Impact of the future liver remnant volume before major hepatectomy.

INTRODUCTION: Following major liver resection, posthepatectomy liver failure (PHLF) is associated with a high mortality rate. As there is no therapy for PHLF available, avoidance remains the main goal. A sufficient future liver remnant (FLR) is one of the most important factors to reduce the risk for PHLF; however, it is not known which patients benefit of volumetric assessment prior to major surgery. METHODS: A retrospective, bi-institutional cohort study was conducted including all patients who underwent major hepatectomy (extended right hepatectomy, right hepatectomy, extended left hepatectomy and left hepatectomy) between 2010 and 2023. RESULTS: A total of 1511 major hepatectomies were included, with 29.4 % of patients undergoing FLR volume assessment preoperatively. Overall, PHLF B/C occurred in 9.8 % of cases. Multivariate analysis identified diabetes mellitus, extended right hepatectomy, perihilar cholangiocarcinoma (pCCA), gallbladder cancer (GBC) and cirrhosis as significant risk factors for PHLF B/C. High-risk patients (with one or more risk factors) had a 15 % overall incidence of PHLF, increasing to 32 % with a FLR <30 %, and 13 % with an FLR of 30-40 %. Low-risk patients with a FLR <30 % had a PHLF rate of 21 %, which decreased to 8 % and 5 % for FLRs of 30-40 % and >40 %, respectively. For right hepatectomy, the PHLF rate was 23 % in low-risk and 38 % in high-risk patients with FLR <30 %. CONCLUSION: Patients scheduled for right hepatectomy and extended right hepatectomy should undergo volumetric assessment of the FLR. Volumetry should always be considered before major hepatectomy in patients with risk factors such as diabetes, cirrhosis, GBC and pCCA. In high-risk patients, a FLR cut-off of 30 % may be insufficient to prevent PHLF, and additional liver function assessment should be considered.

Importance of resection margin after resection of colorectal liver metastases in the era of modern chemotherapy: population-based cohort study.

BACKGROUND: Resection margin has been associated with overall survival following liver resection for colorectal liver metastasis. The aim of this study was to examine how resection margins of 0.0 mm, 0.1-0.9 mm and ≥1 mm influence overall survival in patients resected for colorectal liver metastasis in a time of modern perioperative chemotherapy and surgery. METHODS: Using data from the national registries Swedish Colorectal Cancer Registry and Swedish National Quality Registry for Liver, Bile Duct and Gallbladder Cancer, patients that had liver resections for colorectal liver metastasis between 2009 and 2013 were included. In patients with a narrow or unknown surgical margin the original pathological reports were re-reviewed. Factors influencing overall survival were analysed using a Cox proportional hazard model. RESULTS: A total of 754 patients had a known margin status, of which 133 (17.6%) patients had a resection margin <1 mm. The overall survival in patients with a margin of 0 mm or 0.1-0.9 mm was 42 (95% c.i. 31 to 53) and 48 (95% c.i. 35 to 62) months respectively, compared with 75 (95% c.i. 65 to 85) for patients with ≥1 mm margin, P < 0.001. Margins of 0 mm or 0.1-0.9 mm were associated with poor overall survival in the multivariable analysis, HR 1.413 (95% c.i. 1.030 to 1.939), P = 0.032, and 1.399 (95% c.i. 1.025 to 1.910), P = 0.034, respectively. CONCLUSIONS: Despite modern chemotherapy the resection margin is still an important factor for the survival of patients resected for colorectal liver metastasis, and a margin of ≥1 mm is needed to achieve the best possible outcome.

Hepatocellular carcinoma in cirrhotic versus non-cirrhotic liver: Treatment and survival differences in a nationwide cohort.

