Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma.

Importance: National guidelines on transplant selection have adopted successful downstaging to within Milan criteria (MC) as a viable option for the treatment of hepatocellular carcinoma (HCC) before liver transplant (LT). Recurrence of HCC after LT carries a poor prognosis, and treatment modalities remain challenging. Objective: To establish the 10-year outcomes of patients with HCC after LT in a large, multicenter US study based on individual data; provide robust data on the long-term role of downstaging; and evaluate the association of treatment modalities with postrecurrence survival. Design, Setting, and Participants: In this cohort study, a retrospective, multicenter analysis of prospectively collected data was conducted for 2645 adults who had undergone LT for HCC at 5 US academic centers between January 2001 and December 2015. The analysis was performed from May 2019 through June 2021. Outcomes of 341 patients whose disease was downstaged to within MC were compared with those in 2122 patients whose disease was always within MC and 182 patients whose disease was not downstaged. The associations of tumor and treatment factors on postrecurrence survival were analyzed using Cox proportional hazards regression and multivariable logistic regression models. Main Outcomes and Measures: The primary outcome was overall survival for the whole cohort and according to downstaging status. Secondary outcomes were time to recurrence, recurrence-free survival, and recurrence after specific post-LT therapies. Results: Of the 2645 patients studied, the median age was 59.9 years (IQR, 54.7-64.7 years). The majority of the patients were men (2028 [76.7%] vs 617 [23.3%] women). The 10-year post-LT survival and recurrence rates were, respectively, 52.1% and 20.6% among those whose disease was downstaged; 61.5% and 13.3% in those always within MC; and 43.3% and 41.1% in those whose disease was not downstaged. Independent variables associated with downstaging failure were tumor size greater than 7 cm at diagnosis (OR, 2.62; 95% CI, 1.20-5.75; P = .02), more than 3 tumors at diagnosis (OR, 2.34; 95% CI, 1.22-4.50; P = .01), and α-fetoprotein response of at least 20 ng/mL with less than 50% improvement from maximum α-fetoprotein before LT (OR, 1.99; 95% CI, 1.14-3.46; P = .02). Surgically treated patients with recurrent HCC differed in clinicopathologic characteristics and had improved 5-year postrecurrence survival rates (31.6% vs 7.3%; P < .001). Conclusions and Relevance: In a large, multicenter cohort of patients with HCC successfully downstaged to within MC, 10-year post-LT outcomes were excellent, validating national downstaging policies and showing a clear utility benefit for LT prioritization decision making. Surgical management of HCC recurrence after LT was associated with improved survival in well-selected patients and should be pursued, if feasible.

Evaluation of the LI-RADS treatment response algorithm in hepatocellular carcinoma after trans-arterial chemoembolization.

PURPOSE: To evaluate the diagnostic performance of LI-RADS treatment response algorithm (LR-TRA) and modified RECIST (mRECIST) for the detection of viable hepatocellular carcinoma (HCC) on MRI after trans-arterial chemoembolization (TACE). MATERIALS AND METHODS: This retrospective study includes cirrhotic patients that underwent trans-arterial chemoembolization prior to liver transplantation from 2013 to 2017 with a pre- and post-treatment MRI available. Three blinded readers assigned a LR-TRA and mRECIST category to each lesion. Lesions on MRI and explant pathology were matched and characterized as complete (100% necrosis) or incomplete necrosis (≤99% necrosis). Diagnostic performance of LR-TRA and mRECIST were calculated with a generalized estimating equation. RESULTS: A total of 52 patients with 71 lesions were included, 47 with incomplete and 24 with complete necrosis. In consensus, 45 lesions were categorized as LR-TR Nonviable, of which 62.2% (28/45) had incomplete and 37.8% (17/45) had complete necrosis. Six lesions were categorized as LR-TR Equivocal, of which 33.3% (2/6) had incomplete and 66.7% (4/6) had complete necrosis. Twenty lesions were categorized as LR-TR Viable of which 85.0% (17/20) had incomplete and 15.0% (3/20) had complete necrosis. The sensitivity of LR-TR Viable for detecting incompletely necrotic tumor when LR-TR Equivocal was considered as viable, in consensus was 40.4%; specificity 70.8%; accuracy 50.7%. The sensitivity of mRECIST for detecting incompletely necrotic tumor was 37.0%; specificity 79.2%; accuracy 51.4%. There was no significant difference in diagnostic performance between mRECIST and LR-TRA (p = 0.14-0.33). Agreement for LR-TRA category was moderate (k = 0.53 [95% CI: 0.45, 0.67]). CONCLUSION: LI-RADS treatment response algorithm demonstrates high specificity and low to moderate sensitivity for the detection of viable HCC after TACE in a North American cirrhotic cohort, without significant difference in diagnostic performance between LR-TRA and mRECIST.

