Health-related quality of life following neoadjuvant chemoradiotherapy versus perioperative chemotherapy and esophagectomy for esophageal cancer: a European multicenter study.

Curative treatment for locally advanced esophageal cancer consists of (neo)adjuvant treatment followed by esophagectomy. Both neoadjuvant chemoradiotherapy and perioperative chemotherapy improve the 5-year overall survival rate compared with surgery alone. However, it is unknown whether these treatment strategies are associated with differences in long-term health-related quality of life (HRQL). The aim of this study is to compare long-term HRQL in patients after esophagectomy treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy. Disease-free cancer patients having undergone esophagectomy and (neo)adjuvant treatment in one of the participating lasting symptoms after esophageal resection (LASER) study centers between 2010 and 2016, were identified from the LASER study dataset. Included patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), EORTC QLQ-OG25, and LASER questionnaires at least 1 year after the completion of treatment. Long-term HRQL was compared between patients treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy, using univariable and multivariable regression and presented as differences in mean score. Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) perioperative chemotherapy. Patients treated with perioperative chemotherapy reported more symptomatology for diarrhea (difference in means 5.93), reflux (difference in means 7.40), and odynophagia (difference in means 4.66). The differences did not exceed the 10 points to be of clinical relevance. No significant differences for the LASER key symptoms were observed. The observed differences in long-term HRQL are in favor of patients treated with neoadjuvant chemoradiotherapy compared with patients treated with perioperative chemotherapy; however, the differences were small. Patients need to be informed about long-term HRQL when considering allocation of (neo)adjuvant treatment.

Health-related quality of life following total minimally invasive, hybrid minimally invasive or open oesophagectomy: a population-based cohort study.

BACKGROUND: Minimally invasive oesophagectomy has been shown to reduce the risk of pulmonary complications compared with open oesophagectomy, but the effects on health-related quality of life (HRQoL) and oesophageal cancer survivorship remain unclear. The aim of this study was to assess the longitudinal effects of minimally invasive compared with open oesophagectomy for cancer on HRQoL. METHODS: All patients who had surgery for oesophageal cancer in Sweden from January 2013 to April 2018 were identified. The exposure was total or hybrid minimally invasive oesophagectomy, compared with open surgery. The study outcome was HRQoL, evaluated by means of the European Organisation for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-OG25 at 1 and 2 years after surgery. Mean differences and 95 per cent confidence intervals were adjusted for confounders. RESULTS: Of the 246 patients recruited, 153 underwent minimally invasive oesophagectomy, of which 75 were hybrid minimally invasive and 78 were total minimally invasive procedures. After adjustment for age, sex, Charlson Co-morbidity Index score, pathological tumour stage and neoadjuvant therapy, there were no clinically and statistically significant differences in overall or disease-specific HRQoL after oesophagectomy between hybrid minimally invasive and total minimally invasive surgical technique versus open surgery. CONCLUSION: In this population-based nationwide Swedish study, longitudinal HRQoL after minimally invasive oesophagectomy was similar to that of the open surgical approach.

Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Human Immunodeficiency Virus-infected men who have sex with men with syphilis: A 5-year multicentre study in Malaysia.

OBJECTIVES: High rates of syphilis have been reported worldwide among men who have sex with men (MSM). This study aims to describe the clinical pattern and treatment response of syphilis among human immunodeficiency virus (HIV)-infected MSM in Malaysia. METHODS: This is a retrospective study on all HIV-infected MSM with syphilis between 2011 and 2015. Data was collected from case notes in five centres namely Hospital Kuala Lumpur, Hospital Sultanah Bahiyah, Hospital Umum Sarawak, University of Malaya Medical Centre and Hospital Sungai Buloh. RESULTS: A total of 294 HIV seropositive MSM with the median age of 29 years (range 16-66) were confirmed to have syphilis. Nearly half (47.6%) were in the age group of 20-29 years. About a quarter (24.1%) was previously infected with syphilis. Eighty-three patients (28.2%) had other concomitant sexually transmitted infection with genital warts being the most frequently reported (17%). The number of patients with early and late syphilis in our cohort were almost equal. The median pre-treatment non-treponemal antibody titre (VDRL or RPR) for early syphilis (1:64) was significantly higher than for late syphilis (1:8) (p<0.0001). The median CD4 count and the number of patients with CD4 <200/µl in early syphilis were comparable to late syphilis. Nearly four-fifth (78.9%) received benzathine-penicillin only, 5.8% doxycycline, 1.4% Cpenicillin, 1% procaine penicillin, and 12.4% a combination of the above medications. About 44% received treatment and were lost to follow-up. Among those who completed 1 -year follow-up after treatment, 72.3% responded to treatment (serological non-reactive - 18.2%, four-fold drop in titre - 10.9%; serofast - 43.6%), 8.5% failed treatment and 17% had re-infection. Excluding those who were re-infected, lost to follow-up and died, the rates of treatment failure were 12.1% and 8.8% for early and late syphilis respectively (p=0.582). CONCLUSION: The most common stage of syphilis among MSM with HIV was latent syphilis. Overall, about 8.5% failed treatment at 1-year follow-up.

Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial).

BACKGROUND: There are few data comparing health-related quality of life (HRQoL) after neoadjuvant chemotherapy alone (nCT) compared with neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal cancer. METHODS: In the NeoRes trial, patients were assigned randomly in a 1 : 1 ratio to receive either cisplatin 100 mg/m2 on day 1 and an infusion of 750 mg per m2 5-fluorouracil over 24 h on days 1-5 in three 21-day cycles (nCT) or the same chemotherapy regimen, but with the addition of 40 Gy radiotherapy (nCRT). HRQoL data were collected at baseline, after neoadjuvant therapy and at 1, 3 and 5 years after surgery. The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease-specific modules were used. RESULTS: Of 181 patients randomized, 165 were included in the analysis of HRQoL. In a direct comparison between the allocated treatments, odynophagia after completion of neoadjuvant therapy but before surgery (P = 0·047) and troublesome coughing at 3 years' follow-up (P = 0·011) were more pronounced in the nCRT arm. In the longitudinal analyses within each treatment arm, a large deterioration in HRQoL was noted at 1 year. Some recovery was seen in both arms over time but, after 3 and 5 years, patients in the nCRT arm reported more symptoms compared with baseline than patients in the nCT arm. CONCLUSION: HRQoL after multimodal treatment for cancer of the oesophagus or gastro-oesophageal junction was impaired and more pronounced in patients who underwent nCRT, with only partial recovery over time.

ANTECEDENTES: Se dispone de poca información sobre la calidad de vida relacionada con la salud (health-related quality of life, HRQOL) en pacientes con cáncer de esófago después de quimioterapia neoadyuvante sola en comparación con quimiorradioterapia neoadyuvante. MÉTODOS: En el ensayo NeoRes, los pacientes fueron asignados de forma aleatoria 1:1 a tratamiento con cisplatino 100 mg/m2 en el día uno y 5-Fluorouracilo 750 mg/m2 /infusión de 24 horas en los días 1-5 en tres ciclos de 21 días (nCT) o al mismo régimen de quimioterapia, pero con la adición de radioterapia 40 Gy (nCRT). Los datos de HRQOL se recogieron al inicio, tras el tratamiento neoadyuvante y al cabo de 1, 3 y 5 años tras la cirugía. Se utilizaron los cuestionarios QLQ-C30 de la European Organisation for Research and Treatment of Cancer (EORTC) y los módulos específicos para la enfermedad. RESULTADOS: De 181 pacientes aleatorizados, 165 fueron incluidos en el análisis de la HRQOL. En la comparación directa entre los tratamientos asignados, la odinofagia tras terminar nCRT pero antes de la cirugía (P = 0,047) y la tos molesta a los 3 años de seguimiento (P = 0,011), fueron más acentuadas en el brazo de nCRT. En el análisis longitudinal dentro de cada rama de tratamiento hubo un fuerte deterioro en la HRQOL al año. Se observó cierta recuperación en ambas ramas con el tiempo, pero a los 3 y 5 años de seguimiento, los pacientes de la rama de nCRT describieron más síntomas en comparación con la situación de inicio que los pacientes de la rama de nCT. CONCLUSIÓN: La HRQOL después del tratamiento multimodal del cáncer de esófago o de la unión gastroesofágica se ve afectada, siendo dicha afectación más pronunciada en pacientes que recibieron nCRT, recuperándose solo parcialmente con el tiempo.

Outcomes of nutritional jejunostomy in the curative treatment of esophageal cancer.

