Prospective study of circulating T-lymphocyte subpopulations and disease progression in colorectal cancer

PURPOSE: It has recently been reported that CD4 ⁺ T-lymphocytes are reduced in advanced colorectal cancer patients. However, it is not clear whether such changes in T-lymphocyte subsets are an early or late event in such patients. The aim of this study was to examine the relationship between these subsets and disease progression in colorectal cancer. METHODS: Flow cytometric analysis of T-lymphocyte subsets was performed in 39 patients who, approximately 12 months previously, had undergone surgery for colorectal cancer. These patients were grouped according to whether they developed a recurrence in the following two years. A group of healthy subjects was studied as controls. RESULTS: There was a significant increase in the median neutrophil count (4.3 vs.3.7 10 ⁶ /ml) and the median numbers of platelets (282 vs.216 10 ⁶/ml)of the recurrence group compared with the control group, respectively (P <0.05). The median numbers (0.28 vs.0.73 10 ⁶/ml)and percentage (29 vs.38 percent) of CD4 ⁺ T-lymphocytes of the recurrence group were significantly reduced compared with that of the control group (P <0.05). There were also reductions in the median percentage of CD3 ⁺ cells (67 vs.74 percent) and the median numbers of CD4 ⁺ T-lymphocytes (0.28 vs.0.46 10 ⁶ /ml) of the recurrence group compared with the no recurrence group (P < 0.05). CONCLUSIONS: Reduction of CD4 ⁺ T-lymphocytes occurs before detectable recurrence of colorectal cancer. Results of the present study are consistent with impaired immunity, as measured by such lymphocyte subset populations, being important in tumor recurrence in colorectal cancer.     

晚期血吸虫病肝纤维化患者血清维生素D表达水平及与肝纤维化进展关系

目的比较晚期血吸虫病肝纤维化I、II级患者血清维生素D表达水平,初步探索其与患者门静脉主干内径宽度及肝纤维化进展的关系。方法回顾性分析2012年3月至2015年9月就诊于嘉兴市第一医院血吸虫病科的126例晚期血吸虫病肝纤维化I、II级患者临床资料,比较两组患者门静脉主干内径宽度、25羟维生素D3[25(OH)D3]等指标;随访观察上述患者肝纤维化进展情况,比较病情进展者和病情稳定者维生素D表达水平。结果 126例晚期血吸虫病患者中,男性72例,女性54例;年龄62~80岁;肝纤维化I级58例,II级68例。肝纤维化I级和II级患者血红蛋白、白细胞计数、凝血酶原时间、国际标准化比值、活化部分凝血活酶时间、纤维蛋白原含量、25(OH)D3水平差异均无统计学意义(P均> 0.05),丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、血钙、血磷、门静脉主干内径宽度值差异均有统计学意义(P均<0.05);门静脉主干内径增宽者血清中25(OH)D3表达水平低于正常组[(19.08±1.36)nmol/L vs.(25.61±6.69)nmol/L],差异有统计学意义(P <0.05);随访3年,发现73例患者肝纤维化病情进展,病情进展患者血清中维生素D表达水平低于病情稳定组[(20.00±0.81)nmol/L vs.(25.47±5.91)nmol/L],差异有统计学意义(P <0.05)。结论维生素D缺乏在晚期血吸虫病肝纤维化患者中较常见,其可能与患者门静脉主干内径及病情进展有关。     

KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients

AIM:To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer(CRC)and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.METHODS:KISS1 promoter methylation,mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction(PCR),real-time quantitative PCR and Western blotting,respectively,in 126 CRC tissues and 142 normal colorectal tissues.Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2’-deoxycytidine(5-Aza-CdR).After treatment,KISS1 promoter methylation,KISS1 mRNA and protein expression and cell migration and invasion were evaluated.RESULTS:Hypermethylation of KISS1 occurred frequently in CRC samples(83.1%,105/126),but was infrequent in normal colorectal tissues(6.34%,9/142).Moreover,KISS1 methylation was associated with tumor differentiation,the depth of invasion,lymph node metastasis and distant metastasis(P<0.001).KISS1methylation was also associated with low KISS1 expression(P<0.001).Furthermore,we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line.CONCLUSION:These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.     

