Multiple staging investigations may not change management in patients with high-grade dysplasia or early esophageal adenocarcinoma.

The clinical value of multiple staging investigations for high-grade dysplasia or early adenocarcinoma of the esophagus is unclear. A single-center prospective cohort of patients treated for early esophageal cancer between 2000 and 2019 was analyzed. This coincided with a transition period from esophagectomy to endoscopic mucosal resection (EMR) as the treatment of choice. Patients were staged with computed tomography (CT), endoscopic ultrasound (EUS) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography(PET)/CT. The aim of this study was to assess their accuracy and impact on clinical management. 297 patients with high-grade dysplasia or early adenocarcinoma were included (endoscopic therapy/EMR n = 184; esophagectomy n = 113 [of which a 'combined' group had surgery preceded by endoscopic therapy n = 23]). Staging accuracy was low (accurate staging EMR: CT 40.1%, EUS 29.6%, FDG-PET/CT 11.0%; Esophagectomy: CT 43.3%, EUS 59.7%, FDG-PET/CT 29.6%; Combined: CT 28.6%, EUS46.2%, FDG-PET/CT 30.0%). Staging inaccuracies across all groups that could have changed management by missing T2 disease were CT 12%, EUS 12% and FDG-PET/CT 1.6%. The sensitivity of all techniques for detecting nodal disease was low (CT 12.5%, EUS 12.5%, FDG-PET/CT0.0%). Overall, FDG-PET/CT and EUS changed decision-making in only 3.2% of patients with an early cancer on CT and low-risk histology. The accuracy of staging with EUS, CT and FDG-PET/CT in patients with high-grade dysplasia or early adenocarcinoma of the esophagus is low. EUS and FDG-PET/CT added relevant staging information over standard CT in very few cases, and therefore, these investigations should be used selectively. Factors predicting the need for esophagectomy are predominantly obtained from EMR histology rather than staging investigations.

Clinical Relevance of the Tumor Location-Modified Laurén Classification System for Gastric Cancer in a Western Population.

BACKGROUND: The Tumor Location-Modified Laurén Classification (MLC) system combines Laurén histologic subtype and anatomic tumor location. It divides gastric tumors into proximal non-diffuse (PND), distal non-diffuse (DND), and diffuse (D) types. The optimum classification of patients with Laurén mixed tumors in this system is not clear due to its grouping with both diffuse and non-diffuse types in previous studies. The clinical relevance of the MLC in a Western population has not been examined. METHODS: A cohort study investigated 404 patients who underwent gastrectomy for gastric adenocarcinoma between 2005 and 2020. The classification of Laurén mixed tumors was evaluated using receiver operating characteristic (ROC) curve analysis and comparison of clinicopathologic characteristics (chi-square). Survival analysis was performed using multivariable Cox regression. RESULTS: The ROC curve analysis demonstrated a slightly higher area under the curve value for predicting survival when Laurén mixed tumors were grouped with intestinal-type rather than diffuse-type tumors (0.58 vs 0.57). Survival, tumor recurrence, and resection margin positivity in mixed tumors also was more similar to intestinal type. Distal non-diffuse tumors had the best 5-year survival (DND 64.7 % vs PND 56.1 % vs diffuse 45.1 %; p = 0.006) and were least likely to have recurrence (DND 27.0 % vs PND 34.3 % vs diffuse 48.3 %; p = 0.001). Multivariable analysis demonstrated that MLC was an independent prognostic factor for survival (PND: hazard ratio [HR], 1.64; 95 % confidence interval [CI], 1.16-2.32 vs diffuse: HR, 2.20; 95 % CI, 1.56-3.09) CONCLUSIONS: The MLC was an independent prognostic marker in this Western cohort of patients with gastric adenocarcinoma. The patients with PND and D tumors had worse survival than those with DND tumors.

Survival after antireflux surgery versus medication in patients with reflux oesophagitis or Barrett's oesophagus: multinational cohort study.

