糖尿病与恶性肿瘤发病的现代看法

国内外研究表明,在糖尿病人群中恶性肿瘤患病率明显增加[1-2],尤其是乳腺癌、子宫内膜癌、结直肠癌、肝癌和胰腺癌,在新诊断的癌症病人中糖尿病的发生率高达8-18%[3].认为可能与高血糖、胰岛素及胰岛素样生长因子、脂肪细胞因子等因素有关.本文就2型糖尿病及恶性肿瘤的发生机制作一综述,旨在引起进一步的关注.     

结肠直肠癌的普查

在美国,结肠癌是恶性肿瘤的第二大死亡原因。1985年约有60,000例死亡,并新发现138,000例。国际肿瘤协会1977～1982年的统计指出,结肠癌的5年生存率是54％,直肠癌是51％。为了增加结肠直肠癌的生存率,必须集中力量预防和早期发现恶性肿瘤和癌前病变。结肠直肠癌的预防可以分两方面:①认识饮食、     

结直肠癌合并2型糖尿病患者的临床病理特征

目的:分析结直肠癌合并2型糖尿病患者的临床病理特征.方法:本研究的观察组对象是2018年12月至2020年12月在我院接受治疗的30例结直肠癌合并2型糖尿病患者,对照组对象是同时间段内于我院接受治疗的30例结直肠癌患者(未合并2型糖尿病),统计两组研究对象的各项基础资料,以及两组病患的TNM分期、肿瘤浸润深度、淋巴结转...     

结肠癌的筛选

在美国,每年有新发现的结肠直肠癌140000例,死于结肠直肠癌的患者约55000例。结肠直肠癌已成为第二主要的癌性和或癌症有关的死亡疾病,其发生率随年龄的增长而持续增高,新发现的结肠直肠癌患者年龄大多数大于75岁。人们在一生中患结肠癌的危险为2.6％,临床新诊断的结肠直肠患者多达60％已发生局部或远处转移,其5年的生存率分别约为60％和6％,而对局限性未发生转移的患者进行治疗,其5年生存率要望达到91％。鉴于结肠直肠癌可预防性和严重的危害性,加强对结肠癌的筛选很有必要,其目的主要的是发现早期癌肿,发现和切除息肉,从而预防癌肿。     

结肠癌近20年临床特点的变迁分析

目的 探讨近20年来结肠癌临床特征表现的异同,为临床早期诊断以及肿瘤筛查方案的选择提供一定依据.方法 回顾性分析1989-2008年北京协和医院1233例结肠癌住院患者,按时间阶段分为1989-1998年和1999-2008年两组,分别对结肠癌的临床表现、实验室检查、结肠镜检查、病变部位以及临床分期等特点进行分析.结果 与1989-1998年相比,近10年来结肠癌的患病率明显升高,女性及老年患者有所增加;便血的患者明显减少(51.8%比31.7%, P<0.05),腹部包块和出现肠梗阻的患者也呈下降趋势(30.2%比13.6%, P<0.05);血红蛋白下降的患者有所减少,但大便潜血的阳性率有所增加(43.6%比61.2%, P<0.05);随着癌胚抗原(CEA)检测的普遍开展,其阳性率也明显增加(32.4%比57.9%, P<0.05);结肠镜已成为结肠癌诊断的主要手段,早期病变和合并息肉的患者近年来逐渐增多;肿瘤部位1989-1998年以升结肠为主(44.6%),近10年来逐渐以乙状结肠和降结肠(38.7%和22.7%)为主.手术切除是主要治疗方法,与1989-1998年相比,近10年来早期手术病例(Duke A期)明显增加(9.3%比23.8%,P<0.05).结论 近年来结肠癌的患病率呈上升趋势,女性和老年患者明显增加;临床表现变得更缺乏特异性;随着大便潜血、CEA检测和结肠镜检查手段的提高和完善,早期患者的检出率有所增加;肿瘤部位从以右半结肠为主转变为以左半结肠为主,与西方国家的特点更为接近.     