Dynamic α-Fetoprotein Response and Outcomes After Liver Transplant for Hepatocellular Carcinoma.

Importance: Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured. Objective: To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models. Design, Setting, and Participants: A retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020. Main Outcomes and Measures: The primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome. Results: Of 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0. Conclusions and Relevance: This study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. STUDY DESIGN: Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. RESULTS: Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001). CONCLUSIONS: Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.

Activin type II receptor ligand signaling inhibition after experimental ischemic heart failure attenuates cardiac remodeling and prevents fibrosis.

Myostatin (MSTN) is a transforming growth factor (TGF)-ß superfamily member that acts as a negative regulator of muscle growth and may play a role in cardiac remodeling. We hypothesized that inhibition of activin type II receptors (ACTRII) to reduce MSTN signaling would reduce pathological cardiac remodeling in experimental heart failure (HF). C57BL/6J mice underwent left anterior descending coronary artery ligation under anesthesia to induce myocardial infarction (MI) or no ligation (sham). MI and sham animals were each randomly divided into groups (n ≥ 10 mice/group) receiving an ACTRII or ACTRII/TGFß receptor-signaling inhibiting strategy: 1) myo-Fc group (weekly 10 mg/kg Myo-Fc) or 2) Fol + TGFi group (daily 12 µg/kg follistatin plus 2 mg/kg TGFß receptor inhibitor), versus controls. ACTRII/TGFBR signaling inhibition preserved cardiac function by echocardiography and prevented an increase in brain natriuretic peptide (BNP). ACTRII/TGFBR inhibition resulted in increased phosphorylation (P) of Akt and decreased P-p38 mitogen-activated protein kinase (MAPK) in MI mice. In vitro, Akt contributed to P-SMAD2,3, P-p38, and BNP regulation in cardiomyocytes. ACTRII/TGFBR inhibition increased sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) levels and decreased unfolded protein response (UPR) markers in MI mice. ACTRII/TGFBR inhibition was associated with a decrease in cardiac fibrosis and fibrosis markers, connective tissue growth factor (CTGF), type I collagen, fibronectin, α-smooth muscle actin, and matrix metalloproteinase (MMP)-12 in MI mice. MSTN exerted a direct regulation on the UPR marker eukaryotic translation initiation factor-2α (eIf2α) in cardiomyocytes. Our study suggests that ACTRII ligand inhibition has beneficial effects on cardiac signaling and fibrosis after ischemic HF.NEW & NOTEWORTHY Activin type II receptor ligand inhibition resulted in preserved cardiac function, a decrease in cardiac fibrosis, improved SERCA2a levels, and a prevention of the unfolded protein response in mice with myocardial infarction.

From a Philosophical Framework to a Valid Prognostic Staging System of the New "Comprehensive Assessment" for Transplantable Hepatocellular Carcinoma.

The comprehensive assessment of the transplantable tumor (TT) proposed and included in the last Italian consensus meeting still deserve validation. All consecutive patients with hepatocellular carcinoma (HCC) listed for liver transplant (LT) between January 2005 and December 2015 were post-hoc classified by the tumor/patient stage as assessed at the last re-staging-time (ReS-time) before LT as follow: high-risk-class (HRC) = stages TTDR, TTPR; intermediate-risk-class (IRC) = TT0NT, TTFR, TTUT; low-risk-class (LRC) = TT1, TT0L, TT0C. Of 376 candidates, 330 received LT and 46 dropped-out. Transplanted patients were: HRC for 159 (48.2%); IRC for 63 (19.0%); LRC for 108 (32.7%). Cumulative incidence function (CIF) of tumor recurrence after LT was 21%, 12%, and 8% at 5-years and 27%, 15%, and 12% at 10-years respectively for HRC, IRC, and LRC (P = 0.011). IRC patients had significantly lower CIF of recurrence after LT if transplanted >2-months from ReS-time (28% vs 3% for <2 and >2 months, P = 0.031). HRC patients had significantly lower CIF of recurrence after-LT if transplanted <2 months from the ReS-time (10% vs 33% for <2 and >2 months, P = 0.006). The proposed TT staging system can adequately describe the post-LT recurrence, especially in the LRC and HRC patients. The intermediate-risk-class needs to be better defined and further studies on its ability in defining intention-to-treat survival (ITT) and drop-out are required.

