Robotic sectionectomy versus robotic hemihepatectomy for anatomic liver resection: a comparative analysis of perioperative outcomes.

Sectionectomy is a parenchma-sparing alternative to (extended) right or left hemihepatectomy. However, the effectiveness and safety of robotic sectionectomy (RS) versus robotic (extended) hemihepatectomy (RH) for the treatment of liver tumors remains unclear. We reviewed our prospective database for consecutive patients who had undergone robotic hepatectomies between March 2021 and July 2023 and included all patients with RS and RH. Demographic data, perioperative outcomes and long-term outcomes were analyzed and compared between both groups. Thirty patients met our inclusion criteria, of whom 16 patients underwent RS as opposed to 14 patients who underwent RH. Baseline characteristics were comparable between the study groups. The duration of Pringle maneuver was significantly longer in the RS group, while the remaining operative details were comparable. There were no significant differences in posthepatectomy outcomes between the study groups. All patients had negative resection margins. RS is a safe and effective parenchyma-sparing treatment modality.

Robotic or laparoscopic repeat hepatectomy after open hepatectomy: a cohort study.

BACKGROUND: Repeat hepatectomies are technically complex procedures. The evidence of robotic or laparoscopic (= minimally invasive) repeat hepatectomies (MIRH) after previous open hepatectomy is poor. Therefore, we compared postoperative outcomes of MIRH vs open repeat hepatectomies (ORH) in patients with liver tumors after previous open liver resections. METHODS: Consecutive patients who underwent repeat hepatectomies after open liver resections were identified from a prospective database between April 2018 and May 2023. Postoperative complications were graded in line with the Clavien-Dindo classification. We stratified patients by intention to treat into MIRH or ORH and compared outcomes. Logistic regression analysis was performed to define variables associated with the utilization of a minimally invasive approach. RESULTS: Among 46 patients included, 20 (43%) underwent MIRH and 26 (57%) ORH. Twenty-seven patients had advanced or expert repeat hepatectomies (59%) according to the IWATE criteria. Baseline characteristics were comparable between the study groups. The use of a minimally invasive approach was not dependent on preoperative or intraoperative variables. All patients had negative resection margins on final histology. MIRH was associated with less blood loss (450 ml, IQR (interquartile range): 200-600 vs 600 ml, IQR: 400-1500 ml, P = 0.032), and shorter length of stay (5 days, IQR: 4-7 vs 7 days, IQR: 5-9 days, P = 0.041). Postoperative complications were similar between the groups (P = 0.298). CONCLUSIONS: MIRH is feasible after previous open hepatectomy and a safe alternative approach to ORH. (German Clinical Trials Register ID: DRKS00032183).

Development and Validation of a Model for Postpancreatectomy Hemorrhage Risk.

Importance: Postpancreatectomy hemorrhage (PPH) due to postoperative pancreatic fistula (POPF) is a life-threatening complication after pancreatoduodenectomy. However, there is no prediction tool for early identification of patients at high risk of late PPH. Objective: To develop and validate a prediction model for PPH. Design, Setting, and Participants: This retrospective prognostic study included consecutive patients with clinically relevant POPF who underwent pancreatoduodenectomy from January 1, 2009, to May 20, 2023, at the University Hospital Mannheim (derivation cohort), and from January 1, 2012, to May 31, 2022, at the University Hospital Dresden (validation cohort). Data analysis was performed from May 30 to July 29, 2023. Exposure: Clinical and radiologic features of PPH. Main Outcomes and Measures: Accuracy of a predictive risk score of PPH. A multivariate prediction model-the hemorrhage risk score (HRS)-was established in the derivation cohort (n = 139) and validated in the validation cohort (n = 154). Results: A total of 293 patients (187 [64%] men; median age, 69 [IQR, 60-76] years) were included. The HRS comprised 4 variables with associations: sentinel bleeding (odds ratio [OR], 35.10; 95% CI, 5.58-221.00; P < .001), drain fluid culture positive for Candida species (OR, 14.40; 95% CI, 2.24-92.20; P < .001), and radiologic proof of rim enhancement of (OR, 12.00; 95% CI, 2.08-69.50; P = .006) or gas within (OR, 12.10; 95% CI, 2.22-65.50; P = .004) a peripancreatic fluid collection. Two risk categories were identified with patients at low risk (0-1 points) and high risk (≥2 points) to develop PPH. Patients with PPH were predicted accurately in the derivation cohort (C index, 0.97) and validation cohort (C index 0.83). The need for more invasive PPH management (74% vs 34%; P < .001) and severe complications (49% vs 23%; P < .001) were more frequent in high-risk patients compared with low-risk patients. Conclusions and Relevance: In this retrospective prognostic study, a robust prediction model for PPH was developed and validated. This tool may facilitate early identification of patients at high risk for PPH.

Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis.

The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

Management of Anastomotic Leakage after Colorectal Resection: Survey among the German CHIR-Net Centers.

(1) Background: A widely accepted algorithm for the management of colorectal anastomotic leakage (CAL) is difficult to establish. The present study aimed to evaluate the current clinical practice on the management of CAL among the German CHIR-Net centers. (2) Methods: An online survey of 38 questions was prepared using the International Study Group of Rectal Cancer (ISREC) grading score of CAL combined with both patient- and surgery-related factors. All CHIR-Net centers received a link to the online questionary in February 2020. (3) Results: Most of the answering centers (55%) were academic hospitals (41%). Only half of them use the ISREC definition and grading for the management of CAL. A preference towards grade B management (no surgical intervention) of CAL was observed in both young and fit as well as elderly and/or frail patients with deviating ostomy and non-ischemic anastomosis. Elderly and/or frail patients without fecal diversion are generally treated as grade C leakage (surgical intervention). A grade C management of CAL is preferred in case of ischemic bowel, irrespective of the presence of an ostomy. Within grade C management, the intestinal continuity is preserved in a subgroup of patients with non-ischemic bowel, with or without ostomy, or young and fit patients with ischemic bowel under ostomy protection. (4) Conclusions: There is no generally accepted therapy algorithm for CAL management within CHIR-Net Centers in Germany. Further effort should be made to increase the application of the ISREC definition and grading of CAL in clinical practice.

Proteomics of immune cells from liver tumors reveals immunotherapy targets.

Elucidating the mechanisms by which immune cells become dysfunctional in tumors is critical to developing next-generation immunotherapies. We profiled proteomes of cancer tissue as well as monocyte/macrophages, CD4+ and CD8+ T cells, and NK cells isolated from tumors, liver, and blood of 48 patients with hepatocellular carcinoma. We found that tumor macrophages induce the sphingosine-1-phospate-degrading enzyme SGPL1, which dampened their inflammatory phenotype and anti-tumor function in vivo. We further discovered that the signaling scaffold protein AFAP1L2, typically only found in activated NK cells, is also upregulated in chronically stimulated CD8+ T cells in tumors. Ablation of AFAP1L2 in CD8+ T cells increased their viability upon repeated stimulation and enhanced their anti-tumor activity synergistically with PD-L1 blockade in mouse models. Our data reveal new targets for immunotherapy and provide a resource on immune cell proteomes in liver cancer.

Spatial Omics Imaging of Fresh-Frozen Tissue and Routine FFPE Histopathology of a Single Cancer Needle Core Biopsy: A Freezing Device and Multimodal Workflow.

