Association between sigmoid diverticulitis and left‐sided colon cancer: a nested,population‐based,case control study

Background: An increased risk of left‐sided colon cancer in patients with diverticular disease of the sigmoid colon has been reported. The aim of this study was to investigate to what extent patients with diverticulitis of the sigmoid colon differ in long‐term risk of colon cancer compared to patients with diverticulosis of the colon without any clinical signs of diverticulitis. Methods: A total of 7159 patients (2478 M, 4681 F) discharged with a diagnosis of diverticulosis or diverticulitis in 1965–83 in the Uppsala Health Care Region were followed‐up with the Swedish Cancer Registry. Sixty‐four cases with colon cancer were identified and compared with 123 controls without cancer matched for sex, age and year of first discharge. Based on information from the patients' charts, an independent observer blinded to the outcome assigned a clinical diagnosis of diverticulitis or not diverticulitis to cases and controls. Results: In patients classified as having sigmoid diverticulitis there was an increased risk of left‐sided colon cancer compared with patients with diverticulosis without any clinical signs of diverticulitis (odds ratio?=?4.2, 95% CI 1.3–13.0) which remained after mutually adjusting for several clinical parameters in a multivariate conditional logistic regression analysis. Conclusion: The results of the study indicate a causal association between sigmoid diverticulitis and a long‐term increased risk of left‐sided colon cancer.     

左右半结肠癌与Programmed Death-1信号通路

目的探讨程序性杀伤因子1（PD1）信号通路对左、右半结肠癌预后的影响以及在左、右半结肠癌差异中所起到的作用。 方法采用数据分析等手段分析左右半结肠癌的差异基因,分析PD1信号通路主要的PD1（PDCD1）,PDL1（CD274）,PDL2（PDCD1L2）在左右半结肠癌中的表达和预后差异,并采用免疫组化方法对数据分析结果进行验证。 结果TCGA数据分析结果显示,左、右半结肠癌差异基因富集于免疫相关信号通路,其中包括PD1信号通路。PDCD1,CD274,PDCD1L2在右半肠癌的表达量显著高于左半肠癌。Kaplan-Meier生存分析显示,右半结肠癌总体生存率（OS）差于左半结肠癌,在PDCD1,CD274,PDCD1L2高表达组,右半结肠癌总体生存率差于左半结肠癌（P<0.05）。免疫组化结果显示PD1,PDL1在左、右半结肠癌中的蛋白表达与TCGA数据分析具有相同的结果,Kaplan-Meier生存分析结果显示PDL1的蛋白表达影响结肠癌的预后,表达量越高总体生存率越低。 结论PD1/PDL1信号通路的表达差异影响左、右半结肠癌的预后。     

Colorectal Cancer Localization in Young Patients: Should We Expand the Screening Program?

We sought to investigate the frequency and distribution of colorectal cancer (CRC) in patients by age and to evaluate whether there is a difference between young (<40 years of age) and older patients (≥40 years of age) with regard to cancer localizations. From a total of 5165 colonoscopies, 314 (6.0%) cases were identified to have colorectal carcinoma. Forty-one (13%) of 314 CRC patients were young, with a mean age of 31.1±5.7 years. When cancer localizations were compared with reference to age, it was seen that CRCs in young patients were mostly localized at the right colon, versus at the left colon and rectum (P=013) in patients >40 years of age. Tumor localizations in colon cancer patients change with age. In our study, young patients tended to have right-sided colon tumors, but those in patients >40 years of age were frequently localized at the left colon and rectum.     