Outcomes of the Arterial Switch Operation in ≤2.5-kg Neonates.

Although low birth weight is a known risk factor for mortality in congenital heart lesions and may consequently delay surgical repair, outcomes in low-weight neonates undergoing the arterial switch operation (ASO) have not been well described. Our objective was to assess the safety of this procedure in infants weighing ≤2.5 kg at the time of surgery. We retrospectively analyzed outcomes for all neonates undergoing the ASO at our institution from 2005 to 2015. Our primary outcome of interest was major morbidity or operative mortality, assessed as a composite outcome. From 2005 to 2015, 217 neonates underwent the ASO, with 31 (14%) weighing ≤2.5 kg at the date of surgery, and 8 weighing <2.0 kg. Neonates weighing ≤2.5 kg were more likely to be premature than those weighing >2.5 kg, but there was no difference in the age at operation between these groups. Overall, 32 infants experienced a major morbidity or mortality, including 37.5% (n = 3) weighing <2.0 kg, 8.7% (n = 2) weighing 2.0-2.5 kg, and 14.5% (n = 7) weighing >2.5 kg (P = 0.141). One infant weighing <2.0 kg (1.1 kg) and 4 infants weighing >2.5 kg died. In multivariable models, odds of major morbidity or mortality were significantly higher for infants weighing <2 kg compared with infants weighing >2.5 kg (odds ratio 3.93, 95% confidence interval 1.04-14.85, P = 0.044), but there was no difference between infants weighing 2.0-2.5 kg and those weighing >2.5 kg (P = 0.225). The ASO can be performed safely in 2.0- to 2.5-kg neonates and yields results comparable with higher weight infants. Imposed delays for corrective surgery may not be necessary for these low-weight infants with transposition of the great arteries.

Minor laparoscopic liver resection for Hepatocellular Carcinoma is safer than minor open resection, especially for less compensated cirrhotic patients: Propensity score analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has gained significant popularity over the last 10 years. First experiences of LLR compared to open liver resection (OLR) reported a similar survival and a better safety profile for LLR. MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data of all consecutive patients treated by liver resection for HCC on liver cirrhosis between January 2005 and March 2017. The choice of procedure (LLR vs OLR) was generally based on tumor localization, history of previous upper abdominal surgery and patient's preference. The type of resection and indication for surgery were unrelated to the adopted technique. Based on pre-operative variables and confirmed cirrhosis, a 1:1 propensity score matching (PSM) model was developed to compare outcomes of LLR and OLR in patients with HCC. Outcomes of interest included morbidity, mortality and long-term cure potential. RESULTS: After-PSM, the LLR group demonstrated better perioperative results including: lower complication rate (50.7% in OLR vs 29.3% in LLR, p = 0.0035), significantly lower intra-operative blood loss (200 ml in OLR vs 150 ml in LLR, p = 0.007) and shorter hospital length of stay (median 9 days in OLR vs 7 days in LLR, p = 0.0018). Moreover there was no significant difference between the two groups in 3-year survival (76%, CI: 60%-86% in LLR vs 68%, CI: 55%-79% in OLR, p = 0.32) or recurrence-free survival rates (44%, CI: 28%-58%, vs 44%, CI: 31%-57%, p = 0.94). CONCLUSIONS: Minor LLR appeared significantly safer compared to minor OLR for HCC. LLR was associated with fewer post-operative complication, lower operative blood loss and a shorter hospital stay along with similar survival and recurrence-free survival rates.

Is it Time to Abandon the Milan Criteria?: Results of a Bicoastal US Collaboration to Redefine Hepatocellular Carcinoma Liver Transplantation Selection Policies.

