Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trial.

Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30-65) days. Nine of 47 patients (19%, 95% CI: 9-33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique - Hôpitaux de Paris (AP-HP).

Combination of a Glissonean Approach and Indocyanine Green Fluorescence Imaging to Perform a Laparoscopic Right Anterior Sectionectomy.

BACKGROUND: Laparoscopic right anterior sectionectomy (LRAS) remains a technically demanding procedure as it requires two transection planes where the middle and right hepatic veins run; however, the main difficulty is locating these two planes1-3. The aim of this video was to show the technique of an LRAS performed with a transparenchymal glissonean pedicle approach and guided by indocyanine green (ICG) staining. METHODS: This was the case of an 80-year-old man with a history of hemochromatosis and normal liver function. He was diagnosed with a 6 cm hepatocellular carcinoma (HCC) located at segment 8, close to the right anterior pedicle. RESULTS: The technique consisted of parenchymal transection along the main portal fissure along the right border of the middle hepatic vein. Opening the liver facilitated access to the right anterior glissonean pedicle and selective transparenchymal clamping. A negative-stain ICG test permitted to demarcate the transection line along the right lateral portal fissure. The parenchymal transection was carried out in a caudal approach, along two perfectly marked planes, preserving the middle and right hepatic veins. The duration of the procedure was 200 min and blood loss was 300 mL. Postoperative course was uneventful and the patient was discharged on the third postoperative day. CONCLUSION: Guidance during resection, and protection of the right posterior pedicle and right hepatic vein are the key points of the LRAS. The glissonean approach and the ICG imaging technology are of great help in resolving these difficulties.

Clinical care pathways of patients with biliary tract cancer: A French nationwide longitudinal cohort study.

BACKGROUND: Although the incidence of BTC is raising, national healthcare strategies to improve care lack. We aimed to explore patient clinical care pathways and strategies to improve biliary tract cancer (BTC) care. METHODS: We analysed the French National Healthcare database of all BTC inpatients between January 1, 2017 and December 31, 2021. Multinomial logistic regression adjusted odds ratios (aOR) were used to identify healthcare organisation factors that influenced access to curative care both overall and in a longitudinal sensibility analysis using optimal matching and hierarchical ascending classification to detect a subgroup of curative-care patients with a high survival over a two-year period. RESULTS: A total of 19,825 new BTC patients and three clinical care pathways (CCP) were identified: 'Palliative care' (PC-CCP), 'Non-curative Care' (NCC-CCP) and 'Curative Care' (CC-CCP) involving 7669 (38.7%), 7721 (38.9%) and 4435 (22.4%) patients respectively. Out of 1200 centers involved in BTC treatment, 84%, 11% and 5% were of low- (<15 patients/year), medium- (15-30 patients/year) and high-volume (>30 patients/year) respectively. Among patient, tumor and hospital factors, BTC management in academic (aOR: 2.32; 95%CI: 1.98-2.71), private (2.51; 2.22-2.83), semi-private (2.25; 1.91-2.65) and in high- (2.09; 1.81-2.42) or medium-volume (1.49; 1.33-1.68) centers increased probability to CC-CCP. These results were maintained in a longitudinal cluster of 2363 (53%) CC-CCP patients presenting a higher two-year survival compared with the rest [96.4% (95.1; 97.6) vs. 38.8% (36.3; 41.4), log-rank p < 0.001]. CONCLUSIONS: Among factors subject to healthcare policy improvement, the volume and type of centers managing BTC strongly influenced access to curative care.

Predictive value of C-reactive protein for postoperative liver-specific surgical site infections.