Substantial weight loss and eating problems are common before and after esophagectomy for cancer. The use of jejunostomy might prevent postoperative weight loss, but studies evaluating other outcomes are scarce. This study aims to assess the influence of jejunostomy on postoperative health-related quality of life (HRQOL), complications, reoperation, hospital stay, and survival. This prospective and population-based cohort study included all patients operated on for esophageal or gastroesophageal junction cancer in Sweden in 2001-2005 with follow-up until 31st December 2016. Data regarding patient and tumor characteristics and treatment were prospectively collected. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), whereas Cox regression provided hazard ratios with 95% CI. All risk estimates were adjusted for age, sex, tumor histology, stage, comorbidity, surgical approach, neoadjuvant therapy, and body mass index and weight loss at baseline. Among 397 patients, 181 (46%) received a jejunostomy during surgery. The use of jejunostomy did not influence the HRQOL at 6 months or 3 years after treatment. Jejunostomy users had no statistically significantly increased risk of postoperative complications (OR 1.27; 95% CI 0.86-1.87) or reoperation (OR 1.70; 95% CI 0.88-3.28). Intensive unit care and length of hospital stay was the same independent of the use of jejunostomy. The all-cause mortality was not increased in the jejunostomy group (HR 0.89, 95% CI: 0.74-1.07). This study indicates that jejunostomy does not influence postoperative HRQOL, complications, or survival after esophageal cancer surgery, it can be considered a safe method for early enteral nutrition after esophageal cancer surgery but benefits for the patients need further investigations.

Impact of weight loss and eating difficulties on health-related quality of life up to 10 years after oesophagectomy for cancer.

BACKGROUND: Severe weight loss is experienced by patients with eating difficulties after surgery for oesophageal cancer. The aim of this prospective cohort study was to asssess the influence of eating difficulties and severe weight loss on health-related quality of life (HRQoL) up to 10 years after oesophagectomy. METHODS: Data on bodyweight and HRQoL were collected at 6 months, 3, 5 and 10 years in patients who underwent surgery for oesophageal cancer in Sweden between 2001 and 2005. Exposures were percentage weight loss, and eating difficulties defined by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OES18 questionnaire. Outcomes were HRQoL scores from the EORTC QLQ-C30 questionnaire. Repeated-measures ANOVA, adjusting for potential confounders, was used to assess the association between eating difficulties and weight loss (4 exposure groups) and HRQoL scores at each time point. Mean score differences (MDs) between time points or exposure groups were defined as clinically relevant in accordance with evidence-based interpretation guidelines. RESULTS: In total, 92 of 104 10-year survivors (88·5 per cent) responded to the questionnaires. Weight loss was greatest within 6 months of surgery. Patients with eating difficulties with or without weight loss reported clinically and statistically significantly worsened HRQoL in almost all aspects. The largest MD was seen between 5 and 10 years after surgery for global quality of life, physical, role and social function (MD -22 to -30), as well for fatigue, nausea, dyspnoea, insomnia, appetite loss and diarrhoea (MD 24-36). CONCLUSION: Eating difficulties are associated with deterioration in several aspects of HRQoL up to 10 years after surgery for oesophageal cancer.

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

BACKGROUND: 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. METHODS: Patients undergoing transhiatal or transthoracic surgery for lower-third oesophageal or gastro-oesophageal junctional cancer between 2011 and 2015 were selected from an institutional database. HRQoL outcomes were measured at 6 and 12 months after surgery using validated written questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25). Linear mixed models provided mean score differences (MSDs) with 95 per cent confidence intervals, adjusted for preoperative HRQoL, age, physical status (ASA fitness grade), tumour location, tumour stage, neoadjuvant therapy, adjuvant therapy and postoperative complications. MSD values of 10 or more were regarded as clinically relevant. RESULTS: Some 146 patients underwent transhiatal (86, 58·9 per cent) or transthoracic (60, 41·1 per cent) oesophagectomy. The HRQoL questionnaires were returned by 111 patients at 6 months and 74 at 12 months. At 6 months, transthoracic oesophagectomy was associated with worse role function (MSD -12, 95 per cent c.i. -23 to 0; P = 0·046). At 12 months, patients in the transthoracic group had more nausea and vomiting (MSD 11, 0 to 22; P = 0·045), dyspnoea (MSD 13, 1 to 25; P = 0·029) and constipation (MSD 20, 7 to 33; P = 0·003) than those in the transhiatal group. CONCLUSION: Transhiatal oesophagectomy seems to offer better HRQoL than transthoracic oesophagectomy 6 and 12 months after surgery.

