Hepatic Resection For Colorectal Liver Metastases Research Articles

Detection and Real-Time Surgical Assessment of Colorectal Liver Metastases Using Near-Infrared Fluorescence Imaging during Laparoscopic and Robotic-Assisted Resections.

The European Association of Endoscopic Surgery (EAES) recommends, with strong evidence, the use of indocyanine green (ICG) fluorescence imaging combined with intraoperative ultrasound (IOUS) to improve identification of superficial liver tumors. This study reports the use of ICG for the detection of colorectal liver metastases (CRLMs) during minimally invasive liver resection. A single-center consecutive series of minimally invasive (laparoscopic and robotic) hepatic resections for CRLMs was prospectively evaluated (April 2019 and October 2023). A total of 25 patients were enrolled-11 undergoing laparoscopic and 14 undergoing robotic procedures. The median age was 65 (range 50-85) years. Fifty CRLMs were detected: twenty superficial, eight exophytic, seven shallow (<8 mm from the hepatic surface), and fifteen deep (>10 mm from the hepatic surface) lesions. The detection rates of CRLMs through preoperative imaging, laparoscopic ultrasound (LUS), ICG fluorescence, and combined modalities (ICG and LUS) were 88%, 90%, 68%, and 100%, respectively. ICG fluorescence staining allowed us to detect five small additional superficial lesions (not identified with other preoperative/intraoperative techniques). However, two lesions were false positive fluorescence accumulations. All rim fluorescence pattern lesions were CRLMs. ICG fluorescence was used as a real-time guide to assess surgical margins during parenchymal-sparing liver resections. All patients with integrity of the fluorescent rim around the CRLM displayed a radical resection during histopathological analysis. Four patients (8%) with a protruding rim or residual rim patterns had positive resection margins. ICG fluorescence imaging can be integrated with other conventional intraoperative imaging techniques to optimize intraoperative staging. Rim fluorescence proved to be a valid indicator of the resection margins: by removing the entire fluorescent area, a tumor-negative resection (R0) is achieved.

Differential effects of KRAS mutational status on long-term survival according to the timing of colorectal liver metastases

BackgroundThe relationship between KRAS mutational status and timing of colorectal liver metastasis (CRLM) remains unclear. This study evaluated the relationship between KRAS mutational status and long-term survival in patients with synchronous CRLM.MethodsOf the 255 patients who underwent initial hepatic resection for CRLM between January 2001 and December 2018, the KRAS mutational status was examined in 101 patients. Medical records of these patients were reviewed to evaluate recurrence and survival outcomes.ResultsKRAS mutant status was identified in 38 patients (37.6%). The overall survival (OS) was significantly better in patients with wild-type KRAS than in those with mutant KRAS status. In patients with synchronous metastases, the OS of patients with wild-type KRAS was significantly better than those with mutant KRAS. Multivariate analyses indicated shorter OS to be independently associated with positive primary lymph node, and large tumor size and R1 resection in patients with metachronous metastasis, whereas to be independently associated with mutant KRAS status in patients with synchronous metastasis. Furthermore, in the subgroup of patients with synchronous metastases, the repeat resection rate for hepatic recurrence was significantly high in those with wild type KRAS than in those with mutant KRAS.ConclusionKRAS mutation is an independent prognostic factor in patients with synchronous CRLM, but not in patients with metachronous CRLM.

