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Background: Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma. Methods: This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality. Results: Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82–1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79–1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1. Conclusions: Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden. [ABSTRACT FROM AUTHOR]

It is unclear how increasing body mass index (BMI) influences risk of cancer in young women. We used data from the Medical Birth, Patient and Cause of Death registers collected between 1982 and 2014 to determine the risk of obesity-related cancer types, breast cancer, all cancer and cancer-related death in relation to BMI in 1,386,725 women, aged between 18 and 45 years, in Sweden. During a median follow-up of 16.3 years (IQR 7.7–23.5), 9808 women developed cancer. The hazard ratio (HR) of endometrial and ovarian cancer increased with higher BMI from 1.08 (95% CI 0.93–1.24) and 1.08 (95% CI 0.96–1.21) among women with BMI 22.5–< 25 to 2.33 (95% CI 1.92–2.83) and 1.48 (95% CI 1.24–1.77), respectively, among women with BMI ≥ 30. There were linear and positive associations between BMI and incident cancer in the ovary, colon, endometrium, pancreas, rectum, gallbladder, esophageal cancer and renal cell carcinoma, as well as death from obesity-related cancer forms. In conclusion, we found that elevated BMI in young women linearly associated with several obesity-related cancer forms, including death from these cancers. [ABSTRACT FROM AUTHOR]

Background: Recent research indicates that use of proton pump inhibitors (PPIs) is associated with pneumonia, but existing evidence is inconclusive because of methodological issues. This study aimed to answer whether PPI-use increases risk of pneumonia while taking the methodological concerns of previous research into account. Methods: This population-based and nationwide Swedish study conducted in 2005–2019 used a self-controlled case series design. Data came from national registries for medications, diagnoses, and mortality. Conditional fixed-effect Poisson regression provided incidence rate ratios (IRR) with 95% confidence intervals (CI) for pneumonia comparing PPI-exposed periods with unexposed periods in the same individuals, thus controlling for confounding. Analyses were stratified by PPI-treatment duration, sex, age, and smoking-related diseases. Use of histamine type-2 receptor antagonists (used for the same indications as PPIs) and risk of pneumonia was analysed for assessing the validity and specificity of the results for PPI-therapy and pneumonia. Results: Among 519,152 patients with at least one pneumonia episode during the study period, 307,709 periods of PPI-treatment occurred. PPI-use was followed by an overall 73% increased risk of pneumonia (IRR 1.73, 95% CI 1.71–1.75). The IRRs were increased across strata of PPI-treatment duration, sex, age, and smoking-related disease status. No such strong association was found between histamine type-2 receptor antagonist use and risk of pneumonia (IRR 1.08, 95% CI 1.02–1.14). Conclusions: PPI-use seems to be associated with an increased risk of pneumonia. This finding highlights a need for caution in using PPIs in individuals with a history of pneumonia. [ABSTRACT FROM AUTHOR]

Background: The age-specific risks of mortality for patients with esophagogastric cancer and their probability of surgical treatment are not well-known. Methods: This population-based, nationwide cohort study included all patients with esophageal or gastric (esophagogastric) cancer in Sweden between 1990 and 2013, with follow-up evaluation throughout 2018. Age at diagnosis (exposure) was categorized into nine 5-year groups. The main outcome was 5-year all-cause mortality. The secondary outcomes were 90-day all-cause mortality, 5-year disease-specific mortality, 5-year disease-specific mortality excluding 90-day all-cause mortality, and non-operation. For mortality outcomes, Cox regression provided hazard ratios (HRs) with 95% confidence intervals (95% CIs) adjusted for confounders. For non-operation, logistic regression provided odds ratios (ORs) with 95% CIs. Results: Among 28,725 patients, 11,207 (39.0%) underwent surgery. For those who underwent surgery, the HRs of 5-year all-cause mortality were stable before the ages of 65 to 69 years. After that, it gradually increased for patients 65 to 69 years old (HR, 1.13; 95% CI, 1.01–1.26), patients 75 to 79 years old (HR, 1.29; 95% CI, 1.56–1.44), and patients older than 85 years (HR, 1.84; 95% CI, 1.60–2.11) compared with those younger than 50 years. Analyses of age as a continuous variable, other mortality outcomes and stratification by comorbidity and tumor type showed similar results. The odds of non-operation increased for patients 75 to 79 years old (OR, 2.09 [95% CI, 1.84–2.94] for patients 80 to 84 years old and OR, 5.00 [95% CI, 4.31–5.78] for patients ≥85 years old or older), compared with those younger than 50 years. Conclusion: Older age, starting from 65 years, is associated with worse survival after surgery for esophagogastric cancer, and from 75 years with lower odds of surgical treatment. [ABSTRACT FROM AUTHOR]

Objectives : 2-deoxy-2[18F]Fluoro-d-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival. Methods: Cohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy's and St Thomas' NHS Foundation Trust, London (2017–2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression. Results: Optimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03–0.34; mTR HR 0.17 95% CI 0.06–0.48; pNR HR 0.17 95% CI 0.06–0.54; mNR HR 0.13 95% CI 0.02–0.66). Conclusions: Metabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival. Key Points: • FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer. • Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection. • Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence. [ABSTRACT FROM AUTHOR]

Patients with pancreatic ductal adenocarcinoma (PDAC) commonly develop symptoms and signs in the 1–2 years before diagnosis that can result in changes to medications. We investigate recent medication changes and PDAC diagnosis in Nurses' Health Study (NHS; females) and Health Professionals Follow-up Study (HPFS; males), including up to 148,973 U.S. participants followed for 2,994,057 person-years and 991 incident PDAC cases. Here we show recent initiation of antidiabetic (NHS) or anticoagulant (NHS, HFS) medications and cessation of antihypertensive medications (NHS, HPFS) are associated with pancreatic cancer diagnosis in the next 2 years. Two-year PDAC risk increases as number of relevant medication changes increases (P-trend <1 × 10−5), with participants who recently start antidiabetic and stop antihypertensive medications having multivariable-adjusted hazard ratio of 4.86 (95%CI, 1.74–13.6). These changes are not associated with diagnosis of other digestive system cancers. Recent medication changes should be considered as candidate features in multi-factor risk models for PDAC, though they are not causally implicated in development of PDAC. Pancreatic cancer patients have previously been noted to have a change in medication history prior to diagnosis. Here, the authors utilise two large population cohorts to show associations between recent medication changes and risk of a subsequent pancreatic cancer diagnosis. [ABSTRACT FROM AUTHOR]