BACKGROUND: C-reactive protein is a useful biological tool to predict infectious complications, but its predictive value in detecting organ-specific surgical site infection after liver resection has never been studied. We aimed to evaluate the predictive value of c-reactive protein and determine the cut-off values to detect postoperative liver resection-surgical site infection. METHODS: A multicentric analysis of consecutive patients with liver resection between 2018 and 2021 was performed. The predictive value of postoperative day 1, postoperative day 3, and postoperative day 5 C-reactive protein levels was evaluated using the area under the receiver operating characteristic curve. Cut-off values were determined using the Youden index in a 500-fold bootstrap resampling of 500 patients treated at 3 centers, who comprised the development cohort and were tested in an external independent validation cohort of 166 patients at a fourth center. RESULTS: Among the 500 patients who underwent liver resection of the development cohort, liver resection-surgical site infection occurred in 66 patients (13.2%), and the median time to diagnosis was 6.0 days (interquartile range, 4.0-9.0) days. Median C-reactive protein levels were significantly higher on postoperative day 1, postoperative day 3, and postoperative day 5 in the liver resection-surgical site infection group compared with the non-surgical site infection group (50.5 vs 34.5 ng/mL, 148.0 vs 72.5 ng/mL, and 128.4 vs 35.2 ng/mL, respectively; P < .001). Postoperative day 3 and postoperative day 5 C-reactive protein-level area under the curve values were 0.76 (95% confidence interval, 0.64-0.88, P < .001) and 0.82 (95% confidence interval, 0.72-0.92, P < .001), respectively. Postoperative day 3 and postoperative day 5 optimal cut-off values of 100 mg/L and 87.0 mg/L could be used to rule out liver resection-surgical site infection, with a negative predictive value of 87.0% (interquartile range, 70.2-93.8) and 76.0% (interquartile range, 65.0-88.0), respectively, in the validation cohort. CONCLUSION: Postoperative day 3 and postoperative day 5 C-reactive protein levels may be valuable predictive tools for liver resection-surgical site infection and aid in hospital discharge decision-making in the absence of other liver-related complications.

Resection Postradioembolization in Patients With Single Large Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of yttrium-90 transarterial radioembolization (TARE) to convert to resection initially unresectable, single, large (≥5 cm) hepatocellular carcinoma (HCC). BACKGROUND: TARE can downsize cholangiocarcinoma to resection but its role in HCC resectability remains debatable. METHODS: All consecutive patients with a single large HCC treated between 2015 and 2020 in a single tertiary center were reviewed. When indicated, patients were either readily resected (upfront surgery) or underwent TARE. TARE patients were converted to resection (TARE surgery) or not (TARE-only). To further assess the effect of TARE on the long-term and short-term outcomes, a propensity score matching analysis was performed. RESULTS: Among 216 patients, 144 (66.7%) underwent upfront surgery. Among 72 TARE patients, 20 (27.7%) were converted to resection. TARE-surgery patients received a higher mean yttrium-90 dose that the 52 remaining TARE-only patients (211.89±107.98 vs 128.7±36.52 Gy, P <0.001). Postoperative outcomes between upfront-surgery and TARE-surgery patients were similar. In the unmatched population, overall survival at 1, 3, and 5 years was similar between upfront-surgery and TARE-surgery patients (83.0%, 60.0%, 47% vs 94.0%, 86.0%, 55.0%, P =0.43) and compared favorably with TARE-only patients (61.0%, 16.0% and 9.0%, P <0.0001). After propensity score matching, TARE-surgery patients had significantly better overall survival than upfront-surgery patients ( P =0.021), while disease-free survival was similar ( P =0.29). CONCLUSION: TARE may be a useful downstaging treatment for unresectable localized single large HCC providing comparable short-term and long-term outcomes with readily resectable tumors.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

Liver Transplantation as a New Standard of Care in Patients With Perihilar Cholangiocarcinoma? Results From an International Benchmark Study.

OBJECTIVE: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. BACKGROUND: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. METHODS: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. RESULTS: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001). CONCLUSION: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

Liver Resection for Type IV Perihilar Cholangiocarcinoma: Left or Right Trisectionectomy?

