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A letter to the editor is presented related to hepatic venoocclusive disease (VOD) following liver transplantation in a 20-year-old female.

Objective: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT)., Background: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation., Methods: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict., Results: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%-94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term., Conclusions: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach., Methods: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis., Results: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003)., Conclusion: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard., (© 2021. The Author(s).)

Objective: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers., Summary of Background Data: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients., Methods: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018., Results: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS., Conclusion: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers., Summary Background Data: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection., Methods: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998)., Results: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%., Conclusion: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

Objective: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD)., Background: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative., Methods: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches., Results: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases., Conclusion: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.

Background: Supervised (SE) and home-based exercise (HBE) training regimes are effective on reconditioning patients with familial amyloidotic polyneuropathy (FAP) after liver transplantation, but research of the long-term retention of the benefits attained in patients with FAP has not yet been conducted., Purpose: In this 5-year follow-up study, we aimed to determine whether the exercise training gains in body composition, physical activity, and function promoted by a 24-week SE or HBE training regimes are retained in patients with FAP who resume normal activity., Methodology: Sixteen liver-transplanted patients with FAP were reassessed for body composition (dual X-ray absorptiometry), physical activity (questionnaire), and function (handgrip strength and 6-minute walk test)., Results: Total body fat increased with both exercise regimes during follow-up ( P < .05; η 2 = 0.432-0.625) as well as femoral neck bone density ( P = .048; η 2 = 0.119). However, gains in upper limbs muscle quality during follow-up ( P < .001; η 2 = 0.597) were only found in the SE group ( P = .042; η 2 = 0.245). Both exercise regimes showed retaining aptitudes in walking capacity ( P < .05; η 2 = 0.329-0.460) and muscle mass ( P = .05; η 2 = 0.245). Still, none could retain the physical activity levels., Conclusion: Long-term resumption of normal activity following a 24-week SE or HBE regime in patients with FAP resulted in loss of exercise induced increases in physical activity but counterweighted postoperative losses in bone mineral density and substantially retained the benefits in walking capacity, muscle mass, and quality, in particular, in the SE group.

Total tumor volume (TTV) has been proposed as a more accurate means of selecting patients for liver transplantation (LT) due to hepatocellular carcinoma (HCC). We aim to analyze the role of TTV in a population with a short waiting time on list., Methods: Analysis of a prospective database of patients submitted to LT for HCC between September 1992 and February 2014. TTV, Milan criteria (MC), UCSF (University of California San Francisco), and "Up to Seven" criteria were calculated both with preoperative imaging exams and histological data., Results: The study population consisted of 231 out of patients. Median waiting time on list was 62.5 days. MC included 187 patients, while TTV ≤115 cm3 included 214. Microvascular invasion (HR 2.601, 95% CI 1.529-4.426), MC (HR 1.666, 95% CI 0.990-2.804), UCSF criteria (HR 2.995, 95% CI 1.875-4.875), TTV ≤115 cm3 (HR 2.898, 95% CI 1.398-6.007), and "Up to Seven" criteria (HR 2.139, 95% CI 1.353-3.383) proved to be independent factors for prognosis for disease-free survival., Conclusions: TTV ≤115 cm3 may be a useful tool to properly identify the best HCC candidates for LT in a population with a short waiting time on list. TTV gives more patients the opportunity of undergoing LT while maintaining similar rates of tumor recurrence and patient survival., (© 2018 S. Karger AG, Basel.)

Introduction: The resting energy expenditure (REE) evolution after liver transplantation is not fully understood., Objective: To assess longitudinally the REE evolution in adults undergoing liver transplantation, in association with other nutritional measurements that characterize the metabolic profile., Methods: A single-center cohort of consecutive end-stage liver disease patients with indication for liver transplantation was recruited. REE, subjective global assessment (SGA), handgrip strength and body composition measurements were assessed before transplantation (T0) and at median nine (T1) and 36 (T2) days after transplantation. Mixed effects regression models were used for analysis., Results: Fifty-six patients with a mean age of 53.7 (8.5) years were included; 87.5% were males. In T0, 41% of patients were normometabolic, 37.5% were hypometabolic and 21.4% were hypermetabolic. After transplantation, the mean REE decreased progressively in patients initially hypermetabolic and the opposite occurred in those initially hypometabolic. The REE evolution was positively associated with body weight (β = 9.6, p < 0.001) and energy intake (β= 13.6, p = 0.005) in the whole sample; it was positively associated with body weight (β= 7.1, p = 0.018) and percentage of energy intake from lipids (β= 18.9, p = 0.003) in initially hypometabolic patients, and positively associated with body weight (β= 14.1, p < 0.001) and negatively associated with SGA-undernourishment (β = -171, p = 0.007) in initially normometabolic patients., Conclusion: Different REE evolutions after liver transplantation are associated with the preoperative metabolic status. In patients initially hypometabolic, the REE evolution is positively associated with body weight and percentage of energy intake from lipids, and in those initially normometabolic, it is positively associated with body weight and negatively associated with SGA-undernourishment.

