Objective: To assess whether administration of surgical antimicrobial prophylaxis (SAP) versus absence of SAP is associated with a decreased risk of surgical site infections (SSIs) after low-risk cholecystectomies (LR-CCEs). Background: Current guidelines do not recommend routine SAP administration before LR-CCE. Methods: This cohort study included adult patients who underwent LR-CCE and were documented by the Swissnoso SSI surveillance system between January 2009 and December 2020 at 66 Swiss hospitals. LR-CCE was specified as elective endoscopic surgery, age <70, no active cholecystitis, ASA score <3, operating time <120 minutes without implantation of foreign material. Exposure was defined as the administration of cefuroxime or cefazoline +/- metronidazole within 120 minutes before incision versus no SAP administration. Our main outcome was the occurrence of SSI until day 30. Logistic regression models were used to adjust for institutional, patient, and perioperative variables. Results: Of 44,682 surveilled adult patients undergoing cholecystectomy, 12,521 [8726 women (69.7%); median (interquartile range) age, 49.0 (38.1-58.2) years] fulfilled the inclusion criteria. SSI was identified in 143 patients (1.1%). SAP was administered in 9269 patients (74.0%) and was associated with a lower SSI rate (adjusted odds ratio, 0.50; 95% CI, 0.35-0.70; P < 0.001). The number needed to treat to prevent 1 SSI episode is 100. Conclusions: The overall LR-CCE SSI rate was 1.1%. SAP was associated with a 50% lower overall SSI rate. Patients undergoing LR-CCE may benefit from routine SAP.

INTRODUCTION:Standardization has the potential to serve as a measure to mitigate complication rates. The objective was to assess the impact of standardization by implementing a colorectal bundle (CB), which comprises nine elements, on the complication rates in left-sided colorectal resections. PATIENTS AND METHODS:This prospective, multicentre, observational, cohort trial was conducted in Switzerland at nine participating hospitals. During the control period, each patient was treated in accordance with the local standard protocol at their respective hospital. In the CB period, all patients were treated in accordance with the CB. The primary endpoint was the Comprehensive Complication Index (CCI) at 30 days. RESULTS:A total of 1141 patients were included (723 in the No CB group and 418 in the CB group). The median age was 66 years, and 50.6% were female. Median CCI before and after CB implementation was 0.0 (interquartile range [IQR]: 0.0-20.9). A hurdle model approach was used for the analysis. The CB was not associated with the presence or severity of complications. Older age (odds ratio [OR] 1.02, 95% CI: 1.00-1.03), surgery for malignancy (OR 1.34, 95% CI: 1.01-1.92), emergency surgery (OR 2.19, 95% CI: 1.31-3.41), elevated nutritional risk score (OR 1.13, 95% CI: 1.01-1.24), and BMI (OR 1.04, 95% CI: 1.00-1.06) were associated with higher odds of postoperative complications. In a supplementary per-protocol analysis, for each additional item of the CB fulfilled, the odds of anastomotic leakage (AL) were 24% lower (OR 0.76, 95% CI: 0.64-0.93). CONCLUSIONS:Dedicated teams can establish high-quality colorectal services in a network of hospitals with a joint standard. The study can serve as a model for other healthcare settings to conduct and implement quality improvement programs. The consistent implementation of the CB items can reduce the occurrence of AL.

Objective: To assess whether administration of surgical antimicrobial prophylaxis (SAP) versus absence of SAP is associated with a decreased risk of surgical site infections (SSI) after low-risk cholecystectomies (LR-CCE). Summary Background Data: Current guidelines do not recommend routine SAP administration prior to LR-CCE. Methods: This cohort study included adult patients who underwent LR-CCE and were documented by the Swissnoso SSI surveillance system between 1/2009-12/2020 at 66 Swiss hospitals. LR-CCE was specified as elective endoscopic surgery, age <70, no active cholecystitis, ASA score <3, operating time <120 minutes without implantation of foreign material. Exposure was defined as the administration of cefuroxime or cefazoline ± metronidazole within 120 minutes prior to incision versus no SAP administration. Our main outcome was occurrence of SSI until day 30. Logistic regression models were used to adjust for institutional, patient, and perioperative variables. Results: Of 44 682 surveilled adult cholecystectomy patients, 12 521 (8 726 women [69.7%]; median [IQR] age, 49.0 [38.1-58.2] years), fulfilled inclusion criteria. SSI was identified in 143 patients (1.1%). SAP was administered in 9 269 patients (74.0%) and was associated with a lower SSI rate (adjusted odds ratio [aOR], 0.50; 95% CI, 0.35-0.70; P < 0.001). The number needed to treat to prevent one SSI episode is 100. Conclusions: The overall LR-CCE SSI rate was 1.1%. SAP was associated with a 50% lower overall SSI rate. Patients undergoing LR-CCE may benefit from routine surgical antimicrobial prophylaxis.

