Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited. Patients and methods: For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology. Results: A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR) = 1.12; 95 % confidence interval (CI) = 1.04-1.20] and current smoking (HR = 1.29; 95% CI = 1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10 years = 0.78; 95% CI = 0.69-0.88; HR≥10 years = 0.78; 95% CI = 0.63-0.97) and CRC-specific survival (HR≥10 years = 0.76; 95% CI = 0.67-0.85). Conclusion: In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.

Social capital, deprivation and self-rated health: Does reporting heterogeneity play a role? Results from the English Longitudinal Study of Ageing.

Self-rated health (SRH) is commonly assessed in large surveys, though responses can be influenced by different individuals' perceptions of and beliefs about health. Therefore, instead of providing evidence of 'true' health disparities across groups, findings may actually reflect reporting heterogeneity. Using data from participants aged 50 years and older from the English Longitudinal Study of Ageing (ELSA) Wave 3 (2006/07; participation rate = 73%), associations between three dimensions of social capital (local area & trust, social support and social networks), deprivation and SRH were examined using the vignette methodology in 2341 individuals who completed both the self-report and at least one of the 18 vignettes. Analysis employed a hierarchical probit model (HOPIT). Individuals expressing low local area & trust social capital (beta = -0.276, p < 0.001) and those with poor social networks (beta = -0.280, p < 0.001) were more likely to report poor SRH in HOPIT models accounting for reporting heterogeneity, but unadjusted ordered probit analyses still correctly show a negative relationship between low local area & trust social capital (beta = -0.243, p < 0.001) and those with poor social networks (beta = -0.210, p < 0.01), though they somewhat tend to underestimate its strength. Neither social support nor deprivation appeared to have any effect on SRH regardless of reporting heterogeneity. Anchoring vignettes offer a relatively uncomplicated and cost-effective way of identifying and correcting for reporting heterogeneity to improve comparative validity of self-report measures of health. This analysis underlines the need for caution when using unadjusted self-reported measures to study the effects of social capital on health.

Fruit and vegetable intake and risk of incident of type 2 diabetes: results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES).

BACKGROUND/OBJECTIVES: There is limited information to support definitive recommendations concerning the role of diet in the development of type 2 Diabetes mellitus (T2DM). The results of the latest meta-analyses suggest that an increased consumption of green leafy vegetables may reduce the incidence of diabetes, with either no association or weak associations demonstrated for total fruit and vegetable intake. Few studies have, however, focused on older subjects. SUBJECTS/METHODS: The relationship between T2DM and fruit and vegetable intake was investigated using data from the NIH-AARP study and the EPIC Elderly study. All participants below the age of 50 and/or with a history of cancer, diabetes or coronary heart disease were excluded from the analysis. Multivariate logistic regression analysis was used to calculate the odds ratio of T2DM comparing the highest with the lowest estimated portions of fruit, vegetable, green leafy vegetables and cabbage intake. RESULTS: Comparing people with the highest and lowest estimated portions of fruit, vegetable or green leafy vegetable intake indicated no association with the risk of T2DM. However, although the pooled OR across all studies showed no effect overall, there was significant heterogeneity across cohorts and independent results from the NIH-AARP study showed that fruit and green leafy vegetable intake was associated with a reduced risk of T2DM OR 0.95 (95% CI 0.91,0.99) and OR 0.87 (95% CI 0.87,0.90) respectively. CONCLUSIONS: Fruit and vegetable intake was not shown to be related to incident T2DM in older subjects. Summary analysis also found no associations between green leafy vegetable and cabbage intake and the onset of T2DM. Future dietary pattern studies may shed light on the origin of the heterogeneity across populations.

Alcoholic beverage preference and diabetes incidence across Europe: the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project.

BACKGROUND/OBJECTIVES: It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol. SUBJECTS/METHODS: Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when ⩾70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis. RESULTS: Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases. CONCLUSIONS: This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.

