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Introduction Enhanced recovery after surgery (ERAS) programs provide a format for multidisciplinary care and has been shown to predictably improve short term outcomes associated with surgical procedures. Esophagectomy has historically been associated with significant levels of morbidity and mortality and as a result routine application and audit of ERAS guidelines specifically designed for esophageal resection has significant potential to improve outcomes associated with this complex procedure. Methods A team of international experts in the surgical management of esophageal cancer was assembled and the existing literature was identified and reviewed prior to the production of the guidelines. Well established procedure specific components of ERAS were reviewed and updated with changes relevant to esophagectomy. Procedure specific, operative and technical sections were produced utilizing the best current level of evidence. All sections were rated regarding the level of evidence and overall recommendation according to the evaluation (GRADE) system. Results Thirty-nine sections were ultimately produced and assessed for quality of evidence and recommendations. Some sections were completely new to ERAS programs due to the fact that esophagectomy is the first guideline with a thoracic component to the procedure. Conclusions The current ERAS society guidelines should be reviewed and applied in all centers looking to improve outcomes and quality associated with esophageal resection.

Background Population-based patient reported outcome data in oesophageal cancer are rare. The main purpose of this study was to describe health-related quality of life (HRQOL) 1 year after the diagnosis of oesophageal cancer, comparing subgroups of curatively and palliatively managed patients. Methods This is a nationwide population-based cohort study, based on the Swedish National Registry for Oesophageal and Gastric Cancer (NREV) with prospectively registered data, including HRQOL instruments from the European Organisation for Research and Treatment of Cancer including the core and disease specific questionnaires (EORTC QLQ-C30 and QLQ-OG25). Patients diagnosed with oesophageal cancer between 2009 and 2016 and with complete HRQOL data at 1 year follow-up were included. HRQOL of included patients was compared to a reference population matched by age and gender to to a previous cohort of unselected Swedish oesophageal cancer patients. Linear regression was performed to calculate mean scores with 95% confidence intervals (CI) and adjusted linear regression analysis was used to calculate mean score differences (MD) with 95% CI. Results A total of 1156 patients were included. Functions and global health/quality of life were lower in both the curative and palliative cohorts compared to the reference population. Both curatively and palliatively managed patients reported a severe symptom burden compared to the reference population. Patients who underwent surgery reported more problems with diarrhoea compared to those treated with definitive chemoradiotherapy (dCRT) (MD -14; 95% CI − 20 to − 8). Dysphagia was more common in patiens treated with dCRT compared to surgically treated patients (MD 11; 95% CI 4 to 18). Those with palliative intent due to advanced tumour stage reported more problems with dysphagia compared to those with palliative intent due to frailty (MD -18; 95% CI − 33 to − 3). Conclusions One year after diagnosis both curative and palliative intent patients reported low function scores and severe symptoms. Dysphagia, choking, and other eating related problems were more pronounced in palliatively managed patients and in the curative intent patients treated with dCRT.

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.

Previous haplotype Genome Wide Association Studies (GWASs) have suggested several rare loci with a shared increased risk of colorectal, gastric, and prostate cancer. This study aimed to find out more about markers specifically addressing the shared risk of colorectal and gastric cancer, as well as the shared risk of colorectal and prostate cancer. One analysis used 426 colorectal cancer cases with gastric cancer, with no prostate cancer cases in their families, and another analysis used 324 colorectal cancer cases with prostate cancer but no gastric cancer among relatives. The computational program PLINK v1.07 was used for the analysis and for the calculation of corresponding ORs, standard errors, and 95% confidence intervals (CI). The study found support for the loci from previous studies and many new loci with a shared risk of colorectal cancer and gastric cancer. There were no significant loci from the second analysis for a shared risk of colorectal and prostate cancer. Altogether, more than 100 new loci with a shared risk of colorectal cancer and gastric cancer were suggested. A shared risk of colorectal and prostate cancer at some loci could not be ruled out. Haplotype GWAS has again demonstrated its ability to find rare risk loci mostly associated with coding genes.

Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesophageal cancer. DNA was isolated from blood plasma and a tissue sample from each patient. Array-CGH was applied to the tissue DNA. The cell-free plasma DNA was sequenced by low-coverage whole-genome sequencing using a clinical pipeline for non-invasive prenatal testing. WISECONDOR and ichorCNA, two bioinformatic tools, were used to process the output data and were compared to each other. Cancer-associated CNAs could be seen in 59% (26/44) of the tissue biopsies. In the plasma samples, a targeted approach analysing 61 regions of special interest in gastro-oesophageal cancer detected cancer-associated CNAs with a z-score >5 in 11 patients. Broadening the analysis to a whole-genome view, 17/44 patients (39%) had cancer-associated CNAs using WISECONDOR and 13 (30%) using ichorCNA. Of the 26 patients with tissue-verified cancer-associated CNAs, 14 (54%) had corresponding CNAs in plasma. Potentially clinically actionable amplifications overlapping the genes VEGFA, EGFR and FGFR2 were detected in the plasma from three patients. We conclude that low-coverage whole-genome sequencing without prior knowledge of the tumour alterations could become a useful tool for cell-free tumour DNA analysis of total CNAs in plasma from patients with gastro-oesophageal cancer.

Background Adjuvant postoperative treatment with aspirin and statins may improve survival in several solid tumors. This study aimed to assess whether these medications improve the survival after curatively intended treatment (including esophagectomy) for esophageal cancer in an unselected setting. Methods This nationwide cohort study included nearly all patients who underwent esophagectomy for esophageal cancer in Sweden from 2006 to 2015, with complete follow-up throughout 2019. Risk of 5-year disease-specific mortality in users compared to non-users of aspirin and statins was analyzed using Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI). The HRs were adjusted for age, sex, education, calendar year, comorbidity, aspirin/statin use (mutual adjustment), tumor histology, pathological tumor stage, and neoadjuvant chemo(radio)therapy. Results The cohort included 838 patients who survived at least 1 year after esophagectomy for esophageal cancer. Of these, 165 (19.7%) used aspirin and 187 (22.3%) used statins during the first postoperative year. Neither aspirin use (HR 0.92, 95% CI 0.67–1.28) nor statin use (HR 0.88, 95% CI 0.64–1.23) were associated with any statistically significant decreased 5-year disease-specific mortality. Analyses stratified by subgroups of age, sex, tumor stage, and tumor histology did not reveal any associations between aspirin or statin use and 5-year disease-specific mortality. Three years of preoperative use of aspirin (HR 1.26, 95% CI 0.98–1.65) or statins (HR 0.99, 95% CI 0.67–1.45) did not decrease the 5-year disease-specific mortality. Conclusions Use of aspirin or statins might not improve the 5-year survival in surgically treated esophageal cancer patients.

An association between education level and survival after esophageal cancer has recently been indicated, but remains uncertain. We conducted a large study with long follow-up to address this issue. This population-based cohort study included all patients operated for esophageal cancer in Sweden between 1987 and 2010 with follow-up until 2012. Level of education was categorized as compulsory (≤9 years), intermediate (10-12 years), or high (≥13 years). The main outcome measure was overall 5-year mortality after esophagectomy. Cox regression was used to estimate associations between education level and mortality, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), with adjustment for sex, age, co-morbidity, tumor stage, tumor histology, and assessing the impact of education level over time. Compared to patients with high education, the adjusted HR for mortality was 1.29 (95% CI 1.07-1.57) in the intermediate educated group and 1.42 (95% CI 1.17-1.71) in the compulsory educated group. The largest differences were found in early tumor stages (T-stage 0-1), with HRs of 1.73 (95% CI 1.00-2.99) and 2.58 (95% CI 1.51-4.42) for intermediate and compulsory educated patients respectively; and for squamous cell carcinoma, with corresponding HRs of 1.38 (95% CI 1.07-1.79) and 1.52 (95% CI 1.19-1.95) respectively. This Swedish population-based study showed an association between higher education level and improved survival after esophageal cancer surgery, independent of established prognostic factors. The associations were stronger in patients of an early tumor stage and squamous cell carcinoma.

