Pernilla Lagergren

Cachexia in patients with oesophageal cancer.

Oesophageal cancer is a debilitating disease with a poor prognosis, and weight loss owing to malnutrition prevails in the majority of patients. Cachexia, a multifactorial syndrome characterized by the loss of fat and skeletal muscle mass and systemic inflammation arising from complex host–tumour interactions is a major contributor to malnutrition, which is a determinant of tolerance to treatment and survival. In patients with oesophageal cancer, cachexia is further compounded by eating difficulties owing to the stage and location of the tumour, and the effects of neoadjuvant therapy. Treatment with curative intent involves exceptionally extensive and invasive surgery, and the subsequent anatomical changes often lead to eating difficulties and severe postoperative malnutrition. Thus, screening for cachexia by means of percentage weight loss and BMI during the cancer trajectory and survivorship periods is imperative. Additionally, markers of inflammation (such as C-reactive protein), dysphagia and appetite loss should be assessed at diagnosis. Routine assessments of body composition are also necessary in patients with oesophageal cancer to enable assessment of skeletal muscle loss, which might be masked by sarcopenic obesity in these patients. A need exists for clinical trials examining the effectiveness of therapeutic and physical-activity-based interventions in mitigating muscle loss and counteracting cachexia in these patients.

Health-related quality of life 10 years after oesophageal cancer surgery

PURPOSEnTo determine whether oesophageal cancer survivors recover in health-related quality of life (HRQOL) within 10 years of surgery.nnnMETHODSnA prospective, nationwide, population-based cohort study including 90% of all oesophageal cancer surgery patients in Sweden in 2001-2005, with follow-up through 2015. HRQOL was assessed 5 and 10 years postoperatively, using questionnaires for cancer in general (EORTC QLQ-C30) and oesophageal cancer specifically (EORTC QLQ-OES18). The HRQOL measures at 10 years after surgery were compared with the 5-year assessment. The 10-year HRQOL scores were compared with a population-based reference population (4910 individuals), individually matched for age, sexxa0and comorbidity, by means of mean score differences with 95% confidence intervals.nnnRESULTSnAmong 616 patients, 104 (17%) survived at least 10 years. Of these, 92 (88%) responded to the HRQOL questionnaires at 5 and 10 years after surgery. Among the responders, 71% were older than 70 years. Patients did not improve in HRQOL between 5 and 10 years. Instead, the scores for 23 out of 25 HRQOL aspects declined, with clinically relevant and statistically significant deterioration in role function and appetite loss. Compared to the reference population, the 10 year-survivors had worse scores in all 25 HRQOL aspects, with significant deterioration in global quality of life, role functioning, social functioningxa0and most symptoms. The most severe problems compared to the reference population were reflux, eating difficulties, diarrhoeaxa0and appetite loss.nnnCONCLUSIONnPatients who have undergone curative treatment for oesophageal cancer experience reduced HRQOL with persisting symptoms 10 years after surgery.

Meta-analysis of health-related quality of life after minimally invasive versus open oesophagectomy for oesophageal cancer

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.

University hospital status and prognosis following surgery for esophageal cancer

BACKGROUNDnWe hypothesized that such prognosis is independently improved by surgery conducted within university hospitals.nnnMETHODSnPatients undergoing esophagectomy for esophageal cancer between 1987 and 2010 with follow-up until 2014 were identified from population-based nationwide Swedish cohort study. The association between university hospital status in and mortality was analyzed using a multivariable Cox-proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs). The HRs were adjusted for surgeon volume as well as age, comorbidity, tumor stage, histological subtype, neoadjuvant therapy and calendar period.nnnRESULTSnAmong 1820 included patients, 989 (54.3%) had surgery at one of the six university hospitals. Of the 83 and 569 patients operated on by the higher surgeon volume (17-46 cases) and middle surgeon volume groups (7-16 cases), 60 (72.3%) and 430 cases (75.6%) respectively were performed within university hospitals. University hospitals status indicated a non-significant reduction in all-cause 90-day mortality (HRxa0=xa00.82, 95% CI 0.61-1.10), but all-cause 5-year (HRxa0=xa00.94, 95% CI 0.83-1.05) and disease-specific 5-year mortality (HRxa0=xa01.00, 95% CI 0.88-1.14) were similar to non-university hospitals. Higher surgeon volume (17-46 cases), showed non-significant reductions in all-cause 90-day (HRxa0=xa00.49, 95% CI 0.21-1.14), all-cause 5-year (HRxa0=xa00.80, 95% CI 0.61-1.06) and disease-specific 5-year mortality (HRxa0=xa00.81, 95% CI 0.60-1.09).nnnCONCLUSIONSnThis study found no improvements in long-term mortality from esophagectomy performed within university hospitals after adjustment for surgeon volume and other confounders.

Health‑related quality of life after gastrectomy, esophagectomy, and combined esophagogastrectomy for gastroesophageal junction adenocarcinoma

BackgroundThe 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 6xa0months after extended total gastrectomy, subtotal esophagectomy, and combined esophagogastrectomy.MethodsPatients 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 6xa0months 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. MSDsxa0>xa010 were regarded as clinically relevant.ResultsAmong 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.ConclusionsExtended total gastrectomy, subtotal esophagectomy, and combined esophagogastrectomy seemed to yield similar 6-month postoperative HRQOL outcomes for patients with GEJ adenocarcinoma.

Health-related quality of life after open transhiatal and transthoracic oesophagectomy for cancer

Transhiatal and transthoracic oesophagectomy in patients with oesophageal cancer have similar survival rates. Whether these approaches differ in health‐related quality of life (HRQoL) is uncertain and was examined in this study.