结肠癌合并2型糖尿病病人胰岛素样生长因子-1表达与淋巴结转移的相关性分析

目的 探讨结肠癌合并2型糖尿病病人胰岛素样生长因子-Ⅰ的表达与淋巴结转移的相关性.方法 选取2012年1月2013年7月该院收治的结肠癌合并2型糖尿病患者129例,采用酶联免疫法(ELISA)检测发生淋巴结转移的患者与未发生转移的患者的IGF-Ⅰ表达水平,与20例非肿瘤正常人的IGF-Ⅰ水平对比分析.结果 结肠癌合并2型糖尿病患者的IGF-Ⅰ水平显著高于正常对照组,其中发生淋巴结转移的结肠癌患者IGF-Ⅰ表达水平显著高于未发生转移的结肠癌患者,具有统计学差异.结论 该研究提示结肠癌合并2型糖尿病患者的胰岛素样生长因子Ⅰ表达水平与淋巴结转移具有较强的相关性,为肿瘤的诊断与治疗提供思路.     

手术治疗结直肠癌合并急性肠梗阻156例临床分析

目的探讨结直肠癌合并急性肠梗阻患者的手术治疗方法。方法回顾性分析156例行手术治疗的结直肠癌合并急性肠梗阻患者的临床资料。结果本组131例行结肠一期切除吻合术,其中21例行左半结肠切除,行横结肠切除8例,行右半结肠切除术61例,行乙状结肠切除26例,Dixon术15例;行分期手术13例;3例行一期造瘘、二期肿瘤切除肠吻合术;因肿瘤无法切除而行单纯造瘘术9例。本组围手术期死亡3例。153例肠梗阻得到缓解。术后发生切口感染9例,吻合口漏8例,肺部感染2例,输尿管损伤1例,经对症处理后痊愈。随访9个月～5年。术后1年生存率为90.1%(136/151),3年生存率为51.7%(78/151),5年生存率为40.4%(61/151)。结论结直肠癌合并急性肠梗阻确诊后应及早手术治疗。应根据患者的具体情况选择术式,在严格掌握适应证的情况下,尽量争取行一期肠切除吻合术。     

糖尿病治疗药物与癌症的相关性及临床对策

糖尿病和癌症是目前分布广泛且患者人数快速增长的疾病。2010年美国糖尿病学会（ADA）和美国癌症学会（ACS）联合发表糖尿病与癌症共识报告,该报告指出糖尿病患者（主要是2型糖尿病）罹患肿瘤的风险增加,包括肝癌、胰腺癌、子宫内膜癌、结肠癌／直肠癌、乳腺癌、胆囊癌等,且糖尿病患者合并肿瘤的预后及死亡风险增加,糖尿病患者前列腺癌风险降低,对于其他部位癌症无相关性或不确定。糖尿病患者肿瘤风险增加的原因可能部分由于两者共同的危险因素,如增龄、肥胖、不合理膳食、运动减少,直接相关机制可能包括胰岛素抵抗、高胰岛素血症、生长因子、高血糖慢性炎症和氧化应激有关。不同类型及作用机制的降糖药物与糖尿病患者肿瘤的发生、发展及预后也有重要影响。目前关于降糖药与肿瘤的发生风险的研究结果尚存在一定争议,关于降糖药的安全性也是目前学术界关注的焦点,本文将简要综述部分常用降糖药物与癌症的关系。     

结直肠癌的低剂量螺旋CT分期与病理对照研究

目的探讨低剂量多层螺旋CT（LDMSCT）结肠成像对结直肠癌分期的临床意义.方法采用50mAs LDMSCT扫描法对33例结肠癌进行术前分期,并与术后病理分期进行诊断性实验分析.结果LDMSCT术前T分期的准确度为75.7%（25/33）,对局限于黏膜肌层肿瘤的阳性预测（PPV）为63.6%,对浸润浆膜层及突破浆膜肿瘤的阴性预测（NPV）为86.4%.LDMSCT术前N分期的敏感度为85.71%（18/21）,N分期阳性诊断准确度为83.3%（15/18）.结论LDMSCT能够预测结肠癌,对结直肠癌能进行准确的术前分期;但对早期病变T分期还有一定限度,准确N分期必须结合肿瘤大小、形态及其生物学行为进行全面的判断.     