BACKGROUND: The aim was to examine the hypothesis that antireflux surgery with fundoplication improves long-term survival compared with antireflux medication in patients with reflux oesophagitis or Barrett's oesophagus. METHOD: Individuals aged between 18 and 70 years with reflux oesophagitis or Barrett's oesophagus (intestinal metaplasia) documented from in-hospital and specialized outpatient care were selected from national patient registries in Denmark, Finland, Iceland, and Sweden from 1980 to 2014. The study investigated all-cause mortality and disease-specific mortality, comparing patients who had undergone open or laparoscopic antireflux surgery with fundoplication versus those using antireflux medication. Multivariable Cox regression analysis was used to estimate hazard ratios (HRs) with 95 per cent confidence intervals for all-cause mortality and disease-specific mortality, adjusted for sex, age, calendar period, country, and co-morbidity. RESULTS: Some 240 226 patients with reflux oesophagitis or Barrett's oesophagus were included, of whom 33 904 (14.1 per cent) underwent antireflux surgery. The risk of all-cause mortality was lower after antireflux surgery than with use of medication (HR 0.61, 95 per cent c.i. 0.58 to 0.63), and lower after laparoscopic (HR 0.56, 0.52 to 0.60) than open (HR 0.80, 0.70 to 0.91) surgery. After antireflux surgery, mortality was decreased from cardiovascular disease (HR 0.58, 0.55 to 0.61), respiratory disease (HR 0.62, 0.57 to 0.66), laryngeal or pharyngeal cancer (HR 0.35, 0.19 to 0.65), and lung cancer (HR 0.67, 0.58 to 0.80), but not from oesophageal cancer (HR 1.05, 0.87 to 1.28), compared with medication, The decreased mortality rates generally remained over time. CONCLUSION: In patients with reflux oesophagitis or Barrett's oesophagus, antireflux surgery is associated with lower mortality from all causes, cardiovascular disease, respiratory disease, laryngeal or pharyngeal cancer, and lung cancer, but not from oesophageal cancer, compared with antireflux medication.

Risk factors for implant failure following revision surgery in breast cancer patients with a previous immediate implant-based breast reconstruction.

PURPOSE: The aim of the current study was to evaluate risk factors and timing of revision surgery following immediate implant-based breast reconstruction (IBR). METHODS: This retrospective cohort included women with a previous therapeutic mastectomy and implant-based IBR who had undergone implant revision surgery between 2005 and 2015. Data were collected by medical chart review and registered in the Stockholm Breast Reconstruction Database. The primary endpoint was implant removal due to surgical complications, i.e. implant failure. RESULTS: The cohort consisted of 475 women with 707 revisions in 542 breasts. Overall, 33 implants were removed due to complications. The implant failure rate (4.7%) was lower without RT (2.4%) compared to RT administered after mastectomy (7.5%) and prior to IBR (6.5%) (p = 0.007). While post-mastectomy RT (OR 3.39, 95% CI 1.53-7.53), smoking (OR 3.90, 95% CI 1.76-8.65) and diabetes (OR 5.40, 95% CI 1.05-27.85) were confirmed as risk factors, time from completion of RT (> 9 months, 6-9 months, < 6 months) was not (OR 3.17, 95% CI 0.78-12.80, and OR 0.74, 95% CI 0.20-2.71). Additional risk factors were a previous axillary clearance (OR 4.91, 95% CI 2.09-11.53) and a history of a post-IBR infection (OR 15.52, 95% CI 4.15-58.01, and OR 12.93, 95% CI 3.04-55.12, for oral and intravenous antibiotics, respectively). CONCLUSIONS: Previous axillary clearance and a history of post-IBR infection emerged as novel risk factors for implant failure after revision surgery. While known risk factors were confirmed, time elapsed from RT completion to revision surgery did not influence the outcome in this analysis.

Socioeconomic status differs between breast cancer patients treated with mastectomy and breast conservation, and affects patient-reported preoperative information.

