The trajectory of anti-recEm18 antibody levels determines follow-up after curative resection of hepatic alveolar echinococcosis.

INTRODUCTION: Recurrence after curative resection of hepatic alveolar echinococcosis remains a clinical challenge. The current study tested if assessment of anti-recEm18 allows for postsurgical patient surveillance. METHODS: A retrospective study with patients undergoing liver resection for alveolar echinococcosis (n = 88) at the University Hospital Bern from 2002 to 2020 and at the University Hospital and Medical Center Ulm from 2011 to 2017 was performed. Analysis was directed to determine a potential association of pre- and postoperative values of anti-recEm18 with clinical outcomes. RESULTS: Anti-recEm18 had a linear correlation to the maximum lesion diameter (R2 = 0.558). Three trajectories of anti-recEm18 were identified based on a threshold of 10 AU/ml: "Em18-low" (n = 31), "responders" (n = 53) and "residual disease" (n = 4). The decline of anti-recEm18 in "responders" reached a plateau after 10.9 months at which levels decreased by 90%. The only patient with recurrence in the entire population was also the only patient with a secondary increase of anti-recEm18. CONCLUSION: In patients with preoperative elevated values, anti-recEm18 confirms curative surgery at 12 months follow-up and allows for long-term surveillance.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.

Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies. METHODS: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays. RESULTS: Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p <0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs. 2% in viral/alcohol-HCC, p = 0.03). Tumour mutational burden was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 vs. 0.94 mutations/megabase; p <0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/TGF-ß proliferation subclass tumours (42% vs. 26%, p = 0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of an immunosuppressive cancer field. In 3 murine models of NASH-HCC, key features of human NASH-HCC were preserved. CONCLUSIONS: NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature. LAY SUMMARY: The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH) is increasing globally, but its molecular traits are not well characterised. In this study, we uncovered higher rates of ACVR2A mutations (10%) - a potential tumour suppressor - and the presence of a novel mutational signature that characterises NASH-related HCC.

Investigating new serological and tissue markers for the follow-up of patients operated for alveolar echinococcosis.

AIMS: Alveolar echinococcosis (AE) is characterized by a chronically progressing hepatic injury caused by Echinococcus multilocularis. Surgery presently remains the best curative option. Currently, biological predictive features derived from the resected specimens are not suitable to assess surgery efficacy. The present study was designed to investigate whether a selection of markers measured on the resected specimens exhibits predictive features related to parasite viability, or to a total elimination of the parasite, in addition to serological markers. METHODS AND RESULTS: In a collaboration between two centres, one in France (Besançon), and one in Switzerland (Bern), samples from 40 AE patients were analysed by microarray and serology techniques, individually. Paired serum samples before and after surgery were obtained for 26 patients. In the sera, a significant decrease in PD-L1 levels was observed after surgery, in addition to anti-Em18 levels. In the liver tissue, low levels of Cluster of Differentiation (CD)-3 were correlated with the absence of serum anti-Em18 after surgery. CONCLUSION: This study showed PD-L1 is promising as a potential serological marker and further confirmed the performance of anti-Em18 serology. Further studies on a larger cohort are needed to confirm the utility of performing systematically microarray on resected liver tissue.

CAN MICROWAVE ABLATION BE AN ALTERNATIVE TO RESECTION FOR THE TREATMENT OF NEUROENDOCRINE LIVER METASTASES?

