Laparoscopic Portal Vein Ligation and Embolization During First-Stage Hepatectomy for Initially Unresectable Colorectal Liver Metastases.

BACKGROUND: Two-stage hepatectomy (TSH) is the only treatment for the patients with multiple bilobar colorectal liver metastases (CRMs) who are not candidates for one-step hepatectomy because of insufficient future remnant liver volume and/or impaired liver function.1-5 Although laparoscopic approaches have been introduced for TSH,6-8 the postoperative morbidity and mortality remains high because of the technical difficulties during second-stage hepatectomy.9,10 The authors present a video of laparoscopic TSH with portal vein (PV) ligation and embolization, which minimizes adhesions and PV thrombosis risk in the remnant liver, thereby facilitating second-stage hepatectomy. METHODS: Three patients with initially unresectable bilateral CRMs received a median of chemotherapy 12 cycles, followed by conversion TSH. After right PV ligation, laproscopic PV embolization was performed by injection of 100% ethanol into the hepatic side of the right PV using a 23-gauge winged needle. After PV embolization, a spray adhesion barrier (AdSpray, Terumo, Tokyo, Japan)11 was applied. RESULTS: During the first stage of hepatectomy, two patients underwent simultaneous laparoscopic colorectal resection (left hemicolectomy and high anterior resection). In the initial hepatectomy, two patients underwent two limited hepatectomies each, and one patient underwent six hepatectomies in the left lobe. After hepatectomy, all the patients underwent right PV embolization. During the second stage, two patients underwent open extended right hepatectomy (right adrenalectomy was performed because of adrenal invasion in one patient), and one patient underwent laparoscopic extended right hepatectomy. No postoperative complications occurred in the six surgeries. CONCLUSIONS: Laparoscopic TSH with PV embolization is recommended for safe completion of the second hepatectomy.

Prognostic factors associated with early recurrence following liver resection for colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR. METHODS: Systematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger's P value. RESULTS: The study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1-36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER. CONCLUSION: This review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.

Establishing the clinical relevance of grade A post-hepatectomy liver failure.

INTRODUCTION: The International Study Group of Liver Surgery's criteria stratifies post-hepatectomy liver failure (PHLF) into grades A, B, and C. The clinical significance of these grades has not been fully established. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) hepatectomy-targeted database was analyzed. Outcomes between patients without PHLF, with grade A PHLF, and grade B or C PHLF were compared. Univariate and multivariable logistic regression were performed. RESULTS: Six thousand two hundred seventy-four adults undergoing elective major hepatectomy were included in the analysis. The incidence of grade A PHLF was 4.3% and grade B or C was 5.3%. Mortality was similar between patients without PHLF (1.2%) and with grade A PHLF (1.1%), but higher in those with grades B or C PHLF (25.4%). Overall morbidities rates were 19.3%, 41.7%, and 72.8% in patients without PHLF, with grade A PHLF, and with grade B or C PHLF, respectively (p < 0.001). Grade A PHLF was associated with increased morbidity (grade A: odds ratios [OR] 2.7 [95% CI: 2.0-3.5]), unplanned reoperation (grade A: OR 3.4 [95% CI: 2.2-5.1]), nonoperative intervention (grade A: OR 2.6 [95% CI: 1.9-3.6]), length of stay (grade A: OR 3.1 [95% CI: 2.3-4.1]), and readmission (grade A: OR 1.8 [95% CI: 1.3-2.5]) compared to patients without PHLF. CONCLUSIONS: Although mortality was similar between patients without PHLF and with grade A PHLF, other postoperative outcomes were notably inferior. Grade A PHLF is a clinically distinct entity with relevant associated postoperative morbidity.

Development and external validation of MRI-based RAS mutation status prediction model for liver metastases of colorectal cancer.