Previous studies indicate differences in short-term postoperative outcomes depending on the surgical starting time of the day, but long-term data are lacking. The aim of this study was to clarify if surgical starting time of the day influences long-term survival in gastric cancer patients. This cohort study consecutively included 2728 patients who underwent curatively intended gastrectomy for gastric cancer in 2011–2015 at a high-volume hospital in China, with follow-up until June 2019. Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for 3-year all-cause mortality, adjusted for age, sex, health insurance, pathological tumor stage, surgical approach, neoadjuvant therapy, and weekday of surgery. Compared with patients with early starting time of gastrectomy (08:00–09:29), the point estimates for 3-year all-cause mortality were modestly increased in patients with a starting time in the middle of day (09:30–13:29; HR 1.15, 95% CI 0.97 to 1.37) and later (13:30–21:25; HR 1.10, 0.91 to 1.32). The corresponding HRs were increased particularly in patients who underwent laparoscopic gastrectomy (HR 1.54, 1.10 to 2.14 and HR 1.59, 1.12 to 2.25, respectively) and in those with stage II tumors (HR 1.74, 1.11 to 2.73 and HR 1.60, 1.00 to 2.58, respectively). Our study indicated that in patients who underwent laparoscopic gastrectomy and in those who with stage II tumors, starting surgery in the early morning might be associated with better long-term survival. [ABSTRACT FROM AUTHOR]

Purpose: Due to shared hepatic metabolism, concomitant medication with a proton pump inhibitor (PPI) and clopidogrel might reduce the effectiveness of clopidogrel in the prevention of cardiovascular events after percutaneous coronary intervention (PCI). We aimed to examine the risk of major cardiovascular events after PCI comparing patients who used clopidogrel together with PPI with those who used clopidogrel alone. Methods: This Swedish nationwide cohort study included patients who received clopidogrel after primary PCI in 2005–2019. Patients were followed for up to 12 months after PCI. Data were retrieved from the Swedish Prescribed Drug Registry, Patient Registry, Cancer Registry, and Cause of Death Registry. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events comparing PPI users (exposed) with non-users of PPI (non-exposed). The HRs were adjusted for sex, age, comorbidity, calendar period, obesity, diabetes, anti-diabetic medication, tobacco-related diseases, hypertension, and congestive heart failure. Results: The cohort included 99,836 patients who received clopidogrel after primary PCI. Among these, 35,772 (35.8%) received concomitant PPI. Compared to non-users, PPI users had increased adjusted HRs of all study outcomes, i.e., the main outcome myocardial infarction (HR = 1.23, 95% CI 1.15–1.32) and the secondary outcomes coronary heart disease (HR = 1.28, 95% CI 1.24–1.33), stroke (HR = 1.21, 95% CI 1.05–1.40), and death due to coronary heart disease (HR = 1.52, 95% CI 1.37–1.69). The results were similar in analyses including both primary and secondary PCIs. Conclusions: In patients who receive clopidogrel after PCI, concomitant use of PPI seems to increase the risk of major cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty whether long-term use of proton-pump inhibitors can cause gastric adenocarcinoma (GAC) and oesophageal adenocarcinoma (OAC). This study aimed to determine how discontinuation of long-term PPI therapy influences the risk of GAC and OAC. Methods: This population-based cohort study included all long-term users of PPI therapy in Sweden in 2005–2018 was based on Swedish nationwide health registry data. The exposure was discontinuation of long-term PPI therapy, defined as no dispensation of PPI following inclusion and used as a time-varying variable, compared to remaining on PPI. Main outcomes were GAC and OAC, while oesophageal squamous cell carcinoma (OSCC) was included as a comparison outcome. Incidence rate ratios (IRR) with 95% CI adjusted for age, sex, comorbidity, obesity, diabetes, hyperlipidaemia, NSAIDs/aspirin, and statins were calculated with Poisson regression. Results: Among 730,176 long-term PPI users (mean age 65.6 years, 58.4% females) with 4,210,925 person-years at risk (median 5.5 person-years), 439,390 (60.2%) discontinued PPIs. In total, 495 developed GAC, 598 OAC, and 188 developed OSCC. PPI discontinuation was associated with decreased risk of GAC (IRR 0.81, 95% CI 0.67–0.98) and OAC (IRR 0.80, 95% CI 0.68–0.96), but not OSCC (IRR 1.10, 95% CI 0.82–1.49) compared to continued PPI use. Stratified analyses showed decreased point estimates across most age categories and both sexes for GAC and OAC risk among participants discontinuing PPI therapy. Conclusion: Discontinuation of long-term PPI therapy may decrease the risk of GAC and OAC, suggesting that physicians should consider ceasing prescribing long-term PPI in patients without continued indication for its use. [ABSTRACT FROM AUTHOR]

Background: To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site. Methods: A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed. Results: The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82–1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80–1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39–0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37–0.65). Conclusion: Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Recent research indicates long-term survival benefits of minimally invasive esophagectomy (MIE) compared with open esophagectomy (OE) for patients with esophageal and gastroesophageal junction (GEJ) cancers, but there is a need for more population-based studies. Methods: We conducted a prospective population-based nationwide cohort study including all patients in Sweden diagnosed with esophageal or junctional cancer who underwent a transthoracic esophagectomy with intrathoracic anastomosis. Data were collected from the Swedish National Register for Esophageal and Gastric Cancer in 2006–2019. Patients were grouped into OE and MIE including hybrid MIE (HMIE) and totally MIE (TMIE). Overall survival and short-term postoperative outcomes were compared using Cox regression and logistic regression models, respectively. All models were adjusted for age, sex, American Society of Anesthesiologists (ASA) score, clinical T and N stage, neoadjuvant therapy, year of surgery, and hospital volume. Results: Among 1404 patients, 998 (71.1%) underwent OE and 406 (28.9%) underwent MIE. Compared with OE, overall survival was better following MIE (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.55–0.94), TMIE (HR 0.67, 95% CI 0.47–0.94), and possibly also after HMIE (HR 0.76, 95% CI 0.56–1.02). MIE was associated with shorter operation time, less intraoperative bleeding, higher number of resected lymph nodes, and shorter hospital stay compared with OE. MIE was also associated with fewer overall complications (odds ratio [OR] 0.70, 95% CI 0.47–1.03) as well as non-surgical complications (OR 0.64, 95% CI 0.40–1.00). Conclusions: MIE seems to offer better survival and similar or improved short-term postoperative outcomes in esophageal and GEJ cancers compared with OE in this unselected population-based cohort. [ABSTRACT FROM AUTHOR]

Purpose: Long-lasting symptoms and reductions in quality of life are common after oesophago-gastric surgery. Post-operative follow-up has traditionally focussed on tumour recurrence and survival, but there is a growing need to also identify and treat functional sequelae to improve patients' recovery.Methods: An electronic survey was circulated via a British national charity for patients undergoing oesophago-gastric surgery and their families. Patients were asked about post-operative symptoms they deemed important to their quality of life, as well as satisfaction and preferences for post-operative follow-up. Differences between satisfied and dissatisfied patients with reference to follow-up were assessed.Results: Among 362 respondents with a median follow-up of 58 months since surgery (range 3-412), 36 different symptoms were reported as being important to recovery and quality of life after surgery, with a median of 13 symptoms per patient. Most (84%) respondents indicated satisfaction with follow-up. Satisfied patients were more likely to have received longer follow-up (5-year or longer follow-up 60% among satisfied patients vs 27% among unsatisfied, p < 0.001). These were also less likely to have seen a dietitian as part of routine follow-up (37% vs 58%, p = 0.005).Conclusion: This patient survey highlights preferences regarding follow-up after oesophago-gastrectomy. Longer follow-up and dietician involvement improved patient satisfaction. Patients reported being concerned by a large number of gastrointestinal and non-gastrointestinal symptoms, highlighting the need for multidisciplinary input and a consensus on how to manage the poly-symptomatic patient. [ABSTRACT FROM AUTHOR]