左右半大肠癌临床特征对比研究

目的探讨左、右半大肠癌临床特征差异。方法总结分析经病理确诊的8551例大肠癌患者的临床资料,以结肠脾曲为界区分左、右半大肠,分别计算两者的性别、年龄、组织学类型和Duke分期的频数和比例,比较其差异。结果大肠癌分布于左半大肠和右半大肠分别占77.9%、22.1%。随着年份推移,左半大肠癌的比例从80.9%降至75.1%,右半大肠癌的比例从19.1%增至24.9%,(P0.05);随着年龄增长,左半大肠癌的比例从79.3%下降至76.2%,右半大肠癌的比例从20.7%增至23.8%(P0.05);右半大肠癌比例男性为21.6%(1094/5058),女性为22.7%(792/3493),(P0.05);粘液腺癌和印戒细胞癌的比例右半大肠为18.7%(352/1886),左半大肠为10.1%(670/6665),(P0.05);Duke分期C期和D期的比例右半大肠为48.3%(602/1246),左半大肠为42.8%(1893/4424),(P0.05)。结论大肠癌发病部位逐渐右移,右半大肠癌恶性程度较高,晚期癌比例较高,提示应重视全结肠镜检查。     

Relationship between age and clinical characteristics of patients with gastric cancer

The relationship between the prognosis and age of patients with gastric cancer is controversial. To evaluate whether there is a biological characteristic specific to the age of patients, we examined the clinical characteristics of patients with gastric cancer with special reference to their age. Based on a prospective database, a retrospective study of 419 patients who underwent radical gastrectomy for cure in the past 6 years was conducted. Clinical characteristics including gender, gross appearance of the tumour (Borrmann's classification, tumour location), histopathology (depth of tumour invasion, lymph node status, Lauren's classification and degree of tumour cell differentiation) and TNM tumour stage were analysed in six different age groups (< 39, 40–49, 50–59, 60–69, 70–79, > 80 years). The mean age of the 419 patients was 64.6 years (range from 26–91) and the peak age incidence of gastric cancer (46.3%) was in the 60–69 year old age group. The male: female ratio was 4.6: 1 on the whole and male gender predominated at ages > 60. The proportion of diffuse type tumours (68.4%) by Lauren's criteria in the young age group (< 39 yrs) decreased with age (25% in the > 80 years group; P<0.001). Similarly, the proportion of poorly-differentiated tumours (89.5%) in the young age group (< 39 yrs) decreased with advancing age (P<0.001). These findings suggest that both diffuse type and poorly-differentiated tumours predominate in younger patients and, without considering the factor of delay in diagnosis, may explain the poorer prognosis demonstrated in younger patients.     

Differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer

OBJECTIVE: Colon cancer is more common in the USA and Europe than that in China, for reasons that are unclear. The aim of this study was to investigate the differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer. METHODS: Expression profiling of primary tumor tissues from 12 colon and 12 rectal cancers was performed using oligonucleotide microarray analysis. All samples were strictly matched by clinical features. Bioinformatic analyses such as the Kyoto Encyclopedia of Genes and Genomes were used to identify genes and pathways specifically associated with colon or rectal cancers. RESULTS: A total of 824 genes were differentially expressed in colon and rectal cancers. All differential gene interactions in the Signal‐Net were analyzed. More genes were differentially expressed and included in the Signal‐Net for rectal than colon cancer. Of the genes differentially expressed between colon and rectal cancer, S100P, the Reg family, ACTN1, CAMK2G and ACAT1 were the most significantly altered. Genes involved in the cell cycle pathway were present in rectal and colon cancers, but were more important in rectal cancer. The p53 and metabolic signaling pathways were significantly different in colon and rectal cancers. Gene expression profiles differed between colon and rectal cancer, with metabolic pathways being more important in rectal cancer. CONCLUSION: The oncogenesis of rectal cancer may be more complex than that of colon cancer. Some genes could be new biomarkers for distinguishing between these two cancers.     

