Synchronous resection for colorectal liver metastases: The future

Colorectal Cancer is a common malignancy. Many patients have metastatic disease at presentation and a significant proportion subsequently go onto develop metastatic disease, following surgery for the primary disease.     

Systematic review of outcomes of patients undergoing resection for colorectal liver metastases in the setting of extra hepatic disease

BackgroundSurgical resection for patients with colorectal liver metastases (CRLM) can offer patients a significant survival benefit. We hypothesised that patients with CRLM and extra hepatic disease (EHD) undergoing metastasectomy had comparable survival and describe outcomes based on the distribution of metastatic disease.MethodsA systematic search using a predefined registered protocol was undertaken between January 2003 and June 2012. Primary exposure was hepatic resection for CRLM and primary outcome measure was overall survival. Meta-regression techniques were used to analyse differences between patients with and without extra hepatic disease.FindingsFrom a pool of 4996 articles, 50 were retained for data extraction (3481 CRLM patients with EHD). The median survival (MS) was 30.5 (range, 9–98) months which was achieved with an operative mortality rate of 0–4.2%. The 3-year and 5-year overall survival (OS) were 42.4% (range, 20.6–77%) and 28% (range, 0–61%) respectively. Patients with EHD of the lungs had a MS of 45 (range, 39–98) months versus lymph nodes (portal and para-aortic) 26 (range, 21–48) months versus peritoneum 29 (range, 18–32) months. The MS also varied by the amount of liver disease – 42.2 months (<two lesions) versus 39.6 months (two lesions) versus 28 months (⩾three lesions).InterpretationIn the evolving landscape of multimodality therapy, selective hepatic resection for CRLM patients with EHD is feasible with potential impact on survival. Patients with minimal liver disease and EHD in the lung achieve the best outcome.     

Systematic review and meta-analysis of local ablative therapies for resectable colorectal liver metastases

IntroductionLocal ablative therapies (LAT) have shown positive but heterogenous outcomes in the treatment of colorectal liver metastases (CRLM). The aim of this systematic review is to evaluate LAT and compare them with surgical resection.MethodsIn accordance with PRISMA guidelines, Medline, EMBASE, Cochrane and Web of Science databases were searched for reports published before January 2019. We included papers assessing radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (CA) and electroporation (IRE) treating resectable CRLM with curative intention. We evaluated LAT related complications and oncological outcomes as tumour progression (LTP), disease-free survival (DFS) and overall survival (OS).ResultsThe literature search yielded 6767 records; 20 papers (860 patients) were included. No included studies related mortality with LAT. Median adverse events percentage was 7%: (8% RFA;7% MWA). Median 3y-DFS was 32% (24% RFA; 60% MWA); 5y-DFS was 27%: (18% RFA; 38.5% MWA). Median 3y-OS was 59% (60% RFA; 70% MWA; 34% CA), 5y-OS was 44.5% (43% RFA; 55% MWA; 20% CA).Surgical resection showed decreased LTP, improved DFS and OS than those reported with LAT, with RFA accounting for reduced 1y-DFS (RR 0.83, 95%CI 0.71–0.98), 3y-DFS (RR 0.5, 95%CI 0.33–0.76), 5y-DFS (RR 0.53, 95%CI 0.28–0.98) and 5y-OS (RR 0.76, 95%CI 0.58–0.98) in comparison with surgical resection.ConclusionsLow quality evidence suggests that both RFA and MWA seem superior to CA. MWA presents similar adverse events when compared to RFA with a possible increase in DFS and OS. Surgical resection still seems to provide superior DFS and OS in comparison with LAT.     

Laparoscopic liver resection compared to open approach in patients with colorectal liver metastases improves further resectability: Oncological outcomes of a case-control matched-pairs analysis

Aims

Liver resection is considered the standard treatment of colorectal metastases (CRLM). However, to date, no long term oncological results and data regarding repeat hepatectomy after laparoscopic approach are known. The aim of this study is to analyze single center long-term surgical and oncological outcomes after liver resection for CRLM.

Methods

A total of 57 open resections (OR) were matched with 57 laparoscopic resections (LR) for CRLM. Matching was based mainly on number of metastases, tumor size, segmental position of lesions, type of hepatectomy and type of resection.

