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1.  Marital status and survival after oesophageal cancer surgery: a population-based nationwide cohort study in Sweden 
BMJ Open  2014;4(6):e005418.
A beneficial effect of being married on survival has been shown for several cancer types, but is unclear for oesophageal cancer. The objective of this study was to clarify the potential influence of the marital status on the overall and disease-specific survival after curatively intended treatment of oesophageal cancer using a nationwide population-based design, taking into account the known major prognostic variables.
Prospective, population-based cohort.
All Swedish hospitals performing surgery for oesophageal cancer during 2001–2005.
This study included 90% of all patients with oesophageal or junctional cancer who underwent surgical resection in Sweden in 2001–2005, with follow-up until death or the end of the study period (2012).
Primary and secondary outcome measures
Cox regression was used to estimate associations between the marital status and the 5-year overall and disease-specific mortality, expressed as HRs with 95% CIs, with adjustment for sex, age, tumour stage, histological type, complications, comorbidities and annual surgeon volume.
Of all 606 included patients (80.4% men), 55.1% were married, 9.2% were remarried, 22.6% were previously married and 13% were never married. Compared with the married patients, the never married (HR 1.02, 95% CI 0.77 to 1.35), previously married (HR 0.90, 95% CI 0.71 to 1.15) and remarried patients (HR 0.79, 95% CI 0.55 to 1.13) had no increased overall 5-year mortality. The corresponding HRs for disease-specific survival, and after excluding the initial 90 days of surgery, were similar to the HRs for the overall survival.
This study showed no evidence of a better 5-year survival in married patients compared with non-married patients undergoing surgery for oesophageal cancer.
PMCID: PMC4054621  PMID: 24907248
Oesophageal Cancer; Marital Status; Survival
2.  Reoperation after oesophageal cancer surgery in relation to long-term survival: a population-based cohort study 
BMJ Open  2014;4(3):e004648.
The influence of reoperation on long-term prognosis is unknown. In this large population-based cohort study, it was aimed to investigate the influence of a reoperation within 30 days of oesophageal cancer resection on survival even after excluding the initial postoperative period.
This was a nationwide population-based retrospective cohort study.
All hospitals performing oesophageal cancer resections during the study period (1987–2010) in Sweden.
Patients operated for oesophageal cancer with curative intent in 1987–2010.
Primary and secondary outcomes
Adjusted HRs of all cause, early and late mortality up to 5 years after reoperation following oesophageal cancer resection.
Among 1822 included patients, the 200 (11%) who were reoperated had a 27% increased HR of all-cause mortality (adjusted HR 1.27, 95% CI 1.05 to 1.53) and 28% increased HR of disease-specific mortality (adjusted HR 1.28, 95% CI 1.04 to 1.59), compared to those not reoperated. Reoperation for anastomotic insufficiency in particular was followed by an increased mortality (adjusted HR 1.82, 95% CI 1.19 to 2.76).
This large and population-based nationwide cohort study shows that reoperation within 30 days after primary oesophageal resection was associated with increased mortality, even after excluding the initial 3 months after surgery. This finding stresses the need to consider any actions that might prevent complications and reoperation after oesophageal cancer resection.
PMCID: PMC3963069  PMID: 24650808
3.  Education level and survival after oesophageal cancer surgery: a prospective population-based cohort study 
BMJ Open  2013;3(12):e003754.
This study aimed to investigate whether a higher education level is associated with an improved long-term survival after oesophagectomy for cancer.
A prospective, population-based cohort study.
90% of all patients with oesophageal and cardia cancer who underwent a resection in Sweden in 2001–2005 were enrolled in this study (N=600; 80.3% male) and followed up until death or the end of the study period (2012). The study exposure was level of education, defined as compulsory (≤9 years), moderate (10–12 years) or high (≥13 years).
Outcome measures
The main outcome measure was overall 5-year survival after oesophagectomy. Cox regression was used to estimate the associations between education level and mortality, expressed as HRs with 95% CIs, with adjustment for sex, age, tumour stage, histological type, complications, comorbidities and annual surgeon volume. The patient group with highest education was used as the reference category.