辅助内分泌治疗子宫内膜癌合并糖尿病疗效探讨

目的探讨辅助内分泌治疗子宫内膜癌合并糖尿病的疗效。方法选取该科2010年6月—2015年6月收治的84例子宫内膜癌合并糖尿病患者,随机分为2组各42例,对照组采用常规治疗,观察组采用辅助内分泌治疗,比较疗效。结果观察组复发或转移3例,复发或转移平均时间为(21.5±4.3)个月,明显优于对照组(P0.05);观察组2、3年生存率明显优于对照组(P0.05)。结论子宫内膜癌合并糖尿病患者辅助内分泌治疗,可降低患者复发或转移,延长生存时间。     

2004至2010年中山大学附属江门医院住院2型糖尿病患者伴恶性肿瘤分布情况的回顾性调查

目的分析2型糖尿病患者恶性肿瘤的检出率和患者在不同性别、年龄及病程等情况下各种恶性肿瘤的分布情况,为糖尿病患者的肿瘤早期防治提供依据。方法回顾性调查2004至2010年中山大学附属江门医院住院的2型糖尿病患者8772例,选取其中先诊断糖尿病后确诊恶性肿瘤或同时诊断糖尿病与恶性肿瘤的患者共542例,对患者的肿瘤分布情况进行统计学分析,计量资料采用t检验,计数资料采用x。检验,危险因素分析用logistic回归分析。结果住院2型糖尿病患者中肿瘤的检出率为6．2％（542／8772）,年龄≥50岁是2型糖尿病患者发生恶性肿瘤的危险因素（OR=1．666,95％CI：1．269—2．186）,不同性别患者恶性肿瘤的发生存在统计学差异（OR=1．231,95％CI：1．034～1．467）。542例糖尿病合并肿瘤患者中前3位分别是肠癌（16．1％,87／542）、肺癌（15．5％,84／542）、肝癌（13．8％,75／542）,其男女比例为1．18：1,男性前3位肿瘤分别为肝癌（20．1％,59／293）、肺癌（19．8％,58／293）、肠癌（14．7％,43／293）,女性前3位肿瘤分别为肠癌（17．7％,44／249）、子宫内膜癌（11．2％,28／249）、乳腺癌（10．8％,27／249）;患者年龄≤40、41～50、51～60、61～70、〉70岁分别占2．0％（11／542）、11．1％（60／542）、33．8％（183／542）、30．8％（167／542）、22．3％（121／542）,糖尿病病程〈2年、2～5年、6—10年、〉10年分别为44．6％（242／542）、31．4％（170／542）、17．2％（93／542）、6．8％（37／542）,不同性别、不同年龄段、不同糖尿病病程的患者其各系统恶性肿瘤的分布不全相同。结论江门地区2型糖尿病患者发生恶性肿瘤的患病率随年龄增长而增加,且在糖尿病病程早期检出较多,2型糖尿病患者中肠癌、肺癌、肝癌的检出率较高。     

Diabetes mellitus negatively impacts survival of patients with colon cancer, particularly in stage II disease

Purpose

This retrospective study aimed to determine the effects of diabetes on overall survival (OS) and cancer-specific survival (CSS) in patients with newly diagnosed colon cancers, with particular focus on the impact of diabetes on survival at each stage of colon cancer.

Methods

From January 1999 to January 2008, 2762 consecutive patients diagnosed with colon cancer in Taipei Veterans General Hospital were enrolled. The general characteristics as well as presence of diabetes prior to colon cancer diagnosis were identified. Cox proportional hazard analyses were used for prognostic factors determination; and survival was analyzed using the Kaplan?CMeier method with log-rank test.

Results

A total of 469 patients (17%) had diabetes at diagnosis of colon cancer. Patients with diabetes had baseline characteristics comparable to those without diabetes with the exception that the patients with diabetes were older (>65?years). Diabetes significantly and negatively impacted OS and CSS in multivariate analyses. After adjusting for possible confounding factors, the prognostic impact of diabetes on OS and CSS was particularly significant in patients with stage II colon cancer.

