Robotic Versus Laparoscopic Liver Resection in Various Settings: An International Multicenter Propensity Score Matched Study of 10.075 Patients.

OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

Hybrid optical-vision tracking in laparoscopy: accuracy of navigation and ultrasound reconstruction.

INTRODUCTION: The use of laparoscopic and robotic liver surgery is increasing. However, it presents challenges such as limited field of view and organ deformations. Surgeons rely on laparoscopic ultrasound (LUS) for guidance, but mentally correlating ultrasound images with pre-operative volumes can be difficult. In this direction, surgical navigation systems are being developed to assist with intra-operative understanding. One approach is performing intra-operative ultrasound 3D reconstructions. The accuracy of these reconstructions depends on tracking the LUS probe. MATERIAL AND METHODS: This study evaluates the accuracy of LUS probe tracking and ultrasound 3D reconstruction using a hybrid tracking approach. The LUS probe is tracked from laparoscope images, while an optical tracker tracks the laparoscope. The accuracy of hybrid tracking is compared to full optical tracking using a dual-modality tool. Ultrasound 3D reconstruction accuracy is assessed on an abdominal phantom with CT transformed into the optical tracker's coordinate system. RESULTS: Hybrid tracking achieves a tracking error < 2 mm within 10 cm between the laparoscope and the LUS probe. The ultrasound reconstruction accuracy is approximately 2 mm. CONCLUSION: Hybrid tracking shows promising results that can meet the required navigation accuracy for laparoscopic liver surgery.

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Evolution of laparoscopic liver surgery: 20-year experience of a Norwegian high-volume referral center.

BACKGROUND: Laparoscopic liver surgery has evolved to become a standard surgical approach in many specialized centers worldwide. In this study we present the evolution of laparoscopic liver surgery at a single high-volume referral center since its introduction in 1998. METHODS: Patients who underwent laparoscopic liver resection (LLR) between August 1998 and December 2018 at the Oslo University Hospital were analyzed. Perioperative outcomes were compared between three time periods: early (1998 to 2004), middle (2005 to 2012) and recent (2013-2018). RESULTS: Up to December 2020, 1533 LLRs have been performed. A total of 1232 procedures were examined (early period, n = 62; middle period, n = 367 and recent period, n = 803). Colorectal liver metastasis was the main indication for surgery (68%). The rates of conversion to laparotomy and hand-assisted laparoscopy were 3.2% and 1.4%. The median operative time and blood loss were 130 min [interquartile range (IQR), 85-190] and 220 ml (IQR, 50-600), respectively. The total postoperative complications rate was 20.3% and the 30-day mortality was 0.3%. The median postoperative stay was two (IQR, 2-4) days. When comparing perioperative outcomes between the three time periods, shorter operation time (median, from 182 to 120 min, p < 0.001), less blood loss (median, from 550 to 200 ml, p = 0.023), decreased rate of conversions to laparotomy (from 8 to 3%) and shorter postoperative hospital stay (median, from 3 to 2 days, p < 0.001) was observed in the later periods, while the number of more complex liver resections had increased. CONCLUSION: During the last two decades, the indications, the number of patients and the complexity of laparoscopic liver procedures have expanded significantly. Initially being an experimental approach, laparoscopic liver surgery is now safely implemented across our unit and has become the method of choice for surgical treatment of most liver tumors.

Long-Term Oncologic Outcomes After Laparoscopic Versus Open Resection for Colorectal Liver Metastases : A Randomized Trial.