Efficacy of upfront hepatectomy without neoadjuvant chemotherapy for resectable colorectal liver metastasis

BackgroundHepatectomy for resectable colorectal liver metastasis (CRLM) is recommended. However, the efficacy of upfront hepatectomy without neoadjuvant chemotherapy (NAC) is unclear due to the uncertainty of perioperative systemic chemotherapy. Moreover, it is crucial to predict the prognosis when considering perioperative chemotherapy. This study evaluated the impact of neoadjuvant chemotherapy on the prognosis of patients with resectable CRLM and assessed the usefulness of Beppu’s nomogram for predicting prognosis.MethodsThis retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for CRLM; 58 received neoadjuvant chemotherapy and 30 underwent upfront surgery. Factors associated with recurrence-free survival were identified via univariate and multivariate analysis. Furthermore, propensity score analysis using inverse probability of treatment weighting (IPTW) was performed.ResultsOn univariate analysis, poor recurrence-free survival was associated with multiple tumors, advanced primary tumor stage, vascular invasion by the primary tumor, a Beppu’s nomogram score ≥ 6, and neoadjuvant chemotherapy. On multivariate analysis, a Beppu’s nomogram score ≥ 6 and neoadjuvant chemotherapy were independent risk factors for recurrence. Neoadjuvant chemotherapy recipients had a higher incidence of lymph node metastasis and vascular invasion than non-recipients. Propensity score analysis revealed no significant difference in the recurrence-free survival rate between these groups.ConclusionsOur results show that upfront hepatectomy without neoadjuvant chemotherapy can be considered for resectable CRLM treatment. Beppu’s nomogram score can be a tool for predicting the prognosis of patients with CRLM.

Correlation between CT morphologic appearance and histologic findings in colorectal liver metastasis after preoperative chemotherapy.

Radiological evaluation of the efficacy of preoperative chemotherapy for colorectal liver metastasis (CRLM) is the most important tool for determining treatment strategies. The aim of this study was to identify a correlation between morphologic appearance on computed tomography (CT) and histologic findings of CRLM after preoperative chemotherapy. We examined 47 patients who had undergone a first hepatic resection for CRLM after preoperative chemotherapy and had received contrast-enhanced CT scans. We assessed the morphologic appearance of the overall attenuation based on metastases changing from heterogeneous to mixed and homogenous lesions, the tumor-liver interface, and the peripheral rim enhancement on CT. Histologic parameters included usual necrosis (UN), infarct-like necrosis (ILN), three-zonal change, dangerous halo, mucous lake, shape of ILN, dominant type of necrosis, and presence of viable tumor cells. The relationship between morphologic appearance and histologic findings was evaluated. CT overall attenuation revealed that UN predominance was more common in the heterogeneous group than in the mixed and homogeneous groups (P = 0.011). The frequency of ILN increased sequentially from ill-defined to variable and sharp at the tumor-liver interface (P = 0.038), and the frequency of UN decreased sequentially from present to partially resolved and completely resolved in the peripheral rim enhancement (P = 0.023). The histologic presence of viable tumor cells was closely associated with the tumor-liver interface (P = 0.0003) and the peripheral rim enhancement (P = 0.004). CT morphologic appearance of CRLM after preoperative chemotherapy is correlated with histologic findings regarding necrosis.

Impact of fresh frozen plasma transfusion on postoperative inflammation and prognosis of colorectal liver metastases

BackgroundBlood transfusion has been reported to be associated with immunomodulation and poor oncologic outcomes in several malignancies. The aim of the study is to investigate the influence of the use of fresh frozen plasma (FFP) on long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. Materials and methodsThe study comprised 127 patients who had undergone first hepatic resection for CRLM between April 2000 and December 2013. We retrospectively investigated the influence of the use of FFP on disease-free survival as well as overall survival and assessed the impact of such a practice on postoperative inflammation markers. ResultsIn multivariate analysis, more than four lymph node metastases of the primary cancer (P = 0.001), bilobar distribution (P = 0.002), and perioperative FFP transfusion (P = 0.005) were independent risk factors for cancer recurrence, while more than four lymph node metastases of the primary cancer (P < 0.001), presence of neoadjuvant chemotherapy (P = 0.002), and perioperative FFP transfusion (P = 0.004) were independent risk factors for poor overall survival. In patients who underwent FFP transfusion, tumor size (P = 0.004), anatomic resection (P < 0.001), duration of operation (P = 0.039), and intraoperative blood loss (P < 0.001) were significantly greater. Moreover, FFP transfusion was associated with a higher white blood cell level on postoperative day 3 (P < 0.001) and day 5 (P = 0.010) and lower serum C-reactive protein level on postoperative day 1 (P < 0.001) and day 3 (P = 0.017). ConclusionsPerioperative FFP transfusion is independently associated with poor long-term outcomes in patients with CRLM after hepatic resection. FFP may have an influence on postoperative inflammation because of its immunosuppressive effects.

