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Determination of microsatellite instability (MSI) and mismatch repair deficiency (MMRD), respectively, in endometrial carcinomas (ECs) is important for diagnostic and prognostic purposes, identification of Lynch syndrome carriers, and selection of patients for immunotherapy. The Idylla™ MSI assay is fully automated, does not require non-tumoral tissue, and can be performed in about 150 min. Two hundred forty-two formalin-fixed paraffin-embedded (FFPE) EC samples from 7 international centers were tested by the Idylla™ MSI assay and compared to the Promega™ MSI Analysis System and immunohistochemistry (IHC) for MMR proteins. The cases were selected with an enrichment of MSI EC to around 40%. Concordance was 87.5% between the Idylla™ MSI assay and IHC and 88.58% between IHC and Promega™ MSI assay. Concordance between Idylla™ and Promega™ MSI assays was 89.91%. Discordant results occurred more frequently in cases with MSH6 or PMS2 deficiency. Invalid cases occurred with the three techniques (IHC, 7.00%; Promega™ MSI assay, 5.37%; and Idylla™ MSI assay, 2.47%). The concordance rate between Idylla™ MSI assay and the other 2 methods increased to 88.83% for IHC and to 91.22% for the Promega™ MSI assay when the cutoff of instability in the scoring system was moved from 0.5 to 0.3. The Idylla™ MSI assay is a rapid and highly concordant test for MSI in EC. Modification of the Idylla™ scoring system could increase the sensitivity and specificity of the MSI assay for EC analysis.

Triple-negative breast cancer (TNBC) patients have an increased risk of developing visceral metastases and other primary nonbreast cancers, particularly lung cancer. The differential diagnosis of TNBC metastases and primary cancers from other organs can be difficult due to lack of a TNBC standard immunoprofile. We analyzed the diagnostic value of estrogen receptor, progesterone receptor, human epidermal growth factor receptor, thyroid transcription factor-1 (TTF1), Napsin A, mammaglobin, gross cystic disease fluid protein 15 (GCDFP15), Sry-related HMg-Box gene 10 (SOX10), GATA-binding protein 3 (GATA3), and androgen receptor in a series of 207 TNBC and 152 primary lung adenocarcinomas (LA). All tested TNBCs were TTF1 and Napsin A-negative. When comparing TNBC and TTF1-positive or negative LA, SOX10 had the best sensitivity (62.3%) and specificity (100%) as a marker in favor of TNBC compared with LA, irrespective of TTF1 status (P

AIMS Breast hamartomas are an under-recognised lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude 'no significant lesion' or 'normal breast tissue', leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas with the aim of identifying specific signs to facilitate their diagnosis and to differentiate them from normal breast and fibroepithelial lesions. METHODS AND RESULTS Forty-seven breast hamartomas were reassessed (histological diagnosis and imaging features). An immunohistochemical study [oestrogen receptor (ER), progesterone receptor (PR), CD34, high-mobility group A2 (HMGA2)] was performed. On breast imaging, hamartomas most often presented as probably benign solid masses with circumscribed margins and variable densities. Histologically, breast hamartomas resembled normal breast, although their stromal component was predominant, separating randomly scattered epithelial elements with areas of pure collagenous stroma. Pseudoangiomatous stromal hyperplasia (PASH) was present in 93.6% of cases and CD34 antibody highlighted intralobular, perilobular and interlobular distribution of CD34-positive fibroblasts. By comparison, CD34 was mainly expressed in the intralobular normal breast tissue stroma. Hamartoma stromal cells expressed HMGA2, ER and PR in 79%, 66% and 76.3% of our cases, respectively, compared to 7.7%, 23% and 19% in normal breast tissue, respectively (P

International audience; Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n = 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient's age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n = 12/14) and soft tissue (n = 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n = 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALK fusion on break-apart FISH (n = 5) nor next-generation sequencing (n = 14). ALK upregulation was frequently associated with an internal deletion at genomic level. TFCP2 was fused in 5' either to EWSR1 (n = 6) or FUS (n = 8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n = 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2A deletions. FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.

