Differences in Prostate Cancer Incidence and Mortality in Lower Saxony (Germany) and Groningen Province (Netherlands): Potential Impact of Prostate-Specific Antigen Testing.

BACKGROUND: Prostate cancer (PCa) is the most frequent cancer among men in Europe. Differences in PCa incidence around the world can be partly explained by variations in recommendations for prostate-specific antigen (PSA), particularly for early detection. For example, the PSA testing policy is more conservative in the Netherlands than in Germany. To better understand the relationship between PSA testing recommendations and PCa incidence, stage distribution, and mortality, we compared these variables over time between Lower Saxony in northwestern Germany and the neighboring province of Groningen in the Netherlands. METHODS: Population data, tumor stage- and age group-specific PCa incidence (ICD-10 C61) and mortality rates for Lower Saxony and Groningen were obtained from the Lower Saxony Epidemiological Cancer Registry, the Netherlands Comprehensive Cancer Organization, and Statistics Netherlands for 2003-2012. Incidence and mortality rates per 100,000 person-years were age-standardized (ASR, old European standard). Trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR) for specific age groups were assessed using joinpoint regression. RESULTS: The mean annual PCa ASIR between 2003 and 2012 was on average 19.9% higher in Lower Saxony than in Groningen (120.5 vs. 100.5 per 100,000), while the mean annual ASMR was on average 24.3% lower in Lower Saxony than in Groningen (21.5 vs. 28.4 per 100,000). Between 2003 and 2012, the average annual percentage change (AAPC) in PCa incidence rates did not change significantly in either Lower Saxony (-1.8%, 95% CI -3.5, 0.0) or Groningen (0.2%, 95% CI -5.0, 5.7). In contrast, the AAPC in mortality rate decreased significantly during the same time period in Lower Saxony (-2.5%, 95% CI -3.0, -2.0) but not in Groningen (0.1%, 95% CI -2.4, 2.6). CONCLUSIONS: Higher PCa incidence and lower PCa-related mortality was detected in Lower Saxony than in Groningen. Although recommendations on PSA testing may play a role, the assessed data could not offer obvious explanations to the observed differences. Therefore, further investigations including data on the actual use of PSA testing, other influences (e.g., dietary and ethnic factors), and better data quality are needed to explain differences between the regions.

Comparison of National Comprehensive Cancer Network and European Position Statement protocols for nodule management in low-dose computed tomography lung cancer screening in a general Chinese population.

BACKGROUND: Low-dose computed tomography (LDCT) lung cancer screening often refers individuals to unnecessary examinations. This study aims to compare the European Position Statement (EUPS) and National Comprehensive Cancer Network (NCCN) protocols in management of participants at baseline screening round. METHODS: LDCT lung cancer screening was prospectively performed in a Chinese asymptomatic population aged 40-74 years. A total of 1,000 consecutive baseline LDCT scans were read twice independently. All screen-detected lung nodules by the first reader were included. The first reader manually measured the diameter of lung nodules (NCCN protocol), and the second reader semi-automatically measured the volume and diameter (EUPS volume and diameter protocols). The protocols were used to classify the participants into three management groups: next screening round, short-term repeat LDCT scan and referral to a pulmonologist. Groups were compared using Wilcoxon test for paired samples. Number of lung cancers by protocols was provided. RESULTS: Of the 1,000 participants (61.4±6.7 years old), 168 lung nodules in 124 participants were visually detected and manually measured in the first reading, and re-measured semi-automatically. Applying the NCCN protocol, EUPS volume and diameter protocol, the proportion of referrals among all participants was 0.6%, 1.9%, and 1.4%, respectively. The proportion of short-term repeat scans was 4.5%, 9.7% and 4.5%, respectively. Among the 10 lung cancer patients, one would have been diagnosed earlier if the EUPS volume protocol would have been followed. CONCLUSIONS: In a first round screening in a Chinese general population, the lower threshold for referral in the EUPS protocol as compared to the NCCN protocol, leads to more referrals to a pulmonologist, with the potential of earlier cancer diagnosis. The EUPS volume protocol recommends fewer participants to short-term repeat LDCT scan than the EUPS diameter protocol. Follow-up studies should show the impact of both protocols on (interval) cancer diagnosis.