BACKGROUND: Despite the recent worldwide dissemination of laparoscopic liver surgery, no high-level evidence supports the oncologic safety of this approach. OBJECTIVE: To evaluate long-term oncologic outcomes after laparoscopic versus open liver resection in patients with colorectal metastases. DESIGN: A single-center, assessor-blinded, randomized controlled trial (OSLO-COMET [Oslo Randomized Laparoscopic Versus Open Liver Resection for Colorectal Metastases Trial]). (ClinicalTrials.gov: NCT01516710). SETTING: Oslo University Hospital, the only provider of liver surgery for the 3 million inhabitants of southeastern Norway. PARTICIPANTS: Patients with resectable colorectal liver metastases were randomly assigned to have open or laparoscopic liver resection. INTERVENTION: From February 2012 to January 2016, a total of 280 patients were included in the trial (laparoscopic surgery: n = 133; open surgery: n = 147). MEASUREMENTS: The primary outcome was postoperative morbidity within 30 days. Five-year rates of overall and recurrence-free survival were predefined secondary end points. RESULTS: At a median follow-up of 70 months, rates of 5-year overall survival were 54% in the laparoscopic group and 55% in the open group (between-group difference, 0.5 percentage point [95% CI, -11.3 to 12.3 percentage points]; hazard ratio, 0.93 [CI, 0.67 to 1.30]; P = 0.67). Rates of 5-year recurrence-free survival were 30% in the laparoscopic group and 36% in the open group (between-group difference, 6.0 percentage points [CI, -6.7 to 18.7 percentage points]; hazard ratio, 1.09 [CI, 0.80 to 1.49]; P = 0.57). LIMITATION: The trial was not powered to detect differences in secondary end points and was not designed to address a noninferiority hypothesis for survival outcomes. CONCLUSION: In this randomized trial of laparoscopic and open liver surgery, no difference in survival outcomes was found between the treatment groups. However, differences in 5-year overall survival up to about 10 percentage points in either direction cannot be excluded. This trial should be followed by pragmatic multicenter trials and international registries. PRIMARY FUNDING SOURCE: The South-Eastern Norway Regional Health Authority.

Use of mixed reality for surgery planning: Assessment and development workflow.

Meticulous preoperative planning is an important part of any surgery to achieve high levels of precision and avoid complications. Conventional medical 2D images and their corresponding three-dimensional (3D) reconstructions are the main components of an efficient planning system. However, these systems still use flat screens for visualisation of 3D information, thus losing depth information which is crucial for 3D spatial understanding. Currently, cutting-edge mixed reality systems have shown to be a worthy alternative to provide 3D information to clinicians. In this work, we describe development details of the different steps in the workflow for the clinical use of mixed reality, including results from a qualitative user evaluation and clinical use-cases in laparoscopic liver surgery and heart surgery. Our findings indicate a very high general acceptance of mixed reality devices with our applications and they were consistently rated high for device, visualisation and interaction areas in our questionnaire. Furthermore, our clinical use-cases demonstrate that the surgeons perceived the HoloLens to be useful, recommendable to other surgeons and also provided a definitive answer at a multi-disciplinary team meeting.

A systematic review and meta-analysis comparing the short- and long-term outcomes for laparoscopic and open liver resections for liver metastases from colorectal cancer.

BACKGROUND: The laparoscopic approach to liver resection has experienced exponential growth in recent years. However, evidence-based guidelines are needed for its safe future progression. The main aim of our study was to perform a systematic review and meta-analysis comparing the short- and long-term outcomes of laparoscopic and open liver resections for colorectal liver metastases (CRLM). METHODS: To identify all the comparative manuscripts between laparoscopic and open liver resections for CRLM, all published English language studies with more than ten cases were screened. In addition to the primary meta-analysis, 3 specific subgroup analyses were performed on patients undergoing minor-only, major-only and synchronous resections. The quality of the studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology and Newcastle-Ottawa Score. RESULTS: From the initial 194 manuscripts identified, 21 were meta-analysed, including results from the first randomized trial comparing open and laparoscopic resections of CRLM. Five of these were specific to patients undergoing a synchronous resection (399 cases), while six focused on minor (3 series including 226 cases) and major (3 series including 135 cases) resections, respectively. Thirteen manuscripts compared 2543 cases but could not be assigned to any of the above sub-analyses, so were analysed independently. The majority of short-term outcomes were favourable to the laparoscopic approach with equivalent rates of negative resection margins. No differences were observed between the approaches in overall or disease-free survival at 1, 3 or 5 years. CONCLUSION: Laparoscopic liver resection for CRLM offers improved short-term outcomes with comparable long-term outcomes when compared to open approach.

