Change in tissue resistance after irreversible electroporation in liver tumors as an indicator of treatment success - A multi-center analysis with long term follow-up.

INTRODUCTION: A nationwide multicenter study was performed to examine whether there is a correlation between decrease in tissue resistance and time to local tumor recurrence after irreversible electroporation (IRE) in patients with hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). METHODS: All patients treated with IRE for liver tumors in Sweden from 2011 until 2018 were included. Patient characteristics and recurrence patterns were obtained from medical records and radiological imaging. All procedural data from the IRE hardware at the three hospitals performing IRE were retrieved. The resistance during each pulse and the change during each treatment were calculated. The electrode pair with the smallest decrease in tissue resistance was used and compared with the time to LTP. RESULTS: 149 patients with 206 tumors were treated. Exclusion due to missing and inaccurate data resulted in 124 patients with 170 tumors for the analyses. In a multivariable Cox regression model, a smaller decrease in tissue resistance and larger tumor size were associated with shorter time to local tumor recurrence for CRCLM, but not for HCC. CONCLUSION: There was an association between a decrease in tissue resistance and time to local tumor recurrence for CRCLM. The decrease in resistance, in combination with a rise in current, may be the parameters the interventionist should use during IRE to decide if the treatment is successful.

Irreversible electroporation of hepatocellular carcinoma and colorectal cancer liver metastases: A nationwide multicenter study with short- and long-term follow-up.

INTRODUCTION: A nationwide multicenter study was performed to examine short- and long-term effects of irreversible electroporation (IRE) for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). IRE is an alternative method when thermal ablation is contraindicated because of risk for serious thermal complications. METHODS: All consecutive patients in Sweden treated with IRE because of HCC or CRCLM, were included between 2011 and 2018. We evaluated medical records and radiological imaging to obtain information regarding patient-, tumor-, and treatment characteristics. We also assessed local tumor progression, and survival. RESULTS: In total 206 tumors in 149 patients were treated with IRE. Eighty-seven patients (58.4%) had colorectal cancer liver metastases, and 62 patients (41.6%) had hepatocellular carcinoma. Median tumor size was 20 mm (i.q.r. 14-26 mm). Median overall survival for CRCLM and HCC, were 27.0 months (95% CI 22.2-31.8 months), and 35.0 months (95% CI 13.8-56.2 months), respectively. Median follow-up time was 58 months (95% CI 50.6-65.4). Local ablation success at six and twelve months for HCC was 58.3% and 40.3%, and for CRCLM 37.7% and 25.4%. The median time to local tumor progression (LTP) for HCC was 21.0 months (95% CI: 9.5-32.5 months), and for CRCLM 6.0 months (95% CI: 4.5-7.5 months). At 30-day follow-up, 15.4% (n = 23) of patients suffered from a complication rated as Clavien-Dindo grade 1-3a. Three patients (2.0%) had grade 3b-5 with one death in a thromboembolic event. CONCLUSION: IRE is a safe ablation modality for patients with liver tumors that are located in such a way that other treatment options are unsuitable.

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.

Quantitative assessment of atelectasis formation under high frequency jet ventilation during liver tumour ablation-A computer tomography study.

BACKGROUND: High frequency jet ventilation (HFJV) can be used to minimise sub-diaphragmal organ displacements. Treated patients are in a supine position, under general anaesthesia and fully muscle relaxed. These are factors that are known to contribute to the formation of atelectasis. The HFJV-catheter is inserted freely inside the endotracheal tube and the system is therefore open to atmospheric pressure. AIM: The aim of this study was to assess the formation of atelectasis over time during HFJV in patients undergoing liver tumour ablation under general anaesthesia. METHOD: In this observational study twenty-five patients were studied. Repeated computed tomography (CT) scans were taken at the start of HFJV and every 15 minutes thereafter up until 45 minutes. From the CT images, four lung compartments were defined: hyperinflated, normoinflated, poorly inflated and atelectatic areas. The extension of each lung compartment was expressed as a percentage of the total lung area. RESULT: Atelectasis at 30 minutes, 7.9% (SD 3.5, p = 0.002) and at 45 minutes 8,1% (SD 5.2, p = 0.024), was significantly higher compared to baseline 5.6% (SD 2.5). The amount of normoinflated lung volumes were unchanged over the period studied. Only a few minor perioperative respiratory adverse events were noted. CONCLUSION: Atelectasis during HFJV in stereotactic liver tumour ablation increased over the first 45 minutes but tended to stabilise with no impact on normoinflated lung volume. Using HFJV during stereotactic liver ablation is safe regarding formation of atelectasis.

