The relationship between ethnicity,social deprivation and late presentation of colorectal cancer

IntroductionTumour staging at time of presentation is an important factor in determining survival in colorectal cancer. The aim of this paper is to investigate the relationship between ethnicity and deprivation in late (Stage IV) presentation of colorectal cancer.MethodsData from the Thames Cancer Registry comprising 77,057 colorectal cancer patients between the years 2000 and 2012 were analysed.ResultsA total of 17,348 patients were identified with complete data, of which 53.9% were male. Patients from a Black Afro/Caribbean background were diagnosed with CRC at a much younger age than the White British group (median age 67 compared with 72, p < 0.001). In multiple regression, ethnicity, deprivation and age were positive predictors of presenting with advanced tumour stage at time of diagnosis. Black patients were more likely to present with Stage IV tumours than white patients (OR 1.37, 95% CI 1.18–1.59, p < 0.001). Social deprivation was also a predictor of Stage IV cancer presentation, with the most deprived group (Quintile 5) 1.26 times more likely to be diagnosed with Stage IV cancer compared with the most affluent group (CI 1.13–1.40, p < 0.001). Sub-group analyses demonstrated that Black & Affluent patients were still at greater risk of Stage IV CRC than their White & Affluent counterparts (OR 1.24, 95% CI 1.11–1.45, p = 0.023). Patients with rectal cancer were less likely to present with Stage IV CRC (OR 0.66, 95% CI 0.61–0.71, p < 0.001).ConclusionRacial and age related disparities exist in tumour presentation in the United Kingdom. Patients from black and socially deprived backgrounds as well as the elderly are more likely to present with advanced tumours at time of diagnosis.     

Effect of Hospital Admission on Glycemic Control 1 Year After Discharge

ObjectiveTo assess the effect of hospital admission on glycemic control in patients with diabetes up to 1 year after discharge.MethodsWe retrospectively studied 826 adults with diabetes admitted to a tertiary care medical center and with available hemoglobin A_1c (A1C) values for 6 months before admission and 1 year after discharge. We compared them with 826 nonhospitalized adults with diabetes matched for age, sex, race, comorbidity, and baseline A1C level. We determined the change in A1C value relative to hospitalization and baseline A1C level by using multivariate random effects models for repeated measures. Logistic regression analysis was performed to determine predictors of achieving recommended A1C levels at 1 year.ResultsPatients with baseline A1C levels ≥ 9% had an adjusted rate of change in A1C value of − 0.10% per month (95% confidence interval [CI], − 0.18 to − 0.022; P = .012) during the course of 1 year, without significant differences between hospitalized and nonhospitalized patients in the mean rate of change. Hospitalized patients, however, were less likely to achieve an A1C goal of ≤ 7% at 1 year (odds ratio, 0.68; 95% CI, 0.55 to 0.86; P < .001) or an A1C of < 8% at 1 year (odds ratio, 0.62; 95% CI, 0.48 to 0.81; P < .001) in comparison with the nonhospitalized patients.ConclusionDespite an overall trend toward improved glycemia over time, hospitalized patients with uncontrolled diabetes were less likely to achieve glycemic targets at 1 year in comparison with matched nonhospitalized patients. These results suggest a missed opportunity to improve long-term glycemic control in hospitalized patients with diabetes. (Endocr Pract. 2012;18:456-463)     

Value of 111In-Pentetreotide scintigraphy and 18F-FDG PET for clinical prognosis of patients with neuroendocrine neoplasms