Background: Occasionally, right hepatectomy, rather than parenchyma-preserving hepatectomy, has been performed for solitary small colorectal liver metastasis. The relative oncologic benefits of parenchyma-preserving hepatectomy and right hepatectomy are unclear. This study compared the outcomes of patients with solitary small colorectal liver metastasis in the right liver who underwent parenchyma-preserving hepatectomy and those who underwent right hepatectomy., Methods: The study population consisted of a multicentric cohort of 21,072 patients operated for colorectal liver metastasis between 2000 and 2015 whose data were collected in the LiverMetSurvey registry. Patients with a pathologically confirmed solitary tumor of less than 30 mm in size in the right liver were included. The short- and long-term outcomes of patients who underwent parenchyma-preserving hepatectomy were compared to those of patients who underwent right hepatectomy., Results: Of the 1,720 patients who were eligible for the study, 1,478 (86%) underwent parenchyma-preserving hepatectomy and 242 (14%) underwent right hepatectomy. The parenchyma-preserving hepatectomy group was associated with lower rates of major complications (3% vs 10%; P < .001) and 90-day mortality (1% vs 3%; P = .008). Liver recurrence occurred similarly in both groups (20% vs 22%; P = .39). The 5-year recurrence-free survival and overall survival rates were similar in both groups. However, in patients with liver-only recurrence, repeat hepatectomy was more frequently performed in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (67% vs 31%; P < .001), and the overall 5-year survival rate was significantly higher in the parenchyma-preserving hepatectomy group than in the right hepatectomy group (55% vs 23%; P < .001)., Conclusion: Parenchyma-preserving hepatectomy should be considered the standard procedure for solitary small colorectal liver metastasis in the right liver when technically feasible., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line., Patients and Methods: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed., Results: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2., Conclusion: CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Biliary complications occur in 10-30% of liver transplants. The aim of this study was to compare the incidence of these complications in liver transplants when the T-tube was or was not used during the biliary anastomosis., Material and Methods: Analysis of 2 groups of patients undergoing liver transplantation between 2008 and 2012. Patients were divided considering if the T-tube was used (G1) or if it was not (G2). We sought explanatory models of the occurrence of biliary complications by logistic regression, including the variables identified in the univariate analysis., Results: We reviewed 506 consecutive patients who underwent a first liver transplant (G1 = 363, G2 = 143). The overall incidence of biliary complications was 24.7% (95% CI 21.1 to 28.6): 27.0% in G1 and 18.9% in G2 (p = 0.057). The incidences of stenosis and biliary fistula tended to be higher in G1: 19.6% (95% CI 15.7 to 23.8) vs 15.4% (95% CI 10.1 to 22.0) (p = 0.275) and 6.6% (95% CI 4.4 to 9.5) vs 2.8% (95% CI 0.9 to 6.6) (p = 0.091). We did not find statistically significant differences in the rates of endoscopic retrograde cholangiopancreatography, reoperation and retransplantation. There were two deaths in G1. There was no association between the occurrence of biliary complications and the diameters of the biliary tract nor the time of cold ischemia. The explanatory model, adjusted to the recipient and the donor age's and to the initial diagnosis, identifies the use of the T-tube as increasing the possibility of the occurrence of biliary complications (AdjOR 1.71, 95% CI 1.04 to 2.80; p = 0.034)., Discussion and Conclusion: The use of the T-tube should be a decision taken on a case-based intraoperative judgment of experienced surgeons.

