Multiple Colorectal Liver Metastases Research Articles

Prognosis of a Heterogeneous TRG Pathological Response to Neoadjuvant Chemotherapy in Patients who Undergo Resection for Colorectal Liver Metastases.

Optimal management of colorectal liver metastasis (CRLM) is based on a combination of chemotherapy and surgical resection. The tumor regression grade (TRG) score is a histological scoring system to evaluate response to chemotherapy. The prognosis of a heterogeneous response in cases of multiple metastases has not been evaluated according to the TRG score. All patients who underwent liver resection for multiple CRLM after neoadjuvant chemotherapy in two tertiary centers from January 2015 to April 2019 were retrospectively included. Oncological characteristics and outcome between TRG 1-2-3 (good response group), TRG 4-5 (poor response group) and heterogeneous TRG (good and poor TRG among different lesions within the same patient) groups were compared. Among the 327 patients included, 134 (41.0%) had good response (TRG 1-2-3), 120 (36.7%) had poor response (TRG 4-5), and 73 (22.3%) had heterogeneous response. The type and number of cycles of chemotherapy, k-Ras mutational status, and tumor number or size did not differ between the three groups. Use of irinotecan-based and anti-VEGF neoadjuvant therapy was associated with better TRG response [irinotecan-based: hazard ratio (OR) = 1.744; p = 0.045; anti-VEGF neoadjuvant therapy: 2.054; p = 0.005). Overall survival (OS) was higher in the 1-2-3 TRG group than in the heterogeneous TRG group (2-year OS = 81.3% vs. 60.3%, respectively; p = 0.003) and the 4-5 TRG group (2-year OS = 81.3% vs. 55.0%, respectively; p = 0.012) and similar between the heterogeneous and 4-5 TRG groups. The proportion of heterogeneous pathological response according to TRG is 22.3%, and the prognosis is comparable to that of poor pathological response.

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

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. Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM≤3cm 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 4weeks. 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. 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.

Combined hepatic resection and ablation for high burden of colorectal liver metastases demonstrates safety and durable survival

BackgroundHepatic resection (HR) and thermal ablation of Colorectal Liver Metastases (CRLM) have each individually demonstrated safety and survival benefit. We sought to provide our experience with the combination of HR + ablation within one operation for patients with multiple CRLM. MethodsReview of a single institution database of patients who underwent HR + ablation between 2010 and 2019. Results161 patients were identified who underwent HR + ablation for isolated CRLM (mean age: 59, male 63.4%). 125 (77.6%) patients had bilobar disease and 92 (57.1%) patients had ≥5 tumors. 28 (17.4%) patients experienced minor (grade 1 or 2) complications while 20 (12.4%) had grade 3–5 complications. Patients who underwent simultaneous colon resection with HR + ablation had a higher complication rate (22 of 47, 46.8%) than those undergoing HR + ablation only (26 of 114, 22.8%, p = 0.002). Median and 5-year OS for all patients undergoing HR + ablation was 38.2 months and 33.2%, respectively. 5-year hepatic recurrence free survival was 23.5%. Patients with 5 or more tumors demonstrated no difference in median survival compared to those with fewer than 5 tumors (37.0 months vs 38.4 months, p = 0.326). ConclusionsIn this population of CRLM patients with a relatively high burden of disease, HR + ablation demonstrated an acceptable safety profile as well as durable long-term survival.

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial

BackgroundThe efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. MethodsIn this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). Results35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%−96%) among evaluable patients (n = 32), and 95% (95% CI 70–100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15–23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1–19). Treatment toxicity was manageable, without toxic death. ConclusionHAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.

Multiple Laparoscopic Liver Resection for Colorectal Liver Metastases.

Over the past decades, liver cancer's minimally invasive approach has primarily become as a new standard of oncological care. Colorectal liver metastases (CRLM) are one of the most developed indications of laparoscopic liver resection (LLR). CRLM resection is still the best treatment known in terms of survival. As multiple CRLM are found in up to 80% of cases at diagnosis (Manfredi S. and al, Annals of Surgery 2006), a lot of possible technical management approaches are described. With the development of the parenchymal-sparing strategy, multiple concomitant laparoscopic liver resections (LLR) are gaining acceptance. However, no recommendation is available regarding its indications and feasibility. Also, laparoscopic two-stage hepatectomy is developing for bilobar CRLM, and this also does not have established recommendation. The purpose of this paper was to highlight novelty and updates in the field of multiple minimally invasive liver resections. A review of the international literature was performed. The feasibility of laparoscopic concomitant multiple LLR and two-stage hepatectomy for CRLM as well as their outcomes were discussed. These clarifications could further guide the implementation of minimal resection in multiple colorectal liver metastases therapies.