Results

Morbidity rate was significantly less in the LR group (p = 0.002); the length of hospital stay was 6.5 ± 5 days for the LR group and 9.2 ± 4 days for the OR group (p = 0.005). After a median follow up of 53.7 months for the OR group and 40.9 months for the LR group, the 5-y overall survival rate was 65% and 60% respectively (p = 0.36) and the 5-y disease free survival rate was 38% and 29% respectively (p = 0.24). More patients in the LR group received a third hepatectomy for CRLM relapse than in the OR group (80% vs. 14.3% respectively; p = 0.015).

Conclusions

Laparoscopic resection for CRLM offers advantages in terms of reduced blood loss, morbidity rate and hospital stay. It provides comparable long-term oncological outcomes but can improve further resectability in patients with recurrent disease.     

Selective resection of colorectal liver metastases.

AIMS: Safety of liver surgery for colorectal cancer liver metastases after neoadjuvant chemotherapy has to be re-evaluated. PATIENTS AND METHODS: Two hundred Patients were prospectively analyzed after surgery for colorectal cancer liver metastases between 2001 and 2004 at our institution. Special emphasis was given to perioperative morbidity and mortality under modern perioperative care. RESULTS: There was no in-hospital mortality and the perioperative morbidity was 10% (20/200). Four patients had to be reoperated due to bile leak or intraabdominal abscess. The remainder either had infectious complications or pleural effusion and/or ascites requiring tapping. Variables strongly associated with decreased survival were T, N, G and UICC (International Union against cancer) classification of the primary, hepatic lesions>5 cm and elevated tumour markers. Short disease free interval and neoadjuvant chemotherapy without response predicted impaired recurrence free survival (RFS). Multivariate analysis revealed lymph node status and differentiation of the primary, presence of extrahepatic tumour and gender as factors associated with decreased survival. Administration of neoadjuvant chemotherapy was not associated with higher postoperative morbidity or prolonged hospital stay. CONCLUSIONS: Modern dissection techniques and improved perioperative care contributed to a very low rate of surgery-related morbidity (10%) and a zero percent mortality which was also observed in patients pretreated with neoadjuvant chemotherapy prior to resection. Liver resection in experienced hands has become a safe part in the potentially curative attempt of treating patients with metastatic colorectal cancer.     

Propensity score matching demonstrates similar results for radiofrequency ablation compared to surgical resection in colorectal liver metastases

PurposeMinimally invasive ablative treatments, such as radiofrequency ablation (RFA), are increasingly used in the curative treatment of patients with colorectal liver metastases (CRLM). Selection bias plays an important role in the evaluation of early and late results between RFA and surgery. The purpose of this study was to evaluate recurrences and oncological survival following these two treatment modalities using single pair propensity score matching.MethodsBetween 2000 and 2018, patients curatively treated for CRLM were included in a multicentre database. Patients were excluded when receiving two-staged treatment, synchronous treatment with primary tumor or combination of modalities. Propensity score matching was used to minimize influence of known covariates, i.e., age, ASA, FONG CRS, location and T-stage of the primary tumor.ResultsBefore matching, the RFA group contained 39 patients and the surgery group 982 patients, after matching both groups contained 36 patients. After matching, mean age was 69 years (53–86) for RFA and 68 (50–86) for surgery, with a mean tumor size of respectively 2.5 cm (0.8–6.5) and 3.4 cm (1–7.5). Both groups showed similar complication rate according to Clavien-Dindo (17vs.33%; p = 0.18), recurrence rate (58vs.64%; p = 0.09) without significant differences in 5-year DFS and OS (RFA compared to surgery respectively 25vs.37%; p = 0.09 and 42vs.53%; p = 0.09).ConclusionAfter propensity score matching, RFA showed lower complications and similar oncological survival compared to surgical resection. In patients who are suboptimal candidates for surgery, RFA seems to be a good and safe alternative.     

PET-CT accurately predicts the pre-operative characteristics of colorectal hepatic metastases

Background

Since 2002, Positron Emission Tomography (PET-CT) has been considered to be an essential pre-operative investigation in the management of colorectal liver metastases (CRLM) in our institution. This study aimed to compare characteristics of hepatic metastases on PET-CT with post-operative histological findings and pathology of the primary tumour.

Methods

All patients with CRLM, who underwent surgical intervention from 2002 to 2008, were reviewed. PET-CT and pathology reports of hepatic resections and original colorectal resections were retrieved. Patient demographics, colorectal staging, number of metastases and their maximum diameter from both PET-CT and pathology reports were recorded. Values were expressed as mean (±SD).