It is unknown whether the survival of patients cured of esophageal cancer differs from that of the corresponding background population. This nationwide and population-based cohort study included all patients who survived for at least 5 years after surgery for esophageal cancer in Sweden between 1987 and 2015, with follow-up throughout 2020. Relative survival rates with 95% confidence intervals (95% CI) were calculated by dividing the observed with the expected survival. The expected survival was assessed from the entire Swedish population of the corresponding age, sex, and calendar year. Yearly relative survival rates were calculated between 6 and 10 years postoperatively. Among all 762 participants, the relative survival was initially similar to the background population (96.1%, 95% CI 94.3–97.9%), but decreased each following postoperative year to 83.5% (95% CI 79.5–87.6%) by year 10. The drop in relative survival between 6 and 10 years was more pronounced in participants with a history of squamous cell carcinoma [from 94.5% (95% CI 91.2–97.8%) to 70.8% (95% CI 64.0–77.6%)] than in those with adenocarcinoma [from 96.9% (95% CI 94.8–99.0%) to 91.5% (95% CI 86.6–96.3%)], and in men [from 96.0% (95% CI 93.8–98.1%) to 81.8% (95% CI 76.8–86.8%)] than in women [from 96.4% (95% CI 93.4–99.5%) to 88.1% (95% CI 81.5–94.8%)]. No major differences were found between age groups. In conclusion, esophageal cancer survivors had a decline in survival between 6 and 10 years after surgery compared with the corresponding general population, particularly those with a history of squamous cell carcinoma of the esophagus and male sex. [ABSTRACT FROM AUTHOR]

Background: Low-dose aspirin use may reduce cancer incidence and mortality, but its influence on gastric adenocarcinoma survival is unclear. This study aimed to assess whether aspirin use improves long-term survival following gastrectomy for gastric adenocarcinoma. Methods: This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden from 2006 to 2015, with follow-up throughout 2020. Preoperative exposure to a daily low-dose (75–160 mg) aspirin for 1 (main exposure), 2 and 3 years and for 1 year after gastrectomy was examined in relation to 5-year all-cause mortality (primary outcome) and disease-specific mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, statin use, tumour location, tumour stage, neoadjuvant chemotherapy, surgeon volume of gastrectomy and surgical radicality. Results: Among 2025 patients, 545 (26.9%) used aspirin at the date of gastrectomy. Aspirin use within 1 year before surgery did not decrease the adjusted risk of 5-year all-cause mortality (HR = 0.98, 95% CI 0.85–1.13) or disease-specific mortality (HR = 1.00, 95% CI 0.86–1.17). Preoperative aspirin use for 2 years (HR = 0.98, 95% CI 0.84–1.15) or 3 years (HR = 0.94, 95% CI 0.79–1.12) did not decrease the risk of 5-year all-cause mortality. Patients remaining on aspirin during the first year after gastrectomy had a similar 5-year all-cause mortality as non-users of aspirin (HR = 1.01, 95% CI 0.82–1.25). Conclusions: Low-dose aspirin use might not improve long-term survival after gastrectomy for gastric adenocarcinoma and may thus not be a target for adjuvant therapy in this group of patients. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta-analysis examined associations between serum levels of haemoglobin A1c (HbA1c) and glucose and the risk of gastric cancer. Methods: MEDLINE, Embase, and Cochrane Library were searched for studies examining associations between serum levels of HbA1c or glucose and the risk of gastric cancer. Inclusion of studies, quality assessment, and data extraction were conducted independently by two authors. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were synthesised using random-effects models. Cochran's Q test and I2 statistic were used to assess heterogeneity. Results: Among 3473 identified studies, 12 were included. Of these, 5 studies examined HbA1c levels and 7 studies examined serum glucose levels. Serum HbA1c levels >6% were associated with an increased risk of gastric cancer (HR 1.36, 95% CI 1.06–1.74). When compared with the lowest glucose categories, the highest glucose categories were associated with a borderline increased risk of gastric cancer (HR 1.11, 95% CI 0.98–1.26). In subgroup analyses, studies that adjusted for Helicobacter pylori infection indicated stronger associations between elevated HbA1c levels and gastric cancer (HR 2.08, 95% CI 1.46–2.98) than those without such adjustment (HR 1.10, 95% CI 0.91–1.32). Conclusions: Long-standing poor glycaemic control may increase the risk of gastric cancer. Registration number: PROSPERO CRD42020157453. [ABSTRACT FROM AUTHOR]