BACKGROUND AND AIMS: Numerous studies have reported superior outcome for patients with hepatocellular carcinoma (HCC) in non-cirrhotic compared to cirrhotic livers. This cohort study aims to describe the clinical presentation, disease course, treatment approaches, and survival differences in a population-based setting. METHODS: Data on patients diagnosed with HCC in Sweden between 2008 and 2018 were identified and extracted from the Swedish Liver registry (SweLiv). Descriptive and survival statistics were applied. RESULTS: Among the 4259 identified patients, 34% had HCC in a non-cirrhotic liver. Cirrhotic patients presented at a younger age (median = 64 vs 74 years, p < 0.001) and with a poorer performance status (Eastern Cooperative Oncology Group (ECOG) = 0-1: 64% vs 69%, p = 0.024). Underlying liver disease was more prevalent among cirrhotic patients (81% vs 19%, p < 0.001). Tumors in non-cirrhotic livers were diagnosed at a more advanced stage (T3-T4: 46% vs 31%) and more frequently with metastatic disease at diagnosis (22% vs 10%, p < 0.001). Tumors were significantly larger in non-cirrhotic livers (median size of largest tumor 7.5 cm) compared to cirrhotic livers (3.5 cm) (p < 0.001). Curative interventions were more commonly intended (45% vs 37%, p < 0.001) and performed (40% vs 31%, p < 0.001) in the cirrhotic vs non-cirrhotic patients. Median survival was 19 months (95% confidence interval (CI) = 18-21 months), in patients with cirrhosis as compared to 13 months in non-cirrhotic patients (95% CI = 11-15) (p < 0.001). In the multivariable Cox regression model, cirrhosis was not an independent predictor of survival, neither among curatively nor palliatively treated patients. CONCLUSION: These population-based data show that patients with HCC in a cirrhotic liver receive curative treatment to a greater extent and benefit from superior survival compared to those with HCC in a non-cirrhotic liver. The differences in survival are more attributable to patient and tumor characteristics rather than the cirrhotic status itself. CLINICAL TRIAL REGISTRATION: not applicable. Patient confidentially: not applicable.

Comparing the accuracy of prediction models to detect clinically relevant post-hepatectomy liver failure early after major hepatectomy.

BACKGROUND: Arterial lactate measurements were recently suggested as an early predictor of clinically relevant post-hepatectomy liver failure (PHLF). This needed to be evaluated in the subgroup of major hepatectomies only. METHOD: This observational cohort study included consecutive elective major hepatectomies at Karolinska University Hospital from 2010 to 2018. Clinical risk factors for PHLF, perioperative arterial lactate measurements and routine lab values were included in uni- and multivariable regression analysis. Receiver operating characteristics and risk cut-offs were calculated. RESULTS: In total, 649 patients constituted the study cohort, of which 92 developed PHLF grade B/C according to the International Study Group of Liver Surgery (ISGLS). Lactate reached significantly higher intra- and postoperative levels in PHLF grades B and C compared to grade A or no liver failure (all P < 0.002). Lactate on postoperative day (POD) 1 was superior to earlier measurement time points in predicting PHLF B/C (AUC 0.75), but was outperformed by both clinical risk factors (AUC 0.81, P = 0.031) and bilirubin POD1 (AUC 0.83, P = 0.013). A multivariable logistic regression model including clinical risk factors and bilirubin POD1 had the highest AUC of 0.87 (P = 0.006), with 56.6% sensitivity and 94.7% specificity for PHLF grade B/C (cut-off ≥0.32). The model identified 46.7% of patients with 90-day mortality and had an equally good discriminatory potential for mortality as the established ISGLS criteria for PHLF grade B/C but could be applied already on POD1. CONCLUSION: The potential of lactate to predict PHLF following major hepatectomy was inferior to a prediction model consisting of clinical risk factors and bilirubin on first post-operative day.

Histopathological growth patterns and tumor-infiltrating lymphocytes in breast cancer liver metastases.

Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP'). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0.001). 'Pure r-HGP' predicts worse PFS (HR: 2.65; CI: (1.45-4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29-7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'. These findings suggest that HGP could be considered to refine treatment approaches.