Complications during neoadjuvant therapy and prognosis following surgery for esophageal cancer.

Previous researchers have focused upon the influence of postoperative complications upon prognosis from esophagectomy, with very little attention paid to the potential negative effects of complications during neoadjuvant therapy. The hypothesis under investigation in this study was that the prognosis after esophageal cancer surgery is negatively influenced by complications causing hospital admission during neoadjuvant therapy. Patients receiving neoadjuvant therapy and surgery for esophageal cancer between 1987 and 2010 were identified from a population-based nationwide Swedish cohort study and followed up until 2016. The association between hematological and nonhematological complications during neoadjuvant therapy and risk of short- and long-term mortality following surgery was analyzed using a multivariable Cox proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs). The HRs were adjusted for appropriate confounding variables.Among 587 patients, complications during neoadjuvant therapy requiring emergency hospitalization affected 65 (12%) patients. Hematological complications were associated with an increased 90-day overall mortality (HR = 5.60; 95% CI 1.27-24.75), particularly in subgroups of patients of tumor stage 0-II, adenocarcinoma, and radical and nonradical resection margins, and rendered increased 5-year disease-specific mortality specifically for esophageal adenocarcinoma (HR = 3.22; 95% CI 1.00-10.40). Occurrence of nonhematological complications was followed by an increase in 5-year mortality (HR = 2.35; 95% CI 1.15-4.81) in poor prognostic groups (tumor stage III-IV). There was no increased 5-year mortality following hematological or nonhematological complications in other subgroups of patients. Complications during neoadjuvant therapy may adversely impact short and long-term mortality in subgroups of patients with esophageal cancer receiving esophagectomy. Patient selection, optimization of neoadjuvant therapy, and timing of surgical resection, remain important areas for future development in the management of esophageal cancer.

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

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.

APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer's disease.

Alzheimer's disease (AD) age of onset (ADAOO) varies greatly between individuals, with unique causal mutations suggesting the role of modifying genetic and environmental interactions. We analyzed ~50 000 common and rare functional genomic variants from 71 individuals of the 'Paisa' pedigree, the world's largest pedigree segregating a severe form of early-onset AD, who were affected carriers of the fully penetrant E280A mutation in the presenilin-1 (PSEN1) gene. Affected carriers with ages at the extremes of the ADAOO distribution (30s-70s age range), and linear mixed-effects models were used to build single-locus regression models outlining the ADAOO. We identified the rs7412 (APOE*E2 allele) as a whole exome-wide ADAOO modifier that delays ADAOO by ~12 years (ß=11.74, 95% confidence interval (CI): 8.07-15.41, P=6.31 × 10(-8), PFDR=2.48 × 10(-3)). Subsequently, to evaluate comprehensively the APOE (apolipoprotein E) haplotype variants (E1/E2/E3/E4), the markers rs7412 and rs429358 were genotyped in 93 AD affected carriers of the E280A mutation. We found that the APOE*E2 allele, and not APOE*E4, modifies ADAOO in carriers of the E280A mutation (ß=8.24, 95% CI: 4.45-12.01, P=3.84 × 10(-5)). Exploratory linear mixed-effects multilocus analysis suggested that other functional variants harbored in genes involved in cell proliferation, protein degradation, apoptotic and immune dysregulation processes (i.e., GPR20, TRIM22, FCRL5, AOAH, PINLYP, IFI16, RC3H1 and DFNA5) might interact with the APOE*E2 allele. Interestingly, suggestive evidence as an ADAOO modifier was found for one of these variants (GPR20) in a set of patients with sporadic AD from the Paisa genetic isolate. This is the first study demonstrating that the APOE*E2 allele modifies the natural history of AD typified by the age of onset in E280A mutation carriers. To the best of our knowledge, this is the largest analyzed sample of patients with a unique mutation sharing uniform environment. Formal replication of our results in other populations and in other forms of AD will be crucial for prediction, follow-up and presumably developing new therapeutic strategies for patients either at risk or affected by AD.

Contact sensitisation in adults: a 5-year retrospective review in hospital Kuala Lumpur.

