Factors Associated with and Impact of Open Conversion in Laparoscopic and Robotic Minor Liver Resections: An International Multicenter Study of 10,541 Patients.

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

Propensity-score Matched and Coarsened-exact Matched Analysis Comparing Robotic and Laparoscopic Major Hepatectomies: An International Multicenter Study of 4822 Cases.

OBJECTIVE: To compare the outcomes between robotic major hepatectomy (R-MH) and laparoscopic major hepatectomy (L-MH). BACKGROUND: Robotic techniques may overcome the limitations of laparoscopic liver resection. However, it is unknown whether R-MH is superior to L-MH. METHODS: This is a post hoc analysis of a multicenter database of patients undergoing R-MH or L-MH at 59 international centers from 2008 to 2021. Data on patient demographics, center experience volume, perioperative outcomes, and tumor characteristics were collected and analyzed. Both 1:1 propensity-score matched (PSM) and coarsened-exact matched (CEM) analyses were performed to minimize selection bias between both groups. RESULTS: A total of 4822 cases met the study criteria, of which 892 underwent R-MH and 3930 underwent L-MH. Both 1:1 PSM (841 R-MH vs. 841 L-MH) and CEM (237 R-MH vs. 356 L-MH) were performed. R-MH was associated with significantly less blood loss {PSM:200.0 [interquartile range (IQR):100.0, 450.0] vs 300.0 (IQR:150.0, 500.0) mL; P = 0.012; CEM:170.0 (IQR: 90.0, 400.0) vs 200.0 (IQR:100.0, 400.0) mL; P = 0.006}, lower rates of Pringle maneuver application (PSM: 47.1% vs 63.0%; P < 0.001; CEM: 54.0% vs 65.0%; P = 0.007) and open conversion (PSM: 5.1% vs 11.9%; P < 0.001; CEM: 5.5% vs 10.4%, P = 0.04) compared with L-MH. On subset analysis of 1273 patients with cirrhosis, R-MH was associated with a lower postoperative morbidity rate (PSM: 19.5% vs 29.9%; P = 0.02; CEM 10.4% vs 25.5%; P = 0.02) and shorter postoperative stay [PSM: 6.9 (IQR: 5.0, 9.0) days vs 8.0 (IQR: 6.0 11.3) days; P < 0.001; CEM 7.0 (IQR: 5.0, 9.0) days vs 7.0 (IQR: 6.0, 10.0) days; P = 0.047]. CONCLUSIONS: This international multicenter study demonstrated that R-MH was comparable to L-MH in safety and was associated with reduced blood loss, lower rates of Pringle maneuver application, and conversion to open surgery.

Risk Factors and Outcomes of Open Conversion During Minimally Invasive Major Hepatectomies: An International Multicenter Study on 3880 Procedures Comparing the Laparoscopic and Robotic Approaches.

INTRODUCTION: Despite the advances in minimally invasive (MI) liver surgery, most major hepatectomies (MHs) continue to be performed by open surgery. This study aimed to evaluate the risk factors and outcomes of open conversion during MI MH, including the impact of the type of approach (laparoscopic vs. robotic) on the occurrence and outcomes of conversions. METHODS: Data on 3880 MI conventional and technical (right anterior and posterior sectionectomies) MHs were retrospectively collected. Risk factors and perioperative outcomes of open conversion were analyzed. Multivariate analysis, propensity score matching, and inverse probability treatment weighting analysis were performed to control for confounding factors. RESULTS: Overall, 3211 laparoscopic MHs (LMHs) and 669 robotic MHs (RMHs) were included, of which 399 (10.28%) had an open conversion. Multivariate analyses demonstrated that male sex, laparoscopic approach, cirrhosis, previous abdominal surgery, concomitant other surgery, American Society of Anesthesiologists (ASA) score 3/4, larger tumor size, conventional MH, and Institut Mutualiste Montsouris classification III procedures were associated with an increased risk of conversion. After matching, patients requiring open conversion had poorer outcomes compared with non-converted cases, as evidenced by the increased operation time, blood transfusion rate, blood loss, hospital stay, postoperative morbidity/major morbidity and 30/90-day mortality. Although RMH showed a decreased risk of conversion compared with LMH, converted RMH showed increased blood loss, blood transfusion rate, postoperative major morbidity and 30/90-day mortality compared with converted LMH. CONCLUSIONS: Multiple risk factors are associated with conversion. Converted cases, especially those due to intraoperative bleeding, have unfavorable outcomes. Robotic assistance seemed to increase the feasibility of the MI approach, but converted robotic procedures showed inferior outcomes compared with converted laparoscopic procedures.