Angiogenesis potentially underlies the pathway between excess adiposity and prostate carcinogenesis. This study examined the association between lifetime body shape trajectories and prostate cancer angiogenesis. 521 prostate cancer patients who underwent prostatectomy or transurethral resection between 1986 and 2000 were enrolled from the Health Professionals Follow-up Study. Cancers were immunostained and quantitated for cancer vessel regularity, diameter, area, and density, and composite angiogenesis (factor analysis). To identify distinct groups of body shape change, we conducted group-based trajectory modeling. We used multivariable linear regression to estimate the percentage difference in angiogenesis score and 95% confidence interval (CI) between body shape change trajectories during lifetime (age 5–60 years), early life (age 5–30 years), or later life (age 30–60 years). Compared to men with lifetime lean or medium body shape, higher angiogenesis scores were observed in men with moderate increase [percentage difference of 35% (95% CI 5–64)], marked increase [24% (95% CI − 2 to 51)], and constantly heavy with mild increase body shape [38% (95% CI 8–69)]. However, a lower angiogenesis score was noted in men with early-life marked increase (− 22%, 95% CI − 44 to 0) and stable medium body shape (− 14%, 95% CI − 40 to 12), compared to moderate increase body shape. Increased angiogenesis was also found for absolute weight gain from age 21–60 years. Lifetime body fatness accumulation, especially after age 21, was associated with increased prostate cancer angiogenesis, while weight gain in early-life adulthood was associated with lower cancer angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Oesophageal adenocarcinoma is characterised by a strong male predominance. We aimed to test the hypothesis that menopausal hormonal therapy decreases the risk of oesophageal adenocarcinoma.Methods: This population-based cohort study included all women who used systemic menopausal hormonal therapy (exposed) in Sweden between 2005 and 2018. For each exposed participant, five randomly selected female age-matched non-users of menopausal hormonal therapy (unexposed) were included. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking-related diagnoses, Helicobacter pylori eradication, use of non-steroidal anti-inflammatory drugs/aspirin, use of statins and hysterectomy.Results: The study included 296,964 users of menopausal hormonal therapy and 1,484,820 non-users. Ever-users of menopausal hormonal therapy had an overall decreased risk of oesophageal adenocarcinoma (HR 0.78, 95% CI 0.63-0.97), which remained unchanged after further adjustment for gastro-oesophageal reflux disease (HR 0.78, 95% CI 0.63-0.97) and obesity/diabetes (HR 0.79, 95% CI 0.63-0.98). Decreased HRs were indicated both in users of oestrogen only (HR 0.82, 95% CI 0.60-1.12) and oestrogen combined with progestogen (HR 0.75, 95% CI 0.56-1.00). The risk reduction was more pronounced in users younger than 60 years (HR 0.57, 95% CI 0.38-0.86).Conclusions: Menopausal hormone therapy in women may decrease the risk of oesophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Metformin may improve the prognosis in gastric adenocarcinoma, but the existing literature is limited and contradictory.Methods: This was a Swedish population-based cohort study of diabetes patients who were diagnosed with gastric adenocarcinoma in 2005-2018 and followed up until December 2019. The data were retrieved from four national health data registries: Prescribed Drug Registry, Cancer Registry, Patient Registry and Cause of Death Registry. Associations between metformin use before the gastric adenocarcinoma diagnosis and the risk of disease-specific and all-cause mortality were assessed using multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for sex, age, calendar year, comorbidity, use of non-steroidal anti-inflammatory drugs or aspirin, and use of statins.Results: Compared with non-users, metformin users had a decreased risk of disease-specific mortality (HR 0.79, 95% CI 0.67-0.93) and all-cause mortality (HR 0.78, 95% CI 0.68-0.90). The associations were seemingly stronger among patients of female sex (HR 0.66, 95% CI 0.49-0.89), patients with tumour stage III or IV (HR 0.71, 95% CI 0.58-0.88), and those with the least comorbidity (HR 0.71, 95% CI 0.57-0.89).Conclusions: Metformin use may improve survival in gastric adenocarcinoma among diabetes patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the male predominance in esophageal and gastric adenocarcinoma by evaluating the preventive potential of androgen deprivation therapy (ADT). This matched cohort study was based on a national Swedish database of prostate cancer patients in 2006–2013. Prostate cancer patients receiving ADT were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for confounders. There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24–0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60–2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40–2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31–3.13]). This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Esophagectomy for esophageal cancer is associated with a substantial risk of life-threatening complications and a limited long-term survival. This study aimed to clarify the controversial questions of how age influences short-term and long-term survival. Methods: This population-based cohort study included almost all patients who underwent curatively intended esophagectomy for esophageal cancer in Sweden in 1987–2010, with follow-up through 2016. The exposure was age, analyzed both as a continuous and categorical variable. The probability of mortality was computed using a novel flexible parametric model approach. The reported probabilities are proper measures of the risk of dying, and the related odds ratios (OR) are therefore more suitable measures of association than hazard ratios. The outcomes were 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality. A novel flexible parametric model was used to derive the instantaneous probability of dying and the related OR along with 95% confidence intervals (CIs), adjusted for sex, education, comorbidity, tumor histology, pathological tumor stage, and resection margin status. Results: Among 1737 included patients, the median age was 65.6 years. When analyzed as a continuous variable, older age was associated with slightly higher odds of 90-day all-cause mortality (OR 1.05, 95% CI 1.02–1.07), 5-year all-cause mortality (OR 1.02, 95% CI 1.01–1.03), and 5-year disease-specific mortality (OR 1.01, 95% CI 1.01–1.02). Compared with patients aged < 70 years, those aged 70–74 years had no increased risk of any mortality outcome, while patients aged ≥ 75 years had higher odds of 90-day mortality (OR 2.85, 95% CI 1.68–4.84), 5-year all-cause mortality (OR 1.56, 95% CI 1.27–1.92), and 5-year disease-specific mortality (OR 1.38, 95% CI 1.09–1.76). Conclusions: Patient age 75 years or older at esophagectomy for esophageal cancer appears to be an independent risk factor for higher short-term mortality and lower long-term survival. [ABSTRACT FROM AUTHOR]

Purpose: Obesity increases the risk of several cancers, but the influence of bariatric surgery on the risk of individual obesity-related cancers is unclear. This study aimed to assess the impact of bariatric surgery on cancer risk in a multi-national setting. Materials and Methods: This cohort study included all adults with an obesity diagnosis identified from national patient registries in all Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) from 1980 to 2012. Cancer risk in bariatric surgery patients was compared with non-operated patients with obesity. Multivariable Cox regression provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Age, sex, calendar year, country, length of follow-up, diabetes, chronic obstructive pulmonary disease and alcohol-related diseases were evaluated as confounders. Results: Among 482,572 participants with obesity, 49,096 underwent bariatric surgery. Bariatric surgery was followed by a decreased overall cancer risk in women (HR 0.86, 95% CI 0.80–0.92), but not in men (HR 0.98, 95% CI 0.95–1.01). The risk reduction was observed only within the first five post-operative years. Among specific tumours, HRs decreased for breast cancer (HR 0.81, 95% CI 0.69–0.95), endometrial cancer (HR 0.69, 95% CI 0.56–0.84) and non-Hodgkin lymphoma (HR 0.64, 95% CI 0.42–0.97) in female bariatric surgery patients, while the risk of kidney cancer increased in both sexes (HR 1.44, 95% CI 1.13–1.84). Conclusion: Bariatric surgery may decrease overall cancer risk in women within the first five years after surgery. This decrease may be explained by a decreased risk of breast and endometrial cancer and non-Hodgkin lymphoma in women. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer surgery reduces patients' health-related quality of life (HRQoL). This study examined whether comorbidities influence HRQoL in these patients. Methods: This prospective cohort study included esophageal cancer patients having undergone curatively intended esophagectomy at St Thomas' Hospital London in 2011–2015. Clinical data were collected from patient reports and medical records. Well-validated cancer-specific and esophageal cancer-specific questionnaires (EORTC QLQ-C30 and QLQ-OG25) were used to assess HRQoL before and 6 months after esophagectomy. Number of comorbidities, American Society of Anesthesiologists physical status classification (ASA), and specific comorbidities were analyzed in relation to HRQoL aspects using multivariable linear regression models. Mean score differences with 95% confidence intervals were adjusted for potential confounders. Results: Among 136 patients, those with three or more comorbidities at the time of surgery had poorer global quality of life and physical function and more fatigue compared with those with no comorbidity. Patients with ASA III–IV reported more problems with the above HRQoL aspects and worse social function and pain compared with those with ASA I–II. Cardiac comorbidity was associated with worse global quality of life and dyspnea, while pulmonary comorbidities were related to coughing. Patients assessed both before and 6 months after surgery (n = 80) deteriorated in most HRQoL aspects regardless of comorbidity status, but patients with several comorbidities had worse physical function and fatigue and more trouble with coughing compared with those with fewer comorbidities. Conclusion: Comorbidity appears to negatively influence HRQoL before esophagectomy, but appears not to severely impact 6-month recovery of HRQoL. [ABSTRACT FROM AUTHOR]