Cryptogenic pyogenic liver abscess as the herald of colon cancer

Background and Aim: Colonic mucosal defects might be a route for bacterial invasion into the portal system, with subsequent hematogenous spread to the liver. We retrospectively investigated the results of colonoscopy and the clinical characteristics of patients with pyogenic liver abscess of colonic origin. Methods: A total of 230 consecutive patients with pyogenic liver abscess were reviewed between 2003 and 2010. The 230 patients were categorized into three groups (pancreatobiliary [n = 135], cryptogenic [n = 81], and others [n = 14]). Of the 81 cryptogenic patients, 37 (45.7%) underwent colonoscopy. Colonic lesions with mucosal defects were considered colonic causes of abscess. Results: In the 37 colonoscopic investigations, colon cancer was found in six patients (16.2%), laterally‐spreading tumor (LST) in two patients (5.4%), multiple colon ulcers in one patient (2.7%), colon polyps in 17 patients (45.9%), and diverticula in four patients (10.8%). Nine (11%) of 81 cryptogenic abscesses were therefore reclassified as being of colonic origin (colon cancer = 6, LST = 2, ulcer = 1). Three cases were stage III colon cancer, and the others were stage I. Two LST were high‐grade dysplasia. The percentage of patients with Klebsiella pneumoniae (K. pneumoniae) and diabetes mellitus (DM) of colonic origin was 66.7%, which was significantly higher than the 8.6% for other causes (P < 0.001). Conclusions: Of the 37 patients with cryptogenic pyogenic liver abscess who underwent colonoscopy, nine (24.3%) were diagnosed with a colonic cause. Colonoscopy should be considered for the detection of hidden colonic malignant lesions in patients with cryptogenic pyogenic liver abscess, especially for patients with K. pneumoniae and DM.     

A population‐based audit for diagnosing colorectal cancer

Background: Knowledge of the diagnostic work‐up of colorectal cancer is a prerequisite to improve its quality. Family history is one of few known risk factors of the disease and it is therefore important to investigate to what extent this factor is used in routine management. Methods: Copies of records from all health‐care suppliers visited during diagnostic work‐up were requested for 227/235 (97%) patients with recently diagnosed colorectal cancer in the county of Västmanland during 1998–99. A first consultation was identified and records and all diagnostic measures related to the initial consultation were scrutinized. A family history of colorectal cancer was known for 179 patients. Results: Most of the patients, 107 (66%) colon and 57 (86%) rectal cancer patients, had consulted with a general practitioner. The median diagnostic work‐up time was 42 days (IQ 12–110) for colon and 23 days (IQ 0–49) for rectal cancer. A double‐contrast barium enema was the most commonly used diagnostic method for colon cancer. Family history was documented at the first consultation in 2/179 (1%) cases. In patients with right‐sided cancer, median diagnostic work‐up time was 53 days in patients with a positive result of faecal occult blood test (FOBT) as compared with 448 in patients with a negative result (P?Conclusion: Primary care is the key actor in diagnosing rectal cancer. The restricted capacity for X‐ray is one of the main obstacles in detection of colon cancer. Family history is rarely documented during diagnostic work‐up of colorectal cancer. The benefit of using FOBT in symptomatic patients is questioned.     

Clinical characteristics of synchronous colorectal cancer are different according to tumour location

AIMS: The purpose of this study was to investigate the clinical characteristics of synchronous cancer patients, with particular attention given to variations in tumour location. METHODS: A retrospective evaluation of 249 synchronous cancer cases out of 3061 consecutive colorectal cancer patients. RESULTS: Multivariate analysis of risk factors for synchronous cancer according to tumour location revealed that male gender was a significant risk for synchronous lesions in the left colon only (odds ratio=2.05, 95% confidence interval 1.34-3.13). Meanwhile, aging was a risk factor for synchronous cancer in the right colon only (odds ratio=1.05, 95% confidence interval 1.02-1.08), and in both sides of the colon (odds ratio=1.03, 95% confidence interval 1.01-1.05), but not in the left colon only (odds ratio=0.98, 95% confidence interval 0.97-1.00). In addition, patients with synchronous lesions in the right colon only tended to have adenomas in the right colon, while those with synchronous lesions in the left colon only tended to have adenomas in the left colon (each P value <0.05). CONCLUSION: The risk factors and status of concurrent adenomas of synchronous cancer cases varied according to tumour location, suggesting that the colonic site susceptible to neoplasia varies according to patient characteristics.     

