Cyclosporine vs. tacrolimus after liver transplantation for primary sclerosing cholangitis - a propensity score-matched intention-to-treat analysis.

BACKGROUND & AIMS: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US. METHODS: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates. RESULTS: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant. CONCLUSIONS: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC. IMPACT AND IMPLICATIONS: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation.

Propensity Score-Matching Analysis Comparing Robotic Versus Laparoscopic Limited Liver Resections of the Posterosuperior Segments: An International Multicenter Study.

OBJECTIVE: The purpose of this study was to compare the outcomes of robotic limited liver resections (RLLR) versus laparoscopic limited liver resections (LLLR) of the posterosuperior segments. BACKGROUND: Both laparoscopic and robotic liver resections have been used for tumors in the posterosuperior liver segments. However, the comparative performance and safety of both approaches have not been well examined in the existing literature. METHODS: This is a post hoc analysis of a multicenter database of 5446 patients who underwent RLLR or LLLR of the posterosuperior segments (I, IVa, VII, and VIII) at 60 international centers between 2008 and 2021. Data on baseline demographics, center experience and volume, tumor features, and perioperative characteristics were collected and analyzed. Propensity score-matching (PSM) analysis (in both 1:1 and 1:2 ratios) was performed to minimize selection bias. RESULTS: A total of 3510 cases met the study criteria, of whom 3049 underwent LLLR (87%), and 461 underwent RLLR (13%). After PSM (1:1: and 1:2), RLLR was associated with a lower open conversion rate [10 of 449 (2.2%) vs 54 of 898 (6.0%); P =0.002], less blood loss [100 mL [IQR: 50-200) days vs 150 mL (IQR: 50-350); P <0.001] and a shorter operative time (188 min (IQR: 140-270) vs 222 min (IQR: 158-300); P <0.001]. These improved perioperative outcomes associated with RLLR were similarly seen in a subset analysis of patients with cirrhosis-lower open conversion rate [1 of 136 (0.7%) vs 17 of 272 (6.2%); P =0.009], less blood loss [100 mL (IQR: 48-200) vs 160 mL (IQR: 50-400); P <0.001], and shorter operative time [190 min (IQR: 141-258) vs 230 min (IQR: 160-312); P =0.003]. Postoperative outcomes in terms of readmission, morbidity and mortality were similar between RLLR and LLLR in both the overall PSM cohort and cirrhosis patient subset. CONCLUSIONS: RLLR for the posterosuperior segments was associated with superior perioperative outcomes in terms of decreased operative time, blood loss, and open conversion rate when compared with LLLR.

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.

Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma.

BACKGROUND & AIMS: Single-agent anti-PD1 checkpoint inhibitors convey outstanding clinical benefits in a small fraction (∼20%) of patients with advanced hepatocellular carcinoma (aHCC) but the molecular mechanisms determining response are unknown. To fill this gap, we herein analyze the molecular and immune traits of aHCC in patients treated with anti-PD1. METHODS: Overall, 111 tumor samples from patients with aHCC were obtained from 13 centers before systemic therapies. We performed molecular analysis and immune deconvolution using whole-genome expression data (n = 83), mutational analysis (n = 72), and histologic evaluation with an endpoint of objective response. RESULTS: Among 83 patients with transcriptomic data, 28 were treated in frontline, whereas 55 patients were treated after tyrosine kinase inhibitors (TKI) either in second or third line. Responders treated in frontline showed upregulated interferon-γ signaling and major histocompatibility complex II-related antigen presentation. We generated an 11-gene signature (IFNAP), capturing these molecular features, which predicts response and survival in patients treated with anti-PD1 in frontline. The signature was validated in a separate cohort of aHCC and >240 patients with other solid cancer types where it also predicted response and survival. Of note, the same signature was unable to predict response in archival tissue of patients treated with frontline TKIs, highlighting the need for fresh biopsies before immunotherapy. CONCLUSION: Interferon signaling and major histocompatibility complex-related genes are key molecular features of HCCs responding to anti-PD1. A novel 11-gene signature predicts response in frontline aHCC, but not in patients pretreated with TKIs. These results must be confirmed in prospective studies and highlights the need for biopsies before immunotherapy to identify biomarkers of response.

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.

Impact of Tumor Size on the Difficulty of Laparoscopic Major Hepatectomies: An International Multicenter Study.

