OBJECTIVE: Hepatic artery infusion pump (HAIP) therapy is an available option at highly specialized centers to treat unresectable liver tumors (e.g., colorectal liver metastases [CRLM]). This study describes the safety and outcomes of HAIP program implementation at an academic-based cancer center.
METHODS: Patients who underwent HAIP placement (2021-2023) were included. Categorical and continuous variables were compared using Chi-square and Kruska-Wallis tests, respectively. Survival and variables associated with survival were calculated using the Kaplan-Meier method and Cox proportional hazards model, respectively.
RESULTS: Of the 26 HAIP procedures for unresectable CRLM, four were done as adjuvant therapy. Median duration of HAIP therapy was 9.2 months and four patients subsequently underwent hepatectomy. Complication rate was 37.5%, with biliary complication rate of 23.1%. Median overall survival (OS) from date of diagnosis was 55.2 months. Concurrent primary tumor resection was associated with inferior OS (p = 0.030). Multivariable regression did not identify independent predictors of OS. Progression-free survival from time of HAIP placement was 7.8 months.
CONCLUSIONS: HAIP placement was technically successful in most patients with an acceptable complication rate. Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic therapy. The significant difference in outcomes for those with concurrent colectomy warrants further investigation.

BACKGROUND: This study investigates the impact of margin status after colorectal liver metastasis (CLM) resection on outcomes of patients after neoadjuvant treatment versus those who underwent upfront resection.
METHODS: An international collaborative database of CLM patients who underwent surgical resection was used. Proportional hazard regression models were created for single and multivariable models to assess the relationship between independent measures and median overall survival (mOS).
RESULTS: R1 was associated with worse OS in the neoadjuvant group (mOS: 51.8 m for R0 vs. 26.0 m for R1; HR: 2.18). In the patients who underwent upfront surgery, R1 was not associated with OS. (mOS: 46.7 m for R0 vs. 42.6 m for R1). When patients with R1 in each group were stratified by adjuvant treatment, there was no significant difference in the neoadjuvant group, while in the upfront surgery group with R1, adjuvant treatment was associated with significant improvement in OS (mOS: 42.6 m for adjuvant vs. 25.0 m for no adjuvant treatment; HR: 0.21).
CONCLUSIONS: R1 is associated with worse outcomes in the patients who receive neoadjuvant treatment with no significant improvement with the addition of adjuvant therapy, likely representing an aggressive tumor biology. R1 did not impact OS in patients with upfront surgery who received postoperative chemotherapy.

OBJECTIVE: We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients.
METHODS: This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum.
RESULTS: Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group.
CONCLUSIONS: Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

BACKGROUND: Thermal ablation has recently become a key therapy for the treatment of colorectal liver metastasis (CLM). However, the role of ablation in combination with resection has not yet been firmly established. We hypothesize that in patients with CLM, those who undergo liver resection with ablation (RA) have similar outcomes compared with those who undergo liver resection only.
METHODS: We reviewed a multicenter international database of 906 surgical procedures for CLM from 5 high volume hepatobiliary surgical units. Patients undergoing RA (n = 63) were matched based on the number of lesions and tumor size using a 1:1 balanced propensity score analysis with those having resection only (n = 63). Our primary outcomes were overall survival (OS) and disease-free survival (DFS).
RESULTS: The mean age of our cohort was 58 ± 11 years, with 43% females. With a median follow-up of 70.8 months, patients in the resection and RA group had a median OS of 45.1 and 54.8 months (p = 0.71), respectively. The median DFS was 22.7 and 14.2 months (p = 0.045), respectively. Using a multivariate Cox proportional hazards regression model, the treatment approach was not associated with OS (p = 0.94) or DFS (p = 0.059). A higher number of lesions is independently associated with worse DFS (hazard ratio: 1.12, p < 0.01). When there was disease recurrence, the region of recurrence was similar between the RA versus resection only groups (p = 0.27), but there was a shorter time to recurrence in the RA group (p = 0.002).
CONCLUSIONS: For CLM, the treatment approach was not significantly associated with OS or DFS, while tumor biology likely played an important role. Prospective research on the quality and effectiveness of thermal ablation combined with hepatic resection is warranted.