RER and LOH association with sporadic colorectal cancer in Taiwanese patients

BACKGROUND/AIMS: This association study was undertaken to determine replication error and loss of heterozygosity in colorectal tumors using a set of 10 microsatellite markers linked to APC, hMSH2, hMLH1, DCC, P53, NM23, HPC1 and MET genes as well as tumor suppressor genes on 8p22. METHODOLOGY: Thirty-nine patients diagnosed and confirmed with sporadic colorectal cancer were biopsied. Their stored frozen tissues were subsequently retrieved for simultaneous analyses of replication error and loss of heterozygosity via an automated fluorescent microsatellite assay. RESULTS: Replication error was observed in 8/39 of the cases (20.5%) and had significantly higher frequency in the patients younger than 60 yr (P = 0.049). More than one third of informative tumors showed loss of heterozygosity at P53, DCC and APC genes (57.9%, 35.3% and 33.3%, respectively). Loss of heterozygosity at TP53-Dint marker was significantly associated with survival status (P = 0.038) in which a higher frequency was observed in the patients who died from colorectal cancer. Of 22 informative tumors, 6 (27.3%) showed loss of heterozygosity at the D8S254 marker that is suspected to be near one or more tumor suppressor genes and was significantly associated with gender (P = 0.046). All 6 cases of loss of heterozygosity at D8S254 were found in male patients. The frequencies of loss of heterozygosity at the NM23, hMSH2, hMLH1 and HPC1 genes were 18.5%, 12.1%, 9.1% and 7.4%, respectively. None of the cases examined displayed loss of heterozygosity at the MET oncogene. CONCLUSIONS: Additional microsatellite markers other than those associated with colorectal cancer were used to conduct the study of genomic instability and alterations in colorectal cancer tumors. The present results for the sporadic occurrence of colorectal cancer in Taiwanese patients further extend the correlation of clinical pathology and prognosis with the analysis of replication error and loss of heterozygosity.     

Laparoscopic and robot-assisted one-stage resection of colorectal cancer with synchronous liver metastases: a pilot study

Background/purpose

One-stage resection of primary colon cancer and synchronous liver metastases is considered an effective strategy of cure. A laparoscopic approach may represent a safe and advantageous choice for selected patients with the aim of improving the early outcome.

Methods

Between January 2008 and October 2008, 7 patients underwent one-stage laparoscopic resection for primary colorectal cancer combined with laparoscopic or robot-assisted liver resection.

Results

A total of five laparoscopic left-colon, one right-colon, and one rectal resections were performed. Three patients underwent preoperative left-colon stenting and two received neoadjuvant chemotherapy. The patient with rectal cancer underwent neoadjuvant radiotherapy. Liver procedures included one bisegmentectomy (segments 2, 3), 3 segmentectomies, 6 metastasectomies, and four laparoscopic ultrasound-guided radiofrequency ablations (LUG-RFAs). One patient with multiple liver metastases was managed by a two-stage hepatectomy partially conducted by a totally laparoscopic approach. The overall postoperative morbidity was null. The median hospital stay was 10 days (range 7–10 days).

Conclusions

This pilot study suggests that laparoscopic one-stage colon and liver resection is feasible and safe. Robot assistance may facilitate liver resection, increasing the number of patients who may benefit from a minimally invasive operation.     

Hexaminolevulinate-induced fluorescence endoscopy in patients with rectal adenoma and cancer: a pilot study

