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BackgroundThe liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach.MethodsPatients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis.ResultsOverall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003).ConclusionIn patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

Background Laparoscopic liver resection (LLR) is reported as a safe procedure with potential advantages over open surgery albeit with inherent limitations, such as loss of haptic perception and spatial orientation. Ultrasound is considered the best tool to identify anatomic landmarks and the transection plane during liver surgery. The aim of this study was to analyse the outcomes of LLR performed with a standardized US guidance technique. Methods We have standardized a 4-step technique for ultrasound-guided LLR: (1) compose a 3-D mind map by studying relationships among lesions and surrounding anatomic structures, (2) sketch the map on the liver surface, (3) check, and (4) correct the transection plane in real time. Results Between 01/2006 and 12/2016, 190 consecutive patients treated with US-guided LLR were analysed. The indications for LLR included malignant tumours in 148 patients (81.8%). The procedures were classified according to a difficulty scale. There were 18 major hepatectomies (9.9%), 80 anatomic bi- and monosegmentectomies (44.2%), and 101 non-anatomic resections (55.8%). Redo resection was performed in 17 patients (9.4%), and multiple liver resections were performed in 25 patients (24.7%). Median intraoperative blood loss was 100 ± 154 mL. Overall and major morbidity rates were 14.9% and 1.6%, respectively. Mortality was nil. Conclusions Ultrasound liver map technique enables planning and real-time guidance during laparoscopic liver resections.

BackgroundIntraoperative liver ultrasound appears superior to liver-specific contrast-enhanced magnetic resonance imaging (MRI) to stage colorectal liver metastases (CRLMs). Most of the data come from studies on open surgery. Laparoscopic ultrasound (LUS) is technically demanding and its reliability is poor investigated. Aim of the study was to assess the accuracy of LUS staging for CRLMs compared to MRI.MethodsAll patients with CRLMs scheduled for laparoscopic liver resection (LLR) between 01/2010 and 06/2019 who underwent preoperative MRI were considered for the study. LUS and MRI performance was compared on a patient by patient basis. Reference standards were final pathology and 6 months follow-up results.ResultsAmongst 189 LLR for CRLMs, 146 met inclusion criteria. Overall, 391 CRLMs were preoperatively detected by MRI. 24 new nodules in 16 (10.9%) patients were found by LUS and resected. Median diameter of new nodules was 5.5 mm (2–10 mm) and 10 (41.6%) were located in the hepatic dome. Pathology confirmed 17 newly detected malignant nodules (median size 4 mm) in 11 (7.5%) patients. Relationships between intrahepatic vessels and tumours differed between LUS and MRI in 9 patients (6.1%). Intraoperative surgical strategy changed according LUS findings in 19 (13%) patients, requiring conversion to open approach in 3 (15.8%) of them. The sensitivity of LUS was superior to MRI (93.1% vs 85.6% whilst specificity was similar (98.6% MRI vs 96.5% LUS).ConclusionsLaparoscopic liver ultrasound improves liver staging for CRLMs compared to liver-specific MRI.

BackgroundDifficulty scores (DSs) have been proposed to rate laparoscopic liver resection (LLR) technical difficulty increasing surgical safety. The aim of the study was to validate three DSs (Hasegawa, Halls and Kawaguchi) and compare their ability to predict technical difficulty and postoperative outcomes.Materials and methodsAll patients who underwent LLR from January 2006 to January 2019 were analyzed. Exclusion criteria were cyst fenestrations, thermal ablation, missing data for the computation of the DS and a follow-up < 90 days.ResultsThe population comprised 300 patients. The DS distribution in the study population was: Halls low 55 (18.3%), moderate 82 (27.3%), high 111 (37%) and extremely high 52 (17.3%); Hasegawa low 130 (43.3%), medium 105 (35%) and high 65 (21.7%); Kawaguchi Grade I 194 (64.7%), Grade II 47 (15.7%) and Grade III 59 (19.7%). Hasegawa and Kawaguchi showed the strongest correlation (r = 0.798, p < 0.001). Technical complexity, evaluated using the Pringle maneuver, Pringle time, blood loss and operative time, increased significantly with Hasegawa and Kawaguchi score classes (p < 0.001 for all comparisons). None of the scores properly stratified postoperative complications. The highest Kawaguchi (23.7% grade III vs. 13.7% grades I and II, p = 0.057) and Hasegawa (24.6% high vs. 13.2% low/medium, p = 0.025) classes had a higher overall morbidity rate than medium–low ones.ConclusionsKawaguchi and Hasegawa scores predicted LLR’s technical difficulty. None of the scores discriminated the postoperative complication risk of low classes compared with medium ones.