OBJECTIVES: European liver transplant (LT) centers have moved away from using the Milan Criteria (MC) for hepatocellular carcinoma (HCC) patient selection, turning to models including tumor biological indices, namely alpha-fetoprotein (AFP). We present the first US model to incorporate an AFP response (AFP-R), with comparisons to MC and French-AFP models (F-AFP). METHODS: AFP-R was measured as differences between maximum and final pre-LT AFP in HCC patients undergoing LT at 3 US centers (2001 to 2013). Cox and competing risk-regression analyses identified predictors of recurrence-free survival (RFS). RESULTS: Of 1450 patients, 235 (16.2%) were outside MC. Tumor size, number, and AFP-R were independent predictors of RFS and were assigned weighted points based on Cox-regression analysis. An AFP-R consistently < 200 ng/mL predicted the best outcome. A 3-tiered competing-risk RFS model, the New York/California (NYCA) score, was developed, accurately discriminating between groups (P < 0.001), and correlating with overall survival (P < 0.001). Two hundred one of 235 patients outside MC (85.5%) would be recategorized into NYCA low/acceptable-risk groups. The c-statistic for our NYCA score is 0.731 compared with 0.613 for MC and 0.658 for F-AFP (P < 0.0001). CONCLUSION: Incorporation of AFP-R into HCC selection criteria allows for MC expansion. As United Network for Organ Sharing considers adding AFP to selection algorithms, the NYCA score provides an objective, user-friendly tool for centers to appropriately risk-stratify patients.

Reestablishment of Lymphatic Drainage after Vascularized Lymph Node Transfer in a Rat Model.

BACKGROUND: Vascularized lymph node transfer has recently received attention as a potential surgical treatment for lymphedema. Despite good results in some series, the mechanism and benefits of vascularized lymph node transfer have yet to be fully understood. This study aimed to investigate the reestablishment of drainage into transferred lymph nodes following vascularized lymph node transfer in a rat model. METHODS: Seven rats underwent vascularized lymph node transfer. The operation performed on each rat consisted of two parts. First, the left groin lymph node basin with superficial epigastric vessels was harvested as a free flap. Second, the flap was reattached in the left groin of the rat by means of end-to-end microvascular anastomoses. Anastomosis patency was assessed immediately postoperatively and at the time of animal sacrifice. The rats were evaluated for reestablishment of lymphatic flow into the transplanted nodes at 1-month intervals for at least 6 months postoperatively. This was accomplished noninvasively by injecting the rats in their flanks with fluorescent indocyanine green, which was detected using a Photodynamic Eye infrared camera. RESULTS: Anastomoses were patent in all seven rats immediately postoperatively. No indocyanine green uptake was seen in the transplanted lymph node basins in the first 2 months postoperatively in any of the rats. In five of seven rats, however, indocyanine green uptake was demonstrated in the transplanted lymph node basin by 6 months (average, 13 weeks). CONCLUSION: The authors report uptake of indocyanine green in five of seven rats at an average of 13 weeks after lymph node transplantation, consistent with the reestablishment of lymphatic drainage into the transplanted nodes.

Proposal of Prognostic Survival Models before and after Liver Resection for Hepatocellular Carcinoma in Potentially Transplantable Patients.

BACKGROUND: Transplantable hepatocellular carcinoma (HCC) represents a highly debated issue due to the overlap between indications for liver resection (LR) and transplantation (LT) in patients suitable for both. STUDY DESIGN: Between January 2000 and December 2012, five hundred and twenty-four transplantable patients affected by HCC were identified among resected patients. Two regression models were constructed to classify patients into 2 groups pre-low and pre-high risk based on preoperative variables and then to reclassify pre-low-risk patients according to postoperative variables into either post-low or post-high-risk. Additionally, a cohort of patients with comparable baseline characteristics who underwent LT were similarly classified into pre-low and pre-high-risk groups and compared with the resected patients in terms of survival. RESULTS: Cirrhosis, aspartate transaminase, α-fetoprotein, Model for End-Stage Liver Disease score, number of nodules, and diameter of the largest nodule were preoperatively found to be significantly related to overall survival post-LR. Microvascular invasion and satellites were selected to reclassify prognosis in the resulting preoperative low-risk group into post-high risk. The converted group (post-high) demonstrated the same 5-year survival as the pre-high group. Patients undergoing LT had better survival overall than those undergoing LR, with the exception of pre-low LT and post-low LR (confirmed low-risk LR) who had similar outcomes. CONCLUSIONS: The new models were strongly predictive of patients' likelihood of survival after LR for HCC on liver cirrhosis. Liver transplantation offers a survival advantage over LR, except in low-risk groups where both modalities might be comparable.