Among the 600 included patients, 281 (46.8%) had compulsory education, 238 (39.7%) had moderate education and 81 (13.5%) had high education. The overall 5-year survival rate was 23.1%, 24.4% and 32.1% among patients with compulsory, moderate and high education, respectively. After adjustment for confounders, a slightly higher, yet not statistically significantly increased point HR was found among the compulsory educated patients (HR 1.08, 95% CI 0.80 to 1.47). In patients with tumour stage IV, increased adjusted HRs were found for compulsory (HR 2.88, 95% CI 1.07 to 7.73) and moderately (HR 2.83, 95% CI 1.15 to 6.95) educated patients. No statistically significant associations were found for the other tumour stages.
This study provides limited evidence of an association between lower education and worse long-term survival after oesophagectomy for cancer.
PMCID: PMC3855588  PMID: 24302504
4.  Clinical implementation of a new antibiotic prophylaxis regimen for percutaneous endoscopic gastrostomy 
BMJ Open  2013;3(5):e003067.
This study was undertaken to test the extent to which a new antibiotic prophylaxis regimen for percutaneous endoscopic gastrostomy (PEG), identified as a justified and simpler alternative to conventional regimen in a randomised clinical trial, has been adopted in clinical practice.
A Swedish nationwide implementation survey, conducted in February 2013, assessed the level of clinical implementation of a 20 ml dose of oral solution of sulfamethoxazole and trimethoprim deposited in the PEG catheter immediately after insertion. All hospitals inserting at least five PEGs annually were identified from the Swedish Patient Registry. A clinician involved in the PEG insertions at each hospital participated in a structured telephone interview addressing their routine use of antibiotic prophylaxis.
All Swedish hospitals inserting PEGs (n=60).
Representatives of PEG insertions at each of the 60 eligible hospitals participated (100% participation).
Main outcome measures
Use of routine antibiotic prophylaxis for PEG.
A total of 32 (53%) of the 60 hospitals had adopted the new regimen. It was more frequently adopted in university hospitals (67%) than in community hospitals (41%). An annual total of 1813 (70%) of 2573 patients received the new regimen. Higher annual hospital volume was associated with a higher level of adoption of the new regimen (80% in the highest vs 31% in the lowest).
The clinical implementation of the new antibiotic prophylaxis regimen for PEG was high and rapid (70% of all patients within 3 years), particularly in large hospitals.
PMCID: PMC3668416  PMID: 23793708
5.  Number and burden of cardiovascular diseases in relation to health-related quality of life in a cross-sectional population-based cohort study 
BMJ Open  2012;2(5):e001554.
To clarify whether a greater number of cardiovascular diseases or a larger burden of disease are associated with poorer health-related quality of life (HRQoL) in an unselected general population.
A population-based cross-sectional postal survey.
A random sample of the Swedish general population aged 40–79 years matched for national distributions of age, gender and region.
Out of 6969 eligible individuals, 4910 (70.5%) participated.
Primary and secondary measures
To create a reference database for HRQoL outcomes in the general population. To assess certain diseases and their relation to HRQoL.
Predefined cardiovascular diseases and HRQoL were assessed from validated questionnaires (EORTC QLQ-C30). Aspects of HRQoL included in the analyses were global quality of life, physical function, role function, emotional function, fatigue and dyspnoea. Individuals were categorised into: ‘good function’ versus ‘poor function’ and ‘no or minor symptoms’ versus ‘symptomatic’. Multivariable logistic regression calculated OR with 95% CI for poor HRQoL. The exposures were the number of cardiovascular diseases and the subjective disease burden.
Out of the 4910 participants, 1358 (28%) reported having a cardiovascular disease and hypertension was most common. Reporting a greater number of cardiovascular diseases was associated with an increased risk of poor HRQoL, especially regarding dyspnoea. The OR for symptomatic dyspnoea was 1.37 (95% CI 1.08 to 1.74) for participants with one cardiovascular disease, 4.81 (95% CI 3.24 to 7.13) for two diseases and 4.18 (95% CI 2.24 to 7.80) for those with three or more cardiovascular diseases. Among the 271 participants who assessed their cardiovascular disease burden as major, the highest risk for poor HRQoL was found for physical function (OR 6.18, 95% CI 3.72 to 10.30).
Increased number of cardiovascular diseases and a greater burden of disease are generally associated with poorer HRQoL in people with cardiovascular disease from an unselected population.