BackgroundLaparoscopic segment 7 segmentectomy and segment 6–7 bisegmentectomy are challenging resections because of the posterior position and the lack of landmarks. The anatomy of the right posterior Glissonean pedicle and the caudal view of laparoscopy make such resections suitable for the Glissonean pedicle-first approach.MethodsThe study population included all consecutive patients treated with laparoscopic liver resection from August 2019 to February 2020. The approach is based on the ultrasonographic identification of the right posterior or segmental pedicle from the dorsal side of the liver after complete mobilization. The pedicle of interest is isolated through mini-hepatotomy and clamped. The segment anatomy is defined by ischemia. The transection starts from the ventral side, close to the right hepatic vein that is exposed and followed craniocaudally.ResultsTen patients underwent anatomical laparoscopic resection of right posterolateral segments. There were 7 colorectal liver metastases, 2 hepatocellular carcinoma, and 1 biliary cysto-adenoma. Five patients underwent Sg7 resection, one patient underwent a Sg7 subsegmentectomy, and 4 underwent Sg6-7 bisegmentectomy. The Glissonean pedicle-first approach was feasible in eight patients. The craniocaudal approach to the RHV was feasible in six patients, not indicated in three cases and was abandoned in one patient for technical difficulty. There was no operative morbidity or mortality. Median post-operative hospital stay was 5 days.ConclusionsThe Glissonean pedicle-first approach is safe and effective for laparoscopic anatomic resections of the right posterior sector. The craniocaudal approach to right hepatic vein from the ventral side is a convenient procedure to follow the segmental anatomy deep in the parenchyma.

Background Liver surgery is the gold-standard treatment of colorectal liver metastases. Five-year survival rates may be inadequate to evaluate surgical outcomes because some patients are alive with recurrence and late recurrences are possible. The aim of this study was to analyze 10-year survival outcome in terms of late recurrence rate and prognostic factors of survival. Methods One hundred twenty-five patients underwent liver resection for colorectal liver metastases between 1985 and 1996. Four patients who experienced postoperative mortality were excluded. The analysis was performed on 121 patients. Results Five- and 10-year survival rates were 23.1% and 15.7%, respectively. Nineteen patients were alive 10 years after liver resection and 17 were disease-free (5 after re-resection). Five- and 10-year disease-free survival rates were 17.4% and 14.8%, respectively. In patients with recurrence, re-resection significantly improved survival ( P  < 0.001); 98% of recurrences occurred within the first 5 years, but 15% of patients disease-free at 5 years developed later recurrence. Multivariate analysis evidenced five independent negative prognostic factors of survival: male sex ( P  = 0.029), synchronous metastases ( P  = 0.011), >3 metastases ( P  < 0.001), metastatic infiltration of nearby structures ( P  < 0.001), and postoperative morbidity ( P  < 0.001). In 17 patients without negative prognostic factors the 10-year survival rate was 35.3%. Conclusion Liver resection for colorectal liver metastases may be curative in more than one-third of patients without negative prognostic factors. Postoperative morbidity significantly worsens long-term outcomes. The risk of recurrence after liver resection is high even after 5 years of follow-up, but re-resection can improve the outcome.

Background To evaluate early outcomes of venous reconstruction with peritoneal patch (PP) during resection for hepatic malignancies. Methods Since May 2015, PP was considered as the first option for venous reconstruction in the case of lateral resection. Between May 2015 and June 2019, 579 consecutive hepatectomies for malignancies were performed at our institution. Among 27 patients requiring venous resection, PP was used in 22, who were included in the present study. Data from a prospectively collected database were analysed. Results Tumour types were ten colorectal metastases (CRLM), six intrahepatic cholangiocarcinomas, four hilar cholangiocarcinomas, one hepatocellular carcinoma and one gallbladder carcinoma. Hepatectomies were major in 50% of cases. Eleven patients had hepatic vein resections, eight portal vein and three inferior vena cava. Venous reconstruction enabled resection in 12 (54.5%) patients, otherwise non-resectable. Among CRLM, the venous reconstruction allowed avoidance of major resection in eight (80%) cases. Median operative time was 456 min (range 270–960). Blood loss was a median 300 cc (range 40–1500), and blood transfusions were required in three patients (13.6%). At pathological examination, venous infiltration was confirmed in 14 (63.6%) patients. No vascular complications related to the patch were recorded. Post-operative major (Dindo III/IV) complications were observed in two (9%) patients. One patient died because of liver failure without vascular thrombosis and one due to biliary fistula complicated by arterial bleeding. Overall, post-operative mortality was 9% (2/22). Conclusions Venous reconstruction with peritoneal patch during hepatectomy for malignancies can feasibly allow resection in otherwise unresectable patients and decrease the rate of major resection in colorectal liver metastases.