Reliability of Multidisciplinary Approach in Multiple Colorectal Liver Metastases

Reliability of Multidisciplinary Approach in Multiple Colorectal Liver Metastases

Three-dimensional quantitative margin assessment in patients with colorectal liver metastases treated with percutaneous thermal ablation using semi-automatic rigid MRI/CECT-CECT co-registration

PurposeTo assess the quantitative minimal ablation margin (MAM) in patients with colorectal liver metastases (CRLM) treated with percutaneous thermal ablation (TA) and correlate the quantitative MAM with local tumour recurrence (LTR). MethodThirty-nine of 143 patients with solitary or multiple CRLM who underwent a first percutaneous TA procedure between January 2011 and May 2020 were considered eligible for study enrolment. Image fusion of pre- and post-ablation scans and 3D quantitative MAM assessment was performed using the in-house developed semi-automatic rigid MRI/CECT-CECT co-registration software deLIVERed. The quantitative MAM was analysed and correlated with LTR. ResultsEighteen (46 %) patients were additionally excluded from further analyses due to suboptimal co-registration (quality co-registration score ≤ 3). The quality of co-registration was considered sufficient in 21 (54 %) patients with a total of 29 CRLM. LTR was found in 5 of 29 (17 %) TA-treated CRLM. In total, 12 (41 %) negative MAMs were measured (mean MAM −4.7 ± 2.7 mm). Negative MAMs were significantly more frequently seen in patients who developed LTR (100 %) compared to those without LTR (29 %; p = 0.003). The median MAM of patients who developed LTR (−6.6 mm (IQR −9.5 to −4.6)) was significantly smaller compared to the median MAM of patients without LTR (0.5 mm (IQR −1.8 to 3.0); p < 0.001). The ROC curve showed high accuracy in predicting LTR for the quantitative MAM (area under the curve of 0.975 ± 0.029). ConclusionThis study demonstrated the feasibility of 3D quantitative MAM assessment, using deLIVERed co-registration software, to assess technical success of TA in patients with CRLM and to predict LTR.

Optimal cytoreductive LIVER surgery for unresectable colorectal liver metastases: A prospective observational study.

3570 Background: Patients with multiple colorectal liver metastases (CLM) involving all the hepatic segments are currently not eligible for potentially curative liver surgery. Transplantation is a promising alternative but graft shortage and stringent selection criteria limit its accessibility. Owing to the improving efficacy of chemotherapy, the impossibility to resect all the initial metastatic sites could lead to revisit the role of optimal cytoreductive liver surgery (CLS) aiming to treat by resection ± radiofrequency, all the macroscopic residual tumors after a good response to chemotherapy. Although validated for ovarian cancer and peritoneal carcinomatosis, this strategy remains unexplored in CLM. Our objective was to evaluate the outcome of this strategy in patients with definitively unresectable CLM. Methods: Within a prospective monocentric study, we enrolled for debulking surgery, between 2017 and 2021, all consecutive patients with multinodular unresectable CLM involving all segments on initial imaging and consequently ineligible for a curative surgery either after a one or two-stage hepatectomy. These patients should have a strong response to chemotherapy ( &gt; 50 % on RECIST criteria) for at least a 3-month period and no or limited extrahepatic disease, to be included. End-points of the analysis were overall and disease-free survival at 3 years. Results: Among 26 patients considered for this strategy, optimal CLS could be achieved in 21 patients after a median interval of 10 months from CLM diagnosis. The median number of lesions was 11 (7 - 26) on initial imaging. Four patients (19%) had synchronous lung metastases. Liver-first strategy was undertaken in 19 patients (90%). Postoperative complications (Grade ≥ III) occured in 5 patients (24%). One patient died within 90-day after operation from intra-abdominal hemorrage while on anticoagulation therapy. After a median follow-up of 25 months from hepatectomy, the 3-year OS rates was 85%. Median survival was not reached at the time of the analysis. Of the 4 (19%) patients with complete pathological response on the liver specimen, 3 developed recurrence. A total of 17 patients (81%) developed recurrence after a median time of 10,5 months from hepatectomy. Among them, repeat hepatectomy could be undertaken in four patients. The survival time to surgical failure (recurrence untreatable with curative intent) was 32% and 16% at 2 and 3 years. At last follow-up, seven patients (33%) are alive and recurrence-free. Conclusions: The promising results of this prospective series suggest that CLS may be worthy in patients with diffuse CLM non curatively treatable by surgery but responding well to chemotherapy. This strategy should however be reserved to hyperselected patients, super responders, eligible for an optimal resection of all the macroscopic residual tumors, and confimed by other expert centers, to be definitively validated.

