Simultaneous resection of colorectal cancer and synchronous liver metastases: what determines the risk of unfavorable outcomes? An international multicenter retrospective cohort study

BACKGROUND: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes. METHODS: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression. RESULTS: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013). CONCLUSIONS: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections

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Bridging patients with hepatocellular cancer waiting for liver transplant: all the patients are the same?

Liver transplant (LT) is considered the best curative treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. The possibility to perform LT in HCC patients is limited by the liver grafts supply; indeed, the shortage of donors often leads to a long time on waiting list and then to dropout because of tumor progression. Bridging therapies are neo-adjuvant treatments given to patients on LT waitlist, with the aim to prevent tumor progression and to reduce dropout rate. Many bridging modalities have been proposed. The choice of each treatment is based on the characteristics of the patient, liver function, comorbidities and on the number, dimensions and localization of HCC. This review article describes several types of bridging therapies, focusing on the indications for different kind of patients

Liver transplantation for metastatic wild-type gastrointestinal stromal tumor in the era of molecular targeted therapies: report of a first case.

The gastrointestinal stromal tumor (GIST) is a digestive neoplasm of mesenchymal lineage. The treatment strategy for receptor tyrosine kinase-mutated GISTs is well defined. Wild-type GISTs (WT-GISTs) respond unsatisfactorily to specific kinase inhibitors. Moreover, evidence shows that repeat surgery has limited benefit. We report the case of a young female patient who was diagnosed with liver metastatic WT-GIST, after initial radical resection and adjuvant therapy with molecular targeted drugs. Due to the disease progression, a two-stage surgery was performed, with the removal of extrahepatic lesions followed by a total hepatectomy. The patient is disease-free after four years from liver transplantation (LT), performed under everolimus-based immunosuppression. The treatment of WT-GISTs remains a significant challenge due to the frequent resistance to tyrosine kinase inhibitors (TKIs). Liver transplantation might represent an effective treatment option for such disease

Effectiveness and safety of octogenarian donors in liver transplantation: propensity score matched study from two Italian liver transplant centers

Background: Due to organ shortage, the use of older donors is an acceptable option to decrease waiting list mortality. However, survival outcomes of liver transplantation (LT) with octogenarian grafts remain controversial. Methods: Data were retrieved from the prospectively maintained databases of two Italian liver transplant centers (Bergamo and Ancona), including first, adult, non-urgent, ABO-identical LTs from January 2004 to June 2017. LTx with HCV positive and partial liver grafts were also excluded. Among 732 recipients included, 78 (10.7%) received an octogenarian graft (Oct-Group) and 654 a standard graft (18-79 years:Std-Group). A propensity score approach with 1:2 match was applied to balance 12 possible risk factors for graft loss related to the recipient (LT-year, age, gender, liver disease etiology, presence of HCC, lab-MELD) and to the donor (gender, cause of death, Na peak, BMI, anti-HBc positivity, cold ischemia time). Results: Oct-Group recipients were successfully matched with 156 Std-Group patients in terms of donor, recipient and perioperative characteristics. After a median follow-up of 51 (IQR:20.3-93.4) months, 1- 3- and 5-year patient survival was 85.4%, 75.3% and 71.1% in the Oct-Group vs 85.7%, 78.6% and 75.1% in the Std-Group, respectively (log-rank p-value:0.283). Five-year graft survival was also similar (Oct-Group: 69.8% vs 72.9% Std-Group; p-value: 0.423). Early (within 30 days) re-LTx rate (1.3% vs 1.3%; p-value:0.538) and HCV-related deaths (1.3 vs 2.6%; p-value:0.874) were identical in the two groups. Subgroup analysis revealed similar 5-year survival outcomes when octogenarian grafts were allocated in HCV positive (54.2% vs 68.1%;p-value:0.224) or higher (≥25) MELD (67.9% vs 65.2%; p-value:0.831) recipients. After multivariate analysis, the only independent prognostic factor for graft loss was a pre-LT MELD-score ≥ 30 [Exp(b):1.92;p-value:0.035]. Conclusions: Use of octogenarian grafts, even when these are allocated to high-risk recipients, is not associated with a worse outcome

Incidence and Clinical Impact of Bile Leakage after Laparoscopic and Open Liver Resection: An International Multicenter Propensity Score-Matched Study of 13,379 Patients

Background: Despite many developments, postoperative bile leakage (POBL) remains a relatively common postoperative complication after laparoscopic liver resection (LLR) and open liver resection (OLR). This study aimed to assess the incidence and clinical impact of POBL in patients undergoing LLR and OLR in a large international multicenter cohort using a propensity score-matched analysis. Study design: Patients undergoing LLR or OLR for all indications between January 2000 and October 2019 were retrospectively analyzed using a large, international, multicenter liver database including data from 15 tertiary referral centers. Primary outcome was clinically relevant POBL (CR-POBL), defined as Grade B/C POBL. Results: Overall, 13,379 patients met the inclusion criteria and were included in the analysis (6,369 LLR and 7,010 OLR), with 6.0% POBL. After propensity score matching, a total of 3,563 LLR patients were matched to 3,563 OLR patients. In both groups, propensity score matching accounted for similar extent and types of resections. The incidence of CR-POBL was significantly lower in patients after LLR as compared with patients after OLR (2.6% vs 6.0%; p < 0.001). Among the subgroup of patients with CR-POBL, patients after LLR experienced less severe (non-POBL) postoperative complications (10.1% vs 20.9%; p = 0.028), a shorter hospital stay (12.5 vs 17 days; p = 0.001), and a lower 90-day/in-hospital mortality (0% vs 5.4%; p = 0.027) as compared with patients after OLR with CR-POBL. Conclusion: Patients after LLR seem to experience a lower rate of CR-POBL as compared with the open approach. Our findings suggest that in patients after LLR, the clinical impact of CR-POBL is less than after OLR