Conclusions

Diabetes is a poor prognostic factor in patients with newly diagnosed colon cancer, and it may directly impact the tumor behavior of stage II disease. Further study is required to elucidate the underlying pathophysiologic mechanisms.     

Cause of Death in Older Men After the Diagnosis of Prostate Cancer

OBJECTIVES: To compare survival and cause of death in men aged 65 and older diagnosed with prostate cancer and with survival and cause of death in a noncancer control population.
DESIGN: Retrospective cohort from a population-based tumor registry linked to Medicare claims data.
SETTING: Eleven regions of the Surveillance, Epidemiology and End Results (SEER) Tumor Registry.
PARTICIPANTS: Men aged 65 to 84 (N=208,601) diagnosed with prostate cancer from 1988 through 2002 formed the basis for different analytical cohorts.
MEASUREMENTS: Survival as a function of stage and tumor grade (low, Gleason grade<7; moderate, grade=7; and high, grade=8–10) was compared with survival in men without any cancer using Cox proportional hazards regression. Cause of death according to stage and tumor grade were compared using chi-square statistics.
RESULTS: Men with early-stage prostate cancer and with low- to moderate-grade tumors (59.1% of the entire sample) experienced a survival not substantially worse than men without prostate cancer. In those men, cardiovascular disease and other cancers were the leading causes of death.
CONCLUSION: The excellent survival of older men with early-stage, low- to moderate-grade prostate cancer, along with the patterns of causes of death, implies that this population would be well served by an ongoing focus on screening and prevention of cardiovascular disease and other cancers.     

Diabetes mellitus: influences on cancer risk

Diabetes mellitus and cancer are common conditions, and their co‐diagnosis in the same individual is not infrequent. The relative risks associated with type 2 diabetes are greater than twofold for hepatic, pancreatic, and endometrial cancers. The relative risk is somewhat lower, at 1.2–1.5‐fold for colorectal, breast, and bladder cancers. In comparison, the relative risk of lung cancer is less than 1. The evidence for other malignancies (e.g. kidney, non‐Hodgkin lymphoma) is inconclusive, whereas prostatic cancer occurs less frequently in male patients with diabetes. The potential biologic links between the two diseases are incompletely understood. Evidence from observational studies suggests that some medications used to treat hyperglycemia are associated with either increased or reduced risk of cancer. Whereas anti‐diabetic drugs have a minor influence on cancer risk, drugs used to treat cancer may either cause diabetes or worsen pre‐existing diabetes. If hyperinsulinemia acts as a critical link between the observed increased cancer risk and type 2 diabetes, one would predict that patients with type 1 diabetes would have a different cancer risk pattern than patients with type 2 diabetes because the former patients are exposed to lower levels of exogenous administered insulin. Obtained results showed that patients with type 1 diabetes had elevated risks of cancers of the stomach, cervix, and endometrium. Type 1 diabetes is associated with a modest excess cancer risk overall and risks of specific cancers that differ from those associated with type 2 diabetes. Copyright © 2014 John Wiley & Sons, Ltd.     

Rectal bleeding and previous anticoagulant treatment in patients with colorectal cancer do not predict outcome

Background The aim of this study was to determine whether the outcome of patients with colorectal cancer who presented with bleeding and a history of anticoagulant treatment was different from those who did not have bleeding or previous anticoagulant treatment. Methods This was a single institution, retrospective study of patients with colorectal cancer with and without a history of rectal bleeding and treatment with anticoagulants, assessed for age, gender, tumor site, stage, recurrence rate, and survival. Results A total of 621 consecutive patients (309 men) with a mean age of 70 years (range, 36–94 years) diagnosed with colorectal cancer between 1998 and 2004 were studied. Of these, 149 patients (24%) were referred for symptoms of rectal bleeding and 161 patients (26%) had been previously treated with anticoagulants. A total of 592 patients (95%) underwent curative or palliative surgery; endoscopic polypectomy was performed in 3 cases only and in 26 patients (4%) surgery was not performed due to advanced disease or critical illness. Patients with bleeding and a history of anticoagulant treatment presented commonly with stage I cancer. In addition, tumor stage III was less common in patients with previous anticoagulant treatment irrespective of presenting signs. Disease-free and overall survival rates were similar in all groups, irrespective of bleeding at presentation or anticoagulant treatment. Conclusions Rectal bleeding and anticoagulant treatment do not affect the outcome of newly diagnosed patients with colorectal cancer.     

Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients

BACKGROUND & AIMS: Endogenous hyperinsulinemia in the context of type 2 diabetes mellitus is potentially associated with an increased risk of colorectal cancer. We aimed to determine whether insulin therapy might increase the risk of colorectal cancer among type 2 diabetes mellitus patients. METHODS: We conducted a retrospective cohort study among all patients with a diagnosis of type 2 diabetes mellitus in the General Practice Research Database from the United Kingdom. We excluded patients with <3 years of colorectal cancer-free database follow-up after the diabetes diagnosis as well as those insulin users who developed colorectal cancer after <1 year of insulin therapy. The remaining insulin users and the noninsulin-using type 2 diabetic patients were followed for the occurrence of colorectal cancer. Hazard ratios (HR) were determined in Cox proportional hazard analysis. A nested case-control study was conducted to perform multivariable analysis and to determine a duration-response effect. RESULTS: The incidence of colorectal cancer in insulin users (n = 3160) was 197 per 100,000 person-years, compared with 124 per 100,000 person-years in type 2 diabetes mellitus patients not receiving insulin (n = 21,758). The age- and sex-adjusted HR of colorectal cancer associated with > or =1 year of insulin use was 2.1 (95% CI: 1.2-3.4, P = 0.005). The positive association strengthened after adjusting for potential confounders. The multivariable odds ratio associated with each incremental year of insulin therapy was 1.21 (95% CI: 1.03-1.42, P = 0.02). CONCLUSIONS: Chronic insulin therapy significantly increases the risk of colorectal cancer among type 2 diabetes mellitus patients.     

QTc interval and scintigraphically assessed myocardial perfusion in newly diagnosed and long-term type 1 diabetes mellitus

In diabetes mellitus, heart rate corrected QT interval (QTc) has been suggested to be related to ischemic heart disease and increased risk of sudden cardiac death. The aim of the study was to analyze the length of QTc interval with regard to global and regional myocardial perfusion in type 1 diabetic patients. Myocardial perfusion was investigated in 20 newly diagnosed and 40 long-term type 1 diabetic patients without clinical evidence for coronary artery disease by means of Tc-99-methoxyisobutylisonitrile (Tc-99m-MIBI)-scintigraphy (myocardial uptake (MU) score: 1-6). Five consecutive RR and QT intervals of resting electrocardiogram (ECG) tracing were measured and corrected for the previous cycle length. ECG-based cardiac autonomic neuropathy (CAN) was assessed with five cardiac reflex tests. Length of QTc interval was 423+/-29 ms in newly diagnosed and 433+/-26 ms in long-term type 1 diabetic patients. Nine (45%) newly diagnosed and 18 (45%) long-term diabetic patients demonstrated a prolonged QTc interval (>440 ms). Both newly diagnosed and long-term diabetic patients did not display significant global or regional myocardial perfusion defects (mean MU scores<3). In newly diagnosed diabetic patients, the length of QTc interval was related to global, posterior and septal Tc-99m-MIBI uptake (p<0.05, respectively). In long-term diabetic patients, the length of QTc interval was associated with apical Tc-99m-MIBI uptake (p<0.05). Two (10%) newly diagnosed and 19 (48%) long-term type 1 diabetic patients demonstrated ECG-based CAN. In long-term type 1 diabetic patients, global myocardial Tc-99m-MIBI uptake did not differ significantly between patients with and without CAN. QTc interval was not significantly different between diabetic patients with and without ECG-based CAN (433+/-19 ms vs. 428+/-17 ms). Long-term diabetic patients, of whom 10 (25%) patients had microalbuminuria and seven (18%) patients had macroalbuminuria, demonstrated an association between QTc interval and albuminuria (p<0.05). The results somewhat suggest an association between QTc interval and vascular factors in type 1 diabetes mellitus. Future investigations are required to analyze the role of QTc interval in the pathogenesis of abnormalities of myocardial perfusion.     