Despite the existence of biological markers of aggressiveness, the clinical course of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN) remains difficult to predict. Discrepancies between imaging data generated with ¹¹¹In-pentetreotide scintigraphy and ¹⁸F-FDG-PET could reflect the degree of cellular de-differentiation. NEN patients with both types of studies were identified retrospectively from the SwissNET database, which is collecting information on Swiss NEN patients since 2008. Progression free survival (PFS) and overall survival (OS) were assessed depending on functional imaging results. Correlation between histological grading (according to the WHO 2010 classification) and functional imaging status was also assessed. We identified 31 patients with both imaging studies, either on the primary tumor site (21/31) or for metastases (21/31), with 12/31 on both sites. Mean follow-up was 36 months (95% CI 27–45). 21 patients had a metastatic disease at diagnosis and 11 died at follow-up. 7/31 (22%) were NET G1, 16/31 (52%) were NET G2 and 8/31 (26%) were NEC G3. Only ¹⁸F-FDG PET status almost reached statistical significance (P = 0.054) with histological grading. Progression free-survival was significantly poorer in the ¹⁸F-FDG positive group (n = 21), with a median time for progression of 8 months, compared to 51 months in the negative group (n = 10) with a HR of 3.2 (97.5% CI 1.1–9.5, P = 0.04). Overall survival tended to be worse with a positive PET and a negative ¹¹¹In-pentetreotide scintigraphy status with a HR 1.63 (97.5%CI 0.11–21, P = 0.08). ¹¹¹In-pentetreotide scintigraphy status was not found to be predictive of survival nor progression.ConclusionThese data demonstrate the poorer prognostic value of a positive ¹⁸F-FDG-PET imaging in this cohort of patients.     

Colder-to-warmer changes in children's blood lead concentrations are related to previous blood lead status: Results from a systematic review of prospective studies

ObjectiveTo estimate the extent of changes in mean BLLs from colder to warmer months, in children aged 1–5 years with different status of lead in colder months.MethodologyWe performed a systematic review using an in-house algorithm developed in MEDLINE, EMBASE, Web of Science, and CINHAL. Search was performed between November 2012 and July 2013, and data evaluation and extraction were subsequently conducted. The mean BLLs observed in the warmer months was divided by the one observed in the colder months to obtain the warmer-to-colder ratio (WCR). Study-specific WCRs were pooled using the fixed-effects method of Mantel–Haenszel to estimate the combined WCR.ResultsFrom 4040 papers initially identified, eight cohort studies were considered relevant for inclusion. The combined WCR was inversely related to the BLLs observed during colder months. The values were 1.25 (95% CI: 0.90–1.60), 1.06 (95% CI: 0.92–1.19), and 0.95 (95% CI: 0.51–1.39) for children showing baseline BLLs of <10 μg dL⁻¹, 10–20 μg dL⁻¹and ≥20 μg dL⁻¹, respectively. The combined WCR was influenced neither by children's age nor place/date of study.ConclusionThe extent of the summer increase in BLLs depends on the BLLs in the colder months.     

Mortalidad en pacientes con demencia que cursaron internación en unidades de cuidados críticos

ObjectiveTo determine the mortality and comorbidities associated of patients with dementia admitted to the Intensive Care Unit (ICU) on the hospitalization and at one year of follow-up.Materials and methodsA retrospective observational cohort study was carried out between 2012 and 2017 at the Hospital Italiano de San Justo, of patients who were admitted to the ICU, these were observed up to hospitalary death, out hospital death one year of hospitalization, the disenrollment from the institution's health plan or the end of the follow-up.ResultsA total of 163 patients were included for analysis. We recorded those 79 patients (48.47%) died one year after the hospitalization, of them 25 (15.34%) in ICU and 8 (4.91%) in general room. The most frequent causes of death were respiratory. The factors most associated with mortality were: orotracheal intubation (HR = 2.01; 95% CI: 1.11-3.65; P = .02), history of leukemia (HR = 8.55; 95% CI: 1.82-40.05; P ≤ .05), elevated Charlson (HR = 1.16, 95% CI: 1.04-1.41; P = .05), and elevated APACHE II at admission (HR = 1.07; 95% CI: 1.03-1.11; P ≤ .05).ConclusionsThe present study expresses the prognosis of patients with a diagnosis of dementia admitted to the ICU and that depends not only on their baseline neurological status but also on the severity at admission and comorbidities.     