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.

Volumetric analyses of ablation dimensions in microwave ablation for colorectal liver metastases.

BACKGROUND: In thermal ablation of malignant liver tumors, ablation dimensions remain poorly predictable. This study aimed to investigate factors influencing volumetric ablation dimensions in patients treated with stereotactic microwave ablation (SMWA) for colorectal liver metastases (CRLM). METHODS: Ablation volumes from CRLM ≤3 cm treated with SMWA within a prospective European multicentre trial were segmented. Correlations between applied ablation energies and resulting effective ablation volumes (EAV) and ablation volume irregularities (AVI) were investigated. A novel measure for AVI, including minimum enclosing and maximum inscribed ellipsoid ablation volumes, and a surrogate parameter for the expansion of ablation energy (EAV per applied energy), was introduced. Potential influences of tumor and patient-specific factors on EAV per applied energy and AVI were analyzed using multivariable mixed-effects models. RESULTS: A total of 116 ablations from 71 patients were included for analyses. Correlations of EAV or AVI and ablation energy were weak to moderate, with a maximum of 25% of the variability in EAV and 13% in AVI explained by the applied ablation energy. On multivariable analysis, ablation expansion (EAV per applied ablation energy) was influenced mainly by the tumor radius (B = -0.03, [CI -0.04, -0.007]). AVI was significantly larger with higher applied ablation energies (B = 0.002 [CI 0.0007, 0.002]]); liver steatosis, KRAS mutation, subcapsular location or proximity to major blood vessels had no influence. CONCLUSIONS: This study confirmed that factors beyond the applied ablation energy might affect volumetric ablation dimensions, resulting in poor predictability. Further clinical trials including tissue sampling are needed to relate physical tissue properties to ablation expansion.

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.

Association of Manganese Biomarker Concentrations with Blood Pressure and Kidney Parameters among Healthy Adolescents: NHANES 2013-2018.

Deficiency or excess exposure to manganese (Mn), an essential mineral, may have potentially adverse health effects. The kidneys are a major organ of Mn site-specific toxicity because of their unique role in filtration, metabolism, and excretion of xenobiotics. We hypothesized that Mn concentrations were associated with poorer blood pressure (BP) and kidney parameters such as estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and albumin creatinine ratio (ACR). We conducted a cross-sectional analysis of 1931 healthy U.S. adolescents aged 12-19 years participating in National Health and Nutrition Examination Survey cycles 2013-2014, 2015-2016, and 2017-2018. Blood and urine Mn concentrations were measured using inductively coupled plasma mass spectrometry. Systolic and diastolic BP were calculated as the average of available readings. eGFR was calculated from serum creatinine using the Bedside Schwartz equation. We performed multiple linear regression, adjusting for age, sex, body mass index, race/ethnicity, and poverty income ratio. We observed null relationships between blood Mn concentrations with eGFR, ACR, BUN, and BP. In a subset of 691 participants, we observed that a 10-fold increase in urine Mn was associated with a 16.4 mL/min higher eGFR (95% Confidence Interval: 11.1, 21.7). These exploratory findings should be interpreted cautiously and warrant investigation in longitudinal studies.

Stereotactic navigation versus ultrasound guidance in placing IRE applicators in a liver phantom.