PURPOSE: Breast cancer treatment is reported to be influenced by socioeconomic status (SES). Few reports, however, stem from national, equality-based health care systems. The aim of this study was to analyse associations between SES, rates of breast-conserving surgery (BCS), patient-reported preoperative information and perceived involvement in Sweden. METHODS: All women operated for primary breast cancer in Sweden in 2013 were included. Tumour and treatment data as well as socioeconomic data were retrieved from national registers. Postal questionnaires regarding preoperative information about breast-conserving options and perceived involvement in the decision-making process had previously been sent to all women receiving mastectomy. RESULTS: Of 7735 women, 4604 (59.5%) received BCS. In addition to regional differences, independent predictors of BCS were being in the middle or higher age groups, having small tumours without clinically involved nodes, being born in Europe outside Sweden, having a higher education than primary school and an intermediate or high income per household. Women with smaller, clinically node-negative tumours felt more often involved in the surgical decision and informed about breast-conserving options (both p < 0.001). In addition, women who perceived that BCS was discussed as an alternative to mastectomy were more often in a partnership (p < 0.001), not born in Sweden (p = 0.035) and had an employment (p = 0.031). CONCLUSION: Socioeconomic factors are associated with surgical treatment even in a national health care system that is expected to offer all women the same standard of care. This should be taken into account and adapted to in preoperative counselling on surgical options in breast cancer.

Reintervention or mortality within 90 days of bariatric surgery: population-based cohort study.

BACKGROUND: Bariatric surgery carries a risk of severe postoperative complications, sometimes leading to reinterventions or even death. The incidence and risk factors for reintervention and death within 90 days after bariatric surgery are unclear, and were examined in this study. METHODS: This population-based cohort study included all patients who underwent bariatric surgery in one of the five Nordic countries between 1980 and 2012. Data on surgical and endoscopic procedures, diagnoses and mortality were retrieved from national high-quality and complete registries. Multivariable Cox regression analysis was used to calculate hazard ratios (HRs), adjusted for country, age, sex, co-morbidity, type of surgery and approach, year and hospital volume of bariatric surgery. RESULTS: Of 49 977 patients, 1111 (2·2 per cent) had a reintervention and 95 (0·2 per cent) died within 90 days of bariatric surgery. Risk factors for the composite outcome reintervention/mortality were older age (HR 1·65, 95 per cent c.i. 1·36 to 2·01, for age at least 50 years versus less than 30 years) and co-morbidity (HR 2·66, 1·53 to 4·62, for Charlson co-morbidity index score 2 or more versus 0). The risk of reintervention/mortality was decreased for vertical banded gastroplasty compared with gastric bypass (HR 0·37, 0·28 to 0·48) and more recent surgery (HR 0·51, 0·39 to 0·67, for procedures undertaken in 2010 or later versus before 2000). Sex, surgical approach (laparoscopic versus open) and hospital volume did not influence risk of reintervention/mortality, but laparoscopic surgery was associated with a lower risk of 90-day mortality (HR 0·29, 0·16 to 0·53). CONCLUSION: Reintervention and death were uncommon events within 90 days of bariatric surgery even in this unselected nationwide cohort from five countries. Older patients with co-morbidities have an increased relative risk of these outcomes.