Propensity score-matched analysis of laparoscopic-assisted and hand-assisted laparoscopic liver resection versus pure laparoscopic liver resection: an international multicenter study.

BACKGROUND: Laparoscopic-assisted (LALR) and hand-assisted (HALR) liver resections have been utilized during the early adoption phase by surgeons when transitioning from open surgery to pure LLR. To date, there are limited data reporting on the outcomes of LALR or HALR compared to LLR. The objective was to compare the perioperative outcomes after LALR and HALR versus pure LLR. METHODS: This is an international multicentric analysis of 6609 patients undergoing minimal-invasive liver resection at 21 centers between 2004 and 2019. Perioperative outcomes were analyzed after propensity score matching (PSM) comparison between LALR and HALR versus LLR. RESULTS: 5279 cases met study criteria of whom 5033 underwent LLR (95.3%), 146 underwent LALR (2.8%) and 100 underwent HALR (1.9%). After 1:4 PSM, LALR was associated with inferior outcomes as evidenced by the longer postoperative stay, higher readmission rate, higher major morbidity rate and higher in-hospital mortality rate. Similarly, 1:6 PSM comparison between HALR and LLR also demonstrated poorer outcomes associated with HALR as demonstrated by the higher open conversion rate and higher blood transfusion rate. All 3 approaches technical variants demonstrated the same oncological radicality (R1 rate). CONCLUSION: LALR and HALR performed during the learning curve was associated with inferior perioperative outcomes compared to pure LLR.

An international multicentre propensity score matched analysis comparing between robotic versus laparoscopic left lateral sectionectomy.

BACKGROUND: Left lateral sectionectomy (LLS) is one of the most commonly performed minimally invasive liver resections. While laparoscopic (L)-LLS is a well-established technique, over traditional open resection, it remains controversial if robotic (R)-LLS provides any advantages of L-LLS. METHODS: A post hoc analysis of 997 patients from 21 international centres undergoing L-LLS or R-LLS from 2006 to 2020 was conducted. A total of 886 cases (214 R-LLS, 672 L-LLS) met study criteria. 1:1 and 1:2 propensity score matched (PSM) comparison was performed between R-LLS & L-LLS. Further subset analysis by Iwate difficulty was also performed. Outcomes measured include operating time, blood loss, open conversion, readmission rates, morbidity and mortality. RESULTS: Comparison between R-LLS and L-LLS after PSM 1:2 demonstrated statistically significantly lower open conversion rate in R-LLS than L-LLS (0.6% versus 5%, p = 0.009) and median blood loss was also statistically significantly lower in R-LLS at 50 (80) versus 100 (170) in L-LLS (p = 0.011) after PSM 1:1 although there was no difference in the blood transfusion rate. Pringle manoeuvre was also found to be used more frequently in R-LLS, with 53(24.8%) cases versus to 84(12.5%) L-LLS cases (p < 0.001). There was no significant difference in the other key perioperative outcomes such as operating time, length of stay, postoperative morbidity, major morbidity and 90-day mortality between both groups. CONCLUSION: R-LLS was associated with similar key perioperative outcomes compared to L-LLS. It was also associated with significantly lower blood loss and open conversion rates compared to L-LLS.

Robotic versus laparoscopic liver resections for hepatolithiasis: an international multicenter propensity score matched analysis.

