No correlation to collagen synthesis disorders in patients with Perthes' disease: a nationwide Swedish register study of 3488 patients.

BACKGROUND: Mutations of the COL2A1 gene have been identified in patients with Perthes' disease. Several studies have hypothesised a connection between Perthes' disease and collagen synthesis disorders, especially COL2A1-related disorders, but no large studies on the subject have been made. The aim of this study was thus to discover if there is a connection between patients presenting with Perthes' disease, and collagen synthesis disorders. A secondary aim was to see if the children with both disorders had less optimal birth characteristics than the rest. METHODS: Swedish national registers were used to collect data on children diagnosed with Perthes' disease or a collagen synthesis disorder. These registers include all births in Sweden, and data from both outpatient and in-hospital visits. A wide range of data is included besides diagnoses. All children with follow-up data to the age of 15 years were included. Pearson's chi-square was used for analysis. Statistical significance was further analysed with Fisher's Exact Test. RESULTS: In total, 3488 children with either diagnosis were included. 1620 children had only Perthes disease, while 1808 children had only a collagen synthesis disorder. Five children were found to have both the diagnosis Perthes' disease and a collagen synthesis disorder. One child was large for their gestational age and none of the children had a low birthweight. Two of the children were moderately preterm. CONCLUSIONS: The distinct lack of overlap in such a large body of material raises doubt about a connection between the presentation of Perthes' disease and collagen synthesis disorders, either COL2A1-related or not. We could not find an overrepresentation of less optimal birth characteristics either.

Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

ERAS guidelines-driven upper gastrointestinal contrast study after esophagectomy can detect delayed gastric conduit emptying and improve outcomes.

BACKGROUND: Delayed gastric conduit emptying can occur after esophagectomy and has been shown to be associated with increased risk for postoperative complications. Application of a standardized clinical protocol after esophagectomy including an upper gastrointestinal contrast study has the potential to improve postoperative outcomes. METHODS: Prospective cohort including all patients operated with esophagectomy at two high-volume centers for esophageal surgery. The standardized clinical protocol included an upper gastrointestinal contrast study on day 2 or 3 after surgery. All images were compiled and evaluated for the purpose of the study. Clinical data was collected in IRB approved institutional databases at the participating centers. RESULTS: The study included 119 patients treated with esophagectomy of whom 112 (94.1%) completed an upper gastrointestinal contrast study. The results showed that 8 (7.1%) patients had radiological delayed gastric conduit emptying defined as no emptying of contrast through the pylorus. Partial conduit emptying was seen in 34 (30.4%) patients, and 70 (62.5%) patients had complete conduit emptying. Complete or partial emptying was associated with significantly earlier nasogastric tube removal (3 vs. 6 days) and hospital discharge 8 vs. 17 days, P < 0.001). Radiological signs of delayed gastric conduit emptying were shown to be associated with increased risk of postoperative complications. There was, however, no association with severe postoperative complications according to Clavien-Dindo score, pulmonary complications, anastomotic leak or need for intensive care. CONCLUSION: The results of the study demonstrate that postoperative upper gastrointestinal contrast studies can be used to assess the level of emptying of the gastric conduit after esophagectomy. Application of upper gastrointestinal contrast study in the ERAS guidelines-driven standardized clinical pathway after esophagectomy has the potential to improve postoperative outcomes.

Tension-free mesh versus suture-alone cruroplasty in antireflux surgery: a randomized, double-blind clinical trial.