PMCID: PMC3488712  PMID: 23100444
Epidemiology; Health Economics
6.  Patients’ perspectives of living with a percutaneous endoscopic gastrostomy (PEG) 
BMC Gastroenterology  2012;12:126.
Since enteral nutrition therapy is the preferred nutritional support for dysphagic patients with a range of diagnoses, PEG has become part of traditional care. However, enteral nutrition with PEG transfers treatment responsibility and activity to the patients and their carers, so the advantages should be discussed. The aim of this study was therefore to investigate patients’ experience of living with a percutaneous endoscopic gastrostomy (PEG) in order to increase the understanding of patients’ need for support.
In a prospective study at Karolinska University Hospital in Sweden, data were collected consecutively at the time of PEG and two months later using a study-specific questionnaire about each patient’s experience of living with a PEG. Fishers exact test was used to test for statistically significant difference at five per cent level.
There were 104 responders (response rate of 70%). Women felt more limited in daily activity compared to men (p = 0.004). Older patients experienced a more limited ability to influence the number of feeding times compared to younger (p = 0.026). Highly educated patients found feeding more time-consuming (p = 0.004). Patients with a cancer diagnosis reported that the PEG feeding interfered with their oral feeding more than patients with a neurological disease (p = 0.009). Patients mostly contacted the PEG outpatient clinic with problems regarding their PEG, and were mainly assisted by their spouse rather than district nurses.
PEG feeding is time-consuming and interferes with daily life. Although 73% was satisfied, patients’ experiences of living with a PEG may be dependent on age, sex, education and diagnosis. Spouses are the main carers for PEG patients at home, and patients prefer to go to the PEG outpatient clinic for help if problems occur.
PMCID: PMC3503865  PMID: 22989321
Experience; Impact; Nutrition; Support
7.  Physical activity, obesity and gastroesophageal reflux disease in the general population 
AIM: To clarify the association between physical activity and gastroesophageal reflux disease (GERD) in non-obese and obese people.
METHODS: A Swedish population-based cross-sectional survey was conducted. Participants aged 40-79 years were randomly selected from the Swedish Registry of the Total Population. Data on physical activity, GERD, body mass index (BMI) and the covariates age, gender, comorbidity, education, sleeping problems, and tobacco smoking were obtained using validated questionnaires. GERD was self-reported and defined as heartburn or regurgitation at least once weekly, and having at least moderate problems from such symptoms. Frequency of physical activity was categorized into three groups: (1) “high” (several times/week); (2) “intermediate” (approximately once weekly); and (3) “low” (1-3 times/mo or less). Analyses were stratified for participants with “normal weight” (BMI < 25 kg/m2), “overweight” (BMI 25 to ≤ 30 kg/m2) and “obese” (BMI > 30 kg/m2). Multivariate logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounding by covariates.
RESULTS: Of 6969 eligible and randomly selected individuals, 4910 (70.5%) participated. High frequency of physical activity was reported by 2463 (50%) participants, GERD was identified in 472 (10%) participants, and obesity was found in 680 (14%). There were 226 (5%) individuals with missing information about BMI. Normal weight, overweight and obese participants were similar regarding distribution of gender and tobacco smoking status, while obese participants were on average slightly older, had fewer years of education, more comorbidity, slightly more sleeping problems, lower frequency of physical activity, and higher occurrence of GERD. Among the 2146 normal-weight participants, crude point estimates indicated a decreased risk of GERD among individuals with high frequency of physical activity (OR: 0.59, 95% CI: 0.39-0.89), compared to low frequency of physical activity. However, after adjustment for potential confounding factors, neither intermediate (OR: 1.30, 95% CI: 0.75-2.26) nor high (OR: 0.99, 95% CI: 0.62-1.60) frequency of physical activity was followed by decreased risk of GERD. Sleeping problems and high comorbidity were identified as potential confounders. Among the 1859 overweight participants, crude point estimates indicated no increased or decreased risk of GERD among individuals with intermediate or high frequency of physical activity, compared to low frequency. After adjustment for confounding, neither intermediate (OR: 0.75, 95% CI: 0.46-1.22) nor high frequency of physical activity were followed by increased or decreased risk of GERD compared to low frequency among nonobese participants. Sleeping problems and high comorbidity were identified as potential confounders for overweight participants. In obese individuals, crude ORs were similar to the adjusted ORs and no particular confounding factors were identified. Intermediate frequency of physical activity was associated with a decreased occurrence of GERD compared to low frequency of physical activity (adjusted OR: 0.41, 95% CI: 0.22-0.77).