Pretreatment neutrophil-lymphocyte ratio: useful prognostic biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common liver malignancy and the third most common cause of cancer-related deaths. Liver resection (LR) and liver transplantation (LT) are the only curative modalities for HCC. Despite recent advances and the adoption of the Milan and University of California, San Francisco, criteria, HCC recurrence after LR and LT remains a challenge. Several markers and prognostic scores have been proposed to predict tumor aggressiveness and supplement radiological data; among them, neutrophil-lymphocyte ratio (NLR) has recently gained significant interest. An elevated NLR is thought to predispose to HCC recurrence by creating a protumorigenic microenvironment through both relative neutrophilia and lymphocytopenia. In the present review, we attempted to summarize the published work on the role of pretreatment NLR as a prognostic marker for HCC following LR and LT. A total of 13 LT and 18 LR studies were included from 2008 to 2015. Pretransplant NLR was most often predictive of HCC recurrence, recurrence-free survival, and overall survival. NLR was, however, more variably and less clearly associated with worse outcomes following LR.

Anti-Hu paraneoplastic brainstem encephalitis caused by a pancreatic neuroendocrine tumor presenting with central hypoventilation.

Paraneoplastic neurological syndromes are rare autoimmune manifestations of malignancies associated with specific antibodies. Anti-Hu associated brainstem encephalitis, a well-described syndrome, usually presents subacutely with preferential involvement of the medulla. Anti-Hu antibodies target intraneuronal antigens and are therefore highly correlated with neurological syndromes when present concomitantly with a neoplasm. Reported is a case of anti-Hu brainstem encephalitis associated with a pancreatic neuroendocrine tumor (PNET) presenting with central hypoventilation. This is the first described case of brainstem encephalitis associated with a well-differentiated PNET as well as the first case of Anti-Hu antibodies associated with a PNET. There are no standardized protocols for the treatment of paraneoplastic brainstem encephalitis however, as in the present case, surgical resection and oncological treatment of the tumor is the first line treatment.

Cardiac Function After Tetralogy of Fallot/Complete Atrioventricular Canal Repair.

BACKGROUND: Repair of complete atrioventricular canal (CAVC) with tetralogy of Fallot (TOF) is a challenging operation increasingly being performed as a complete, primary repair in infancy. Previous studies have focused on perioperative outcomes; however, midterm valve function, ventricular function, and residual obstruction have received little attention. METHODS: We retrospectively reviewed 20 patients who underwent CAVC/TOF repair (January 2005 to December 2014). A two-patch repair was used in all patients to correct the CAVC defect. Tetralogy of Fallot repair included transannular patch in 11 (65%) patients and valve-sparing in 6 (35%) patients. RESULTS: The average age at surgery was 72 ± 122 weeks, 40% were male, and 80% had trisomy 21. Mean echo follow-up was 3.0 ± 3.0 years. There were no in-hospital or late mortalities. The rate of reoperation was 20%. At the latest follow-up, moderate left atrioventricular valve regurgitation was present in three (15%) patients and mild stenosis present in seven (35%) patients. One (5%) patient had moderate right ventricular outflow tract (RVOT) obstruction. The valve-sparing population was smaller at the time of surgery than the non-valve-sparing cohort (body surface area: 0.28 ± 0.04 vs 0.42 ± 0.11, P = .002) and less likely to have had a previous shunt (0% vs 64%, P = .01). Among the valve-sparing patients (six), at the latest follow-up, moderate pulmonary insufficiency was present in two (33%) patients. CONCLUSION: Repair of CAVC concomitant with TOF can be performed with low mortality and acceptable perioperative morbidity. Management of the RVOT remains a challenge for the long term.

Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story.

