Laparoscopic versus open resection of intrahepatic cholangiocarcinoma: nationwide analysis.

BACKGROUND: The relevance of laparoscopic resection of intrahepatic cholangiocarcinoma (ICC) remains debated. The aim of this study was to compare laparoscopic (LLR) and open (OLR) liver resection for ICC, with specific focus on textbook outcome and lymph node dissection (LND). METHODS: Patients undergoing LLR or OLR for ICC were included from two French, nationwide hepatopancreatobiliary surveys undertaken between 2000 and 2017. Patients with negative margins, and without transfusion, severe complications, prolonged hospital stay, readmission or death were considered to have a textbook outcome. Patients who achieved both a textbook outcome and LND were deemed to have an adjusted textbook outcome. OLR and LLR were compared after propensity score matching. RESULTS: In total, 548 patients with ICC (127 LLR, 421 OLR) were included. Textbook-outcome and LND completion rates were 22.1 and 48.2 per cent respectively. LLR was independently associated with a decreased rate of LND (odds ratio 0.37, 95 per cent c.i. 0.20 to 0.69). After matching, 109 patients remained in each group. LLR was associated with a decreased rate of transfusion (7.3 versus 21.1 per cent; P = 0.001) and shorter hospital stay (median 7 versus 14 days; P = 0.001), but lower rate of LND (33.9 versus 73.4 per cent; P = 0.001). Patients who underwent LLR had lower rate of adjusted TO completion than patients who had OLR (6.5 versus 17.4 per cent; P = 0.012). CONCLUSION: The laparoscopic approach did not substantially improve quality of care of patients with resectable ICC.

Relevance of liver surface nodularity for preoperative risk assessment in patients with resectable hepatocellular carcinoma.

BACKGROUND: Quantification of liver surface nodularity (LSN) on routine preoperative CT images allows detection of cirrhosis and clinically significant portal hypertension. This study aimed to assess the relevance of LSN in preoperative assessment of operative risks for patients with resectable hepatocellular carcinoma (HCC). METHODS: All patients undergoing hepatectomy for HCC between 2012 and 2017 were analysed retrospectively. LSN was assessed at the liver-fat interface on the left liver lobe on preoperative CT images. The feasibility of LSN quantification was assessed. The association between LSN and outcomes (severe complications and posthepatectomy liver failure (PHLF)) was evaluated by multivariable analysis and after propensity score matching. RESULTS: Among 210 patients, LSN measurement was successful in 187 (89·0 per cent). Among these, the median LSN score was 2·42 (i.q.r. 2·21-2·66) and 52·9 per cent had severe fibrosis, including 33·7 per cent with cirrhosis. LSN score increased with hepatic venous pressure gradient (P = 0·048), severity of steatosis (P = 0·011) and fibrosis grade (P = 0·001). LSN score was independently associated with severe complications (odds ratio (OR) 5·25; P = 0·006) and PHLF (OR 6·78; P = 0·003). After matching with respect to model for end-stage liver disease, aspartate aminotransferase-to-platelet ratio index and fibrosis-4 score, patients with a LSN score of 2·63 or higher retained an increased risk of PHLF (OR 5·81; P = 0·018). In the subgroup of patients without severe fibrosis, LSN was accurate in predicting severe complications (P = 0·005). Patients with (P = 0·039) or without (P = 0·018) severe fibrosis with increased LSN score had a higher comprehensive complication index score. Among patients with cirrhosis who had clinically significant portal hypertension, a LSN value below 2·63 ruled out the risk of PHLF. CONCLUSION: LSN measurement represents a practical tool that may allow improvement in the preoperative evaluation and management of patients with HCC.