Till death do us part: the effect of marital status on health care utilization and costs at end-of-life. A register study on all colorectal cancer decedents in Norway between 2009 and 2013.

BACKGROUND: Economic analyses of end-of-life care often focus on single aspects of care in selected cohorts leading to limited knowledge on the total level of care required to patients at their end-of-life. We aim at describing the living situation and full range of health care provided to patients at their end-of-life, including how informal care affects formal health care provision, using the case of colorectal cancer. METHODS: All colorectal cancer decedents between 2009 and 2013 in Norway (n = 7695) were linked to six national registers. The registers included information on decedents' living situation (days at home, in short- or long-term institution or in the hospital), their total health care utilization and costs in the secondary, primary and home- and community-based care setting. The effect of informal care was assessed through marital status (never married, currently married, or previously married) using regression analyses (negative binominal, two-part models and generalized linear models), controlling for age, gender, comorbidities, education, income, time since diagnosis and year of death. RESULTS: The average patient spent four months at home, while he or she spent 27 days in long-term institutions, 16 days in short-term institutions, and 21 days in the hospital. Of the total costs (~NOK 400,000), 58, 3 and 39% were from secondary carers (hospitals), primary carers (general practitioners and emergency rooms) and home- and community-based carers (home care and nursing homes), respectively. Compared to the never married, married patients spent 30 more days at home and utilized less home- and community-based care, but more health care services at the secondary and primary health care level. Their total healthcare costs were significantly lower (-NOK 65,621) than the never married. We found similar, but weaker, patterns for those who had been married previously. CONCLUSION: End-of-life care is primarily provided in the secondary and home-and community-based care level, and informal caregivers have a substantial influence on formal end-of-life care provision. Excluding aspects of care such as home and community-based care or informal care in economic analyses of end-of-life care provides a biased picture of the total resources required, and might lead to inefficient resource allocations.

Intravenous Patient-controlled Analgesia Versus Thoracic Epidural Analgesia After Open Liver Surgery: A Prospective, Randomized, Controlled, Noninferiority Trial.

OBJECTIVE: We conducted a randomized, controlled, noninferiority trial to investigate if intravenous, multimodal, patient-controlled analgesia (IV-PCA) could be noninferior to multimodal thoracic epidural analgesia (TEA) in patients undergoing open liver surgery. SUMMARY BACKGROUND DATA: The increasing use of minimally invasive techniques and fast track protocols have questioned the position of epidural analgesia as the optimal method of pain management after abdominal surgery. METHODS: Patients operated with open liver resection between February 2012 and February 2016 were randomly assigned to receive either IV-PCA enhanced with ketorolac/diclofenac (IV-PCA, n = 66) or TEA (n = 77) within an enhanced recovery after surgery protocol. Noninferiority would be declared if the mean pain score on the numeric rating scale (NRS) for postoperative days (PODs) 0 to 5 in the IV-PCA group was no worse than the mean pain score in the TEA group by a margin of <1 point on an 11-point scale (0-10). RESULTS: The primary endpoint, mean NRS pain score was 1.7 in the IV-PCA group and 1.6 in the TEA group, establishing noninferiority. Pain scores were lower in the TEA group on PODs 0 and 1, but higher or equal on PODs 2 and 5. Postoperative hospital stay was significantly shorter for patients in the IV-PCA group (74 vs 104 h, P < 0.001). The total opioid consumption during the first 3 days was significantly lower in the IV-PCA group. CONCLUSIONS: IV-PCA was noninferior to TEA for the treatment of postoperative pain in patients undergoing open liver resection.