Colorectal liver metastasis (CRLM) is challenging in the clinical treatment of colorectal cancer. Limited research has been conducted on how CRLM develops. RNA sequencing data were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Four machine learning algorithms were used to screen the hub CRLM-specific genes, including Least Absolute Shrinkage and Selection Operator (Lasso), Random forest, SVM-RFE, and XGboost. The model for identifying CRLM was developed using stepwise logistic regression and was validated using internal and independent datasets. The prognostic value of hub CRLM-specific genes was assessed using the Lasso-Cox method. The in vitro experiments were performed using SW620 cells. The CRLM identification model was developed based on four CRLM-specific genes (SPP1, ZG16, P2RY14, and PRKAR2B), and the model efficacy was validated using GSE41258 and three external cohorts. Five CRLM-specific prognostic hub genes, SPP1, ZG16, P2RY14, CYP2E1, and C5, were identified using the Lasso-Cox algorithm, and a risk score was constructed. The risk score was validated using the GSE39582 cohort. Three genes have both efficacy in identifying CRLM and prognostic value: ZG16, P2RY14, and SPP1. Immune infiltration and enrichment analyses demonstrated that SPP1 was associated with M2 macrophage polarization and extracellular matrix remodeling. In vitro experiments indicated that SPP1 may act as a cancer-promoting factor. The hub CRLM-specific gene SPP1 can help determine the diagnosis, prognosis, and immune infiltration of patients with CRLM.

UNASSIGNED: This study comprehensively compared laparoscopic liver resection (LLR) to open liver resection (OLR) in treating colorectal cancer liver metastasis (CRLM).
UNASSIGNED: A systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes.
UNASSIGNED: Findings indicate that minimally invasive surgery (MIS) did not significantly prolong the duration of surgery compared to open liver resection and notably demonstrated lower blood transfusion rates and reduced intraoperative blood loss. While some studies favored MIS for its lower complication rates, others did not establish a statistically significant difference. One study identified a lower post-operative mortality rate in the MIS group. Furthermore, MIS consistently correlated with shorter hospital stays, indicative of expedited post-operative recovery. Concerning oncological outcomes, while certain meta-analyses reported a lower rate of cancer recurrence in the MIS group, others found no significant disparity. Overall survival and disease-free survival remained comparable between the MIS and open liver resection groups.
UNASSIGNED: The analysis emphasizes the potential advantages of LLR in terms of surgical outcomes and aligns with existing literature findings in this field.
UNASSIGNED: [website], identifier [registration number].

OBJECTIVE: Histopathological growth patterns (HGPs) of colorectal liver metastases (CRLMs) have prognostic value. However, the differentiation of HGPs relies on postoperative pathology. This study aimed to develop a magnetic resonance imaging (MRI)-based radiomic model to predict HGP pre-operatively, following the latest guidelines.
METHODS: This retrospective study included 93 chemotherapy-naïve patients with CRLMs who underwent contrast-enhanced liver MRI and a partial hepatectomy between 2014 and 2022. Radiomic features were extracted from the tumor zone (RTumor), a 2-mm outer ring (RT+2), a 2-mm inner ring (RT-2), and a combined ring (R2+2) on late arterial phase MRI images. Analysis of variance method (ANOVA) and least absolute shrinkage and selection operator (LASSO) algorithms were used for feature selection. Logistic regression with five-fold cross-validation was used for model construction. Receiver operating characteristic curves, calibrated curves, and decision curve analyses were used to assess model performance. DeLong tests were used to compare different models.
RESULTS: Twenty-nine desmoplastic and sixty-four non-desmoplastic CRLMs were included. The radiomic models achieved area under the curve (AUC) values of 0.736, 0.906, 0.804, and 0.794 for RTumor, RT-2, RT+2, and R2+2, respectively, in the training cohorts. The AUC values were 0.713, 0.876, 0.785, and 0.777 for RTumor, RT-2, RT+2, and R2+2, respectively, in the validation cohort. RT-2 exhibited the best performance.
CONCLUSIONS: The MRI-based radiomic models could predict HGPs in CRLMs pre-operatively.