INTRODUCTION: Minimally invasive liver resection (MILR) is widely recognized as a safe and beneficial procedure in the treatment of both malignant and benign liver diseases. Hepatolithiasis has traditionally been reported to be endemic only in East Asia, but has seen a worldwide uptrend in recent decades with increasingly frequent and invasive endoscopic instrumentation of the biliary tract for a myriad of conditions. To date, there has been a woeful lack of high-quality evidence comparing the laparoscopic (LLR) and robotic (RLR) approaches to treatment hepatolithiasis. METHODS: This is an international multicenter retrospective analysis of 273 patients who underwent RLR or LRR for hepatolithiasis at 33 centers in 2003-2020. The baseline clinicopathological characteristics and perioperative outcomes of these patients were assessed. To minimize selection bias, 1:1 (48 and 48 cases of RLR and LLR, respectively) and 1:2 (37 and 74 cases of RLR and LLR, respectively) propensity score matching (PSM) was performed. RESULTS: In the unmatched cohort, 63 (23.1%) patients underwent RLR, and 210 (76.9%) patients underwent LLR. Patient clinicopathological characteristics were comparable between the groups after PSM. After 1:1 and 1:2 PSM, RLR was associated with less blood loss (p = 0.003 in 1:2 PSM; p = 0.005 in 1:1 PSM), less patients with blood loss greater than 300 ml (p = 0.024 in 1:2 PSM; p = 0.027 in 1:1 PSM), and lower conversion rate to open surgery (p = 0.003 in 1:2 PSM; p < 0.001 in 1:1 PSM). There was no significant difference between RLR and LLR in use of the Pringle maneuver, median Pringle maneuver duration, 30-day readmission rate, postoperative morbidity, major morbidity, reoperation, and mortality. CONCLUSION: Both RLR and LLR were safe and feasible for hepatolithiasis. RLR was associated with significantly less blood loss and lower open conversion rate.

Hepatitis B Virus-Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear. APPROACH AND RESULTS: We adopted a targeted sequencing strategy to survey HBV integrations in human HBV-associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients' HCCs. Furthermore, we performed array-based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis-activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere-forming ability in HCC cells. CONCLUSIONS: Our results reveal a cis-activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV-integrated HCCs may achieve TERT activation in hepatocarcinogenesis.

Robotic Versus Laparoscopic Left and Extended Left Hepatectomy: An International Multicenter Study Propensity Score-Matched Analysis.

BACKGROUND: Controversies exist among liver surgeons regarding clinical outcomes of the laparoscopic versus the robotic approach for major complex hepatectomies. The authors therefore designed a study to examine and compare the perioperative outcomes of laparoscopic left hepatectomy or extended left hepatectomy (L-LH/L-ELH) versus robotic left hepatectomy or extended left hepatectomy (R-LH/R-ELH) using a large international multicenter collaborative database. METHODS: An international multicenter retrospective analysis of 580 patients undergoing L-LH/L-ELH or R-LH/R-ELH at 25 specialized hepatobiliary centers worldwide was undertaken. Propensity score-matching (PSM) was used at a 1:1 nearest-neighbor ratio according to 15 perioperative variables, including demographics, tumor characteristics, Child-Pugh score, presence of portal hypertension, multiple resections, histologic diagnosis, and Iwate difficulty grade. RESULTS: Before the PSM, 190 (32 %) patients underwent R-LH/R-ELH, and 390 (68 %) patients underwent L-LH/L-ELH. After the matching, 164 patients were identified in each arm without significant differences in demographics, preoperative variables, medical history, tumor pathology, tumor characteristics, or Iwate score. Regarding intra- and postoperative outcomes, the rebotic approach had significantly less estimated blood loss (EBL) (100 ml [IQR 200 ml] vs 200 ml [IQR 235 ml]; p = 0.029), fewer conversions to open operations (n = 4 [2.4 %] vs n = 13, [7.9 %]; p = 0.043), and a shorter hospital stay (6 days [IQR 3 days] vs 7 days [IQR 3.3 days]; p = 0.009). CONCLUSION: Both techniques are safe and feasible in major hepatic resections. Compared with L-LH/L-ELH, R-LH/R-ELH is associated with less EBL, fewer conversions to open operations, and a shorter hospital stay.