ANTECEDENTES: La cirugía bariátrica conlleva un riesgo de complicaciones postoperatorias graves, que algunas veces ocasionan reintervenciones o incluso son causa de mortalidad. La incidencia y los factores de riesgo de reinterveniones y mortalidad a los 90 días tras cirugía bariátrica no están claros, y fueron examinados en este estudio. MÉTODOS: Todos los pacientes que fueron sometidos a cirugía bariátrica en uno de los cinco países nórdicos en 1980-2012 fueron incluidos en un estudio de cohortes de base poblacional. Los datos de los procedimientos quirúrgicos y endoscópicos, diagnóstico, y mortalidad se obtuvieron a partir de registros nacionales completos y de alta calidad. Mediante una regresión de Cox multivariable se obtuvieron los cocientes de riesgos instantáneos (hazard ratios, HR) y los intervalos de confianza 95% (i.c. del 95%) ajustados por país, edad, sexo, comorbilidad, y tipo, abordaje, año y volumen de casos de cirugía bariátrica del hospital. RESULTADOS: De un total de 49.977 pacientes, 1.111 (2,2%) precisaron una reintervención y 95 (0,2%) fallecieron durante los primeros 90 días tras la cirugía bariátrica. Los factores de riesgo para el resultado compuesto reintervención/mortalidad fueron la edad avanzada (HR = 1,7 (i.c. del 95% 1,4-2,0) edad ≥ 50 versus < 30 años)) y la comorbilidad (HR = 2,7 (i.c. del 95% 1,5-4,6) puntuación del índice de comorbilidad de Charlson ≥ 2 versus 0)). Se observó una disminución de los HRs tras la gastroplastia vertical con banda en comparación con el bypass gástrico (HR = 0,4, (i.c. del 95% 0,3-0,5)) y el periodo de estudio más reciente (HR = 0,5 (i.c. del 95% 0,4-0,7) ≥ 2010 versus < 2000)). El sexo, el abordaje quirúrgico laparoscópico versus abierto y el volumen del hospital no influyeron sobre el riesgo de reintervención/mortalidad, pero la cirugía laparoscópica se asoció con una mortalidad a los 90 días más baja (HR 0,3, i.c. del 95% 0,2-0,5). CONCLUSIÓN: La reintervención y la mortalidad son eventos infrecuentes durante los primeros 90 días tras la cirugía bariátrica, incluso en esta cohorte nacional y no seleccionada de cinco paises. Los pacientes mayores con comorbilidades tienen un riesgo relativo aumentado de reintervención y mortalidad.

Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin.

BACKGROUND: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. METHODS: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. RESULTS: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4-5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. CONCLUSION: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.

ANTECEDENTES: El papel del tratamiento adyuvante en pacientes con adenocarcinoma esofagogástrico tratados con quimioterapia neoadyuvante es polémico. En la práctica del Reino Unido, el estado del margen de resección quirúrgico se utiliza a menudo para identificar a los pacientes que reciben tratamiento adyuvante. El objetivo de este estudio fue evaluar el beneficio en la supervivencia del tratamiento adyuvante en pacientes con márgenes de resección positivos (R1). MÉTODOS: Se combinaron dos bases de datos de instituciones del Reino Unido que recogen información de forma prospectiva para identificar pacientes elegibles. Se utilizaron análisis de regresión de Cox ajustados para comparar la supervivencia global y la supervivencia libre de recidiva según el tratamiento adyuvante. Los patrones de recidiva se evaluaron como resultado secundario. También se realizó un análisis de emparejamiento por puntaje de propensión. RESULTADOS: De 616 pacientes incluidos en la base de datos combinada, se incluyeron en el estudio 242 pacientes con resección R1. De estos pacientes, 112 (46%) recibieron quimiorradioterapia adyuvante, 46 (19%) pacientes fueron tratados con quimioterapia adyuvante y 84 (35%) pacientes no recibieron ningún tratamiento. En el análisis ajustado, la quimiorradioterapia adyuvante mejoró la supervivencia libre de recidiva (cociente de riesgos instantáneos, hazard ratio, HR 0,59, i.c. del 95% 0,38-0,94; P = 0,026) con un beneficio tanto para la recidiva local (HR 0,48, i.c. del 95% 0,24-0,99; P = 0,047) como para la sistémica (HR 0,56, i.c. del 95% 0,33-0,94; P = 0,027). Cuando los pacientes se clasificaron según la respuesta tumoral a la quimioterapia neoadyuvante, los no respondedores (Mandard Grado 4/5) tratados con quimiorradioterapia adyuvante obtuvieron un beneficio en la supervivencia (HR 0,61, i.c. del 95% 0,38-0,97; P = 0,037). En el análisis por emparejamiento por puntaje de propensión, se observó un beneficio en la supervivencia global (HR 0,62, i.c. del 95% 0,39-0,98; P = 0,042) y en la supervivencia libre de recidiva (HR 0,51.i.c. del 95% 0,30-0,87; P = 0,004) con la quimiorradioterapia adyuvante frente a no recibir tratamiento adyuvante. CONCLUSIÓN: El tratamiento adyuvante puede mejorar la supervivencia global y la supervivencia libre de recidiva en pacientes con margen de resección positivo. Este patrón parece más pronunciado con la quimiorradioterapia adyuvante en pacientes que no responden a la quimioterapia.

