Clinical Significance of Microvessel Count in Patients with Metastatic Liver Cancer Originating from Colorectal Carcinoma

Background  Microvessel count (MVC) has been correlated with patient prognosis in hepatocellular carcinoma. We investigated whether MVC assessed by staining with CD34 antibody was associated with disease-free and overall survival in patients with metastatic liver cancer (MLC). Methods  We examined relationships between MVC and clinicopathologic factors or postoperative outcomes in 139 MLC patients who underwent hepatectomy between 1990 and 2006. CD34 expression was analyzed by the immunohistochemical method. Results  MVC was associated with fibrous pseudocapsular formation on histological examination. By means of the modern Japanese classification of liver metastasis, poorer survival was associated with higher score, poorly differentiated adenocarcinoma, higher preoperative carcinoembryonic antigen (CEA) level, fibrous pseudocapsular formation, and smaller surgical margin. Shorter disease-free survival was associated with higher score when the Japanese classification of liver metastasis was used, multiple or bilobar tumor, regional lymph node metastasis in primary colon carcinoma, preoperative CEA level, fibrous pseudocapsular formation, and smaller surgical margin (<5 mm). Higher MVC (≥406/mm²) was associated with decreased disease-free and overall survival by univariate analysis (P = .034 and P = .021, respectively), and higher MVC represented an independently poor prognostic factor in overall survival by Cox multivariate analysis (risk ratio, 2.71; P = .023) in addition to histological differentiation. Conclusions  Tumor MVC seems to be a useful prognostic marker of MLC patient survival.     

结直肠癌患者血清微小RNA-615-5p和音猬因子表达与临床病理特征及预后的关系

目的：探究血清微小RNA(miR)-615-5p、音猬因子（SHH）表达与结直肠癌（CRC）患者临床病理特征及预后的关系。方法：以本院136例CRC患者为CRC组,同时段体检健康者（100例）为健康组;分析两组血清miR-615-5p、SHH表达水平差异,比较miR-615-5p、SHH不同表达水平与患者临床病理特征的关系,并分析影响CRC预后的相关因素;Pearson法分析miR-615-5p与SHH的相关性;采用Kaplan-Meier生存曲线分析血清miR-615-5p、SHH表达与CRC患者预后的关系。结果：CRC组血清miR-615-5p表达水平（0.57±0.13）低于健康组（1.02±0.05）,SHH表达水平（1.85±0.31）高于健康组（0.98±0.10）(P <0.05);miR-615-5p与SHH呈负相关（r=-0.631,P<0.05）;血清miR-615-5p、SHH表达水平与肿瘤T分期、N分期相关（P <0.05）;T分期高、SHH高表达是CRC预后的独立危险因素,miR-615-5p高表达是CRC预后的保护因素。生存分析显示miR-...     

Bevacizumab Efficacy in Metastatic Colorectal Cancer is Dependent on Primary Tumor Resection

Purpose

Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis.

Methods

We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients.

Results

In the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60–1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55–0.92, P = 0.009). Similar results were observed in the validation cohort.

Conclusions

Addition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC.     

Outcomes in Patients with Obstructive Jaundice from Metastatic Colorectal Cancer and Implications for Management

Introduction

Patients with metastatic colorectal cancer can develop jaundice from intrahepatic or extrahepatic causes. Currently, there is little data on the underlying causes and overall survival after onset of jaundice. The purpose of this study was to characterize the causes of jaundice and determine outcomes.

Methods

Six hundred twenty-nine patients treated for metastatic colorectal cancer between 2004 and 2010 were retrospectively reviewed. Those developing jaundice were grouped as having intrahepatic or extrahepatic obstruction. Demographics, clinicopathologic, and outcome data were analyzed.

Results

Sixty-two patients with metastatic colorectal cancer developed jaundice. Intrahepatic biliary obstruction was most common, occurring in younger patients. Time from metastatic diagnosis to presentation of jaundice was similar between groups, as was the mean number of prior lines of chemotherapy. Biliary decompression was successful 41.7 % of the time and was attempted more commonly for extrahepatic causes. Median overall survival after onset of jaundice was 1.5 months and it was similar between groups, but improved to 9.6 months in patients who were able to receive further chemotherapy.