Results

141 patients were identified. The maximum diameter on PET-CT (4.2 ± 2.6) was similar to pathology (4.8 ± 3.6; p = 0.39), with significant correlation (r = 0.72, p < 0.0001). The number of lesions on PET-CT (1.6 ± 1.0) was similar to pathology (1.7 ± 1.3; p = 0.43) with significant correlation (r = 0.80, p < 0.0001). Mean SUV max was 9.22 (±4.39), with no correlation to lesion diameter (r = 0.25, p = 0.045), but significantly increased with decreasing differentiation (p = 0.01).

Conclusions

PET-CT scanning accurately detected the number of lesions and their maximum diameter, with radiological evidence of poorer differentiation. Further studies of non-surgical patients are required to assess its overall accuracy.     

Regional lymph node involvement in patients undergoing liver resection for colorectal cancer metastases

Background

While the indications for surgery among patients with colorectal cancer liver metastases (CRCLM) are expanding, the role of surgery in patients with hepatic lymph node involvement remains controversial. We report management and outcomes in a population-based cohort of patients undergoing hepatectomy with concomitant hepatic lymphadenectomy for CRCLM.

Laparoscopic liver resection for colorectal liver metastases — short- and long-term outcomes: A systematic review

BACKGROUNDFor well-selected patients and procedures, laparoscopic liver resection (LLR) has become the gold standard for the treatment of colorectal liver metastases (CRLM) when performed in specialized centers. However, little is currently known concerning patient-related and peri-operative factors that could play a role in survival outcomes associated with LLR for CRLM.AIMTo provide an extensive summary of reported outcomes and prognostic factors associated with LLR for CRLM.METHODSA systematic search was performed in PubMed, EMBASE, Web of Science and the Cochrane Library using the keywords “colorectal liver metastases”, “laparoscopy”, “liver resection”, “prognostic factors”, “outcomes” and “survival”. Only publications written in English and published until December 2019 were included. Furthermore, abstracts of which no accompanying full text was published, reviews, case reports, letters, protocols, comments, surveys and animal studies were excluded. All search results were saved to Endnote Online and imported in Rayyan for systematic selection. Data of interest were extracted from the included publications and tabulated for qualitative analysis.RESULTSOut of 1064 articles retrieved by means of a systematic and grey literature search, 77 were included for qualitative analysis. Seventy-two research papers provided data concerning outcomes of LLR for CRLM. Fourteen papers were eligible for extraction of data concerning prognostic factors affecting survival outcomes. Qualitative analysis of the collected data showed that LLR for CRLM is safe, feasible and provides oncological efficiency. Multiple research groups have reported on the short-term advantages of LLR compared to open procedures. The obtained results accounted for minor LLR, as well as major LLR, simultaneous laparoscopic colorectal and liver resection, LLR of posterosuperior segments, two-stage hepatectomy and repeat LLR for CRLM. Few research groups so far have studied prognostic factors affecting long-term outcomes of LLR for CRLM.CONCLUSIONIn experienced hands, LLR for CRLM provides good short- and long-term outcomes, independent of the complexity of the procedure.     

Parenchymal-sparing hepatectomy for colorectal liver metastases reduces postoperative morbidity while maintaining equivalent oncologic outcomes compared to non-parenchymal-sparing resection

BackgroundModern chemotherapy and repeat hepatectomy allow to tailor the surgical strategies for the treatment of colorectal liver metastases (CRLM). This study addresses the hypothesis that parenchymal-sparing hepatectomy reduces postoperative complications while ensuring similar oncologic outcomes compared to the standardized non-parenchymal-sparing procedures.MethodsClinicopathological data of patients who underwent liver resection for CRLM between 2012 and 2019 at a hepatobiliary center in Switzerland were assessed. Patients were stratified according to the tumor burden score [TBS² = (maximum tumor diameter in cm)² + (number of lesions)²)] and were dichotomized in a lower and a higher tumor burden cohort according to the median TBS. Postoperative outcomes, overall survival (OS) and recurrence-free survival (RFS) of patients following parenchymal-sparing resection (PSR) for CRLM were compared with those of patients undergoing non-PSR.ResultsDuring the study period, 153 patients underwent liver resection for CRLM with curative intent. PSR was performed in 79 patients with TBS <4.5, and in 42 patients with TBS ≥4.5. Perioperative chemotherapy was administered in equal rates in both groups (PSR vs. non-PSR) both in TBS ≥4.5 and TBS <4.5. In patients with lower tumor burden (TBS <4.5), PSR was associated with lower overall complication rate (15.2% vs. 46.2%, p = 0.009), a trend for lower major complication rate (8.9% vs. 23.1%, p = 0.123), and shorter length of hospital stay (5 vs. 9 days, p = 0.006) in comparison to non-PSR. For TBS <4.5, PSR resulted in equivalent 5-year OS (48% vs. 39%, p = 0.479) and equivalent 5-year RFS rates (44% vs. 29%, p = 0.184) compared to non-PSR. For TBS ≥4.5, PSR resulted in lower postoperative complication rate (33.3% vs. 63.2%, p = 0.031), a trend for lower major complication rate (23.8% vs. 42.2%, p = 0.150), lower length of hospital stay (6 vs. 9 days, p = 0.005), equivalent 5-year OS (29% vs. 22%, p = 0.314), and equivalent 5-year RFS rates (29% vs. 18%, p = 0.156) compared to non-PSR. Among all patients treated with PSR, patients undergoing minimal-invasive hepatectomy had equivalent 5-year OS (42% vs. 37%, p = 0.261) and equivalent 5-year RFS (34% vs. 34%, p = 0.613) rates compared to patients undergoing open hepatectomy.ConclusionsPSR for CRLM is associated with lower postoperative morbidity, shorter length of hospital stay, and equivalent oncologic outcomes compared to non-PSR, independently of tumor burden. Our findings suggest that minimal-invasive PSR should be considered as the preferred method for the treatment of curatively resectable CRLM, if allowed by tumor size and location.     