Menopausal hormone therapy and biliary tract cancer: a population-based matched cohort study in Sweden.

BACKGROUND: This study tested the hypothesis that contemporary menopausal hormonal therapy (MHT) increases the risk of biliary tract cancer. The risk of cancer of the biliary tract (gallbladder and extra-hepatic bile ducts) may be increased following estrogen exposure. MATERIAL AND METHODS: This was a nationwide population-based matched cohort study in Sweden. Data from the Swedish Prescribed Drug Register identified all women exposed to systemic MHT in 2005-2012. Group-level matching (1:3 ratio) was used to select women unexposed to MHT from the same study base, matched for history of delivery, thrombotic events, hysterectomy, age, smoking- and alcohol related diseases, obesity, and diabetes. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Comparing 290,186 women exposed to MHT with 870,165 unexposed, MHT did not increase the OR of biliary tract cancer. The OR of gallbladder cancer was rather decreased in MHT users (OR 0.58, 95% CI 0.43-0.79), but this association became attenuated and statistically non-significant after adjusting for gallstone disease (OR 0.84, 95% CI 0.60-1.15). The OR of extra-hepatic bile duct cancers was 0.83 (95% CI 0.61-1.15). There were no clear differences when the analyses were stratified for estrogen or estrogen/progestogen combinations. MHT increased the risk of gallstone disease (OR 6.95, 95% CI 6.64-7.28). CONCLUSIONS: Contemporary MHT does not seem to increase the risk of biliary tract cancer. The decreased risk of gallbladder cancer may be explained by the increased use of surgery for symptomatic gallstones in MHT users.

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.

Different menopausal hormone regimens and risk of breast cancer.

Background: There are considerable knowledge gaps concerning different estrogen and progestin formulations, regimens, and modes of administration of menopausal hormone therapy (HT) and the risk of breast cancer. Our objective was to assess the different treatment options for menopausal HT and the risk of breast cancer. Patients and methods: This Swedish prospective nationwide cohort study included all women who received ≥1 HT prescription during the study period 2005-2012 (290 186 ever-users), group-level matched (1 : 3) to 870 165 never-users; respectively, 6376 (2.2%) and 18 754 (2.2%) developed breast cancer. HT, ascertained from the Swedish Prescribed Drug Register, was subdivided by estrogen and progestogen formulation types, regimens (continuous versus sequential) and modes of administration (oral versus transdermal). The risk of invasive breast cancer was presented as adjusted odds ratios (OR) and 95% confidence intervals. Results: Current use of estrogen-only therapy was associated with a slight excess breast cancer risk [odds ratio (OR) = 1.08 (1.02-1.14)]. The risk for current estrogen plus progestogen therapy was higher [OR = 1.77 (1.69-1.85)] and increased with higher age at initiation [OR = 3.59 (3.30-3.91) in women 70+ years]. In contrast, past use was associated with reduced breast cancer risk. Current continuous estrogen/progestin use was associated with higher risk [OR = 2.18 (1.99-2.40) for progesterone-derived; OR = 2.66 (2.49-2.84) for testosterone-derived] than sequential use [OR = 1.37 (0.97-1.92) for progesterone-derived; OR = 1.12 (0.96-1.30) for testosterone-derived]. The OR for current use was 1.12 (1.04-1.20) for estradiol, 0.76 (0.69-0.84) for estriol, 4.47 (2.67-7.48) for conjugated estrogens, and 1.68 (1.51-1.87) for tibolone. Oral and cutaneous HT showed similar associations. Conclusion: Different HT regimens have profoundly different effects on breast cancer risk. Because of registry limitations some confounders could not be assessed. This knowledge may guide clinical decision-making when HT is considered.