Características y resultados tras un año en pacientes ancianos ingresados con insuficiencia cardiaca y fracción de eyección reducida,intermedia o conservada

IntroductionThe latest European Society of Cardiology Heart Failure (HF) guidelines define three types of HF according to the ejection fraction (EF): HF with reduced EF (HFrEF) when EF < 40%, HF with mid-range EF (HFmrEF), when EF 40-49%, and HF with preserved EF (HFpEF) when EF ≥ 50%. The objective of this study was to analyse the characteristics and results of elderly patients hospitalised with HF according to the new classification using EF.MethodsA prospective study was carried out with 531 HF patients aged ≥ 75 years classified according to EF, and admitted in the geriatric wards of 6 hospitals in Spain. An analysis was performed on the demographic and clinical characteristics, as well as well as the morbidity and mortality at one year of follow-up.ResultsAs regards EF, 17.1% had HFrEF, 10% had HFmrEF, and 72.9% had HFpEF. Patients with HFmrEF were more similar to those with HFrEF in terms of a younger age, predominance of men, and previous admission due to HF. This was also the case with the use of drugs for neurohormonal blockade. Patients with HFrEF (compared to those with HFmrEF and HFpEF), had higher mortality (35.2%, 24.5%, and 25.6%, respectively), more readmissions for HF (17.6%, 15.1%, and 14.5%, respectively), and more events (61.5%, 45.3%, and 52.5%, respectively), although there were no significant differences. There were also no differences observed in the survival analysis between the EF groups and the time-dependent outcome variables.ConclusionsIn elderly patients hospitalised with HF, those classified as HFmrEF did not show any clear differences with respect to those with HFrEF or HFpEF. There were no differences in terms of morbidity and mortality.     

Occupation and risk of prostate cancer in Canadian men: A case-control study across eight Canadian provinces

BackgroundThe etiology of prostate cancer continues to be poorly understood, including the role of occupation. Past Canadian studies have not been able to thoroughly examine prostate cancer by occupation with detailed information on individual level factors.MethodsOccupation, industry and prostate cancer were examined using data from the National Enhanced Cancer Surveillance System, a large population-based case-control study conducted across eight Canadian provinces from 1994 to 1997. This analysis included 1737 incident cases and 1803 controls aged 50 to 79 years. Lifetime occupational histories were used to group individuals by occupation and industry employment. Odds ratios and 95% confidence intervals were calculated and adjustments were made for known and possible risk factors.ResultsBy occupation, elevated risks were observed in farming and farm management (OR = 1.37, 95% CI 1.02–1.84), armed forces (OR = 1.33, 95% CI 1.06-1.65) and legal work (OR = 2.58, 95% CI 1.05–6.35). Elevated risks were also observed in office work (OR = 1.20, 95% CI 1.00–1.43) and plumbing (OR = 1.77, 95% CI 1.07–2.93) and with ≥10 years duration of employment. Decreased risks were observed in senior management (OR = 0.65, 95% CI 0.46–0.91), construction management (OR = 0.69, 95% CI 0.50–0.94) and travel work (OR = 0.37, 95% CI 0.16–0.88). Industry results were similar to occupation results, except for an elevated risk in forestry/logging (OR = 1.54, 95% CI 1.06–2.25) and a decreased risk in primary metal products (OR = 0.70, 95% CI 0.51–0.96).ConclusionThis study presents associations between occupation, industry and prostate cancer, while accounting for individual level factors. Further research is needed on potential job-specific exposures and screening behaviours.     