Background: Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM)., Methods: Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed., Results: Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS., Discussion: In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: The use of neo-adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo-adjuvant chemotherapy on outcomes following liver resection for synchronous CLM., Methods: An analysis of a multi-centric cohort from the LiverMetSurvey International Registry, who had undergone curative resections for synchronous CLM was undertaken. Patients who received neo-adjuvant chemotherapy prior to liver surgery (group NAS; n = 693) were compared with those treated by surgery alone (group SG; n = 608). Baseline clinicopathological variables were compared. Predictors of overall (OS) and disease free survival (DFS) were subsequently identified., Results: Clinicopathological comparison of the groups revealed a greater proportion of solitary metastasis in the SG compared to the NAS group (58.8% versus 38.4%; P < 0.001) therefore a separate analysis of solitary versus multi-centric analysis was performed. N-stage (> N1), number of metastasis (> 3), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer OS, while N-stage (> N1), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer DFS. Neo-adjuvant chemotherapy did not independently affect outcome., Conclusion: We present an analysis of a large multi-center series of the role of neo-adjuvant chemotherapy in resectable CLM and demonstrate no survival advantage in this setting., (© 2015 Wiley Periodicals, Inc.)

Actinomycosis is a rare disorder caused by an anaerobic gram-positive bacillus ( Actinomyces ), predominantly by the Actinomyces israelii species. Only 20% of cases show an abdominal manifestation, the appendix and ileocecal valve being the most frequent locations. Definitive diagnosis is based on microbiological cultures, microscopy or macroscopy examination. Nevertheless, histological examination of the percutaneous biopsy and blood microbiological cultures are rarely positives. Preoperative diagnosis is hampered by the lack of specific clinical and imaging manifestations, which often mimic malignancy. The rate of preoperative diagnosis is less than 10%, however, the outcome is excellent, with a low mortality rate. The authors describe the case of a patient who was diagnosed with primary hepatic actinomycosis only by a histological examination of the surgical specimen of left hepatectomy extended to segments V and VIII, for suspected malignant lesion. This case demonstrates the difficulties in diagnosing hepatic actinomycosis.

Importance: Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined., Objective: To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram., Design, Setting, and Participants: We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots., Interventions: Surgical resection of ICC at a participating hospital., Main Outcomes and Measures: Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram., Results: Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients (74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (<3 segments) (132 [25.7%]). Most patients underwent R0 resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31; P < .001), tumor size (HR, 1.50; P < .001), multiple tumors (HR, 1.58; P < .001), cirrhosis (HR, 1.51; P = .08), lymph node metastasis (HR, 1.78; P = .01), and macrovascular invasion (HR, 2.10; P < .001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692)., Conclusions and Relevance: On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve individualized predictions of survival for patients undergoing resection of ICC.

Purpose: The aims of this study were to assess the risk of early recurrence after liver resection for colorectal metastases (CRLM) and its prognostic value; identify early recurrence predictive factors; clarify the effect of perioperative chemotherapy on its occurrence; and elucidate the best early recurrence management., Methods: Patients of the LiverMetSurvey registry who underwent complete liver resection (R0/R1) between 1998 and 2009 were reviewed. Early recurrence was defined as any recurrence that occurred within 6 months after resection., Results: A total of 6,025 patients were included; 2,734 (45.4 %) had recurrence, including 639 (10.6 %) early recurrences. Early recurrence was mainly hepatic (59.5 vs. 54.4 % for late recurrences; p = 0.023). Independent risk factors of early recurrence were: T3-4 primary tumor (p = 0.0002); synchronous CRLM (p = 0.0001); >3 CRLM (p < 0.0001); 0-mm margin liver resection (p = 0.003); and associated intraoperative radiofrequency ablation (p = 0.0005). Response to preoperative chemotherapy (complete/partial) and administration of adjuvant chemotherapy reduced early recurrence risk (p = 0.003 and p < 0.0001, respectively). Intraoperative ultrasonography reduced hepatic early recurrence rate (p = 0.025). Early recurrence negatively affected prognosis: 5-year survival 26.9 versus 49.4 % for the late recurrence group (p < 0.0001, median follow-up 34.4 months). Overall, 234 (36.6 %) patients with early recurrence underwent re-resection. These patients had survival rates higher than non-re-resected patients (5-year survival 47.2 vs. 8.9 %; p < 0.0001) and similar to re-resected patients for late recurrence (48.7 %). Chemotherapy before early recurrence resection improved later survival (5-year survival 61.5 vs. 43.7 %; p = 0.028)., Conclusions: Early recurrence risk is enhanced for extensive disease after poor preoperative disease control and inadequate surgical treatment, but is reduced after adjuvant chemotherapy. Although early recurrence negatively affects prognosis, re-resection may restore better survival. Chemotherapy before early recurrence resection is advocated.