Limited liver resections in the posterosuperior segments: international multicentre propensity score-matched and coarsened exact-matched analysis comparing the laparoscopic and robotic approaches.

BACKGROUND: Limited liver resections (LLRs) for tumours located in the posterosuperior segments of the liver are technically demanding procedures. This study compared outcomes of robotic (R) and laparoscopic (L) LLR for tumours located in the posterosuperior liver segments (IV, VII, and VIII). METHODS: This was an international multicentre retrospective analysis of patients who underwent R-LLR or L-LLR at 24 centres between 2010 and 2019. Patient demographics, perioperative parameters, and postoperative outcomes were analysed; 1 : 3 propensity score matching (PSM) and 1 : 1 coarsened exact matching (CEM) were performed. RESULTS: Of 1566 patients undergoing R-LLR and L-LLR, 983 met the study inclusion criteria. Before matching, 159 R-LLRs and 824 L-LLRs were included. After 1 : 3 PSM of 127 R-LLRs and 381 L-LLRs, comparison of perioperative outcomes showed that median blood loss (100 (i.q.r. 40-200) versus 200 (100-500) ml; P = 0.003), blood loss of at least 500 ml (9 (7.4 per cent) versus 94 (27.6 per cent); P < 0.001), intraoperative blood transfusion rate (4 (3.1 per cent) versus 38 (10.0 per cent); P = 0.025), rate of conversion to open surgery (1 (0.8 per cent) versus 30 (7.9 per cent); P = 0.022), median duration of Pringle manoeuvre when applied (30 (20-46) versus 40 (25-58) min; P = 0.012), and median duration of operation (175 (130-255) versus 224 (155-300); P < 0.001) were lower in the R-LLR group compared with the L-LLR group. After 1 : 1 CEM of 104 R-LLRs with 104 L-LLRs, R-LLR was similarly associated with significantly reduced blood loss and a lower rate of conversion to open surgery. CONCLUSION: Based on a matched analysis of well selected patients, both robotic and laparoscopic access could be undertaken safely with good outcomes for tumours in the posterosuperior liver segments.

Utility of the Iwate difficulty scoring system for laparoscopic right posterior sectionectomy: do surgical outcomes differ for tumors in segments VI and VII?

INTRODUCTION: The Iwate Score (IS) have not been well-validated for specific procedures, especially for right posterior sectionectomy (RPS). In this study, the utility of the IS was determined for laparoscopic (L)RPS and the effect of tumor location on surgical outcomes was investigated. METHODS: Post-hoc analysis of 647 L-RPS performed in 40 international centers of which 596L-RPS cases met the inclusion criteria. Baseline characteristics and perioperative outcomes of patients stratified based on the Iwate score were compared to determine whether a correlation with surgical difficulty existed. A 1:1 Mahalanobis distance matching was utilized to investigate the effect of tumor location on L-RPS outcomes. RESULTS: The patients were stratified into 3 levels of difficulty (31 intermediate, 143 advanced, and 422 expert) based on the IS. When using a stepwise increase of the IS excluding the tumor location score, only Pringle's maneuver was more frequently used in the higher surgical difficulty level (35.5%, 54.6%, and 65.2%, intermediate, advanced, and expert levels, respectively, Z = 3.34, p = 0.001). Other perioperative results were not associated with a statistical gradation toward higher difficulty level. 80 of 85 patients with a segment VI lesion and 511 patients with a segment VII lesion were matched 1:1. There were no significant differences in the perioperative outcomes of the two groups including open conversion, operating time, blood loss, intraoperative blood transfusion, postoperative stay, major morbidity, and mortality. CONCLUSION: Among patients undergoing L-RPS, the IS did not significantly correlate with most outcome measures associated with intraoperative difficulty and postoperative outcomes. Similarly, tumor location had no effect on L-RPS outcomes.

RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma.

BACKGROUND & AIMS: Mutational profiling of patient tumors has suggested that hepatocellular carcinoma (HCC) development is mainly driven by loss-of-function mutations in tumor suppressor genes. p90 ribosomal S6 kinase 2 (RSK2) functions as a direct downstream kinase of ERK1/2 and elevated RSK2 expression has been reported to support oncogenic functions in some cancers. We investigated if RSK2 was also dysregulated by inactivating mutations in cancers including HCC. METHODS: We performed exome sequencing and targeted DNA sequencing on HBV-associated HCCs to examine recurrent RSK2 mutations. The functional significance and mechanistic consequences of RSK2 mutations were examined in natural RSK2-null HCC cells, and RSK2-knockout HCC cells. The potential downstream pathways underlying RSK2 mutations were investigated by RNA sequencing, qRT-PCR and mass spectrometry. RESULTS: We detected recurrent somatic RSK2 mutations at a rate of 6.3% in our HCC cohorts and revealed that, among many cancer types, HCC was the cancer most commonly harboring RSK2 mutations. The RSK2 mutations were inactivating and associated with a more aggressive tumor phenotype. We found that, functionally, restoring RSK2 expression in natural RSK2-null HBV-positive Hep3B cells suppressed proliferation and migration in vitro and tumorigenicity in vivo. Mechanistically, RSK2-inactivating mutations attenuated a SOS1/2-dependent negative feedback loop, leading to the activation of MAPK signaling. Of note, this RSK2 mutation-mediated MAPK upregulation rendered HCC cells more sensitive to sorafenib, a first-line multi-kinase inhibitor for advanced HCC. Furthermore, such activation of MAPK signaling enhanced cholesterol biosynthesis-related gene expression in HCC cells. CONCLUSIONS: Our findings reveal the mechanistic and functional significance of RSK2-inactivating mutations in HCC. These inactivating mutations may serve as an alternative route to activate MAPK signaling and cholesterol metabolism in HCC. LAY SUMMARY: In this study, we identified and functionally characterized RSK2-inactivating mutations in human hepatocellular carcinoma and demonstrated their association with aggressive tumor behavior. Mutations in RSK2 drive signaling pathways with known oncogenic potential, leading to enhanced cholesterol biosynthesis and potentially sensitizing tumors to sorafenib treatment.

International multicentre propensity score-matched analysis comparing robotic versus laparoscopic right posterior sectionectomy.

BACKGROUND: Minimally invasive right posterior sectionectomy (RPS) is a technically challenging procedure. This study was designed to determine outcomes following robotic RPS (R-RPS) and laparoscopic RPS (L-RPS). METHODS: An international multicentre retrospective analysis of patients undergoing R-RPS versus those who had purely L-RPS at 21 centres from 2010 to 2019 was performed. Patient demographics, perioperative parameters, and postoperative outcomes were analysed retrospectively from a central database. Propensity score matching (PSM) was performed, with analysis of 1 : 2 and 1 : 1 matched cohorts. RESULTS: Three-hundred and forty patients, including 96 who underwent R-RPS and 244 who had L-RPS, met the study criteria and were included. The median operating time was 295 minutes and there were 25 (7.4 per cent) open conversions. Ninety-seven (28.5 per cent) patients had cirrhosis and 56 (16.5 per cent) patients required blood transfusion. Overall postoperative morbidity rate was 22.1 per cent and major morbidity rate was 6.8 per cent. The median postoperative stay was 6 days. After 1 : 1 matching of 88 R-RPS and L-RPS patients, median (i.q.r.) blood loss (200 (100-400) versus 450 (200-900) ml, respectively; P < 0.001), major blood loss (> 500 ml; P = 0.001), need for intraoperative blood transfusion (10.2 versus 23.9 per cent, respectively; P = 0.014), and open conversion rate (2.3 versus 11.4 per cent, respectively; P = 0.016) were lower in the R-RPS group. Similar results were found in the 1 : 2 matched groups (66 R-RPS versus 132 L-RPS patients). CONCLUSION: R-RPS and L-RPS can be performed in expert centres with good outcomes in well selected patients. R-RPS was associated with reduced blood loss and lower open conversion rates than L-RPS.