Effect of mental disorders on diagnosis, treatment, and survival of older adults with colon cancer

OBJECTIVES: To evaluate the extent to which preexisting mental disorders influence diagnosis, treatment, and survival in older adults with colon cancer. DESIGN: Retrospective cohort study. SETTING: The Surveillance, Epidemiology and End Results (SEER)–Medicare linked database. PARTICIPANTS: Eighty thousand six hundred seventy participants, aged 67 and older with a diagnosis of colon cancer. MEASUREMENTS: The association between the presence of a preexisting mental disorder and the stage of colon cancer at diagnosis, receipt of cancer treatment, and overall and colon cancer‐specific mortality were assessed using Cox proportional hazards regression and logistic regression. RESULTS: Participants with mental disorders were more likely to have been diagnosed with colon cancer at autopsy (4.4% vs 1.1%; P<.001) and at an unknown stage of cancer (14.6% vs 6.2%; P<.001); to have received no surgery, chemotherapy, or radiation therapy (adjusted risk ratio (ARR)=2.09, 95% confidence interval (CI)=1.86–2.35); and to have received no chemotherapy for Stage 3 cancer (ARR=1.63, 95% CI=1.49–1.79). The rate of overall mortality (hazard ratio (HR)=1.33, 95% CI=1.31–1.36) and colon cancer‐specific mortality (HR=1.23, 95% CI=1.19–1.27) was substantially higher in participants with a preexisting mental disorder than in their counterparts. All of these associations were particularly pronounced in participants with psychotic disorders and those with dementia. CONCLUSION: Public health initiatives are needed to improve colon cancer detection and treatment in older adults with mental disorders.     

Flat-Type Early Colorectal Cancer Preferentially Develops in Right-Sided Colon in Older Patients

BACKGROUND Flat-type colorectal cancer is frequently reported in Japan and Europe, but its clinical features remain obscure. Thus, we investigated the clinical features of flat-type early colorectal cancer with respect to tumor location and patient age and compared them with those of polypoid-type early and advanced cancer.METHODS Between January 1999 and June 2001, total colonoscopy was performed in 6,178 patients (mean age, 61 years; 4,290 males and 1,888 females). Of these patients, 402 patients with 429 colorectal cancers were found: 202 at advanced stage (invading beyond muscularis propria) and 227 at early stage (carcinoma in situ or invading within submucosa). Early-stage cancer was classified into two macroscopic subgroups: flat-type and polypoid-type.RESULTS Out of 227 early cancers, 44 were flat type and 183 were polypoid. Flat-type early cancer was more frequently located in the right colon (57 percent, 25/44) than polypoid-type cancer (19 percent, 35/183; P < 0.001). Adenomatous component in flat-type early cancer was less frequent than in polypoid-type cancer (23 percent vs. 92 percent, P < 0.001). The proportion of right-sided colon in flat-type early cancer increased with age (33 percent in patients 59 years, 50 percent in patients between 60 and 69 years, and 72 percent in patients 70 years), whereas polypoid-type early cancer showed minimal change (16 percent, 18 percent, and 25 percent, respectively). An increase in the proportion of right-sided colon with age was also found in advanced cancer (20 percent, 38 percent, and 52 percent, respectively).CONCLUSION The incidence of flat-type early cancer in right-sided colon increased with age, similar to the pattern of advanced cancer. This suggests that flat-type early cancer may be a precursor of advanced cancer in the right colon, especially in older people.Presented in part at the meeting of the American Gastroenterological Association, San Diego, California, May 14 to 17, 2000.     