Introduction: Several skin disorders, immunosuppression-induced, have been described in transplant recipients. The aim of our study is to characterize the clinical spectrum of skin disorders and to compare the findings in liver and kidney transplant recipients., Material and Methods: A retrospective descriptive study was conducted. Data were collected from the medical records of all liver and kidney transplant recipients from 2000 - 2010 who had been referred to our Dermato-Venereology Department., Results: Three hundred nineteen transplant recipients (23.5%) have been seen, resulting in 410 diagnoses (230 in the subpopulation of liver transplant recipients and 180 in the subpopulation of kidney transplant recipients) grouped into 4 categories: 1) cutaneous infections; 2) skin cancer or premalignant skin lesions; 3) cutaneous side-effects; 4) non-iatrogenic skin disorders. Cutaneous infections were the most common presentations (42.2%), on average 32.7 months after transplantation. The latter group included 20.5% of fungal, 12.7% viral and 8.5% bacterial infections. Skin cancer and premalignant skin lesions made up 11.7% of all diagnoses, over a mean of 44.8 months post transplant and occurring primarily in kidney transplant recipients (20.6% vs 4.8% in liver transplantation patients; P < 0.001). The kidney transplant population had a squamous cell carcinoma (SCC) to basal cell carcinoma (BCC) ratio of 1.3:1 with SCC predominance, and the liver transplant population had a BCC:SCC ratio of 3.5:1. We also identified 10.5% of cutaneous side-effects and 35.6% of non-iatrogenic skin disorders., Discussion: Although neoplastic pathology is more frequently mentioned in the literature, cutaneous infections were the most common diagnoses in our study. The significant differences between the two subpopulations studied may be related to higher immunosuppression after kidney transplantation., Conclusion: The high number of skin disorders reported in these patients makes it essential for Dermato-Venereology to be included within the multidisciplinary post-transplant care provided.

Introduction: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC., Methods: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed., Results: During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥ 5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively., Conclusion: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Purpose: Tumor progression while receiving neoadjuvant chemotherapy (PD) has been associated with poor outcome and is commonly considered a contraindication to liver resection (LR). This study aims to clarify in a large multicenter setting whether PD is always a contraindication to LR., Methods: Data from the LiverMetSurvey international registry were analyzed. Patients undergoing LR for colorectal metastases without extrahepatic disease after neoadjuvant chemotherapy between 1990 and 2009 were reviewed., Results: Among 2143 patients, PD occurred in 176 (8.2 %). Risk of progression was increased after 5-FU or irinotecan (22.7 % vs. 6.8 % after other regimens, p < 0.0001; 14.9 % vs. 7.2 %, p < 0.0001), while it was reduced after oxaliplatin (5.6 % vs. 12.0 %, p < 0.0001) and still diminished among patients receiving targeted therapies (2.6 %). PD was an independent prognostic factor of survival at multivariate analysis (35 % vs. 49 %, p = 0.0006). In the PD group, 3 independent prognostic factors were identified: carcinoembryonic antigen (CEA) ≥ 200 ng/mL (p = 0.003), >3 metastases (p = 0.028), and tumor diameter ≥ 5 0 mm (p = 0.002). A survival predictive model showed that patients without any risk factors had 5-year survival rates of 53.3 %; good survival results were still observed if metastases were >3 or ≥ 50 mm (29.9 and 19.1 %, respectively). On the contrary, survival was less than 10 % at 3 years in the presence of >1 prognostic factor or CEA of ≥ 200 ng/mL., Conclusions: PD is a negative prognostic factor, but it is not an absolute contraindication to LR. Patients with PD could be scheduled for LR except for those with >3 metastases and ≥ 50 mm, or CEA ≥ 200 ng/mL in whom further chemotherapy is recommended.