A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial.

Background: Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse. Patients and methods: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort. Results: Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings. Conclusions: These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.

Population-based cohort study of diabetes mellitus and mortality in gastric adenocarcinoma.

BACKGROUND: Gastric adenocarcinoma is a common cause of cancer death globally. It remains unclear whether coexisting diabetes mellitus influences survival in patients with this tumour. A cohort study was conducted to determine whether coexisting diabetes increases mortality in gastric adenocarcinoma. METHODS: This nationwide population-based cohort study included all patients diagnosed with gastric adenocarcinoma in Sweden between 1990 and 2014. Cox proportional hazards regression and competing risks regression were used to assess the influence of coexisting diabetes on disease-specific mortality in gastric adenocarcinoma with adjustment for sex, age, calendar year and co-morbidity (Charlson Co-morbidity Index score excluding diabetes). RESULTS: Among 23 591 patients with gastric adenocarcinoma, 2806 (11·9 per cent) had coexisting diabetes. Overall, patients with diabetes had a moderately increased risk of disease-specific mortality after diagnosis of gastric adenocarcinoma compared with those without diabetes, as shown by both Cox regression (hazard ratio (HR) 1·17, 95 per cent c.i. 1·11 to 1·22) and competing risks regression (sub-HR 1·08, 1·02 to 1·13). The HRs for disease-specific mortality were notably increased in diabetic patients without other co-morbidity (HR 1·23, 1·15 to 1·32) and in diabetic patients who had surgery with curative intent (HR 1·27, 1·16 to 1·38). CONCLUSION: These findings indicate a worse prognosis in patients with gastric adenocarcinoma and coexisting diabetes compared with those without diabetes.

Obesity surgery and risk of cancer.

BACKGROUND: Obesity increases the risk of several types of cancer. Whether bariatric surgery influences the risk of obesity-related cancer is not clear. This study aimed to uncover the risk of hormone-related (breast, endometrial and prostate), colorectal and oesophageal cancers following obesity surgery. METHODS: This national population-based cohort study used data from the Hospital Episode Statistics database in England collected between 1997 and 2012. Propensity matching on sex, age, co-morbidity and duration of follow-up was used to compare cancer risk among obese individuals undergoing bariatric surgery (gastric bypass, gastric banding or sleeve gastrectomy) and obese individuals not undergoing such surgery. Conditional logistic regression provided odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: In the study period, from a cohort of 716 960 patients diagnosed with obesity, 8794 patients who underwent bariatric surgery were matched exactly with 8794 obese patients who did not have surgery. Compared with the no-surgery group, patients who had bariatric surgery exhibited a decreased risk of hormone-related cancers (OR 0·23, 95 per cent c.i. 0·18 to 0·30). This decrease was consistent for breast (OR 0·25, 0·19 to 0·33), endometrium (OR 0·21, 0·13 to 0·35) and prostate (OR 0·37, 0·17 to 0·76) cancer. Gastric bypass resulted in the largest risk reduction for hormone-related cancers (OR 0·16, 0·11 to 0·24). Gastric bypass, but not gastric banding or sleeve gastrectomy, was associated with an increased risk of colorectal cancer (OR 2·63, 1·17 to 5·95). Longer follow-up after bariatric surgery strengthened these diverging associations. CONCLUSION: Bariatric surgery is associated with decreased risk of hormone-related cancers, whereas gastric bypass might increase the risk of colorectal 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.