Esophagectomy is the mainstay of curative treatment for most patients with a diagnosis of esophageal cancer. This procedure needs to be optimized to secure the best possible chance of cure for these patients. Research comparing various surgical approaches of esophagectomy generally has failed to identify any major differences in long-term prognosis. Comparisons between minimally invasive and open esophagectomy, transthoracic and transhiatal approaches, radical and moderate lymphadenectomy, and high and moderate hospital volume generally have provided only moderate alterations in long-term survival rates after adjustment for established prognostic factors. In contrast, some direct surgeon-related factors, which remain independent of known prognostic factors, seem to influence the long-term survival more strongly in esophageal cancer. Annual surgeon volume is strongly prognostic, and recent studies have suggested the existence of long surgeon proficiency gain curves for achievement of stable 5-year survival rates and possibly also a prognostic influence of surgeon age and weekday of surgery. The available literature indicates a potentially more critical role of the individual surgeon's skills than that of variations in surgical approach for optimizing the long-term survival after esophagectomy for esophageal cancer. This finding points to the value of paying more attention to how the skills of the individual esophageal cancer surgeon can best be achieved and maintained. Careful selection and evaluation of the most suitable candidates, appropriate and structured training programs, and regular peer-review assessments of experienced surgeons may be helpful in this respect. [ABSTRACT FROM AUTHOR]

Background: Whether or not the use of metformin decreases the risk of gastric adenocarcinoma is unclear.Methods: This was a population-based cohort study in 2005-2015. Associations between metformin use and gastric non-cardia and cardia adenocarcinomas were examined within two cohorts; a diabetes cohort of participants using anti-diabetes medications, and a matched cohort of common-medication users, where metformin non-users were frequency matched (10:1) with metformin users for sex and age. Multivariable Cox proportional hazard regression analyses provided hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs or aspirin and use of statins.Results: During the follow-up for a median of 5.8 years, 892 (0.1%) participants in the diabetes cohort and 6395 (0.1%) participants in the matched cohort of common-medication users developed gastric adenocarcinoma. Metformin users had no significantly decreased risk of gastric non-cardia adenocarcinoma (diabetes cohort: HR 0.93, 95% CI 0.78-1.12; matched cohort: HR 1.30, 95% CI 1.18-1.42) or cardia adenocarcinoma (diabetes cohort: HR 1.49, 95% CI 1.09-2.02; matched cohort: HR 1.58, 95% CI 1.38-1.81) compared with non-users in both cohorts.Conclusions: This cohort study with <10 years of follow-up suggests metformin use may not prevent gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Individuals with Barrett's esophagus (BE) are at increased risk of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC), but the cost-effectiveness of general surveillance of BE is low. This study aimed to identify a risk prediction model for tumor progression in individuals with BE based on age, sex, and risk factors found at upper endoscopy, enabling tailored surveillance.Methods: This nested case-control study originated from a cohort of 8171 adults diagnosed with BE in 2006-2013 in the Swedish Patient Registry. Cases had EAC/HGD (n = 279) as identified from the Swedish Cancer Registry, whereas controls had no EAC/HGD (n = 1089). Findings from endoscopy and histopathology reports were extracted from medical records at 71 Swedish hospitals and from the Swedish Patient Registry. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CIs).Results: Older age (OR 1.02 [95% CI 1.01-1.03] per year), male sex (OR 2.8 [95% CI 1.9-4.1]), and increasing maximum BE length (OR 2.3 [95% CI 1.4-3.9] for segments 3-8 cm and OR 4.3 [95% CI 2.5-7.2] for segments ≥ 8 cm) increased the risk of EAC/HGD, while the circumferential extent of the BE, hiatal hernia or reflux esophagitis did not. A model based on age, sex, and maximum BE length predicted 71% of all EAC/HGD cases.Conclusions: A simple combination of the variables age, sex and maximum BE length showed fairly good accuracy for predicting tumor progression in BE. This clinical risk prediction model may help to tailor future surveillance programs. [ABSTRACT FROM AUTHOR]

Background: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear.Methods: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level.Results: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79-1.44), diabetes (HR 0.77, 95% CI 0.46-1.29) or any of these exposures (HR 0.96, 95% CI 0.73-1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma.Conclusions: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Surgery proficiency gain curves must be shortened to reduce patient harm during esophagectomy learning.Objective: This study aimed to test whether surgeon volume and surgeon age influenced the length of period of surgical proficiency gain. Methods: This population-based cohort study included 1384 patients with esophageal cancer who underwent esophagectomy by any of the 36 highest-volume surgeons in Sweden between 1987 and 2010, with follow-up until 2016. Annual surgeon volume was dichotomized by the median values into 'higher-volume surgeons' (≥ 4 cases per year) and 'lower-volume surgeons' (< 4 cases per year), and surgeon age at the start of practicing esophagectomies into 'younger surgeons' (aged < 45 years) and 'older surgeons' (aged ≥ 45 years). Proficiency gain curves were constructed using risk-adjusted cumulative sum analysis for 1- to 5-year mortality (main outcome) and secondary outcomes (presented below). The results were adjusted for all established prognostic factors.Results: For 1- to 5-year mortality, the change point was at 14 cases among 'higher-volume surgeons', while 'lower-volume surgeons' had a later change point at 31 cases. The corresponding change points were at 13 cases among 'younger surgeons' and at 48 cases among 'older surgeons'. Similar patterns of differences in the proficiency gain curves were seen for the secondary outcomes of 30-day mortality and resection margin status (tumor involvement).Conclusion: Higher-volume- and younger surgeons seem to have a substantially shorter period of proficiency gain for long-term mortality and other outcomes following surgery for esophageal cancer. This indicates a value of intensified training of younger surgeons for these complex operations. [ABSTRACT FROM AUTHOR]

Background. Gastric adenocarcinoma is the second most common cancer-related death globally. Assessing survival trends can help evaluate changes in detection and treatment. We aimed to determine recent prognosis trends in gastric non-cardia and cardia adenocarcinoma in an unselected cohort with complete follow-up. Methods. Population-based nationwide cohort study, including 17,491 patients with gastric non-cardia adenocarcinoma and 4698 with cardia adenocarcinoma recorded in the Swedish Cancer Registry in 1990–2013 with followup until 2017. Observed and relative 5-year survival was calculated and stratified by resectional surgery and no such surgery. Prognostic factors were evaluated using multivariable Cox regression. Results. The relative overall 5-year survival remained stable at 18% for gastric non-cardia adenocarcinoma throughout the study period and increased from 12 to 18% for cardia adenocarcinoma. Concurrently, the proportion of patients who underwent resectional surgery decreased from 49 to 38% for non-cardia adenocarcinoma and from 48 to 33% for cardia adenocarcinoma. The relative postoperative 5-year survival increased from 33 to 44% for non-cardia adenocarcinoma and from 21 to 43% for cardia adenocarcinoma, whereas in nonoperated patients it decreased from 3 to 2% in non-cardia adenocarcinoma and increased from 3 to 5% in cardia adenocarcinoma. Poor prognostic factors were higher tumor stage, older age, and more comorbidity. Conclusions. Despite decreasing resectional rates, the 5-year overall survival has remained unchanged for gastric non-cardia adenocarcinoma and improved for cardia adenocarcinoma over the last two decades in Sweden and is now similar for these sublocations. The postoperative survival has improved for both sublocations, but particularly for cardia adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Randomized clinical trials (RCTs) can provide a high level of evidence for medical decision making, but it is unclear if the results apply to patients treated outside such trials.Objective: The aim of this study was to retrospectively compare outcomes of patients with esophageal cancer treated within and outside an RCT. Methods: All patients receiving neoadjuvant chemoradiotherapy (nCRT) plus surgery for esophageal cancer between 2002 and 2008 (ChemoRadiotherapy for Esophageal cancer followed by Surgery Study [CROSS] cohort) who participated in multicenter, phase II-III trials were compared with patients who underwent the same treatment outside the trial between 2008 and 2013 (post-CROSS cohort). The differences between these cohorts were analyzed using t tests, while logistic regression models were used to evaluate adverse events. Overall and disease-free survival were calculated using the Kaplan-Meier method and Cox regression analyses.Results: A total of 208 CROSS patients and 173 post-CROSS patients were included in this study. Patients from the post-CROSS cohort were older, had more co morbidities, and had poorer performance status. Clinical N stage, but not cT stage, was worse in the post-CROSS cohort. There were no statistically significant differences in adverse events (pulmonary, cardiac, or anastomotic complications) or survival between the comparison cohorts.Conclusion: The outcomes of patients treated with nCRT plus esophagectomy for cancer have a high external consistency and can be extrapolated to the daily practice of physicians involved in the treatment and care of esophageal cancer patients. [ABSTRACT FROM AUTHOR]