Adult granulosa cell tumor (AGCT) is a low-grade malignant neoplasm with a significant propensity for late recurrence and metastasis. Almost all AGCTs are composed of cells with bland nuclear features and even when these tumors recur or metastasize, the nuclear features are almost always low-grade. We report 5 cases of AGCT in patients aged 37 to 88 years composed of areas of typical AGCT with low-grade morphology admixed with areas of high-grade morphology, with marked nuclear atypia, often with bizarre multinucleate cells and high mitotic activity; this is the first reported series of high-grade transformation in AGCTs. The high-grade areas often morphologically closely resembled juvenile granulosa cell tumor with abundant eosinophilic cytoplasm, significant mitotic activity, and intermediate sized follicles. Four cases were FIGO stage IA at diagnosis and 1 was stage IIIC with omental involvement. FOXL2 mutation analysis of both the morphologically low-grade and high-grade areas in 4 of 5 cases confirmed the presence of missense point mutation, c.402C>G, p.(Cys134Trp), providing conclusive evidence that the high-grade component represents transformation of typical AGCT rather than the coexistence of another sex cord-stromal tumor, such as juvenile granulosa cell tumor, which has been suggested for such neoplasms. In 3 of 4 cases where immunohistochemistry was undertaken, there was a striking difference between the p53 staining in the low-grade and high-grade components with wild-type staining in the former and diffuse mutation-type immunoreactivity in the latter, suggesting that TP53 mutation is likely to play a role in high-grade transformation. TP53 mutation analysis covering exons 4 to 10 was undertaken in 4 cases and TP53 mutations were identified in the high-grade component of 2 of the cases. In 1 case, there was diffuse block-type p16 staining in the high-grade component. Follow-up in the 4 stage IA neoplasms revealed no evidence of tumor recurrence in 3 (6 to 9 mo follow-up) while the other patient developed mediastinal, peritoneal, and pulmonary metastasis 17 months after diagnosis. High-grade transformation is uncommon in AGCTs and given that one of our cases was advanced stage at diagnosis, another exhibited widespread metastasis within a short period and there have been occasional case reports of aggressive behavior in AGCTs with high-grade transformation, this event may herald an aggressive clinical course.

Background: Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes. Patients and methods: Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis. Results: Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex ( P = .01), pre-operative platelets 0.36 ( P = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m2 ( P = .004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively). Conclusions: There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery.

The treatment of advanced colorectal liver metastases (CRLMs) follows the biphasic pattern characteristic of oncological surgery. A phase of escalation-the therapeutic aggressiveness-is followed by a phase of de-escalation aimed at decreasing the morbidity, while preserving the gains in survival. From a maximum of three lesions, the rule no longer limits the number, provided the intervention does not cause lethal liver failure. Technically feasible non-anatomical resections, two-stage hepatectomies, portal vein obliteration and so forth, have pushed the boundaries of surgery far. However, the impact and the biology of metastatic processes have been long ignored. Parenchymal sparing surgery (PSS) is a de-escalation strategy that targets only metastasis by minimising the risk of stimulating tumour growth, while enabling iterative interventions. Reducing the loss of healthy parenchyma increases the tolerance of the liver to interval chemotherapy. Technically, PSS could use any type of hepatectomy, providing it is centred on the metastatic load alongside intraoperative ablation. The PSS concept sometimes wrongly comes across as a debate between minor versus major hepatectomies. Hence, we propose a clear definition, both quantitative and qualitative, of what PSS is and what it is not. Conversely, the degree of selectivity of PSS as a percentage of the volume of resected metastases versus the volume of total liver removed has not been stopped to date and should be the subject of prospective studies. Ultimately, the treatment of advanced CRLMs, of which PSS is a part, needs to be personalised by the multidisciplinary team by adapting its response to each new recurrence.

Intraneural perineurioma is a benign tumor developed from the perineurium and responsible for localized nerve hypertrophy. This uncommon tumor is characterized by a proliferation of perineural cells with a "pseudo-onion bulb" pattern. We report a sciatic nerve intraneural perineurioma in a 39-year-old patient.

Background The definition of parenchymal sparing surgery (PSS) for colorectal liver metastases (CRLM) diverges requiring a clarification of the concept. Method A consecutive series of patients were treated by PSS for their CRLMs, either by resection or intra-operative ablation (IOA), whenever possible a one-stage surgery and minimal usage of portal vein embolization. Post-operative complications were the primary endpoint with a special focus on post-operative liver failure. Results Three hundred and eighty-seven patients underwent a PSS out of which 328 patients received a median of 9 pre-operative cycles of chemotherapy. One hundred and twenty-eight patients had a major resection, combined with IOA in 137 patients and IOA alone in 50 cases. The 5yr-overall survival was 50.3%. There was no difference in post-operative complications between minor and major resections, validating our PSS definition based on the Tumor burden/Healthy liver ratio and not just the retrieved volume. Conclusions PSS is defined as a high ratio of tumoral burden per specimen retrieved while favoring one-stage surgery approach. Our series, using combined resections and IOAs, matches this definition well. Furthermore, complications were correlated neither to chemotherapy nor to liver-induced toxicities, contrary to extended hepatectomies.

Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations.One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors. Fluorescence in situ hybridization analysis for ALK rearrangement was performed on tissue microarrays. A panel of 50 genes using next-generation sequencing and TERT promoter mutations using Sanger sequencing were also screened.Fluorescence in situ hybridization was interpretable for 90 (62.5%) cases. One (1.1%) case was positive for an ALK rearrangement with a borderline threshold (15% positive cells). Next-generation sequencing results were interpretable for 94 (65.3%) cases, and Sanger sequencing (TERT) for 98 (68.1%) cases. A total of 210 mutations (intronic and exonic) were identified. TP53 alterations were the most frequent (54.4%). Forty-three percent harbored a mutation in the (H-K-N)RAS genes, 13.8% a mutation in the BRAF gene (essentially p.V600E), 17% a PI3K-AKT pathway mutation, 6.4% both RAS and PI3K pathway mutations, and 4.3% both TP53 and PTEN mutations. Nearly 10% of the cases showed no mutations of the RAS, PI3K-AKT pathways, or TP53, with mutations of ALK, ATM, APC, CDKN2A, ERBB2, RET, or SMAD4, including mutations not yet described in thyroid tumors. Genes encoding potentially druggable targets included: mutations in the ATM gene in four (4.3%) cases, in ERBB2 in one (1.1%) case, in MET in one (1.1%) case, and in ALK in one (1.1%) case. A TERT promoter alteration was found in 53 (54.0%) cases, including 43 C228T and 10 C250T mutations. Three out of our cases did not harbor mutations in the panel of genes with therapeutic interest.This study confirms that ALK rearrangements in ATC are rare and that the mutational landscape of ATC is heterogeneous, with many genes implicated in the follicular epithelial cell dedifferentiation process. This may explain the limited effectiveness of targeted therapeutic options tested so far.

Intraneural perineurioma is a benign tumor developed from the perineurium and responsible for localized nerve hypertrophy. This uncommon tumor is characterized by a proliferation of perineural cells with a "pseudo-onion bulb" pattern. We report a sciatic nerve intraneural perineurioma in a 39-year-old patient.

Les cancers anaplasiques thyroidiens (ATC) sont des cancers rares et de pronostic effroyables [1] . Les traitements classiquement utilises (chirurgie et radio-chimiotherapie concomitante) n’ameliore que tres peu le pronostic. Ainsi, la decouverte d’alterations moleculaires pouvant etre la cible de therapie ciblee est essentielle. En ce sens, la decouverte d’une translocation du gene ALK, meme si celle-ci est rare [2] , peut radicalement changer a la fois le traitement, mais aussi le pronostic. En effet, nous avons precedemment decrit des reponses durables sous crizotinib (therapie ciblee anti-ALK) apres echappement aux therapies conventionnelles [3] . Nous decrivons ici le premier cas de reponse complete en traitement de seconde ligne par ceritinib apres echappement au crizotinib. Il s’agit d’une patiente de 75 ans, prise en charge pour un ATC avec translocation du gene ALK traite par crizotinib. Apres deux ans de traitement par crizotinib, celle-ci presente un echappement brutal sous forme d’une pleuresie. Apres recherche des differents mecanismes d’echappement, un traitement de deuxieme ligne par ceritinib est introduit. Les differents controles a trois, six et douze mois, montrent un aspect de reponse complete, associee a une tres bonne tolerance du traitement. Apres presentation du cas clinique et explication des differents mecanismes de resistance, nous discutons du principe de la prise en charge et de la conduite a tenir en cas d’echappement therapeutique.