BACKGROUND: The mutation status of rat sarcoma viral oncogene homolog (RAS) has prognostic significance and serves as a key predictive biomarker for the effectiveness of antiepidermal growth factor receptor (EGFR) therapy. However, there remains a lack of effective models for predicting RAS mutation status in colorectal liver metastases (CRLMs). This study aimed to construct and validate a diagnostic model for predicting RAS mutation status among patients undergoing hepatic resection for CRLMs. METHODS: A diagnostic multivariate prediction model was developed and validated in patients with CRLMs who had undergone hepatectomy between 2014 and 2020. Patients from Institution A were assigned to the model development group (i.e., Development Cohort), while patients from Institutions B and C were assigned to the external validation groups (i.e., Validation Cohort_1 and Validation Cohort_2). The presence of CRLMs was determined by examination of surgical specimens. RAS mutation status was determined by genetic testing. The final predictors, identified by a group of oncologists and radiologists, included several key clinical, demographic, and radiographic characteristics derived from magnetic resonance images. Multiple imputation was performed to estimate the values of missing non-outcome data. A penalized logistic regression model using the adaptive least absolute shrinkage and selection operator penalty was implemented to select appropriate variables for the development of the model. A single nomogram was constructed from the model. The performance of the prediction model, discrimination, and calibration were estimated and reported by the area under the receiver operating characteristic curve (AUC) and calibration plots. Internal validation with a bootstrapping procedure and external validation of the nomogram were assessed. Finally, decision curve analyses were used to characterize the clinical outcomes of the Development and Validation Cohorts. RESULTS: A total of 173 patients were enrolled in this study between January 2014 and May 2020. Of the 173 patients, 117 patients from Institution A were assigned to the Model Development group, while 56 patients (33 from Institution B and 23 from Institution C) were assigned to the Model Validation groups. Forty-six (39.3%) patients harbored RAS mutations in the Development Cohort compared to 14 (42.4%) in Validation Cohort_1 and 8 (34.8%) in Validation Cohort_2. The final model contained the following predictor variables: time of occurrence of CRLMs, location of primary lesion, type of intratumoral necrosis, and early enhancement of liver parenchyma. The diagnostic model based on clinical and MRI data demonstrated satisfactory predictive performance in distinguishing between mutated and wild-type RAS, with AUCs of 0.742 (95% confidence interval [CI]: 0.651─0.834), 0.741 (95% CI: 0.649─0.836), 0.703 (95% CI: 0.514─0.892), and 0.708 (95% CI: 0.452─0.964) in the Development Cohort, bootstrapping internal validation, external Validation Cohort_1 and Validation Cohort_2, respectively. The Hosmer-Lemeshow goodness-of-fit values for the Development Cohort, Validation Cohort_1 and Validation Cohort_2 were 2.868 (p = 0.942), 4.616 (p = 0.465), and 6.297 (p = 0.391), respectively. CONCLUSIONS: Integrating clinical, demographic, and radiographic modalities with a magnetic resonance imaging-based approach may accurately predict the RAS mutation status of CRLMs, thereby aiding in triage and possibly reducing the time taken to perform diagnostic and life-saving procedures. Our diagnostic multivariate prediction model may serve as a foundation for prognostic stratification and therapeutic decision-making.

Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases.

The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.

Achievement of textbook outcome after hepatectomy combined with thermal ablation for colorectal liver metastases.

BACKGROUND: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach. METHODS: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks. RESULTS: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99-7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11-0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82-0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03-0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not. CONCLUSIONS: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease.

Laparoscopic versus open parenchymal sparing liver resections for high tumour burden colorectal liver metastases: a propensity score matched analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has proved effective in the treatment of oligometastatic disease (1 or 2 colorectal liver metastases CRLM) with similar long-term outcomes and improved short-term results compared to open liver resection (OLR). Feasibility of parenchymal sparing LLR for high tumour burden diseases is largely unknown. Aim of the study was to compare short and long-term results of LLR and OLR in patients with ≥ 3 CRLM. METHODS: Patients who underwent first LR of at least two different segments for ≥ 3 CRLM between 01/2012 and 12/2021 were analysed. Propensity score nearest-neighbour 1:1 matching was based on relevant prognostic factors. RESULTS: 277 out of 673 patients fulfilled inclusion criteria (47 LLR and 230 OLR). After match two balanced groups of 47 patients with a similar mean number of CRLM (5 in LLR vs 6.5 in OLR, p = 0.170) were analysed. The rate of major hepatectomy was similar between the two group (10.6% OLR vs. 12.8% LLR). Mortality (2.1% OLR vs 0 LLR) and overall morbidity rates (34% OLR vs 23.4% LLR) were comparable. Length of stay (LOS) was shorter in the LLR group (5 vs 9 days, p = 0.001). No differences were observed in median overall (41.1 months OLR vs median not reached LLR) and disease-free survival (18.3 OLR vs 27.9 months LLR). CONCLUSION: Laparoscopic approach should be considered in selected patients scheduled to parenchymal sparing LR for high tumour burden disease as associated to shorter LOS and similar postoperative and long-term outcomes compared to the open approach.