Background: The postoperative health-related quality of life (HRQOL) outcomes in patients with gastroesophageal junction (GEJ) adenocarcinoma after gastrectomy and esophagectomy are unclear. The aim was to evaluate HRQOL outcomes 6 months after extended total gastrectomy, subtotal esophagectomy, and combined esophagogastrectomy.Methods: Patients who underwent surgery for GEJ adenocarcinoma of Siewert type 2 or 3 in 2001-2005 were identified from a nationwide Swedish prospective and population-based cohort. Three surgical strategies, i.e., gastrectomy, esophagectomy, or esophagogastrectomy, were analyzed in relationship to HRQOL measured at 6 months after surgery (main outcome). HRQOL was assessed using well-validated questionnaires for general (EORTC QLQ-C30) and esophageal cancer-specific (EORTC QLQ-OES18) symptoms. Mean score differences (MSD) and 95% confidence intervals (CI) were analyzed using ANCOVA and adjusted for age, sex, tumor stage, comorbidity, education level, hospital volume, and postoperative complications. MSDs > 10 were regarded as clinically relevant.Results: Among 176 patients with complete information on HRQOL and covariates, none of the MSDs for HRQOL among the three surgery groups were clinically and statistically significant. MSDs comparing esophagectomy and gastrectomy showed no major differences in global quality of life (MSD, +8, 95% CI, 0 to +16), physical function (MSD, +2, 95% CI, −5 to +9), pain (MSD, −3, 95% CI, −12 to +7), or reflux (MSD, +5, 95% CI, −4 to +14). Also, complication rates and 5-year survival rates were similar comparing esophagectomy and gastrectomy.Conclusions: Extended total gastrectomy, subtotal esophagectomy, and combined esophagogastrectomy seemed to yield similar 6-month postoperative HRQOL outcomes for patients with GEJ adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Population-based studies comparing minimally invasive esophagectomy (MIE) and open esophagectomy (OE) relative to 90-day postoperative mortality are needed. Objective: The aim of this study was to compare short-term outcomes following these two techniques for esophageal cancer. Methods: Patients undergoing MIE ( n = 217) or OE ( n = 1397) for esophageal cancer between 2007 and 2014 were identified from nationwide complete registries in Finland and Sweden. The primary outcome was 90-day mortality, and secondary outcomes were 30-day mortality, length of hospital stay, and 30- and 90-day readmission rate. Results were adjusted for age, sex, comorbidity, tumor histology, surgery year, and country. Results: Ninety-day mortality rates were 4.1% ( n = 9 of 217) for MIE and 6.8% ( n = 95 of 1397) for OE; 90-day mortality was halved after MIE [adjusted hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.24-0.99]. There was no difference in 30-day mortality (adjusted HR 0.87, 95% CI 0.29-2.66). Median hospital stay was 15 days for MIE and 16 days for OE (adjusted β −0.17, standard error 0.08, p = 0.030). The 30-day readmission rates were 8.9% after MIE and 12.0% after OE (adjusted HR 0.57, 95% CI 0.34-0.94), while the 90-day readmission rates were 28.8% and 33.6%, respectively, without a statistically significant difference (adjusted HR 0.82, 95% CI 0.61-1.10). Conclusions: This population-based study from Finland and Sweden revealed lower 90-day mortality, shorter hospital stay, and lower 30-day readmission rates after MIE compared with OE for esophageal cancer. These findings support the use of minimally invasive approaches. [ABSTRACT FROM AUTHOR]

Background: Obesity surgery involves mechanical and physiological changes of the gastrointestinal tract that might promote colorectal cancer progression. Thus, we hypothesised that obesity surgery is associated with poorer prognosis in patients with colorectal cancer. Methods: This nationwide population-based cohort study included all patients with an obesity diagnosis who subsequently developed colorectal cancer in Sweden from 1980 to 2012. The exposure was obesity surgery, and the main and secondary outcomes were disease-specific mortality and all-cause mortality, respectively. Cox proportional hazard survival models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for sex, age, calendar year and education level. Results: The exposed and unexposed cohort included 131 obesity surgery and 1332 non-obesity surgery patients with colorectal cancer. There was a statistically significant increased rate of colorectal cancer deaths following obesity surgery (disease-specific HR 1.50, 95% CI 1.00-2.19). When analysed separately, the mortality rate was more than threefold increased in rectal cancer patients with prior obesity surgery (disease-specific HR 3.70, 95% CI 2.00-6.90), while no increased mortality rate was found in colon cancer patients (disease-specific HR 1.10, 85% CI 0.67-1.70). Conclusion: This population-based study among obese individuals found a poorer prognosis in colorectal cancer following obesity surgery, which was primarily driven by the higher mortality rate in rectal cancer. [ABSTRACT FROM AUTHOR]

Dear Editor, We are grateful for the interest in our study examining how discontinuation of long-term use of a proton-pump inhibitor (PPI) influences risk of developing gastric and oesophageal adenocarcinoma. We agree that the biological mechanisms linking PPI use with an increased risk of oesophageal adenocarcinoma is more farfetched than that for gastric adenocarcinoma, and that confounding by indication in particular is a concern in observational research. [Extracted from the article]

Background: Esophageal cancer has a poor prognosis, and many patients undergoing surgery have a low chance of cure. Imaging studies suggest that tumor volume is prognostic. The study aimed to evaluate pathological tumor volume (PTV) as a prognostic variable in esophageal cancer. Methods: This single-center cohort study included 283 patients who underwent esophageal cancer resections between 2000 and 2012. PTVs were obtained from pathological measurements using a validated volume formula. The prognostic value of PTV was analyzed using multivariable regression models, adjusting for age, tumor grade, tumor (T) stage, nodal stage, lymphovascular invasion, resection margin, resection type, and chemotherapy response, which provided hazard ratios (HRs) with 95 % confidence intervals (CIs). Primary outcomes were time to death and time to recurrence. Secondary outcomes were margin involvement and lymph node positivity. Correlation analysis was performed between imaging and PTVs. Results: On unadjusted analysis, increasing PTV was associated with worse overall mortality (HR 2.30, 95 % CI 1.41-3.73) and disease recurrence (HR 1.87, 95 % CI 1.14-3.07). Adjusted analysis demonstrated worse overall mortality with increasing PTV but reached significance in only one subgroup (HR 1.70, 95 % CI 1.09-2.38). PTV was an independent predictor of margin involvement (OR 2.28, 95 % CI 1.02-5.13) and lymph node-positive status (OR 2.77, 95 % CI 1.23-6.28). Correlation analyses demonstrated significant positive correlation between computed tomography (CT) software and formula tumor volumes ( r = 0.927, p < 0.0001), CT and positron emission tomography tumor volumes ( r = 0.547, p < 0.0001), and CT and PTVs ( r = 0.310, p < 0.001). Conclusions: Tumor volume may predict survival, margin status, and lymph node positivity after surgery for esophageal cancer. [ABSTRACT FROM AUTHOR]