Contemporary practice and short-term outcomes after liver resections in a complete national cohort.

BACKGROUND: Improved outcome after liver resections have been reported in several series, but outcomes from national cohorts are scarce. Our aim was to evaluate nationwide practice and short-term outcomes after liver surgery in a universal healthcare system. METHODS: A complete 5-year cohort of all liver resections from the Norwegian Patient Registry (NPR). Short-term outcomes were aggregated length of stay (a-LoS), reoperation and 90-day mortality. RESULTS: Of 2118 liver resections, 605 (28.6%) were major, median age was 65 years and 1184 (55%) were male. Most common indication was metastatic disease (n = 1554; 73.4%) and primary malignancy (n = 328; 15.3%). Laparoscopy was performed in 513 (33.9%) of minor and 37 (6.1%) of major liver resections and increased over time to 39.1% of minor resections in 2016. Median a-LoS was 12 days for major resections, 8 days for open minor and 3 days for laparoscopic minor resections. Reoperation was reported for 159 (7.4%) and 90-day mortality for 44 (2.1%). Primary malignancy, male gender, elderly patients and major resections were associated with poorer outcome. CONCLUSIONS: In a national cohort, laparoscopy is used for a substantial proportion of minor resections and was associated with reduced a-LoS. Risk factors for reoperation and mortality were male gender, increased age and major resection for primary malignancy.

Laparoscopic liver resection for non-colorectal non-neuroendocrine metastases: perioperative and oncologic outcomes.

BACKGROUND: Liver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed. MATERIAL AND METHODS: In this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12-41) months. RESULTS: Fifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95-225) min, while the median blood loss was 200 (IQR, 50-500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months. CONCLUSION: Laparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.

Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial.

OBJECTIVE: To perform the first randomized controlled trial to compare laparoscopic and open liver resection. SUMMARY BACKGROUND DATA: Laparoscopic liver resection is increasingly used for the surgical treatment of liver tumors. However, high-level evidence to conclude that laparoscopic liver resection is superior to open liver resection is lacking. METHODS: Explanatory, assessor-blinded, single center, randomized superiority trial recruiting patients from Oslo University Hospital, Oslo, Norway from February 2012 to January 2016. A total of 280 patients with resectable liver metastases from colorectal cancer were randomly assigned to undergo laparoscopic (n = 133) or open (n = 147) parenchyma-sparing liver resection. The primary outcome was postoperative complications within 30 days (Accordion grade 2 or higher). Secondary outcomes included cost-effectiveness, postoperative hospital stay, blood loss, operation time, and resection margins. RESULTS: The postoperative complication rate was 19% in the laparoscopic-surgery group and 31% in the open-surgery group (12 percentage points difference [95% confidence interval 1.67-21.8; P = 0.021]). The postoperative hospital stay was shorter for laparoscopic surgery (53 vs 96 hours, P < 0.001), whereas there were no differences in blood loss, operation time, and resection margins. Mortality at 90 days did not differ significantly from the laparoscopic group (0 patients) to the open group (1 patient). In a 4-month perspective, the costs were equal, whereas patients in the laparoscopic-surgery group gained 0.011 quality-adjusted life years compared to patients in the open-surgery group (P = 0.001). CONCLUSIONS: In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued implementation of laparoscopic liver resection.

Laparoscopic liver resection for metastatic melanoma.