Prognostic significance of socioeconomic deprivation in patients with colorectal liver metastasis undergoing liver resection: a retrospective cohort study.

AIMS: To evaluate the effect of socioeconomic deprivation on overall survival (OS) in patients undergoing liver resection for colorectal liver metastasis (CRLM). METHODS: The STROCSS guideline for observational studies was followed to conduct a single-centre retrospective cohort study. All consecutive patients undergoing resection of CRLM between 2013 and 2021 were considered eligible for inclusion. The Welsh Index of Multiple Deprivation (WIMD) rank was used to determine socioeconomic deprivation status of each patient. Prognostic significance of socioeconomic deprivation was determined by Kaplan-Meier survival statistics and stepwise Cox proportional-hazards regression model. RESULTS: A total of 455 patients were eligible for inclusion; 237 patients were classed as least socioeconomically deprived and 218 patients as most socioeconomically deprived. Kaplan-Meier survival statistics showed that socioeconomic deprivation was associated with significantly lower probability of overall survival (HR: 1.55, 95% CI 1.23-1.95; logrank test: P = 0.0001). The stepwise Cox proportional-hazards regression analysis identified socioeconomic deprivation as predictor of OS (HR: 1.56, P = 0.0003) alongside the following variables: ASA status 1 (HR: 0.43, P = 0.0349), presence of extrahepatic disease (HR: 1.51, P = 0.0075), number of tumours (HR: 1.07, P = 0.0221), size of largest tumour (HR: 1.01, P = 0.0003), extended hemihepatectomy (HR: 3.24, P = 0.0018) and absence of recurrence (HR: 0.55, P < 0.0001). CONCLUSIONS: Socioeconomic deprivation reduces the probability of long-term overall survival following liver resection in patients with CRLM. This should be taken into account at different levels of health care planning for management of patients with CRLM including preoperative risk assessment, health care need assessment and allocation of resources.

6,126 hepatectomies in 2022: current trend of outcome in Italy.

PURPOSE: Whether hospital volume affects outcome of patients undergoing hepatobiliary surgery, and whether the centralization of such procedures is justified remains to be investigated. The aim of this study was to analyze the outcome of liver surgery in Italy in relationship of hospital volume. METHODS: This is a nationwide retrospective observational study conducted on data collected by the National Italian Registry "Piano Nazionale Esiti" (PNE) 2023 that included all liver procedures performed in 2022. Outcome measure were case volume and 30-day mortality. Hospitals were classified as very high-volume (H-Vol), intermediate-volume (I-Vol), low-volume (L-Vol) and very low-volume (VL-VoL). A review on centralization process and outcome measures was added. RESULTS: 6,126 liver resections for liver tumors were performed in 327 hospitals in 2022. The 30-day mortality was 2.2%. There were 14 H-Vol, 19 I-Vol, 31 L-Vol and 263 VL-Vol hospitals with 30-day mortality of 1.7%, 2.2%, 2.6% and 3.6% respectively (P < 0.001); 220 centers (83%) performed less than 10 resections, and 78 (29%) centers only 1 resection in 2022. By considering the geographical macro-areas, the median count of liver resection performed in northern Italy exceeded those in central and southern Italy (57% vs. 23% vs. 20%, respectively). CONCLUSIONS: High-volume has been confirmed to be associated to better outcome after hepatobiliary surgical procedures. Further studies are required to detail the factors associated with mortality. The centralization process should be redesigned and oversight.

Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence.