Objective: Surgical resection of neuroendocrine tumor liver metastases has been proven to improve survival, but the benefit of microwave ablation as an alternative or adjunct to surgery has yet to be assessed. Our hypothesis is that ablation is equal to surgery in terms of local recurrence and survival. Methods: We conducted a retrospective analysis including all patients treated with microwave ablation and/or surgical resection for neuroendocrine liver metastases in our institution between 2008 and 2017. Results: A total of 47 patients and 68 treatments were analyzed, including 34 liver resections, 20 ablations, and 14 combined procedures. A total of 130 individual metastases were treated with ablation, representing a median of 4 per session (range 1-30). While no major complications occurred after ablation, we observed 11 minor and 3 major complications after open surgical resection (P = .0135). Length of stay was significantly shorter after ablation (P = .0008). The majority of patients (33/47, 70.2%) underwent curative procedures, 14 patients underwent (29.8%) debulking procedures. There was no difference in local recurrence rate between tumors treated with ablation or resection. Liver-only disease progression was detected in 29% of the patients and overall progression was detected in 66% of the patients. The mean survival was not significantly different between patients treated with ablation only versus resection with or without ablation (P = .1570). Overall survival was mean 75.3 months (6 to 374 months). Conclusion: Depending on the extent of the liver metastases, microwave ablation might be a safe alternative or addition to resection for neuroendocrine tumor liver metastases with low morbidity and high local efficiency. Abbreviations: CT = computed tomography; MWA = microwave ablation; NET = neuroendocrine tumor; PET = positron emission tomography; RFA = radiofrequency ablation; RFS = recurrence-free survival; SMWA = stereotactic microwave ablation.

In situ split plus portal vein ligation (ISLT) - a salvage procedure following inefficient portal vein embolization to gain adequate future liver remnant volume prior to extended liver resection.

BACKGROUND: Right extended liver resection is frequently required to achieve tumor-free margins. Portal venous embolization (PVE) of the prospective resected hepatic segments for conditioning segments II/III does not always induce adequate hypertrophy in segments II and III (future liver remnant volume (FLRV)) for extended right-resection. Here, we present the technique of in situ split dissection along segments II/III plus portal disruption to segments IV-VIII (ISLT) as a salvage procedure to overcome inadequate gain of FLRV after PVE. METHODS: In eight patients, FLRV was further pre-conditioned following failed PVE prior to hepatectomy (ISLT-group). We compared FLRV changes in the ISLT group with patients receiving extended right hepatectomy following sufficient PVE (PVEres-group). Survival of the ISLT-group was compared to PVEres patients and PVE patients with insufficient FLRV gain or tumor progress who did not receive further surgery (PVEnores-group). RESULTS: Patient characteristics and surgical outcome were comparable in both groups. The mean FLRV-to-body-weight ratio in the ISLT group was smaller than in the PVEres-group pre- and post-PVE. One intraoperative mortality due to a coronary infarction was observed for an ISLT patient. ISLT was successfully completed in the remaining seven ISLT patients. Liver function and 2-year survival of ~ 50% was comparable to patients with extended right hepatectomy after efficient PVE. Patients who received a PVE but who were not subsequently resected (PVEnores) demonstrated no survival beyond 4 months. CONCLUSION: Despite extended embolization of segments I and IV-VIII, ISLT should be considered if hypertrophy was not adequate. Liver function and overall survival after ISLT was comparable to patients with trisectionectomy after efficient PVE.

Stereotactic image-guided microwave ablation of hepatocellular carcinoma using a computer-assisted navigation system.

BACKGROUND & AIMS: Ablation plays an important role in the treatment of hepatocellular carcinoma. Because image-guided navigation technology has recently entered the clinical setting, we aimed to analyse its safety, therapeutic and procedural efficiency. METHODS: Retrospective analysis of patients treated with stereotactic image-guided microwave ablation (SMWA) between January 2015 and December 2017. Interventions were performed using computertomography-guidance with needle trajectory, ablation planning and automatic single-marker patient registration. Needle placement and ablation coverage was controlled by image fusion under general anaesthesia with jet-ventilation. RESULTS: In total 174 ablations were performed in 88 patients during 119 interventions. Mean age was 66 (46-84) years, 74 (84.1%) were men and 74% were Child Pugh Class A. Median tumour size was 16 (4-45) mm, 62.2% were BCLC A. Median lateral and longitudinal error of needle placement were 3.2 (0.2-14.1) and 1.6 (0-15.8) mm. Median one tumour (1-4) was ablated per session. One patient developed a Dindo IIIb (0.8%) complication, six minor complications. After re-ablation of 12 lesions, an efficacy rate of 96.3% was achieved. Local tumour progression was 6.3% (11/174). Close proximity to major vessels was significantly correlated with local tumour progression (P < .05). Median overall follow-up was 17.5 months after intervention and 24 months after initial diagnosis. BCLC stage, child class and previous treatment were significantly correlated with overall survival (P < .05). CONCLUSION: Stereotactic image-guided microwave ablation is a safe and efficient treatment for HCC offering a curative treatment approach in general and in particular for lesions not detectable on conventional imaging or untreatable because of difficult anatomic locations.