Resection versus Radiofrequency Thermal Ablation of Colorectal Liver Metastasis: A Retrospective Comparative Study

Hepatic resection (HR) has been reported as the standard treatment for colorectal liver metastasis. Nevertheless, HR might not be suitable for some situations where those patients might be helped by chemoembolization or radiofrequency ablation (RFA) to treat their disease. RFA was first introduced in the late 1990s, however, it is questionable that RFA has similar survival rates as HR for patients with resectable liver metastasis. The aim of the present study was to compare the survival rates in patients with colorectal liver metastasis who were offered RFA versus HR. Patients and methods: This was a retrospective study conducted on 40 patients, 16 underwent RFA and 24 underwent HR for colorectal liver metastasis. Kaplan–Meier curves were used to determine survival and the log-rank test was used for comparison between groups. Results: The 3-year overall survival rates for patients with HR and RFA were 51.5 and 44.1% respectively (p=0.285). Conclusion: The 3-year overall and disease-free survival with RFA were similar to those treated with HR.

Recent advances in the treatment of colorectal liver metastases

Liver metastasis is the leading cause of death from colorectal cancer (CRC). Multidisciplinary team model has become standard strategy for the diagnosis and treatment of colorectal liver metastases (CRLM), making individuali-zed treatment through precise staging and molecular typing. Preoperative hepatic and regional arterial infusion chemotherapy and portal vein chemotherapy during surgery can reduce the incidence of liver metastases for stage Ⅲ CRC. Surgical resection of CRLM has been accepted by all scholars, and can be performed by minimally invasive surgery. The criteria for hepatic resection of CRLM have been extended including complete tumor resection, negative resection margin and adequate remnant liver volume. Simultaneous resections of primary tumor and liver metastases are safe and feasible. However, neoadjuvant chemotherapy is still controversial. For unresectable liver metastases, conversion therapy should be implemented to make the liver metastases become resectable. For unconvertible and unresectable CRLM, aggressive and comprehensive treatment is required to control the disease progression. Key words: Colorectal neoplasms; Liver metastases; Multidisciplinary team; Surgical indications

Effect of intratumoral CD3+ and NKp46+ cells on tumor progression in resected colorectal liver metastases treated with neoadjuvant chemotherapy.

281 Background: The long-term outcome of patients resected for colorectal liver metastases (CLM) after neoadjuvant chemotherapy (CHT) depends by several tumoral and non-tumoral factors, such as the immune response to the tumor and to the CHT. The aim of this study was to investigate the impact of the pathological and immunological response in patients undergoing liver resection for CLM after CHT in regards to the long-term outcome. Methods: The immunoreactivity to CD3+ and NKp46+ cells inside the tumor, at the border between the tumor and the normal liver, and inside the normal liver was tested by computer-assisted image analyses in 121 patients undergoing liver resection for CLM between 2005 and 2013 preoperatively treated with oxaliplatin or irinotecan with or without bevacizumab or cetuximab. The survival was assessed in relation to several prognostic factors and to that immunoreactivity. Results: At univariate analysis T1/T2- and N0-status of the primary tumor, metachronous CLM, the radiological response, and the higher density of intratumoral CD3+ ( &gt; 1%) and of NKp46+ (mean &gt; 1) were found to be significantly associated with prolonged survival, but only intratumoral CD3+ ( &gt; 1%) and NKp46+ (mean &gt; 1) were significant on multivariate analysis (P = 0.005 and P = 0.004 respectively). On logistic regression analysis the metachronous CLM (OR = 2.781; P = 0.002), the use of irinotecan and cetuximab (OR = 3.891; P = 0.001) and the radiological response (OR = 3.219; P = 0.001) were found to be associated with increasing density of intratumoral CD3+ and NKp46+ cells. No significant associations were found with CLM number or size, CEA, or number of CHT courses. Combining the intratumoral CD3+ and NKp46+ cells density we defined four stages of survival (P = 0.003): patients presenting intratumoral CD3+ ( &gt; 1%) and NKp46+ (mean &gt; 1) had 100% overall survival at 5 years. Conclusions: Intratumoral CD3+ and NKp46+ cells density is a crucial prognostic factor in patients undergoing hepatic resection for CLM after CHT, and the kind of CHT seems related to their density. Further external validations are required to confirm our promising findings.