Randomized Controlled Trial for Paclitaxel-coated Balloon versus Plain Balloon Angioplasty in Dysfunctional Hemodialysis Vascular Access: 12-month Outcome from a Nonsponsored Trial.

BACKGROUND: Plain balloon angioplasty is regarded as the mainstay of treatment for failing vascular access with high success rate, but the poor treatment durability creates significant workload and increases patient morbidity. The study aims to compare target lesion primary patency rate at 12 months between paclitaxel-coated balloon (DCB) versus plain old balloon angioplasty (POBA) for treatment of dysfunctional vascular access. METHODS: This nonsponsored-randomized trial enrolled 40 patients with dysfunctional dialysis access at a single center. Patients were randomized into In.Pact Admiral Paclitaxel DCB or POBA after lesion crossing regardless of lesion type. Patients are followed up under surveillance protocol. Patients, hemodialysis staff, and sonographer are blinded to the treatment arms. Twelve-month primary patency rate in both arms are evaluated. RESULTS: 40 patients were recruited since June 2016 and were allocated to the DCB or POBA group. The mean age is 58 and 57 years with comparable demographic parameters. The locations of target lesion were comparable in both groups (juxta and arteriovenous anastomosis, cannulation site, and fistula/graft), with similar mean target lesion stenosis 69.8 +/- 15.8% for DCB and 69.5 +/- 13.6% for POBA (P = 0.95), and the lesion length for DCB is 45.8 +/- 38.4 mm and 50.2 +/- 33.5 mm for POBA (P = 0.70). Patients in DCB performed significantly better in terms of primary patency at 6 months 85% versus 55% (P = 0.007). The superiority in primary patency in DCB group exists at 12 months 65% versus 30% (P = 0.007). CONCLUSIONS: Paclitaxel balloon angioplasty approach provides significant better primary patency in dysfunctional arteriovenous access at 12 months in our nonsponsored-randomized trial.

Indocyanine green fluorescence angiography to evaluate anastomotic perfusion in colorectal surgery.

BACKGROUND: The aim of this study was to evaluate the efficacy of indocyanine green (ICG) fluorescence angiography with respect to the anastomotic leakage rate for patients undergoing colorectal operations. METHODS: This prospective cohort involved patients who underwent colorectal surgery between August 2018 and September 2019. ICG was injected after colonic transection. Vascular perfusion was observed by ICG fluorescence system before completing anastomosis. Data was compared with those by subjective visual evaluation. The primary outcome was anastomotic leakage rate within 30 days from surgery. RESULTS: A total of 131 patients were enrolled, of which ICG was injected in 63 of them. Demographic data were similar between the two groups. There were two (3.23%) and three (4.35%) anastomotic leaks in the ICG and non-ICG group respectively (p = 1.000). Change of resection plane occurred in one patient in the ICG group. There was no ICG related toxicity or adverse events. CONCLUSION: ICG fluorescent imaging is a feasible and safe tool to assess colonic vascularisation for patients undergoing colorectal surgery. However, it did not significantly lower the anastomotic leakage rate. ICG should not be routinely used in colorectal surgery before an available large scale randomised controlled trial to prove any clinical benefits.

Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka.