e15013 Background: Colorectal cancer metastases (CRLM) are major public health issue. Recently, surgeons have advocated the use of parenchymal sparing surgery (PSS) however, a common definition of the concept is lacking.To clarify and try to validate the concept of PSS to treat CRLM through the available retrospectives studies, including ours. Methods: Retrospective analysis of a cohort of patients treated by combined resections and intra-operative ablation (IOA) based on PSS, prospectively recorded in a database from 2003 to 2015 in a regional referral cancer center. All the patients benefited from the same strategy, constituting a homogenous series.PSS consists of using resection or IOA in order to spare the healthy parenchyma. One-stage is favored over two-stage surgery and use of portal vein embolization was restricted to the minimum.Post-operative complications were the primary endpoint with a special focus on post-operative liver failure. Liver toxicities and overall survival were also scrutinized. Results: Three hundred and eighty-seven patients underwent a PSS out of which 348 patients received a median of 9 pre-operative cycles of oxaliplatin or irinotecan with targeted therapies for half of them. Resection was major in 128 patients, combined with IOA in 137 patients and IOA alone in 50 cases. Thirty-eight patients had a PVO by strict necessity. The 5yr-overall survival was 50.3%. Seventy-eight patients had a complication > grade 3 out of which 10 patients died. Nine patients had a liver failure (LF) grade B and C and four died. There was no difference in post-operative complications comparing minor and major resections, validating our PSS definition. Chemotherapy and liver toxicity were not related to more post-operative complications. Only one patient died from a primitive LF. Conclusions: With PSS, healthy liver is no more a target. Routine use of chemotherapy does not impair the results and severe LFs are rare. PSS is the optimal strategy to treat CRLM. Definition of PSS cannot be based just on the retrived volume but on the ratio Tumor burden/Healthy liver. A major hepatectomy can be a PSS and a minor may not be one. That is why PSS defintion must be clarify especially for further prospective validations.

Introduction Nous decrivons ici une tumeur hepatique maligne presentant une triple differenciation neuroendocrine, hepatocytaire et biliaire. L’expression conjointe de ces marqueurs au sein d’une meme tumeur est etonnante et pose des questions quant a l’origine de ce carcinome hepatique. Objectif Rapporter un cas d’hepatocholangiocarcinome a differenciation neuroendocrine, entite encore jamais decrite. Methode Etude retrospective a propos d’un cas unique et didactique. Cas clinique Une patiente de 52 ans sans antecedent presente une tumeur hepatique du segment IV, necrotique, associee a une thrombose portale. La biopsie de cette lesion retrouve au sein d’un foie non cirrhotique un carcinome peu differencie de haut grade, d’architecture massive mais ebauchant des aspects glandulaires en rosettes avec une focale mucosecretion. Les cellules tumorales expriment en immunohistochimie une triple differenciation : – hepatocellulaire avec l’expression de l’anti-hepatocyte (specificite 80–90 %) et du TTF1 (cytoplasmique granuleux) ; – biliaire avec l’expression forte de la cytokeratine 19 et celle plus focale de la cytokeratine 7 (la cytokeratine 20 etait negative) ; – neuroendocrine avec l’expression franche de la chromogranine A et celle, plus focale, de la synaptophysine. Au total, il s’agit d’une tumeur primitivement hepatique de type hepatocholangiocarcinome presentant une differenciation neuroendocrine. Discussion La presence d’une differenciation neuroendocrine au sein d’une tumeur hepatique doit faire eliminer en priorite une metastase. L’hepatocholangiocarcinome est une tumeur hepatique rare ( La presence d’une composante neuroendocrine dans ces tumeurs composites peut s’expliquer par : 1) la presence de cellules neuroendocrines tumorales au sein de la tumeur hepatocellulaire ou cholangiocarcinomateuse initiale 2) l’existence d’une transdifferenciation phenotypique des cellules tumorales initiales 3) la differenciation neuroendocrine d’une tumeur issue d’une cellule souche. Plusieurs travaux suggerent que les carcinomes hepatocellulaires peu differencies proviendraient de cellules souches ou de cellules ovales (intermediaires). Il n’existe pas de marqueurs absolument specifiques des cellules souches hepatiques. Certains auteurs rapportent que la chromogranine-A pourrait etre un marqueur de ces cellules progenitrices hepatiques. De plus, les hepatoblastes humains co-exprimeraient la cytokeratine 19 et l’anti-hepatocyte HepPar1. Ces hypotheses physiopathologiques expliqueraient la triple differenciation de notre tumeur hepatique. Le traitement de ces tumeurs n’est pas codifie compte tenu du peu de cas rapportes. Cependant, du fait de leur differenciation neuroendocrine, ces tumeurs semblent agressives et de plus mauvais pronostic. Conclusion A notre connaissance, il s’agit ici du premier cas d’hepatocholangiocarcinome a differenciation neuroendocrine rapporte, illustrant la remarquable plasticite phenotypique des cellules tumorales et corroborant l’hypothese de la possible genese de certaines tumeurs primitives hepatiques a partir de cellules souches progenitrices multipotentes.