BACKGROUND: The pattern of contact sensitisation should be monitored in order to detect the changing trend of sensitising allergens. We aim to evaluate contact sensitisation in adults suspected to have allergic contact dermatitis. METHODS: This is a five-year retrospective review on contact sensitisation in adults patch-tested with the European Standard and extended series between 2011 and 2015 in the Department of Dermatology, Hospital Kuala Lumpur. RESULTS: There were 689 adults (M:F= 1:2.04; mean age 40.5 years) who were patch-tested. The majority (175, 25.4%) were white collar workers and 118 (17.1%) were healthcare workers. The provisional diagnoses of patients included contact dermatitis (80.8%); endogenous eczema (7.9%); hand eczema (3.2%); hand and foot eczema (3.5%); foot eczema (1.4%) and photodermatitis (1.2%). The allergens selected for testing were based on past and present history of exposure. Almost all (688, 99.8%) were patch-tested with the European standard allergens and 466 (67.6%) were tested with the extended series. About three quarter (528, 76.6%) developed at least one positive reaction. The top five most frequent reactions were to nickel sulphate (35.3%); potassium dichromate (16.5%); methylchloroisothiazolinone (12.9%), fragrance mix I (12.6%), and cobalt chloride (10.2%). The commonest sensitisations identified in the extended series were palladium chloride (23/105, 21.9%), stannous chloride (18/85, 21.2%), miconazole (7/44, 15.9%), gold(I)sodium thiosulfate (16/105, 15.2%) and thimerosal (29/202, 14.4%). CONCLUSION: Contact sensitisation was detected in 76.6% of adults patch-tested. Nickel sulphate was found to be the most frequently sensitising allergen. The rising prevalence of methylchloroisothiazolinone/methylisothiazolinone sensitization poses significant concern.

Conventional versus molecular detection of Chlamydia trachomatis and Neisseria gonorrhoeae among males in a sexually transmitted infections clinic.

BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae are important bacterial pathogens of sexually transmitted infections (STIs) worldwide. This study sought to compare the analytical sensitivity and specificity of conventional methods against a rapid molecular method in detecting STIs caused by these bacteria. METHODS: Ninety five first-time male attendees of the Genito-urinary Medicine Clinic in Hospital Kuala Lumpur were included in this cross-sectional study. The detection of C. trachomatis was achieved through direct fluorescence antibody (DFA) staining of urethral swabs and real-time polymerase chain reaction testing (Xpert® CT/NG assay) on urine specimens. N. gonorrhoeae was detected through Gram staining and culture of urethral swabs and Xpert® CT/ NG assay on urine specimens. RESULTS: From the Xpert® CT/NG results, 11 (11.6%) attendees had chlamydia, 23 (24.2%) had gonorrhoea and 8 (8.4%) had both STIs. The sensitivity and specificity of DFA in detecting chlamydia compared to Xpert® CT/NG were 5.3% (95% CI: 0-28) and 94.7% (95% CI: 86-98), respectively. For gonorrhoea, the sensitivity and specificity of Gram staining were 90.3% (95% CI: 73-98) and 95.3% (86-99), respectively, whereas the sensitivity and specificity of culture compared to Xpert® CT/NG were 32.2% (95% CI: 17-51) and 100% (95% CI: 93-100), respectively. CONCLUSION: Although Gram-stained urethral swab smears are sensitive enough to be retained as a screening tool for gonorrhoea, culture as well as DFA lack sensitivity and are poorly suited to screen for gonorrhoea and chlamydia, respectively. However, owing to their high specificity, conventional detection methods are still suitable as confirmatory tests for gonorrhoea and chlamydia.

Co-morbidity after oesophageal cancer surgery and recovery of health-related quality of life.

BACKGROUND: Although health-related quality of life (HRQoL) recovers after surgery for oesophageal cancer in most long-term survivors, one in seven patients experiences a deterioration in HRQoL for reasons yet unknown. The aim of this study was to assess whether co-morbidities diagnosed after surgery influence recovery of HRQoL. METHODS: Patients who underwent surgery for cancer of the oesophagus or gastro-oesophageal junction in Sweden between 2001 and 2005 were included. HRQoL was assessed by means of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OES18 questionnaires. Repeated-measures ANOVA was used to assess mean differences in HRQoL scores between three co-morbidity status groups (healthy, stable and increased) over time. Probabilities of deterioration in HRQoL were calculated based on marginal probabilities from logistic regression models. RESULTS: At 5 years' follow-up, 153 (24·8 per cent) of 616 patients were alive and 137 responded to at least two of three questionnaires. The healthy and increased co-morbidity groups showed deterioration in almost all aspects of HRQoL at 6 months after surgery compared with baseline. The increased co-morbidity group also deteriorated in several aspects from 3 to 5 years after surgery. Patients with an increase in co-morbidity did not have a significantly increased probability of deterioration in HRQoL over time compared with healthy or stable patients, except with respect to cognitive function, loss of appetite, choking and coughing. CONCLUSION: Patients with an increase in co-morbidities after oesophagectomy experience long-term deterioration in HRQoL.

