Long-Term Outcomes of Perioperative Versus Neoadjuvant Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-Score Matched Analysis with Stratification by Contemporary Risk-Scoring.

BACKGROUND: There is still debate regarding the principal role and ideal timing of perioperative chemotherapy (CTx) for patients with upfront resectable colorectal liver metastases (CRLM). This study assesses long-term oncological outcomes in patients receiving neoadjuvant CTx only versus those receiving neoadjuvant combined with adjuvant therapy (perioperative CTx). METHODS: International multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010 and 2015. Characteristics and outcomes were compared before and after propensity score matching (PSM). Primary endpoints were long-term oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS). Furthermore, stratification by the tumour burden score (TBS) was applied. RESULTS: Of 967 patients undergoing hepatectomy, 252 were analysed, with a median follow-up of 45 months. The unmatched comparison revealed a bias towards patients with neoadjuvant CTx presenting with more high-risk patients (p = 0.045) and experiencing increased postoperative complications ≥Clavien-Dindo III (20.9% vs. 8%, p = 0.003). Multivariable analysis showed that perioperative CTx was associated with significantly improved RFS (hazard ratio [HR] 0.579, 95% confidence interval [CI] 0.420-0.800, p = 0.001) and OS (HR 0.579, 95% CI 0.403-0.834, p = 0.003). After PSM (n = 180 patients), the two groups were comparable regarding baseline characteristics. The perioperative CTx group presented with a significantly prolonged RFS (HR 0.53, 95% CI 0.37-0.76, p = 0.007) and OS (HR 0.58, 95% CI 0.38-0.87, p = 0.010) in both low and high TBS patients. CONCLUSIONS: When patients after resection of CRLM are able to tolerate additional postoperative CTx, a perioperative strategy demonstrates increased RFS and OS in comparison with neoadjuvant CTx only in both low and high-risk situations.

Surgical treatment of an intraductal papillary mucinous neoplasm of the biliary tract diagnosed by SpyGlass®.

We present the case of a 76-year-old male with a history of acute cholecystitis who underwent a scheduled laparoscopic cholecystectomy. Chronic cholecystitis with a thickened cystic duct was observed intraoperatively. The anatomic pathology report found high-grade dysplasia that affected the distal edge of the cystic duct. In view of these findings, an endoscopic retrograde cholangiopancreatography (ERCP) was performed with SpyGlass® and an excrescent lesion suggestive of malignancy adjacent to the cystic-common bile duct junction was observed. A resection of the extrahepatic bile duct was performed with lymphadenectomy of the hepatic hilum and hepaticojejunostomy in a subsequent procedure. The definitive pathology report confirmed pancreaticobiliary intraductal papillary mucinous neoplasia with high-grade dysplasia and free margins.

Perioperative chemotherapy versus surgery alone for resectable colorectal liver metastases: an international multicentre propensity score matched analysis on long-term outcomes according to established prognostic risk scores.

BACKGROUND: There is still uncertainty regarding the role of perioperative chemotherapy (CTx) in patients with resectable colorectal liver metastases (CRLM), especially in those with a low-risk of recurrence. METHODS: Multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010-2015. Patients were divided into two groups according to whether they received perioperative CTx or not and were compared using propensity score matching (PSM) analysis. Then, they were stratified according to prognostic risk scores, including: Clinical Risk Score (CRS), Tumour Burden Score (TBS) and Genetic And Morphological Evaluation (GAME) score. RESULTS: The study included 967 patients with a median follow-up of 68 months. After PSM analysis, patients with perioperative CTx presented prolonged overall survival (OS) in comparison with the surgery alone group (82.8 vs 52.5 months, p = 0.017). On multivariable analysis perioperative CTx was an independent predictor of increased OS (HR 0.705, 95%CI 0.705-0.516, p = 0.029). The benefits of perioperative CTx on survival were confirmed in patients with CRS and TBS scores ≤2 (p = 0.022 and p = 0.020, respectively) and in patients with a GAME score ≤1 (p = 0.006). CONCLUSION: Perioperative CTx demonstrated an increase in OS in patients with CRLM. Patients with a low-risk of recurrence seem to benefit from systemic treatment.

Impact of type and severity of postoperative complications on long-term outcomes after colorectal liver metastases resection.