ASO Visual Abstract: Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection

ASO Visual Abstract: Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection

Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection.

Pathologic response to preoperative chemotherapy predicts survival in patients with colorectal liver metastases (CLMs) who undergo hepatectomy. In multiple CLMs, mixed pathologic response, wherein tumors exhibit different degrees of treatment response, is possible. We sought to evaluate survival outcomes of mixed response in patients with multiple CLMs. We conducted a retrospective cohort study using a single-institution database of patients with two or more CLMs who underwent preoperative chemotherapy and hepatectomy (2010-2018). Pathologic response of each tumor was measured on pathology. Patients were stratified by pathologic response as complete (pCR)=0-1% viability; major (pMajR)=2-49% viability; minor (pMinR)=50-99% viability; or mixed (pMixR)=at least one pCR/MajR tumor and one pMinR. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adjusted risk of death was evaluated using Cox regression. Among 444 patients, 6% had pCR, 34% had pMajR, 36% had pMinR, and 24% had pMixR. Median and 5-year RFS for patients with pMixR was 10.4 months and 16%, respectively, compared with pMajR (11.3 months and 18%, respectively), pMinR (7.7 months and 13%, respectively), and pCR (23.1 months and 38%, respectively) [log-rank p<0.001]. Median and 5-year OS for patients with pMixR was 77.4 months and 60%, respectively, compared with pMajR (80.5 months and 63%, respectively), pMinR (49.9 months and 39%, respectively), and pCR (median OS not reached; median follow-up of 37.1 months and 5-year OS of 65%) [log-rank p=0.002]. pMixR was associated with a 52% risk of death reduction (hazard ratio 0.48, 95% confidence interval 0.30-0.78 vs. pMinR). One-quarter of patients with multiple CLMs have pMixR following preoperative chemotherapy and hepatectomy. OS and RFS for patients with pMixR mirror those of pMajR rather than pMinR, suggesting the greatest response achieved in any metastasis best predicts survival.

Targeted Endoradiotherapy with Lu2O3-iPSMA/-iFAP Nanoparticles Activated by Neutron Irradiation: Preclinical Evaluation and First Patient Image.

Prostate-specific membrane antigen (PSMA) is expressed in a variety of cancer cells, while the fibroblast activation protein (FAP) is expressed in the microenvironment of tumors. Previously, we reported the ability of iPSMA and iFAP ligands to specifically target PSMA and FAP proteins, as well as the preparation of stable 177Lu2O3 nanoparticles (<100 nm) functionalized with target-specific peptides. This research aimed to evaluate the dosimetry and therapeutic response of Lu2O3-iPSMA and Lu2O3-iFAP nanoparticles activated by neutron irradiation to demonstrate their potential for theranostic applications in nuclear medicine. The biokinetic behavior, radiation absorbed dose, and metabolic activity ([18F]FDG/micro-PET, SUV) in preclinical tumor tissues (athymic mice), following treatment with 177Lu2O3-iPSMA, 177Lu2O3-iFAP or 177Lu2O3 nanoparticles, were assessed. One patient with multiple colorectal liver metastases (PSMA-positive) received 177Lu2O3-iPSMA under a “compassionate use” protocol. Results indicated no significant difference (p < 0.05) between 177Lu2O3-iPSMA and 177Lu2O3-iFAP, regarding tumor radiation absorbed doses (105 ± 14 Gy, 99 ± 12 Gy and 58 ± 7 Gy for 177Lu2O3-iPSMA, 177Lu2O3-iFAP, and 177Lu2O3, respectively) and tumor metabolic activity (SUV of 0.421 ± 0.092, 0.375 ± 0.104 and 1.821 ± 0.891 for 177Lu2O3-iPSMA, 177Lu2O3-iFAP, and 177Lu2O3, respectively) in mice after treatment, which correlated with the observed therapeutic response. 177Lu2O3-iPSMA and 177Lu2O3-iFAP significantly inhibited tumor progression, due to the prolonged tumor retention and a combination of 177Lu radiotherapy and iPSMA or iFAP molecular recognition. There were negligible uptake values in non-target tissues and no evidence of liver and renal toxicity. The doses received by the patient’s liver metastases (42–210 Gy) demonstrated the potential of 177Lu2O3-iPSMA for treating colorectal liver metastases.