The complex molecular alterations that underlie cancer pathophysiology are studied in depth with omics methods using bulk tissue extracts. For spatially resolved tissue diagnostics using needle biopsy cores, however, histopathological analysis using stained FFPE tissue and the immunohistochemistry (IHC) of a few marker proteins is currently the main clinical focus. Today, spatial omics imaging using MSI or IRI is an emerging diagnostic technology for the identification and classification of various cancer types. However, to conserve tissue-specific metabolomic states, fast, reliable, and precise methods for the preparation of fresh-frozen (FF) tissue sections are crucial. Such methods are often incompatible with clinical practice, since spatial metabolomics and the routine histopathology of needle biopsies currently require two biopsies for FF and FFPE sampling, respectively. Therefore, we developed a device and corresponding laboratory and computational workflows for the multimodal spatial omics analysis of fresh-frozen, longitudinally sectioned needle biopsies to accompany standard FFPE histopathology of the same biopsy core. As a proof-of-concept, we analyzed surgical human liver cancer specimens using IRI and MSI with precise co-registration and, following FFPE processing, by sequential clinical pathology analysis of the same biopsy core. This workflow allowed for a spatial comparison between different spectral profiles and alterations in tissue histology, as well as a direct comparison for histological diagnosis without the need for an extra biopsy.

Stereotactic Body Radiation Therapy versus Surgical Resection for Stage I/II Hepatocellular Carcinoma.

SBRT is an emerging locoregional treatment modality for hepatocellular carcinoma (HCC). Although local tumor control rates seem encouraging, large-scale survival data comparing SBRT to surgical resection are lacking. We identified patients with stage I/II HCC from the National Cancer Database amenable for potential surgical resection. Patients undergoing hepatectomy were matched by propensity score (1:2) with patients who underwent SBRT as primary treatment. A total of 3787 (91%) and 366 (9%) patients underwent surgical resection or SBRT between 2004 and 2015, respectively. After propensity matching, the 5-year overall survival was 24% (95% CI 19-30%) in the SBRT group versus 48% (95% CI 43-53%) in the surgery group (p < 0.001). The association of surgery with overall survival was consistent in all subgroups. In patients treated with SBRT, a biologic effective dose (BED) of ≥100 Gy (31%, 95% CI 22%-40%) compared with BED < 100 Gy (13%, 95% CI 8-22%) was associated with a higher 5-year overall survival rate (hazard ratio of mortality of 0.58, 95% CI 0.43-0.77; p < 0.001). Surgical resection may be associated with prolonged overall survival compared with SBRT in patients with stage I/II HCC.

Development of a conceptual framework to detect perioperative symptom burden following abdominal surgery for cancer.

BACKGROUND: Abdominal surgery for gastrointestinal malignancies has a significant impact on patients' health-related quality of life. However, there is so far no patient-reported outcome measures (PROM) in the immediate postoperative period to detect the perioperative symptom burden and patients' needs which may precede occult and severe complications. The aim of the study was to create a conceptual framework for the development of a PROM to measure perioperative symptom burden in abdominal cancer patients. METHODS: This mixed method study was performed between March 2021, and July 2021 as part of a multiphase approach to develop a new PROM. A systematic review of the literature was performed health domains were identified. The relevance of the health domains was assessed in a two-round Delphi study with clinical experts. Qualitative interviews were performed in patients who underwent abdominal surgery for cancer. RESULTS: The systematic literature review yielded 12 different PROM with 168 items and 55 health domains. The most common health domains involved the "digestive system" and "pain". In total, 30 patients (median age 66 years, 20 men [60%]) were included for qualitative patient interviews. Of 16 health domains identified by the Delphi study, a total 15 health domains were confirmed during patients' interviews. The final conceptual framework included 20 health domains. CONCLUSION: This study provides the essential groundwork to develop and validate a new PROM for the immediate postoperative period of patients undergoing abdominal surgery for cancer.

Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes.