Design and implementation of an electromagnetic ultrasound-based navigation technique for laparoscopic ablation of liver tumors.

BACKGROUND: Efficient laparoscopic ablation of liver tumors relies on precise tumor visualization and accurate positioning of ablation probes. This study evaluates positional accuracy and procedural efficiency of a dynamic navigation technique based on electromagnetic-tracked laparoscopic ultrasound (ELUS) for laparoscopic ablation of liver tumors. METHODS: The proposed navigation approach combines intraoperative 2D ELUS-based planning for navigated positioning of ablation probes, with immediate 3D ELUS-based validation of intrahepatic probe position. The environmental influence on electromagnetic-tracking stability was evaluated in the operation room. Accuracy of navigated ablation probe positioning assessed as the target-positioning error (TPE), and procedural efficiency defined as time efforts for target definition/navigated targeting and number of probe repositionings, were evaluated in a laparoscopic model and compared with conventional laparoscopic ultrasound (LUS) guidance. RESULTS: The operation-room environment showed interferences < 1 mm on the EM-tracking system. A total of 60 targeting attempts were conducted by three surgeons, with ten targeting attempts using ELUS and ten using conventional LUS each. Median TPE and time for targeting using ELUS and LUS were 4.2 mm (IQR 2.9-5.3 mm) versus 6 mm (IQR 4.7-7.5 mm), and 39 s (IQR 24-47 s) versus 76 s (IQR 47-121 s), respectively (p < 0.01 each). With ELUS, median time for target definition was 48.5 s, with 0 ablation probe repositionings compared to 17 when using LUS. The navigation technique was rated with a mean score of 85.5 on a Standard Usability Scale. CONCLUSIONS: The proposed ELUS-based navigation approach allows for accurate and efficient targeting of liver tumors in a laparoscopic model. Focusing on a dynamic and tumor-targeted navigation technique relying on intraoperative imaging, this avoids potential inaccuracies due to organ deformation and yields a user-friendly technique for efficient laparoscopic ablation of liver tumors.

Unique genomic profile of fibrolamellar hepatocellular carcinoma.

BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer that develops in children and young adults without cirrhosis. Little is known about its pathogenesis, and it can be treated only with surgery. We performed an integrative genomic analysis of a large series of patients with FLC to identify associated genetic factors. METHODS: By using 78 clinically annotated FLC samples, we performed whole-transcriptome (n = 58), single-nucleotide polymorphism array (n = 41), and next-generation sequencing (n = 48) analyses; we also assessed the prevalence of the DNAJB1-PRKACA fusion transcript associated with this cancer (n = 73). We performed class discovery using non-negative matrix factorization, and functional annotation using gene-set enrichment analyses, nearest template prediction, ingenuity pathway analyses, and immunohistochemistry. The genomic identification of significant targets in a cancer algorithm was used to identify chromosomal aberrations, MuTect and VarScan2 were used to identify somatic mutations, and the random survival forest was used to determine patient prognoses. Findings were validated in an independent cohort. RESULTS: Unsupervised gene expression clustering showed 3 robust molecular classes of tumors: the proliferation class (51% of samples) had altered expression of genes that regulate proliferation and mammalian target of rapamycin signaling activation; the inflammation class (26% of samples) had altered expression of genes that regulate inflammation and cytokine enriched production; and the unannotated class (23% of samples) had a gene expression signature that was not associated previously with liver tumors. Expression of genes that regulate neuroendocrine function, as well as histologic markers of cholangiocytes and hepatocytes, were detected in all 3 classes. FLCs had few copy number variations; the most frequent were focal amplification at 8q24.3 (in 12.5% of samples), and deletions at 19p13 (in 28% of samples) and 22q13.32 (in 25% of samples). The DNAJB1-PRKACA fusion transcript was detected in 79% of samples. FLC samples also contained mutations in cancer-related genes such as BRCA2 (in 4.2% of samples), which are uncommon in liver neoplasms. However, FLCs did not contain mutations most commonly detected in liver cancers. We identified an 8-gene signature that predicted survival of patients with FLC. CONCLUSIONS: In a genomic analysis of 78 FLC samples, we identified 3 classes based on gene expression profiles. FLCs contain mutations and chromosomal aberrations not previously associated with liver cancer, and almost 80% contain the DNAJB1-PRKACA fusion transcript. By using this information, we identified a gene signature that is associated with patient survival time.

Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma.

BACKGROUND & AIMS: Epigenetic silencing of tumor suppressor genes contributes to the pathogenesis of hepatocellular carcinoma (HCC). To identify clinically relevant tumor suppressor genes silenced by DNA methylation in HCC, we integrated DNA methylation data from human primary HCC samples with data on up-regulation of gene expression after epigenetic unmasking. METHODS: We performed genome-wide methylation analysis of 71 human HCC samples using the Illumina HumanBeadchip27K array; data were combined with those from microarray analysis of gene re-expression in 4 liver cancer cell lines after their exposure to reagents that reverse DNA methylation (epigenetic unmasking). RESULTS: Based on DNA methylation in primary HCC and gene re-expression in cell lines after epigenetic unmasking, we identified 13 candidate tumor suppressor genes. Subsequent validation led us to focus on functionally characterizing 2 candidates, sphingomyelin phosphodiesterase 3 (SMPD3) and neurofilament, heavy polypeptide (NEFH), which we found to behave as tumor suppressor genes in HCC. Overexpression of SMPD3 and NEFH by stable transfection of inducible constructs into an HCC cell line reduced cell proliferation by 50% and 20%, respectively (SMPD3, P = .003 and NEFH, P = .003). Conversely, knocking down expression of these genes with small hairpin RNA promoted cell invasion and migration in vitro (SMPD3, P = .0001 and NEFH, P = .022), and increased their ability to form tumors after subcutaneous injection or orthotopic transplantation into mice, confirming their role as tumor suppressor genes in HCC. Low levels of SMPD3 were associated with early recurrence of HCC after curative surgery in an independent patient cohort (P = .001; hazard ratio = 3.22; 95% confidence interval: 1.6-6.5 in multivariate analysis). CONCLUSIONS: Integrative genomic analysis identified SMPD3 and NEFH as tumor suppressor genes in HCC. We provide evidence that SMPD3 is a potent tumor suppressor gene that could affect tumor aggressiveness; a reduced level of SMPD3 is an independent prognostic factor for early recurrence of HCC.

Comparison of transarterial bland embolization and drug-eluting beads transarterial chemoembolization for very early and early hepatocellular carcinoma not amenable for surgery or ablation: a single center retrospective data analysis.

Background: Transarterial chemoembolization (TACE) is the accepted therapy for intermediate hepatocellular carcinoma (HCC). Although recent data suggests that bland transarterial embolization (TAE) is equally effective in intermediate HCC, not much is known about the efficacy in very early and early HCC not amenable for ablation or resection. We aimed to compare the outcome of patients with very early and early HCC treated by drug-eluting beads TACE (DEB-TACE), a specific technique of TACE using DC beads, and TAE using microparticles with a size of 100 µm up to 700 µm. Methods: Clinical data of totally 95 patients with very early and early HCC not amenable for surgery or ablation, treated between 2009 and 2019 at the Department of Visceral Surgery and Medicine and the Interdisciplinary Center of Vascular Interventions, University Hospital Bern, Switzerland, were retrospectively analyzed (52 patients in DEB-TACE and 42 patients in TAE group, respectively). All images were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Primary endpoint was overall survival (OS). Secondary endpoints were local response rate and time to local progression. Results: Most patients presented with Child-Pugh A. Thrombocytes were significantly lower in patients treated by TAE. Minor side effects occurred equally in both groups. No differences were detected in terms of OS, local tumor recurrence and response rate. Conclusions: Compared with DEB-TACE, TAE is an equally effective and save therapy for very early and early HCC not amenable for resection or ablation without differences in local tumor control and OS.