Anastomotic leakage (AL), a severe complication following colorectal surgery, arises from defects at the anastomosis site. This study evaluates the feasibility of predicting AL using machine learning (ML) algorithms based on preoperative data. We retrospectively analyzed data including 21 predictors from patients undergoing colorectal surgery with bowel anastomosis at four Swiss hospitals. Several ML algorithms were applied for binary classification into AL or non-AL groups, utilizing a five-fold cross-validation strategy with a 90

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Neoadjuvant chemo-radiotherapy (nCRT) of locally advanced rectal cancer is associated with challenging surgical treatment and increased postoperative morbidity. Robotic technology overcomes laparoscopy limitations by enlarged 3D view, improved anatomical transection accuracy, and physiologic tremor reduction. Patients with UICC stage II–III rectal cancer, consecutively referred to our institution between March 2015 and June 2020 (n = 102) were treated with robotic (Rob-G, n = 38) or laparoscopic (Lap-G, n = 64) low anterior resection (LAR) for total meso-rectal excision (TME) following highly standardized and successful nCRT treatment. Feasibility, conversion rates, stoma creation, morbidity and clinical/pathological outcome were comparatively analysed. Sex, age, BMI, ASA scores, cTN stages and tumour distance from dentate line were comparable in the two groups. Robotic resection was always feasible without conversion to open surgery, which was necessary in 11/64 (17%) Lap-G operations (p = 0.006). Primary or secondary stomata were created in 17/38 (45%) Rob-G and 52/64 (81%) Lap-G patients (p < 0.001). Major morbidity occurred in 7/38 (18.4%) Rob-G and 6/64 (9.3%) Lap-G patients (p = 0.225). Although median operation time was longer in Rob-G compared with Lap-G (376; IQR: 330–417 min vs. 300; IQR: 270–358 min; p < 0.001), the difference was not significant in patients (Rob-G, n = 6; Lap-G, n = 10) with ≥30 BMI (p = 0.106). Number of resected lymph nodes, ypTN staging and circumferential resection margins (CRM) were comparable. Resection was complete in 87% of Rob-G and 89% of Lap-G patients (p = 0.750). Robotic LAR is not inferior to laparoscopic LAR following nCRT. Larger, randomized studies are needed to confirm lower conversion in robotic, compared to laparoscopic resection.

OBJECTIVE:The use of machine learning (ML) has revolutionized every domain of medicine. Surgeons are now using ML models for disease detection and outcome prediction with high precision. ML-guided colorectal surgeries are more efficient than conventional surgical procedures. The primary aim of this paper is to provide an overview of the latest research on "ML in colorectal surgery", with its viable applications. METHODS:PubMed, Google Scholar, Medline, and Cochrane library were searched. RESULTS:After screening, 27 articles out of 172 were eventually included. Among all of the reviewed articles, those found to fit the criteria for inclusion had exclusively focused on ML in colorectal surgery, with justified applications. We identified existing applications of ML in colorectal surgery. Additionally, we discuss the benefits, risks, and safety issues. CONCLUSIONS:A better, more sustainable, and more efficient method, with useful applications, for ML in surgery is possible if we and data scientists work together to address the drawbacks of the current approach. Potential problems related to patients' perspectives also need to be resolved. The development of accurate technologies alone will not solve the problem of perceived unreliability from the patients' end. Confidence can only be developed within society if more research with precise results is carried out.