BACKGROUND AND OBJECTIVES: Postoperative complications (POCs) after hepatic resection for colorectal liver metastases (CRLM) adversely affect long-term survival. The aim of this study was to analyze the effect of POC etiology and severity on overall survival (OS) and disease-free survival (DFS). METHODS: A retrospective study of 254 consecutive hepatectomies for CRLM was performed. Univariate and multivariate analyses were performed to determine the effects of demographic, tumor-related and perioperative variables on OS and DFS. A 1:1 propensity score matching (PSM) was then used to compare patients with different POC etiology: infective (Inf-POC), noninfective (Non-inf POC), and no-complications (No-POC). RESULTS: Inf-POC, Non-inf POC, and No-POC patients represented 18.8%, 19.2%, and 62% of the sample, respectively. In univariate and multivariate analyses infectious POC were independent risk factors for decreased OS and DFS. After PSM, Inf-POC group presented decreased OS and DFS when compared with Non-inf POC (5-year OS 31.8% vs 51.6%; P = .05 and 5-year DFS 13.6% vs 31.9%; P = .04) and with No-POC (5-year OS 29.4% vs 58.7%; P = .03 and 5-year DFS 11.8% vs 39.7%; P = .03). There were no differences between Non-inf POC and No-POC patients. POC severity calculated using the Comprehensive Complications Index did not influence OS and DFS before and after PSM. CONCLUSION: The negative oncological impact of POCs after CRLM resection is determined by infective etiology not by severity.

Impact of Postoperative Complications on Survival and Recurrence After Resection of Colorectal Liver Metastases: Systematic Review and Meta-analysis.

OBJECTIVE: To study the effect of postoperative complications (POC) on overall survival (OS) and disease-free survival (DFS) after surgical resection of colorectal liver metastases (CRLM). SUMMARY BACKGROUND DATA: Morbidity rates after liver resection can reach 45%. The negative impact of POC on oncologic outcomes has been reported in various types of cancer, especially colorectal. However, data on the consequences of POC after CRLM resection on long-term survival are scarce. METHODS: Eligible studies examining the association between POC after CRLM resection and OS/DFS were sought using the PubMed and Web of Science databases. A random-effects model was used to calculate pooled effect estimate for OS and DFS hazard ratios (HR), estimating between-study variance with restricted maximum likelihood estimator with Hartung-Knapp adjustment. Subgroup analysis was used to control the effect of POC on OS and DFS for: 1) Method used to define postoperative complications, 2) Exclusion of early postoperative death from survival analysis, 3) Method of data extraction used, and 4) Tumor and treatment characteristics. RESULTS: Forty-one studies were deemed eligible, including 12,817 patients. POC patients had a significant risk of reduced OS compared with no POC group (HR 1.43 [95% CI: 1.3, 1.57], P < 0.0001). POC had also a negative impact on DFS. The HR for reduced DFS was 1.38 [95% CI 1.27, 1.49], P < 0.0001. The negative impact of POC on survival and recurrence was confirmed in subgroup analysis. CONCLUSIONS: Our findings evidence the negative impact of POC on survival and recurrence after CRLM resection.

Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy?: A Multicenter, Randomized, Controlled Trial.

OBJECTIVE: To compare the rates of R0 resection in pancreatoduodenectomy (PD) for pancreatic and periampullary malignant tumors by means of standard (ST-PD) versus artery-first approach (AFA-PD). BACKGROUND: Standardized histological examination of PD specimens has shown that most pancreatic resections thought to be R0 resections are R1. "Artery-first approach" is a surgical technique characterized by meticulous dissection of arterial planes and clearing of retropancreatic tissue in an attempt to achieve a higher rate of R0. To date, studies comparing AFA-PD versus ST-PD are retrospective cohort or case-control studies. METHODS: A multicenter, randomized, controlled trial was conducted in 10 University Hospitals (NCT02803814, ClinicalTrials.gov). Eligible patients were those who presented with pancreatic head adenocarcinoma and periampullary tumors (ampulloma, distal cholangiocarcinoma, duodenal adenocarcinoma). Assignment to each group (ST-PD or AFA-PD) was randomized by blocks and stratified by centers. The primary end-point was the rate of tumor-free resection margins (R0); secondary end-points were postoperative complications and mortality. RESULTS: One hundred seventy-nine patients were assessed for eligibility and 176 randomized. After exclusions, the final analysis included 75 ST-PD and 78 AFA-PD. R0 resection rates were 77.3% (95% CI: 68.4-87.4) with ST-PD and 67.9% (95% CI: 58.3-79.1) with AFA-PD, P=0.194. There were no significant differences in postoperative complication rates, overall 73.3% versus 67.9%, and perioperative mortality 4% versus 6.4%. CONCLUSIONS: Despite theoretical oncological advantages associated with AFA-PD and evidence coming from low-level studies, this multicenter, randomized, controlled trial has found no difference neither in R0 resection rates nor in postoperative complications in patients undergoing ST-PD versus AFA-PD for pancreatic head adenocarcinoma and other periampullary tumors.