Routine Preoperative Liver-specific Magnetic Resonance Imaging Does Not Exclude the Necessity of Contrast-enhanced Intraoperative Ultrasound in Hepatic Resection for Colorectal Liver Metastasis

To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) during surgery for colorectal liver metastases (CRLM) when gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) is performed as a part of preoperative imaging work-up. EOB-MRI is expected to supersede CE-IOUS, which is reportedly indispensable in surgery for CRLM. One hundred consecutive patients underwent EOB-MRI, contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound within 1 month before surgery for CRLM. Conventional IOUS and subsequent CE-IOUS using perflubutane were performed after the laparotomy. All the nodules identified in any of the preoperative or intraoperative examinations were resected and were submitted for histological examination, in principle. Preoperative imaging examinations identified 242 nodules; 25 additional nodules were newly identified using IOUS, 22 additional nodules were newly identified during CE-IOUS, and a histological examination further identified 4 nodules. Among the 25 nodules newly identified using IOUS, all 21 histologically proven CRLMs and 3 of the 4 benign nodules were correctly diagnosed using CE-IOUS. Among the 22 nodules newly identified using CE-IOUS, 17 nodules in 16 patients were histologically diagnosed as CRLMs. The planned surgical procedure was modified on the basis of IOUS and CE-IOUS findings in 12 and 14 patients, respectively. The sensitivity, positive-predictive value, and accuracy of CE-IOUS were 99%, 98%, and 97%, respectively. Those values of EOB-MRI (82%, 99%, 83%, respectively) were similar to CE-CT (81%, 99%, 81%, respectively). CE-IOUS is useful in hepatic resection for CRLM, even if EOB-MRI and CE-CT are performed.

Positive Impact of Epidural Analgesia on Oncologic Outcomes in Patients Undergoing Resection of Colorectal Liver Metastases.

Previous studies have suggested that the use of regional anesthesia can reduce recurrence risk after oncologic surgery. The purpose of this study was to assess the effect of epidural anesthesia on recurrence-free (RFS) and overall survival (OS) after hepatic resection for colorectal liver metastases (CLM). After approval of the institutional review board, the records of all adult patients who underwent elective hepatic resection between January 2006 and October 2011 were retrospectively reviewed. Patients were categorized according to use of perioperative epidural analgesia versus intravenous analgesia. Univariate and multivariate analyses were performed to identify factors influencing RFS and OS. Of 510 total patients, 390 received epidural analgesia (EA group) and 120 patients received intravenous analgesia (IVA group). Compared with the IVA group, more patients in the EA group underwent associated surgical procedures with consequently longer operative times (p < 0.001). In addition, the EA group received more intraoperative fluids and had higher urine output volumes (p ≤ 0.001). Five-year RFS was longer in the EA group (34.7%) compared with the IVA group (21.1%). On multivariate analysis, the receipt of epidural analgesia was an independent predictor of improved RFS (p = 0.036, hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.56-0.95), but not OS (p = 0.102, HR 0.72; 95% CI 0.49-1.07). This study suggests an association between epidural analgesia and improved RFS, but not OS, after CLM resection. These results warrant further prospective, randomized studies on the benefits of regional anesthesia on oncologic outcomes after hepatic resection for CLM.

