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  • LAGERGREN, Jesper, et al. (författare)
  • Extent of lymphadenectomy and prognosis after esophageal cancer surgery
  • 2015
  • Ingår i: JAMA Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2168-6254. ; 151:1, s. 32-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. Objective: To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. Design, Setting, and Participants: Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. Exposures: The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. Main Outcomes and Measures: The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95% CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. Results: Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95% CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95% CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mortality rates, and these associations showed dose-response associations. Conclusions and Relevance: This study indicated that the extent of lymphadenectomy during surgery for esophageal cancer might not influence 5-year all-cause or disease-specific survival. These results challenge current clinical guidelines.
  • Ek, W. E., et al. (författare)
  • Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma
  • 2016
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 138:5, s. 1146-1152
  • Tidskriftsartikel (refereegranskat)abstract
    • The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p=0.002) and in males (p=0.003), but not in females separately (p=0.3). This association was found in tobacco smokers (p=0.003) and in BE patients without reflux (p=0.004), but not in nonsmokers (p=0.2) or those with reflux (p=0.036). SNPs within JMJD1C were associated with risk of EAC in females (p=0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.
  • Lagergren, K., et al. (författare)
  • Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium
  • 2015
  • Ingår i: Plos One. - 1932-6203. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.
  • Backemar, Lovisa, et al. (författare)
  • Comorbidities and Risk of Complications After Surgery for Esophageal Cancer : A Nationwide Cohort Study in Sweden.
  • 2015
  • Ingår i: World Journal of Surgery. - 0364-2313 .- 1432-2323. ; 39:9, s. 2282-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The selection for surgery is multifaceted for patients diagnosed with esophageal cancer. Since it is uncertain how comorbidity should influence the selection, this study addressed comorbidities in relation to risk of severe complications following esophageal cancer surgery.METHODS: This population-based cohort study was based on prospectively included patients who underwent surgical resection for an esophageal or gastro-esophageal junctional cancer in Sweden during 2001-2005. The participation rate was 90%. Associations between pre-defined comorbidities and pre-defined post-operative complications occurring within 30 days of surgery were analyzed using multivariable logistic regression. The resulting odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for age, sex, tumor stage, tumor histology, neoadjuvant therapy, type of surgery, annual hospital volume, other comorbidities, and other complications.RESULTS: Among 609 included patients, those with cardiac disease (n = 92) experienced an increased risk of pre-defined complications in general (adjusted OR 1.81, 95% CI 1.13-2.90), while patients with hypertension (n = 137), pulmonary disorders (n = 79), diabetes (n = 67), and obesity (n = 66) did not. Patients with a Charlson comorbidity index score ≥2 had substantially increased risks of pre-defined complications (adjusted OR 2.44, 95% CI 1.60-3.72).CONCLUSION: Cardiac disease and a Charlson comorbidity index score ≥2 seem to increase the risk of severe and early post-operative complications in patients with esophageal cancer, while hypertension, pulmonary disorders, diabetes, and obesity do not. These findings should be considered in the clinical decision-making for improved selection of patients for surgery.
  • Backemar, Lovisa, et al. (författare)
  • The Influence of Comorbidity on Health-Related Quality of Life After Esophageal Cancer Surgery
  • 2020
  • Ingår i: Annals of Surgical Oncology. - 1068-9265 .- 1534-4681. ; 27:8, s. 2637-2645
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundEsophageal cancer surgery reduces patients’ health-related quality of life (HRQoL). This study examined whether comorbidities influence HRQoL in these patients.MethodsThis 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.ResultsAmong 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.ConclusionComorbidity appears to negatively influence HRQoL before esophagectomy, but appears not to severely impact 6-month recovery of HRQoL.
  • Brusselaers, Nele, et al. (författare)
  • Marital status and survival after oesophageal cancer surgery : a population-based nationwide cohort study in Sweden
  • 2014
  • Ingår i: BMJ Open. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. ; 4:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives 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. Design Prospective, population-based cohort. Setting All Swedish hospitals performing surgery for oesophageal cancer during 2001–2005. Participants 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. Results 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. Conclusions This study showed no evidence of a better 5-year survival in married patients compared with non-married patients undergoing surgery for oesophageal cancer.
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