An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver.

A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFRhigh stroma at the liver edge to FAPhigh stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.

Risk Factors, Management, and Outcome of Gastric Venous Congestion After Total Pancreatectomy: An Underestimated Complication Requiring Standardized Identification, Grading, and Management.

BACKGROUND: Gastric venous congestion (GVC) after total pancreatectomy (TP) is rarely studied despite its high 5% to 28% incidence and possible association with mortality. This study aimed to provide insight about incidence, risk factors, management, and outcome of GVC after TP. METHODS: This retrospective observational single-center study included all patients undergoing elective TP from 2008 to 2021. The exclusion criteria ruled out a history of gastric resection, concomitant (sub)total gastrectomy for oncologic indication(s) or celiac axis resection, and postoperative (sub)total gastrectomy for indication(s) other than GVC. RESULTS: The study enrolled 268 patients. The in-hospital major morbidity (Clavien-Dindo grade ≥IIIa) rate was 28%, and the 90-day mortality rate was 3%. GVC was identified in 21% of patients, particularly occurring during index surgery (93%). Intraoperative GVC was managed with (sub)total gastrectomy for 55% of the patients. The major morbidity rate was higher for the patients with GVC (44% vs 24%; p = 0.003), whereas the 90-day mortality did not differ significantly (5% vs 3%; p = 0.406). The predictors for major morbidity were intraoperative GVC (odds ratio [OR], 2.207; 95% confidence interval [CI], 1.142-4.268) and high TP volume (> 20 TPs/year: OR, 0.360; 95% CI, 0.175-0.738). The predictors for GVC were portomesenteric venous resection (PVR) (OR, 2.103; 95% CI, 1.034-4.278) and left coronary vein ligation (OR, 11.858; 95% CI, 5.772-24.362). CONCLUSIONS: After TP, GVC is rather common (in 1 of 5 patients). GVC during index surgery is predictive for major morbidity, although not translating into higher mortality. Left coronary vein ligation and PVR are predictive for GVC, requiring vigilance during and after surgery, although gastric resection is not always necessary. More evidence on prevention, identification, classification, and management of GVC is needed.

A prospective multicentre trial on survival after Microwave Ablation VErsus Resection for Resectable Colorectal liver metastases (MAVERRIC).

AIM: This multi-centre prospective cohort study aimed to investigate non-inferiority in patients' overall survival when treating potentially resectable colorectal cancer liver metastasis (CRLM) with stereotactic microwave ablation (SMWA) as opposed to hepatic resection (HR). METHODS: Patients with no more than 5 CRLM no larger than 30 mm, deemed eligible for both SMWA and hepatic resection at the local multidisciplinary team meetings, were deliberately treated with SMWA (study group). The contemporary control group consisted of patients with no more than 5 CRLM, none larger than 30 mm, treated with HR, extracted from a prospectively maintained nationwide Swedish database. After propensity-score matching, 3-year overall survival (OS) was compared as the primary outcome using Kaplan-Meier and Cox regression analyses. RESULTS: All patients in the study group (n = 98) were matched to 158 patients from the control group (mean standardised difference in baseline covariates = 0.077). OS rates at 3 years were 78% (Confidence interval [CI] 68-85%) after SMWA versus 76% (CI 69-82%) after HR (stratified Log-rank test p = 0.861). Estimated 5-year OS rates were 56% (CI 45-66%) versus 58% (CI 50-66%). The adjusted hazard ratio for treatment type was 1.020 (CI 0.689-1.510). Overall and major complications were lower after SMWA (percentage decrease 67% and 80%, p < 0.01). Hepatic retreatments were more frequent after SMWA (percentage increase 78%, p < 0.01). CONCLUSION: SMWA is a valid curative-intent treatment alternative to surgical resection for small resectable CRLM. It represents an attractive option in terms of treatment-related morbidity with potentially wider options regarding hepatic retreatments over the future course of disease.

