Synchronous colorectal liver metastases may be managed with primary-first, simultaneous, or liver-first resection. Relative oncologic outcomes based on treatment sequencing are understudied.

This study aimed to assess oncologic survival outcomes in patients with synchronous colorectal liver metastases managed with each of the 3 treatment strategies, with respect to early or delayed removal of the primary tumor.

Retrospective analysis of the prospectively maintained database, with 1:1 propensity score matching of relevant clinicopathologic variables comparing liver-first to primary-first/simultaneous approaches.

Single-institution, tertiary cancer center.

Patients undergoing curative-intent hepatectomy for synchronous colorectal liver metastases from 2003 to 2019.

Overall and recurrence-free survival.

Of 151 patients, 23% (n = 35) had liver-first and 77% (n = 116; primary-first = 93 and simultaneous = 23) had primary-first/simultaneous approaches. The median follow-up was 45 months. Recurrence-free survival was worse for liver-first versus primary-first/simultaneous groups (median 12 versus 16 months, p = 0.02), driven by 3-year extrahepatic recurrence-free survival of 19%, 58%, and 50% for liver-first, primary-first, and simultaneous groups, respectively. Three-year overall survival was not significantly different at 86%, 79%, and 86%, respectively. Oncologic outcomes did not differ significantly between primary-first and simultaneous groups (all p > 0.4). Matching yielded 34 clinicopathologically similar patients per group (liver-first = 34, primary-first = 28, simultaneous = 6). The liver-first approach was associated with shorter recurrence-free survival (median 12 versus 23 months, p = 0.004), driven by extrahepatic recurrence-free survival (3 years: 20% versus 55%, p = 0.04). Overall survival was not significantly different at 3 years (79% versus 80%, p = 0.95) or 5 years (59% versus 59%, p > 0.99).

This study has a retrospective design and a limited sample size.

A liver-first approach is associated with worse recurrence-free survival compared to primary-first or simultaneous resection, driven by extrahepatic recurrence. A prospective study of whether oncologic risk is associated with leaving the primary in situ is needed. Multidisciplinary treatment sequencing and enhanced postoperative surveillance for patients receiving liver-first resection are recommended. See Video Abstract .

ANTECEDENTES:Las metástasis hepáticas colorrectales sincrónicas se pueden tratar con resección primaria, simultánea o hepática. Los resultados oncológicos relativos basados en la secuenciación del tratamiento están poco estudiados.OBJETIVO:Este estudio tuvo como objetivo evaluar los resultados de supervivencia oncológica en pacientes con metástasis hepáticas colorrectales sincrónicas tratadas con cada una de las tres estrategias de tratamiento, con respecto a la extirpación temprana o tardía del tumor primario.DISEÑO:Análisis retrospectivo de una base de datos mantenida prospectivamente, con coincidencia de propensión 1:1 de variables clínico-patológicas relevantes que comparan enfoques de hígado primero con enfoques primarios primero/simultáneos.AJUSTES:Centro oncológico terciario de una sola institución.PACIENTES:Pacientes sometidos a hepatectomía con intención curativa por metástasis hepáticas colorrectales sincrónicas entre 2003 y 2019.MEDIDAS PRINCIPALES DE RESULTADOS:Supervivencia general y libre de recurrencia.RESULTADOS:De 151 pacientes, el 23% (n=35) tuvo un abordaje hepático primero y el 77% (n=116; primario primero=93 y simultáneo=23) tuvo un abordaje primario primero/simultáneo. La mediana de seguimiento fue de 45 meses. La supervivencia libre de recurrencia fue peor para los grupos de hígado primero versus primario primero/simultáneo (mediana 12 versus 16 meses, p = 0,02), impulsada por la supervivencia libre de recurrencia extrahepática a tres años del 19%, 58% y 50% para grupos de hígado primero, primario primero y simultáneo, respectivamente. La supervivencia general a tres años no fue significativamente diferente: 86%, 79% y 86%, respectivamente. Los resultados oncológicos no difirieron significativamente entre los grupos primario-primero y simultáneo (todos p > 0,4). El emparejamiento produjo 34 pacientes clínico-patológicamente similares por grupo (hígado primero = 34, primario primero = 28/simultáneo = 6). El enfoque de hígado primero se asoció con una supervivencia libre de recurrencia más corta (mediana de 12 frente a 23 meses, p = 0,004), impulsada por la supervivencia libre de recurrencia extrahepática (3 años: 20 % frente a 55 %, p = 0,04). La supervivencia general no fue significativamente diferente a los 3 años (79% versus 80%, p = 0,95) o a los 5 años (59% versus 59%, p > 0,99).LIMITACIONES:Este estudio tiene un diseño retrospectivo y un tamaño de muestra limitado.CONCLUSIONES:Un enfoque de hígado primero se asocia con una peor supervivencia libre de recurrencia en comparación con la resección primaria o simultánea, impulsada por la recurrencia extrahepática. Es necesario un estudio prospectivo sobre si el riesgo oncológico se asocia con dejar el primario in situ . Se recomienda la secuenciación del tratamiento multidisciplinario y una vigilancia posoperatoria mejorada para los pacientes que reciben una primera resección del hígado. (Traducción-Yesenia Rojas-Khalil ).