Bone morphogenetic protein (BMP)-9, a member of the TGFß-family of cytokines, is believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21. However, whether BMP-9 also regulates the expression of the related FGF19 is not clear. Because both FGF21 and 19 were described to protect the liver from steatosis, we have further investigated the role of BMP-9 in this context. We first analyzed BMP-9 levels in the serum of streptozotocin (STZ)-induced diabetic rats (a model of type I diabetes) and confirmed that BMP-9 serum levels decrease during diabetes. Microarray analyses of RNA samples from hepatic and intestinal tissue from BMP-9 KO- and wild-type mice (C57/Bl6 background) pointed to basal expression of BMP-9 in both organs and revealed a down-regulation of hepatic Fgf21 and intestinal Fgf19 in the KO mice. Next, we analyzed BMP-9 levels in a cohort of obese patients with or without diabetes. Serum BMP-9 levels did not correlate with diabetes, but hepatic BMP-9 mRNA expression negatively correlated with steatosis in those patients that did not yet develop diabetes. Likewise, hepatic BMP-9 expression also negatively correlated with serum LPS levels. In situ hybridization analyses confirmed intestinal BMP-9 expression. Intestinal (but not hepatic) BMP-9 mRNA levels were decreased with diabetes and positively correlated with intestinal E-Cadherin expression. In vitro studies using organoids demonstrated that BMP-9 directly induces FGF19 in gut but not hepatocyte organoids, whereas no evidence of a direct induction of hepatic FGF21 by BMP-9 was found. Consistent with the in vitro data, a correlation between intestinal BMP-9 and FGF19 mRNA expression was seen in the patients' samples. In summary, our data confirm that BMP-9 is involved in diabetes development in humans and in the control of the FGF-axis. More importantly, our data imply that not only hepatic but also intestinal BMP-9 associates with diabetes and steatosis development and controls FGF19 expression. The data support the conclusion that increased levels of BMP-9 would most likely be beneficial under pre-steatotic conditions, making supplementation of BMP-9 an interesting new approach for future therapies aiming at prevention of the development of a metabolic syndrome and liver steatosis.

Structural expression of bovine milk and meat factors in tissues of colorectal, lung and pancreatic cancer patients.

Chronic inflammation, linked to the presence of bovine milk and meat factors (BMMFs) and specific subsets of macrophages, results in oxygen radical synthesis and induction of mutations in DNA of actively replicating cells and replicating single stranded DNA. Cancers arising from this process have been characterized as indirect carcinogenesis by infectious agents (without persistence of genes of the agent in premalignant or cancers cells). Here, we investigate structural properties of pleomorphic vesicles, regularly identified by staining peritumor tissues of colorectal, lung and pancreatic cancer for expression of BMMF Rep. The latter represents a subgroup of BMMF1 proteins involved in replication of small single-stranded circular plasmids of BMMF, but most likely also contributing to pleomorphic vesicular structures found in the periphery of colorectal, lung and pancreatic cancers. Structurally dense regions are demonstrated in preselected areas of colorectal cancer, after staining with monoclonal antibodies against BMMF1 Rep. Similar structures were observed in human embryonic cells (HEK293TT) overexpressing Rep. These data suggest that Rep or Rep isoforms contribute to the structural formation of vesicles.

[Robotic Left Hepatectomy Using the Glissonean Pedicle Approach for the Treatment of Caroli's Syndrome]. / Roboter-assistierte Hemihepatektomie links mittels Glissonean pedicle approach bei Caroli Syndrom.

BACKGROUND: Caroli's syndrome is a rare disease characterised by non-obstructive dilation of intrahepatic bile ducts, hepatic fibrosis, and an increased risk of developing cholangiocarcinoma. Minimally invasive liver resection has recently been increasingly adopted for the treatment of patients with localised Caroli's syndrome. However, robot-assisted liver resection for the treatment of Caroli's syndrome has not been published. MATERIALS AND METHODS: We report a case of a 72-year-old Asian female who was referred to our hospital with multifocal cystic dilation of liver segments II, III, and IV. She had no family history of congenital cysts. Her past medical history was uneventful except for an open appendectomy. The liver function tests were normal, with a negative echinococcus serology test. On MRI, the biliary anatomy at the hilum and right liver appeared to be regular. Therefore, a robotic left hepatectomy was carried out for the unilobar involvement of Caroli's syndrome using the Da Vinci Xi-system. RESULTS: We performed a Glissonean pedicle approach while preserving the caudate lobe. After removing surgical adhesions from the anterior abdominal wall using robotic scissors, a routine cholecystectomy was performed. An aberrant left hepatic artery arising from the left gastric artery was clipped and divided. The left portal pedicle was controlled after lowering the hilar plate. The ischemic demarcation line on the liver surface was followed after clamping the left pedicle, and parenchymal dissection was performed using Maryland bipolar forceps. A Pringle manoeuvre was not applied. The left pedicle and the left hepatic vein were transected using a GIA stapling device while the middle hepatic vein was preserved. Indocyanin green fluorescence imaging confirmed adequate perfusion of the remnant liver tissue including the caudate lobe. The specimen was placed in an extraction bag and removed via a Pfannenstiel incision. The total operation time was 239 min, including a total blood loss of 100 ml. The postoperative course was uneventful. The patient was discharged on postoperative day 5. On 6 months follow-up, the patient had normal liver function and no signs of recurrent disease. CONCLUSION: Robotic left hepatectomy using an extrahepatic Glissonean pedicle approach is technically feasible.