The Resection Rate of Synchronously Detected Liver and Lung Metastasis from Colorectal Cancer Is Low-A National Registry-Based Study.

Population-based data on the incidence and surgical treatment of patients with colorectal cancer (CRC) and synchronous liver and lung metastases are lacking as are real-life data on the frequency of metastasectomy for both sites and outcomes in this setting. This is a nationwide population-based study of all patients having liver and lung metastases diagnosed within 6 months of CRC between 2008 and 2016 in Sweden identified through the merging of data from the National Quality Registries on CRC, liver and thoracic surgery and the National Patient Registry. Among 60,734 patients diagnosed with CRC, 1923 (3.2%) had synchronous liver and lung metastases, of which 44 patients had complete metastasectomy. Surgery of liver and lung metastases yielded a 5-year OS of 74% (95% CI 57-85%) compared to 29% (95% CI 19-40%) if liver metastases were resected but not the lung metastases and 2.6% (95% CI 1.5-4%) if non-resected, p < 0.001. Complete resection rates ranged from 0.7% to 3.8% between the six healthcare regions of Sweden, p = 0.007. Synchronous liver and lung CRC metastases are rare, and a minority undergo the resection of both metastatic sites but with excellent survival. The reasons for differences in regional treatment approaches and the potential of increased resection rates should be studied further.

Ablation versus resection for resectable colorectal liver metastases - Health care related cost and survival analyses from a quasi-randomised study.

BACKGROUND: The aim of this study was to compare healthcare related costs and survival in patients treated with microwave ablation (MWA) versus surgical resection for resectable colorectal liver metastases (CRLM), in patients from a quasi-randomised setting. METHODS: The Swedish subset of data from a prospective multi-centre study investigating survival after percutaneous computer-assisted Microwave Ablation VErsus Resection for Resectable CRLM (MAVERRIC study) was analysed. Patients with CRLM ≤ 3 cm amenable to ablation and resection were considered for study inclusion only on even calendar weeks, while treated with gold standard resection every other week, creating a quasi-randomised setting. Survival and costs (all inpatient hospital admissions, outpatient visits, oncological treatments and radiological imaging) in the 2 years following treatment were investigated. RESULTS: MWA (n = 52) and resection (n = 53) cohorts had similar baseline patient and tumour characteristics and health care consumption within 1 year prior to CRLM treatment. Treatment related morbidity and length of stay were significantly higher in the resected cohort. Overall health care related costs from decision of treatment and 2 years thereafter were lower in the MWA versus resection cohort (mean ± SD USD 80'964±59'182 versus 110'059±59'671, P < 0.01). Five-year overall survival was 50% versus 54% in MWA versus resection groups (P = 0.95). CONCLUSIONS: MWA is associated with decreased morbidity, time spent in medical facilities and healthcare related costs within 2 years of initial treatment with equal overall survival, highlighting its benefits for patient and health care systems.