INTRODUCTION: Although tumor size (TS) is known to affect surgical outcomes in laparoscopic liver resection (LLR), its impact on laparoscopic major hepatectomy (L-MH) is not well studied. The objectives of this study were to investigate the impact of TS on the perioperative outcomes of L-MH and to elucidate the optimal TS cutoff for stratifying the difficulty of L-MH. METHODS: This was a post-hoc analysis of 3008 patients who underwent L-MH at 48 international centers. A total 1396 patients met study criteria and were included. The impact of TS cutoffs was investigated by stratifying TS at each 10-mm interval. The optimal cutoffs were determined taking into consideration the number of endpoints which showed a statistically significant split around the cut-points of interest and the magnitude of relative risk after correction for multiple risk factors. RESULTS: We identified 2 optimal TS cutoffs, 50 mm and 100 mm, which segregated L-MH into 3 groups. An increasing TS across these 3 groups (≤ 50 mm, 51-100 mm, > 100 mm), was significantly associated with a higher open conversion rate (11.2%, 14.7%, 23.0%, P < 0.001), longer operating time (median, 340 min, 346 min, 365 min, P = 0.025), increased blood loss (median, 300 ml,  ml, 400 ml, P = 0.002) and higher rate of intraoperative blood transfusion (13.1%, 15.9%, 27.6%, P < 0.001). Postoperative outcomes such as overall morbidity, major morbidity, and length of stay were comparable across the three groups. CONCLUSION: Increasing TS was associated with poorer intraoperative but not postoperative outcomes after L-MH. We determined 2 TS cutoffs (50 mm and 10 mm) which could optimally stratify the surgical difficulty of L-MH.

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.

Gd-EOB-DTPA-MRCP to localize bile leakage after liver trauma and surgery: impact on treatment and outcome.

OBJECTIVES: Bile leakage (BL) is a challenging complication after hepatobiliary surgery and liver trauma. Gadolinium ethoxybenzyl (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiopancreatography (MRCP) is used to diagnose BL non-invasively. We assessed the value of Gd-EOB-DTPA-MRCP in the detection of postoperative and post-traumatic BL hypothesizing that exact identification of the leakage site is pivotal for treatment planning and outcome. METHODS: We retrospectively enrolled 39 trauma and postoperative patients who underwent Gd-EOB-DTPA-MRCP for suspected BL. Three readers rated the presence of BL and leakage site (intraparenchymal, central, peripheral ± aberrant or disconnected ducts). Imaging findings were compared to subsequent interventional procedures and their complexity and outcome. RESULTS: BL was detected in Gd-EOB-DTPA-MRCP in 25 of patients and was subsequently confirmed. Sites of BL differed significantly between postoperative (central [58%] and peripheral [42%]) and trauma patients (intraparenchymal [100%]; p < 0.001). Aberrant or disconnected ducts were diagnosed in 8%/26% of cases in the postoperative subgroup. Inter-rater agreement for the detection and localization of BL was almost perfect (Κ = 0.85 and 0.88; p < 0.001). Intraparenchymal BL required significantly less complex interventional procedures (p = 0.002), whereas hospitalization and mortality did not differ between the subgroups (p > 0.05). CONCLUSIONS: Gd-EOB-DTPA-MRCP reliably detects and exactly locates BL in postoperative and trauma patients. Exact localization of biliary injuries enables specific treatment planning, as intraparenchymal leakages, which occur more frequently after trauma, require less complex interventions than central or peripheral leaks in the postoperative setting. As a result of specific treatment based on exact BL localization, there was no difference in the duration of hospitalization or mortality. CLINICAL RELEVANCE STATEMENT: Gd-EOB-DTPA-MRCP is a reliable diagnostic tool for exactly localizing iatrogenic and post-traumatic biliary leakage. Its precise localization helps tailor local therapies for different injury patterns, resulting in comparable clinical outcomes despite varying treatments. KEY POINTS: • Gd-EOB-DTPA-MRCP enables adequate detection and localization of bile leakages in both postoperative and post-traumatic patients. • The site of bile leakage significantly impacts the complexity of required additional interventions. • Intraparenchymal bile leakage is commonly seen in patients with a history of liver trauma and requires less complex interventions than postoperative central or peripheral bile leakages, while hospitalization and mortality are similar.

Simplifying minimally invasive right hepatectomy.