ANTECEDENTES: La cuantificación de la nodularidad de la superficie hepática (liver surface nodularity, LSN) en las imágenes de la tomografía computarizada (TC) de rutina preoperatoria permite detectar la cirrosis y la hipertensión portal clínicamente significativa (clinically significant portal hypertension, CSPH). Este estudio tuvo como objetivo evaluar la relevancia de la LSN en la evaluación preoperatoria del riesgo quirúrgico en pacientes con carcinoma hepatocelular resecable (hepatocellular carcinoma, HCC). MÉTODOS: Todos los pacientes sometidos a hepatectomía por HCC entre 2012 y 2017 fueron analizados de forma retrospectiva. La LSN se evaluó en la interfase hígado-grasa en el lóbulo hepático izquierdo en la TC preoperatoria. Se evaluó la viabilidad de la cuantificación de la LSN. La asociación entre la LSN y los resultados (complicaciones graves e insuficiencia hepática poshepatectomía (post-hepatectomy liver failure, PHLF) se analizó en un análisis multivariable y después del método de emparejamiento por puntaje de propensión. RESULTADOS: Del total de 210 pacientes, la medición de la LSN fue exitosa en 187 (89,0%). En estos pacientes, la mediana de LSN fue de 2,42 (rango intercuartílico 2,21-2,66) y el 53,0% tenía fibrosis severa, incluyendo un 33,7% con cirrosis. La LSN aumentó con el gradiente de presión venosa hepática (P = 0,048), la gravedad de la esteatosis (P = 0,011) y el grado de fibrosis (P = 0,001). La LSN se asoció de forma independiente con complicaciones graves (razón de oportunidades, odds ratio, OR = 5,25; P = 0,006) y PHLF (OR = 6,78; P = 0,003). Después de emparejar para el modelo de enfermedad hepática terminal, el índice de relación aspartato amino transferase-plaquetas y el grado de fibrosis-4, los pacientes con LSN ≥ 2,63 mantuvieron un mayor riesgo de PHLF (OR = 5,81; P = 0,018). Dentro del subgrupo de pacientes sin fibrosis severa, la LSN fue precisa en predecir complicaciones graves (P = 0,005). Los pacientes con (P = 0,039) y sin (P = 0,018) fibrosis severa con aumento de la LSN tuvieron un índice de complicación global más alto. De los pacientes cirróticos con CSPH, un valor de LSN de 2,63 descartó el riesgo de PHLF. CONCLUSIÓN: La LSN representa una herramienta práctica, que puede permitir mejorar la evaluación preoperatoria y el manejo de pacientes con HCC.

Hepatocellular carcinoma tumour burden score to stratify prognosis after resection.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. METHODS: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. RESULTS: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). CONCLUSION: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

ANTECEDENTES: Aunque el sistema de estadificación del Barcelona Clinic Liver Cancer (BCLC) ha sido adoptado en gran medida en la práctica clínica, estudios recientes han enfatizado la necesidad de un mayor refinamiento y subclasificación del sistema BCLC. MÉTODOS: Los pacientes con carcinoma hepatocelular (hepatocellular cancer, HCC) BCLC-0, A y B que se sometieron a una hepatectomía con intención curativa entre 2000 y 2017 fueron identificados utilizando una base de datos multi-institucional. Se calculó la puntuación de carga tumoral (tumour burden score, TBS) y se examinó la supervivencia global (overall survival, OS) en relación con la TBS y los estadios BCLC. RESULTADOS: En la serie de 1.053 pacientes, 63 (6%) tenían HCC BCLC-0, 826 (78,4%) HCC BCLC-A y 164 (15,6%) HCC BCLC-B. La OS disminuyó de forma incremental en función de la mayor TBS (OS a 5 años; TBS baja: 77,9% versus TBS media: 61% versus TBS alta: 39%, P < 0,001). No se observaron diferencias en la OS entre pacientes con una puntuación TBS similar, independientemente del estadio BCLC (BCLC-A/TBS media: 61,6% versus BCLC-B/TBS media: 58,9%, P = 0,93; BCLC-A/TBS alta: 45,1% versus BCLC-B/TBS alta: 12,8%, P = 0,175). Los pacientes con BCLC-B/TBS media tuvieron una mejor OS que los pacientes con BCLC-A/TBS alta (58,9% versus 45,1%, P = 0,005). En el análisis multivariable, la TBS se mantuvo asociada a la OS en el caso de BCLC-A (TBS media: cociente de riesgos instantáneos, hazard ratio, HR = 2,07, i.c. del 95%: 1,42-3,02, P < 0,001; TBS alta: HR = 4,05, i.c. del 95%: 2,40-6,82, P < 0,001) y BCLC-B pacientes (TBS alta: HR = 3,85, i.c. del 95%: 2,03-7,30, P < 0,001). La TBS también pudo estratificar el pronóstico entre pacientes en una cohorte de validación externa (OS a 5 años; TBS baja: 78,7% versus TBS media: 51,2% versus TBS alta: 27,6%, P = 0,01). CONCLUSIÓN: El pronóstico de los pacientes con HCC varió según el estadio BCLC, pero dependió en gran medida de la TBS.

Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

Risk score to predict biliary leakage after elective liver resection.

BACKGROUND: Biliary leakage remains a major cause of morbidity after liver resection. Previous prognostic studies of posthepatectomy biliary leakage (PHBL) lacked power, population homogeneity, and model validation. The present study aimed to develop a risk score for predicting severe PHBL. METHODS: In this multicentre observational study, patients who underwent liver resection without hepaticojejunostomy in one of nine tertiary centres between 2012 and 2015 were randomly assigned to a development or validation cohort in a 2 : 1 ratio. A model predicting severe PHBL (International Study Group of Liver Surgery grade B/C) was developed and further validated. RESULTS: A total of 2218 procedures were included. PHBL of any severity and severe PHBL occurred in 141 (6·4 per cent) and 92 (4·1 per cent) patients respectively. In the development cohort (1475 patients), multivariable analysis identified blood loss of at least 500 ml, liver remnant ischaemia time 45 min or more, anatomical resection including segment VIII, transection along the right aspect of the left intersectional plane, and associating liver partition and portal vein ligation for staged hepatectomy as predictors of severe PHBL. A risk score (ranging from 0 to 5) was built using the development cohort (area under the receiver operating characteristic curve (AUROC) 0·79, 95 per cent c.i. 0·74 to 0·85) and tested successfully in the validation cohort (AUROC 0·70, 0·60 to 0·80). A score of at least 3 predicted an increase in severe PHBL (19·4 versus 2·6 per cent in the development cohort, P < 0·001; 15 versus 3·1 per cent in the validation cohort, P < 0·001). CONCLUSION: The present risk score reliably predicts severe PHBL. It represents a multi-institutionally validated prognostic tool that can be used to identify a subset of patients at high risk of severe PHBL after elective hepatectomy.

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent.

BACKGROUND: The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. METHODS: Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. RESULTS: A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). CONCLUSION: Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma.

BACKGROUND: The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC. METHODS: Patients undergoing curative intent resection for ICC in 2000-2015 were identified from an international multi-institutional database. Use of lymphadenectomy was evaluated over time and by geographical region (West versus East); LND use and final nodal status were analysed relative to AJCC T categories. RESULTS: Among the 1084 patients identified, half (535, 49·4 per cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the proportion of patients undergoing LND for ICC nearly doubled: 44·4 per cent in 2000 versus 81·5 per cent in 2015 (P < 0·001). Use of LND increased over time among both Eastern and Western centres. The odds of LND was associated with the time period of surgery and the extent of the tumour/T status (referent T1a: OR 2·43 for T2, P = 0·001; OR 2·13 for T3, P = 0·016). Among the 535 patients who had LND, lymph node metastasis (LNM) was noted in 209 (39·1 per cent). Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in T1b, 42·9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P < 0·001). AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of satellite lesions were independently associated with LNM. CONCLUSION: The rate of LNM was high across all T categories, with one in five patients with T1 disease having nodal metastasis. The trend in increased use of LND suggests a growing adoption of AJCC recommendations in the treatment of ICC.

Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases.