Background Laparoscopic (LSC) Heller myotomy (HM) is considered the standard procedure for the treatment of achalasia. Robotic platforms, established over the last years, provide important advantages to surgeons, such as binocular 3-dimensional vision and improvement of fine motor control. However, whether perioperative outcomes and long-term results of robotic-assisted laparoscopic (RAL) HM are similar or even superior to LSC technique, especially concerning long-term follow-up, is still debated. Therefore, the aim of the present study was to evaluate intra- and postoperative results as well as long-term quality of life after RAL compared to LSC surgery for achalasia in a single high-volume visceral surgery center. Methods Between August 2007 and April 2020, 43 patients undergoing minimally invasive HM for achalasia in a single high-volume Swiss visceral surgery center, were included in the present study. Intra- and postoperative outcome parameters were collected and evaluated, and a long-term follow-up was performed using the gastroesophageal-reflux disease health-related quality of life (GERD-Hr-QuoL) questionnaire. Results A total of 11 patients undergoing RAL and 32 undergoing LSC HM were analyzed. Baseline demographics and clinical characteristics were similar. A trend (p = 0.052) towards a higher number of patients with ASA III score treated with RAL was detectable. Operation time was marginally, but significantly, shorter in LSC (140 min, IQR: 136–150) than in RAL (150 min, IQR: 150–187, p = 0.047). Postoperative complications graded Clavien-Dindo ≥ 3 were only observed in one patient in each group. Length of hospital stay was similar in both groups (LSC: 11 days, IQR: 10–13 vs. RAL: 11 days, IQR: 10–14, p = 0.712). Long-term follow-up (LSC: median 89 months, vs. RAL: median 28 months, p = 0.001) showed comparable results and patients from both groups expressed similar levels of satisfaction (p = 0.181). Conclusions LSC and RAL HM show similar peri- and postoperative results and a high quality of life, even in long-term (> 24 months) follow-up. Prospective, randomized, controlled multicenter trials are needed to overcome difficulties associated to small sample sizes in a rare condition and to confirm the equality or demonstrate the superiority of robotic-assisted procedures for achalasia. Meanwhile, the choice of the treatment technique could be left to the operating surgeon’s preferences.

Robotic-assisted colorectal surgery has gained more and more popularity over the last years. It seems to be advantageous to laparoscopic surgery in selected situations, especially in confined regions like a narrow male pelvis in rectal surgery. Whether robotic-assisted, left-sided colectomies can serve as safe training operations for less frequent, low anterior resections for rectal cancer is still under debate. Therefore, the aim of this study was to evaluate intra- and postoperative results of robotic-assisted laparoscopy (RAL) compared to laparoscopic (LSC) surgery in left-sided colectomies. Between June 2015 and December 2019, 683 patients undergoing minimally invasive left-sided colectomies in two Swiss, high-volume colorectal centers were included. Intra- and postoperative outcome parameters were collected and analyzed. A total of 179 patients undergoing RAL and 504 patients undergoing LSC were analyzed. Baseline characteristics showed similar results. Intraoperative complications occurred in 0.6% of RAL and 2.0% of LSC patients (p = 0.193). Differences in postoperative complications graded Dindo ≥ 3 were not statistically significant (RAL 3.9% vs. LSC 6.3%, p = 0.227). Occurrence of anastomotic leakages showed no statistically significant difference [RAL n = 2 (1.1%), LSC n = 8 (1.6%), p = 0.653]. Length of hospital stay was similar in both groups. Conversions to open surgery were significantly higher in the LSC group (6.2% vs.1.7%, p = 0.018), while stoma formation was similar in both groups [RAL n = 1 (0.6%), LSC n = 5 (1.0%), p = 0.594]. Operative time was longer in the RAL group (300 vs. 210.0 min, p < 0.001). Robotic-assisted, left-sided colectomies are safe and feasible compared to laparoscopic resections. Intra- and postoperative complications are similar in both groups. Most notably, the rate of anastomotic leakages is similar. Compared to laparoscopic resections, the analyzed robotic-assisted resections have longer operative times but less conversion rates. Further prospective studies are needed to confirm the safety of robotic-assisted, left-sided colectomies as training procedures for low anterior resections.