Survival Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-2)

Introduction: Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM) was a propensity score matched (PSM) study that reported short-term outcomes of patients with CRLM who met the Milan criteria and underwent either open (OLR), laparoscopic (LLR) or robotic liver resection (RLR). This study, designated as SIMMILR-2, reports the long-term outcomes from that initial study, now referred to as SIMMILR-1. Methods: Data regarding neoadjuvant chemotherapeutic (NC) and neoadjuvant biological (NB) treatments received were collected, and Kaplan&ndash;Meier curves reporting the 5-year overall (OS) and recurrence-free survival (RFS) for OLR, LLR and RLR were created for patients who presented with synchronous lesions only, as there was insufficient follow-up for patients with metachronous lesions. Results: A total of 73% of patients received NC and 38% received NB in the OLR group compared to 70% and 28% in the LLR group, respectively (p = 0.5 and p = 0.08). A total of 82% of patients received NC and 40% received NB in the OLR group compared to 86% and 32% in the RLR group, respectively (p &gt; 0.05). A total of 71% of patients received NC and 53% received NB in the LLR group compared to 71% and 47% in the RLR group, respectively (p &gt; 0.05). OS at 5 years was 34.8% after OLR compared to 37.1% after LLR (p = 0.4), 34.3% after OLR compared to 46.9% after RLR (p = 0.4) and 30.3% after LLR compared to 46.9% after RLR (p = 0.9). RFS at 5 years was 12.1% after OLR compared to 20.7% after LLR (p = 0.6), 33.3% after OLR compared to 26.3% after RLR (p = 0.6) and 22.7% after LLR compared to 34.6% after RLR (p = 0.6). Conclusions: When comparing OLR, LLR and RLR, the OS and RFS were all similar after utilization of the Milan criteria and PSM. Biological agents tended to be utilized more in the OLR group when compared to the LLR group, suggesting that highly aggressive tumors are still managed through an open approach

Survival Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-2)

Introduction: Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM) was a propensity score matched (PSM) study that reported short-term outcomes of patients with CRLM who met the Milan criteria and underwent either open (OLR), laparoscopic (LLR) or robotic liver resection (RLR). This study, designated as SIMMILR-2, reports the long-term outcomes from that initial study, now referred to as SIMMILR-1. Methods: Data regarding neoadjuvant chemotherapeutic (NC) and neoadjuvant biological (NB) treatments received were collected, and Kaplan-Meier curves reporting the 5-year overall (OS) and recurrence-free survival (RFS) for OLR, LLR and RLR were created for patients who presented with synchronous lesions only, as there was insufficient follow-up for patients with metachronous lesions. Results: A total of 73% of patients received NC and 38% received NB in the OLR group compared to 70% and 28% in the LLR group, respectively (p = 0.5 and p = 0.08). A total of 82% of patients received NC and 40% received NB in the OLR group compared to 86% and 32% in the RLR group, respectively (p > 0.05). A total of 71% of patients received NC and 53% received NB in the LLR group compared to 71% and 47% in the RLR group, respectively (p > 0.05). OS at 5 years was 34.8% after OLR compared to 37.1% after LLR (p = 0.4), 34.3% after OLR compared to 46.9% after RLR (p = 0.4) and 30.3% after LLR compared to 46.9% after RLR (p = 0.9). RFS at 5 years was 12.1% after OLR compared to 20.7% after LLR (p = 0.6), 33.3% after OLR compared to 26.3% after RLR (p = 0.6) and 22.7% after LLR compared to 34.6% after RLR (p = 0.6). Conclusions: When comparing OLR, LLR and RLR, the OS and RFS were all similar after utilization of the Milan criteria and PSM. Biological agents tended to be utilized more in the OLR group when compared to the LLR group, suggesting that highly aggressive tumors are still managed through an open approach

Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM)

(1) Background: Here we report on a retrospective study of an international multicentric cohort after minimally invasive liver resection (SIMMILR) of colorectal liver metastases (CRLM) from six centers. (2) Methods: Resections were divided by the approach used: open liver resection (OLR), laparoscopic liver resection (LLR) and robotic liver resection (RLR). Patients with macrovascular invasion, more than three metastases measuring more than 3 cm or a solitary metastasis more than 5 cm were excluded, and any remaining heterogeneity found was further analyzed after propensity score matching (PSM) to decrease any potential bias. (3) Results: Prior to matching, 566 patients underwent OLR, 462 LLR and 36 RLR for CRLM. After PSM, 142 patients were in each group of the OLR vs. LLR group and 22 in the OLR vs. RLR and 21 in the LLR vs. RLR groups. Blood loss, hospital stay, and morbidity rates were all highly statistically significantly increased in the OLR compared to the LLR group, 636 mL vs. 353 mL, 9 vs. 5 days and 25% vs. 6%, respectively (p &lt; 0.001). Only blood loss was significantly decreased when RLR was compared to OLR and LLR, 250 mL vs. 597 mL, and 224 mL vs. 778 mL, p &lt; 0.008 and p &lt; 0.04, respectively. (4) Conclusions: SIMMILR indicates that minimally invasive approaches for CRLM that follow the Milan criteria may have short term advantages. Notably, larger studies with long-term follow-up comparing robotic resections to both OLR and LLR are still needed