Abstract 3169: Influence of systemic and local immune response on overall survival after hepatic resection of colorectal liver metastasis

Abstract Background: Colorectal cancer progression is dependent on complex interactions between the tumor and the host. Tumor infiltrating lymphocytes (TIL) have been reported as a prognostic factor in colorectal cancer. The aim of this study was to assess the prognostic value of pre-operative systemic immune biomarkers and TIL in patients with resectable colorectal liver metastases (CLM). Methods: Clinicopathological data were reviewed for patients (n = 31) underwent hepatic resections for CLM between 2000 and 2008. Prognostic variables are factors of the primary lesion, factors of the metastatic lesion, and factors of host inflammatory biomarkers measured from routine pre-operative blood tests (modified Glasgow Prognostic Score and neutrophil to lymphocyte ratio (NLR)). Univariate and multivariate analyses for prognostic factors were performed. To evaluate the local immune responses for resected metastatic lesion, immunohistochemical analysis was performed. The immune subsets were CD8+ T cells, CD45RO+ T cells, Fork head box p3+ (FOXP3+) T cells, and CD66b+ neutrophils. Results: The number of metastases ≥ 4, extrahepatic metastasis, adjuvant chemotherapy, and raised NLR &amp;gt; 4.1 were correlated with cancer-specific survival in univariate analysis. On multivariate analysis, the number of metastases ≥ 4, adjuvant chemotherapy, and elevated NLR remained independent prognostic indicators (metastases ≥ 4: HR = 0.09, CI = 0.01-0.56, p = 0.0102, adjuvant chemotherapy: HR = 0.08, CI = 0.01-0.39, p = 0.0025, NLR: HR = 0.11, CI = 0.01-0.99, p = 0.0494). Accumulation of CD45RO+ T cells and FOXP3+ T cells in the metasatic tumors were significantly associated with favorable survival in patients with resectable CLM (P = 0.02 and 0.04, respectively). Conclusions: The results of the present study show that the NLR has prognostic value in patients who conduct a hepatic resection for CLM. Moreover, accumulation of CD45RO+ T cells and FOXP3+ T cells in metastatic lesions are independent favorable prognostic factor. Based on the present results and previously literature, systemic immune response including NLR and local immune response may be promising as prognostic factor of patients with resectable CLM. Citation Format: Takeomi Hamada, Ishizaki Hidenobu, Yukihiro Haruyama, Rouko Hamada, Koichi Yano, Kazuhiro Otani, Yoshiro Fujii, Kazuhiro Kondo, Hiroaki Kataoka. Influence of systemic and local immune response on overall survival after hepatic resection of colorectal liver metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3169. doi:10.1158/1538-7445.AM2015-3169

The current role of intraoperative ultrasound during the resection of colorectal liver metastases: A retrospective cohort study

IntroductionLiver resections with negative margins improve survival in patients with colorectal liver metastases (CRLM). Intraoperative ultrasound (IOUS) is a valuable tool that gives information about lesions that ultimately changes surgical strategy to ensure complete removal, which subsequently improves disease free survival (DFS). MethodsA retrospective review of patients who underwent a resection for CRLM from 2009 to 2012 was completed to determine the impact of IOUS. ResultsA total of 103 patients had a hepatic resection for CRLM. All patients had preoperative imaging to assist with operative planning. IOUS was performed in 72 cases. Surgical strategy changed in 31 (43.1%) cases with IOUS, compared to three (9.7%) with no IOUS (P < 0.001). A new lesion was detected in 13 (18.1%) of the cases. A higher proportion of nonanatomic liver resections were performed in the IOUS group (N = 27, 37.5%) compared to the non-IOUS group (N = 6, 19.4%) (P = 0.07). ConclusionAchievement of a negative resection margin was comparable between the two groups. However, there was a trend toward improved DFS in the IOUS group. Despite advances in preoperative imaging, IOUS demonstrates utility in providing novel information that allows removal of the entire tumor burden, using parenchymal-preserving techniques when feasible, leading to improved DFS.