BACKGROUND: Extrahepatic transection of the right hepatic artery and right portal vein before parenchymal dissection is a widely used standard for minimal invasive right hepatectomy. Hereby, hilar dissection represents a technical difficulty. We report our results of a simplified approach in which the hilar dissection is omitted and the line of dissection is defined with ultrasound. METHODS: Patients undergoing minimally invasive right hepatectomy were included. Ultrasound-guided hepatectomy (UGH) was defined by the following main steps: (1) ultrasound-guided definition of the transection line, (2) dissection of the liver parenchyma according to the caudal approach, (3) intraparenchymal transection of the right pedicle and (4) of the right liver vein, respectively. Intra- and postoperative outcomes of UGH were compared to the standard technique. Propensity score matching was performed to adjust for parameters of perioperative risk. RESULTS: Median operative time was 310 min in the UGH group compared to 338 min in the control group (p = 0.013). No differences were observed for Pringle maneuver duration (35 min vs. 25 min; p = ns) nor postoperative transaminases levels (p = ns). There was a trend toward a lower major complication rate in the UGH group (13 vs. 25%) and a shorter median hospital stay (8 days vs. 10 days); however, both being short of statistical significance (p = ns). Bile leak was observed in zero cases of UGH compared to 9 out of 32 cases (28%) for the control group (p = 0.020). CONCLUSIONS: UGH appears to be at least comparable to the standard technique in terms of intraoperative and postoperative outcomes. Accordingly, transection of the right hepatic artery and right portal vein prior to the transection phase can be omitted, at least in selected cases. These results need to be confirmed in a prospective and randomized trial.

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.

A surgical strategy for intrahepatic cholangiocarcinoma - the hilar first concept.

PURPOSE: The present study assesses long-term overall survival (OS) and disease-free survival (DFS) after curative resection for intrahepatic cholangiocarcinoma (ICCA) depending on resection margin (RM) status and lymph node (LN) status. METHODS: Clinical data of all consecutively resected patients with ICCA at a single high-volume center between 2005 and 2018 were collected. Minimum follow-up was 36 months. Perioperative and long-term oncological outcome was assessed. RESULTS: One hundred ninety-two cases were included in the analysis. Thirty- and 90-day-mortality was 5.2% (n = 10) and 10.9% (n = 21). OS was 26 months with 1-, 2-, and 5-year-OS rates of 72%, 53%, and 26%. One-, 2-, and 5-year-DFS rates were 54%, 42%, and 35% (N0 vs. N1: 29 vs. 9 months, p = 0.116). R1 was not found to be an independent risk factor for reduced survival in the overall cohort (p = 0.098). When differentiating according to the LN status, clear resection margins were significantly associated with increased DFS for N0 cases (50 months vs. 9 months, p = 0.004). For N1 cases, no significant difference in DFS was calculated for R0 compared to R1 cases (9 months vs. 9 months, p = 0.88). For N0 cases, clear resection margins > 10 mm were associated with prolonged OS (p = 0.048). CONCLUSION: For N1 cases, there was no significant survival benefit when comparing R0 versus R1, while the complication rate remained high for the extended resection types. In view of merging multimodal treatment, the hilar first concept assesses locoregional LN status for optimal surgical therapy.

Robotic versus laparoscopic versus open major hepatectomy - an analysis of costs and postoperative outcomes in a single-center setting.

PURPOSE: In the era of minimal-invasive surgery, the introduction of robotic liver surgery (RS) was accompanied by concerns about the increased financial expenses of the robotic technique in comparison to the established laparoscopic (LS) and conventional open surgery (OS). Therefore, we aimed to evaluate the cost-effectiveness of RS, LS and OS for major hepatectomies in this study. METHODS: We analyzed financial and clinical data on patients who underwent major liver resection for benign and malign lesions from 2017 to 2019 at our department. Patients were grouped according to the technical approach in RS, LS, and OS. For better comparability, only cases stratified to the Diagnosis Related Groups (DRG) H01A and H01B were included in this study. Financial expenses were compared between RS, LS, and OS. A binary logistic regression model was used to identify parameters associated with increased costs. RESULTS: RS, LS and OS accounted for median daily costs of 1,725 €, 1,633 € and 1,205 €, respectively (p < 0.0001). Median daily (p = 0.420) and total costs (16,648 € vs. 14,578 €, p = 0.076) were comparable between RS and LS. Increased financial expenses for RS were mainly caused by intraoperative costs (7,592 €, p < 0.0001). Length of procedure (hazard ratio [HR] = 5.4, 95% confidence interval [CI] = 1.7-16.9, p = 0.004), length of stay (HR [95% CI] = 8.8 [1.9-41.6], p = 0.006) and development of major complications (HR [95% CI] = 2.9 [1.7-5.1], p < 0.0001) were independently associated with higher costs. CONCLUSIONS: From an economic perspective, RS may be considered a valid alternative to LS for major liver resections.

Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.

BACKGROUND: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. METHODS: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. RESULTS: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. CONCLUSION: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.

FIRE-9 - PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer.

BACKGROUND: Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer. METHODS: Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer-either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3-10 weeks before randomization-and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm. DISCUSSION: Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020-006,144-18).

Hepatic artery reconstruction using an operating microscope in pediatric liver transplantation-Is it worth the effort?

INTRODUCTION: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. METHODS: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1-year patient and graft survival determined by Kaplan-Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. RESULTS: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full-size grafts. One-year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p = .276 and p = .077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p = .013). One-year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p < .001). Multivariate analysis revealed HAR with SL (p = .022) and deceased donor liver transplantation (DDLT) (p = .014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p < .001) and biliary leakage (p = .045). CONCLUSION: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT).

Challenges of single-stage pancreatoduodenectomy: how to address pancreatogastrostomies with robotic-assisted surgery.

INTRODUCTION: Establishing a sufficient pancreatico-enteric anastomosis remains one of the most important challenges in open single stage pancreatoduodenectomy as they are associated with persisting morbidity and mortality. Applicability on a robotic-assisted approach, however, even increases the requirements. With this analysis we introduce a dorsal-incision-only invagination type pancreatogastrostomy (dioPG) to the field of robotic assistance having been previously proven feasible in the field of open pancreatoduodenectomy and compare initial results to the open approach by means of morbidity and mortality. METHODS: An overall of 142 consecutive patients undergoing reconstruction via the novel dioPG, 38 of them in a robotic-assisted and 104 in an open approach, was identified and further reviewed for perioperative parameters, complications and mortality. RESULTS: We observed a comparable R0-resection rate (p = 0.448), overall complication rate (p = 0.52) and 30-day mortality (p = 0.71) in both groups. Rates of common complications, such as postoperative pancreatic fistula (p = 0.332), postoperative pancreatic hemorrhage (p = 0.242), insufficiency of pancreatogastrostomy (p = 0.103), insufficiency of hepaticojejunostomy (p = 0.445) and the re-operation rate (p = 0.103) were comparable. The procedure time for the open approach was significantly shorter compared to the robotic-assisted approach (p = 0.024). DISCUSSION: The provided anastomosis appeared applicable to a robotic-assisted setting resulting in comparable complication and mortality rates when compared to an open approach. Nevertheless, also in the field of robotic assistance establishing a predictable pancreatico-enteric anastomosis remains the most challenging aspect of modern single-stage pancreatoduodenectomy and requires expertise and experience.

Robotic vs. laparoscopic liver surgery: a single-center analysis of 600 consecutive patients in 6 years.

BACKGROUND: While laparoscopic liver surgery has become a standard procedure, experience with robotic liver surgery is still limited. The aim of this prospective study was to evaluate safety and feasibility of robotic liver surgery and compare outcomes with conventional laparoscopy. METHODS: We here report the results of a single-center, prospective, post-marketing observational study (DRKS00017229) investigating the safety and feasibility of robotic liver surgery. Baseline characteristics, surgical complexity (using the IWATE score), and postoperative outcomes were then compared to laparoscopic liver resections performed at our center between January 2015 and December 2020. A propensity score-based matching (PSM) was applied to control for selection bias. RESULTS: One hundred twenty nine robotic liver resections were performed using the da Vinci Xi surgical system (Intuitive) in this prospective study and were compared to 471 consecutive laparoscopic liver resections. After PSM, both groups comprised 129 cases with similar baseline characteristics and surgical complexity. There were no significant differences in intraoperative variables, such as need for red blood cell transfusion, duration of surgery, or conversion to open surgery. Postoperative complications were comparable after robotic and laparoscopic surgery (Clavien-Dindo ≥ 3a: 23% vs. 19%, p = 0.625); however, there were more bile leakages grade B-C in the robotic group (17% vs. 7%, p = 0.006). Length of stay and oncological short-term outcomes were comparable. CONCLUSIONS: We propose robotic liver resection as a safe and feasible alternative to established laparoscopic techniques. The object of future studies must be to define interventions where robotic techniques are superior to conventional laparoscopy.

Safety and feasibility of robotic liver resection after previous abdominal surgeries.

BACKGROUND: While minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches. METHODS: Clinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses. RESULTS: Out of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien-Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery. CONCLUSIONS: We propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.