Lymph node regression and survival following neoadjuvant chemotherapy in oesophageal adenocarcinoma.

BACKGROUND: The aim was to define the pathological response in lymph nodes following neoadjuvant chemotherapy for oesophageal adenocarcinoma and to quantify any associated survival benefit. METHODS: Lymph nodes retrieved at oesophagectomy were examined retrospectively by two pathologists for evidence of a response to chemotherapy. Patients were classified as lymph node-negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive (allocated a lymph node regression score based on the proportion of fibrosis to residual tumour). Lymph node responders (score 1, complete response; 2, less than 10 per cent remaining tumour; 3, 10-50 per cent remaining tumour) and non-responders (score 4, more than 50 per cent viable tumour; 5, no response) were compared in survival analyses using Kaplan-Meier and Cox regression analysis. RESULTS: Among 377 patients, 256 had neoadjuvant chemotherapy. Overall, 68 of 256 patients (26·6 per cent) had a lymph node response and 115 (44·9 per cent) did not. The remaining 73 patients (28·5 per cent) had negative lymph nodes with no evidence of regression. Some patients had a lymph node response in the absence of a response in the primary tumour (27 of 99, 27 per cent). Lymph node responders had a significant survival benefit (P < 0·001), even when stratified by patients with or without a response in the primary tumour. On multivariable analysis, lymph node responders had decreased overall (hazard ratio 0·53, 95 per cent c.i. 0·36 to 0·78) and disease-specific (HR 0·42, 0·27 to 0·66) mortality, and experienced reduced local and systemic recurrence. CONCLUSION: Lymph node regression is a strong prognostic factor and may be more important than response in the primary tumour.

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.

A comparison of the left thoracoabdominal and Ivor-Lewis esophagectomy.

The purpose of this study was to assess the oncological outcomes of a large multicenter series of left thoracoabdominal esophagectomies, and compare these to the more widely utilized Ivor-Lewis esophagectomy. With ethics approval and an established study protocol, anonymized data from five centers were merged into a structured database. The study exposure was operative approach (ILE or LTE). The primary outcome measure was time to death. Secondary outcome measures included time to tumor recurrence, positive surgical resection margins, lymph node yield, postoperative death, and hospital length of stay. Cox proportional hazards models provided hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, pathological tumor stage, tumor grade, lymphovascular invasion, and neoadjuvant treatment. Among 1228 patients (598 ILE; 630 LTE), most (86%) had adenocarcinoma (AC) and were male (81%). Comparing ILE and LTE for AC patients, no difference was seen in terms of time to death (HR 0.904 95%CI 0.749-1.1090) or time to recurrence (HR 0.973 95%CI 0.768-1.232). The risk of a positive resection margin was also similar (OR 1.022 95%CI 0.731-1.429). Median lymph node yield did not differ between approaches (LTE 21; ILE 21; P = 0.426). In-hospital mortality was 2.4%, significantly lower in the LTE group (LTE 1.3%; ILE 3.6%; P = 0.004). Median hospital stay was 11 days in the LTE group and 14 days in the ILE group (P < 0.0001). In conclusion, this is the largest series of left thoracoabdominal esophagectomies to be submitted for publication and the only one to compare two different transthoracic esophagectomy strategies. It demonstrates oncological equivalence between operative approaches but possible short- term advantages to the left thoracoabdominal esophagectomy.

Weekday of cancer surgery in relation to prognosis.