BACKGROUND: The impact of chemotherapy-associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres. METHODS: PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords 'chemotherapy', 'liver resection', 'outcome' and 'colorectal metastases' to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo-Clavien grade III-V; OR 1·73, 95 per cent c.i. 1·02 to 2·95; P = 0·043). Severe steatosis was associated with decreased liver surgery-specific complications (OR 0·52, 95 per cent c.i. 0·27 to 1·00; P = 0·049), whereas steatohepatitis was linked to an increase in these complications (OR 2·08, 1·18 to 3·66; P = 0·012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2·22, 1·48 to 3·34; P = 0·001) and liver surgery-specific complications (OR 3·35, 2·11 to 5·32; P < 0·001). Finally, oxaliplatin treatment was linked to severe SD (OR 2·74, 1·67 to 4·49; P < 0·001). CONCLUSION: An increase in postoperative major morbidity and liver surgery-specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD.

Should ALPPS be Used for Liver Resection in Intermediate-Stage HCC?

BACKGROUND: Extended liver resections in patients with hepatocellular carcinoma (HCC) are problematic due to hepatitis, fibrosis, and cirrhosis. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has been promoted as a novel method to induce hypertrophy for patients with extensive colorectal liver metastases, but outcomes in HCC have not been well investigated. METHODS: All patients registered in the international ALPPS Registry ( www.alpps.org ) from 2010 to 2015 were studied. Hypertrophy of the future liver remnant, perioperative morbidity and mortality, age, overall survival, and other parameters were compared between patients with HCC and patients with colorectal liver metastases (CRLM). RESULTS: The study compared 35 patients with HCC and 225 patients with CRLM. The majority of patients undergoing ALPPS for HCC fall into the intermediate-stage category of the Barcelona clinic algorithm. In this study, hypertrophy was rapid and extensive for the HCC patients, albeit lower than for the CRLM patients (47 vs. 76 %; p < 0.002). Hypertrophy showed a linear negative correlation with the degrees of fibrosis. The 90-day mortality for ALPPS used to treat HCC was almost fivefold higher than for CRLM (31 vs. 7 %; p < 0.001). Multivariate analysis showed that patients older than 61 years had a significantly reduced overall survival (p < 0.004). CONCLUSION: The ALPPS approach induces a considerable hypertrophic response in HCC patients and allows resection of intermediate-stage HCC, albeit at the cost of a 31 % perioperative mortality rate. The use of ALPPS for HCC remains prohibitive for most patients and should be performed only for a highly selected patient population younger than 60 years with low-grade fibrosis.

Risk factors and consequences of conversion in laparoscopic major liver resection.

BACKGROUND: Although recent reports have suggested potential benefits of the laparoscopic approach in patients requiring major hepatectomy, it remains unclear whether conversion to open surgery could offset these advantages. This study aimed to determine the risk factors for and postoperative consequences of conversion in patients undergoing laparoscopic major hepatectomy (LMH). METHODS: Data for all patients undergoing LMH between 2000 and 2013 at two tertiary referral centres were reviewed retrospectively. Risk factors for conversion were determined using multivariable analysis. After propensity score matching, the outcomes of patients who underwent conversion were compared with those of matched patients undergoing laparoscopic hepatectomy who did not have conversion, operated on at the same centres, and also with matched patients operated on at another tertiary centre during the same period by an open laparotomy approach. RESULTS: Conversion was needed in 30 (13·5 per cent) of the 223 patients undergoing LMH. The most frequent reasons for conversion were bleeding and failure to progress, in 14 (47 per cent) and nine (30 per cent) patients respectively. On multivariable analysis, risk factors for conversion were patient age above 75 years (hazard ratio (HR) 7·72, 95 per cent c.i. 1·67 to 35·70; P = 0·009), diabetes (HR 4·51, 1·16 to 17·57; P = 0·030), body mass index (BMI) above 28 kg/m(2) (HR 6·41, 1·56 to 26·37; P = 0·010), tumour diameter greater than 10 cm (HR 8·91, 1·57 to 50·79; P = 0·014) and biliary reconstruction (HR 13·99, 1·82 to 238·13; P = 0·048). After propensity score matching, the complication rate in patients who had conversion was higher than in patients who did not (75 versus 47·3 per cent respectively; P = 0·038), but was not significantly different from the rate in patients treated by planned laparotomy (79 versus 67·9 per cent respectively; P = 0·438). CONCLUSION: Conversion during LMH should be anticipated in patients with raised BMI, large lesions and biliary reconstruction. Conversion does not lead to increased morbidity compared with planned laparotomy.