This study sought to evaluate the potential impact of domino liver transplantation (DLT) on initial graft function and early postoperative outcome in patients with cirrhosis in a Portuguese liver transplantation center. A retrospective comparative analysis was performed between 77 domino recipients (from familial amyloidotic polyneuropathy donors) and 91 deceased donor recipients, all submitted to primary elective whole liver transplantation, using the piggyback technique, in a 42-month period. Outcome parameters included graft dysfunction (defined as either primary nonfunction or initial poor function, according to the Ploeg-Maring criteria) and Clavien II-IV complications in the first postoperative week. Domino and deceased donor recipients had similar preoperative severity indices (Child-Pugh classification and Model for End-Stage Liver Disease score) and immediate postoperative severity scores (APACHE II [Acute Physiology and Chronic Health Evaluation II] and SAPS II [Simplified Acute Physiology Score II]). In DLT, donors were younger, cold ischemia time was shorter, and intraoperative transfusion requirements of packed red blood cells and fresh-frozen plasma were significantly lower. Graft dysfunction incidence was 3.4-fold lower in DLT: 5.2% (only 4 cases of initial poor function) versus 18.0% (1 primary nonfunction and 15 cases of initial poor function), P = 0.010. Postoperative bleeding was the most frequent early Clavien II-IV complication (n = 29, 17.3%), with an incidence 2.2-fold lower in domino recipients. A statistically significant difference was not found in the other analyzed Clavien II-IV complications, intensive care unit stay, mechanical ventilation time, intensive care unit mortality, and 1-year survival rate. In conclusion, in this study the younger donors and shorter ischemic time associated with DLT may provide a protective role in regards to graft dysfunction and perioperative bleeding, which are 2 important determinants of early morbidity after liver transplantation., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Introduction: Familial amiloidotic polyneuropathy (FAP) is an autossomical and dominant neurodegenerative disease related with systemic deposition of amyloid fibre mainly on peripheral nervous system. Clinically, is translated by an autonomous sensitive-motor polyneuropathy with beginning nearly always in foot, involving subsequently the hands. Until now, the unique available treatment for FAP disease is liver transplantation requiring medication that negatively affect muscle metabolism and force production mechanism. To our knowledge there are no quantitative characterizations of peak force in FAP patients or any comparison with healthy people. This knowledge will be extremely important to verify clinical and functional evolution of this disease and eventually prescribe an effective rehabilitation program., Purpose: The purpose of this study was to analyse and compare levels of hand grip strength (peak force and endurance) in FAP patients with (FAPTx) or without (FAPNTx) a liver transplant with a group of healthy people (GC)., Material and Methods: The total sample of individuals where two hundred and six, assigned in 3 groups: 59 patients PAFNTx (23 males, 36 female; age 35 ± 8 years); 90 patients PAFTx (53 males, 37 females; age 34 ± 8 years) e 62 healthy persons (GC) (30 males, 32 females; age 33 ± 9 years). Grip strength was assessed by a portable grip dynamometer E-link (Biometrics Ltd, UK). All measurements were taken on standardized positions with standardized orders. The value noted to peak force was classified according to American College of Sports Medicine norms for grip strength., Results: The 3 groups are differents (p < 0,05) for weigth, body mass index (BMI) and grip strength in both hands and endurance for left hand. Negative correlations between age and grip strength were found for PAFNTx and PAFTx but not for GC., Conclusions: According to our results FAP patients have lower values for grip strength in both hands than healthy subjects and consequently a worse classification in ACSM norms. Most patients present grip strength values lower than medium values or even precarious. These results could present predictable negative functional implications, showing also the necessity of a rehabilitation program with specificity at hand motor level.

Purpose: To identify, characterize and perform a relative quantification of human transthyretin (TTR) variants in human saliva., Experimental Design: Serum and saliva samples were collected from healthy and familial amyloidotic polyneuropathy (FAP) patients, proteins separated by SDS-PAGE, TTR bands excised, in-gel digested and analyzed by MALDI-FTICR., Results: We identified and performed a relative quantification of mutated and native TTR forms in human saliva, based on FTICR-MS. The results are quantitatively identical to the ones obtained with human serum. In FAP patients subjected to cadaveric liver transplant, the TTR mutant form is no longer detected in saliva, while in patients receiving a domino liver from a FAP donor the mutant form of TTR becomes detectable in saliva, thus demonstrating the serum origin of TTR in saliva., Conclusions and Clinical Relevance: Saliva TTR originates in serum and the ratio of mutant to native TTR is preserved. The method provides a non-invasive detection of mutated TTR and a relative quantification of TTR forms. Diagnostic and disease prognosis of FAP is crucial at early stages of the disease and after liver transplantation, the only curative therapy. A suitable non-invasive method was developed for monitoring the most important FAP biomarker in human saliva.