Influence of systemic and local immune response on overall survival after hepatic resection of colorectal liver metastasis.

756 Background: Colorectal cancer progression is dependent on complex interactions between the tumor and the host. Tumor infiltrating lymphocytes (TIL) have been reported as a prognostic factor in colorectal cancer. The aim of this study was to assess the prognostic value of pre-operative systemic immune biomarkers and TIL in patients with resectable colorectal liver metastases (CLM). Methods: Clinicopathological data were reviewed for patients (n=31) who underwent hepatic resections for CLM between 2000 and 2008. Prognostic variables from the primary lesion, metastatic lesion, and host inflammatory biomarkers measured as routine pre-operative blood tests (modified Glasgow Prognostic Score and neutrophil to lymphocyte ratio [NLR]) were evaluated by univariate and multivariate analyses. To evaluate the local immune responses of resected metastatic lesion, immunohistochemical analysis was performed. The immune subsets were CD8+ T cells, CD45RO+ T cells, Fork head box p3+ (FOXP3+) T cells, and CD66b+ neutrophils. We also evaluated PD-L1 expression in the metastatic lesion. Results: The number of metastases ≥ 4, extrahepatic metastasis, adjuvant chemotherapy, and NLR &gt; 4.1 were correlated with cancer-specific survival in univariate analysis. On multivariate analysis, the number of metastases (HR: 0.09, CI: 0.01-0.56, p=0.0102), adjuvant chemotherapy (HR: 0.08, CI: 0.01-0.39, p=0.0025), and raised NLR (HR: 0.11, CI: 0.01-0.99, p=0.0494) remained independent prognostic indicators. Accumulation of CD45RO+ memory T cells in the metastatic tumors was significantly associated with favorable survival in patients with resectable CLM (p=0.020). Interestingly, increased neutrophils in peripheral blood showed significant correlation with reduced accumulation of CD45RO+ memory T cells in metastatic lesion (p=0.023). Conclusions: Based on the present results and the existing validation literature, systemic immune response including NLR and local immune response including CD45RO+ memory T cells may be promising prognostic factor of patients with resectable CLM. Further functional analysis of neutrophils in CLM patient will be needed.

Effect of KRAS mutation on long-term outcomes of patients undergoing hepatic resection for colorectal liver metastases.

282 Background: The impact of KRAS mutation on overall (OS) and recurrence-free (RFS) survival of patients with colorectal liver metastases (CLM) remains poorly defined. We sought to investigate the prognostic value of KRAS in a large cohort of patients undergoing liver resection for CLM. Methods: Between 2003 and 2013, 334 patients underwent hepatic resection for CLM at Johns Hopkins Hospital and met the inclusion criteria. Somatic mutations at codons 12/13 were evaluated through a sequencing analysis of the tumor samples. Clinicopathological characteristics, perioperative details, and outcomes were stratified by KRAS status (mtKRAS vs. wtKRAS) and analyzed. Results: Among 334 patients undergoing liver resection for CLM, mtKRAS was identified in 115 (34.4%) patients. Median CEA was 7.3 ng/dL; 40.4% of patients had a solitary tumor and median tumor size was 2.5 cm. At a median follow-up of 28.2 months, recurrence was observed in 59 (51.3%) patients with mtKRAS and 117 (53.4%) patients with wtKRAS (P=0.71); there was no difference in the pattern of recurrence (liver: mtKRAS, 39.0% vs. wtKRAS, 52.1%; lung: mtKRAS, 55.6% vs. wtKRAS, 64.3%; both P&gt;0.05). While 5-year log-rank OS was comparable among mtKRAS (41.6%) vs. wtKRAS (48.5%), on multivariable Cox survival analysis mtKRAS was associated with worse OS(HR, 1.65; 95%CI, 1.07-2.54). Moreover, among patients who experienced a recurrence, 5-year OS was worse among those patients who had mtKRAS (mtKRAS, 28.1% vs. wtKRAS, 44.5%; P=0.004). After controlling for tumor factors, as well as receipt of chemotherapy, mtKRAS status remained independently associated with a worse outcome among patients who recurred(HR 2.07, 95% CI 1.31-3.27; P=0.002). Conclusions: mtKRAS was noted in one-third of patients with CLM. While KRAS status did not impact pattern of recurrence, mtKRAS was an independent predictor of worse OS among patients who experienced a recurrence following resection of CLM.