Analysis of K-ras, BRAF, and PIK3CA mutations in laterally-spreading tumors of the colorectum

Background and Aims: Laterally‐spreading tumors (LST) are a newly‐recognized category of colorectal neoplasia, and are defined as lesions larger than 10 mm in diameter and extending circumferentially rather than vertically. However, genetic features of this new category of tumors are not fully elucidated. The aim of this study was to evaluate genetic alterations in LST. Methods: We examined K‐ras, BRAF, and phosphoinositide‐3‐kinase catalytic‐α polypeptide (PIK3CA) mutations in 101 LST, including 68 LST‐granular type (LST‐G) and 33 LST‐non‐granular type by direct sequencing. As controls, we examined these gene mutations in 66 protruded colon adenomas (10 mm or larger) and 44 advanced colon cancers. Results: K‐ras, BRAF, and PIK3CA mutations were observed in 59 (58%), zero (0%), and three (3%) LST, respectively. LST‐G morphology in the right‐sided colon was significantly correlated with the existence of K‐ras mutations, whereas a size of 20 mm or larger was the only predictor of mutations in the left‐sided colorectum. The frequency of K‐ras mutations in LST was particularly marked in the left‐sided colorectum compared to protruded adenomas or advanced cancers (LST vs protruded adenomas, P < 0.001; LST vs advanced cancers, P = 0.002), whereas in the right‐sided colon, K‐ras mutations were equally frequent. PIK3CA mutations were not familiar in either LST (3%) or advanced cancers (9%). Conclusions: K‐ras mutations were involved in colorectal LST in different manners according to tumor location.     

性别与结直肠癌发病特点关系的分析

[目的]分析性别与结直肠癌临床特点的关系.[方法]收集2001-10-2011-10期间在华北地区6家医院检出结直肠癌患者资料,分析性别与发病年龄、肿瘤发生部位、腺癌分化程度的关系.[结果]2450例结直肠癌患者中男性1377例,女性1073例.男∶女为1.28∶1.00;女性发病率升高.右半结肠癌比例升高.性别与结直肠癌发生年龄、发生部位、腺癌分化程度均无明显的相关性(P＞0.05).[结论]结直肠癌发病率呈上升趋势,女性大肠癌患者比例有增加趋势.筛查是结直肠癌早诊早治的关键,筛查的起始年龄应按筛查目标确定.结直肠癌发病部位应重视右半结肠发病率升高现象,全结肠镜检查为首选.     

Lack of Relationship between Cholecystectomy and Colorectal Cancer

To study the postulated relationship between prior cholecystectomy and occurrence of subsequent colorectal cancer, we examined the prevalence of cholecystectomy in all patients with histologically confirmed colorectal cancer registered during 1966–75 in the city of Malmö. In addition, we studied the frequency of colon cancer in all females autopsied in 1978–79 with a previous cholecystectomy. Of all 1061 cases of colon cancer diagnosed during the 1966–75 period. 94 (8.9%) had undergone cholecystectomy, as compared with 106 (10.0%) in the age-matched controls. In the female subgroup (n = 503) the corresponding figure for cholecystectomy was 58 (11.5%), as compared with 70 (13.9%) in the controls. The incidence of right-sided colon cancer among the 58 females with previous cholecystectomy did not differ from that of age-matched controls (28.6 and 28.1%, respectively). The incidence of colon cancer among 305 females with a prior cholecystectomy autopsied during 1978–79 was 24 (7 right-sided), as compared with 22 (8 right-sided) in age-matched controls without gallbladder disease. Gastric cancer was more frequent (p < 0.01) in cholecystectomized women than in controls. These results refute the suggested relationship between cholecystectomy and development of colon cancer in any location.     