BACKGROUND: Hepatic artery infusion chemotherapy (HAI) has been proposed as a valuable adjunct for multimodal therapy of primary and secondary liver malignancies. This review provides an overview of the currently available evidence of HAI, taking into account tumor response and long-term oncologic outcome. SUMMARY: In colorectal liver metastases (CRLM), HAI in combination with systemic therapy leads to high response rates (85-90%) and conversion to resectablity in primary unresectable disease in up to 50%. HAI in combination with systemic therapy in CRLM in the adjuvant setting shows promising long-term outcomes with up to 50% 10-year survival in a large, non-randomized single-center cohort. For hepatocellular carcinoma patients, response rates as high as 20-40% have been reported for HAI and long-term outcomes compare well to other therapies. Similarly, survival for patients with unresectable intrahepatic cholangiocarcinoma 3 years after treatment with HAI is reported as high as 34%, which compares well to trials of systemic therapy where 3-year survival is usually below 5%. However, evidence is mainly limited by highly selected, heterogenous patient groups, and outdated chemotherapy regimens. The largest body of evidence stems from small, often non-randomized cohorts, predominantly from highly specialized single centers. KEY MESSAGE: In well-selected patients with primary and secondary liver malignancies, HAI might improve response rates and, possibly, long-term survival. Results of ongoing randomized trials will show whether a wider adoption of HAI is justified, particularly to increase rates of resectability in advanced malignant diseases confined to the liver.

The Usefulness of Total Tumor Volume as a Prognostic Factor and in Selecting the Optimal Treatment Strategy of Chemotherapeutic Intervention in Patients with Colorectal Liver Metastases.

BACKGROUND: Few reports have discussed the association between total tumor volume (TTV) and prognosis in patients with colorectal liver metastases (CRLM). The present study aimed to evaluate the usefulness of TTV for predicting recurrence-free survival and overall survival (OS) in patients receiving initial hepatic resection or chemotherapy, and to investigate the value of TTV as an indicator for optimal treatment selection for patients with CRLM. PATIENTS AND METHODS: This retrospective cohort study included patients with CRLM who underwent hepatic resection (n = 93) or chemotherapy (n = 78) at the Kobe University Hospital. TTV was measured using 3D construction software and computed tomography images. RESULTS: A TTV of 100 cm3 has been previously reported as a significant cut-off value for predicting OS of CRLM patients receiving initial hepatic resection. For patients receiving hepatic resection, the OS for those with a TTV ≥ 100 cm3 was significantly reduced compared with those with a TTV < 100 cm3. For patients receiving initial chemotherapy, there were no significant differences between the groups divided according to TTV cut-offs. Regarding OS of patients with TTV ≥ 100 cm3, there was no significant difference between hepatic resection and chemotherapy (p = 0.160). CONCLUSIONS: TTV can be a predictive factor of OS for hepatic resection, unlike for initial chemotherapy treatment. The lack of significant difference in OS for CRLM patients with TTV ≥ 100 cm3, regardless of initial treatment, suggests that chemotherapeutic intervention preceding hepatic resection may be indicated for such patients.

Prognostic Impact of Tumor Markers (CEA and CA19-9) on Patients with Resectable Colorectal Liver Metastases Stratified by Tumor Number and Size: Potentially Valuable Biologic Markers for Preoperative Treatment.

BACKGROUND: Although patients with resectable colorectal liver metastasis (CLM), a population with good prognosis, have been treated with upfront surgery, some patients have had a poor prognosis. This study aimed to investigate biologic prognostic factors in patients with resectable CLMs. METHODS: This single-center retrospective study enrolled consecutive patients who underwent liver resection for initial CLMs at the Cancer Institute Hospital between 2010 and 2020. The study defined CLMs as resectable (tumor size < 5 cm; < 4 tumors; no extrahepatic metastasis) or borderline resectable (BR). Preoperative chemotherapy was administered to patients with BR CLMs. RESULTS: During the study period, 309 CLMs were classified as resectable without preoperative chemotherapy and 345 as BR with preoperative chemotherapy. For the 309 patients with resectable CLMs, the independent poor prognostic factors associated with overall survival in the multivariable analysis were high tumor marker levels (CEA ≥ 25 ng/mL and/or CA19-9 ≥ 50 U/mL; (hazard ratio [HR], 2.45; p = 0.0007), no adjuvant chemotherapy (HR, 1.69; p = 0.043), and age of 75 years or older (HR, 2.09; p = 0.012). The 5-year survival rates for the patients with high tumor marker (TM) levels (CEA ≥25 ng/mL and/or CA19-9 ≥50 U/mL) were significantly worse than for those with low TM levels (CEA < 25 ng/mL and CA19-9 < 50 U/mL) (55.3% vs. 81.1%; p <0.0001) and similar to the rate for those with BR CLMs (52.1%; p = 0.864). Postoperative adjuvant chemotherapy had an impact on prognosis only in the high-TM group (HR, 2.65; p = 0.007). CONCLUSIONS: High TM levels have a prognostic impact on patients with resectable CLMs stratified by tumor number and size. Perioperative chemotherapy improves long-term outcomes for patients with CLM and high TM levels.

Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network.

BACKGROUND: An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. METHODS: Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. RESULTS: Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. CONCLUSIONS: Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.

CT versus MR guidance for radiofrequency ablation in patients with colorectal liver metastases: a 10-year follow-up favors MR guidance.

OBJECTIVES: To compare the results of CT- vs MR-guided radiofrequency ablation (RFA) of liver metastases (LM) from colorectal cancer after 10 years of follow-up in an observational, retrospective, and multicentric study. METHODS: A total of 238 patients with 496 LM were treated with RFA either with CT (CT group) or magnetic resonance (MR group) guidance. Every ablated LM was assessed and followed up with diagnostic MRI. Technical success, technique efficacy, predictive factors, recurrence rates, and overall survival were assessed. RESULTS: The CT group comprised 143 patients and the MR group 77 patients. Eighteen patients underwent ablation with both modalities. Technical success per patient and per lesion was 88% and 93% for CT and 87% and 89.6% for MR, and technique efficacy was 97.1% and 98.6% for CT and 98.7% and 99.3% for MR respectively. Local recurrence following the first ablation (primary patency) occurred in 20.1% (CT) vs 4.6% (MR) (p < 0.001). Residual liver tumor, size of LM, and advanced N and M stage at initial diagnosis were independent predictors for overall survival in both groups. The median overall survival measured from first RFA treatment was 2.6 years. The 1-year, 5-year, and 10-year survival were 85.9%, 25.5%, and 19.1% respectively. CONCLUSIONS: The MR group had significantly better local control compared to the CT group. There was no significant difference in patient survival between the two groups. CLINICAL RELEVANCE STATEMENT: MR-guided radiofrequency ablation of colorectal liver metastases is safe and effective, and offers better local control than CT-guided ablation. KEY POINTS: • Imaging modality for radiofrequency ablation guidance is an independent predictor of local recurrence in colorectal liver metastases. • MR-guided radiofrequency ablation achieved better local control of liver metastases from colorectal cancer than CT-guided. • The number and size of liver metastases are, among others, independent predictors of survival. Radiofrequency ablation with MR guidance improved clinical outcome but does not affect survival.

Combined Liver and Colon Resection of Synchronous Colorectal Liver Metastases at a Quaternary Center.

INTRODUCTION: Existing literature on the safety of combined liver and colorectal resections for synchronous colorectal liver metastases is mixed. Using a retrospective review of our institutional data, we aimed to show that combined colorectal and liver resections for synchronous metastases is both feasible and safe in a quaternary center. METHODS: A retrospective review of combined resections for synchronous colorectal liver metastases at a quaternary referral center from 2015 to 2020 was completed. Clinicopathologic and perioperative data was collected. Univariate and multivariable analyses were performed to identify risk factors for major postoperative complications. RESULTS: One hundred one patients were identified, with 35 undergoing major liver resections ( ≥ 3 segments) and 66 undergoing minor liver resections. The vast majority of patients (94%) received neoadjuvant therapy. There was no difference in postoperative major complications (Clavien-Dindo grade 3+) between major and minor liver resections (23.9% versus 12.1%, P = 0.16). On univariate analysis, Albumin-Bilirubin (ALBI) score >1 (P < 0.05) was predictive of major complication. However, on multivariable regression analysis, no factor was associated with significantly increased odds of major complication. CONCLUSIONS: This work demonstrates that with thoughtful patient selection, combined resection for synchronous colorectal liver metastases can be safely performed at a quaternary referral center.

Autofluorescence-Raman Spectroscopy for Ex Vivo Mapping Colorectal Liver Metastases and Liver Tissue.