Combination therapy for hepatocellular carcinoma: additive preclinical efficacy of the HDAC inhibitor panobinostat with sorafenib.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous cancer in which sorafenib is the only approved systemic therapy. Histone deacetylases (HDAC) are commonly dysregulated in cancer and therefore represent promising targets for therapies, however their role in HCC pathogenesis is still unknown. We analyzed the expression of 11 HDACs in human HCCs and assessed the efficacy of the pan-HDAC inhibitor panobinostat alone and in combination with sorafenib in preclinical models of liver cancer. METHODS: Gene expression and copy number changes were analyzed in a cohort of 334 human HCCs, while the effects of panobinostat and sorafenib were evaluated in three liver cancer cell lines and a murine xenograft model. RESULTS: Aberrant HDAC expression was identified and validated in 91 and 243 HCCs, respectively. Upregulation of HDAC3 and HDAC5 mRNAs was significantly correlated with DNA copy number gains. Inhibiting HDACs with panobinostat led to strong anti-tumoral effects in vitro and vivo, enhanced by the addition of sorafenib. Cell viability and proliferation declined, while apoptosis and autophagy increased. Panobinostat increased histone H3 and HSP90 acetylation, downregulated BIRC5 (survivin) and upregulated CDH1. Combination therapy with panobinostat and sorafenib significantly decreased vessel density, and most significantly decreased tumor volume and increased survival in HCC xenografts. CONCLUSIONS: Aberrant expression of several HDACs and copy number gains of HDAC3 and HDAC5 occur in HCC. Treatment with panobinostat combined with sorafenib demonstrated the highest preclinical efficacy in HCC models, providing the rationale for clinical studies with this novel combination.

MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous tumor that develops via activation of multiple pathways and molecular alterations. It has been a challenge to identify molecular classes of HCC and design treatment strategies for each specific subtype. MicroRNAs (miRNAs) are involved in HCC pathogenesis, and their expression profiles have been used to classify cancers. We analyzed miRNA expression in human HCC samples to identify molecular subclasses and oncogenic miRNAs. METHODS: We performed miRNA profiling of 89 HCC samples using a ligation-mediated amplification method. Subclasses were identified by unsupervised clustering analysis. We identified molecular features specific for each subclass using expression pattern (Affymetrix U133 2.0; Affymetrix, Santa Clara, CA), DNA change (Affymetrix STY Mapping Array), mutation (CTNNB1), and immunohistochemical (phosphor[p]-protein kinase B, p-insulin growth factor-IR, p-S6, p-epidermal growth factor receptor, ß-catenin) analyses. The roles of selected miRNAs were investigated in cell lines and in an orthotopic model of HCC. RESULTS: We identified 3 main clusters of HCCs: the wingless-type MMTV integration site (32 of 89; 36%), interferon-related (29 of 89; 33%), and proliferation (28 of 89; 31%) subclasses. A subset of patients with tumors in the proliferation subclass (8 of 89; 9%) overexpressed a family of poorly characterized miRNAs from chr19q13.42. Expression of miR-517a and miR-520c (from ch19q13.42) increased proliferation, migration, and invasion of HCC cells in vitro. MiR-517a promoted tumorigenesis and metastatic dissemination in vivo. CONCLUSIONS: We propose miRNA-based classification of 3 subclasses of HCC. Among the proliferation class, miR-517a is an oncogenic miRNA that promotes tumor progression. There is rationale for developing therapies that target miR-517a for patients with HCC.

Trends in adrenal surgery: institutional review of 528 consecutive adrenalectomies.