The aim of this study was to compare the accuracy of stereotactic CT-guided navigation and ultrasound guided navigation for placing electrodes in Irreversible electroporation in a liver phantom. A liver phantom with multiple tumours was used and interventionists placed four IRE electrodes around each tumour guided either by stereotactic CT-guided navigation or ultrasound. The goal was to place them in a perfect 20 × 20 mm square with parallel electrodes. After each treatment, a CT-scan was performed. The accuracy in pairwise electrode distance, pairwise parallelism and time per tumour was analysed. Eight interventionists placed four electrodes around 55 tumours, 25 with ultrasound and 30 with stereotactic CT-guided navigation. 330 electrode pairs were analysed, 150 with ultrasound and 180 with stereotactic CT-navigation. The absolute median deviation from the optimal distance was 1.3 mm (range 0.0 to 11.3 mm) in the stereotactic CT-navigation group versus 7.1 mm (range 0.3 to 18.1 mm) in the Ultrasound group (p < 0.001). The mean angle between electrodes in each pair was 2.7 degrees (95% CI 2.4 to 3.1 degrees) in the stereotactic CT-navigation group and 5.5 degrees (95% CI 5.0 to 6.1 degrees) in the Ultrasound group (p < 0.001). The mean time for placing the electrodes was 15:11 min (95% CI 13:05 to 17:18 min) in the stereotactic CT-navigation group and 6:40 min (95% CI 5:28 to 7:52 min) in the Ultrasound group. The use of stereotactic CT-navigation in placing IRE-electrodes in a liver phantom is more accurate, but more time consuming, compared to ultrasound guidance.

Newborn Pulse Oximetry for Infants Born Out-of-Hospital.

BACKGROUND AND OBJECTIVES: Conventional timing of newborn pulse oximetry screening is not ideal for infants born out-of-hospital. We implemented a newborn pulse oximetry screen to align with typical midwifery care and measure its efficacy at detecting critical congenital heart disease. METHODS: Cohort study of expectant mothers and infants mainly from the Amish and Mennonite (Plain) communities with limited prenatal ultrasound use. Newborns were screened at 1 to 4 hours of life ("early screen") and 24 to 48 hours of life ("late screen"). Newborns were followed up to 6 weeks after delivery to report outcomes. Early screen, late screen, and combined results were analyzed on the basis of strict algorithm interpretation ("algorithm") and the midwife's interpretation in the field ("field") because these did not correspond in all cases. RESULTS: Pulse oximetry screening in 3019 newborns (85% Plain; 50% male; 43% with a prenatal ultrasound) detected critical congenital heart disease in 3 infants. Sensitivity of combined early and late screen was 66.7% (95% confidence interval [CI] 9.4% to 99.2%) for algorithm interpretation and 100% (95% CI 29.2% to 100%) for field interpretation. Positive predictive value was similar for the field interpretation (8.8%; 95% CI 1.9% to 23.7%) and algorithm interpretation (5.4%; 95% CI 0.7% to 18.2%). False-positive rates were ≤1.2% for both algorithm and field interpretations. Other pathologies (noncritical congenital heart disease, pulmonary issues, or infection) were reported in 12 of the false-positive cases. CONCLUSIONS: Newborn pulse oximetry can be adapted to the out-of-hospital setting without compromising sensitivity or prohibitively increasing false-positive rates.

Post-operative hypertension during early recovery following liver tumour ablation: A retrospective study.

BACKGROUND: High-frequency jet ventilation is necessary to reduce organ movements during stereotactic liver ablation. However, post-operative hypertensive episodes especially following irreversible electroporation ablation compared with microwave ablation initiated this study. The hypothesis was that hypertensive episodes could be related to ventilation or ablation method. METHODS: The aim of this retrospective study was to assess the proportion of patients with hypertensive events during recovery following liver ablation under general anaesthesia and to analyse the relation to ventilation and ablation technique. A medical chart review of 134 patients undergoing either high-frequency jet ventilation and microwave ablation (n = 45), high-frequency jet ventilation and irreversible electroporation (n = 44), or conventional ventilation and microwave ablation (n = 45) was performed. The proportion of patients with at least one episode of systolic arterial pressure 140-160, 160-180 or >180 mmHg during early recovery and the impact of ventilation method was studied. RESULTS: Out of 134 patients, 100, 75 and 34 patients had at least one episode of mild, moderate and severe hypertension. Microwave ablation, as well as high frequency jet ventilation, was associated with an increased odds ratio for post-operative hypertension. The proportion of patients with at least one severe hypertensive event was 18/45, 9/44 and 7/45, respectively. CONCLUSION: Both ventilation and ablation technique had an impact on post-operative hypertensive episodes. The microwave ablation/high-frequency jet ventilation combination increased the risk as compared with irreversible electroporation/high-frequency jet ventilation and microwave ablation/conventional ventilation.