女性肺癌手术后病理及临床特点研究

目的探讨女性肺癌手术后病理及临床特点。方法回顾性分析2002年10月01日-2007年09月31日在我院住院，经手术后病理证实为肺癌的101例女性患者，与相同条件下的246例男性肺癌患者，进行比较。结果女性肺癌的患病年龄54．60±11．88岁，明显小于男性；患病部位右肺与左肺之比为1．53：1，右侧多于左侧，与男性相似；腺癌占68．32％，明显高于男性，鳞癌占11．88％，明显低于男性；术后临床分期中Ⅲa占18．81％，Ⅲb占15．84％，1V占15．84％，晚期病人多；平均住院日（26．40±10．82）d，平均术后住院日（16．30±7．63）d，比男性肺癌长，两组患者的手术切除范围比较无显著性差异。结论女性肺癌有其自身的特点。发病年龄早，病期晚，腺癌居多，住院时间长。需要提高认识，早期发现，早期诊断，早期治疗，进一步提高女性肺癌的防治效果。     

Identifying patients with T3-T4 node-negative colon cancer at high risk of recurrence

PURPOSE: Adjuvant chemotherapy is effective for node-positive colon cancer patients. In node-negative patients, it could be justified in high-risk patients. The purpose of this study was to determine clinical and pathological findings associated with tumor recurrence in T3-T4 node-negative colon cancer patients. METHODS: From 1974 to 1993, 108 patients undergoing colectomy for T3-4N0M0 colon cancer, without adjuvant chemotherapy, followed until death or for a minimum of five years, were divided into two groups: patients without recurrence (n=74) and those dead from colon cancer or alive with recurrence (n=34). Thirty-three clinical and pathological findings were studied. RESULTS: In univariate analysis, the following were significantly associated with a high risk of tumor recurrence: male patients (P=0.006), bowel obstruction (P<0.001), weight loss >5 Kg (P=0.03), circumferential tumor (P=0.02), macroscopic or microscopic pericolic organ invasion (T4 stage;P<0.001), perineural invasion (P=0.02), vascular invasion (P=0.045), poor tumor differentiation (P=0.005), mesocolic invasion>1cm (P=0.009), less than 14 uninvolved nodes on the specimen (P=0.03), and visceral peritoneal invasion (T4;P<0.001). In multivariate analysis, the following were independent prognostic factors of recurrence: male patients (P=0.005), bowel obstruction (P=0.002), pericolic organ invasion (i.e., T4 tumor;P=0.02), and less than 14 uninvolved nodes on a specimen (P=0.01). On the other hand, preoperative carcinoembryonic antigen serum level, size and tumor location, blood transfusion, and mucin production were not associated with higher risk of tumor recurrence. CONCLUSION: Our study identifies a subgroup of patients with node-negative colon cancer at high risk of recurrence, who could be included in priority trials of adjuvant chemotherapy.Presented at the meeting of The American Society of Colon and Rectal Surgeons in Boston, Massachusetts, June 24 to 29, 2000.     

Comparative effectiveness of different chemotherapeutic regimens on survival of people aged 66 and older with stage III colon cancer: a "real world" analysis using Surveillance, Epidemiology, and End Results-Medicare data

OBJECTIVES: To compare the effectiveness and utilization trends of irinotecan (IRI)‐based and oxaliplatin (OX)‐based regimens with those of 5‐fluorouracil and leucovorin (5FU/LV) alone in people aged 66 and older with Stage III colon cancer. DESIGN: Retrospective cohort study. SETTING: Data from the Surveillance, Epidemiology, and End Results (SEER)–Medicare data. PARTICIPANTS: People with Stage III surgically resected colon cancer who received adjuvant chemotherapy were categorized into 5FU/LV‐alone (n=3,581), OX‐based regimen (n=814), and IRI‐based regimen (n=219) subgroups. MEASUREMENTS: Multivariable Cox proportional hazards models examined the effect of chemotherapies on overall survival, colon cancer–specific survival, and non‐colon cancer–specific survival. RESULTS: Use of the OX‐based regimen increased, and use of the 5FU/LV‐alone and IRI‐based regimens decreased over time. OX was statistically significantly associated with longer overall survival (hazard ratio (HR)=0.73, 95% confidence interval (CI)=0.62–0.86, P<.001) and colorectal cancer–specific survival (HR=0.39, 95% CI, 0.28–0.55, P<.001) than 5FU/LV alone. There was a greater risk of overall mortality (HR=1.38, 95% CI=1.14–1.67, P<.001) and cancer‐specific mortality (HR=1.92, 95% CI=1.49–2.47, P<.001) associated with IRI than with 5FU/LV. The superiority of OX on survival was found in participants aged 66 to 79 but not in those aged 80 and older. CONCLUSION: This “real world” comparative effectiveness research extends randomized controlled trial results by documenting the relative survival benefit of OX in older adults with Stage III colon cancer. The associated shift in treatment away from 5FU/LV alone or IRI toward OX is consistent with evidence‐based medicine from real‐world outcomes research.     