BACKGROUND: Fluorescence endoscopy is a promising new method for detection and treatment of premalignant and malignant lesions. The aim of this pilot study was to investigate the feasibility of hexaminolevulinate-based photodetection of rectal adenoma and cancer, including safety, dose finding, and efficacy. METHODS: Ten patients with known rectal adenoma or cancer were sensitized by instillation of 3.2 mM of hexaminolevulinate as an enema. Fluorescence endoscopy was performed after retention of the enema for 30 to 60 minutes, followed by a rest time of up to 30 minutes before endoscopy. Biopsy specimens were taken from fluorescent and non-fluorescent areas and fluorescence microscopy studies were performed to assess the distribution of protoporphyrin IX fluorescence in different tissue layers. Adverse events were reported by direct questioning of all patients; skin photosensitivity, changes in biochemical tests of liver function, blood pressure and heart rate, and the occurrence of GI symptoms (nausea, vomiting) were recorded for 5 patients. OBSERVATIONS: Hexaminolevulinate-induced fluorescence endoscopy produced selective fluorescence of all rectal adenomas with intraepithelial neoplasia. For rectal cancer, there was only weak fluorescence or none at all. No hexaminolevulinate-induced side effect was observed. In two patients, fluorescence differentiated adenomas and hyperplastic polyps. CONCLUSIONS: Hexaminolevulinate-based fluorescence endoscopy (3.2 mM administered as an enema) in patients with rectal cancer and adenoma was well tolerated and produced no significant skin sensitivity or other side effects. The optimal duration of application is 30 to 45 minutes, with a rest time of 30 minutes. Selective fluorescence of adenoma with intraepithelial neoplasia suggests that hexaminolevulinate-based fluorescence endoscopy may be useful for detection of premalignant lesions.     

Pan-intestinal capsule endoscopy in patients with postoperative Crohn's disease: a pilot study

Background: Patients are at increased risk of disease recurrence after surgical treatment of Crohn’s disease. Endoscopic detection of postoperative, ileo-colonic inflammation is well established, but the potential of pan-intestinal endoscopy is yet unknown.

Methods: This prospective multicenter pilot study assessed the value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the detection of inflammatory recurrence of Crohn´s disease. Patients who had been operatively treated for Crohn´s disease were included. Colon capsule endoscopy was performed 4–8 weeks (d1) and 4–8 months (d2) postoperatively together with ileo-colonoscopy at d2 using a modified Ruttgeerts index for evaluating disease activity.

Results: Twenty-two patients were included into this study. At d1, significant disease activity (Ruttgeerts index ≥2) was detected in 3/16 (19%) of the patients. At d2, half of the patients (6/12) showed active disease, whereas ileo-colonoscopy revealed significant inflammation in 5/15 (33%). All patients rated as having active disease by ileo-colonoscopy had been revealed by PICE as well. These findings influenced the medical treatment in every case.

Conclusion: Pan-intestinal capsule endoscopy seems to be feasible in the postoperative surveillance of Crohn's disease. Disease activity is reliably detected. Especially, the findings in the small bowl might be a significant advantage in comparison to ileo-colonoscopy, as they can have significant impact on clinical management. Further studies with a larger number of patients are needed to confirm these findings and might lead to a replacement of the flexible ileo-colonoscopy with pan-intestinal capsule endoscopy in this indication in the future.     

Saliva and plasma TIMP-1 in patients with colorectal cancer: a prospective study

Abstract

Background and aims. A prospective cross-sectional study was designed to test if total levels of TIMP-1 in saliva and plasma correlated with the diagnosis of colorectal cancer (CRC) in a population with symptoms consistent with this disease. Materials and methods. Stimulated whole saliva and blood samples were collected from 161 individuals referred to colonoscopy with symptoms associated with CRC. The results of the examination, as well as previous and/or current other diseases were recorded. In a blinded study, the authors used an in-house TIMP-1 ELISA previously validated for use in saliva and plasma to determine total levels of TIMP-1. Results. Fifty-six of the patients (35%) were diagnosed with CRC. Plasma TIMP-1 levels were significantly elevated in CRC patients compared with patients with other, non-malignant diseases and individuals without disease. Significant differences in saliva TIMP-1 levels between CRC patients and individuals without CRC could not be demonstrated. In addition, no correlation was found between levels of TIMP-1 in plasma and saliva. Conclusion. Total levels of TIMP-1 in saliva do not reflect the presence of CRC, and TIMP-1 saliva measurements thus cannot substitute plasma TIMP-1 measurements in detection of CRC.     