How the side of an extended liver resection impacts the postoperative prognosis of advanced perihilar cholangiocarcinoma (PHC) is still controversial. We compared the outcomes of right (RTS) and left trisectionectomies (LTS) in Bismuth-Corlette (BC) type IV PHC resection. All patients undergoing RTS or LTS for BC type IV PHC in a single tertiary center between January 2012 and December 2019 were compared retrospectively. The endpoints were perioperative outcomes, long-term overall (OS), and disease-free survival (DFS). Among 67 hepatic resections for BC type IV PHC, 25 (37.3%) were LTS and 42 (63.7%) were RTS. Portal vein and artery resection rates were 40% and 52.4% (p = 0.29), and 24% and 0% (p < 0.001) in the LTS and RTS groups, respectively. The severe complication (Clavien−Dindo > IIIa) rate was comparable (36% vs. 21.5%, p = 0.357) while the postoperative liver failure (POLF) rate was lower in the LTS group (16% vs. 38%, p = 0.048). The R0 resection rate was similar between groups (81% vs. 92%; p = 0.154). The five-year OS rate was higher in the LTS group (66% vs. 30%, p = 0.009) while DFS was comparable (43% vs. 18%, p = 0.11). Based on multivariable analysis, the side of the trisectionectomy was an independent predictor of OS. Compared with RTS, LTS is associated with lower POLF and higher overall survival despite more frequent arterial reconstructions in type IV PHC. Although technically more demanding, LTS may be preferred in the treatment of advanced PHC.

Perihilar Cholangiocarcinoma - Novel Benchmark Values for Surgical and Oncological Outcomes From 24 Expert Centers.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

Kasai-Like Portoenterostomy for Multiple Biliary Duct Reconstruction After Extended Liver Resection of Perihilar Cholangiocarcinoma.

BACKGROUND: Surgical resection remains the best therapeutic option for the long-term survival of patients with perihilar cholangiocarcinoma (PCC).1 For patients presenting with Bismuth type 3 or 4 tumors, left or right extended liver resection has been shown to be feasible.2 The Achilles heel of the procedure remains biliary reconstruction due to multiple small-diameter remnant liver bile ducts.3 This study showed how a Kasai-like portoenterostomy allows circumvention of this difficulty. METHODS: A 57-year-old woman with a type 3a PCC invading the main portal vein bifurcation underwent a right hepatectomy with en bloc resection of segment 4b, the caudate lobe, and the extrahepatic common bile duct; hepatic pedicle lymphadenectomy; and main portal vein bifurcation reconstruction.4 The cross-section of the left biliary plate was tumor-free at frozen section analysis but involved three small biliary ducts originating from segments 2, 3, and 4a. The biliary plate and the distance between each duct were too large to allow unification. A Roux-en-Y portoenterostomy, inspired by the Kasai procedure,5 was performed between the umbilical plate and the extramucosal wall of an efferent Roux-en-Y jejunal limb. Two temporary external trans-portoenterostomy drains were placed according to the Voelker technique. RESULTS: The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The two trans-portoenterostomy drains were removed after 6 weeks, and patient was disease-free at the 2-year follow-up evaluation. CONCLUSIONS: In extended PCC, Kasai-like portoenterostomy may facilitate complex biliodigestive reconstructions when multiple biliary ducts are involved.

Right Hepatectomy with Vascular and Biliary Reconstruction for a Portal Vein Leiomyosarcoma.

BACKGROUND: Vascular leiomyosarcomas (LMS) are rare malignant mesenchymal tumors arising from vessel smooth muscle cells. They represent only 2% of soft tissue sarcomas and most commonly (50%) originate from the inferior vena cava.1-3 Portal vein LMS are very rare, and their resection combines en bloc negative margin sarcoma surgery principles and complex liver surgery procedures with vascular reconstructions.3-5 METHODS: This is the case of a 42-year-old female presenting with a moderate cholestasis. Imaging revealed a 3-cm tumor originating from the main portal vein and its right branch while being in contact with both the right hepatic artery and biliary confluence. No metastases were identified. Core needle biopsy confirmed the diagnosis and tumor board decision was surgical resection. RESULTS: The procedure included anatomic right hepatectomy with en bloc resection of the portal vein bifurcation, common bile duct, and biliary confluence. Portal venous reconstruction was performed using an autogenous external iliac vein interposition graft, while biliary reconstruction was performed via a Roux-en-Y end-to-side hepatico-jejunostomy. Duration of surgery was 300 min, and blood loss was 300 ml. Postoperative outcomes were uneventful and patient was discharged on postoperative day 8 with a transient right limb edema. Pathology confirmed R0 resection of a T1N0M0 leiomyosarcoma, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade 2 tumor. Patient was free of disease at 20 months post-surgery. CONCLUSIONS: Portal vein leiomyosarcomas are extremely rare. En bloc extensive surgical resection should be proposed to obtain R0 resection, and achieve prolonged survival.4,6,7.