Outcomes following synchronous liver resection,cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases: A bi-institutional study

PurposeSynchronous liver resection, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal liver (CRLM) and peritoneal metastases (CRPM) has traditionally been contraindicated. However, latest practice promotes specialist, multidisciplinary-led consideration for select patients. This study aimed to evaluate the perioperative and oncological outcomes of synchronous resection in the management of CRLM and CRPM from two tertiary referral centres.MethodThis bi-institutional, retrospective, cohort study included patients undergoing simultaneous liver resection, CRS and HIPEC for metastatic colorectal cancer from 2013 to 2020. Patients treated with ablative liver techniques, staged operative approaches and extra abdominal disease were excluded. Overall survival (OS) and disease-free survival (DFS) rates were assessed. Univariate and multivariate analyses identified variables associated with survival and major morbidity (Clavien-Dindo grade III/IV).ResultsTwenty-three patients were included. The median peritoneal carcinomatosis index (PCI) was 9 (range 0–22). There were two major liver resections and 21 minor resections. CC-0 resections were achieved in all patients. Major morbidity occurred in 7 patients. There were no deaths at 90 days. PCI was independently associated with morbidity (p = 0.04). PCI >10 (p = 0.069), major morbidity (p = 0.083) and presence of KRAS mutation (p = 0.052) approached significance for poor OS. Median follow up was 21 months (4–54 months). Median OS was 37 months, 3-year survival 54%, and median DFS 18 months.ConclusionSynchronous liver resection, cytoreductive surgery and HIPEC is feasible in selected patients with low-volume CRPM and CRLM. Increasing PCI is associated with postoperative major morbidity, and should be considered during operative planning.     

Neoadjuvant chemotherapy for colorectal liver metastases: A contemporary review of the literature

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide, and up to 50% of patients with CRC develop colorectal liver metastases (CRLM). For these patients, surgical resection remains the only opportunity for cure and long-term survival. Over the past few decades, outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy, as well as improvements in operative technique and perioperative care. Chemotherapy in the modern era of oxaliplatin- and irinotecan-containing regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents. The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery. Consequently, the use of neoadjuvant strategies is becoming progressively more established. For patients with CRLM, the primary advantage of neoadjuvant chemotherapy (NCT) is the potential to down-stage metastatic disease in order to facilitate hepatic resection. On the other hand, the routine use of NCT for patients with resectable metastases remains controversial, especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy. Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk, reserving NCT for patients with borderline resectable or unresectable disease and high operative risk. Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability. In light of the growing number of treatment options available to patients with metastatic CRC, it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.     

Liver resection for colorectal cancer metastases

Questions

1. Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)?
2. What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)?
3. What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy?

Perspectives

Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required.

Methodology

Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline.

Practice Guideline

These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent.