结直肠癌AIM2和血清CEA表达水平及其临床意义

目的探讨结直肠癌患者黑色素瘤缺乏因子2（AIM2）和血清癌胚抗原（CEA）表达水平及其临床意义。 方法收集辽宁省肿瘤医院2010年1月~2013年3月118例结直肠癌患者的肿瘤组织标本及其50例癌旁正常组织标本,采用免疫组织化学法测定组织中AIM2的表达,回顾性搜集患者临床病理参数及术前通过电化学发光法（ECUA）测定的血清CEA水平。通过相关性分析癌组织中AIM2表达水平和血清CEA水平的相关性,分析两种指标与临床病理参数的关系。采用Kaplan-Meier法对不同AIM2、CEA水平组别进行生存分析。 结果118例肿瘤组织中有42例AIM2呈高表达,有39例癌旁正常组织呈高表达,差异具有统计学意义（χ²=25.295,P<0.001）;结直肠癌患者术前血清CEA阳性率为44.07%（52/118）。Spearman等级相关性分析结果显示,结直肠癌组织AIM2和血清CEA表达呈负相关（r=-0.660,P<0.001）。肿瘤的浸润深度、TNM分期以及淋巴结转移是影响癌组织AIM2表达水平的相关因素（χ²=4.847,7.794,3.961;均P<0.05）;肿瘤大小、TNM分期以及分化程度是影响患者术前血清CEA水平的相关因素（χ²=17.14,5.779,5.293;均P<0.05）。K-M生存分析显示,AIM2高表达组生存时间明显长于低表达组,术前CEA阴性组生存时间明显长于阳性组,AIM2高表达联合CEA阴性患者生存时间明显长于AIM2低表达联合CEA阳性患者,差异具有统计学意义。 结论结直肠癌患者AIM2和血清CEA表达可能与结直肠癌的进展有关,联合分析两个指标有助于评估结直肠癌患者预后。     

Saliva and plasma TIMP-1 in patients with colorectal cancer: a prospective study

Abstract Background and aims. A prospective cross-sectional study was designed to test if total levels of TIMP-1 in saliva and plasma correlated with the diagnosis of colorectal cancer (CRC) in a population with symptoms consistent with this disease. Materials and methods. Stimulated whole saliva and blood samples were collected from 161 individuals referred to colonoscopy with symptoms associated with CRC. The results of the examination, as well as previous and/or current other diseases were recorded. In a blinded study, the authors used an in-house TIMP-1 ELISA previously validated for use in saliva and plasma to determine total levels of TIMP-1. Results. Fifty-six of the patients (35%) were diagnosed with CRC. Plasma TIMP-1 levels were significantly elevated in CRC patients compared with patients with other, non-malignant diseases and individuals without disease. Significant differences in saliva TIMP-1 levels between CRC patients and individuals without CRC could not be demonstrated. In addition, no correlation was found between levels of TIMP-1 in plasma and saliva. Conclusion. Total levels of TIMP-1 in saliva do not reflect the presence of CRC, and TIMP-1 saliva measurements thus cannot substitute plasma TIMP-1 measurements in detection of CRC.     

结直肠癌患者围手术期营养评估进展

结直肠癌是最常见的消化道恶性肿瘤之一,其发病率和死亡率在全球仍呈上升趋势,严重威胁着人类的健康。结直肠癌围手术期的病理生理特点决定了疾病进程中,极易发生营养不良,继而导致免疫功能障碍,降低机体对各种抗癌治疗的耐受性,增加术后的并发症,延长住院时间,降低患者生存质量并影响预后。因此,结直肠癌患者在进行营养治疗前,应进行客观的个体化营养评估,为适时、适度的营养治疗提供依据。笔者以近期国内外研究为基础,回顾了目前结直肠癌围手术期营养评估的主要方法和热点问题,希望能为营养干预提供参考。     

Poor prognosis of young patients with colorectal cancer: a retrospective study

Purpose

The present study aimed to explore the survival outcomes of patients with colorectal cancer (CRC) aged 35 years and younger.

Methods

This retrospective cohort study included a total of 995 patients with CRC treated between January 2003 and September 2011. The patients were assorted into the young (aged 18–35 years) and older (aged 36–75 years) groups. The clinical characteristics and survival outcomes of the patients in the young group were compared with those of the patients in the older group for evaluation.