Birth weight and other perinatal factors and childhood CNS tumors: A case–control study in California

AimsWe conducted a large registry-based study in California to investigate the association of perinatal factors and childhood CNS tumors, with analysis by tumor subtype.MethodsWe linked California cancer and birth registries to obtain information on 3308 cases and 3308 controls matched on age and sex. We examined the association of birth weight, gestational age, birth order, parental ages, maternal conditions during pregnancy, newborn abnormalities and the risk of childhood CNS tumors using conditional logistic regression, with adjustment for potential confounders.ResultsThe odds ratio (OR) per 1000 g increase in birth weight was 1.11 (95% CI: 0.99–1.24) for total childhood CNS tumors, 1.17 (95% CI: 0.97–1.42) for astrocytoma and 1.28 (95% CI: 0.90–1.83) for medulloblastoma. Compared to average-for-gestational age, large-for-gestational age infants were at increased risk of glioma (OR = 1.86, 95% CI: 0.99–3.48), while small-for-gestational age infants were at increased risk of ependimoma (OR = 2.64, 95% CI: 1.10–6.30). Increased risk of childhood CNS tumors was observed for 5-year increase in maternal and paternal ages (OR = 1.06, 95% CI: 1.00–1.12 and 1.05, 95% CI: 1.00–1.10 respectively). Increased risk of astrocytoma was detected for 5-year increase in paternal age (OR = 1.08; 95% CI: 1.00–1.16) and increased risk of glioma for maternal age ≥ 35 years old (OR = 1.87; 95% CI: 1.00–3.52). Maternal genital herpes during pregnancy was associated with a pronounced increase in risk of total CNS tumors (OR = 2.74; 95% CI: 1.16–6.51). Other (non-sexually transmitted) infections during pregnancy were associated with decreased risk of total CNS tumors (OR = 0.28, 95% CI: 0.09–0.85). Maternal blood/immune disorders during pregnancy were linked to increased risk of CNS tumors (OR = 2.28, 95% CI: 1.08–4.83) and medulloblastoma (OR = 7.13, 95% CI: 0.82–61.03). Newborn CNS abnormalities were also associated with high risk of childhood CNS tumors (OR = 4.08, 95% CI: 1.13–14.76).ConclusionsOur results suggest that maternal genital herpes, blood and immunological disorders during pregnancy and newborn CNS abnormalities were associated with increased risk of CNS tumors. Maternal infections during pregnancy were associated with decreased risk of CNS tumors. Advanced maternal and paternal ages may be associated with a slightly increased risk of CNS tumors. Factors associated with CNS tumor subtypes varied by subtype, an indicator of different etiology for different subtypes.     

Neoadjuvant chemotherapy with or without oxaliplatin after short-course radiotherapy in high-risk rectal cancer: A subgroup analysis from a prospective study

AimTo evaluate the role of oxaliplatin in neoadjuvant chemotherapy delivered after short-course irradiation.BackgroundUsing oxaliplatin in the above setting is uncertain.Patients and methodsA subgroup of 136 patients managed by short-course radiotherapy and 3 cycles of consolidation chemotherapy within the framework of a randomised study was included in this post-hoc analysis. Sixty-seven patients received FOLFOX4 (oxaliplatin group) while oxaliplatin was omitted in the second period of accrual in 69 patients because of protocol amendment (fluorouracil-only group).ResultsGrade 3+ acute toxicity from neoadjuvant treatment was observed in 30% of patients in the oxaliplatin group vs. 16% in the fluorouracil-only group (p = 0.053). The corresponding proportions of patients having radical surgery or achieving complete pathological response were 72% vs. 77% (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.39–1.98; p = 0.75) and 15% vs. 7% (OR = 2.25; 95% CI: 0.83–6.94; p = 0.16), respectively. The long-term outcomes were similar in the two groups. Overall and disease-free survival rates at 5 years were 63% vs. 56% (p = 0.78) and 49% vs. 44% (p = 0.59), respectively. The corresponding numbers for cumulative incidence of local failure or distant metastases were 33% vs. 38% (hazard ratio [HR] = 0.89; 95% CI: 0.52–1.52; p = 0.68) and 33% vs. 33% (HR = 0.78; 95% CI: 0.43–1.40; p = 0.41), respectively.ConclusionOur findings do not support adding oxaliplatin to three cycles of chemotherapy delivered after short-course irradiation.     