• 1(a). Patients with liver and lung metastases should be seen in consultation with a thoracic surgeon. Combined or staged metastasectomy is recommended when, taking into account anatomic and physiologic considerations, the assessment is that all pulmonary metastases can also be completely removed. Furthermore, liver resection may be indicated in patients who have had a prior lung resection, and vice versa.
• 1(b). Routine liver resection is not recommended in patients with portal nodal disease. This group includes patients with radiologically suspicious portal nodes or malignant portal nodes found preoperatively or intraoperatively. Liver plus nodal resection, together with perioperative systemic therapy, may be an option—after a full discussion with the patient—in cases with limited nodal involvement and with metastases that can be completely resected.
• 1(c). Routine liver resection is not recommended in patients with nonpulmonary ehms. Liver plus extrahepatic resection, together with perioperative systemic therapy, may be an option—after a full discussion with the patient—for metastases that can be completely resected.
• 2(a). Perioperative chemotherapy, either before and after resection, or after resection, is recommended in patients with resectable liver metastatic disease. This recommendation extends to patients with ehms that can be completely resected (R0). Risks and potential benefits of perioperative chemotherapy should be discussed for patients with resectable liver metastases. The data on whether patients with previous oxaliplatin-based chemotherapy or a short interval from completion of adjuvant therapy for primary crc might benefit from perioperative chemotherapy are limited.
• 2(b). Liver resection is recommended in patients with initially unresectable metastatic liver disease who have a sufficient downstaging response to conversion chemotherapy. If complete resection has been achieved, postoperative chemotherapy should be considered.
• 3. Surgical resection of all lesions, including lesions with rcr, is recommended when technically feasible and when adequate functional liver can be left as a remnant. When a lesion with rcr is present in a portion of the liver that cannot be resected, surgery may still be a reasonable therapeutic strategy if all other visible disease can be resected. Postoperative chemotherapy might be considered in those patients. Close follow-up of the lesion with rcr is warranted to allow localized treatment or further resection for an in situ recurrence.

     

Impact of type of liver resection on the outcome of colorectal liver metastases: a case-matched analysis

BACKGROUND: Wedge resection (WR) for colorectal liver metastases (CLM) has become more common in an attempt to preserve liver parenchyma. However, some investigator have reported that WR is associated with a higher incidence of positive margin and an inferior survival compared with anatomic resection (AR) 1. OBJECTIVES: This study evaluated survival, margin status, and pattern of recurrence of patients with CLM treated with WR or AR. METHODS: We identified 208 consecutive patients, in a single institutional database from 1995 to 2004, who underwent either WR or AR. WR was defined as a nonanatomic resection and AR was defined as single resection of one or two liver segments. Patients with combined WR-AR and patients requiring resection of more than two segments or radiofrequency ablation were excluded from the analysis. RESULTS: One hundred six patients underwent WR and 102 patients had AR. There were no differences in the rate of positive surgical margin (P = 0.146), overall recurrence rates (P = 0.211), and patterns of recurrence between the two groups (P = 0.468). The median survival was 32 months for WR and 42 for AR, with 5-year survival rates of 29% and 27% respectively, with no significant difference (P = 0.308). Morbidity was similar between the two groups. CONCLUSIONS: WR is a safe procedure and does not disadvantage the patients in terms of tumor recurrence and overall survival.     

Proteome biology of primary colorectal carcinoma and corresponding liver metastases

Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.     

Impact of treatment modality and number of lesions on recurrence and survival outcomes after treatment of colorectal cancer liver metastases

Background

Ablative strategies have been used to treat and facilitate hepatic resection (HR) in patients with otherwise unresectable colorectal liver metastases (CLM). We evaluated the efficacy of HR, concomitant HR and ablation and isolated ablation on recurrence and survival outcomes after treatment of CLM in patients with 1-4 and ≥5 lesions, respectively.

Methods

A retrospective review of a prospectively collected hepatobiliary surgery database was performed on patients who underwent treatment for isolated CLM between 1990 and 2010. Pre-operative and treatment characteristics were compared between patients who underwent HR, concomitant HR and ablation and ablation alone. The impact of treatment modality on survival and recurrence outcomes was determined.

Results

A total of 701 patients met inclusion criteria; 550 patients (78%) had 1-4 lesions and 151 patients (22%) had ≥5 lesions. Overall median survival for the entire cohort was 35 months with 5- and 10-year survival of 33% and 20%, respectively. Overall median and 5-year recurrence-free survival (RFS) was 13 months and 21%, respectively. For patients with 1-4 lesions, median survival was 37 months with 5-year survival of 36%. Stratified by procedure type, 5-year survival was 41% in patients who underwent HR, 35% in patients who underwent concomitant HR and ablation and 13% in patients who underwent ablation alone (P<0.001). For patients with ≥5 lesions, median survival was 28 months with 5-year survival of 23% without difference between treatment groups (P=0.078).