Staple Food Fortification with Folic Acid and Iron and Gastrointestinal Cancers: Critical Appraisal of Long-Term National Fortification.

The co-occurrence of wheat flour fortification with folic acid and iron and gastrointestinal cancer incidences were critically assessed in the East Azerbaijan province in Northwest of Iran. In an ecological design, overall gastrointestinal cancer rate ratios and their 95% confidence intervals (95% CI) were calculated as primary outcome before (2004-2006) and after (2007-2015) the introduction of fortification. No consistent changes were observed in esophageal and gastric cancer, but the rate ratios of colorectal cancer increased significantly after fortification in the 35-54 years age group (women: 2.07, 95% CI: 1.79-2.49; men: 1.59, 95% CI: 1.33-1.89) and the 55-74 years age group (women 1.50, 95% CI: 1.27-1.76; men: 2.51, 95% CI: 2.13-2.95). The increased incidence of colorectal cancer was contemporary with long-term fortification; further investigation is required to establish the associations.

Systematic Review of Factors Affecting Quality of Life After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Previous studies have shown that, overall, quality of life (QoL) decreases within the first 3-6 months after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC), returning to baseline levels by 6-12 months. This systematic review aims to evaluate the factors affecting QoL after CRS + HIPEC within 12 months of surgery. METHODS: Electronic databases were investigated searching for articles reporting QoL with validated questionnaires up to September 2019. Risk of bias was assessed with the methodological index for non-randomized studies tool. The primary outcomes were short-term (< 6 months after surgery) and medium-term (6-12 months after surgery) determinants of QoL after CRS + HIPEC. Secondary outcomes were QoL and reported symptoms over time. RESULTS: We included 14 studies that used 12 different questionnaires. The reported data were collected prospectively or retrospectively for 1556 patients (dropout < 50% in four studies). Overall, studies showed diminished QoL within 3 months after surgery and a recovery to baseline or greater by 12 months. QoL was negatively influenced by higher age, female sex, prolonged operation time, extensive disease, residual disease, adjuvant chemotherapy, complications, stoma placement, and recurrent disease. QoL results were comparable between studies, with dropout rates above and below 50%. CONCLUSIONS: QoL returns to baseline levels within 12 months after CRS + HIPEC provided the disease does not recur, and this recovery process is influenced by several factors.

Folic Acid Supplement Intake and Risk of Colorectal Cancer in Women; A Case Control Study.

Background: An ongoing controversy exists on the role of folic acid supplementation in colorectal cancer risk among epidemiological studies. Objective: To assess the association between maternal folic acid supplementation and colorectal cancer risk. Methods: A paired matched case control study of 405 subjects was performed, including women residing in 135 villages of East Azerbaijan, Iran. Per area, subjects were followed regularly in local healthcare centers, where health- and social-related information have been collected prospectively in face to face interviews by well-trained health workers. We extracted folic acid supplement intake, baseline characteristics, and confounders from healthcare records. The data for study participants were linked to national cancer registry repositories, from which we retrieved the data of 135 women diagnosed with colorectal cancer between 2005 to 2015. Two hundred seventy controls were individually matched with cases in terms of residing village, age, and gender. We applied multivariate conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Findings: There was no significant association between folic acid supplementation and colorectal cancer risk in those with history of folic acid intake compared to those with no history of intake (OR 0.95; 95% CI 0.59 to 1.53), in those with less than five years of folic acid (0.79; 0.45 to 1.39) or in those with ≥5 years intake (1.09; 0.52 to 2.26). This risk did not change after adjustment for covariates or further stratification. Conclusions: Maternal folic acid supplementation did not affect colorectal cancer risk in a population where supplemental folic acid is prescribed with regular intervals for women of child-bearing age.