The use of laparoscopy for liver surgery is increasing rapidly. The Second International Consensus Conference on Laparoscopic Liver Resections (LLR) was held in Morioka, Japan, from October 4 to 6, 2014 to evaluate the current status of laparoscopic liver surgery and to provide recommendations to aid its future development. Seventeen questions were addressed. The first 7 questions focused on outcomes that reflect the benefits and risks of LLR. These questions were addressed using the Zurich-Danish consensus conference model in which the literature and expert opinion were weighed by a 9-member jury, who evaluated LLR outcomes using GRADE and a list of comparators. The jury also graded LLRs by the Balliol Classification of IDEAL. The jury concluded that MINOR LLRs had become standard practice (IDEAL 3) and that MAJOR liver resections were still innovative procedures in the exploration phase (IDEAL 2b). Continued cautious introduction of MAJOR LLRs was recommended. All of the evidence available for scrutiny was of LOW quality by GRADE, which prompted the recommendation for higher quality evaluative studies. The last 10 questions focused on technical questions and the recommendations were based on literature review and expert panel opinion. Recommendations were made regarding preoperative evaluation, bleeding controls, transection methods, anatomic approaches, and equipment. Both experts and jury recognized the need for a formal structure of education for those interested in performing major laparoscopic LLR because of the steep learning curve.

European Association of Endoscopic Surgeons (EAES) consensus statement on the use of robotics in general surgery.

Following an extensive literature search and a consensus conference with subject matter experts the following conclusions can be drawn: 1. Robotic surgery is still at its infancy, and there is a great potential in sophisticated electromechanical systems to perform complex surgical tasks when these systems evolve. 2. To date, in the vast majority of clinical settings, there is little or no advantage in using robotic systems in general surgery in terms of clinical outcome. Dedicated parameters should be addressed, and high quality research should focus on quality of care instead of routine parameters, where a clear advantage is not to be expected. 3. Preliminary data demonstrates that robotic system have a clinical benefit in performing complex procedures in confined spaces, especially in those that are located in unfavorable anatomical locations. 4. There is a severe lack of high quality data on robotic surgery, and there is a great need for rigorously controlled, unbiased clinical trials. These trials should be urged to address the cost-effectiveness issues as well. 5. Specific areas of research should include complex hepatobiliary surgery, surgery for gastric and esophageal cancer, revisional surgery in bariatric and upper GI surgery, surgery for large adrenal masses, and rectal surgery. All these fields show some potential for a true benefit of using current robotic systems. 6. Robotic surgery requires a specific set of skills, and needs to be trained using a dedicated, structured training program that addresses the specific knowledge, safety issues and skills essential to perform this type of surgery safely and with good outcomes. It is the responsibility of the corresponding professional organizations, not the industry, to define the training and credentialing of robotic basic skills and specific procedures. 7. Due to the special economic environment in which robotic surgery is currently employed special care should be taken in the decision making process when deciding on the purchase, use and training of robotic systems in general surgery. 8. Professional organizations in the sub-specialties of general surgery should review these statements and issue detailed, specialty-specific guidelines on the use of specific robotic surgery procedures in addition to outlining the advanced robotic surgery training required to safely perform such procedures.

Sorted-Cell Sequencing on HCC Specimens Reveals EPS8L3 as a Key Player in CD24/CD13/EpCAM-Triple Positive, Stemness-Related HCC Cells.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs and identify their regulatory mechanisms in stemness-related cells. METHODS: We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients' resected specimens. Knockdown approach was used, and relevant functional assays were conducted on the identified targets of interest. RESULTS: Flow cytometry on a total of 60 HCC resected specimens showed significant heterogeneity in the expression of LCSC markers, with CD24, CD13, and EpCAM mainly contributing to this heterogeneity. Concomitant expression of CD24, CD13, and EpCAM was detected in 32 HCC samples, and this was associated with advanced tumor stages. Transcriptomic sequencing on the HCC cells sorted for these individual markers identified epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8L3) as a common gene associated with the 3 markers and was functionally validated in HCC cells. Knocking down EPS8L3 suppressed the expression of all 3 markers. To search for the upstream regulation of EPS8L3, we found SP1 bound to EPS8L3 promoter to drive EPS8L3 expression. Furthermore, using Akt inhibitor MK2206, we showed that Akt signaling-driven SP1 drove the expression of the 3 LCSC markers. CONCLUSIONS: Our findings suggest that Akt signaling-driven SP1 promotes EPS8L3 expression, which is critical in maintaining the downstream expression of CD24, CD13, and EpCAM. The findings provide insight into potential LCSC-targeting therapeutic strategies.