CONCLUSION: Intermediate frequency of physical activity might decrease the risk of GERD among obese individuals, while no influence of physical activity on GERD was found in non-obese people.
PMCID: PMC3406423  PMID: 22851863
Physical exercise; Gastroesophageal reflux disease; Population-based study; Risk factor; Body mass index; Obesity
8.  Novel approach to antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG): randomised controlled trial 
Objective To evaluate a new and simpler strategy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG).
Design Single centre, two arm, randomised, controlled, double blind clinical trial.
Setting Endoscopy unit in Karolinska University Hospital, Stockholm, Sweden, between 3 June 2005 and 31 October 2009.
Participants 234 patients with an indication for PEG who gave informed consent to participate.
Intervention A single 20 ml dose of the oral solution of sulfamethoxazole and trimethoprim (also known as co-trimoxazole or Bactrim; F Hoffmann-La Roche Ltd, Basel, Switzerland) deposited in the PEG catheter immediately after insertion. The control group received standard prophylaxis consisting of a single intravenous dose of 1.5 g cefuroxime (Zinacef; GlaxoSmithKline, London) administered before insertion of the PEG tube.
Main outcome measure Primary outcome was the occurrence of clinically evident wound infection within 14 days after insertion of the PEG catheter. Secondary outcomes were positive bacterial culture and blood tests (highly sensitive C reactive protein and white blood cell count). All randomised patients were included in an intention to treat analysis.
Results Of the 234 patients included in this study, 116 were randomly assigned to co-trimoxazole and 118 to cefuroxime. At follow-up 7-14 days after insertion of the PEG catheter, wound infection was found in 10 (8.6%) patients in the co-trimoxazole group and 14 (11.9%) in the cefuroxime group, which corresponds to a percentage point difference of −3.3% (95% confidence interval −10.9% to 4.5%). The per protocol analysis, which comprised 100 patients in each group, gave similar results—10% and 13% infection in the co-trimoxazole and cefuroxime groups, respectively (percentage point difference −3.0%, 95% CI −11.8% to 5.8%). Both these analyses indicate non-inferiority of co-trimoxazole compared with cefuroxime because the upper bounds of the confidence intervals are lower than the pre-determined non-inferiority margin of 15%. Analyses of the secondary outcomes supported this finding.
Conclusion 20 ml of co-trimoxazole solution deposited in a newly inserted PEG catheter is at least as effective as cefuroxime prophylaxis given intravenously before PEG at preventing wound infections in patients undergoing PEG.
Trial registration Current Controlled Trials ISRCTN18677736.
PMCID: PMC2896486  PMID: 20601414
9.  Antralization of the Gastric Mucosa of the Incisura Angularis and its Gastrin Expression 
The frequency of antrum-type mucosa and gastrin expression in gastric biopsies from the incisura angularis was assessed in 60 consecutive patients having gastrointestinal symptoms. Following the recommendations from the updated Sydney System for the classification and grading of gastritis, two biopsies were taken from the antrum, one from the incisura and two from the corpus. Sections were stained with H&E, Giemsa and for gastrin. Gastrin-positive cells were semi-quantified as: 0 (none), ≤ 9, 10- 49 cells and ≥50 gastrin-labelled cells/40× field. Antrum-type mucosa at the incisura (called antralization) occurred in 30% of the biopsies without inflammation, but in 69% of those with H. pylori-induced gastritis, and in 64% of those with autoimmune gastritis. At the incisura, gastrin-labelled cells (≥10) were found in 62% (18/29) of biopsies showing antralization, but in only 20% (3/15) of those having transitional-type mucosa (p<0.05) and in none of the 16 biopsies having fundic-type mucosa. The similarity in gastrin expression between the mucosa of the gastric antrum and the antral-type mucosa at the incisura substantiates the notion that antralization is a metaplastic transformation. The significantly higher frequency of antral-type mucosa at the incisura in patients with gastritis than in those without gastritis strongly suggests that chronic inflammation per se triggers antralization of the incisura, irrespective of the presence or absence of H. pylori infection.
PMCID: PMC2491394  PMID: 18830388
Antralization; incisura; gastrin; chronic gastritis

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