INTRODUCTION: Identifying colorectal liver metastases (CRLM) during liver resection could assist in achieving clear surgical margins, which is an important prognostic variable for both disease-free and overall survival. The aim of this study was to investigate the effect of auto-fluorescence (AF) and Raman spectroscopy for ex vivo label-free discrimination of CRLMs from normal liver tissue. Secondary aims include exploring options for multimodal AF-Raman integration with respect to diagnosis accuracy and imaging speed on human liver tissue and CRLM. METHODS: Liver samples were obtained from patients undergoing liver surgery for CRLM who provided informed consent (15 patients were recruited). AF and Raman spectroscopy was performed on CRLM and normal liver tissue samples and then compared to histology. RESULTS: AF emission spectra demonstrated that the 671 nm and 775/785 nm excitation wavelengths provided the highest contrast, as normal liver tissue elicited on average around eight-fold higher AF intensity compared to CRLM. The use of the 785 nm wavelength had the advantage of enabling Raman spectroscopy measurements from CRLM regions, allowing discrimination of CRLM from regions of normal liver tissue eliciting unusual low AF intensity, preventing misclassification. Proof-of-concept experiments using small pieces of CRLM samples covered by large normal liver tissue demonstrated the feasibility of a dual-modality AF-Raman for detection of positive margins within few minutes. CONCLUSIONS: AF imaging and Raman spectroscopy can discriminate CRLM from normal liver tissue in an ex vivo setting. These results suggest the potential for developing integrated multimodal AF-Raman imaging techniques for intraoperative assessment of surgical margins.

The Role of Colour Segmented Fluorescence (CSF) Mode and Same-day Administration of Low-dose Indocyanine Green in Liver Surgery: Our Initial Experience : Indocyanine Green Fluorescence Guided Resection of Liver Tumours.

Indocyanine green (ICG) fluorescence image guidance (I-FIGS) is increasingly used in liver surgery. Several regimens have been described regarding the optimum timing and dose of administration. This study presents our early experience with utilising monochromatic Colour Segmented Fluorescence (CSF)-mode and same-day administration of low-dose-ICG in the resection of liver tumours. Between November 2020 and March 2022, I-FIGS was used in 15 patients with suspected liver tumours. ICG was administered intravenously at 0.02 to 0.05 mg/kg dose 2-3 h before surgery. ICG camera was switched to CSF-grey-scale mode to visualise the tumour and to avoid the interference of the green background liver. Using the SPY-CSF mode, the image was scaled to near-infra-red (NIR) fluorescence intensity to accurately identify the tumours and resection margins. Fifteen patients (eight males) with a median age of 71 years (range: 36-86) underwent I-FIGS. Of these, 67% underwent laparoscopic liver surgery, 78% had non-anatomical resections, and 33% underwent redo liver surgery. The mean tumour size was 40.6 mm (SD+/-41 mm). The median number of tumours was two (1-7). All colorectal liver metastases (CRLM) had a signet ring appearance. Hepatocellular carcinomas (HCC) showed partial fluorescence. Tumours were well/moderately differentiated, with CRLM in 86% and HCC in two patients. The R0 resection rate was 72%. In our experience, low-dose-ICG administered at least 2-3 h before surgery can identify liver tumours and their margins in CSF-grey-scale mode. Further research is needed to evaluate its role in reducing R1 resection rates and surgical outcomes.

The prognostic significance of clinicopathological characteristics in early-onset versus late-onset colorectal cancer liver metastases.