Conclusions

Jaundice due to metastatic colorectal cancer is an ominous finding, representing aggressive tumor biology or exhaustion of therapies. Biliary decompression is often difficult and should only be pursued when additional treatment options are available.     

Association Between Palliative Resection of the Primary Tumor and Overall Survival in a Population-Based Cohort of Metastatic Colorectal Cancer Patients

Background

The impact of palliative resection of the primary tumor on outcomes in patients with metastatic colorectal cancer (mCRC) remains unclear. The primary objective of this study was to evaluate the association between palliative resection and overall survival (OS) in a population-based cohort of mCRC.

Methods

Patients diagnosed with mCRC between 2006 and 2008 and treated at the BC Cancer Agency were reviewed. Survival analysis was conducted using Kaplan–Meier methods. Cox proportional hazards regression models were fitted to evaluate the relationship between palliative resection and OS while controlling for potential confounders, such as age, gender, Eastern Cooperative Oncology Group status, carcinoembryonic antigen level, primary tumor location, metastatic site and number, and receipt of systemic therapy. To adjust for the heterogeneity and selection bias between the group that underwent palliative resection and the group that did not, a propensity score–matched analysis was also performed.

Results

A total of 517 patients were included. Among these cases, 378 (73 %) patients underwent palliative resection of their primary tumor, and 139 (27 %) patients did not. A total of 327 patients (63 %) were treated with palliative chemotherapy. Palliative resection was associated with a longer median OS (17.9 vs. 7.9 months) and more favorable unadjusted and adjusted hazard ratios (HRs) for death (HR 0.46, 95 % CI 0.37–0.56, p < 0.0001 and HR 0.56, 95 % CI 0.40–0.78, p = 0.0007, respectively) when compared with no resection. In a propensity score–matched analysis, prognosis was also more favorable in the resected group (p = 0.0017).

Conclusions

In this cohort of mCRC patients, palliative resection of the primary tumor was associated with improved OS.     

Patterns of Referral and Resection Among Patients with Liver-Only Metastatic Colorectal Cancer (MCRC)

Background  

Rates of metastatectomy vary among patients with liver-only metastatic colorectal cancer (MCRC). This study describe predictors of referral to a hepatobiliary surgeon (HBS) and hepatic resection in a population-based setting.     

Distribution of Metastatic Cancer Cells in Colorectal Mesentery

Background

To investigate the distribution of metastatic cancer cells in the mesentery (referred to as metastasis V) and enrich the understanding of the metastasis of colorectal cancer.

Methods

A total of two hundred ninety-nine patients who received colorectal operations at the Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2018 and December 2018 were included. Samples were acquired from the dissected mesentery after the operation, and hematoxylin–eosin staining or immunohistochemistry was used to detect metastatic cancer cells. Pathological factors, including tumor position, tumor size, invasion depth, tumor differentiation, lymph node involvement, local vessel invasion, and perineural invasion, were recorded.

Results

Metastatic cancer cells in the colorectal mesentery (metastasis V) were detected in 62 of 299 patients. Metastasis V was closely correlated with tumor invasion depth, lymph node metastasis, tumor differentiation, and perineural and vessel invasion by cancer cells. Metastasis V occurred more frequently in patients with T3 stage (26.27%) and T4 stage (40.00%) than in patients with T1 and T2 stages (0% and 2%, respectively). Metastasis V was frequently detected in patients with N2a and N2b stage tumors (51.72% and 61.54%, respectively). Metastasis V was more frequently detected in patients with perineural metastasis and local vessel invasion. In addition, metastasis V incidences in colon and rectal cancer were similar.

Conclusion

The incidence rate of metastasis V is correlated with tumor staging factors and occurs more frequently in advanced-stage patients.