The role of endoscopic retrograde cholangiopancreatography in the management of iatrogenic bile duct injury after cholecystectomy.

INTRODUCTION: iatrogenic bile duct injury (IBDI) is a complication with a high morbidity after cholecystectomy. In recent years, endoscopy has acquired a fundamental role in the management of this pathology. METHODS: a retrospective study of IBDI after open cholecystectomy (OC) or laparoscopic cholecystectomy (LC) of patients treated in our center between 1993 and 2017 was performed. Clinical characteristics, type of injury according to the Strasberg-Bismuth classification, diagnosis, repair techniques and follow-up were analyzed. RESULTS: 46 patients were studied and IBDI incidence was 0.48%, 0.61% for LC and 0.24% for OC. A diagnosis was made intraoperatively in 12 cases (26%) and by endoscopic retrograde cholangiopancreatography (ERCP) in 10 (21.7%) cases. The most common IBDI patient characteristics were acute cholecystitis (20/46, 43.5%), previous admission due to biliary pathology (16/46, 43.2%) and ERCP prior to cholecystectomy (7/46, 18.9%). The most frequent types of IBDI were D (17/46, 36.9%) and A (15/46, 32.6%). The most commonly used treatment was primary suture (13/46, 28.3%) followed by ERCP (11/46, 23.9%) with sphincterotomy and/or stents. In addition, ERCP was performed during the immediate postoperative period in 6 (13%) patients with a surgical IBDI repair in order to resolve immediate complications. CONCLUSION: ERCP is useful in the management of IBDI that is not diagnosed intraoperatively. This procedure facilitates the localization of the injured area of the bile duct, therapeutic maneuvers and successful outcomes in postoperative complications.

Is Percutaneous Transhepatic Biliary Drainage Better than Endoscopic Drainage in the Management of Jaundiced Patients Awaiting Pancreaticoduodenectomy? A Systematic Review and Meta-analysis.

PURPOSE: To compare postoperative complications in patients who underwent pancreatoduodenectomy after either endoscopic or percutaneous biliary drain (BD). MATERIAL AND METHODS: Data from studies comparing the rate of postoperative complications in patients who underwent endoscopic BD or percutaneous BD before pancreatoduodenectomy were extracted independently by 2 investigators. The primary outcome compared in the meta-analysis was the risk of postoperative complications. Secondary outcomes were the risks of procedure-related complications, postoperative mortality, postoperative pancreatic fistula, severe complications, and wound infection. For dichotomous variables, the odds ratio (OR) with 95% confidence interval (CI) was calculated. RESULTS: Thirteen studies, including 2334 patients (501 in the percutaneous BD group and 1833 in the endoscopic group), met the inclusion criteria. Postoperative and procedure-related complication rates were significantly lower in the percutaneous BD group (OR = .7, 95% CI = .52-.94, P = .02 and OR = .44, 95% CI = .23-.84, P = .01, respectively). No significant differences were observed when severe postoperative complications, postoperative mortality, postoperative pancreatic fistula, and wound infection rates were compared. CONCLUSIONS: In patients awaiting pancreatoduodenectomy, preoperative percutaneous BD is associated with fewer procedure-related or postoperative complications than endoscopic drain.

Impact of monopolar radiofrequency coagulation on intraoperative blood loss during liver resection: a prospective randomised controlled trial.