Background and Aim: Swedish health registries are common sources of data for studies on the effects of obesity surgery, and there is a need to assess the quality of data in these registries. The aim of this study was to validate the registration of obesity surgery in the National Patient Registry (NPR) and the Scandinavian Obesity Surgery Registry (SOReg). Method: We randomly selected 962 out of 8501 registrations of obesity surgery in 2011 from the NPR and SOReg. Registered surgical procedures in the NPR and SOReg were compared to the medical records, and concordance was analyzed by calculating positive predictive value (PPV) with 95 % confidence interval (CI). Results: We received 938 (98 %) medical records for manual review. The overall PPV for obesity surgery was high in the NPR (PPV 97.0; 95 % CI 95.6-98.4) and even higher in SOReg (PPV 99.7; 95 % CI 99.3-100). Accuracy was higher for gastric bypass surgery than for other types of obesity surgery. Registrations that were misclassified as obesity surgery ( n = 44) included reoperations due to complications or reconstruction to normal anatomy after previous obesity surgery ( n = 11) and endoscopic procedures ( n = 10). Conclusion: Obesity surgery registrations in the NPR and SOReg have high accuracy and are reliable sources of data to identify patients having undergone obesity surgery. When it is of importance to distinguish between specific surgical procedures, non-gastric bypass surgeries in the NPR should ideally be supplemented with data from other sources. [ABSTRACT FROM AUTHOR]

Purpose: This project sought to test the role of diet-related inflammation in modulating the risk of oesophageal cancer. Methods: A nationwide population-based case-control study was conducted from 1 December 1994 through 31 December 1997 in Sweden. All newly diagnosed patients with adenocarcinoma of the oesophagus or gastroesophageal junction and a randomly selected half of patients with oesophageal squamous cell carcinoma were eligible as cases. Using the Swedish Registry of the Total Population, the control group was randomly selected from the entire Swedish population and frequency-matched on age (within 10 years) and sex. The literature-derived dietary inflammatory index (DII) was developed to describe the inflammatory potential of diet. DII scores were computed based on a food frequency questionnaire. Higher DII scores indicate more pro-inflammatory diets. Odds ratios and 95 % confidence intervals (CI) were computed to assess risk associated between DII scores and oesophageal cancer using logistic regression adjusted by potential confounders. Results: In total, 189 oesophageal adenocarcinomas, 262 gastroesophageal junctional adenocarcinomas, 167 oesophageal squamous cell carcinomas, and 820 control subjects were recruited into the study. Significant associations with DII were observed for oesophageal squamous cell carcinoma (OR 4.35, 95 % CI 2.24, 8.43), oesophageal adenocarcinoma (OR 3.59, 95 % CI 1.87, 6.89), and gastroesophageal junctional adenocarcinoma (OR 2.04, 95 % CI 1.24, 3.36). Significant trends across quartiles of DII were observed for all subtypes of oesophageal cancer. Conclusions: Diet-related inflammation appears to be associated with an increased risk of oesophageal cancer, regardless of histological type. [ABSTRACT FROM AUTHOR]

Background: Associations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels.Methods: A nested case-control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders.Results: Among 1,574,768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (⩾4 mmol mol(-1) compared with <0 mmol mol(-1)) were followed by an increased OR of pancreatic cancer (OR, 2.16, 95% CI 1.72-2.72 and OR, 5.06, 95% CI 1.52-16.87, respectively). Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55-56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85-2.52), compared with no use of any anti-diabetic medications.Conclusions: New-onset type 2 diabetes and, particularly, diabetes with rising HbA1c seem to be independent risk factors for pancreatic cancer. The relation between different anti-diabetic medications and pancreatic cancer seems to vary in strength, with the highest risk among users of insulin. [ABSTRACT FROM AUTHOR]