Conclusions

HR appears to be the most effective strategy for patients with 1-4 lesions. When ≥5 lesions are present, ablative strategies are useful in facilitating HR in otherwise unresectable patients.     

Hepatic vascular inflow occlusion is associated with reduced disease free survival following resection of colorectal liver metastases

Background

Hepatic vascular inflow occlusion (VIO) can be applied during resection of colorectal liver metastases (CRLM) to control intra-operative blood loss, but has been linked to accelerated growth of micrometastases in experimental models. This study aimed to investigate the effects of hepatic VIO on disease-free and overall survival (DFS and OS) in patients following resection for CRLM.

微小RNA 507靶向调控VEGFC表达及对肝癌细胞生物学行为和PI3K／Akt通路的影响#br# #br#

目的探讨微小RNA 507（miR 507）对肝癌细胞增殖、凋亡和迁移能力及PI3K／Akt信号通路的影响并分析miR 507对血管内皮生长因子C（VEGFC）的靶向调控作用。 方法采用实时荧光定量PCR（QPCR）检测2014年1月至2017年3月经病理确诊的90例肝癌患者的癌组织及癌旁组织中的miR 507和VEGFC mRNA水平;采用脂质体法向人肝癌细胞HepG2转染miR 507 模拟物（过表达组）或阴性对照（NC组）,QPCR检测转染48 h后的miR 507水平,MTT法比较不同处理时间（0、12、24、48 h）各组细胞的增殖情况,Annexin Ⅴ FITC／PI流式细胞术检测细胞凋亡情况,划痕实验比较各组迁移情况,QPCR和Western blotting分别检测VEGFC及PI3K／Akt信号通路中p PI3K和p Akt的mRNA和蛋白水平;采用双荧光素酶报告基因实验验证miR 507与靶基因VEGFC间的靶向关系和结合位点。 结果QPCR检测发现肝癌组织中的miR 507水平为0672±0089,低于癌旁组织的1142±0136,VEGFC mRNA水平为1482±0156,高于癌旁组织的1021±0087,差异均有统计学意义（P＜005）。与NC组和对照组相比,过表达组HepG2细胞的增殖活力在转染24～48 h后明显减弱（P＜001）。过表达组的凋亡率为（1726±196）％,高于NC组的（785±087）％和对照组的（813±069）％,过表达组的愈合率为（3965±487）％,低于NC组的（5818±273）％和对照组的（5724±317）％,差异有统计学意义（P＜005）。过表达组的p Akt、p PI3K和VEGFC的蛋白和mRNA水平均低于NC组和对照组,差异有统计学意义（P＜005）。双荧光素酶报告基因实验证明VEGFC是miR 507的直接作用靶点。 结论VEGFC可能通过PI3K／Akt信号通路介导miR 507对肝癌细胞HepG2增殖、凋亡与迁移能力的调控,因此miR 507可作为肝癌潜在的分子治疗靶点。     

Management of liver metastases in colorectal cancer patients: A retrospective case-control study of systemic therapy versus liver resection

ObjectiveTo evaluate and compare the overall survival (OS) in case-matched patient groups treated either with systemic therapy or surgery for colorectal liver metastases (CRLM).MethodsPatients with CRLM, without extra-hepatic disease, treated with chemotherapy with or without targeted therapy in two phase III studies (n = 480) were selected and case-matched to patients who underwent liver resection (n = 632). Matching criteria were sex, age, established prognostic factors for survival (clinical risk score). Available computed tomography (CT)-scans of patients treated with systemic therapies were reviewed by three independent liver surgeons for resectability. Survival was compared between patients with resectable CRLM (based on CT-scan review) who were treated with systemic therapy versus patients who underwent liver resection.ResultsA total of 96 patients treated with systemic therapy were included. Pre-treatment CT-scans of the liver were available for review in 56 of the systemically treated patients, and metastases were unanimously considered resectable in 36 patients (64.3%) (complex resectable: n = 25; 69%). These 36 patients were case-matched with 36 patients who underwent liver resection (wedge resection or segmentectomy: n = 26; 72%). Median OS in the patient group treated with systemic therapy was 26.5 months (range 0–81 months), which was significantly lower than that in case-matched patients who underwent liver resection (median OS 56 months; range 6–116) (p = 0.027).ConclusionsIn this case-matched control study, surgery provided superior OS rates compared to systemic therapy for CRLM. Resection of CRLM should always be considered, preferably in a dedicated liver centre, since not all patients that qualify for resection are identified as such.