Increased steroid production by the ovarian stromal tissue of postmenopausal women with endometrial cancer.

An increase in ovarian steroid secretion could play a role in the pathogenesis of endometrial cancer in postmenopausal women. The present study was undertaken to investigate steroid production by isolated ovarian stromal tissues of postmenopausal women with endometrial cancer and to study the effect of LH and insulin on ovarian steroidogenesis in postmenopausal women. Ovarian stromal tissue was obtained from 10 postmenopausal women with endometrial cancer and 8 women without cancer. The stroma was incubated in either the medium alone or the medium to which was added LH (50 ng/mL) or insulin (500 ng/mL). The ovarian stroma of postmenopausal women with cancer released significantly more androstenedione (A), testosterone, and dehydroepiandrosterone than that of women without cancer. Addition of LH resulted in a significant increase in A, testosterone, dehydroepiandrosterone, and progesterone release compared to that with vehicle alone. Addition of insulin stimulated the release of A from the ovarian stroma of women with cancer, but had no effect on the normal postmenopausal ovarian stroma. These results indicate that the ovarian stroma of postmenopausal women with endometrial cancer secrete significantly greater amounts of androgens than those of women without cancer and that both LH and insulin may be important factors contributing to this increase in ovarian steroidogenesis.

Chronic plasma cell cervicitis simulating a cervical malignancy: a case report.

BACKGROUND: Only one case of plasma cell cervicitis, a rare variant of chronic cervicitis, has been reported. We report a second case and present data supporting the detection of human papillomavirus (HPV) outside of epithelial tissues. CASE: A 67-year-old woman was found to have a large cervical tumor. Extensive diagnostic evaluation failed to reveal a suspected cervical cancer; subsequently, a hysterectomy was performed. Light microscopic studies confirmed plasma cell cervicitis. Standard virologic tests were used to confirm the presence of HPV 16 in cervical sections. Retrospective study of the first reported case also demonstrated HPV. CONCLUSION: Fulminant cases of chronic cervicitis, presenting with clinical features similar to cervical cancer, are unusual. Even more interesting is the detection of HPV outside of the epithelium; this is the first case that clearly demonstrates HPV in plasma cells.

Clinical implications of tumor volume measurement in stage I adenocarcinoma of the cervix.

OBJECTIVE: To evaluate the prognostic significance of three-dimensional determination of tumor size in stage I cervical adenocarcinoma. METHODS: Tumor volume was measured using hematoxylin and eosin-stained sections of cone biopsy and hysterectomy specimens from 36 patients with stage I adenocarcinoma of the cervix. The volume was then correlated with pelvic lymphatic spread and clinical outcome. RESULTS: The subjects were followed for a mean (+/- SEM) of 63 +/- 8 months. No recurrence or lymphatic seeding was encountered in the 22 tumors measuring no more than 500 mm3. Two of 25 tumors (8%) having up to 5 mm depth of stromal invasion had lymph node metastasis, one of which was 1.5 mm, compared with four of 11 (36%) in the group with deeper than 5 mm invasion (P < .02). The depth of stromal invasion predicted recurrence less significantly. Among the 25 tumors with up to 5 mm stromal invasion, two recurred, compared with three of 11 with more than 5 mm invasion (P < .1). Two women who had tumor volumes below 500 mm3 and depths of stromal invasion up to 8.5 mm were disease-free at 52 and 96 months of follow-up. On the other hand, tumors with 2.6 and 3.8 mm stromal invasion, but with volumes exceeding 500 mm3, recurred. CONCLUSION: Tumor volume is a better predictor of pelvic lymph node metastasis and recurrence than is the depth of stromal invasion in stage I cervical adenocarcinoma.

Management of patients with positive margins after cervical conization.