Background, Natural orifice specimen extraction (NOSE) via the anus or vagina is an alternative to conventional transabdominal specimen extraction in laparoscopic colorectal cancer surgery. NOSE has been shown to be safe and effective, resulting in decreased postoperative pain, analgesia use, and improved recovery, without oncological compromise. We aimed to demonstrate the feasibility of NOSE for combined colectomy with liver metastasectomy. Methods, From July 2022 to April 2024, all cases of laparoscopic colorectal cancer resection and synchronous liver metastasectomy with NOSE were included in the study. Selection criteria included a maximum specimen diameter of less than 5 cm and patient body mass index of less than 35 kg/m2. Results, Over the 22-month duration, four consecutive patients (two males, two females) underwent combined resection with NOSE. Mean age and BMI were 74.8 (range 63-81) years and 20.9 (range 19.5-22.3) kg/m2 respectively. Patient A and D underwent anterior resection for sigmoid cancer, Patient B underwent D3 right hemicolectomy for cecal cancer, and Patient C underwent subtotal colectomy for synchronous cecal and descending colon cancer. All patients underwent liver metastasectomy at the same sitting. Patient A and D had transanal NOSE while Patients B and C underwent transvaginal NOSE. Mean operative time and blood loss was 416 (range 330-535) minutes and 338 (range 50-500) ml respectively. All patients recovered gastrointestinal function within the first two postoperative days. Infected seroma of the liver bed occurred in one patient requiring percutaneous drainage. The average maximum colon tumor diameter was 2.9 (range 1.3-4.0) cm. All resection margins were clear. Mean duration of follow-up was 7.5 (range 2-12) months. Conclusions, Simultaneous colectomy and liver metastasectomy with NOSE for colorectal cancer is feasible and safe in highly selected patients, resulting in good postoperative outcomes. This proof-of-concept analysis paves the way for larger studies to draw definitive conclusions.

BACKGROUND: Accurate prediction of patients at risk for early recurrence (ER) among patients with colorectal liver metastases (CRLM) following preoperative chemotherapy and hepatectomy remains limited.
METHODS: Patients with CRLM who received chemotherapy prior to undergoing curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with ER, and an online calculator was developed and validated.
RESULTS: Among 768 patients undergoing preoperative chemotherapy and curative-intent resection, 128 (16.7 %) patients had ER. Multivariable Cox analysis demonstrated that Eastern Cooperative Oncology Group Performance status ≥1 (HR 2.09, 95%CI 1.46-2.98), rectal cancer (HR 1.95, 95%CI 1.35-2.83), lymph node metastases (HR 2.39, 95%CI 1.60-3.56), mutated Kirsten rat sarcoma oncogene status (HR 1.95, 95%CI 1.25-3.02), increase in tumor burden score during chemotherapy (HR 1.51, 95%CI 1.03-2.24), and bilateral metastases (HR 1.94, 95%CI 1.35-2.79) were independent predictors of ER in the preoperative setting. In the postoperative model, in addition to the aforementioned factors, tumor regression grade was associated with higher hazards of ER (HR 1.91, 95%CI 1.32-2.75), while receipt of adjuvant chemotherapy was associated with lower likelihood of ER (HR 0.44, 95%CI 0.30-0.63). The discriminative accuracy of the preoperative (training: c-index: 0.77, 95%CI 0.72-0.81; internal validation: c-index: 0.79, 95%CI 0.75-0.82) and postoperative (training: c-index: 0.79, 95%CI 0.75-0.83; internal validation: c-index: 0.81, 95%CI 0.77-0.84) models was favorable (https://junkawashima.shinyapps.io/CRLMfollwingchemotherapy/).
CONCLUSIONS: Patient-, tumor- and treatment-related characteristics in the preoperative and postoperative setting were utilized to develop an online, easy-to-use risk calculator for ER following resection of CRLM.

OBJECTIVE: Tumor-infiltrating lymphocytes (TILs) represent a host-tumor interaction, frequently signifying an augmented immunological response. Nonetheless, implications with survival outcomes in patients with colorectal carcinoma liver metastasis (CRLM) warrant rigorous validation. The objective was to demonstrate the association between TILs and survival in patients with CRLM.
METHODS: In a retrospective evaluation conducted in a single institution, we assessed all patients who underwent hepatectomy due to CRLM between 2014 and 2018. Comprehensive medical documentation reviews were executed. TILs were assessed by a liver pathologist, blinded to the clinical information, in all surgical slides.
RESULTS: This retrospective cohort included 112 patients. Median overall survival (OS) was 58 months and disease-free survival (DFS) was 12 months for the entire cohort. Comparison between groups showed a median OS of 81 months in the dense TILs group and 40 months in the weak/absent group (p = 0.001), and DFS was 14 months versus 9 months (p = 0.041). Multivariable analysis showed that TILs were an independent predictor of OS (HR 1.95; p = 0.031).
CONCLUSIONS: Dense TILs are a pivotal prognostic indicator, correlating with enhanced OS. Including TILs information in histopathological evaluations should refine the clinical decision-making process for this group of patients.