Natural history of colorectal cancer in hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II)

Approximately 5 to 6 percent of the total colorectal cancer burden is accounted for by hereditary nonpolyposis colorectal cancer (HNPCC). Because clinical premonitory signs such as those seen in familial polyposis coli (FPC) are lacking, the clinician must recognize clinical findings and family history typical of HNPCC. The authors have described colorectal cancer expression from a survey of ten HNPCC kindreds. Kindred members with colorectal cancer differed significantly (P<.05) from patients with sporadic colorectal cancer: 1) mean age of initial colon cancer diagnosis was 44.6 years; 2) 72.3 percent of first colon cancers were located in the right colon, and only 25 percent were in the sigmoid colon and rectum; 3) 18.1 percent had synchronous colon cancers; and 4) 24.2 percent developed metachronous colon cancer, with a risk for metachronous lesions in ten years of 40 percent. Affecteds and their first-degree relatives should undergo early intensive education and surveillance. In families with an early age of onset, colonoscopy should begin at age 25, and biannually thereafter, with fecal occult blood testing of the stool semiannually. Third-party carriers must become more responsive to the costly surveillance measures required for these otherwise healthy patients. Supported by NIH Grants No. 5 RO1 CA41371-01 and 1 RO1 CA42705-01.     

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas

BACKGROUND: Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised "field defect". AIMS: To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer. METHODS: Pancolonoscopy was performed in 15 patients with resected adenomas (> or =1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment. RESULTS: No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4-5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05). CONCLUSIONS: The colonic mucosa of patients with past adenomas presents diffuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours.     

Do Pre‐Hemodialysis Estimates of Extracellular Volume Excess Using Bioimpedance and N‐Terminal Brain Natriuretic Peptide Correlate With Cardiac Chamber Size Measured by Magnetic Resonance Imaging?

Bioimpedance can be used to measure extracellular water (ECW) and total body water in hemodialysis (HD) patients and estimate ECW excess. However, ECW excess potentially includes both an increase in the plasma volume and also the extravascular volume. Overestimating the amount of fluid to be removed during HD risks intra‐dialytic hypotension. We wished to determine the association between estimates of ECW excess comparing several different equations using bioimpedance, brain N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) with cardiac chamber volumes and function as determined by cardiac magnetic resonance imaging pre‐HD measurements of ECW and total body water were made using multifrequency bioimpedance and cardiac chamber sizes and function were determined by magnetic resonance imaging. Thirty patients, 20 males (66.7%), mean age 64.4 ± 15.3 years were studied. ECW and ECW/height were positively associated with indexed right ventricular end‐systolic (RVESVi) and end‐diastolic volume (RVEDVi) (RVESi r = 0.46, r = 0.43; RVEDi r = 0.50, r = 0.44, all P < 0.05), but not with left sided cardiac volumes. Whereas NT‐proBNP was associated with indexed left atrial and ventricular size (r = 0.47, r = 0.58, P < 0.05), but not right sided cardiac volumes. Pre‐HD NT‐proBNP was associated with left sided cardiac chamber sizes, but not with right sided chamber sizes, whereas ECW/height was associated with right sided cardiac chamber sizes. As right‐sided cardiac chamber size is more responsive to and reflective of changes in intravascular volume than the left atrium and ventricle, then bioimpedance measured ECW is potentially more reliable in estimating plasma volume expansion.