PURPOSE: To evaluate the impact of using monopolar thermal coagulation based on radiofrequency (RF) currents on intraoperative blood loss during liver resection. MATERIALS AND METHODS: A prospective randomised controlled trial was planned. Patients undergoing hepatectomy were randomised into two groups. In the control group (n = 10), hemostasis was obtained with a combination of stitches, vessel-sealing bipolar RF systems, sutures or clips. In the monopolar radiofrequency coagulation (MRFC) group (n = 18), hemostasis was mainly obtained using an internally cooled monopolar RF electrode. RESULTS: No differences in demographic or clinical characteristics were found between groups. Mean blood loss during liver resection in the control group was more than twice that of the MRFC group (556 ± 471 ml vs. 225 ± 313 ml, p = .02). The adjusted mean bleeding/transection area was also significantly higher in the control group (7.0 ± 3.3 ml/cm2 vs. 2.8 ± 4.0 ml/cm2, p = .006). No significant differences were observed in the rate of complications between the groups. CONCLUSIONS: The findings suggest that the monopolar electrocoagulation created with an internally cooled RF electrode considerably reduces intraoperative blood loss during liver resection.

Long-term evolution of acinar-to-ductal metaplasia and ß-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model.

BACKGROUND: Pancreatic duct ligation (PDL) has been used as a model of chronic pancreatitis and as a model to increase ß-cell mass. However, studies in mice have demonstrated acinar regeneration after PDL, questioning the long-term validity of the model. We aim to elucidate whether RF-assisted transection (RFAT) of the main pancreatic duct is a reliable PDL model, both in short (ST, 1-month) and long-term (LT, 6-months) follow-ups. METHODS: Eleven pigs were subjected to RFAT. Biochemical (serum/peripancreatic amylase and glucose) and histological changes (including a semiautomatic morphometric study of over 1000 images/pancreas and IHC analysis) were evaluated after ST or LT follow-up and also in fresh pancreas specimens that were used as controls for 1 (n = 4) and 6 months (n = 6). RESULTS: The distal pancreas in the ST was characterized by areas of acinar-to-ductal metaplasia (56%) which were significantly reduced at LT (21%) by fibrotic replacement and adipose tissue. The endocrine mass showed a normal increase. CONCLUSION: RFAT in the pig seems to be an appropriate PDL model without restoration of pancreatic drainage or reduction of endocrine mass.

Radiofrequency-induced heating versus mechanical stapler for pancreatic stump closure: in vivo comparative study.

PURPOSE: The aim of this study was to assess the capacity of two methods of surgical pancreatic stump closure in terms of reducing the risk of pancreatic fistula formation (POPF): radiofrequency-induced heating versus mechanical stapler. MATERIALS AND METHODS: Sixteen pigs underwent a laparoscopic transection of the neck of the pancreas. Pancreatic anastomosis was always avoided in order to work with an experimental model prone to POPF. Pancreatic stump closure was conducted either by stapler (ST group, n = 8) or radiofrequency energy (RF group, n = 8). Both groups were compared for incidence of POPF and histopathological alterations of the pancreatic remnant. RESULTS: Six animals (75%) in the ST group and one (14%) in the RF group were diagnosed with POPF (p = 0.019). One animal in the RF group and three animals in the ST group had a pseudocyst in close contact with both pancreas stumps. On day 30 post-operation (PO), almost complete atrophy of the exocrine distal pancreas was observed when the main pancreatic duct was efficiently sealed. CONCLUSIONS: Our findings suggest that RF-induced heating is more effective at closing the pancreatic stump than mechanical stapler and leads to the complete atrophy of the distal remnant pancreas.

Results of a laparoscopic approach for the treatment of acute small bowel obstruction due to adhesions and internal hernias.

INTRODUCTION: Laparotomy is the standard approach for the surgical treatment of acute small bowel obstruction (ASBO). PATIENTS AND METHODS: From February 2007 to May 2012 we prospectively recorded all patients operated by laparoscopy in our hospital because of ASBO due to adhesions (27 cases) and/or internal hernia (6 cases). A preoperative abdominal CT was performed in all cases. Patients suffering from peritonitis and/or sepsis were excluded from the laparoscopic approach. It was decided to convert to laparotomy if intestinal resection was required. RESULTS: The mean age of the 33 patients who underwent surgery was 61.1 ± 17.6 years. 64% had previous history of abdominal surgery. 72% of the cases were operated by surgeons highly skilled in laparoscopy. Conversion rate was 21%. Operative time and postoperative length of stay were 83 ± 44 min. and 7.8 ± 11.2 days, respectively. Operative time (72 ± 30 vs 123 ± 63 min.), tolerance to oral intake (1.8 ± 0.9 vs 5.7 ± 3.3 days) and length of postoperative stay (4.7 ± 2.5 vs 19.4 ± 21 days) were significantly lower in the laparoscopy group compared with the conversion group, although converted patients had greater clinical severity (2 bowel resections). There were two severe complications (Clavien-Dindo III and V) in the conversion group. CONCLUSIONS: In selected cases of ASBO caused by adhesions and internal hernias and when performed by surgeons highly skilled in laparoscopy, a laparoscopic approach has a high probability of success (low conversion rate, short hospital length of stay and low morbidity); its use would be fully justified in these cases.

