| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Chidambaram, Swathikan, et al.
(författare)
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Identifying a core symptom set triggering radiological and endoscopic investigations for suspected recurrent esophago-gastric cancer : a modified Delphi consensus process
- 2023
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Ingår i: Diseases of the esophagus. - : Oxford University Press. - 1120-8694 .- 1442-2050. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients.METHODS: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set.RESULTS: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice.CONCLUSION: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value.
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| 3. |
- Gottlieb-Vedi, Eivind, et al.
(författare)
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Extent of Lymphadenectomy and Long-Term Survival in Esophageal Cancer
- 2023
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 277:3, s. 429-436
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenectomy.Summary of Background Data: There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer.Methods: This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors.Results: Among 2,306 patients, the 2nd (4-8 nodes), 7th (21-24 nodes) and 8th decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the 1st decile (HR = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively). In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI 0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8.Conclusion: Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.
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| 4. |
- Hedberg, Jakob, et al.
(författare)
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Randomized controlled trial of nasogastric tube use after esophagectomy : study protocol for the kinetic trial
- 2024
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Ingår i: Diseases of the esophagus. - : John Wiley & Sons. - 1120-8694 .- 1442-2050. ; 37:6
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Tidskriftsartikel (refereegranskat)abstract
- Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.
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| 5. |
- Holmberg, Dag, et al.
(författare)
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Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease
- 2022
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 162:2, s. 431-438.e4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer).METHODS: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).RESULTS: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively.CONCLUSIONS: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.
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| 6. |
- Holmberg, Dag, et al.
(författare)
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Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries : population based cohort study
- 2023
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Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 382, s. e076017-
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population.Design Population based cohort study.Setting All patients in hospital and specialised outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019.Participants 486 556 adults (>18 years) who underwent endoscopy were eligible for inclusion: 285 811 patients were included in the non-erosive gastro-oesophageal reflux disease cohort and 200 745 patients in the validation cohort with erosive gastro-oesophageal reflux disease.Exposures Non-erosive gastro-oesophageal reflux disease was defined by an absence of oesophagitis and any other oesophageal diagnosis at endoscopy. Erosive gastro-oesophageal reflux disease was examined for comparison reasons and was defined by the presence of oesophagitis at endoscopy.Main outcome measures The incidence rate of oesophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardised incidence ratios with 95% confidence intervals were calculated by dividing the observed number of oesophageal adenocarcinomas in each of the gastro-oesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period.Results Among 285 811 patients with non-erosive gastro-oesophageal reflux disease, 228 developed oesophageal adenocarcinomas during 2 081 051 person-years of follow-up. The incidence rate of oesophageal adenocarcinoma in patients with non-erosive gastro-oesophageal reflux disease was 11.0/100 000 person-years. The incidence was similar to that of the general population (standardised incidence ratio 1.04 (95% confidence interval 0.91 to 1.18)), and did not increase with longer follow-up (1.07 (0.65 to 1.65) for 15-31 years of follow-up). For validity reasons, we also analysed people with erosive oesophagitis at endoscopy (200 745 patients, 1 750 249 person-years, and 542 oesophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100 000 person-years) showing an increased overall standardised incidence ratio of oesophageal adenocarcinoma (2.36 (2.17 to 2.57)), which became more pronounced with longer follow-up.Conclusions Patients with non-erosive gastro-oesophageal reflux disease seem to have a similar incidence of oesophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastro-oesophageal reflux disease does not require additional endoscopic monitoring for oesophageal adenocarcinoma.
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| 7. |
- Kauppila, Joonas H, et al.
(författare)
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Gastrectomy compared to oesophagectomy for Siewert II and III gastro-oesophageal junctional cancer in relation to resection margins, lymphadenectomy and survival
- 2017
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Ingår i: Scientific Reports. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2045-2322.
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether gastrectomy or oesophagectomy offer better outcomes for gastro-oesophageal junction (GOJ) cancer. A total of 240 patients undergoing total gastrectomy (n = 85) or oesophagectomy (n = 155) for Siewert II-III GOJ adenocarcinoma were identified from a Swedish prospective population-based nationwide cohort. The surgical approaches were compared in relation to non-radical resection margins (main outcome) using multivariable logistic regression, providing odds ratios (ORs) and 95% confidence intervals (CIs), mean number of removed lymph nodes with standard deviation (SD) using ANCOVA, assessing mean differences and 95% CIs, and 5-year mortality using Cox regression estimating hazard ratios (HRs) and 95% CIs. The models were adjusted for age, sex, comorbidity, tumour stage, and surgeon volume. The non-radical resection rate was 15% for gastrectomy and 14% for oesophagectomy, and the adjusted OR was 1.61 (95% CI 0.68-3.83). The mean number of lymph nodes removed was 14.2 (SD +/- 9.6) for gastrectomy and 14.2 (SD +/- 10.4) for oesophagectomy, with adjusted mean difference of 2.4 (95% CI-0.2-5.0). The 5-year mortality was 76% following gastrectomy and 75% following oesophagectomy, with adjusted HR = 1.07 (95% CI 0.78-1.47). Gastrectomy and oesophagectomy for Siewert II or III GOJ cancer seem comparable regarding tumour-free resection margins, lymph nodes removal, and 5-year survival.