Results

Compared with the older group, a significantly higher number of patients in the young group had right-sided colon cancer (30.9 vs. 19.6%, P = 0.026), high histologic grade tumor (14.7 vs. 6.4%, P = 0.021), and stage III disease (50.0 vs. 35.5%, P = 0.016). In stage III disease, compared with the older group, the patients in the young group had worse survival outcome in terms of 5-year overall survival (OS, P = 0.007), cancer-specific survival (CSS, P = 0.010), and disease-free survival (DFS, P = 0.039). Multivariate analysis revealed that age ≤35 years was an independent risk factor in terms of 5-year OS (hazard ratio [HR] = 1.68; 95% confidence interval [CI]: 1.12–2.54; P = 0.012), CSS (HR = 1.74; 95% CI: 1.15–2.65; P = 0.009), and DFS (HR = 1.58; 95% CI: 1.06–2.35; P = 0.024).

Conclusions

The young patients with CRC aged 35 years and younger had worse prognosis compared with older patients, especially for stage III disease.

     

Risk of colorectal cancer in patients with hematologic disease

BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.     

Survival after colorectal cancer in patients with Crohn's disease: A nationwide population-based Danish follow-up study

BACKGROUND AND AIMS: Patients with Crohn's disease (CD) are at increased risk of colorectal cancer (CRC), but little is known about the impact of CD on CRC prognosis. Based on nationwide population-based registries, we compared survival among CRC patients with CD and CRC patients without CD. METHODS: We used the Danish Cancer Registry and the Danish Hospital Discharge Registry to identify all patients diagnosed with CRC, with and without CD, in Denmark between 1977 and 1999. We ascertained the stage distribution at the time of CRC diagnosis and 1- and 5-yr survival both for patients with Crohn-associated CRC and patients with non-Crohn CRC. Cox regression was used to compute hazard ratios (HRs), adjusting for gender, age, calendar year, and stage. RESULTS: We identified 100 CRC patients with CD and 71,438 CRC patients without CD. At the time of diagnosis, patients with CD were younger, but stage distributions were similar in the two groups. The overall HR for CRC with CD compared to CRC without CD was 1.82 (95% CI 1.36-2.43) after 1 yr of follow-up, and 1.57 (95% CI 1.24-1.99) after 5 yr of follow-up. Subanalyses showed that the effect of CD on CRC survival was more pronounced in the youngest patients (0-59 yr), in men, and in patients whose tumors had regional spread. CONCLUSIONS: We found that CD worsens the prognosis of CRC, particularly CRC with regional spread.     

Carcinoembryonic antigen: its value in the follow-up of patients with colorectal cancer

We examined the value of carcinoembryonic antigen (CEA) monitoring for detecting treatable recurrence of colorectal carcinoma. CEA assays were undertaken in 193 patients over a 2-year period. The levels in 34 patients were raised in one or more assays above the laboratory-defined upper limit of normal; 31 cases were reviewed retrospectively. In 10% of patients there were Dukes' A lesions at the initial resection, in 39% Dukes' B, and in 52% Dukes' C1 or C2. Tumours were rectal in 61%. Median follow-up was 3 years (range, 16 years–2 months). In 23 of 31 (74%) there were symptoms or signs of recurrent disease prior to or simultaneously with an observed rise in CEA; in 8 the CEA rise preceded the onset of symptoms or the appearance of signs. Of the 31 cases 26 underwent investigation for recurrent disease, but in only 6 of these was the investigation driven by the observed rise in CEA rather than the onset of symptoms or presence of signs. Three of these six were false-positive results (50%), one has been lost to follow-up, and two had confirmed recurrence. Neither of the two with recurrence had operable disease. One of the two had no further treatment, and one underwent laparotomy at which multiple peritoneal seedlings were found. In both of the two cases going to laparotomy, one of which was prompted by a high CEA, widely disseminated disease was found. Over a 2-year period, serial CEA measurement thus yielded no patient benefit. Accepted: 13 October 1998