Molecular adsorbent recirculating system treatment in patients with post-hepatectomy liver failure: Long-term results of a pilot study.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the leading cause of postoperative mortality following major liver resection. Between December 2012 and May 2015, 10 consecutive patients with PHLF (according to the Balzan criteria) following major/extended hepatectomy were included in a prospective treatment study with the molecular adsorbent recirculating system (MARS). Sixty- and 90-day mortality rates were 0% and 10%, respectively. Of the nine survivors, four still had liver dysfunction at 90 days postoperatively. One-year overall survival (OS) of the MARS-PHLF cohort was 50%. The present study aims to assess long-term outcome of this cohort compared to a historical control cohort. METHODS: To compare long-term outcome of the MARS-PHLF treatment cohort with PHLF patients not treated with MARS, the present study includes all 655 patients who underwent major hepatectomy at Karolinska University Hospital between 2010 and 2018. Patients with PHLF were identified according to the Balzan criteria. RESULTS: The cohort was split into three time periods: pre-MARS period (n = 192), MARS study period (n = 207), and post-MARS period (n = 256). The 90-day mortality of patients with PHLF was 55% (6/11) in the pre-MARS period, 14% during the MARS study period (2/14), and 50% (3/6) in the post-MARS period (p = 0.084). Median OS (95% confidence interval (CI)) was 37.8 months (29.3-51.7) in the pre-MARS cohort, 57 months (40.7-75.6) in the MARS cohort, and 38.8 months (31.4-51.2) in the post-MARS cohort. The 5-year OS of 10 patients included in the MARS study was 40% and the median survival 11.6 months (95% CI: 3 to not releasable). In contrast, for the remaining 21 patients fulfilling the Balzan criteria during the study period but not treated with MARS, the 5-year OS and median survival were 9.5% and 7.3 months (95% CI, 0.5-25.9), respectively (p = 0.138)). CONCLUSIONS: MARS treatment may contribute to improved outcome of patients with PHLF. Further studies are needed.The initial pilot study was registered at ClinicalTrials.gov (NCT03011424).

Impact of post-hepatectomy liver failure on morbidity and short- and long-term survival after major hepatectomy.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is one of the most serious postoperative complications after hepatectomy. The aim of this study was to assess the impact of the International Study Group of Liver Surgery (ISGLS) definition of PHLF on morbidity and short- and long-term survival after major hepatectomy. METHODS: This was a retrospective review of all patients who underwent major hepatectomy (three or more liver segments) for various liver tumours between 2010 and 2018 at two Swedish tertiary centres for hepatopancreatobiliary surgery. Descriptive statistics, regression models, and survival analyses were used. RESULTS: A total of 799 patients underwent major hepatectomy, of which 218 patients (27 per cent) developed ISGLS-defined PHLF, including 115 patients (14 per cent) with ISGLS grade A, 76 patients (10 per cent) with grade B, and 27 patients (3 per cent) with grade C. The presence of cirrhosis, perihilar cholangiocarcinoma, and gallbladder cancer, right-sided hemihepatectomy and trisectionectomy all significantly increased the risk of clinically relevant PHLF (grades B and C). Clinically relevant PHLF increased the risk of 90-day mortality and was associated with impaired long-term survival. ISGLS grade A had more major postoperative complications compared with no PHLF but failed to be an independent predictor of both 90-day mortality and long-term survival. The impact of PHLF grade B/C on long-term survival was no longer present in patients surviving the first 90 days after surgery. CONCLUSIONS: The presently used ISGLS definition for PHLF should be reconsidered regarding mortality as only PHLF grade B/C was associated with a negative impact on short-term survival; however, even ISGLS grade A had clinical implications.

Treatment intention and outcome in patients with simultaneously diagnosed liver and lung metastases from colorectal cancer.

BACKGROUND: The aim was to assess the likelihood of patients with simultaneously diagnosed liver and lung metastases (SLLM) from colorectal cancer (CRC) to receive the curative treatment decided upon multidisciplinary team meeting (MDT) and to elaborate on the reasons for treatment intention failure and survival outcomes depending on final treatment strategy. METHOD: The study included a retrospective review of all patients discussed at the MDT at a single centre between 2010 and 2018 to identify all patients presenting with SLLM from CRC. Treatment intention, actual treatment outcome and reasons for treatment failure was documented. Descriptive and survival statistics were applied. RESULTS: Of the 160 patients who had SLLM, resection of all metastatic sites was deemed possible in 107 patients (67%) of whom 39 patients (36%) finalized the curative treatment plan. The most common reason for noncompliance with management recommendations was disease progression or recurrence. Complete resection resulted in longer survival compared to patients who did not undergo resection of all metastatic sites with median survival of 63 and 27 months, respectively (p < 0.001). CONCLUSION: A low proportion of patients completed the initially intended curative resections. Simultaneous resection of liver/lung metastases and primary tumour might increase the proportion of fulfilled hepatopulmonary resections.