Delirium prevalence in a Colombian hospital,association with geriatric syndromes and complications during hospitalization

BackgroundThe aim of this paper is to describe the prevalence of Delirium and the factors associated with its presentation and complications identified in a geriatric unit in Colombia.Material and methodsThis is a retrospective observational study that included all patients admitted consecutively for two years in a geriatric unit of a hospital in Bogotá, Colombia. We assessed delirium prevalence with the Confusion Assessment Method (CAM). The independent variables were age, sex, functional impairment (Barthel < 90), malnutrition (MNA < 12), pressure ulcers at admission, state of the social support network, number of comorbidities, polypharmacy (5 or more drugs), complications such as ICU requirement, hospital stay, in-hospital functional impairment and mortality were also evaluated. As an exclusion criterion: not having CAM registered in the medical record, all the patients had this information.ResultsWe studied 1599 subjects with a mean age of 86 years (IQR 9). Delirium prevalence was 51.03%. Delirium was associated with a higher rate of: pressure ulcers on admission [OR 3.76 (CI 2.60–5.43 p < 0.001)], functional impairment [OR 2.38 (CI 1.79–3.16 p < 0.001)], malnutrition [OR 2.06 (CI 1.56–2.73 p < 0.001)], and infection [OR 1.46 (CI 1.17–1.82 p < 0.001)]. Moreover delirium has a higher association with mortality [OR 2.80 (1.03–7.54 p = 0.042)], in-hospital functional decline [OR 1.82 (1.41–2.36 p < 0.001)], and longer hospital stay [OR 1.04 (1.04–1.09 p = 0.006)]; independently of age, sex, pressure ulcers on admission, functional impairment, malnutrition, dementia, infection and limited social network.ConclusionOur study suggests that infectious diseases and geriatric syndromes such as, functional dependence, pressure ulcers, malnutrition or major cognitive impairment are independently associated with the presence of delirium on admission. Additionally, the presence of delirium is independently associated during hospitalization with complications, longer hospital stay, functional impairment and mortality.     

Validez predictiva del cuestionario VIDA considerando pérdida funcional,institucionalización o muerte en pacientes pluripatológicos

IntroductionThe VIDA Spanish questionnaire assesses instrumental activities of daily living (IADL) in elderly people, and has shown to have adequate content, construct validity, and reliability.The objective was to analyse its predictive validity in patients with multiple morbidities aged ≥ 65 years without severe/total dependence in basic activities (BADL, Barthel index ≥ 60 points), by measuring any changes in this severe/total level of dependence, institutionalisation, or death at 8 and 18 months of follow-up.MethodsA prospective study of a diagnostic test was conducted on 197 patients (8 months) and 185 (18 months) included in the multiple morbidities program according to stratification by Adjusted Clinical Groups (ACG) or by fulfilling the Ollero criteria. Patients that were institutionalised, at the end of life, or on dialysis, or with a baseline Barthel index ≥ 60 points were excluded. The VIDA questionnaire was applied at baseline. The other baseline variables included age, gender, Charlson index, number of drugs, and Lawton-Brody index.The outcome event was changing the Barthel index to < 60, or institutionalisation, or death, in each follow-up period.ResultsThe median age was 81 years (IQR 74.5-85), and 45.2% were women.At 8 months, the best cut-off point for VIDA was ≤ 31 points (Sensitivity [S] 81.5%, [95% CI; 61.2-93.0]; Specificity (Sp) 58.2% [95% CI; 50.4-65.7], PPV 23.7%; NPV 95.2%), ≤ 30 in women, ≤ 34 in men. And at 18 months, ≤ 29 points (S 61.4 [95% CI; 47.6-73.7]; Sp 76.6 [95% CI; 68.1-83.4]; PPV 53.9; NPV 81.7).ConclusionsOverall cut-off points are provided as well as those for gender, predicting severe/total BADL decline, or institutionalization or death in patients with multiple morbidities. It seems to detect short-term events better and rules them out in the long term.     