Comparison of extraction methods for intracellular metabolomics of human tissues.

Analyses of metabolic compounds inside cells or tissues provide high information content since they represent the endpoint of biological information flow and are a snapshot of the integration of many regulatory processes. However, quantification of the abundance of metabolites requires their careful extraction. We present a comprehensive study comparing ten extraction protocols in four human sample types (liver tissue, bone marrow, HL60, and HEK cells) aiming to detect and quantify up to 630 metabolites of different chemical classes. We show that the extraction efficiency and repeatability are highly variable across protocols, tissues, and chemical classes of metabolites. We used different quality metrics including the limit of detection and variability between replicates as well as the sum of concentrations as a global estimate of analytical repeatability of the extraction. The coverage of extracted metabolites depends on the used solvents, which has implications for the design of measurements of different sample types and metabolic compounds of interest. The benchmark dataset can be explored in an easy-to-use, interactive, and flexible online resource (R/shiny app MetaboExtract: http://www.metaboextract.shiny.dkfz.de) for context-specific selection of the optimal extraction method. Furthermore, data processing and conversion functionality underlying the shiny app are accessible as an R package: https://cran.r-project.org/package=MetAlyzer.

Impact of spleen preservation on the incidence of postoperative pancreatic fistula after distal pancreatectomy: Is less more?

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major complication after distal pancreatectomy (DP) with a significant impact on patients' quality of life. There is limited evidence that preservation of the spleen reduces the risk of POPF. Therefore, we aimed to investigate the impact of splenectomy on perioperative outcome. METHODS: Data from patients who underwent DP for malignant and benign disease at our institution between 2004 and 2021 were reviewed. Patients were grouped according to spleen preservation (SP-DP) and splenectomy (DPS). Intraoperative parameters and postoperative outcomes were compared between groups. Univariable and multivariable analyses were used to investigate factors that influence the occurrence of clinically relevant (cr)POPF. RESULTS: A total of 199 patients were included, of whom 61 (30.7%) patients underwent SP-DP. Patients who underwent SP-DP had a significantly lower rate of crPOPF (p = 0.022), shorter hospital stay (p = 0.003), and less readmissions (p = 0.012). On multivariate analysis, obesity (OR 2.88, p = 0.021), benign lesions (OR 2.35, p = 0.018), postoperative acute pancreatitis (OR 2.53, p = 0.028), and splenectomy (OR 2.83, p = 0.011) were independent risk factors associated with the onset of crPOPF. DISCUSSION: Preservation of the spleen reduces the risk of crPOPF in patients undergoing distal pancreatectomy for benign and malignant disease.

Prognostic value of disease-free interval in colorectal cancer: Is it time?