Critical review of the prognostic significance of pathological variables in patients undergoing resection for colorectal liver metastases

ObjectiveThe aim of this study was to identify prognostic factors, particularly pathological variables, that influence disease-free and overall survival following resection for colorectal liver metastases (CRLM). MethodsPatients undergoing CRLM resection from January 2005 to December 2011 were included. Data analysed included information on demographics, laboratory results, operative findings, histopathological features and survival. ResultsA total of 259 patients were included. Of these, 138 (53.3%) patients developed recurrent disease, of which 95 died. The median length of follow-up in the remaining patients was 28months (range: 12–96months). There were significant associations between recurrence and higher tumour number (P = 0.002), presence of perineural invasion (P = 0.009) and positive margin (R1) resection (P = 0.002). Multivariate analysis showed all three prognostic factors to be independent predictors of disease-free survival. Significantly poorer overall survival after hepatic resection for CRLM was observed in patients undergoing hemi-hepatectomy or more radical resection (P = 0.021), patients with a higher number of tumours (P = 0.024) and patients with perineural invasion (P < 0.001). Multivariate analysis showed perineural invasion to be the only independent predictor of overall survival. ConclusionsThe presence of perineural invasion, multiple tumours and an R1 margin were associated with recurrent disease. Perineural invasion was also an independent prognostic factor with respect to overall survival.

The prognostic significance of lymphatics in colorectal liver metastases.

Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%–60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

Improved Surgical Management of Colorectal Liver Metastases: A population-based retrospective analysis of 5773 cases in Southern Germany

Background: Purpose of this study was to analyze the development of the surgical management of colorectal liver metastases (CLM) over a period of 10 years as well as the long-term clinical outcome of patients with CLM using data from a regional German tumour registry. Methods: Retrospective analysis of 5773 patients diagnosed with colorectal adenocarcinoma between 2002 and 2007 in Southern Germany. Observation was continued until 2012. Results: In total, 1355 patients (23.5%) had or developed CLM. Hepatic resection for CLM was performed in 357 patients (26.3% of CLM patients; 6.2% of all patients). Patients without CLM had a significantly better 5-year survival (58%) and 10-year survival (32%) than patients with liver metastases (14% and 6% respectively). Resection rates of CLM increased from 18% in 2002 to > 30% in 2006 and later with a significant increase in overall survival in resected CLM patients (up to 42% 5-year survival, 28% 10-year survival). Conclusions: The present study shows a significant improvement of the surgical management of colorectal liver metastases diagnosed from 2002 until 2007 in Southern Germany. However, no hepatic surgery was performed in up to 48% of potentially resectable CLM. The reasons for this relevant undertreatment need to be discussed in an interdisciplinary fashion between medical and surgical oncologists.