Pure laparoscopic right hepatectomy in a living donor.

After reporting the first laparoscopic hepatectomy in a living donor for pediatric liver transplantation, we now report a case of pure laparoscopic right hepatectomy for adult transplantation. A 50-year-old female volunteered for living donation to her sister who suffered from primary biliary cirrhosis. The volume of the planned hepatic graft (segments 5-8) was 620 cm(3) , representing 56% of her entire liver. Five ports were used in the donor to perform the operative procedure. The right hepatic artery and portal vein were isolated. Parenchymal division was performed using an ultrasonic dissector, bipolar coagulation and clips for hemostasis. Cholangiography was performed and the right bile duct was cut at the level of a marker thread. The right liver graft was placed in a bag and removed through a 10-cm suprapubic incision. The veins of segments 5 and 8 were recanalized and the graft was transplanted in the recipient. The postoperative course was uneventful for both the donor and recipient. This case offers evidence that the right liver can be procured via a total laparoscopic approach. This technique may allow for an early rehabilitation for the living donor.

Randomized clinical trial of ischaemic preconditioning in major liver resection with intermittent Pringle manoeuvre.

BACKGROUND: Vascular inflow occlusion is effective in avoiding excessive blood loss during hepatic parenchymal transection but may cause ischaemic damage to the remnant liver. Intermittent portal triad clamping (IPTC) is superior to continuous hepatic pedicle clamping as it avoids severe ischaemia-reperfusion (IR) injury in the liver remnant. Ischaemic preconditioning (IPC) before continuous Pringle manoeuvre may protect against IR during major liver resection. METHODS: This RCT assessed the impact of IPC in major liver resection with intermittent vascular inflow occlusion. Patients undergoing major liver resection with intermittent vascular inflow occlusion were randomized, during surgery, to receive IPC (10 min inflow occlusion followed by 10 min reperfusion) or no IPC (control group). Data analysis was on an intention-to-treat basis. The primary endpoint was serum alanine aminotransferase (ALT) level on the day after surgery. RESULTS: Eighty four patients were enrolled and randomized to IPC (n = 41) and no IPC (n = 43). The groups were comparable in terms of demographic data, preoperative American Society of Anesthesiologists grade and extent of liver resection. Intraoperative morbidity and postoperative outcomes were also similar. ALT levels on the day after operation were not decreased by IPC (mean(s.d.) 537·6(358·5) versus 525·0(400·6) units/ml in IPC and control group respectively; P = 0·881). Liver biochemistry tests in the week after operation showed the same pattern in both groups. CONCLUSION: IPC did not reduce liver damage in patients undergoing major liver resection with IPTC. REGISTRATION NUMBER: NCT00908245 (http://www.clinicaltrials.gov).

Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes.

Hepatocyte transplantation might represent a potential therapeutic alternative to liver transplantation in the future; however, transplanted cells have a limited capacity to repopulate the liver, as they do not proliferate under normal conditions. Recently, studies in urokinase (uPA) transgenic mice and in fumarylacetoacetate hydrolase (FAH)-deficient mice have shown that the liver can be repopulated by genetically engineered hepatocytes harboring a selective advantage over resident hepatocytes. We have reported that transgenic mice expressing human Bcl-2 in their hepatocytes are protected from Fas/CD95-mediated liver apoptosis. We now show that Bcl-2 transplanted hepatocytes selectively repopulate the liver of mice treated with nonlethal doses of the anti-Fas antibody Jo2. FK 506 immunosuppressed mice were transplanted by splenic injection with Bcl-2 hepatocytes. The livers of female recipients were repopulated by male Bcl-2 transgenic hepatocytes, as much as 16%, after 8 to 12 administrations of Jo2. This only occurred after anti-Fas treatment, confirming that resistance to Fas-induced apoptosis constituted the selective advantage of these transplanted hepatocytes. Thus, we have demonstrated a method for increasing genetic reconstitution of the liver through selective repopulation with modified transgenic hepatocytes, which will allow optimization of cell and gene therapy in the liver.