Diabetes and prognosis in a breast cancer cohort

Purpose

Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics.

Methods

The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes.

Results

In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5?years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49?C2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31?C3.97).

Conclusion

In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5?years follow-up period.     

Disease-specific mortality among stage I–III colorectal cancer patients with diabetes: a large population-based analysis

Aims/hypothesis

The aim of our study was to investigate overall and disease-specific mortality of colorectal cancer patients with diabetes.

Methods

In this population-based study, we included all colorectal cancer patients, newly diagnosed with stage I–III cancer, between 1997 and 2007 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by reviewing hospital medical records. Data on patients with and without diabetes were linked to Statistics Netherlands to assess vitality, date of death and underlying cause of death. Follow-up of all patients was completed until 1 January 2009.

Results

We included 6,974 patients with colon cancer and 3,888 patients with rectal cancer, of whom 820 (12%) and 404 (10%), respectively, had diabetes at the time of cancer diagnosis. During follow-up, death occurred in 611 (50%) of 1,224 cancer patients with diabetes and 3,817 (40%) of 9,638 cancer patients without diabetes. Multivariate Cox regression analyses, adjusted for age, sex, socioeconomic status, stage, lymph nodes examined, adjuvant therapy and year of diagnosis, showed that overall mortality was significantly higher for colon (HR 1.12, 95% CI 1.01, 1.25) and rectal (HR 1.21, 95% CI 1.03, 1.41) cancer patients with diabetes than for those without. Disease-specific mortality was only significantly increased for rectal cancer patients (HR 1.30, 95% CI 1.06, 1.60).

Conclusions/interpretation

Diabetes at the time of rectal cancer diagnosis was independently associated with an increased risk of colorectal cancer mortality compared with no diabetes, suggesting a specific interaction between diabetes and rectal cancer. Future in-depth studies including detailed diabetes- and cancer-related variables should elucidate pathways.     

Association of nephropathy and retinopathy, blood pressure, age in newly diagnosed type 2 diabetes mellitus

In this study, we investigated the prevalence of chronic complications, including nephropathy and retinopathy, in patients newly diagnosed as type 2 diabetes mellitus. All hyperglycemic subjects were recruited into our study when they visited the outpatient department at Kaohsiung Medical University Hospital over a one-year period. These subjects had fasting plasma glucose higher than 140 mg/dl, or plasma glucose higher than 200 mg/dl in the 2nd hour during an oral glucose tolerance test. Among 148 patients registered as newly diagnosed type 2 diabetes mellitus, 18.2% of the patients had nephropathy, noted by measuring their urine albumin excretion rate and daily protein loss, and 25.5% had retinopathy, noted by fundoscope and fluorescent angiography. The age of overt proteinuric patients (41.5 +/- 3.4 yrs) was significantly younger than those without nephropathy (51.8 +/- 1.0 yrs). Systolic and diastolic blood pressure was significantly higher in patients with microalbuminuria (142.4 +/- 6.0/88.8 +/- 2.6 mmHg) and overt proteinuria (153.8 +/- 13.6/96.8 +/- 9.5 mmHg) than normoalbuminuric patients (128.3 +/- 2.3/81.9 +/- 1.1 mmHg). There was no significant difference in cholesterol, triglyceride, HbA1C, sex or body mass index among normoalbuminric, microalbuminuric, or overt proteinuric patients. The severity of retinopathy was parallel with the severity of nephropathy. Based on our results, chronic diabetic complications, including nephropathy and retinopathy, may occur even when diabetes is newly diagnosed. It is necessary to look for complications, especially in newly documented diabetic patients who are young and hypertensive.