Background: The role of the metabolic syndrome in the etiology of esophageal and gastric cancer is unclear.Methods: This was a large nationwide cohort study based on data from 11 prospective population-based cohorts in Norway with long-term follow-up, the Cohort of Norway (CONOR) and the third Nord-Trøndelag Health Study (HUNT3). The metabolic syndrome was assessed by objective anthropometric and metabolic biochemical measures and was defined by the presence of at least three of the following five factors: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, hypertension and high glucose. Newly diagnosed cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma and gastric adenocarcinoma were identified from the Norwegian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders.Result: Among 192,903 participants followed up for an average of 10.6 years, 62 developed esophageal adenocarcinoma, 64 had esophageal squamous-cell carcinoma and 373 had gastric adenocarcinoma. The metabolic syndrome was significantly associated with an increased risk of gastric adenocarcinoma (HR 1.44, 95% CI 1.14-1.82), but not associated with esophageal adenocarcinoma (HR 1.32, 95% CI 0.77-2.26) or esophageal squamous-cell carcinoma (HR 1.08, 95% CI 0.64-1.83). Increased waist circumference was associated with an increased HR of esophageal adenocarcinoma (HR 2.48, 95% CI 1.27-4.85). No significant association was found between any single component of the metabolic syndrome and risk of esophageal squamous-cell carcinoma. High waist circumference (HR 1.71, 95% CI 1.05-2.80), hypertension (HR 2.41, 95% CI 1.44-4.03) and non-fasting glucose (HR 1.74, 95% CI 1.18-2.56) were also related to an increased risk of gastric adenocarcinoma in women, but not in men.Conclusion: Metabolic syndrome was associated with an increased risk of gastric adenocarcinoma in women. Of the individual components of the metabolic syndrome, high waist circumference was positively associated with risk of esophageal adenocarcinoma. Positive associations were also observed for women between high waist circumference, hypertension, high non-fasting glucose and risk of gastric adenocarcinoma. However, further evidence is warranted due to the limited number of cases and the inability to effectively identify gastric cardia adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Postoperative mortality is traditionally defined as death within 30 days of surgery. We hypothesised that the declining 30-day mortality after oesophageal cancer resection is, at least partly, explained by a shift towards increased 90-day mortality. Methods: This population-based cohort study included 95 % of all patients who underwent surgical resection for oesophageal cancer in Sweden in 1987-2010. Cox proportional-hazards regression models were used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) of 30-day and 31-90 days postoperative mortality in three calendar periods (1987-1994, 1995-2002, and 2003-2010). Adjustments were made for age, sex, comorbidity, tumour stage, tumour histology, surgical radicality, neoadjuvant therapy, and hospital volume of oesophagectomy. Results: Among 1,822 patients, the 30-day postoperative mortality decreased from 9.3 % in 1987-1994 to 3.0 % in 2003-2010, while the corresponding 31-90 days mortality decreased from 8.4 to 4.6 %. The adjusted HR of 30-day mortality in the earliest period was markedly increased compared to the latest period (HR 3.26; 95 % CI 1.96-5.45), whereas the corresponding HR of 31-90 days mortality was weaker (HR 2.16; 95 % CI 1.34-3.46). Among patients who died within 90 days of surgery, the proportion of 31-90 days mortality increased from 47 to 61 % during the study period. Conclusions: This population-based study indicates a shift of postoperative mortality following surgery for oesophageal cancer from 30 days to 31-90 days with more recent calendar periods. Reporting of 90-day mortality rates might replace 30-day mortality rates in assessing early postoperative mortality in oesophageal cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about cancer incidence among patients with a history of suicide attempt. Suicide attempters have lower levels of oxytocin, a hormone related to lactation, stress, social functioning, and well-being, and recent research indicates influence on carcinogenesis. We hypothesized that the low oxytocin levels among suicide attempters results in an increased risk of cancer in general and in organs with oxytocin receptors in particular. Methods: A nationwide cohort study of patients aged 15 years or older with hospitalization for self-inflicted injury or attempted suicide was identified from the Swedish patient register in 1968-2011. The cancer outcomes were identified from the Swedish cancer register. Cancer risk in suicide attempters was compared with the risk in the background population of the corresponding age, sex, and calendar period by calculating standardized incidence ratios (SIRs) with 95 % confidence intervals (95 % CI). Results: The 186,627 patients (83,637 men and 102,990 women) hospitalized for self-inflicted injury or attempted suicide contributed with 2.6 million person-years at risk. The SIR for all cancer was 1.3 (95 % CI 1.27-1.33) in men and 1.25 (1.22-1.28) in women. For cancers in organs rich in oxytocin receptors (uterus, breast, and brain), the corresponding SIRs were 1.02 (0.87-1.19) and 1.13 (1.09-1.17), respectively. There was a particularly increased risk of cancers related to alcohol and tobacco in both sexes. Conclusion: Patients attempting suicide have an increased risk of cancer. However, this increase does not seem to be associated with low oxytocin levels, but rather to exposures like tobacco smoking and alcohol consumption. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Tobacco smoking increases the risk of gastroesophageal reflux symptoms (GERS), but whether tobacco smoking cessation improves GERS is unclear. The aim of this study was to clarify if tobacco smoking cessation improves GERS.METHODS:The study was based on the Nord-Trøndelag health study (the HUNT study), a prospective population-based cohort study conducted from 1995-1997 to 2006-2009 in Nord-Trøndelag County, Norway. All residents of the county from 20 years of age were invited. The study included 29,610 individuals (61% response rate) who reported whether they had heartburn or acid regurgitation. The association between tobacco smoking cessation and improvement in GERS was assessed by logistic regression, providing odds ratios (ORs) with 95% confidence intervals (CIs). The analyses were stratified by antireflux medication, and the results were adjusted for sex, age, body mass index (BMI), alcohol consumption, education, and physical exercise. Subgroup analyses were also stratified by BMI.RESULTS:Among individuals using antireflux medication at least weekly, cessation of daily tobacco smoking was associated with improvement in GERS from severe to no or minor complaints (adjusted OR 1.78; 95% CI: 1.07-2.97), compared with persistent daily smoking. This association was present among individuals within the normal range of BMI (OR 5.67; 95% CI: 1.36-23.64), but not among overweight individuals. There was no association between tobacco smoking cessation and GERS status among individuals with minor GERS or individuals using antireflux medication less than weekly.CONCLUSIONS:Tobacco smoking cessation was associated with improvement in severe GERS only in individuals of normal BMI using antireflux medication at least weekly, but not in other individual with GERS. [ABSTRACT FROM AUTHOR]

OBJECTIVES:High body mass index (BMI) is an established risk factor of gastroesophageal reflux symptoms (GERS). The aim of this study was to clarify if weight loss reduces GERS.METHODS:The study was part of the Nord-Trøndelag health study (the HUNT study), a prospective population-based cohort study conducted in Nord-Trøndelag County, Norway. All residents of the county from 20 years of age were invited. In 1995-1997 (HUNT 2) and 2006-2009 (HUNT 3), 58,869 and 44,997 individuals, respectively, responded to a questionnaire on heartburn and acid regurgitation. Among these, 29,610 individuals (61% response rate) participated at both times and were included in the present study. The association between weight loss and reduction of GERS was calculated using logistic regression. The analyses were stratified by antireflux medication and the results adjusted for sex, age, cigarette smoking, alcohol consumption, education, and physical exercise.RESULTS:Weight loss was dose-dependently associated with a reduction of GERS and an increased treatment success with antireflux medication. Among individuals with >3.5 units decrease in BMI, the adjusted odds ratio (OR) of loss of any (minor or severe) GERS was 1.98 (95% confidence interval (CI) 1.45-2.72) when using no or less than weekly antireflux medication, and 3.95 (95% CI 2.03-7.65) when using at least weekly antireflux medication. The corresponding ORs of loss of severe GERS was 0.90 (95% CI 0.32-2.55) and 3.11 (95% CI 1.13-8.58).CONCLUSIONS:Weight loss was dose-dependently associated with both a reduction of GERS and an increased treatment success with antireflux medication in the general population. [ABSTRACT FROM AUTHOR]

Purpose: The strong male predominance in esophageal and gastroesophageal junctional adenocarcinoma remains unexplained. Sex hormonal influence has been suggested, but not proven. A protective role of dietary phytoestrogen lignans was hypothesized. Methods: A Swedish nationwide population-based case-control study was conducted in 1995-1997, including 181 cases of esophageal adenocarcinoma, 255 cases of gastroesophageal junctional adenocarcinoma, 158 cases of esophageal squamous cell carcinoma, and 806 control subjects. Data on various exposures, including dietary data, were collected through personal interviews and questionnaires. Dietary intake of lignans was assessed using a food frequency questionnaire and categorized into quartiles based on the consumption among the control participants. Unconditional logistic regression was used to calculate odds ratios (ORs) with 95 % confidence intervals (CIs), including adjustment for all established risk factors. Results: Participants in the highest quartile of intake of lignans compared with the lowest quartile were at a decreased risk of esophageal adenocarcinoma (OR, 0.65; 95 % CI, 0.38-1.12; p for trend =0.03), gastroesophageal junctional adenocarcinoma (OR, 0.37; 95 % CI, 0.23-0.58; p for trend <0.0001), and these adenocarcinomas combined (OR, 0.45; 95 % CI, 0.31-0.67; p for trend <0.0001). No clear associations were found between lignan intake and risk of esophageal squamous cell carcinoma. Conclusions: This population-based study indicates that a high dietary intake of lignans decreases the risk of adenocarcinoma of the esophagus and gastroesophageal junction. [ABSTRACT FROM AUTHOR]