History of first transplantations: Nothing is ever written. Part II.

The history of the first transplants is an ideal model for analyzing the different stages of disruptive innovation in surgery. Pioneers have often taken paths that were strewn with pitfalls, mistakes or failures. Sometimes victory, brilliant or more modest, lies at the end of this path. We propose to re-explore the extraordinary pathways that led to the first transplantations of the kidney, liver, lung and heart. That these first transplants should one day become possible required the concurrence of several factors: basic research, laboratory work to perfect the surgical techniques, a favorable legislative and societal context, and, above all, pioneering surgeons who would dare to apply their expertise to human subjects. Initial failures were not technical but immunological. Not everything would be perfect, especially ethical questions in some cases. Furthermore, initial results often humbled the greatest surgeons. Even though the historical and legislative contexts have evolved considerably as have science, society and the organization of the health system, this analysis of the past is rich in lessons for the modern surgeon who wishes to embark today along innovative pathways in the face of a still unresolved problem. Because nothing is ever carved in stone.

History of transplantation: Nothing is ever written. Part I.

The history of the first transplants is an ideal model for analyzing the different stages of disruptive innovation in surgery. Pioneers have often taken paths that were strewn with pitfalls, mistakes or failures. Sometimes victory, brilliant or more modest, lies at the end of this path. We propose to re-explore the extraordinary pathways that led to the first transplantations of the kidney, liver, lung and heart. That these first transplants should one day become possible required the concurrence of several factors: basic research, laboratory work to perfect the surgical techniques, a favorable legislative and societal context, and, above all, pioneering surgeons who would dare to apply their expertise to human subjects. Initial failures were not technical but immunological. Not everything would be perfect, especially ethical questions in some cases. Furthermore, initial results often humbled the greatest surgeons. Even though the historical and legislative contexts have evolved considerably as have science, society and the organization of the health system, this analysis of the past is rich in lessons for the modern surgeon who wishes to embark today along innovative pathways in the face of a still unresolved problem. Because nothing is ever carved in stone.

Practical model to identify liver transplant recipients at low risk of postoperative haemorrhage, bile leakage and ascites.

BACKGROUND: This study aimed to identify a subgroup of recipients at low risk of haemorrhage, bile leakage and ascites following liver transplantation (LT). METHODS: Factors associated with significant postoperative ascites (more than 10 ml/kg on postoperative day 5), bile leakage and haemorrhage after LT were identified using three separate multivariable analyses in patients who had LT in 2010-2019. A model predicting the absence of all three outcomes was created and validated internally using bootstrap procedure. RESULTS: Overall, 944 recipients underwent LT. Rates of ascites, bile leakage and haemorrhage were 34.9, 7.7 and 6.0 per cent respectively. The 90-day mortality rate was 7.0 per cent. Partial liver graft (relative risk (RR) 1.31; P = 0.021), intraoperative ascites (more than 10 ml/kg suctioned after laparotomy) (RR 2.05; P = 0.001), malnutrition (RR 1.27; P = 0.006), portal vein thrombosis (RR 1.56; P = 0.024) and intraoperative blood loss greater than 1000 ml (RR 1.39; P = 0.003) were independently associated with postoperative ascites and/or bile leak and/or haemorrhage, and were introduced in the model. The model was well calibrated and predicted the absence of all three outcomes with an area under the curve of 0.76 (P = 0.001). Of the 944 patients, 218 (23.1 per cent) fulfilled the five criteria of the model, and 9.6 per cent experienced postoperative ascites (RR 0.22; P = 0.001), 1.8 per cent haemorrhage (RR 0.21; P = 0.033), 4.1 per cent bile leak (RR 0.54; P = 0.048), 40.4 per cent severe complications (RR 0.70; P = 0.001) and 1.4 per cent 90-day mortality (RR 0.13; P = 0.004). CONCLUSION: A practical model has been provided to identify patients at low risk of ascites, bile leakage and haemorrhage after LT; these patients could potentially qualify for inclusion in non-abdominal drainage protocols.

Case series of extended liver resection associated with inferior vena cava reconstruction using peritoneal patch.