Interference with mitochondrial function as part of the antifibrogenic effect of Rilpivirine: A step towards novel targets in hepatic stellate cell activation.

Activated hepatic stellate cells (aHSCs), the main perpetrators of liver fibrosis, are a promising therapeutic target in the treatment of chronic liver disease. During liver injury, HSCs transcend from a quiescent to a fibrotic phenotype, a process which involves major metabolic reprogramming with altered mitochondrial function. The antiretroviral drug Rilpivirine (RPV) has demonstrated a hepatoprotective and specifically antifibrotic effect in several animal models of chronic liver injury, as well as in vitro. Herein, we use HSCs activated with the profibrogenic cytokine TGF-ß to explore whether mitochondrial function is implicated in this effect. The mitochondrial bioenergetic profile, morphology and dynamics of TGF-ß-treated cells (48 h) were altered and these effects were prevented by co-treatment with clinically relevant concentrations of RPV. A MitoStress Test (Seahorse Analyzer) revealed that TGF-ß increased both oxygen consumption rate (basal respiration, maximal respiration and spare respiratory capacity) and extracellular acidification rate (indicative of increased glycolysis). Cells exposed to TGF-ß also displayed diminished mitochondrial membrane potential and enhanced mitochondrial fission. All of these effects were rescued with RPV. RNA sequencing analysis of cells exposed to TGF-ß revealed the presence of 338 differentially expressed genes that encode mitochondrial proteins (mito-DEGs), of which 139 and 199 were significantly up- and down-regulated (adjusted p<0.05). This alteration in 15 (10.79 %) and 31 (22.03 %) of the up-regulated and 16 (8.04 %) and 49 (24.62 %) of the down-regulated mitoDEGs was prevented with co-exposure to RPV 4µM or 8µM, respectively. In conclusion, alterations in mitochondrial function are implicated in the antifibrogenic action of RPV, pointing to potential novel antifibrotic targets.

Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: Should surgical strategy be influenced by tumor biology?

BACKGROUND: KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. METHODS: All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. RESULTS: The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01-2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06-1.91). CONCLUSIONS: KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.

ctDNA whole exome sequencing in pancreatic ductal adenocarcinoma unveils organ-dependent metastatic mechanisms and identifies actionable alterations in fast progressing patients.

Understanding progression mechanisms and developing new targeted therapies is imperative in pancreatic ductal adenocarcinoma (PDAC). In this study, 80 metastatic PDAC patients were prospectively recruited and divided into discovery (n=37) and validation (n=43) cohorts. Tumor and plasma samples taken at diagnosis were pair analyzed using whole exome sequencing (WES) in patients belonging to the discovery cohort alone. The variant allele frequency (VAF) of KRAS mutations was measured by ddPCR in plasma at baseline and response assessment in all patients. Plasma WES identified at least one pathogenic variant across the cohort, uncovering oncogenic mechanisms, DNA repair, microsatellite instability, and alterations in the TGFb pathway. Interestingly, actionable mutations were mostly found in plasma rather than tissue. Patients with shorter survival showed enrichment in cellular organization regulatory pathways. Through WES we could identify a specific molecular profile of patients with liver metastasis, which exhibited exclusive mutations in genes related to the adaptive immune response pathway, highlighting the importance of the immune system in liver metastasis development. Moreover, KRAS mutations in plasma (both at diagnosis and persistent at follow-up) correlated with shorter progression free survival (PFS). Patients presenting a reduction of over 84.75 % in KRAS VAF at response assessment had similar PFS to KRAS-negative patients. Overall, plasma WES reveals molecular profiles indicative of rapid progression, potentially actionable targets, and associations between adaptive immune response pathway alterations and liver tropism.

A machine learning predictive model for recurrence of resected distal cholangiocarcinoma: Development and validation of predictive model using artificial intelligence.

INTRODUCTION: Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA. MATERIAL AND METHODS: This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm. RESULTS: Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%-0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%-94.4 %) and 91.5 % (95 % CI, 88.4%-93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/. CONCLUSIONS: This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up.

Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.