OBJECTIVE: To evaluate conservative management of patients undergoing cervical conization with cone margins positive for dysplasia. METHODS: The outcomes of 93 patients with cone biopsies that had margins positive for dysplasia were tabulated. RESULTS: Thirty of 47 patients (64%) undergoing conization only and followed by cytology had negative Papanicolaou smears for at least 2 years. Twenty-one of 37 women (57%) with conization and immediate hysterectomy had no residual disease in the cervix. Three of nine women (33%) with conization and delayed hysterectomy had no detectable dysplasia in the remaining cervix. There was no case of progression to invasive disease. The overall resolution rate was 58%. Persistence of disease was found most often at the endocervical margins associated with cervical intraepithelial neoplasia grade III. CONCLUSION: Patients with cone margins positive for dysplasia can be followed appropriately with cytology. In cases of recurrent abnormal Papanicolaou smears, colposcopy, biopsies, and endocervical curettage should be repeated.

Adenosquamous carcinoma of the pancreas.

HYPOTHESIS: Adenosquamous carcinoma of the pancreas is a rare but particularly virulent variant of invasive ductal carcinoma. This review will demonstrate the aggressive biologic activity, histopathologic features, and DNA flow cytometric characteristics of this aggressive lesion. In addition, the outcome is less favorable than in other pancreatic neoplasms, in spite of aggressive surgical and postoperative adjuvant therapy. DESIGN: A retrospective review of 6 patients treated during an 8-year period. SETTING: A major urban university tertiary referral hospital. PATIENTS: There were 6 patients with this unusual tumor seen between 1990 and 1998. There were 4 men and 2 women, all white, with a mean+/-SD age of 63.5+/-14.7 years. Symptoms were similar to those in patients with more common pancreatic malignant neoplasms. RESULTS: Four patients with tumors in the head of the pancreas had pancreatoduodenectomy, and 2 with body and or tail lesions had distal pancreatectomy and splenectomy. Pathologically, all the tumors were poorly differentiated and aneuploid, and 5 of the 6 were locally metastatic. All but 1 patient had postoperative complications, but there were no operative deaths. One half of the patients received postoperative adjuvant chemotherapy and radiation therapy. Only 1 patient is still alive at 9 months after surgery, but has known residual cancer around his portal vein noted during palliative distal pancreatectomy. CONCLUSIONS: Adenosquamous carcinoma of the pancreas is an uncommon variant of exocrine pancreatic neoplasm. It is characterized by an admixture of adenomatous and squamous cell elements and demonstrates aggressive biologic behavior. This series of 6 patients is similar to the 134 cases reported since 1907, in that survival is short despite aggressive surgical therapy. Few patients with this disease live more than 1 year. Aggressive therapy should be tempered by the realization of the uniform poor prognosis associated with this malignant neoplasm.

Bone metastasis in epithelial ovarian carcinoma.

Two cases of bone metastasis in patients with epithelial ovarian carcinoma and a review of the literature are presented. Bone metastases detected antemortem are rare and herald a poor prognosis.

Ifosfamide with mesna in squamous carcinoma of the cervix: phase II results in patients with advanced or recurrent disease.

Twenty-four evaluable patients with recurrent or advanced squamous carcinoma of the cervix were treated with ifosfamide (IFX) and mesna every 3 weeks. The initial dose of IFX was 1.5 g/m2 q.d. Days 1-5. Mesna was given by continuous infusion (1.5 g/m2/day Days 1-6). Seventy-four courses of treatment were given to 24 patients. All patients were evaluable for toxicity and response. The median survival was 26 weeks from initiation of chemotherapy. There were 4 complete responders (CR); there was 1 partial responder. The response rate was 20.8% (CI, 4-38%). One CR patient remains in clinical remission 30 months after initiation of therapy. The other 3 responders recurred after a disease-free interval of 8, 12, and 18 weeks. WBC below 3000/mm3 occurred in 19 patients and was life threatening (below 1000/mm3) in 5 patients. One patient had life-threatening hemorrhagic cystitis. Eleven patients developed CNS symptoms during treatment including somnolence, coma, and acute delirium.

Increased bioactive luteinizing hormone levels in postmenopausal women with endometrial cancer.