Volumetric Quantitative Ablation Margins for Assessment of Ablation Completeness in Thermal Ablation of Liver Tumors.

BACKGROUND: In thermal ablation of liver tumors, complete coverage of the tumor volume by the ablation volume with a sufficient ablation margin is the most important factor for treatment success. Evaluation of ablation completeness is commonly performed by visual inspection in 2D and is prone to inter-reader variability. This work aimed to introduce a standardized approach for evaluation of ablation completeness after CT-guided thermal ablation of liver tumors, using volumetric quantitative ablation margins (QAM). METHODS: A QAM computation metric based on volumetric segmentations of tumor and ablation areas and signed Euclidean surface distance maps was developed, including a novel algorithm to address QAM computation in subcapsular tumors. The code for QAM computation was verified in artificial examples of tumor and ablation spheres simulating varying scenarios of ablation margins. The applicability of the QAM metric was investigated in representative cases extracted from a prospective database of colorectal liver metastases (CRLM) treated with stereotactic microwave ablation (SMWA). RESULTS: Applicability of the proposed QAM metric was confirmed in artificial and clinical example cases. Numerical and visual options of data presentation displaying substrata of QAM distributions were proposed. For subcapsular tumors, the underestimation of tumor coverage by the ablation volume when applying an unadjusted QAM method was confirmed, supporting the benefits of using the proposed algorithm for QAM computation in these cases. The computational code for developed QAM was made publicly available, encouraging the use of a standard and objective metric in reporting ablation completeness and margins. CONCLUSION: The proposed volumetric approach for QAM computation including a novel algorithm to address subcapsular liver tumors enables precision and reproducibility in the assessment of ablation margins. The quantitative feedback on ablation completeness opens possibilities for intra-operative decision making and for refined analyses on predictability and consistency of local tumor control after thermal ablation of liver tumors.

Accuracy of Electrode Placement in IRE Treatment with Navigated Guidance.

PURPOSE: Evaluate the accuracy of multiple electrode placements in IRE treatment of liver tumours using a stereotactic CT-based navigation system. METHOD: Analysing data from all IRE treatments of liver tumours at one institution until 31 December 2018. Comparing planned with validated electrode placement. Analysing lateral and angular errors and parallelism between electrode pairs RESULTS: Eighty-four tumours were treated in 60 patients. Forty-six per cent were hepatocellular carcinoma, and 36% were colorectal liver metastases. The tumours were located in all segments of the liver. Data were complete from 51 treatments. Two hundred and six electrodes and 336 electrode pairs were analysed. The median lateral and angular error, comparing planned and validated electrode placement, was 3.6 mm (range 0.2-13.6 mm) and 3.1° (range 0°-16.1°). All electrodes with a lateral error >10 mm were either re-positioned or excluded before treatment. The median angle between the electrode pairs was 3.8° (range 0.3°-17.2°). There were no electrode placement-related complications. CONCLUSION: The use of a stereotactic CT-based system for navigation of electrode placement in IRE treatment of liver tumours is safe, accurate and user friendly.

Microwave ablation versus resection for colorectal cancer liver metastases - A propensity score analysis from a population-based nationwide registry.

INTRODUCTION: Many previous studies comparing liver resection versus thermal ablation for colorectal cancer liver metastases (CRCLM) are subject to severe selection bias. The aim of this study was to compare survival after microwave ablation (MWA) versus liver resection for CRCLM in a population-based cohort study using propensity score analysis to reduce confounding by indication. METHODS: All patients undergoing liver resection or MWA as a first intervention for CRCLM measuring ≤ 3 cm between 2013 and 2016 in Sweden were included from a nationwide registry. Treatment effect was estimated after propensity score matching, adjusting for patient and tumour factors known to affect the choice of treatment approach. Descriptive, regression and survival statistics were applied. RESULTS: The unmatched cohorts (82 MWA patients, 645 resection patients) differed significantly regarding age, American Society of Anaesthesiologists class, Charlson comorbidity index, primary tumour location, number of metastases and previous chemotherapy, with 3-year overall survival (OS) favouring resection over MWA (76 and 69%, p = 0.005). After propensity score matching (70 MWA patients, 201 resection patients), no difference in 3-year OS was shown between resected and ablated patients (76% and 76%, p = 0.253), with a median OS of 54.7 (95% confidence interval 48.6 - 60.9) months and 48 (40.1-56.1) months, respectively. CONCLUSION: After adjusting for factors known to affect treatment choice, no significant difference in OS was shown after MWA versus resection for CRCLM. This supports the potential role of MWA as a valid first-line treatment for patients with small CRCLM.