     

miR-338-5p在结直肠癌组织中的表达及其对结肠癌细胞增殖的影响

目的探讨miR-338-5p在结直肠癌组织中的表达状况,以及miR-338-5p过表达对结肠癌细胞系HCT116和SW620增殖、凋亡及细胞周期的影响。方法使用实时定量PCR方法检测miR-338-5p在40例临床诊断为结直肠癌患者配对癌组织及癌旁组织中的表达情况。随后使用miR-338-5p-mimics转染结肠癌细胞系HCT116和SW620,确认过表达成功后,分别使用CCK-8法、FITC-AnnexinV．PI法及Propidiumiodide法检测肿瘤细胞的增殖、凋亡和细胞周期的改变。结果①miR-338-5p在结直肠癌组织中的表达明显低于其在相应的癌旁组织中的表达（P〈0．01）。②与转染阴性对照比较,转染miR-338．5p．mimics后,HCT116和SW620细胞增殖能力明显减弱（P〈0．01）,凋亡率明显增加[HCT116细胞：（11．43±0．67）％比（7．98±0．36）％,P〈0．01;SW620细胞：（10．5±0．2）％比（7．93±0．5）％,P〈0．01],诱导HCT116和SW620细胞G1期阻滞[HCT116细胞：（80．41±1.34）％比（64．87±1．83）％,P〈0．01;SW620细胞：（68．76±0．41）％比（54．89±0．78）％,P〈0．01]。结论miR-338-5p可能作为抑癌基因在结直肠癌中发挥作用,并对细胞增殖、凋亡和周期有显著影响。     

MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells

Purpose

Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer.

Methods

Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death.

Results

High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P?=?0.0257) and poor prognosis (P?=?0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.

Conclusions

MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.     

Circulating Tumor Cells and Prognosis of Patients with Resectable Colorectal Liver Metastases or Widespread Metastatic Colorectal Cancer: A Meta-Analysis

Background

We performed a systematic review and meta-analysis to investigate the prognostic value of tumor cells in blood (circulating tumor cells [CTCs]) or bone marrow (BM) (disseminated tumor cells) of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer (CRC).

Materials and Methods

The following databases were searched in May 2011: MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cochrane Library. Studies that investigated the association between tumor cells in blood or BM and long-term outcome in patients with metastatic CRC were included. We extracted hazard ratios (HRs) and confidence intervals (CIs) from the included studies and performed random-effects meta-analyses for survival outcomes.

Results

The literature search yielded 16 studies representing 1,491 patients. The results of 12 studies representing 1,329 patients were suitable for pooled analysis. The overall survival (HR, 2.47; 95 % CI 1.74–3.51) and progression-free survival (PFS) (HR, 2.07; 95 % CI 1.44–2.98) were worse in patients with CTCs. The subgroup of studies with more than 35 % CTC-positive patients was the only subgroup with a statistically significant worse PFS. All eight studies that performed multivariable analysis identified the detection of CTCs as an independent prognostic factor for survival.

Conclusion

The detection of CTCs in peripheral blood of patients with resectable colorectal liver metastases or widespread metastatic CRC is associated with disease progression and poor survival.     

Detection of Metastatic Lymph Nodes Using 5-Aminolevulinic Acid in Patients with Gastric Cancer

Background

Precise diagnosis of lymph node metastases is essential to select therapeutic strategy for patients with gastric cancer, and rapid intraoperative diagnosis is useful for performing less invasive surgery. In this study, we focused on a known photosensitizer, 5-aminolevulinic acid (5-ALA), and examined the feasibility of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence to detect metastatic foci in excised lymph nodes of patients with gastric cancer.

Methods

A total of 144 lymph nodes obtained from 14 gastric cancer patients were examined. The patients were administered 5-ALA orally before surgery. Excised lymph nodes were cut in half and observed by fluorescence microscopy. The diagnostic results were compared to those of the routine histopathological examination.

Results

Observed red fluorescence of PpIX was identical to the metastatic focus, with 84 % accuracy. Twelve non-metastatic lymph nodes showed unexpected PpIX accumulation to lymphoid follicles, but these could be discriminated based on their characteristic fluorescence patterns. With incorporation of this morphological consideration, this method demonstrated good diagnostic power with 92.4 % accuracy. On the quantitative analysis using the signal intensity ratio of red to the sum of red, green, and blue (R/(R + G + B) ratio) as an index corresponding to red fluorescence of PpIX, metastatic lymph nodes showed significantly higher value than non-metastatic lymph nodes (p < 0.0001). The area under the curve was calculated as 0.832 throughout Receiver operating characteristic analysis.

Conclusions

Our results demonstrated that 5-ALA-induced fluorescence diagnosis is a simple and safe method and is a potential candidate for a novel rapid intraoperative diagnostic method applicable to clinical practice.     