OBJECTIVE: The purpose of our study was to investigate the secretion of immunoactive and bioactive luteinizing hormone in postmenopausal women with endometrial cancer. STUDY DESIGN: Seventeen postmenopausal women with endometrial cancer and nine without cancer were studied. Blood samples were collected at 15-minute intervals for 360 minutes. All samples were assayed for bioactive luteinizing hormone by rat interstitial cell testosterone assay and for immunoactive luteinizing hormone by radioimmunoassay. Serum pooled from 6-hour sampling was assayed for follicle-stimulating hormone, total estradiol, unbound estradiol, and estrone. RESULTS: Patients with endometrial cancer had significantly (p < 0.01) higher bioactive luteinizing hormone levels (mean +/- SE 276 +/- 26 IU/L) as compared with those of control women (144 +/- 18 IU/L). Bioactive/immunoactive ratios of luteinizing hormone were significantly higher (p < 0.01) in women with cancer (5.8 +/- 0.7) than in those without cancer (2.5 +/- 0.5). There was a significant (p < 0.001) positive correlation (r = 0.582) between unbound estradiol levels and bioactive luteinizing hormone concentrations. CONCLUSIONS: There is an increase in bioactive luteinizing hormone secretion in postmenopausal women with endometrial cancer. This could lead to an increase in ovarian androgen production resulting in increased prehormone availability for estrogen formation from peripheral conversion.

Detection of human papillomavirus type 16 in plasma cells.

Chronic benign plasma cell tumor of the cervix, also called chronic plasma cell cervicitis, is a rare disease of unknown etiology, characterized by a heavy infiltration of plasma cells forming granulation tissue. To identify infectious agents associated with this disease, we extracted and analyzed DNA from the 17-year-old paraffin section of the original case report and from granulation tissue surgically removed from a patient at our institution with a chronic benign plasma cell tumor. The DNA from both patients was shown by a polymerase chain reaction (PCR) technique to contain a human papillomavirus 16 (HPV 16) sequence. Genomic Southern analysis of the fresh-frozen tissue confirmed the initial PCR finding. In situ hybridization further demonstrated that the HPV 16 was present in the plasma cells and not a contaminant from the surrounding epithelial tissue. The etiological role of HPV 16, an oncogenic virus associated with cervical carcinoma, in this disease is not yet clear. Our results, however, suggest that the types of cells that are infected by HPV may include cells of lymphoid origin, and that HPV may be associated with chronic benign plasma cell tumors of the cervix.

Specific binding sites for insulin and insulin-like growth factor I in human endometrial cancer.

Insulin and insulin-like growth factor I are known to be mitogenic and therefore may play a role in the development of endometrial cancer. We undertook this study to investigate whether human endometrial cancer tissue has receptors for these substances. Endometrial cancer tissue samples were obtained at hysterectomy from 10 women with endometrial cancer, and control endometrial tissue was collected from normal cycling women undergoing hysterectomy for nonendocrine problems. Binding studies with iodine 125-insulin and [125I]insulin-like growth factor I revealed the presence of specific binding sites for insulin and insulin-like growth factor I in both normal endometrium and endometrial cancer tissue. The percent binding of [125I]insulin in the endometrial cancer tissue (mean +/- SE 2.4% +/- 0.5%/100 micrograms protein) was not significantly different from that in normal endometrium (3.5% +/- 1%/100 micrograms protein). On the contrary, the percent total binding of [125]insulin-like growth factor I in the endometrial cancer (5.3% +/- 1.5%/100 micrograms protein) was significantly (p less than 0.04) higher than that observed in normal endometrium (2.1% +/- 0.4%/100 micrograms protein). There was a significant positive correlation between the histologic grade of the tumor and the insulin-like growth factor I binding (r = 0.865, p less than 0.02). The affinity constants for the high-affinity receptors were similar in the normal and neoplastic endometrium. These results indicate that insulin and insulin-like growth factor I may play a role in the growth and development of endometrial cancer.