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| 8. |
- Kauppila, Joonas H, et al.
(författare)
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Intratumoral lactate metabolism in Barrett’s esophagus and adenocarcinoma
- 2017
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions. Results: Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer. Low cytoplasmic MCT1 expression associated with high T-class (P < 0.01), positive lymph node metastases (P < 0.05), positive distant metastases (P < 0.01) and high tumor stage (P < 0.01). High cytoplasmic MCT4 expression correlated significantly with positive distant metastases (P < 0.05). Both low MCT1 and high MCT4 histoscore predicted survival in univariate analysis (P < 0.01). MCT4 histoscore predicted survival in multivariate analysis (P = 0.043; HR 1.8 95%CI 1.0–3.1). MTCO1 expression was not correlated to clinicopathological variables or survival. Materials and Methods: MCT1, MCT4 and mitochondrial cytochrome c oxidase (MTCO1) expression were determined with immunohistochemistry in esophageal specimens from 129 patients with columnar dysplasia or adenocarcinoma. Specimens including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51), low-grade (n = 42), high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were evaluated. Conclusions: Major increase in markers of tumor metabolism occurs during carcinogenesis and progression of esophageal adenocarcinoma. MCT1 and MCT4 are prognostic factors in esophageal adenocarcinoma.
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| 9. |
- Kauppila, Joonas H, et al.
(författare)
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Meta-analysis of health-related quality of life after minimally invasive versus open oesophagectomy for oesophageal cancer
- 2017
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Ingår i: British Journal of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0007-1323 .- 1365-2168.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this systematic review and meta-analysis was to compare health-related quality of life (HRQoL) outcomes between minimally invasive and open oesophagectomy for cancer at different postoperative time points. METHODS: A search of PubMed (MEDLINE), Web of Science, Embase, Scopus, CINAHL and the Cochrane Library was performed for studies that compared open with minimally invasive oesophagectomy. A random-effects meta-analysis was conducted for studies that measured HRQoL scores using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OES18 questionnaires. Mean differences (MDs) greater than 10 in scores were considered clinically relevant. Pooled effects of MDs with 95 per cent confidence intervals were estimated to assess statistical significance. RESULTS: Nine studies were included in the qualitative analysis, involving 1157 patients who had minimally invasive surgery and 907 patients who underwent open surgery. Minimally invasive surgery resulted in better scores for global quality of life (MD 11.61, 95 per cent c.i. 3.84 to 19.39), physical function (MD 11.88, 3.92 to 19.84), fatigue (MD -13.18, -17.59 to -8.76) and pain (MD -15.85, -20.45 to -11.24) compared with open surgery at 3 months after surgery. At 6 and 12 months, no significant differences remained. CONCLUSION: Patients report better global quality of life, physical function, fatigue and pain 3 months after minimally invasive surgery compared with open surgery. No such differences remain at longer follow-up of 6 and 12 months.
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| 10. |
- Kauppila, Joonas H, et al.
(författare)
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Neoadjuvant therapy in relation to lymphadenectomy and resection margins during surgery for oesophageal cancer
- 2018
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Ingår i: Scientific Reports. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2045-2322.
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether gastrectomy or oesophagectomy offer better outcomes for gastro-oesophageal junction (GOJ) cancer. A total of 240 patients undergoing total gastrectomy (n = 85) or oesophagectomy (n = 155) for Siewert II-III GOJ adenocarcinoma were identified from a Swedish prospective population-based nationwide cohort. The surgical approaches were compared in relation to non-radical resection margins (main outcome) using multivariable logistic regression, providing odds ratios (ORs) and 95% confidence intervals (CIs), mean number of removed lymph nodes with standard deviation (SD) using ANCOVA, assessing mean differences and 95% CIs, and 5-year mortality using Cox regression estimating hazard ratios (HRs) and 95% CIs. The models were adjusted for age, sex, comorbidity, tumour stage, and surgeon volume. The non-radical resection rate was 15% for gastrectomy and 14% for oesophagectomy, and the adjusted OR was 1.61 (95% CI 0.68-3.83). The mean number of lymph nodes removed was 14.2 (SD +/- 9.6) for gastrectomy and 14.2 (SD +/- 10.4) for oesophagectomy, with adjusted mean difference of 2.4 (95% CI-0.2-5.0). The 5-year mortality was 76% following gastrectomy and 75% following oesophagectomy, with adjusted HR = 1.07 (95% CI 0.78-1.47). Gastrectomy and oesophagectomy for Siewert II or III GOJ cancer seem comparable regarding tumour-free resection margins, lymph nodes removal, and 5-year survival.
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