Prognostic impact of para-aortic lymph node status in resected pancreatic ductal adenocarcinoma and invasive intraductal papillary mucinous neoplasm - Time to consider a reclassification?

BACKGROUND: Para-aortic lymph node (PALN) metastases in pancreatic ductal adenocarcinoma (PDAC) correlates with poor prognosis. The role of PALN in invasive intraductal papillary mucinous neoplasms (inv-IPMN) has not been well explored. The present study investigated the rate of metastatic PALN, lymph node ratio (LNR) and the overall nodal (N) status as prognostic factors in PDAC and inv-IPMN. METHODS: This consecutive single-center series included patients with PDAC or inv-IPMN in the pancreatic head who underwent pancreatoduodenectomy or total pancreatectomy, including PALN resection between 2009 and 2018. Median overall survival (mOS) and impact of clinicopathological factors, including PALN status on survival, were evaluated. RESULTS: 403 patients were included, 314 had PDAC and 89 inv-IPMN. PALN were metastatic in 16% of PDAC and 17% of inv-IPMN. N0 status was present in 6% of the patients with PDAC and 16% of inv-IPMN patients (p = 0.007). LNR >15% was more common in PDAC (52%) than in inv-IPMN (34%) (p = 0.004). mOS was 12.7 months in the presence of PALN metastases and 22.7 months without (p < 0.0001). Age >70 years, CA19-9 >200 U/mL, PDAC and N2 status were significantly associated with worse survival in a multivariable analysis. PALN status and LNR were not independent prognostic factors. In N2 status mOS was similar regardless the presence of PALN metastases. CONCLUSION: The frequency of PALN metastases was similar in PDAC and inv-IPMN. Although PALN positive status entailed a shorter mOS, it was not an independent risk factor for death, and did not influence survival in N2-staged disease. The M1-status for PALN positivity may need reconsideration.

3D Quantitative Ablation Margins for Prediction of Ablation Site Recurrence After Stereotactic Image-Guided Microwave Ablation of Colorectal Liver Metastases: A Multicenter Study.

BACKGROUND: Three-dimensional (3D) volumetric ablation margin assessment after thermal ablation of liver tumors using software has been described, but its predictive value on treatment efficacy when accounting for other factors known to correlate ablation site recurrence (ASR) remains unknown. PURPOSE: To investigate 3D quantitative ablation margins (3D-QAMs) as an algorithm to predict ASR within 1 year after stereotactic microwave ablation (SMWA) for colorectal liver metastases (CRLM). MATERIALS AND METHODS: Sixty-five tumors in 47 patients from a prospective multicenter study of patients undergoing SMWA for CRLM were included in this retrospective 3D-QAM analysis. Using a previously developed algorithm, 3D-QAM defined as the distribution of tumor to ablation surface distances was assessed in co-registered pre- and post-ablation CT scans. The discriminatory power and optimal cutoff values for 3D-QAM were assessed using receiver operating characteristic (ROC) curves. Multivariable logistic regression analysis using generalized estimating equations was applied to investigate the impact of various 3D-QAM outputs on 1-year ASR while accounting for other known influencing factors. RESULTS: Ten of the 65 (15.4%) tumors included for 3D-QAM analysis developed ASR. ROC analyses identified i) 3D-QAM <1 mm for >23% of the tumor surface, ii) 3D-QAM <5 mm for >45%, and iii) the minimal ablation margin (MAM) as the 3D-QAM outputs with optimal discriminatory qualities. The multivariable regression model without 3D-QAM yielded tumor diameter and KRAS mutation as 1-year ASR predictors. When adding 3D-QAM, this factor became the main predictor of 1-year ASR [odds ratio (OR) 21.67 (CI 2.48, 165.21) if defined as >23% <1 mm; OR 0.52 (CI 0.29, 0.95) if defined as MAM]. CONCLUSIONS: 3D-QAM allows objectifiable and standardized assessment of tumor coverage by the ablation zone after SMWA. Our data shows that 3D-QAM represents the most important factor predicting ASR within 1 year after SMWA of CRLM.