Effect of Co-mutation of RAS and TP53 on Postoperative ctDNA Detection and Early Recurrence after Hepatectomy for Colorectal Liver Metastases.

Circulating tumor DNA (ctDNA) is a promising biomarker for patients undergoing hepatectomy for colorectal liver metastases (CLM). We hypothesized that post-hepatectomy ctDNA detection would identify patients at highest risk for early recurrence of CLM. Patients with CLM who underwent curative-intent hepatectomy with ctDNA analysis within 180 days postoperatively (1/2013 and 6/2020) were included. Tissue somatic mutations and ctDNA analyses were performed by next-generation sequencing panels. Survival analyses determined factors associated with clinical recurrence 1 year or earlier after hepatectomy. Patients with primary tumors in situ and without 1-year follow-up were excluded. Median follow-up was 28.3 months. Of 105 patients, 32 (30%) were ctDNA positive (ctDNA+) after curative-intent hepatectomy. Compared with ctDNA-negative patients, ctDNA+ patients had multiple CLM (84% vs 55%, p = 0.002) and co-mutated RAS/TP53 (47% vs 23%, p = 0.018). Multiple CLM (odds ration (OR), 5.43; p = 0.005) and co-mutated RAS/TP53 (OR, 3.30; p = 0.019) were independently associated with post-hepatectomy ctDNA. Although perioperative carcinoembryonic antigen levels were not prognostic, postoperative ctDNA+ (hazard ratio (HR), 2.04; p = 0.011) and extrahepatic disease (HR, 2.45, p = 0.004) were independently associated with worse recurrence-free survival. After adjusting for extrahepatic disease, preoperative chemotherapy, multiple CLM, tumor viability of 50% or greater, and co-mutated RAS/TP53, ctDNA+ within 180 days was the only independent risk factor for recurrence 1 year or earlier after hepatectomy (94% vs 49%; HR, 11.8; p = 0.003). Postoperative ctDNA detection is associated with early recurrence 1 year or earlier after curative-intent hepatectomy for CLM, and RAS/TP53 co-mutations result in a more than 3-fold increased risk for postoperative ctDNA positivity. This highlights the complementary effect of tumor tissue and circulating mutational profiling for patients with CLM.

Prognostic impact of inter-metastatic heterogeneity of viable tumour cells in colorectal liver metastases

BackgroundHeterogenous response to neoadjuvant chemotherapy in patients with multiple colorectal liver metastases (CRLM) has been associated with an acquired resistance to systemic therapy. This study evaluated the occurrence of a heterogenous inter-metastatic tumour response with regards to the proportion of viable tumour cells, and its prognostic impact. MethodsA retrospective cohort study was conducted, including all patients with CRLM surgically treated at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with the proportion of viable tumour cells and inter-metastatic heterogeneity were analysed with regression and survival analyses. ResultsOut of 640 surgically treated patients, 405 patients (1357 CRLM), received neoadjuvant chemotherapy. Multiple CRLM were present in 314 patients (78%), out of whom 72 patients (23%) presented with a heterogenous tumour response. The median overall survival (OS) for patients with a heterogenous inter-metastatic tumour response was 36 months, compared to 57 months for patients with a homogenous inter-metastatic tumour response (p < .001). Poor OS in patients receiving preoperative chemotherapy was significantly associated with a heterogenous inter-metastatic tumour response (hazard ratio (HR) 1.68 (1.02–2.78)), right-sided primary tumour (HR 2.01 (1.29–3.43)) and CRLM diameter >5 cm (HR 1.83 (1.06–3.17)). ConclusionOutcome in patients with a heterogenous inter-metastatic tumour response, illustrated by the proportion of viable tumour cells, is inferior to that of patients with a homogenous response. These results suggest that heterogeneity in treatment response is an important marker of aggressive disease and could be of clinical value for decisions on post-operative therapy.

Hepatectomy with Perioperative Chemotherapy for Multiple Colorectal Liver Metastases is the Available Option for Prolonged Survival.