Impact of co-morbidity on mortality after oesophageal cancer surgery.

BACKGROUND: There is limited knowledge of how co-morbidities influence survival after surgery for oesophageal cancer. This population-based cohort study investigated how Charlson co-morbidity index and specific co-morbidities influenced all-cause and disease-specific mortality. METHODS: Data from all patients who underwent oesophageal cancer surgery in Sweden in 1987-2010, with follow-up until 2012, came from histopathology records, operation charts and nationwide registers. Associations between co-morbidities (Charlson co-morbidity index) and mortality were analysed using Cox proportional hazard regression with adjustment for potential confounding, and presented as hazard ratio (HR) with 95 per cent c.i. RESULTS: Among 1822 patients there were 1474 deaths (80.9 per cent), of which 1139 (77.3 per cent) occurred between 91 days and 5 years after surgery. Overall all-cause mortality was increased in patients with a Charlson score of 2 or more (HR 1.24, 95 per cent c.i. 1.08 to 1.42), and those with a history of myocardial infarction (HR 1.23, 1.01 to 1.49) or congestive heart failure (HR 1.31, 1.04 to 1.67). Patients with squamous cell carcinoma had increased overall all-cause mortality if they had been diagnosed with cerebrovascular disease (HR 1.35, 1.00 to 1.83) or other cancers (HR 1.36, 1.09 to 1.71), whereas those with adenocarcinoma did not. A Charlson score of 1 or exposure to the co-morbidity groups peripheral vascular disease, chronic pulmonary disease, connective tissue disease, peptic ulcer disease, diabetes and liver disease did not increase mortality. The disease-specific results were generally similar to the all-cause mortality data. CONCLUSION: Co-morbidity with a Charlson score of 2 or more, previous myocardial infarction and congestive heart failure were associated with increased mortality after oesophageal cancer surgery undertaken with curative intent.

Surgical prevention of reflux after esophagectomy for cancer.

BACKGROUND: Reflux frequently occurs after a gastric conduit has replaced the resected esophagus. In this Swedish population-based cohort study, the potential antireflux effects of using cervical anastomosis, intrathoracic antireflux anastomosis, or pyloric drainage, and a risk of dysphagia due to cervical anastomosis and intrathoracic antireflux anastomosis were studied. METHODS: Patients undergoing esophagectomy with gastric conduit reconstruction in 2001-2005 were included. Reflux symptoms and dysphagia were assessed 6 months and 3 years postoperatively using a validated questionnaire (EORTC QLQ-OES18). The study exposures were cervical anastomosis, antireflux anastomosis, and pyloric drainage procedure. Multivariable logistic regression and propensity-adjusted analyses based on multinomial logistic regression estimated odds ratios (OR) with 95 % confidence intervals (CI), adjusted for potential confounding. RESULTS: A total of 304 patients were included in the study. Adjusted ORs for reflux symptoms were 0.9 (95 % CI 0.3-2.2) for patients with a cervical anastomosis compared to patients with an intrathoracic anastomosis, 0.9 (95 % CI 0.4-2.0) for patients with an antireflux anastomosis versus patients with a conventional anastomosis, and 1.5 (95 % CI 0.9-2.6) for patients after pyloric drainage versus patients without such a pyloric drainage procedure. Dysphagia was not statistically significantly increased after cervical anastomosis or antireflux anastomosis. ORs were virtually similar 3 years after surgery. No interactions were identified. The propensity analyses rendered similar results as the logistic regression models, except for a possibly increased dysphagia with a cervical anastomosis. CONCLUSIONS: Cervical anastomosis, antireflux anastomosis, and pyloric drainage do not seem to prevent reflux symptoms 6 months or 3 years after esophagectomy for cancer with a gastric conduit.

Influence of postoperative complications following esophagectomy for cancer on quality of life: A European multicenter study.