BACKGROUND: Previous studies have outlined that the onset of synchronous colorectal cancer (CRC) metastases is associated with poor overall survival (OS) compared to patients with metachronous disease. The aim of this study was to evaluate the association of disease-free interval with newly diagnosed CRC scheduled for primary tumor resection. METHODS: Patients who underwent primary CRC resection over an 18-year period were identified from a prospective database at a tertiary-care hospital. In this observational study, the cohort was stratified for the onset of metastases, i.e. synchronous, early-onset and late-onset metachronous disease. The OS was compared using Kaplan-Meier estimators and stratified Cox hazard regression analysis. RESULTS: Of 360 patients, 204 (57%) had synchronous, 61 (17%) had early metachronous, and 95 (26%) had late metachronous metastases, respectively. The onset of synchronous metastases was not associated with worse OS compared to early and late metachronous disease. ASA level > II (P = 0.011), right-sided compared to left-sided cancer (P = 0.032) or rectal cancer (P < 0.001), and high-grade tumors (P = 0.022) were identified as independent predictors of poor OS, whereas the only favorable prognostic factor was surgical resection of metastases (P = 0.047). Additionally, ASA level < III (P = 0.003) and low-grade tumors (P = 0.032) were found to predict resection of metastases. CONCLUSION: Individual patients' and tumor characteristics rather than the timing of metastases are associated with OS in newly diagnosed CRC. These data support curative treatment strategies even in patients with synchronous metastases.

Minimally invasive mesohepatectomy for centrally located liver lesions-a case series.

BACKGROUND: Resection of centrally located liver lesions remains a technically demanding procedure. To date, there are limited data on the effectiveness and safety of minimally invasive mesohepatectomy for benign and malignant lesions. It was therefore the objective of this study to evaluate the perioperative outcomes of minimally invasive mesohepatectomy for liver tumors at a tertiary care hospital. METHODS: Consecutive patients who underwent a minimally invasive anatomic mesohepatectomy using a Glissonean pedicle approach from April 2018 to November 2021 were identified from a prospective database. Demographics, operative details, and postoperative outcomes were analyzed using descriptive statistics for continuous and categorical variables. RESULTS: A total of ten patients were included, of whom five patients had hepatocellular carcinoma, one patient had cholangiocarcinoma, three patients had colorectal liver metastases, and one patient had a hydatid cyst. Two and eight patients underwent robotic-assisted and laparoscopic resections, respectively. The median operative time was 393 min (interquartile range (IQR) 298-573 min). Conversion to laparotomy was required in one case. The median lesion size was 60 mm and all cases had negative resection margins on final histopathological analysis. The median total blood loss was 550 ml (IQR 413-850 ml). One patient had a grade III complication. The median length of stay was 7 days (IQR 5-12 days). Time-to-functional recovery was achieved after a median of 2 days (IQR 1-4 days). There were no readmissions within 90 days after surgery. CONCLUSION: Minimally invasive mesohepatectomy is a feasible and safe approach in selected patients with benign and malignant liver lesions.

Human ILC3 Exert TRAIL-Mediated Cytotoxicity Towards Cancer Cells.

Group 3 helper Innate Lymphoid Cells (ILC3s) are cytokine-producing lymphocytes that respond to stress signals released during disturbed tissue homeostasis and infection. Upon activation, ILC3s secrete IL-22 and IL-17, and orchestrate immune responses against extracellular pathogens. Their role in cancer remains poorly explored. To determine their anti-cancer effector potential, we co-cultured cytokine-activated human ILC3s with cancer cells of different origins. ILC3s were able to directly respond to tumor cells, resulting in enhanced IFN-γ production. Upon tumor cell encounter, ILC3s maintained expression of the transcription factor RORγt, indicating that ILC3s preserved their identity. ILC3s were able to directly kill both hepatocellular carcinoma and melanoma tumor cells expressing cell-death receptor TRAILR2, through the activation of Caspase-8 in target cells. Moreover, liver-derived cytokine-activated ILC3s also expressed TRAIL and were able to eliminate hepatoblastoma cells. Together, our data reveal that ILC3s can participate in anti-tumor immune response through direct recognition of tumor cells resulting in IFN-γ release and TRAIL-dependent cytotoxicity. Thus, ILC3s might be ancillary players of anti-tumor immunity in tissues, acting as primary responders against transformed or metastasizing cells, which might be further exploited for therapies against cancer.