Objectif Malgre les progres recents le cancer anaplasique thyroidien reste de pronostic sombre sans reelle possibilite therapeutique. De facon parallele, les techniques recentes de biologie moleculaire pourraient permettre une meilleure comprehension des differentes voix d’activation et ainsi deboucher sur des traitements plus adaptes au profil moleculaire de ces tumeurs. Methode Cent quarante-quatre cas ont ete collectes. Un panel de 50 genes (Ion AmpliSeq™ Cancer Hotspot Panel v2 de Life technologies) a ete sequence avec le ion PGM system™ NGS. La recherche de la translocation de ALK a ete effectuee par IHC et par FISH. Resultats On retrouve essentiellement des alterations de la voie BRAFV600E/ERK 1/2-MEK 1/2 et de la voie PI3K-AKT dans 53 % et 20 %, respectivement. Elles sont associees dans 67 % des cas (mutations non mutuellement exclusives). Les mutations de BRAF sont presentes dans 13 % des cas et dans 6 % des cas de facon isolee. 18 % des alterations de la voie PI3K-AKT sont isolees. P 53 est mute dans 56 % des cas. Les autres mutations retrouvees de facon plus marginales sont des mutations activatrices des genes ALK, ATM, RET, SMARCB1, ABL, ERRBB2, FGFR1. Une translocation de ALK a ete identifiee. Conclusion Il s’agit de la plus grosse serie publiee qui confirment les alterations predominantes des voies BRAFV600E/ERK 1/2-MEK 1/2 et de la voie PI3K-AKT. Cependant, celle-ci ne sont que tres rarement isolees, associees dans la plupart du temps a une activation de p53 ou une activation des 2 voies expliquant ainsi les tres faibles reponses therapeutiques observees.

689 Background: Neoadjuvant chemotherapy (CT) have been associated with an increased risk of surgery for colorectal liver metastases (CRLM). Irinotecan (IRI) is claimed to induce CT-associated steatohepatitis (CASH) and oxaliplatin (OX) to induce sinusoidal obstruction (SOS). Imputability is sometimes difficult to establish and the impact on postoperative complications is unclear. The objective of this study is to investigate the impact of IRI and OX on induced liver toxicity, and to study the effects of toxicity on surgical outcomes. Methods: Patients (Pts) who received only one line of CT before resection of CRLM were retrospectively included. CASH and SOS were described according to Kleiner and Rubbia-Brandt classifications respectively. Associations were sought between CASH or SOS and various patient and treatment factors, and between patient and treatment factors and the occurrence of post-operative complications grade 3 or over. Results: Among 379 pts operated on for CRLM from 2003 to 2013, 223 were eligible for inclusion; 57 were excluded as there was no healthy hepatic parenchyma to be analyzed. Median age was 64 y [34-88], BMI ≥25 kg/m² for 52%, 8% had diabetes, and 28% had a dyslipidemia. CRLM were synchronous in 76.5%. 65 (39.2%) received Folfox, 95 (57.2%) Folfiri and 6 (3.6%) Folfirinox. Bevacizumab, cetuximab and panitumumab were given in 71 (42.8%), 30 (17.5%), 4 (2.4%) respectively. Extra-hepatic resections were performed in 78 pts (47%). 90-day mortality was 1.8% and 31 pts encountered complications more severe than 3A. Histological hepatoxicity was established for 82 pts (49%) including 33 (19.9%) with grade 2 or 3 SOS and 22 (13%) with CASH. No significant associations were identified between SOS and OX, nor CASH and IRI. BMI ≥ 25 kg/m² was correlated with an increased risk of CASH. Only septic extra-hepatic surgeries were correlated with the prediction of postoperative complications. Conclusions: In this selected series, preoperative CT was not associated to liver toxicity. The presence of histological lesions did not worsen post-operative outcomes. BMI and extra-hepatic surgery were the only co-factors correlated with CASH and post-operative complications respectively.