Background: Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases. The present study assesses the feasibility and outcome of two-stage hepatectomy for the treatment of colorectal liver metastases., Methods: From January 1994 to December 2008, 720 patients underwent liver resections at two institutions for colorectal liver metastases. The feasibility and outcomes of two-staged hepatectomies were evaluated., Results: Forty-five patients were eligible for the two-stage approach and both stages were completed in 35 patients (78%). Reasons for failure included disease progression (n= 7), poor performance status (n= 1) and death after the first stage (n= 2). Patients who completed both stages had significantly fewer lesions than patients who failed to complete the second stage (5 vs. 8; P= 0.02). No differences between the two groups were observed with regard to lesion size, receipt of radiofrequency ablation (RFA) or presence of extrahepatic disease. Post-operative morbidity (24% vs. 26%; P= 0.9) and mortality (4% vs. 5%; P= 0.8) was similar between the first and second stages. Median overall survival was 16 months. Three-year survival was significantly worse for patients failing to complete both stages (18%) compared with patients completing both stages (58%) (P < 0.001). Similar survival rates were observed between patients who completed two-stage vs. patients treated with a planned single-stage hepatectomy (58% vs. 53%; P= 0.34)., Conclusion: The two-stage strategy for colorectal liver metastases can be performed with acceptable morbidity and mortality. The second stage will not be feasible in 20-25% of patients. Patients who are able to complete the two-stage approach, however, may have long-term survival comparable to patients treated with a planned single-stage hepatectomy.

Hepatocellular carcinoma (HCC) usually affects patients with chronic liver disease. While resection is the primary treatment of HCC in patients without cirrhosis, in the setting of moderate to severe cirrhosis, liver transplantation is the preferred therapy, as it simultaneously treats the tumor and the underlying liver condition. The optimal management of patients with HCC and early cirrhosis remains controversial. Although liver transplantation for HCC within the Milan criteria has been shown to have excellent long-term survival rates and low recurrence rates, its application is limited by organ availability. Due to the shortage of donors, a portion of patients drop out from the waiting list due to tumor progression. One alternative to transplantation is hepatic resection. In addition to the reported 50% 5-year survival rates, resection allows a better understanding of tumor biology through pathologic examination of the specimen, which may guide decision-making regarding salvage liver transplantation. Other nonsurgical locoregional therapies, such as transarterial chemoembolization and radiofrequency ablation, also serve as primary therapies and as a bridge to transplantation. The management of patients with early HCC is complex and multidimensional. The care of these patients is best served by a multidisciplinary approach, with consideration of the feasibility of transplantation weighed against the aggressiveness of the tumor biology and underlying hepatic dysfunction. All modalities of therapy should be viewed as complementary, not exclusive, therapeutic strategies.

The theoretical model of coping mechanisms (CM), is based on a discussion between it's main determinant factors: individual and situational (related to the 2 approaches of coping: dispositional and constitutional). Actually the most used classification of CM is based on the division of CM in two main dimensions: coping focused on emotions and coping focused on problem resolution. It is essential that classification methods of CM have in consideration the coexistence of stable dispositional elements with a situational variability. Some instruments to evaluate CM are introduced, based on different theories. Coping can influence health threw different mechanisms (neuroendocrine system, health threatening behaviours and adherence) and is included in two of the more important theoretical models applied to health (Moos & Schafer's and Leventhal's). Based on a systematic literature review we concluded that the most prevalent CM in pre transplantation period are acceptance, active coping, seeking support, and the less used are self-blame and avoidance. In post transplantation period the more prevalent CM continue to be active coping and seeking support associated to confrontation, selfconfidence, religion and coping focused in the problem. Evasive, emotive and fatalistic CM are associated to less control sensed by patients. Confrontation is associated to a better quality of life and avoidance to a reduction of quality of life and higher depression levels and denial to non-adherence increase. Control sensed by patients, CM related to the expression of emotions and denial change threw clinical evolution of transplanted patients.