Endarterectomy patients with elevated levels of circulating IL-16 have fewer cardiovascular events during follow-up

Background and purposeIncreased interleukin 16 (IL-16) levels in carotid plaques have been associated with reduced incidence of cardiovascular (CV) events during follow-up in patients who underwent carotid endarterectomy (CEA). In the present study we aimed to determine whether high circulating levels of IL-16 also are associated with a decreased risk of CV events after CEA.MethodsPatients, who had their carotid plaques surgically removed (n = 473), were followed for a mean follow-up time of 3.1 years. Plasma levels of IL-16 the day before surgery were analyzed by proximity extension assay (PEA) and associated with the occurrence of CV events during follow-up (n = 98).ResultsHigh levels of circulating IL-16 were independently associated with a decreased risk of CV events when comparing the highest versus the lowest IL-16 tertile (hazard ratio [HR] 0.47; 95% CI 0.27–0.81; P = 0.007), as well as with CV deaths (HR 0.25; 95% CI 0.09–0.70; P = 0.008).ConclusionThese present findings indicate an association between IL-16 and less clinical complications of atherosclerosis in a population with known advanced carotid disease.     

Factores de riesgo de mortalidad en pacientes mayores de 65 años hospitalizados por COVID-19

Background and objectiveCOVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has caused a global pandemic that we are currently suffering from.Objectiveto identify factors associated with the death of patients aged 65 years or older hospitalized for COVID-19.Materials and methodsRetrospective cohort study. We included patients aged 65 years or older who were hospitalized for COVID-19 and dead o discharged between March 5 and 25, 2020. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.Results277 patients were included in this study. The bivariate analysis showed significant differences (p < 0.05) between survivors and non survivors: age, increased dependence and comorbidity, history of ischemic heart disease, renal failure and non-hematological neoplasms, heart failure during admission, leukocytosis, elevated creatinine, PCR, GOT and troponin Ic values, lymphopenia, and decreased blood pH and SatO2. Multivariate logistic regression revealed that age ≥ 65 years (OR: 4.23 (95% CI: 1.43-12.52; p = 0.009), lymphopenia < 1000/μL (OR: 2.36 (95% CI: 1.07-5.20; p = 0.033), creatinine > 1.2 mg/dL (OR: 3.08 (95% CI: 1.37-6.92; p = 0.006), SatO₂ < 90% (OR: 2.29 (95% CI: 1.01-5.21; p = 0.049) and troponin Ic > 11 ng/mL (OR: 2.32 (95% CI: 1.04-5.16; p = 0.040) were independently associated with higher hospital mortality.ConclusionsOlder age, lymphopenia, SatO₂ < 90%, elevated creatinine and troponin Ic values were independently associated with higher mortality in hospitalized patients with COVID-19, these factors could help clinicians to identify patients with poor prognosis.     

Safety of adjuvant intensity-modulated postoperative radiation therapy in endometrial cancer: Clinical data and dosimetric parameters according to the International Commission on Radiation Units (ICRU) 83 report

AimTo report a single-institution experience using postoperative pelvic Intensity Modulation Radiation Therapy (IMRT) using tomotherapy accelerators (TA) in postoperative endometrial cancer (EC) regarding ICRU 83 recommendations.BackgroundIMRT in gynecological malignancies provides excellent dosimetric data, lower rates of adverse events and clinical data similar to historical series.Material and methodsSeventy-six patients with EC were postoperatively treated with adjuvant IMRT using TA. The IMRT dose was 45 Gy for patients without positive lymph nodes and Type I histology and 50.4 Gy for patients with positive lymph nodes and/or type II histology.ResultsWith a median follow-up of 29 months, the 12- and 24-month Overall Survival (OS) and Disease-Free Survival (DFS) were 96%, 93%, 87%, and 74%, respectively. Age of less than 60 years was associated with better OS (HR: 8.9; CI: 1.1–68) and DFS (HR: 3.5; CI: 1.2–10.2). Patients with Type II and Type I Grade III histology had a worse OS (HR: 3.3; CI: 1.1–11). Five women (6.6%) presented in-field local vaginal recurrence, 2 (2.6%) presented non-in-field vaginal recurrence, 4 (5.2%) presented pelvic node and distant recurrence and 11 (14.4%) presented only distant metastases. One patient stopped radiation treatment due to Grade III acute diarrhea. No Grade III late toxicity was observed. Planning Target Volume (PTV) coverage showed mean D2, D50, D95, and D98 of 51.64–46.23 Gy, 49.49–44.97 Gy, 48.62–43.96 Gy, and 48.47–43.58 Gy for patients who received 45 and 50.4 Gy, respectively.ConclusionsIMRT with TA in postoperative EC shows excellent conformity and homogeneity of PTV dose. Without Grade III late toxicity, data from this cohort demonstrated the utility of IMRT.     

Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort – Differential effects by tumour subtype,NAT2 status,BMI and alcohol intake

BackgroundInconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking.MethodsWe used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50–74 and diagnosed with invasive tumours 2001–2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed.ResultsOverall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93–1.64, and HR 1.29, 95% CI 0.95–1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13–2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60–1.98; P_{heterogeneity} = 0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02–3.65, and HR 2.08, 95% CI 1.40–3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22–10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (<25 kg/m²: HR 2.52, 95% CI 1.52–4.15 vs. ≥25 kg/m²: HR 0.94, 95% CI 0.38–2.36; P_{heterogeneity} = 0.04).ConclusionThe harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened.     

Impact of HLA-class I alleles on response to HCV treatment in a cohort of Egyptian patients

Extensive allele diversity is observed in HLA associations with response to HCV combined therapy (pegylated interferon + ribavitin) in different global ethnic populations. The aim of the study is to assess the frequency and association of certain HLA-class I alleles in Egyptian persons with persistent HCV and others with sustained viral response (SVR).Material and methodsThe study was a retrospective cohort study that included 246 HCV patients who received combined therapy; 106 cases responded to treatment (SVR) and 140 individuals did not respond to treatment (persistent HCV infection). Both groups are subjected to genotyping for HLA-class I.ResultsAccording to logistic regression analysis, Cw17 was considered as the most predictor allele as it was the highest significant allele (OR = 16.70; 95% CI: 2.64–105.58; P = 0.003), whereas the presence of the HLA-B45 and HLA-B27 alleles has a 19.35-fold risk and 15.7 fold risk, respectively of non-response to interferon therapy in chronic HCV patients (OR = 19.35; 95% CI: 1.05–357.24; P = 0.04) and (OR = 15.69; 95% CI: 1.179–208.9; P = 0.04) can act also as high predictor alleles, and the lowest significant predictor allele was B44 (OR = 6.535; 95% CI: 1.55–27.63; P = 0.01). The presence of the HLA-A alleles might have a limited role in prediction for the non-responders, as the A32 was significantly higher among the SVR patients, but, it cannot have a predictor role (OR: 0.161, CI: 0.03–1.056, P = 0.049).ConclusionCw17, HLA-B45, and HLA-B27 alleles can predict the nonresponders to HCV combined therapy.     

Patterns of metachronous metastases after curative treatment of colorectal cancer

BackgroundThis study aimed to provide information on timing, anatomical location, and predictors for metachronous metastases of colorectal cancer based on a large consecutive series of non-selected patients.MethodsAll patients operated on with curative intent for colorectal cancer (T_anyN_anyM₀) between 2003 and 2008 in the Dutch Eindhoven Cancer Registry were included (N = 5671). By means of active follow-up by the Cancer Registry staff within ten hospitals, data on development of metastatic disease were collected. Median follow-up was 5.0 years.ResultsOf the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases. Most common affected sites were the liver (60%), lungs (39%), extra-regional lymph nodes (22%), and peritoneum (19%). 86% of all metastases was diagnosed within three years and the median time to diagnosis was 17 months (interquartile range 10–29 months). Male gender (HR = 1.2, 95%CI 1.03–1.32), an advanced primary T-stage (T4 vs. T3 HR = 1.6, 95%CI 1.32–1.90) and N-stage (N1 vs. N0 HR = 2.8, 95%CI 2.42–3.30 and N2 vs. N0 HR = 4.5, 95%CI 3.72–5.42), high-grade tumour differentiation (HR = 1.4, 95%CI 1.17–1.62), and a positive (HR = 2.1, 95%CI 1.68–2.71) and unknown (HR = 1.7, 95%CI 1.34–2.22) resection margin were predictors for metachronous metastases.ConclusionsDifferent patterns of metastatic spread were observed for colon and rectal cancer patients and differences in time to diagnosis were found. Knowledge on these patterns and predictors for metachronous metastases may enhance tailor-made follow-up schemes leading to earlier detection of metastasized disease and increased curative treatment options.     