BACKGROUND: Stage IV metastatic melanoma carries a poor prognosis. In the case of melanoma liver metastasis (MLM), surgical resection may improve survival and represents a therapeutic option, with varying levels of success. Laparoscopic liver resection (LLR) for metastatic melanoma is poorly studied. The aim of this study was to analyze the outcomes of LLR in patients with MLM. MATERIALS AND METHODS: Between April 2000 and August 2013, 11 (1 cutaneous, 9 ocular and 1 unknown primary) patients underwent LLR for MLM at Oslo University Hospital-Rikshospitalet and 13 procedures in total were carried out. Perioperative and oncologic outcomes were analyzed. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. RESULTS: A total of 23 liver specimens were resected. The median operative time was 137 (65-470) min, while the median blood loss was less than 50 (<50-900) ml. No intraoperative unfavorable incidents and 30-day mortality occurred. Median follow-up was 33 (9-92) months. Ten patients (91%) developed recurrence within a median of 5 months (2-18 months) and two patients underwent repeat LLR for recurrent liver metastases. One-, three-, and five-year overall survival rates were 82, 45 and 9%, respectively. The median overall survival was 30 (9-92) months. CONCLUSION: Perioperative morbidity and long-term survival after LLR for MLM seems to be comparable to open liver resection. Thus, LLR may be preferred over open liver resection due to the well-known advantages of laparoscopy, such as reduced pain and improved possibility for repeated resections.

Role of laparoscopic enucleation in the treatment of pancreatic lesions: case series and case-matched analysis.

BACKGROUND: Previous studies report successful application of laparoscopic pancreatic enucleation (LPE). However, the evidence is limited to small series. This study aimed to evaluate the indications, technique and outcome of LPE at a tertiary care institution. METHODS: Between February 1998 and April 2016, 45 consecutive LPEs were performed at Oslo University Hospital-Rikshospitalet. Twenty-four (53.3 %) patients subjected to right-sided LPE (RLPE) were compared with 21 (46.7 %) patients who had undergone left-sided LPE (LLPE). A case-matched analysis (1:2) was performed to compare the outcomes following LLPE and laparoscopic distal pancreatectomy (LDP). RESULTS: Patient demographics, BMI, ASA score and pathological characteristics were similar between the RLPE and LLPE groups. Operative time was slightly longer for RLPE [123 (53-320) vs 102 (50-373) min, P = 0.09]. The rates of severe morbidity (≥Accordion grade III) and clinically relevant pancreatic fistula (grades B/C) were comparable, although with a trend for higher rate of complications following LLPE (16.7 vs 33.3 %; P = 0.19 and 20.8 vs 33.3 %, P = 0.34, respectively). The hospital stay was similar between RLPE and LLPE [5 (2-80) vs 7 (2-52), P = 0.49]. A case-matched analysis demonstrated shorter operating time [145 (90-350) vs 103 (50-233) min, P = 0.02], but higher readmission rate following LLPE (25 vs 3.1 %, P = 0.037). CONCLUSION: LLPE seems to be associated with a higher risk of postoperative morbidity and readmission rates than LDP. RLPE is a feasible, safe approach and a reasonable alternative to pancreatoduodenectomy in selected patients with pancreatic lesions.

Mixed reality - new image technology in experimental use. / Blandet virkelighet ­ ny bildeteknologi i klinisk utprøving.

New methods for holographic visualisation provide a true three-dimensional experience of medical images. The technique is generating great interest among surgeons.

Deep learning-assisted survival prognosis in renal cancer: A CT scan-based personalized approach.

This paper presents a deep learning (DL) approach for predicting survival probabilities of renal cancer patients based solely on preoperative CT imaging. The proposed approach consists of two networks: a classifier- and a survival- network. The classifier attempts to extract features from 3D CT scans to predict the ISUP grade of Renal cell carcinoma (RCC) tumors, as defined by the International Society of Urological Pathology (ISUP). Our classifier is a 3D convolutional neural network to avoid losing crucial information on the interconnection of slides in 3D images. We employ multiple procedures, including image augmentation, preprocessing, and concatenation, to improve the performance of the classifier. Given the strong correlation between ISUP grading and renal cancer prognosis in the clinical context, we use the ISUP grading features extracted by the classifier as the input to the survival network. By leveraging this clinical association and the classifier network, we are able to model our survival analysis using a simple DL-based network. We adopt a discrete LogisticHazard-based loss to extract intrinsic survival characteristics of RCC tumors from CT images. This allows us to build a completely parametric survival model that varies with patients' tumor characteristics and predicts non-proportional survival probability curves for different patients. Our results demonstrated that the proposed method could predict the future course of renal cancer with reasonable accuracy from the CT scans. The proposed method obtained an average concordance index of 0.72, an integrated Brier score of 0.15, and an area under the curve value of 0.71 on the test cohorts.