PURPOSE: The increasing detection of adrenal tumors and the availability of a more sophisticated biochemical work-up leading to rising numbers of sub-clinical Conn's and Cushing's syndromes coincide with a rising number of adrenalectomies worldwide. The aim of our study was to report a single institution's experience with adrenal surgery. METHODS: We report data of 528 adrenalectomies, operated at our institution before and after the onset of minimally invasive endoscopic surgery (1986-1994, 1995-2008). Gender, age, indication, imaging, surgical approach, operating time, histology, tumor size, hospital stay, and complications were analyzed retrospectively. RESULTS: A total of 478 patients underwent adrenal surgery during the time observed. The average number of yearly adrenalectomies increased from 14 to 21 (p = 0.001) after the onset of laparoscopic surgery. Imaging techniques showed a significant shift towards magnetic resonance imaging (p < 0.001) and preoperative assessment of tumor size was significantly correlated to malignancy: 10.8 % (11/102) and 42 % (21/50) of tumors measuring 4-6 cm and ≥6 cm, respectively, were malignant in the final histology report (p < 0.001). Patients operated by minimally invasive endoscopy were significantly younger (mean 49.4 years, p = 0.046), had significantly shorter operating times (mean 118 min, p < 0.001), had shorter hospital stays (mean 7.1 days, p < 0.001), and had less complications (6.9 %, p = 0.004) compared to patients resected through open procedures. CONCLUSION: Although adrenalectomy rates increased and minimally invasive endoscopic surgery reduced hospital stay and complications at our institution, the yearly number of procedures was still low with often high surgical complexity. We therefore believe that adrenal surgery remains a highly specialized procedure that should preferably be performed at endocrine surgery centers.

Laparoscopic resection of hepatic alveolar echinococcosis: A single-center experience.

INTRODUCTION: Alveolar echinococcosis (AE) remains a very rare disease requiring complete radical resection for curative treatment. While open approaches are common, safety and efficacy of laparoscopic resections remain unknown. METHODS: This is a single-center, retrospective cohort study with patients undergoing liver resection for hepatic AE at the Department of Visceral Surgery and Medicine, Bern University Hospital from December 2002 to December 2020. Postoperative outcomes of patients following laparoscopic hepatectomy (LH) for hepatic AE were compared with those of patients undergoing open hepatectomy (OH). RESULTS: A total of 93 patients underwent liver resection for hepatic AE. Laparoscopic hepatectomy was performed in 23 patients and open hepatectomy in 70 patients. While there were no significant differences in terms of gender, age and diagnostic tools, the majority of patients of the LH cohort were PNM stage 1 (78%) in contrast to only 39% in the OH cohort (p = 0.002). Patients undergoing laparoscopic hepatectomy were treated by minor liver resections in 91% and in 9% by major liver resections in comparison to the open hepatectomy cohort with 61% major liver resections and 39% minor resections. Laparoscopic hepatectomy was associated with shorter mean operation time (127 minutes vs. 242 minutes, p <0.001), lower major complication rate (0% vs. 11%, p = 0.322) and shorter mean length of hospital stay (4 days vs. 13 days, p <0.001). Patients with LH had a distinct, but not significant lower recurrence rate (0% vs. 4%, p = 0.210) during a mean follow-up of 55 months compared with a follow-up of 76 months in the OH cohort. After subgroup analysis of PNM stage 1 patients, similar results are seen with persistent shorter mean operation time (120 minutes vs. 223 minutes, p <0.001), lower major complication rate (0% vs. 8%, p = 0.759) and shorter length of hospital stay (4 days vs. 12 days, p <0.001). CONCLUSION: Laparoscopy appears as a feasible and safe approach for patients with PNM stage 1 alveolar echinococcosis without impact on early disease recurrence.

Gene-expression signature of vascular invasion in hepatocellular carcinoma.

BACKGROUND & AIMS: Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30-40% of patients with early tumors, remains elusive. METHODS: A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. RESULTS: A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48-7.71, p=0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17-6.05, p=0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p=0.045). CONCLUSIONS: The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.

The Role of Conventional and Stereotactic Microwave Ablation for Intrahepatic Cholangiocarcinoma.