Portal vein embolization (PVE) is currently considered the standard of care to improve the volume of an inadequate future remnant liver (FRL) and decrease the risk of post-hepatectomy liver failure (PHLF). PHLF remains a significant limitation in performing major liver surgery and is the main cause of mortality after resection. The degree of hypertrophy obtained after PVE is variable and depends on multiple factors. Up to 20% of patients fail to undergo the planned surgery because of either an inadequate FRL growth or tumor progression after the PVE procedure (usually 6-8 wk are needed before surgery). The management of PVE failure is still debated, with a lack of consensus regarding the best clinical strategy. Different additional techniques have been proposed, such as sequential transarterial chemoembolization followed by PVE, segment 4 PVE, intra-portal administration of stem cells, dietary supplementation, and hepatic vein embolization. The aim of this review is to summarize the up-to-date strategies to overcome such difficult situations and discuss future perspectives on improving FRL hypertrophy.

Surgery is the cornerstone treatment for patients with primary or metastatic hepatic tumors. Thanks to surgical and anesthetic technological advances, current indications for liver resections have been significantly expanded to include any patient in whom all disease can be resected with a negative margin (R0) while preserving an adequate future residual liver (FRL). Posthepatectomy liver failure (PHLF) is still a feared complication following major liver surgery, associated with high morbidity, mortality and cost implications. PHLF is mainly linked to both the size and quality of the FRL. Significant advances have been made in detailed preoperative assessment to predict and mitigate this complication, even if an ideal methodology has yet to be defined. Several procedures have been described to induce hypertrophy of the FRL when needed. Each technique has its advantages and limitations, and among them portal vein embolization (PVE) is still considered the standard of care. About 20% of patients after PVE fail to undergo the scheduled hepatectomy, and newer secondary procedures, such as segment 4 embolization, ALPPS and HVE, have been proposed as salvage strategies. The aim of this review was to discuss the current modalities available and new perspectives in the optimization of FRL in patients undergoing major liver resection.

Liver resection still represent the treatment of choice for liver malignancies, but in some cases inadequate future remnant liver (FRL) can lead to post hepatectomy liver failure (PHLF) that still represents the most common cause of death after hepatectomy. Several strategies in recent era have been developed in order to generate a compensatory hypertrophy of the FRL, reducing the risk of post hepatectomy liver failure. Portal vein embolization, portal vein ligation, and ALLPS are the most popular techniques historically adopted up to now. The liver venous deprivation and the radio-embolization are the most recent promising techniques. Despite even more precise tools to calculate the relationship among volume and function, such as scintigraphy with ^99mTc-mebrofenin (HBS), no consensus is still available to define which of the above mentioned augmentation strategy is more adequate in terms of kind of surgery, complexity of the pathology and quality of liver parenchyma. The aim of this article is to analyse these different strategies to achieve sufficient FRL.

Recurrence is a frequent concern in curatively resected CRC liver metastases. Translational research suggests that regeneration upon hepatectomy may also alleviate metastatic recurrence; however, the significance in patients is unclear. We therefore sought to study the effect of liver regeneration on tumor recurrence in patients.

In this retrospective cohort study, we included 58 out of 186 potentially eligible patients from our prospectively maintained database of CRC liver metastasis patients between 2001 and 2012 with a median follow-up of 42 months who underwent a formal right or left hemihepatectomy. Liver regeneration in CT volumetry was correlated with recurrence of CRC liver metastases and overall survival.

Liver regeneration increased up to 14 months to 21.0% for left and 122.6% for right hemihepatectomy, respectively, with comparable final volumes. Regeneration was independent of initial tumor stage, number of metastases, and preoperative chemotherapy. Patients with lower liver regeneration showed earlier recurrence of CRC liver metastases (p = 0.006). Overall survival did not differ in patients with weak versus strong liver regeneration.

The extent of liver regeneration after major hepatectomy does not impede overall survival. Therefore, our data encourage aggressive therapeutical regimes for CRC liver metastases involving major hepatectomies as part of a curative approach.

Despite excellent treatment of primary colorectal cancer, the majority of deaths occur as a result of metastasis to the liver. Recent population studies have estimated that one quarter of patients with colorectal cancer will incur synchronous or metachronous colorectal liver metastasis. However, only one quarter of these patients will be eligible for potentially curative resection. Tumor recurrence occurs in reportedly 60% of patients undergoing hepatic resection, and the majority of intrahepatic recurrence occurs within the first 6 months of surgery. The livers innate ability to restore its homeostatic size, and volume facilitates major hepatic resection that currently offers the only chance of cure to patients with extensive hepatic metastases. Experimental and clinical evidence supports the notion that following partial hepatectomy, liver regeneration (LR) paradoxically drives tumor progression and increases the risk of recurrence. It is becoming increasingly clear that the processes that drive liver organogenesis, regeneration, and tumor progression are inextricably linked. This presents a major hurdle in the management of colorectal liver metastasis and other hepatic malignancies because therapies that reduce the risk of recurrence without hampering LR are sought. The processes and pathways underlying these phenomena are multiple, complex, and cross-communicate. In this review, we will summarize the common mechanisms contributing to both LR and tumor recurrence.