The impact of pre- and post-operative weight loss and body mass index on prognosis in patients with oesophageal cancer

BACKGROUNDnWeight loss is a cardinal symptom of oesophageal cancer and is often continued after surgery. High body mass index (BMI) is a strong risk factor for oesophageal adenocarcinoma. This study aimed to assess the impact of pre- and post-operative weight loss and BMI on long-term mortality after resection for oesophageal cancer.nnnMETHODSnThis prospective and nationwide cohort study included 390 patients, operated on for oesophageal cancer in Sweden in 2001-2005 with follow-up until 2016, who responded to a questionnaire on weight history 6 months after surgery. Multivariable Cox proportional hazard models provided hazard ratios (HRs) and 95% confidence intervals (95% CIs) of mortality while adjusting for several prognostic factors, including tumour stage.nnnRESULTSnCompared to weight stable patients, pre-surgery weight loss indicated increased HRs of overall all-cause mortality (HRxa0=xa01.32, 95% CI 0.94-1.86) and disease-specific mortality (HRxa0=xa01.36, 95% CI 0.93-1.98). Patients with >20% weight loss post-surgery had worse overall all-cause mortality (HRxa0=xa01.71, 95% CI 1.01-2.88) and disease-specific mortality (HRxa0=xa02.20, 95% CI 1.24-3.89). Compared to patients with normal BMI, decreased HRs were indicated for patients who were obese at the time of surgery (overall all-cause mortality HR 0.87 95% CI, 0.58-1.31 and disease-specific mortality HRxa0=xa00.89, 95% CI 0.57-1.40), while patients with BMI ≤19.9xa0at 6 months post-surgery had increased all-cause mortality (HRxa0=xa01.41, 95% CI 1.03-1.95) and disease-specific mortality (HRxa0=xa01.55, 95% CI 1.09-2.21).nnnCONCLUSIONnPost-operative weight loss and low BMI at 6 months post-surgery are independent markers of poor prognosis in patients who undergo surgery for oesophageal cancer.

Weekday of cancer surgery in relation to prognosis

Later weekday of surgery seems to affect the prognosis adversely in oesophageal cancer, whereas any such influence on other cancer sites is unknown. This study aimed to test whether weekday of surgery influenced prognosis following commonly performed cancer operations.

Perioperative nutritional intervention: a way to improve long-term outcomes

We would like to thank Molfino and Laviano for their Correspondence article on our Review article (Cachexia in patients with oesophageal cancer. Nat. Rev. Clin. Oncol. http:// dx.doi.org/ 10.1038/nrclinonc.2015.200 (2015))1, in which they acknowledge our work and provide their extended views on the subjects we covered (Perioperative nutritional intervention: a way to improve long-term outcomes. Nat. Rev. Clin. Oncol. http://dx.doi.org/10.1038/nrclinonc.2016.20 (2016))2. We agree with the authors that, in addition to interventions that aim to counteract muscle loss and improve muscle function, perioperative nutritional interventions to improve immune function are of great importance and are an under-researched aspect of oesophageal cancer care. Indeed, we emphasized in our Review1 (in the ‘Treatment: Artificial nutritional support: During the perioperative period’ section) the importance of perioperative immunonutritional support, and stated that the European Society for Clinical Nutrition and Metabolism (ESPEN) has given a grade A recommendation (highly recommended) for the use of enteral nutritional support with immune-modulating substrates, such as arginine, omega-3 fatty acids, and nucleotides, in patients undergoing major abdominal surgery, independent of nutritional status3. In the same section of our Review1, we also discussed the existing evidence that indicates the role of immunonutrition in determining long-term patient outcomes, including survival. We second the views of Molfino and Laviano2, who have highlighted findings from more-recent studies than those discussed in our Review, as well as the possible mechanisms behind the effects of immunonutrition — and, therefore, the need for more and larger-sized clinical trials evaluating its effect in a patient group such as oesophageal cancer survivors, in whom immune function is compromised considerably throughout the cancer trajectory, especially during neoadjuvant therapy. Thus, the authors’ Correspondence adds valuable insights into the potential of immuno nutrition, during the perioperative period, to improve the long-term outcomes of such patients.

Lymphadenectomy and health-related quality of life after oesophageal cancer surgery: a nationwide, population-based cohort study

Objective The purpose of this study was to clarify whether more extensive surgical lymph node resection during oesophageal cancer surgery influences patients health-related quality of life (HRQOL). Setting This was a nationwide Swedish population-based study. Participants A total of 616 patients who underwent curatively intended oesophageal cancer surgery in 2001–2005 were followed up at 6u2005months and 5u2005years after surgery. Outcome measures HRQOL was assessed with the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and the oesophageal cancer-specific module (EORTC QLQ-OES18). The number of removed lymph nodes in relation to HRQOL was analysed using multivariable linear regression, providing mean score differences in HRQOL scores with 95% CIs. The results were adjusted for age, comorbidity, body mass index, tumour stage, tumour histology, postoperative complications and surgeon volume. Results The study included 382 and 136 patients who completed the EORTC questionnaires at 6u2005months and 5u2005years following surgery, respectively. In general, HRQOL remained stable over time, with only improvements in role function and appetite loss. A larger number of removed lymph nodes did not decrease the HRQOL measure at 6u2005months or 5u2005years after surgery. Conclusions More extensive lymphadenectomy during oesophageal cancer surgery might not decrease patients short-term or long-term HRQOL, but larger studies are needed to establish this potential lack of association.