Hepatic resection combined with perioperative chemotherapy is the standard of care for patients with multiple colorectal liver metastases (CLMs). However, the optimal surgical strategy for treating advanced CLMs remains unclear. The role of the two-stage hepatectomy (TSH) strategy in the management of multiple CLMs remains challenging. This study aimed to compare the outcomes of one-step hepatectomy (OSH)-treated and TSH-treated patients with multiple CLMs. This single-institution study included 742 consecutive patients who underwent initial liver resection for histologically confirmed CLMs. The study enrolled patients with 10 or more tumors (n = 106). Clinicopathologic characteristics and long-term outcomes were compared between patients who underwent OSH and those who underwent TSH for 10 or more CLMs. The study planned OSH for 67 patients (63%) and TSH for 39 patients (37%). One of the OSH-planned patients and two of the TSH-planned patients underwent a trial laparotomy because of non-curative factors. Five patients (13%) did not progress to the second stage of TSH. In the entire cohort, the cumulative 3-year overall survival rate was 58.4% for the patients who had 10 or more CLMs treated with OSH compared with 61.1% for the patients treated with TSH (P = 0.746). In the curative resection cohort, the cumulative 1-year recurrence-free survival rate was 18.2% for the patients treated with OSH and 17.9% for the patients treated with TSH (P = 0.640). Hepatectomy with perioperative chemotherapy for advanced CLMs with 10 or more tumors is feasible and effective. To prolong survival, TSH is a promising option when curative resection with OSH is impossible.

Nanoparticle Delivery of miR-122 Inhibits Colorectal Cancer Liver Metastasis.

Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as miR-122, a liver-specific miRNA that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented colorectal cancer liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes involved in metastatic and cancer inflammation pathways, including several proinflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to antitumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA. SIGNIFICANCE: Highly specific and efficient delivery of miRNA to hepatocytes using nanomedicine has therapeutic potential for the prevention and treatment of colorectal cancer liver metastasis.

Combined liver resection and radiofrequency ablation for bilobar multiple colorectal liver metastasis

Combined liver resection and radiofrequency ablation for bilobar multiple colorectal liver metastasis

The role of R0/R1vasc resection in the treatment of patients affected by marginal resectable colorectal liver metastases: A pairwise propensity score match analysis

Increasingly, patients with multiple colorectal liver metastases (CRLM) are surgically treated. R1par surgery remains one of the negative prognostic factors for overall survival (OS). According to our data on R1 in main intrahepatic vascular contact (MVC), we investigate the oncological outcome of patients with multiple bilobar disease with bilateral MVC (BC), compared to patients with unilateral MVC (UC) and patients with disease and no MVC (NC). This single-institution study included patients who underwent hepatectomy for multiple (≥ 4) bilobar CRLM lesions from 2004-2019. Three-hundred-fifty-five patients meet the inclusion criteria. One-hundred-thirty-two patients with R1par resection were excluded. Three groups were defined: NC, UC, BC. After pairwise propensity score match 145 patients were analyzed. No differences between groups were observed in the preoperative variables. Increased surgical time, hilar clamping, and blood loss were reported in the BC group. Postoperative minor morbidity, liver failure rate, overall and local recurrences were higher in the BC group. BC patients were more likely to be re-resected. Cumulative OS 3-5 years survival in NC, UC, BC were 54%-40%, 49%-35%, 57%-24% (p < 0.91). At multivariate analysis, factors influencing OS, were N status of the primitive lesions, RAS status, and repeated hepatectomy. Patients with BC and lesions ≥ 4 are generally considered unresectable or suitable for staged hepatectomy. This retrospective study shows that these patients can be submitted to the so called enhanced-one-staged hepatectomy with the same oncological results, however surgical complexity, postoperative minor morbidity and postoperative liver failure are increased.

Laparoscopic liver resection for bilobar multiple metachronous liver metastases in patient with rectal cancer

Laparoscopic liver resection (LLR) of multiple colorectal liver metastases (CRLM) is challenging but has become more practical recently due to progression in operative technique. We aimed to present laparoscopic detection of multiple CRLM using intraoperative ultrasonography (IOUSG) and LLR for scattered CRLM. A 65-year-old male was admitted with multiple liver metastases during follow-up for mid-rectal cancer. The patient had already undergone laparoscopic lower anterior resection 6 months ago and had completed the sixth adjuvant chemotherapy with capecitabine. Magnetic resonance imaging presented metastatic tumor about 5 cm in size in segment 6 of liver and multiple small metastases in segment 3, 4, 5, 7, and 8 of liver. The surgery was performed in supine position and five trocars were inserted. After detection of tumors using IOUSG to mark the site of the tumors, we performed bisegmentectomy about tumors of segment 5 and 6, and 3 tumorectomy of liver about tumors of segment 3, 4, and 7 + 8. Immediately after surgery, all specimens were cut to check whether the tumors were included and whether the resection margin was sufficient. The operative time was 350 minutes and estimated blood loss was 80 mL. Pringle maneuver was performed 5 times in 15 minutes. All tumor resection margin were grossly confirmed as negative. There were no immediate postoperative complications. The patient was discharged on the day 7 of postoperative hospital stay. LLR is safe and feasible technique even for bilobar multiple CRLM.