INTRODUCTION: Among various reported techniques for inferior vena cava (IVC) reconstruction, the superiority of one technique over another has not been clearly established. This study aimed at reporting the technical aspects of caval reconstruction using peritoneal patch during extended liver resections. METHODS: All consecutive patients who underwent extended liver resection associated with anterolateral caval reconstruction using a peritoneal patch from 2016 to 2019 were included in this study. Technical insights, intra-operative details, short and long-term results were reported. RESULTS: Overall six patients underwent caval reconstruction using peritoneal patch under total vascular exclusion. Half of them required veno-venous bypass. Caval involvement ranged from 30 to 50% of the circumference and from 5 to 7 cm of the length of the IVC. Caval reconstructions was performed using a peritoneal patch harvested from the falciform ligament in four cases and from the right pre-renal peritoneum and right part of the diaphragm in one Case each. Three cases underwent associated reimplantation the remnant hepatic vein. Median intra-operative blood loss and TVE duration were 500 ml and 41 min, respectively. One case experienced a severe complication (liver failure leading to death). R0 resection was achieved in all patients. All patients had patent IVC and remnant hepatic vein at last follow-up and none was on long-term therapeutic anticoagulation. CONCLUSION: Caval reconstruction using a peritoneal patch in patients undergoing extended liver resection is feasible and cost-effective and associated with excellent long-term results.

Metabolic syndrome and hepatic surgery.

In Europe, the prevalence of metabolic syndrome (MS) has reached the endemic rate of 25%. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of MS. Its definition is histological, bringing together the different lesions associated with hepatic steatosis (fat deposits on more than 5% of hepatocytes) without alcohol consumption and following exclusion of other causes. MS and NAFLD are implicated in the carcinogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). At present, HCC and ICC involving MS represent 15-20% and 20-30% respectively of indications for hepatic resection in HCC and ICC. Moreover, in the industrialized nations NAFLD is tending to become the most frequent indication for liver transplantation. MS patients combine the operative risk associated with their general condition and comorbidities and the risk associated with the presence and/or severity of NAFLD. Following hepatic resection in cases of HCC and ICC complicating MS, the morbidity rate ranges from 20 to 30%, and due to cardiovascular and infectious complications, post-transplantation mortality is heightened. The operative risk incurred by MS patients necessitates appropriate management including: (i) precise characterization of the subjacent liver; (ii) an accurately targeted approach privileging detection and optimization of treatment taking into account the relevant cardiovascular risk factors; (iii) a surgical strategy adapted to the histology of the underlying liver, with optimization of the volume of the remaining (postoperative) liver.

Significance of serum tumor markers carcinoembryonic antigen, CA 19-9, CA 125, and CA 15-3 in pre-orthotopic liver transplantation evaluation.

Tumor markers are elevated in a variety of nonneoplastic clinical situations, including liver diseases. Their sensitivity and specificity are lower for tumor screening in these cases. In this study, we investigated the frequency and significance of elevated tumor markers in the pre-orthotopic liver transplantation (OLT) evaluation among patients with end-stage liver disease who did not develop tumors after a long follow-up post-OLT. We performed a retrospective analysis of clinical and biological parameters of 100 OLT candidates comparing data for CA 125, CA 19-9, CA 15-3, and carcinoembryonic antigen (CEA) levels. CA 125, CA 19-9, CA 15-3, and CEA levels were elevated in 59%, 53%, 29%, and 28% of cases, respectively. CA 125, CA 15-3, and CEA were associated with disease severity (Child-Pugh classification). CA 125 was also elevated among patients with ascites, esophageal varices, or alcohol-related cirrhosis. Elevated CA 19-9 levels were associated with increased CA 15-3 and CEA levels. CA 15-3 levels were also increased among patients with elevated alkaline phosphatase, while elevated CEA was related to ascites, bilirubin, and prothrombin time (PT) levels, as well as alcohol-related cirrhosis. There was no association between hepatocellular carcinoma and tumor markers. In conclusion, CA 125, CA 19-9, CA 15-3, and CEA were frequently elevated among end-stage liver disease patients. These elevations were not associated with tumor diseases in this population.