Cryptosporidium is a significant cause of foodborne outbreaks. The 60 kDa glycoprotein gene (gp60) is most often used for subtyping Cryptosporidium species but is not always sufficient for defining clusters and infections sources. The Multilocus Variable-Number Tandem-Repeat Analysis (MLVA) scheme has been developed to better differentiate between subtypes. A cryptosporidiosis outbreak, with 35 cases, was detected in Finland in September 2022. At the same time, in Sweden, three cryptosporidiosis outbreaks, with 107 cases, were detected, leading to international collaboration. In both countries, salad mixes were suspected as being the outbreak source. In the Finnish outbreak, the suspected salad mixes were produced in Sweden. In the Swedish outbreaks, salad mixes from two different producers were suspected. Twenty-nine patient samples which were positive for Cryptosporidium parvum (11 from Finland and 18 from Sweden) were sent for MLVA. The Finnish outbreak samples had different gp60 subtypes and MLVA profiles compared to the Swedish samples. In our investigation, MLVA differentiated C. parvum subtypes in more detail than gp60 typing. MLVA suggested no connection between the Finnish and Swedish outbreaks. A traceback investigation supported this conclusion. To detect outbreaks and identify infection sources, the timely subtyping of patient samples is crucial and should be implemented in routine surveillance and outbreak investigations.

Background A complex inheritance has been suggested in families with colorectal-, gastric- and prostate cancer. Therefore, we conducted a genome-wide association study (GWAS) in colorectal cancer patients, who’s relatives had prostate-, and/or gastric cancer. Methods The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model. Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case–control study. Results Candidate loci/genes on ten chromosomal regions were suggested with odds ratios between 1.71–3.62 and p -values < 5 × 10–8 in the analysis. The regions suggested were 1q32.2, 3q29, 4q35.1, 4p15.31, 4q26, 8p23.1, 13q33.3, 13q13.3, 16q23.3 and 22q11.21. All regions, except one on 1q32.2, had protein coding genes, many already shown to be involved in cancer, such as ZDHHC19, SYNPO2, PCYT1A, MYO16, TXNRD2, COMT, and CDH13 . Sequencing of DNA from 122 colorectal cancer patients with gastric- and/or prostate cancer in their families was performed to search for candidate variants in the haplotype regions. The identified candidate variants were tested in a nested case–control study of similar colorectal cancer cases and controls. There was some support for an increased risk of colorectal-, gastric-, and/or prostate cancer in all the six loci tested. Conclusions This study demonstrated a proof of principle strategy to identify risk variants found by GWAS, and identified ten candidate loci that could be associated with colorectal, gastric- and prostate cancer. Graphical Abstract

PurposeThe Swedish Pancreatitis Cohort (SwePan) was designed to study long-term outcomes following an episode of acute pancreatitis. It can also be used to study various risk factors for developing acute pancreatitis.ParticipantsThe SwePan is a register-based nationwide matched cohort. It includes all Swedish cases of acute pancreatitis during 1990–2019. It contains 95 632 individuals with acute pancreatitis and 952 783 pancreatitis-free individuals matched on sex, age and municipality of residence. Follow-up was censored at death, emigration or end of study (31 December 2019). The dataset includes comprehensive information based on several registries, and includes diagnoses, prescribed medications and socioeconomic factors both prior to inclusion and during follow-up.Findings to dateDuring the study period, the number of cases of acute pancreatitis in Sweden has more than doubled from 1977 cases in 1990 to 4264 cases in 2019. The median age of first episode of acute pancreatitis has increased from 58 years (IQR 44–73 years) in 1990 to 64 years (IQR 49–76 years) in 2019. Cases with acute pancreatitis were generally less healthy compared with the pancreatitis-free individuals (Charlson Comorbidity Index of 0 in 59.2% and 71.4%, respectively).Future plansSwePan will be used to determine the incidence of acute pancreatitis in Sweden over time and assess long-term all-cause and cause-specific mortality after an episode of acute pancreatitis. Some examples of additional planned studies are (1) assessment of long-term risk of diabetes and (2) risk of malignancy in adjacent organs following acute pancreatitis and (3) assessment of risk factors for development of acute pancreatitis including various drugs.