INTRODUCTION: Postoperative complications following major surgery have been shown to be associated with reduced health-related quality of life (HRQL), and severe complications may have profound negative effects. This study aimed to examine whether long-term HRQL differs with the occurrence and severity of complications in a European multicenter prospective dataset of patients following esophagectomy for cancer. METHODS: Disease-free patients following esophagectomy for cancer between 2010 and 2016 from the LASER study were included. Patients completed the LASER, EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires >1 year following treatment. Long-term HRQL was compared between patients with and without postoperative complications, subgroup analysis was performed for severity of complications (no, minor [Clavien-Dindo I-II], severe [Clavien-Dindo ≥ III]), using univariable and multivariable regression. RESULTS: 645 patients were included: 283 patients with no, 207 with minor and 155 with severe complications. Significantly more dyspnea (QLQ-C30) was reported by patients with compared to patients without complications (differenceinmeans6.3). In subgroup analysis, patients with severe complications reported more dyspnea (difference in means 8.3) than patients with no complications. None of the differences were clinically relevant (difference in means ≥ 10 points). LASER-based low mood (OR2.3) was statistically different for minor versus severe complications. CONCLUSION: Comparable HRQL was found in patients with and without postoperative complications following esophagectomy for cancer, after a mean follow-up of 4.4 years. Furthermore, patients with different levels of severity of complications had comparable HRQL. The level of HRQL in esophageal cancer patients are more likely explained by the impact of the complex procedure of the esophagectomy itself.

Wastewater-based epidemiology for tracking bacterial diversity and antibiotic resistance in COVID-19 isolation hospitals in Qatar.

BACKGROUND: Hospitals are hotspots for antimicrobial resistance genes (ARGs), and play a significant role in their emergence and spread. Large numbers of ARGs will be ejected from hospitals via wastewater systems. Wastewater-based epidemiology has been consolidated as a tool to provide real-time information, and represents a promising approach to understanding the prevalence of bacteria and ARGs at community level. AIMS: To determine bacterial diversity and identify ARG profiles in hospital wastewater pathogens obtained from coronavirus disease 2019 (COVID-19) isolation hospitals compared with non-COVID-19 facilities during the pandemic. METHODS: Wastewater samples were obtained from four hospitals: three assigned to patients with COVID-19 patients and one assigned to non-COVID-19 patients. A microbial DNA quantitative polymerase chain reaction was used to determine bacterial diversity and ARGs. FINDINGS: The assay recorded 27 different bacterial species in the samples, belonging to the following phyla: Firmicutes (44.4%), Proteobacteria (33.3%), Actinobacteria (11%), Bacteroidetes (7.4%) and Verrucomicrobiota (3.7%). In addition, 61 ARGs were detected in total. The highest number of ARGs was observed for the Hazem Mebaireek General Hospital (HMGH) COVID-19 patient site (88.5%), and the lowest number of ARGs was found for the HMGH non-patient site (24.1%). CONCLUSION: The emergence of contaminants in sewage water, such as ARGs and high pathogen levels, poses a potential risk to public health and the aquatic ecosystem.

Defunctioning stoma in rectal cancer surgery - A risk factor for Low Anterior Resection Syndrome?

BACKGROUND: In rectal cancer surgery the formation of a defunctioning stoma is common in order to reduce the consequences of an anastomotic leakage. The role of a defunctioning stoma and time to stoma reversal, in relation to major Low Anterior Resection Syndrome (LARS) in the long-term perspective, is still unclear. The aim of the study was to investigate the association between a defunctioning stoma and long-term bowel function. METHOD: Patients who underwent curative rectal cancer surgery between 2007 and 2013 in Stockholm county, Sweden, who had no history of anastomotic leakage, without a remaining stoma, free of cancer and alive in April 2017 were eligible for the study. The exposures were (i) use of defunctioning stoma at cancer surgery and (ii) time to stoma reversal. Main outcome was major LARS with information retrieved from the LARS score questionnaire. Multivariable logistic regression model was used to calculate odds ratios (OR) primary comparing major LARS to no LARS. RESULTS: A total of 430 patients were included in analysis. The mean follow-up time was 6.7 years after surgery (range 3.4-10.7 years). The use of a defunctioning stoma was associated to major LARS with an adjusted OR of 2.43 (95% CI 1.14-5.20) when compared to no stoma. There were no evident associations between time to stoma reversal and the risk of major LARS. CONCLUSION: This study indicates that the presence of a defunctioning stoma is associated with impaired bowel function in the long-term perspective, while failing to show any clear association to time to stoma reversal.