Synchronous and metachronous liver metastases in patients with colorectal cancer-towards a clinically relevant definition.

BACKGROUND: Approximately 25% of patients with colorectal cancer (CRC) will have liver metastases classified as synchronous or metachronous. There is no consensus on the defining time point for synchronous/metachronous, and the prognostic implications thereof remain unclear. The aim of the study was to assess the prognostic value of differential detection at various defining time points in a population-based patient cohort and conduct a literature review of the topic. METHODS: All patients diagnosed with CRC in the counties of Stockholm and Gotland, Sweden, during 2008 were included in the study and followed for 5 years or until death to identify patients diagnosed with liver metastases. Patients with liver metastases were followed from time of diagnosis of liver metastases for at least 5 years or until death. Different time points defining synchronous/metachronous detection, as reported in the literature and identified in a literature search of databases (PubMed, Embase, Cochrane library), were applied to the cohort, and overall survival was calculated using Kaplan-Meier curves and compared with log-rank test. The influence of synchronously or metachronously detected liver metastases on disease-free and overall survival as reported in articles forthcoming from the literature search was also assessed. RESULTS: Liver metastases were diagnosed in 272/1026 patients with CRC (26.5%). No statistically significant difference in overall survival for synchronous vs. metachronous detection at any of the defining time points (CRC diagnosis/surgery and 3, 6 and 12 months post-diagnosis/surgery) was demonstrated for operated or non-operated patients. In the literature search, 41 publications met the inclusion criteria. No clear pattern emerged regarding the prognostic significance of synchronous vs. metachronous detection. CONCLUSION: Synchronous vs. metachronous detection of CRC liver metastases lacks prognostic value. Using primary tumour diagnosis/operation as standardized cut-off point to define synchronous/metachronous detection is semantically correct. In synchronous detection, it defines a clinically relevant group of patients where individualized multimodality treatment protocols will apply.

High Frequency Jet Ventilation during stereotactic ablation of liver tumours: an observational study on blood gas analysis as a measure of lung function during general anaesthesia.

Background: Stereotactic ablation of tumours in solid organs is a promising curative procedure in clinical oncology. The technique demands minimal target organ movements to optimise tumour destruction and prevent injury to surrounding tissues. High frequency jet ventilation (HFJV) is a novel option during these procedures, reducing the respiratory-associated movements of the liver. The effects of HFJV via endotracheal catheter on gas exchange during liver tumour ablation is not well studied. Methods: The aim of this explorative study was to assess lung function and the effects on blood gas and lactate during HFJV in patients undergoing stereotactic liver ablation. Blood gases were analysed in 25 patients scheduled for stereotactic liver ablation under general anaesthesia pre-induction, every 15 minutes during HFJV and following extubation in the recovery room. The HFJV was set at fixed settings. Results: None of the patients developed hypoxia or signs of increased lactate production but a great variation in PaO 2/FiO 2 ratio was found; from 13.1 to 71.3. An increase in mean PaCO 2 was observed, from a baseline of 5.0 to a peak of 7.1 at 30 minutes (p <0.001) and a decrease was found in median pH, from a baseline of 7.44 to 7.31 at 15 minutes (p=0.03). We could not see any clear association between a decrease in PaO 2/FiO 2 ratio and PaCO 2 elevation. Conclusions: HFJV during general anaesthesia in patients undergoing stereotactic liver ablation is feasible and it did not cause hypoxemia or signs of increased lactate production. A reversible mild to moderate impairment of gas exchange was found during HFJV.

Initial experience with irreversible electroporation of liver tumours.