There is a lot evidence about the importance adherence in the transplantated patients. Many theoretical models that can me used to predict adherence, the more important are: the communication model of compliance (Ley), the health belief model (Rosenstock, Becker), and the autoregulation model (Leventhal). The authors explore these models and sugest the one wich is more useful in transplantated patients. It is not possible to classify adherence in a monodimensional way, therefore it is useful to consider several catacteristics like timing (early, late, continuous), frequency (occasional, intermittent, persistant, complete), origin (accidental, invulnerable, decisive) and diagnostic certaincy (definite, probable, possible, unlikely). There are many ways to mesure adherence. These can be classified in direct methods (assays of drug concentrations, use of markers incorporated into pills, direct observation of pill taking) and indirect methods (patient self-reports, compliance ratings by doctors). The authors describe the various methods and suggest the ones that best suite transplantated patients. The non-adherence in transplantated patients is very common, it's medium prevalence is 25,28%, and can be influenced by many factors: demographic (age, civil state, sex, race, social/economic status), psychiatric and psychologic (depression, personality disorders, mental retardation, alcoholism, health/disease beliefs, locus control), and others (medication costs, pervious transplant).

Differentiation of macrophages into foamy (lipid-laden) macrophages is a common pathological observation in tuberculous granulomas both in experimental settings as well as in clinical conditions; however, the mechanisms that regulate intracellular lipid accumulation in the course of mycobacterial infection and their significance to pathophysiology of tuberculosis are not well understood. In this study, we investigated the mechanisms of formation and function of lipid-laden macrophages in a murine model of tuberculosis. Mycobacterium bovis bacillus Calmette-Guérin (BCG), but not Mycobacterium smegmatis, induced a dose- and time-dependent increase in lipid body-inducible nonmembrane-bound cytoplasmic lipid domain size and numbers. Lipid body formation was drastically inhibited in TLR2-, but not in TLR4-deficient mice, indicating a role for TLR2 in BCG recognition and signaling to form lipid bodies. Increase in lipid bodies during infection correlated with increased generation of PGE2 and localization of cyclooxygenase-2 within lipid bodies. Moreover, we demonstrated by intracellular immunofluorescent localization of newly formed eicosanoid that lipid bodies were the predominant sites of PGE2 synthesis in activated macrophages. Our findings demonstrated that BCG-induced lipid body formation is TLR2 mediated and these structures function as signaling platforms in inflammatory mediator production, because compartmentalization of substrate and key enzymes within lipid bodies has impact on the capacity of activated leukocytes to generate increased amounts of eicosanoids during experimental infection by BCG.

There is enough evidence about the importance psychiatric disorders (in the pre or post-operative period) have on the transplanted patient's clinical evolution and quality of life. In this review we describe, the main psychiatric items involved in the selection of candidates and accompaniment of transplanted patients. We concluded that psychiatric disorders are common in candidates in the pre-operative period. In this period the prevalence of depression is 33%, anxiety 34%, alcohol dependence/abuse (in hepatic transplant candidates) 59%, delirium 24% and alexithymia 28%. Psychiatric disorders are also common in candidates in the post-operative period. In this period the prevalence of depression is 30%, anxiety 26%, delirium 30%, PTSD 6.4% and psychosis 7.5%. The alcohol relapse after liver transplant occurs in about 29% of the transplanted patients. Patients with liver disease present metabolic specificities. In this article we list the psychiatric medications that are indicated in these kind of patients. Quality of life of the transplanted patient is determined by many factors such as neuropsychiatric status, psychiatric accompaniment, social support, planification, diet and compliance. Living donors must not be accepted when factors such as coercion and financial incentives or no understanding of the risks inherent in hepatic lobectomy are present.

Mycobacterium bovis-BCG (BCG) and Mycobacterium leprae (ML) have opposite inflammatory properties. Mycobacteria-induced pleurisy in C57Bl/6 and C57Bl/10 mice was evaluated to establish if their innate responses could be comparable, verifying cellular migration and nitrite production. Kinetic responses after ML or BCG intrathoracic injection were compared in those mice, sharing the H-2(b) MHC haplotype. BCG led to acute eosinophilia and late neutrophilia in both mice. In C57Bl/6 late pleurisy, monocytes and neutrophil recruitment was dose- and iNOS-dependent, inhibited by methotrexate but not by indomethacin. Pleural macrophages released nitrites ex vivo after 7 days of BCG stimulus, without "priming" and blocked by the nitrite inhibitor L-N5-(1-iminoethyl)-ornithine (L-NIO). ML did not induce cellular migration or nitrite production, independent of the mouse strain, timing, or number of bacilli. Although these mycobacteria have high homology, there was no effect of ML on BCG-evoked secondary cellular recruitment. Both C57Black mice trigger similar onset of inflammatory responses to these mycobacteria, so far can alternatively be used in experimental studies.