Two stage hepatectomy (TSH) or Associating liver partition and portal vein ligation for staged hepatectomy (ALLPS) for bilobar multiple colorectal liver metastasis

Of patients with colorectal cancer, 30% to 50% present with liver metastasis at the time of diagnosis or develop metastasis later. Hepatectomy is the primary curative treatment option for patients with colorectal liver metastases (CRLMs). Patients with bilateral, multiple CRLMs and a small estimated tumor free future liver remnant (FLR) present a treatment challenge. These patients may need a two-stage hepatectomy (TSH) in which portal venous ligation (PVL) or portal venous embolization (PVE) is included in the first stage to stimulate hypertrophy of the FLR before final resection. This method generates a 27% to 39% increase in FLR volume in 4 to 8 weeks. The risks in this method are tumor progression during the waiting period and insufficient hypertrophy, making resection impossible in 25% to 38% of the patients preparing to undergo TSH. To increase liver growth rate and volume, which renders more patients resectable in a shorter time, a novel concept of liver resection, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), was described in 2011. However, in the early study 68% of the patients experienced complications and the surgical mortality rate was 12%. A recent, the only multicenter randomized controlled trial (RCT) revealed that compared with the use of TSH, the use of ALPPS for patients with CRLM resulted in a higher resection rate (92%) without a higher 90-day mortality rate (8.3%), a higher rate of severe complication rate (43%) or a lower rate of negative surgical margins in the liver. A previous meta-analysis including 9 retrospective studies showed that TSH for CRLM exhibited lower perioperative morbidity and mortality rates than ALPPS, suggesting the superiority of TSH. On the other hand, in a recent meta-analysis in 2020 including 7 retrospective studies and 1 RCT, compared with TSH, ALPPS for advanced CRLM resulted in superior surgical efficacy with comparable perioperative mortality rate and short-term oncological outcomes, while this was at the cost of increased perioperative minor complications. From a clinical perspective, traditional TSH has been frequently regarded as a preferred treatment modality in earlier studies, and ALPPS was reserved as an alternative, typically after failed PVE or PVL. At present, this paradigm may have changed, as there is growing evidence indicating that the surgical benefits given by ALPPS are at least not inferior to those given by TSH according to recent studies. ALPPS may be feasible for bilobar multiple colorectal liver metastasis. Still, long-term outcomes remain to be elucidated and therefore the role of ALPPS regarding oncological outcome remains uncertain.

Short- and long-term outcomes of hepatectomy combined with intraoperative radiofrequency ablation for patients with multiple primarily unresectable colorectal liver metastases: a propensity matching analysis

BackgroundHepatectomy combined with intraoperative radiofrequency ablation (IORFA) is a strategy to eliminate all tumors in patients with multiple colorectal liver metastases (CRLM). This study aimed to evaluate the surgical and oncological outcomes of hepatectomy + IORFA for multiple unresectable CRLM. MethodsWe included patients who underwent combined hepatectomy and IORFA for multiple unresectable CRLM (n = 67) or hepatectomy alone (n = 268) for CRLM. Patients were matched in a 1:1 propensity score analysis to compare the short- and long-term outcomes between groups. ResultsPatients in hepatectomy + IORFA group had a median number of 10 liver lesions. Postoperative morbidity and the rate of major complications was similar between groups (P = 0.362, P = 1.000). The median overall survival (OS), progression free survival (PFS) and hepatic recurrence free survival (HRFS) was similar between groups (3-year OS: 54.2% versus 60.9%, P = 0.389; 3-year PFS: 7.9% versus 19.6%, P = 0.148; 3-year HRFS: 16.7% versus 31.5%, P = 0.202). Re-hepatectomy or radiofrequency ablation was used to treat 47.5% of hepatic recurrences, and the median OS was significantly higher than for patients treated with systemic treatment alone (P < 0.001). ConclusionsCombining hepatectomy and IORFA could provide comparable survival rates for patients with multiple unresectable CRLM compared to those with resectable CRLM treated with hepatectomy alone.