An updated meta-analysis on the association of TGF-β1 gene promoter -509C/T polymorphism with colorectal cancer risk

AimPublished data on the association between transforming growth factor-β1 (TGF-β1) gene promoter-509C/T polymorphism and colorectal cancer (CRC) risk are inconsistent and inconclusive. To derive a more precise estimation of this association, a meta-analysis was carried out.MethodsMeta-analysis was performed to evaluate reported studies of the relationship between TGF-β1 gene promoter-509C/T polymorphism and colorectal cancer risk using fixed-effects model and random-effects model.ResultsWe observed an increased colorectal cancer risk among subjects carrying TGF-β1 gene promoter-509CC + CT genotype (odds ratio (OR) = 1.18%, 95% confidence interval (95% CI): 1.06–1.32) using 4440/6785 cases/controls in total population. We observed an increased risk of the TGF-β1 gene promoter -509CC, CT and CC + CT polymorphisms for colorectal cancer in population-based study (OR = 1.36, 95% CI: 1.19–1.56, OR = 1.18, 95% CI: 1.03–1.34 and OR = 1.26, 95% CI: 1.12–1.43, respectively) in stratified analysis. We observed an increased colorectal risk among CC and CC + CT carriers in European and American population (OR = 1.22, 95% CI: 1.04–1.43 and OR = 1.18, 95% CI: 1.02–1.38, respectively). We also observed an increased risk of colon cancer among subjects carrying CC + CT genotype (OR = 1.31, 95% CI: 1.05–1.63).ConclusionsThe present meta-analysis results suggest that TGF-β1 gene promoter -509C allele variant is a possible risk factor for developing colorectal cancer. Recommendations for further studies include pooling of individual data to verify results from the study and to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.     

Surveillance of effects of HPV vaccination in Belgium

BackgroundEarly effects of HPV (human papillomavirus) vaccination are reflected by changes observable in young women attending cervical cancer screening.Subject and methodsThe SEHIB study included HPV geno-typing of ∼6000 continuous and 650 pathological cervical cell specimen as well as biopsies, collected from women in Belgium in 2010–2014. Data were linked to vaccination status.ResultsHPV vaccination offered protection among women aged <30 years against infection with HPV16 (vaccine effectiveness [VE] = 67%, 95% CI: 48–79%), HPV18 (VE = 93%, 95% CI: 52–99%), and high-risk HPV (VE = 16%, 95% CI: 2–29%). Vaccination protected also against cytological lesions. Vaccination protected against histologically confirmed lesions: significantly lower absolute risks of CIN1+ (risk difference [RD] = −1.6%, 95% CI: −2.6% to −0.7%) and CIN3+ associated with HPV16/18 (RD = −0.3%, 95% CI −0.6% to −0.1%). Vaccine effectiveness decreased with age. Protection against HPV16 and 18 infection was significant in all age groups, however no protection was observed against cytological lesions associated with these types in age-group 25–29.ConclusionThe SEHIB study demonstrates the effectiveness of HPV vaccination in Belgian young women in particular in age group 18–19. Declining effectiveness with increasing age may be explained by higher tendency of women already exposed to infection to get the vaccine.