Introduction: Inguinal hernia repairs are commonly performed procedures. The surgical techniques vary from open procedures to minimally invasive and robotic-assisted surgeries and include totally extra-peritoneal hernia repairs (TEP) and robotic transabdominal pre-peritoneal hernia repairs (rTAPP). So far, there is no randomized and blinded clinical trial comparing these two surgical approaches. Our objective is to investigate whether rTAPP is associated with a decreased postoperative level of pain. Methods: This is a prospective, single center, randomized and blinded clinical trial. Patients will receive either rTAPP or TEP for uni- or bilateral inguinal hernias. All patients and assessors of the study are blinded to the randomization. The perioperative setting is standardized, and all surgeons will perform both rTAPP and TEP to eliminate surgeons' bias. Primary endpoint is the assessment of pain while coughing 24 hours after surgery using the numeric rating scale (NRS). Secondary endpoints include the assessment of multiple pain and quality of life questionnaires at several defined times according to the study schedule. Furthermore, intra- and postoperative complications, duration until discharge, procedure time, duration of postoperative sick leave and the recurrence rate will be evaluated. Registry: The trial has been registered at ClinicalTrials.gov under the registry number NCT05216276. Highlights Trial comparing robotic and conventional minimal-invasive inguinal hernia repair Randomized and patient / assessor blinded trial Early postoperative pain as primary outcome (24 hours) Secondary patient outcomes include pain and quality of life scores up to one year Further secondary outcomes: complications, costs, surgeon's stress level

Purpose:Overall complication and leak rates in colorectal surgery showed only minor improvements over the last years and remain still high. While the introduction of the WHO Safer Surgery Checklist has shown a reduction of overall operative mortality and morbidity in general surgery, only minor attempts have been made to improve outcomes by standardizing perioperative processes in colorectal surgery. Nevertheless, a number of singular interventions have been found reducing postoperative complications in colorectal surgery. The aim of the present study is to combine nine of these measures to a catalogue called colorectal bundle (CB). This will help to standardize pre-, intra-, and post-operative processes and therefore eventually reduce complication rates after colorectal surgery. Methods:The study will be performed among nine contributing hospitals in the extended north-western part of Switzerland. In the 6-month lasting control period the patients will be treated according to the local standard of each contributing hospital. After a short implementation phase all patients will be treated according to the CB for another 6 months. Afterwards complication rates before and after the implementation of the CB will be compared. Discussion:The overall complication rate in colorectal surgery is still high. The fact that only little progress has been made in recent years underlines the relevance of the current project. It has been shown for other areas of surgery that standardization is an effective measure of reducing postoperative complication rates. We hypothesize that the combination of effective, individual components into the CB can reduce the complication rate. Trial registration:Registered in ClinicalTrials.gov on 11/03/2020; NCT04550156. Highlights:Purpose: Overall complications in colorectal surgery remain still highStandardizing can reduce overall operative mortality and morbidityOnly minor attempts have been made to standardize perioperative processes in colorectal surgerySingular interventions have been found reducing postoperative complicationsThe aim is to combine nine of these measures to a colorectal bundle (CB)The CB will help to reduce complication rates after colorectal surgery Methods: The observational study will be performed among nine hospitals in SwitzerlandSix month the patients will be treated according to the local standardsAfterwards patients will be treated according to the CB for another six monthsComplication rates before and after the implementation of the CB will be compared Discussion: Only little progress has been made to reduce complication rate in colorectal surgeryStandardization is an effective measure of reducing complication ratesThe combination of effective, individual components into the CB can reduce the complication rate.

Abstract Background Tumor infiltration with cytotoxic CD8+ T-cells is associated with a favorable outcome in several neoplasms, including thyroid cancer. The chemokine axis CXCR4/SDF-1 correlates with more aggressive tumors, but little is known concerning the prognostic relevance in relation to the tumor immune microenvironment of differentiated thyroid cancer (DTC). Methods A tissue microarray (TMA) of 37 tumor specimens of primary DTC was analyzed by immunohistochemistry (IHC) for the expression of CD8+, CXCR4, phosphorylated CXCR4 and SDF-1. A survival analysis was performed on a larger collective (n = 456) at RNA level using data from The Cancer Genome Atlas (TCGA) papillary thyroid cancer cohort. Results Among the 37 patients in the TMA-cohort, the density of CD8+ was higher in patients with less advanced primary tumors (median cells/TMA-punch: 12.5 (IQR: 6.5, 12.5) in T1–2 tumors vs. 5 (IQR: 3, 8) in T3–4 tumors, p = 0.05). In the TCGA-cohort, CXCR4 expression was higher in patients with cervical lymph node metastasis compared to N0 or Nx stage (CXCR4high/low 116/78 vs. 97/116 vs. 14/35, respectively, p = 0.001). Spearman’s correlation analysis of the TMA-cohort demonstrated that SDF-1 was significantly correlated with CXCR4 (r = 0.4, p = 0.01) and pCXCR4 (r = 0.5, p = 0.002). In the TCGA-cohort, density of CD8+ correlated with CXCR4 and SDF-1 expression (r = 0.58, p < 0.001; r = 0.4, p < 0.001). The combined marker analysis of the TCGA cohort demonstrated that high expression of both, CXCR4 and SDF-1 was associated with reduced overall survival in the CD8 negative TCGA cohort (p = 0.004). Conclusion These findings suggest that the prognostic significance of CXCR4 and SDF-1 in differentiated thyroid cancer depends on the density of CD8 positive T-lymphocytes. Further studies with larger sample sizes are needed to support our findings and inform future investigations of new treatment and diagnostic options for a more personalized approach for patients with differentiated thyroid cancer.