The Relationship of Coronary Artery Calcium and Clinical Coronary Artery Disease with Cognitive Function: A Systematic Review and Meta-Analysis.

AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. METHODS: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). RESULTS: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, p＜0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. CONCLUSIONS: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.

Incidence and predictors of postoperative delirium after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Incidence of, and baseline characteristics associated with delirium in patients after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), were subject of investigation. METHODS: The study was conducted among a consecutive series of prospectively included patients who underwent CRS-HIPEC at the University Medical Center Groningen, Groningen, the Netherlands, between February 2006 and January 2015. A chart-based instrument for delirium during hospitalization was used to identify patients with symptoms of delirium who were not diagnosed by a psychiatrist during admission. Uni- and multivariate logistic regression analyses were performed. RESULTS: Data of 136 patients were included in the analysis. Median age was 60 years (range: 18-76) and 50 (37%) patients were male. During hospitalization, 38 (28%) patients were diagnosed with delirium. Factors that differed significantly between the patients with and without delirium by univariate analysis were included in multivariate analysis. Multivariate analysis showed that after adjustment for age and complications other than delirium, having three or more organs resected and the CRP serum levels were independent predictors for delirium (OR: 3.97; 95% 1.24-12.76; OR: 1.01; 95% 1-1.01, respectively). CONCLUSIONS: This report shows an incidence of 28% of delirium, occurring after CRS-HIPEC and suggests a role for systemic inflammation in the development of postoperative delirium.

Folic acid intake and folate status and colorectal cancer risk: A systematic review and meta-analysis.

BACKGROUND & AIMS: To evaluate the controversies among the studies assessing the association between folic acid intake or folate status and colorectal cancer risk. METHODS: PubMed, Cochrane library and references of related articles were searched from January 2000 to September 2016. Studies on folic acid intake or folate status and colorectal cancer or adenoma risk were included. Full text review was conducted for potentially eligible studies. Quality assessment was performed. Random-effects meta-analysis was used to estimate risk ratio and 95% Confidence Intervals. Analysis was conducted by Comprehensive Meta-Analysis software. RESULTS: Folic acid supplement intake showed no significant effect on colorectal cancer risk in meta-analysis of randomized controlled trials, RR: 1.07 (95% CI: 0.86-1.43). The effect on risk was not significant in cohort studies either; RR = 0.96 (95% CI: 0.76-1.21). However, there was significant reduced colorectal cancer risk in total folate intake in cohort studies; 0.71 (95% CI: 0.59-0.86). Odds Ratio was also significantly reduced in case control studies; 0.77 (95% CI: 0.62-0.95). Nevertheless once folate status was measured as Red Blood Cell folate content, no significant effect on colorectal cancer risk was observed; 1.05 (95% CI: 0.85-1.30). CONCLUSION: The differences in bioavailability and metabolism of synthetic folic acid and natural dietary folate as well as variation in the baseline characteristics of subjects and various methods of folate status assessment might be the main reasons for these controversies. Findings of present study highlight the importance of individualized folic acid supplement intake given the fact that the beneficiary effects of long term folic acid supplementation is not confirmed.

Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fractions.

