax, and SAM as well as reduction in SUVmax (∆SUVmax) and SAM (∆SAM) of all liver metastases were correlated with morphological response, and progression-free and overall survival (PFS and OS). RESULTS: A significant reduction in metabolic activity of the liver metastases was seen after chemotherapy with a median ∆SUVmax of 25.3% and ∆SAM of 94.5% (p = 0.033 and 0.003). Median baseline SUVmax and SAM values were significantly different between morphological responders and nonresponders (3.8 vs. 7.2, p = 0.021; and 34 vs. 211, p = 0.002, respectively), but neither baseline PET parameters nor morphological response was correlated with PFS or OS. Follow-up SUVmax and SAM as well as ∆SAM were found to be prognostic factors. The median PFS and OS in the patient group with a high follow-up SUVmax were 10.4 months and 32 months, compared to a median PFS of 14.7 months and a median OS which had not been reached in the group with a low follow-up SUVmax (p = 0.01 and 0.003, respectively). The patient group with a high follow-up SAM and a low ∆SAM had a median PFS and OS of 9.4 months and 32 months, whereas the other group had a median PFS of 14.7 months and a median OS which had not been reached (p = 0.002 for both PFS and OS). CONCLUSION: (18)F-FDG PET imaging is a useful tool to assess treatment response and predict clinical outcome in patients with mCRC who undergo chemotherapy before liver metastasectomy. Follow-up SUVmax, follow-up SAM and ∆SAM were found to be significant prognostic factors for PFS and OS.

Pathophysiology and management of post resection liver failure.

Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and nonparenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

Meso-Rex shunt using deep femoral vein conduit: first report.

The Meso-Rex shunt (MRS) procedure was first described in 1992 by de VILLE et al. for the treatment of extrahepatic portal vein obstruction (EHPVO) in paediatric liver transplant patients. This technique provides more physiological relief of portal hypertension compared to the porto-systemic shunts, which can lead to long-term complications such as hyperammonaemia and hepato-pulmonary syndrome. Different conduits as autologous and cryopreserved veins or prosthetic grafts have been previously reported. We present herein the first case of a MRS using the autologous deep femoral vein in a 17-year-old female patient affected by EHPVO from unknown reasons.

Value of DCE-MRI and FDG-PET/CT in the prediction of response to preoperative chemotherapy with bevacizumab for colorectal liver metastases.

BACKGROUND: The purpose of this study was to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and (18)F-fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET/CT) for evaluation of response to chemotherapy and bevacizumab and for prediction of progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) with potentially resectable liver lesions. METHODS: A total of 19 mCRC patients were treated with FOLFOX/FOLFIRI and bevacizumab followed by surgery. Dynamic contrast-enhanced magnetic resonance imaging and FDG-PET/CT were performed before treatment and after cycle 5. PET results were quantified by calculating maximum standardised uptake value (SUV(max)) whereas area under the enhancement curve (AUC), initial AUC (iAUC) and the endothelial transfer constant (K(trans)) were used to quantify DCE-MRI. Pathological analysis of the resection specimen was performed, including measurement of microvessel density (MVD) and proliferation index. RESULTS: Both AUC and iAUC were significantly decreased following bevacizumab therapy (median change of 22% (P=0.002) and 40% (P=0.001) for AUC and iAUC, respectively). Progression-free survival benefit was shown for patients with >40% reduction in K(trans) (P=0.019). In the group of radiological responders, the median baseline SUV(max) was 3.77 (IQR: 2.88-5.60) compared with 7.20 (IQR: 4.67-8.73) in nonresponders (P=0.021). A higher follow-up SUV(max) was correlated with worse PFS (P=0.012). Median MVD was 10.9. Progression-free survival was significantly shorter in patients with an MVD greater than 10, compared with patients with lower MVD (10 months compared with 16 months, P=0.016). CONCLUSION: High relative decrease in K(trans), low follow-up SUV(max) and low MVD are favourable prognostic factors for mCRC patients treated with bevacizumab before surgery.

Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial.

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.

Prospective evaluation of intraoperative hemodynamics in liver transplantation with whole, partial and DCD grafts.

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.

Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation.

The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.

Birth defects in the sons and daughters of women who were exposed in utero to diethylstilbestrol (DES).

Prenatal exposure to diethylstilbestrol (DES) is associated with adverse health outcomes, including anatomic anomalies of the reproductive tract in women and of the genitourinary tract in men. The mouse model, which replicates many DES-related effects seen in humans, suggests that prenatal DES exposure causes alterations that may affect the next generation of offspring. We asked women participating in a large, multi-centre study of prenatal DES exposure to report birth defects occurring among 4029 sons and 3808 daughters (i.e., the third generation). A subcohort of 793 third generation daughters was also queried for birth defects. We used logistic regression models to generate odds ratio and 95% confidence intervals for the association between prenatal DES exposure in the mother and birth defects in the offspring. Based on the mothers' reports, overall birth defects were elevated in the sons (OR = 1.53; 95% CI = 1.04, 2.23) and in the daughters (OR = 2.35; 95% CI = 1.44, 3.82). Most estimates of association were imprecise, but daughters appeared to have an excess of heart conditions (OR = 4.56; 95% CI = 1.27, 16.34). Our data suggest a possible association between the mother's prenatal DES exposure and birth defects in their offspring, particularly in daughters. We cannot, however, rule-out the possible influence of reporting bias. In particular, the exposed daughters' elevated risk of cardiac defects may be as a result of the underreporting of these conditions by unexposed mothers.

Infrarenal versus supraceliac aorto-hepatic arterial revascularisation in adult liver transplantation: multicentre retrospective study.

When the standard arterial reconstruction is not feasible during liver transplantation (LT), aorto-hepatic arterial reconstruction (AHAR) can be the only solution to save the graft. AHAR can be performed on the infrarenal (IR) or supraceliac (SC) tract of the aorta, but the possible effect on outcome of selecting SC versus IR reconstruction is still unclear. One hundred and twenty consecutive patients who underwent liver transplantation with AHAR in six European centres between January 2003 and December 2018 were retrospectively analysed to ascertain whether the incidence of hepatic artery thrombosis (HAT) was influenced by the type of AHAR (IR-AHAR vs. SC-AHAR). In 56/120 (46.6%) cases, an IR anastomosis was performed, always using an interposition arterial conduit. In the other 64/120 (53.4%) cases, an SC anastomosis was performed; an arterial conduit was used in 45/64 (70.3%) cases. Incidence of early (≤ 30 days) HAT was in 6.2% (4/64) in the SC-AHAR and 10.7% (6/56) IR-AHAR group (p = 0.512) whilst incidence of late HAT was significantly lower in the SC-AHAR group (4.7% (3/64) vs 19.6% (11/56) - p = 0.024). IR-AHAR was the only independent risk factor for HAT (exp[B] = 3.915; 95% CI 1.400-10.951; p = 0.009). When AHAR is necessary at liver transplantation, the use of the supraceliac aorta significantly reduces the incidence of hepatic artery thrombosis and should therefore be recommended whenever possible.