BackgroundThe high technical difficulty of using a laparoscopic approach to reach the posterosuperior liver segments is mainly associated with their poor accessibility. This study was performed to analyze correlations between anthropometric data and intraoperative outcomes.Study designAll patients who underwent segmentectomy or wedge laparoscopic liver resection (LLR) of segments seven and/or eight from June 2012 to November 2019 were retrospectively analyzed. The exclusion criteria were intrahepatic cholangiocarcinoma, associated resection, multiple concomitant LLR, redo resection, and lack of preoperative imaging. Anthropometric data were correlated with intraoperative outcomes.ResultsForty-one patients (wedge resection, n = 32; segmentectomy, n = 9) were analyzed. A strong correlation was found between the craniocaudal liver diameter (CCliv) and liver volume (r = 0.655, p < 0.001). The anteroposterior liver diameter was moderately correlated with both the laterolateral abdominal diameter (LLabd) (r = 0.372, p = 0.008) and anteroposterior abdominal diameter (r = 0.371, p = 0.008). The body mass index (BMI) was not correlated with liver diameters. Women had a longer CCliv (p = 0.002) and shorter LLabd (p < 0.001) than men. The liver and abdominal measurements were combined to reduce this sex-related disparity. The CCliv/LLabd ratio (CHALLENGE index) was significantly correlated with the time of transection (r = 0.382, p = 0.037) and blood loss (r = 0.352, p = 0.029). The association between the CHALLENGE index and intraoperative blood loss was even stronger when considering only anatomical resection (r = 0.577, p = 0.048). A CHALLENGE index of > 0.4 (area under the curve, 0.757; p = 0.046) indicated a higher bleeding risk. The BMI predicted no intraoperative outcomes.ConclusionAnthropometric data rather than the BMI can help anticipate the difficulty of LLR of segments seven and eight.

Background Preliminary series have shown the feasibility of combined laparoscopic resection of colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM). The aim of this study was to compare the short- and long-term outcomes for matched patients undergoing combined resections. Methods An international multicenter database of 142 patients that underwent combined laparoscopic resection of CRC and SCRLM between 1997 and 2013 was compared to a database of 241 patients treated by open during the same period. Comparison of short- and long-term outcomes was performed after propensity score adjustment. Results After matching, 89 patients were compared in each group including mostly ASA I–II patients, presenting with mean number of 1.5 CRLM, with a mean diameter of 30 mm, and resectable by a wedge resection or a left lateral sectionectomy. A rectal resection was required in 46 and 43 % of laparoscopic and open procedures, respectively ( p  = 0.65). There was no difference in global operative time, blood loss and transfusion rates between the two groups. A conversion was required in 7 % of the laparoscopic procedures. Morbidity rates were similar in the two groups ( p  = 1.0). The 3-year overall survival in the laparoscopy and open groups were 78 and 65 %, respectively ( p  = 0.17). Conclusions In patients without severe comorbidities presenting with one, small (≤3 cm), CRLM resectable by a wedge resection or a left lateral sectionectomy, combined laparoscopic resection of CRC and SCRLM allowed similar short- and long-term outcomes compared with the open approach.

The breadth and depth at which cancer models are interrogated contribute to the successful clinical translation of drug discovery efforts. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, where experimental therapies are typically tested. Here we introduce XENTURION, an open-science resource offering a platform of 128 PDX models from patients with metastatic CRC, along with matched PDX-derived tumoroids. Multidimensional omics analyses indicate that tumoroids retain extensive molecular fidelity with parental PDXs. A tumoroid-based trial with the anti-EGFR antibody cetuximab reveals variable sensitivities that are consistent with clinical response biomarkers, mirror tumor growth changes in matched PDXs, and recapitulate EGFR genetic deletion outcomes. Inhibition of adaptive signals upregulated by EGFR blockade increases the magnitude of cetuximab response. These findings illustrate the potential of large living biobanks, providing avenues for molecularly informed preclinical research in oncology. Improvement of preclinical models is critical for ensuring effective treatment discovery for colorectal cancer. Here, the authors develop a platform of 128 PDX models from metastatic colorectal cancer with matched tumouroid cultures, and use these to demonstrate molecular concordance between PDX-tumouroid pairs, cetuximab sensitivity heterogeneity, and adaptive upregulation of druggable targets under cetuximab pressure.