INTRODUCTION: Thermal ablation of liver tumours is an established technique used in selected patients with relatively small tumours that can be ablated with margin. Thermal ablation methods are not advisable near larger bile ducts that are sensitive to thermal injury causing strictures and severe morbidity. Irreversible electroporation (IRE) has the possibility to treat these tumours without harming the bile tree. The method is relatively new and has been proven to be feasible and safe with promising oncological results. METHODS: 50 treatments were performed on 42 patients that were not resectable or treatable by thermal ablation (12 women and 30 men) with 59 tumours in total. 51% were colorectal cancer liver metastases (CRCLM) and 34% were hepatocellular carcinomas (HCC). 70% of the treatments were performed using stereotactic CT-guidance for needle placement. RESULTS: 81% of the treatments were performed with initial success. All patients with missed ablations were re-treated. Local recurrence rate at 3 months was 3% and 37% at one year. The complication rate was low with 2 patients having major complications (Clavien-Dindo grade 3b-5) and without 30-day mortality. CONCLUSION: IRE is safe for treating tumours not suitable for thermal ablation with 63% of patients being without local recurrence after one year in a group of patients with tumours deemed unresectable. IRE has a role in the treatment of unresectable liver tumours close to heat-sensitive structures not suitable for thermal ablation.Level of Evidence: Level 4, Case Series.

Laparoscopic Roux-en-Y Gastric Bypass Without Division of the Mesentery Reduces the Risk of Postoperative Complications.

BACKGROUND: Anastomotic complications after laparoscopic Roux-en-Y gastric bypass (LRYGB) including leaks, ulceration, and stenosis remain a significant cause of post-operative morbidity and mortality. Our objective was to compare two different surgical techniques regarding short-term anastomotic complications. METHODS: A retrospective analysis of all patients operated with a primary LRYGB from 2006 to June 2015 in one institution, where prospectively collected data from an internal quality registry and medical journals were analyzed. RESULTS: In total, 2420 patients were included in the analysis. 1016 were operated with a technique where the mesentery was divided during the creation of the Roux-limb (DM-LRYGB) and 1404 were operated with a method where the mesentery was left intact (IM-LRYGB). Leakage in the first 30 days [2.6% vs. 1.1% (p < 0.05)], and ulceration or stenosis occurring during the first 6 months after surgery [5.6% vs. 0.1% (p < 0.05)] was significantly higher in the DM-LRYGB group. Adjusted odds ratio for anastomotic leak was 0.46 (95% CI 0.24-0.87) and for stenosis/ulceration 0.01 (95% CI 0.002-0.09). CONCLUSION: IM-LRYGB seems to reduce the risk of complications at the anastomosis. A plausible explanation for this is that the blood supply to the anastomosis is compromised when the mesentery is divided.

1000 consecutive ablation sessions in the era of computer assisted image guidance - Lessons learned.

BACKGROUND: Ablation therapies for tumours are becoming more used as ablation modalities evolve and targeting solutions are getting better. There is an increasing body of long-term results challenging resection and proving lower morbidities and costs. The aim of this paper is to share the experiences from a high-volume centre in introducing computer assisted targeting solutions and efficient ablation modalities like microwave generators and irreversible electroporation. MATERIAL AND METHODS: One thousand consecutive treatments in one high-volume centre were evaluated retrospectively from prospectively collected data. RESULTS: The purpose of this paper is to present the benefits of going into computer assisted targeting techniques and microwave technology; pitfalls and overview of outcomes. The main target organ was the liver and the main indications were ablation of hepatocellular carcinomas and colorectal liver metastases. With the assistance of computer assisted targeting the local recurrence rate within 6 months has dropped from 30 to near 10%. The survival of patients with hepatocellular carcinoma and colorectal liver metastases is not worse if the tumour can be retreated after a local recurrence. Multiple colorectal liver metastases can be treated successfully. DISCUSSION: The incorporation of computer assisted targeting technologies for ultrasound-, ct guided- and laparoscopic tumour ablation has been very successful and without a noticeable learning curve. The same is true for switching from radiofrequency energies to microwave generators and irreversible electroporation. CONCLUSION: It is well worthwhile upgrading ablation and targeting technologies to achieve excellent and reproducible results and minimizing operator dependency.