Stereotactic and Robotic Minimally Invasive Thermal Ablation of Malignant Liver Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Stereotactic navigation techniques aim to enhance treatment precision and safety in minimally invasive thermal ablation of liver tumors. We qualitatively reviewed and quantitatively summarized the available literature on procedural and clinical outcomes after stereotactic navigated ablation of malignant liver tumors. METHODS: A systematic literature search was performed on procedural and clinical outcomes when using stereotactic or robotic navigation for laparoscopic or percutaneous thermal ablation. The online databases Medline, Embase, and Cochrane Library were searched. Endpoints included targeting accuracy, procedural efficiency, and treatment efficacy outcomes. Meta-analysis including subgroup analyses was performed. RESULTS: Thirty-four studies (two randomized controlled trials, three prospective cohort studies, 29 case series) were qualitatively analyzed, and 22 studies were included for meta-analysis. Weighted average lateral targeting error was 3.7 mm (CI 3.2, 4.2), with all four comparative studies showing enhanced targeting accuracy compared to free-hand targeting. Weighted average overall complications, major complications, and mortality were 11.4% (6.7, 16.1), 3.4% (2.1, 5.1), and 0.8% (0.5, 1.3). Pooled estimates of primary technique efficacy were 94% (89, 97) if assessed at 1-6 weeks and 90% (87, 93) if assessed at 6-12 weeks post ablation, with remaining between-study heterogeneity. Primary technique efficacy was significantly enhanced in stereotactic vs. free-hand targeting, with odds ratio (OR) of 1.9 (1.2, 3.2) (n = 6 studies). CONCLUSIONS: Advances in stereotactic navigation technologies allow highly precise and safe tumor targeting, leading to enhanced primary treatment efficacy. The use of varying definitions and terminology of safety and efficacy limits comparability among studies, highlighting the crucial need for further standardization of follow-up definitions.

Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma.

Neutrophil extracellular traps (NETs) are web-like structures consisting of DNA, histones and granule proteins, released from neutrophils in thrombus formation, inflammation, and cancer. We asked if plasma levels of the NET markers myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit)-DNA, are elevated in liver cirrhosis and hepatocellular carcinoma (HCC) and if the levels correlate with clinical parameters. MPO-DNA, H3Cit-DNA, and thrombin-antithrombin (TAT) complex, as a marker of coagulation activity, were measured using ELISA in plasma from 82 patients with HCC, 95 patients with cirrhosis and 50 healthy controls. Correlations were made to clinical parameters and laboratory data and patients were followed for a median of 22.5 months regarding thrombosis development. H3Cit-DNA was significantly (p < 0.01) elevated in plasma from cirrhosis (66.4 ng/mL) and HCC (63.8 ng/mL) patients compared to healthy controls (31.8 ng/mL). TAT levels showed similar pattern (3.1, 3.7, and 0.0 µg/mL respectively, p < 0.01). MPO-DNA was significantly (p < 0.01) elevated in cirrhosis patients (0.53 O.D.) as compared to controls (0.33 O.D.). Levels of MPO-DNA and H3Cit-DNA correlated positively with Child-Pugh and MELD score. TAT was increased in all Child-Pugh and MELD groups. In multivariable logistic regression, Child B and C liver cirrhosis were independent predictors of elevated H3Cit-DNA in plasma. Levels of MPO-DNA and H3Cit-DNA were similar in patients with or without history of thrombosis, or thrombus formation during follow-up. In conclusion, plasma markers of NET formation are elevated in liver cirrhosis and correlate to the degree of liver dysfunction in patients with liver cirrhosis and/or HCC. The presence of HCC did not further increase the plasma levels of NET markers as compared to patients with cirrhosis only.