Local Tumour Control Following Microwave Ablation: Protocol for the Prospective Observational CIEMAR Study.

PURPOSE: Microwave ablation (MWA) is a treatment modality for colorectal liver metastases (CRLM). While potentially curative, more information is needed on factors that contribute to long-term local tumour control. The prospective multicentre observational study CIRSE Emprint Microwave Ablation Registry aims to prospectively collect real-world technical data and clinical outcomes on patients treated with MWA in CRLM. METHODS: Eligible patients are adults with up to 9 local treatment naïve CRLM of ≤ 3 cm completely treatable with either MWA alone or MWA with resection and/or radiotherapy within 8 weeks. Data are collected, at baseline, every 3 months until 12 months, and thereafter every 6 months until the end of the study. The primary outcome measure is local tumour control. Secondary outcome measures are overall survival, (hepatic-) disease-free survival, time-to-progression untreatable by ablation, systemic therapy vacation, safety, and quality of life. Covariates related to the primary outcome measure will be assessed using a stratified log-rank test and an univariable Cox proportional hazard regression. A sample size of 500 patients with 750 lesions produces a two-sided 95% confidence interval with a precision equal to 0.057. RESULTS: Between September 2019 and December 2022, 500 patients have been enrolled with at least 976 treated tumours. CONCLUSION: The prospective observational CIEMAR study will provide valuable insights into the real-world use of MWA, helping in the future patient selection and clarifying factors that may contribute to long-term local tumour control. TRIAL REGISTRATION: NCT03775980.

A PRRX1 Signature Identifies TIM-3 and VISTA as Potential Immune Checkpoint Targets in a Subgroup of Microsatellite Stable Colorectal Cancer Liver Metastases.

Disease recurrence and drug resistance are major challenges in the clinical management of patients with colorectal cancer liver metastases (CLM), and because tumors are generally microsatellite stable (MSS), responses to immune therapies are poor. The mesenchymal phenotype is overrepresented in treatment-resistant cancers and is associated with an immunosuppressed microenvironment. The aim of this work was to molecularly identify and characterize a mesenchymal subgroup of MSS CLM to identify novel therapeutic approaches. We here generated a mesenchymal gene expression signature by analysis of resection specimens from 38 patients with CLM using ranked expression level of the epithelial-to-mesenchymal transition-related transcription factor PRRX1. Downstream pathway analysis based on the resulting gene signature was performed and independent, publicly available datasets were used to validate the findings. A subgroup comprising 16% of the analyzed CLM samples were classified as mesenchymal, or belonging to the PRRX1 high group. Analysis of the PRRX1 signature genes revealed a distinct immunosuppressive phenotype with high expression of immune checkpoints HAVCR2/TIM-3 and VISTA, in addition to the M2 macrophage marker CD163. The findings were convincingly validated in datasets from three external CLM cohorts. Upregulation of immune checkpoints HAVCR2/TIM-3 and VISTA in the PRRX1 high subgroup is a novel finding, and suggests immune evasion beyond the PD-1/PD-L1 axis, which may contribute to poor response to PD-1/PD-L1-directed immune therapy in MSS colorectal cancer. Importantly, these checkpoints represent potential novel opportunities for immune-based therapy approaches in a subset of MSS CLM. Significance: CLM is an important cause of colorectal cancer mortality where the majority of patients have yet to benefit from immunotherapies. In this study of gene expression profiling analyses, we uncovered novel immune checkpoint targets in a subgroup of patients with MSS CLMs harboring a mesenchymal phenotype.