Background Focal nodular hyperplasia (FNH) is typically considered a benign tumor of the liver without malignant potential. The co-occurrence of FNH and hepatocellular carcinoma (HCC) has been reported in rare cases. In this study we sought to investigate the clonal relationship between these lesions in a patient with FNH-HCC co-occurrence. Methods A 74-year-old female patient underwent liver tumor resection. The resected nodule was subjected to histologic analyses using hematoxylin and eosin stain and immunohistochemistry. DNA extracted from microdissected FNH and HCC regions was subjected to whole exome sequencing. Clonality analysis were performed using PyClone. Results Histologic analysis reveals that the nodule consists of an FNH and two adjoining HCC components with distinct histopathological features. Immunophenotypic characterization and genomic analyses suggest that the FNH is clonally related to the HCC components, and is composed of multiple clones at diagnosis, that are likely to have progressed to HCC through clonal selection and/or the acquisition of additional genetic events. Conclusion To the best of our knowledge, our work is the first study showing a clonal relationship between FNH and HCC. We show that FNH may possess the capability to undergo malignant transformation and to progress to HCC in very rare cases.

Purpose Robotic-assisted procedures are increasingly used in esophageal cancer surgery. We compared postoperative complications and early oncological outcomes following hybrid robotic-assisted thoracoscopic esophagectomy (Rob-E) and open Ivor Lewis esophagectomy (Open-E), performed in a single mid-volume center, in the context of evolving preoperative patient and tumor characteristics over two decades. Methods We evaluated prospectively collected data from a single center from 1999 to 2020 including 321 patients that underwent Ivor Lewis esophagectomy, 76 underwent Rob-E, and 245 Open-E. To compare perioperative outcomes, a 1:1 case-matched analysis was performed. Endpoints included postoperative morbidity and 30-day mortality. Results Preoperative characteristics revealed increased rates of adenocarcinomas and wider use of neoadjuvant treatment over time. A larger number of patients with higher ASA grades were operated with Rob-E. In case-matched cohorts, there were no differences in the overall morbidity (69.7% in Rob-E, 60.5% in Open-E, p value 0.307), highest Clavien-Dindo grade per patient (43.4% vs. 38.2% grade I or II, p value 0.321), comprehensive complication index (median 20.9 in both groups, p value 0.401), and 30-day mortality (2.6% in Rob-E, 3.9% in Open-E, p value 1.000). Similar median numbers of lymph nodes were harvested (24.5 in Rob-E, 23 in Open-E, p value 0.204), and comparable rates of R0-status (96.1% vs. 93.4%, p value 0.463) and distribution of postoperative UICC stages (overall p value 0.616) were observed. Conclusions Our study demonstrates similar postoperative complications and early oncological outcomes after Rob-E and Open-E. However, the selection criteria for Rob-E appeared to be less restrictive than those of Open-E surgery.