BACKGROUND: 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. METHODS: This nationwide Swedish population-based cohort study from 1997 to 2014 analysed weekday of elective surgery for ten major cancers in relation to disease-specific and all-cause mortality. Cox regression provided hazard ratios with 95 per cent confidence intervals, adjusted for the co-variables age, sex, co-morbidity, hospital volume, calendar year and tumour stage. RESULTS: A total of 228 927 patients were included. Later weekday of surgery (Thursdays and, even more so, Fridays) was associated with increased mortality rates for gastrointestinal cancers. Adjusted hazard ratios for disease-specific mortality, comparing surgery on Friday with that on Monday, were 1·57 (95 per cent c.i. 1·31 to 1·88) for oesophagogastric cancer, 1·49 (1·17 to 1·88) for liver/pancreatic/biliary cancer and 1·53 (1·44 to 1·63) for colorectal cancer. Excluding mortality during the initial 90 days of surgery made little difference to these findings, and all-cause mortality was similar to disease-specific mortality. The associations were similar in analyses stratified for co-variables. No consistent associations were found between weekday of surgery and prognosis for cancer of the head and neck, lung, thyroid, breast, kidney/bladder, prostate or ovary/uterus. CONCLUSION: Later weekday of surgery (Thursday or Friday) seems to influence the prognosis adversely for cancers of the gastrointestinal tract.

National study of the impact of patient information and involvement in decision-making on immediate breast reconstruction rates.

BACKGROUND: Reconstructive alternatives should be discussed with women facing mastectomy for breast cancer. These include immediate and delayed reconstruction, which both have inherent advantages and disadvantages. Immediate reconstruction rates vary considerably in Swedish healthcare regions, and the aim of the study was to analyse reasons for this disparity. METHODS: All women who underwent mastectomy for primary breast cancer in Sweden in 2013 were included. Tumour data were retrieved from the Swedish National Breast Cancer Registry and from questionnaires regarding patient information and involvement in preoperative decision-making sent to women who were still alive in 2015. RESULTS: Of 2929 women who had undergone 2996 mastectomies, 2906 were still alive. The questionnaire response rate was 76·3 per cent. Immediate reconstruction rates varied regionally, between 3·0 and 26·4 per cent. Tumour characteristics impacted on reconstruction rates but did not explain regional differences. Patient participation in decision-making, availability of plastic surgery services and patient information, however, were independent predictors of immediate breast reconstruction, and varied significantly between regions. Even in younger patients with low-risk tumours, rates of patient information ranged between 34·3 and 83·3 per cent. CONCLUSION: Significant regional differences in immediate reconstruction rates were not explained by differences in tumour characteristics, but by disparities in patient information, availability of plastic surgery services and involvement in decision-making.

Mortality from laparoscopic antireflux surgery in a nationwide cohort of the working-age population.

BACKGROUND: Both medication and surgery are effective treatments for severe gastro-oesophageal reflux disease (GORD). Postoperative risks have contributed to decreased use of antireflux surgery. The aim of this study was to assess short-term mortality following primary laparoscopic fundoplication. METHODS: This was a population-based nationwide cohort study including all Swedish hospitals that performed laparoscopic fundoplication between 1997 and 2013. All patients aged 18-65 years with GORD who underwent primary laparoscopic fundoplication during the study interval were included. The primary outcome was absolute all-cause and surgery-related 90- and 30-day mortality. Secondary outcomes were reoperation and length of hospital stay. Logistic regression was used to calculate odds ratios with 95 per cent confidence intervals of reoperation within 90 days and prolonged hospital stay (4 days or more). RESULTS: Of 8947 included patients, 5306 (59·3 per cent) were men and 551 (6·2 per cent) had significant co-morbidity (Charlson score above 0). Median age at surgery was 48 years, and median hospital stay was 2 days. The annual rate of laparoscopic fundoplication decreased from 15·3 to 2·4 patients per 100 000 population during the study period, whereas the proportion of patients with co-morbidity increased more than twofold. All-cause 90- and 30-day mortality rates were 0·08 per cent (7 patients) and 0·03 per cent (3 patients) respectively. Only one death (0·01 per cent) was directly surgery-related. The 90-day reoperation rate was 0·4 per cent (39 patients). Co-morbidity and older age were associated with an increased risk of prolonged hospital stay, but not reoperation. CONCLUSION: This population-based study revealed very low mortality and reoperation rates following primary laparoscopic fundoplication in the working-age population. The findings may influence clinical decision-making in the treatment of severe GORD.