A recent study showed an association between hookah/opium use and gastric cancer but no study has investigated the relationship with gastric precancerous lesions. We examined the association between hookah/opium and gastric precancerous lesions and subsequent gastric cancer. In a population-based cohort study, 928 randomly selected, healthy, Helicobacter pylori-infected subjects in Ardabil Province, Iran, were followed for 10 years. The association between baseline precancerous lesions and lifestyle risk factors (including hookah/opium) was analyzed using logistic regression and presented as odds ratios (ORs) and 95% confidence intervals (CIs). We also calculated hazard ratios (HRs) and 95% CIs for the associations of lifestyle risk factors and endoscopic and histological parameters with incident gastric cancers using Cox regression models. Additionally, the proportion of cancers attributable to modifiable risk factors was calculated. During 9,096 person-years of follow-up, 36 new cases of gastric cancer were observed (incidence rate: 3.96/1,000 persons-years). Opium consumption was strongly associated with baseline antral (OR: 3.2; 95% CI: 1.2-9.1) and body intestinal metaplasia (OR: 7.3; 95% CI: 2.5-21.5). Opium (HR: 3.2; 95% CI: 1.4-7.7), hookah (HR: 3.4; 95% CI: 1.7-7.1) and cigarette use (HR: 3.2; 95% CI: 1.4-7.5), as well as high salt intake, family history of gastric cancer, gastric ulcer and histological atrophic gastritis and intestinal metaplasia of body were associated with higher risk of gastric cancer. The fraction of cancers attributable jointly to high salt, low fruit intake, smoking (including hookah) and opium was 93% (95% CI: 83-98). Hookah and opium use are risk factors for gastric cancer as well as for precancerous lesions. Hookah, opium, cigarette and high salt intake are important modifiable risk factors in this high-incidence gastric cancer area.

The management of menopausal symptoms in breast cancer survivors: case-based approach.

INTRODUCTION: The intensified treatment of breast cancer improves survival but has a price in terms of side-effects. The main side-effects, such as vasomotor symptoms and impaired sexual functioning, are related to premature menopause due to chemotherapy and/or anti-hormonal therapy. Though for some women these symptoms are bearable, for others they have a large impact on their quality of life. The paper discusses the menopausal symptoms most frequently reported by breast cancer survivors and current treatment options. METHODS: A literature review is presented of menopausal symptoms after breast cancer and management strategies, illustrated by two cases. SUMMARY: Vasomotor symptoms can be relieved by lifestyle adaptation, acupuncture and non-hormonal agents such as venlafaxine, gabapentin or clonidine. Impaired sexual functioning can be treated by couple-based sexual counselling or psycho-educational therapy. Painful intercourse due to vaginal dryness can be alleviated by vaginal lubricants and moisturizers, but is most effectively treated by vaginal estriol. Local estriol seems safe if used for a short period (less than six weeks). Because of proven increased risk of recurrence with hormone replacement therapy (HRT), it should not be prescribed for breast cancer survivors, although exceptions could be made of selected cases of fully informed BRCA mutation carriers after ER-negative breast cancer and with severe menopausal symptoms due to prophylactic oophorectomy at a young age and (preferably) after mastectomy. CONCLUSION: The management of vasomotor symptoms and impaired sexual functioning in breast cancer survivors should focus on lifestyle and, if necessary, non-hormonal pharmacological interventions.

The value of surveillance mammography of the contralateral breast in patients with a history of breast cancer.

PURPOSE: To determine the contribution of surveillance mammography to the early detection of metachronous contralateral breast cancer (MCBC) and to assess its impact on the survival of breast cancer patients with relation to compliance. METHOD: Breast cancer patients (5589) were identified using files from the regional cancer registry of the Comprehensive Cancer Centre North Netherlands (CCCN Groningen, The Netherlands). The programme sensitivity and the impact on prognosis of follow-up mammography with relation to compliance were evaluated in 114 patients who developed MCBC during hospital follow-up. RESULTS: The cumulative MCBC incidence rate at year 10 was 3.4% (95% CI: 2.8-4.0%). The programme sensitivity of surveillance mammography was 59.6% (95% CI: 50.6-68.7). In patients who complied with annual mammography, sensitivity was increased to 70.8% (95% CI: 61.7-80.0). Patients with MCBCs detected by routine mammography have better survival rates than patients with MCBCs detected by other means (HR: 3.18; 95% CI: 1.59-6.34). Though there was a trend towards improved survival in patients being compliant with regular clinical follow-up (HR: 1.69; 95% CI: 0.72-3.96), this was not the case for patients being compliant with annual mammography (HR:1.02; 95% CI:0.50-2.09). CONCLUSION: Mammography is a valuable tool for the early detection of MCBC during hospital follow-up of breast cancer patients and is probably beneficial to survival. The utilisation of follow-up surveillance in breast cancer patients and its potential impact on survival deserve further investigation.