Primary Tumor Resection in Patients with Incurable Localized or Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis

World Journal of Surgery - To assess the impact of primary tumor resection (PTR) on survival and morbidity in incurable colorectal cancer. Systematic literature review and meta-analysis to compare...     

快速流程模式中术后限制补液在老年结直肠癌患者中的应用价值

目的探索在快速流程模式下术后限制补液在老年结直肠癌患者中的应用价值。方法回顾性研究2008年1月至2009年1月期间四川大学华西医院肛肠外科专业组收治的老年结直肠癌患者(≥60岁)的临床资料,分析比较采用不同补液方案(限制补液组和常规补液组)的临床疗效差异。结果限制补液组术后总并发症发生率明显低于常规补液组(P0.05),其中吻合口漏和肺部感染的发生率明显低于常规补液组(P0.05)。2组患者均无围手术期死亡发生。对于2组患者术后恢复情况,限制补液组患者的首次排气、排便和进食时间均早于常规补液组(P0.05)。限制补液组和常规补液组患者术前GLU〔(6.70±2.93)mmol/L比(6.33±3.95)mmol/L〕、BUN〔(5.84±2.03)mmol/L比(7.32±10.83)mmol/L〕及CREA〔(76.19±19.85)μmol/L比(85.36±38.02)μmol/L〕的差异均有统计学意义(P0.05),术后其差异则无统计学意义(P0.05)。结论术后限制补液策略可以降低老年结直肠癌患者术后常见并发症的发生率并加速患者的康复。     

限制补液策略有利于结直肠癌伴糖尿病患者术后的早期安全康复

目的探究限制补液策略对结直肠癌伴糖尿病患者术后早期康复的临床价值。方法回顾性研究2007年1月至2009年10月期间四川大学华西医院结直肠外科专业组收治的伴糖尿病的结直肠癌患者的临床资料,分析比较采用不同补液方案(限制补液组和常规补液组)的术后首次排气、进食、下床活动及住院时间,术后早期并发症(伤口感染、吻合口漏、肠梗阻),生化与血常规检查指标(血红蛋白、白细胞计数、葡萄糖、尿素氮)。结果限制补液组术后首次排气及下床活动时间均早于常规补液组(P0.05),而2组术后首次进食、术后住院时间的差异无统计学意义(P0.05)。在术后早期并发症方面,限制补液组的伤口感染率明显低于常规补液组(P0.05),而2组间吻合口漏及肠梗阻发生率差异无统计学意义(P0.05)。生化与血常规检查指标,术前2组患者各指标的差异均无统计学意义(P0.05);术后限制补液组葡萄糖水平明显低于常规补液组(P0.05),其余指标2组间差异无统计学意义(P0.05)。结论术后限制补液策略可以降低伴糖尿病的结直肠癌患者术后常见并发症的发生率并有利于患者的康复。     

Laparoscopic Bowel Resection in the Setting of Metastatic Colorectal Cancer

Background This study aimed to review the outcomes of laparoscopic colorectal resection for patients with stage IV colorectal cancer. Methods From the prospectively collected database for patients who underwent surgery for colorectal cancer in our institution, those with stage IV colorectal cancer who underwent elective resection of tumor during the period from January 2000 to June 2006 were included. The outcomes of those with laparoscopic resection were reviewed and comparison was made between patients with laparoscopic and open resection. Results A total of 200 patients (127 men) with median age of 69 years (range: 25–91 years) were included, and 77 underwent laparoscopic resection. Conversion was required in ten patients (13.0%) and all except one conversion were due to fixed or bulky tumors. There was no operative mortality in the laparoscopic group. The complication rate was 14% and the median postoperative hospital stay was 7 days. When patients with laparoscopic resection were compared with those with open operations, there was no difference in age, gender, comorbidity, or tumor size between the two groups. However, the complication rate was significantly lower in those with laparoscopic resection (14% versus 32%, P = 0.007) and the median hospital stay was significantly shorter (7 days versus 8 days, P = 0.005).The operative mortalities and the survivals were similar in the two groups. Conclusions Colorectal resection can be performed safely in patients with stage IV colorectal cancer. The operative outcomes in terms of complication rate and hospital stay compare favorably with patients with open resection. Presented in the Scientific Meeting of the Society of American Gastrointestinal and Endoscopic Surgeons on 18–22 April 2007 in Las Vegas, Nevada, USA.