BACKGROUND: The incidence and mortality of intrahepatic cholangiocarcinoma (ICCA) is increasing worldwide and curative treatment options are limited due to the aggressive tumor biology and often late diagnosis. Resection of the primary tumor remains the only curative therapy available, as the benefit of palliative chemotherapy and radiotherapy is relatively small. In contrast to hepatocellular carcinoma, minimal-invasive thermal tumor ablation, and in particular stereotactic tumor ablation for small primary cancers or metastases, is not established and data are scarce. METHODS: We conducted a literature review in the field of ICCA ablation and retrospective analysis of 10 patients treated by stereotactic microwave ablation (SMWA) for either primary ICCA or liver metastases of ICCA. RESULTS: While current guidelines have no consensus for ablation of primary ICCA, some state that it might be an option in inoperable patients or those with recurrent disease. The literature review revealed 11 studies on microwave ablation for ICCA reporting that MWA for ICCA ≤ 5 cm might be safe and could be a treatment option for patients who are not candidates for surgery. No data has been published on stereotactic microwave ablation (SMWA) for ICCA. The analyses of our own data of 10 patients treated by SMWA for primary ICCA (n = 5) or recurrent ICCA (n = 5) show that the treatment is safe and efficient with short hospital stays and low complication rates. CONCLUSION: Although thermal ablation, and in particular SMWA, might be a minimally invasive and tissue-sparing curative treatment alternative for small ICCA in the diseased liver and ICCA metastases, the oncologic benefit still needs to be shown in larger studies with longer follow-up.

Parenchymal-sparing hepatectomy for colorectal liver metastases reduces postoperative morbidity while maintaining equivalent oncologic outcomes compared to non-parenchymal-sparing resection.

BACKGROUND: Modern chemotherapy and repeat hepatectomy allow to tailor the surgical strategies for the treatment of colorectal liver metastases (CRLM). This study addresses the hypothesis that parenchymal-sparing hepatectomy reduces postoperative complications while ensuring similar oncologic outcomes compared to the standardized non-parenchymal-sparing procedures. METHODS: Clinicopathological data of patients who underwent liver resection for CRLM between 2012 and 2019 at a hepatobiliary center in Switzerland were assessed. Patients were stratified according to the tumor burden score [TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2)] and were dichotomized in a lower and a higher tumor burden cohort according to the median TBS. Postoperative outcomes, overall survival (OS) and recurrence-free survival (RFS) of patients following parenchymal-sparing resection (PSR) for CRLM were compared with those of patients undergoing non-PSR. RESULTS: During the study period, 153 patients underwent liver resection for CRLM with curative intent. PSR was performed in 79 patients with TBS <4.5, and in 42 patients with TBS ≥4.5. Perioperative chemotherapy was administered in equal rates in both groups (PSR vs. non-PSR) both in TBS ≥4.5 and TBS <4.5. In patients with lower tumor burden (TBS <4.5), PSR was associated with lower overall complication rate (15.2% vs. 46.2%, p = 0.009), a trend for lower major complication rate (8.9% vs. 23.1%, p = 0.123), and shorter length of hospital stay (5 vs. 9 days, p = 0.006) in comparison to non-PSR. For TBS <4.5, PSR resulted in equivalent 5-year OS (48% vs. 39%, p = 0.479) and equivalent 5-year RFS rates (44% vs. 29%, p = 0.184) compared to non-PSR. For TBS ≥4.5, PSR resulted in lower postoperative complication rate (33.3% vs. 63.2%, p = 0.031), a trend for lower major complication rate (23.8% vs. 42.2%, p = 0.150), lower length of hospital stay (6 vs. 9 days, p = 0.005), equivalent 5-year OS (29% vs. 22%, p = 0.314), and equivalent 5-year RFS rates (29% vs. 18%, p = 0.156) compared to non-PSR. Among all patients treated with PSR, patients undergoing minimal-invasive hepatectomy had equivalent 5-year OS (42% vs. 37%, p = 0.261) and equivalent 5-year RFS (34% vs. 34%, p = 0.613) rates compared to patients undergoing open hepatectomy. CONCLUSIONS: PSR for CRLM is associated with lower postoperative morbidity, shorter length of hospital stay, and equivalent oncologic outcomes compared to non-PSR, independently of tumor burden. Our findings suggest that minimal-invasive PSR should be considered as the preferred method for the treatment of curatively resectable CRLM, if allowed by tumor size and location.