OBJECTIVE: We sought to develop a "Model Of Recurrence After Liver transplant" (MORAL) for hepatocellular carcinoma (HCC). BACKGROUND: The Milan criteria are used to allocate livers to patients with HCC requiring liver transplantation (LT) but do not include objective measures of tumor biology. Biological markers including the neutrophil-lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) have been associated with recurrence risk. METHODS: Prospective cohort study of adults undergoing LT for HCC between January 2001 and December 2012. RESULTS: A total of 339 patients were included. On multivariable Cox regression analysis, 3 preoperatively available factors were independent predictors of worse recurrence-free survival (RFS), namely, an NLR ≥ 5 (P < 0.0001, hazard ratio, HR: 6.2), AFP > 200 (P < 0.0001, HR: 3.8), and Size >3 cm (P < 0.001, HR: 3.2). The Pre-MORAL score was constructed from the hazard ratios and assigning patients points in an additive fashion, with a minimum of 0 points (no factors) and a maximum of 13 points (all 3 factors). The highest risk patients in the Pre-MORAL had a 5-year RFS of 17.9% compared with 98.6% for the low risk group (P < 0.0001). The post-MORAL was constructed similarly using the 4 postoperatively available independent predictors of worse RFS, grade 4 HCC's (P < 0.0001, HR: 5.6), vascular invasion (P = 0.019, HR: 2.0), size >3 cm (P < 0.0001, HR: 3.2) and number >3 (P = 0.048, HR: 1.8). The pre- and post-MORAL were superior to Milan at predicting recurrence with c-statistics of 0.82 and 0.87, compared with 0.63, respectively. We then combined the scores to produce a combo-MORAL, with a c-statistic of 0.91 for predicting recurrence. CONCLUSIONS: The MORAL score provides a simple, highly accurate tool for predicting recurrence and risk-stratification pre- and postoperatively.

Epithelialization Over a Scaffold of Antibiotic-Impregnated PMMA Beads: A Salvage Technique for Open Tibial Fractures with Bone and Soft Tissue Loss When all Else Fails.

The management of soft tissue defects in tibial fractures is essential for limb preservation. Current techniques are not without complications and may lead to poor functional outcomes. A salvage method is described using three illustrative cases whereby a combination of flaps and antibiotic-impregnated polymethylmethacrylate beads are employed to fill the bony defect, fight the infection, and provide a surface for epithelial regeneration and secondary wound closure. This was performed after the partial failure of all other options. All patients were fully ambulatory with no clinical, radiographic or laboratory sign of infection at their most recent follow-up. Although our findings are encouraging, this is the first report of epithelialization of the skin on a polymethylmethacrylate scaffold. Further studies investigating the use of this technique are warranted.

Round Ligament Leiomyoma Presenting as an Incarcerated Inguinal Hernia: Case Report and Review of the Literature.

Leiomyomas are common benign gynecologic tumors occurring in up to 30% of women. Round ligament leiomyomas however are very rare and, if symptomatic, can present as an inguinal hernia. We report the case of a 47-year-old woman who presented with an irreducible inguinal mass consistent with an incarcerated hernia. Intraoperatively, the mass was found to be a round ligament leiomyoma, a diagnosis that was confirmed by histopathology following excision of the mass. Although rare, round ligament leiomyomas should be part of the differential diagnosis of an inguinal hernia in females.

Bridging Anticoagulation After Mechanical Aortic Heart Valve Replacement: A Questionable Routine.

BACKGROUND: This retrospective single-center study evaluates differences in bleeding and thrombotic events between a homogenous group of patients undergoing mechanical aortic valve replacement who either received or did not receive intravenous unfractionated heparin or subcutaneous low-molecular weight heparin as bridging strategy to warfarin therapy. METHODS: Clinical data on a total of 158 patients undergoing mechanical aortic valve replacement at our center between 2001 and 2014 were collected. Patients were grouped according to postoperative anticoagulation strategy: warfarin only (n = 53) and warfarin plus heparin bridge (n = 105). The outcomes of interest were bleeding event and thromboembolic event recorded during hospital stay. RESULTS: Patients' baseline characteristics were comparable between the two groups except for preoperative atrial fibrillation, which was more common in the warfarin plus heparin group than the warfarin group (p = 0.04). There were significantly more bleeding complications in the warfarin plus heparin group versus warfarin group as evidenced by higher rates of pericardial effusions (24% versus 8%, p = 0.02) and reoperation for bleeding (8% versus 0%, p = 0.05). All observed thromboembolic events (n = 4) occurred in the warfarin plus heparin group (p = 0.55). Logistic regression analysis identified group assignment (warfarin plus heparin versus warfarin only) to be significantly associated with the odds of bleeding (odds ratio 4.46, 95% confidence interval:1.42 to 14.02, p = 0.01). CONCLUSIONS: Bridging anticoagulation therapy increases the chances of bleeding in the postoperative phase for mechanical aortic valve replacement patients. Owing to low incidence, no statistically significant difference was detected for thromboembolic event rates.