PURPOSE: This study aimed to explore the prognostic significance of clinicopathological characteristics in early-onset versus late-onset colorectal liver metastases (CRLM). METHODS: The data of CRLM patients who underwent hepatectomy from September 2010 to September 2020 were retrospectively analyzed. According to the age of primary cancer diagnosis, patients were divided into early-onset CRLM (EOCRLM) and late-onset CRLM (LOCRLM) groups. Clinicopathological parameters were compared between the two groups. Cox regression model and Kaplan-Meier method were used to analyze the effect of clinicopathological parameters on overall survival (OS) and recurrence-free survival (RFS). RESULTS: In total, 431 CRLM patients were identified, 130 with EOCRLM and 301 with LOCRLM. Compared with LOCRLM patients, EOCRLM patients had lower American Society of Anesthesia (ASA) grade and longer operation time (204 vs. 179 min). More aggressive features were presented in EOCRLM patients including synchronous liver metastases (76.9% vs. 61.1%) and bilobar involvement (43.8% vs. 33.2%). No significant difference in OS or RFS was found between the two groups. Multivariate analysis of EOCRLM group showed that preoperative CA19-9 level and RAS/BRAF status were predictive of OS, while bilobar involvement and preoperative CEA level were associated with RFS. In LOCRLM group, the number of CRLM, preoperative CA19-9 level, and BRAF status were associated with OS, while the number of CRLM was associated with RFS. CONCLUSIONS: The preoperative CA19-9 level, RAS/BRAF status, bilobar involvement, and preoperative CEA level were predictive of EOCRLM patient prognosis, while the number of CRLM, preoperative CA19-9 level, and BRAF status were predictive of LOCRLM patient prognosis.

SAGES/AHPBA guidelines for the use of minimally invasive surgery for the surgical treatment of colorectal liver metastases (CRLM).

BACKGROUND: Colorectal liver metastases (CRLM) occur in roughly half of patients with colorectal cancer. Minimally invasive surgery (MIS) has become an increasingly acceptable and utilized technique for resection in these patients, but there is a lack of specific guidelines on the use of MIS hepatectomy in this setting. A multidisciplinary expert panel was convened to develop evidence-based recommendations regarding the decision between MIS and open techniques for the resection of CRLM. METHODS: Systematic review was conducted for two key questions (KQ) regarding the use of MIS versus open surgery for the resection of isolated liver metastases from colon and rectal cancer. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Additionally, the panel developed recommendations for future research. RESULTS: The panel addressed two KQs, which pertained to staged or simultaneous resection of resectable colon or rectal metastases. The panel made conditional recommendations for the use of MIS hepatectomy for both staged and simultaneous resection when deemed safe, feasible, and oncologically effective by the surgeon based on the individual patient characteristics. These recommendations were based on low and very low certainty of evidence. CONCLUSIONS: These evidence-based recommendations should provide guidance regarding surgical decision-making in the treatment of CRLM and highlight the importance of individual considerations of each case. Pursuing the identified research needs may help further refine the evidence and improve future versions of guidelines for the use of MIS techniques in the treatment of CRLM.

Global survey on the surgical management of patients affected by colorectal cancer with synchronous liver metastases: impact of surgical specialty and geographic region.

BACKGROUND: Consensus on the best surgical strategy for the management of synchronous colorectal liver metastases (sCRLM) has not been achieved. This study aimed to assess the attitudes of surgeons involved in the treatment of sCRLM. METHODS: Surveys designed for colorectal, hepato-pancreato-biliary (HPB), and general surgeons were disseminated through representative societies. Subgroup analyses were performed to compare responses between specialties and continents. RESULTS: Overall, 270 surgeons (57 colorectal, 100 HPB and 113 general surgeons) responded. Specialist surgeons more frequently utilized minimally invasive surgery (MIS) than general surgeons for colon (94.8% vs. 71.7%, p < 0.001), rectal (91.2% vs. 64.6%, p < 0.001), and liver resections (53% vs. 34.5%, p = 0.005). In patients with an asymptomatic primary, the liver-first two-stage approach was preferred in most respondents' centres (59.3%), while the colorectal-first approach was preferred in Oceania (83.3%) and Asia (63.4%). A substantial proportion of the respondents (72.6%) had personal experience with minimally invasive simultaneous resections, and an expanding role for this procedure was foreseen (92.6%), while more evidence was desired (89.6%). Respondents were more reluctant to combine a hepatectomy with low anterior (76.3%) and abdominoperineal resections (73.3%), compared to right (94.4%) and left hemicolectomies (90.7%). Colorectal surgeons were less inclined to combine right or left hemicolectomies with a major hepatectomy than HPB and general surgeons (right: 22.8% vs. 50% and 44.2%, p = 0.008; left: 14% vs. 34% and 35.4%, p = 0.002, respectively). CONCLUSION: The clinical practices and viewpoints on the management of sCRLM differ between continents, and between and within surgical specialties. However, there appears to be consensus on a growing role for MIS and a need for evidence-based input.