Hepatic Pedicle Clamping Does Not Worsen Survival after Hepatic Resection for Colorectal Liver Metastasis: Results from a Systematic Review and Meta-analysis

Hepatic pedicle clamping (HPC) has been demonstrated to be effective for short-term outcomes during hepatic resection. However, HPC-induced hepatic ischemia/reperfusion injury can accelerate the outgrowth of hepatic micrometastases in experimental studies. The conclusive evidence regarding effects of HPC on long-term patient outcomes after hepatic resection for colorectal liver metastasis (CRLM) has not been determined. A comprehensive electronic literature search was performed to identify studies evaluating the oncological effects of HPC after hepatic resection for CRLM. The main outcome measures were intrahepatic recurrence (IHR), disease-free survival (DFS), and overall survival (OS). A meta-analysis was performed using the random-effects models to compute odds ratio (OR) along with 95% confidence intervals (CI). Four studies, with a total of 2,114 patients (73.7% HPC, 26.3% non-HPC), matched the inclusion criteria. Meta-analyses revealed that IHR (OR 0.88; 95% CI 0.69-1.11; P = 0.27), DFS (OR 0.88; 95% CI 0.70-1.10; P = 0.27) and OS (OR 0.99; 95% CI 0.79-1.24; P = 0.90) did not differ significantly between the HPC and non-HPC groups. This meta-analysis provides persuasive evidence that HPC during hepatic resection for CRLM has no significant adverse oncological outcomes. HPC should be considered an option during parenchymal liver resection from current available evidence.

Postoperative peripheral blood monocyte count correlates with postoperative bile leakage in patients with colorectal liver metastases after hepatic resection

Postoperative bile leakage is one of the most common complications after hepatic surgery. The relationship between the inflammatory response and postoperative bile leakage has not been fully investigated. Therefore, we retrospectively investigated the relation between postoperative peripheral blood monocyte count and bile leakage in patients with colorectal liver metastases (CRLM) after elective hepatic resection. The study comprised 105 patients who had undergone hepatic resection for CRLM between January 2000 and March 2012. Perioperative risk factors pertinent to development of bile leakage were investigated using univariate and multivariate analyses. Bile leakage developed in 9 (8.6%) of 105 patients. In multivariate analysis, intraoperative fresh frozen plasma (FFP) transfusion (p = 0.009) and lower monocyte count of the peripheral blood on postoperative day1 (p = 0.038) were found as independent risk factors of bile leakage. Postoperative lower monocyte count and intraoperative FFP transfusion were associated with the development of postoperative bile leakage after elective hepatic resection in patients with CRLM.

Does Postoperative Complication Have a Negative Impact on Long-Term Outcomes Following Hepatic Resection for Colorectal Liver Metastasis?: A Meta-Analysis

The negative impact of postoperative complications (POCs) on long-term outcomes is well documented for several cancer surgeries, but conclusive evidence has yet to be provided on the influence of POCs on long-term oncological outcomes after hepatic resection for colorectal liver metastasis (CRLM). Studies published through February 2012 evaluating the oncological impact of POCs after hepatectomy for CRLM were identified by an electronic literature search. Finally, 4 studies were identified and included in the meta-analysis. The main outcome measures were 5-year disease-free survival (DFS) and overall survival (OS). A meta-analysis was performed using the DerSimonian-Laird random-effects models to compute odds ratio (OR) along with 95 % confidence intervals (95% CI). The outcomes of 2,280 patients were studied. Meta-analysis of 5-year DFS data extracted from three studies demonstrated a significant reduction in 5-year DFS after POCs, with an OR of 1.98 (95% CI=1.33-2.96; P=.0008). Meta-analysis of 5-year OS data extracted from four studies demonstrated a significant reduction in 5-year OS after POCs, with an OR of 1.68 (95% CI=1.25-2.27; P=.0006). No differences between study heterogeneity were observed in either the DFS or the OS analyses. This study provides persuasive evidence that POCs following hepatic resection for CRLM have significant adverse oncological outcomes. These findings emphasize the need for meticulous surgical technique and careful perioperative management to minimize POCs.