Background Esophageal cancer surgery is technically highly demanding. During the past decade robot-assisted surgery has successfully been introduced in esophageal cancer treatment. Various techniques are being evaluated in different centers. In particular, advantages and disadvantages of continuously sutured (COSU) or linear-stapled (LIST) gastroesophageal anastomoses are debated. Here, we comparatively analyzed perioperative morbidities and short-term outcomes in patients undergoing hybrid robot-assisted esophageal surgery following neoadjuvant chemoradiotherapy (nCRT), with COSU or LIST anastomoses in a single center. Methods Following standardized, effective, nCRT, 53 patients underwent a hybrid Ivor Lewis robot-assisted esophagectomy with COSU ( n = 32) or LIST ( n = 21) gastroesophageal anastomoses. Study endpoints were intra- and postoperative complications, in-hospital morbidity and mortality. Duration of operation, intensive care unit (ICU) and overall hospital stay were also evaluated. Furthermore, rates of rehospitalization, endoscopies, anastomotic stenosis and recurrence were assessed in a 90-day follow-up. Results Demographics, ASA scores and tumor characteristics were comparable in the two groups. Median duration of operation was similar in patients with COSU and LIST anastomosis (467 vs. 453 min, IQR 420–521 vs. 416–469, p = 0.0611). Major complications were observed in 4/32 (12.5%) and 4/21 (19%) patients with COSU or LIST anastomosis, respectively ( p = 0.697). Anastomotic leakage was observed in 3/32 (9.3%) and 2/21 (9.5%) ( p = 1.0) patients with COSU or LIST anastomosis, respectively. Pleural empyema occurred in 1/32 (3.1%) and 2/21 (9.5%) ( p = 0.555) patients, respectively. Mortality was similar in the two groups (1/32, 3.1% and 1/21, 4.7%, p = 1.0). Median ICU stay did not differ in patients with COSU or LIST anastomosis ( p = 0.255), whereas a slightly, but significantly ( p = 0.0393) shorter overall hospital stay was observed for COSU, as compared to LIST cohort (median: 20 vs. 21 days, IQR 17–22 vs. 18–28). Conclusions COSU is not inferior to LIST in the performance of gastroesophageal anastomosis in hybrid Ivor Lewis operations following nCRT.

Increasing attention has been given to postoperative gastrointestinal functional outcome and quality of life after sigmoid resection for diverticulitis. Conversely, very little has been described about postoperative urogenital functional outcome and even less about its potential relationship to the type of vascular approach. The aim of this study was to evaluate whether central ligation of the inferior mesenteric artery (IMA) compared with peripheral dissection could impair urinary and sexual function in the long term. Patients undergoing elective laparoscopic sigmoid resection for diverticulitis from 2004 to 2017 were retrospectively analysed. They were asked to complete the American Urological Association Symptom Index (AUASI) questionnaire. Men received the five-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Patients were then divided according to the type of vascular resection. A response rate of the 36.4% to the AUASI and 43.8% to the IIEF-5 questionnaires was achieved. Three hundred and twenty four patients with a mean age of 62 ± 9.85 years were analysed for their urinary function (IMA preserved n  = 217; IMA resected n  = 107) in a median follow-up of 87 months. Furthermore, 115 men with a mean age of 60 ± 8.97 years were investigated for their sexual function (IMA preserved n  = 80; IMA resected n  = 35) in a median follow-up of 89 months. No difference (AUASI: 8 ± 6.32 IMA preserved vs. 7 ± 6.26 IMA resected, P  = 0.204; IIEF-5: 15 ± 7.67 IMA preserved vs. 15 ± 8.61 IMA resected, P  = 0.674) was found regarding the type of vascular approach during sigmoid resection. No association was found between the type of vascular approach and the long-term urogenital functional outcome in patients undergoing sigmoid resection for diverticulitis.

An amendment to this paper has been published and can be accessed via the original article.

Hepatocellular carcinomas (HCCs) usually arise from chronic liver disease (CLD). Precancerous cells in chronically inflamed environments may be 'epigenetically primed', sensitising them to oncogenic transformation. We investigated whether epigenetic priming in CLD may affect HCC outcomes by influencing the genomic and transcriptomic landscapes of HCC. Analysis of DNA methylation arrays from 10 paired CLD-HCC identified 339 shared dysregulated CpG sites and 18 shared differentially methylated regions compared with healthy livers. These regions were associated with dysregulated expression of genes with relevance in HCC, including ubiquitin D (UBD), cytochrome P450 family 2 subfamily C member 19 (CYP2C19) and O-6-methylguanine-DNA methyltransferase (MGMT). Methylation changes were recapitulated in an independent cohort of nine paired CLD-HCC. High CLD methylation score, defined using the 124 dysregulated CpGs in CLD and HCC in both cohorts, was associated with poor survival, increased somatic genetic alterations and TP53 mutations in two independent HCC cohorts. Oncogenic transcriptional and methylation dysregulation is evident in CLD and compounded in HCC. Epigenetic priming in CLD sculpts the transcriptional landscape of HCC and creates an environment favouring the acquisition of genetic alterations, suggesting that the extent of epigenetic priming in CLD could influence disease outcome.