BACKGROUND: Antireflux surgery is effective for the treatment of gastro-oesophageal reflux disease (GORD) but recurrence of hiatal hernia remains a challenge. In other types of hernia repair, use of mesh is associated with reduced recurrence rates. The aim of this study was to compare the use of mesh versus sutures alone for the repair of hiatal hernia in laparoscopic antireflux surgery. METHODS: Patients undergoing laparoscopic Nissen fundoplication for GORD between January 2006 and December 2010 were allocated randomly to closure of the diaphragmatic hiatus with crural sutures or non-absorbable polytetrafluoroethylene mesh (CruraSoft®). The primary outcome was recurrence of hiatal hernia, as determined by barium swallow study 12 months after surgery. Secondary outcomes were: intraoperative and postoperative complications, use of antireflux medication, postoperative oesophageal acid exposure, quality of life, dysphagia and duration of hospital stay. RESULTS: Some 77 patients were randomized to the suture technique and 82 patients underwent mesh repair. At 1 year, the hiatal hernia had recurred in six of 64 patients (9 per cent) in the mesh group and two of 64 (3 per cent) in the suture group (P = 0·144). Reflux symptoms, use of proton pump inhibitors and oesophageal acid exposure did not differ between the groups. At 3 years, recurrence rates were 13 and 10 per cent in the mesh and suture groups respectively (P = 0·692). Dysphagia scores decreased in both groups, but more patients had dysphagia for solid food after mesh closure (P = 0·013). Quality-of-life scores were comparable between the groups. CONCLUSION: Tension-free crural repair with non-absorbable mesh does not reduce the incidence of recurrent hiatal hernia compared with use of sutures alone in patients undergoing laparoscopic fundoplication. NCT03730233 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía antirreflujo es efectiva para el tratamiento de la enfermedad por reflujo gastroesofágico (gastro-oesophageal reflux disease, GORD), pero la recidiva de la hernia de hiato sigue siendo un desafío. En otros tipos de reparación herniaria, la utilización de mallas se asocia con tasas reducidas de recidiva. El objetivo de este estudio fue comparar la utilización de una malla con suturas solo para la reparación de la hernia de hiato en cirugía antirreflujo laparoscópica. MÉTODOS: Pacientes sometidos a funduplicatura de Nissen por GORD entre enero 2006 y diciembre 2010 fueron asignados de forma aleatoria a cierre del hiato diafragmático con suturas de la crura o malla PTFE no absorbible (CruraSoft®). El resultado primario fue la recidiva de la hernia hiatal determinada mediante estudio radiológico con papilla de bario a los 12 meses de la cirugía. Los resultados secundarios fueron las complicaciones intra- y postoperatorias, utilización de medicación antirreflujo, exposición postoperatoria del esófago al reflujo ácido, calidad de vida, disfagia y duración de la estancia postoperatoria. RESULTADOS: Un total de 77 pacientes fueron aleatorizados a la técnica con suturas y 82 pacientes fueron sometidos a reparación con malla. Al año, se observó recidiva de la hernia de hiato en 6 de 64 pacientes en el grupo con malla (9%) y 2 de 64 pacientes (3%) en el grupo con suturas (P = 0,144). Los síntomas de reflujo, utilización de inhibidores de la bomba de protones (IBPs) y exposición del esófago al ácido no difirieron entre los grupos. A los 3 años, las tasas de recidiva fueron 13% y 10% para el grupo con malla y para el grupo con sutura, respectivamente (P = 0,692). Las puntuaciones de disfagia se redujeron en ambos grupos, pero más pacientes presentaron disfagia para sólidos tras el cierre con malla (P = 0,013). Las puntuaciones de calidad de vida posteriores fueron similares en ambos grupos. CONCLUSIÓN: En pacientes sometidos a funduplicatura laparoscópica, la reparación de la crura sin tensión con malla no absorbible no reduce la incidencia de recidiva de la hernia de hiato en comparación con el uso de suturas solo.

Geographical differences in cancer treatment and survival for patients with oesophageal and gastro-oesophageal junctional cancers.

BACKGROUND: Only around one-quarter of patients with cancer of the oesophagus and the gastro-oesophageal junction (GOJ) undergo surgical resection. This population-based study investigated the rates of treatment with curative intent and resection, and their association with survival. METHODS: Patients diagnosed with oesophageal and GOJ cancer between 2006 and 2015 in Sweden were identified from the National Register for Oesophageal and Gastric Cancer (NREV). The NREV was cross-linked with several national registries to obtain information on additional exposures. The annual proportion of patients undergoing treatment with curative intent and surgical resection in each county was calculated, and the counties divided into groups with low, intermediate and high rates. Treatment with curative intent was defined as definitive chemoradiation therapy or surgery, with or without neoadjuvant oncological treatment. Overall survival was analysed using a multilevel model based on county of residence at the time of diagnosis. RESULTS: Some 5959 patients were included, of whom 1503 (25·2 per cent) underwent surgery. Median overall survival after diagnosis was 7·7, 8·8 and 11·1 months respectively in counties with low, intermediate and high rates of treatment with curative intent. Corresponding survival times for the surgical resection groups were 7·4, 9·3 and 11·0 months. In the multivariable analysis, a higher rate of treatment with curative intent (time ratio 1·17, 95 per cent c.i. 1·05 to 1·30; P < 0·001) and a higher resection rate (time ratio 1·24, 1·12 to 1·37; P < 0·001) were associated with improved survival after adjustment for relevant confounders. CONCLUSION: Patients diagnosed in counties with higher rates of treatment with curative intent and higher rates of surgery had better survival.

ANTECEDENTES: En los pacientes con cáncer en el esófago y de la unión gastroesofágica (gastroesophageal junction, GOJ), solamente en una cuarta parte se practica una resección quirúrgica. Este estudio de base poblacional analizó las tasas de tratamiento con intención curativa y de resección y su asociación con la supervivencia. MÉTODOS: A partir del Registro Nacional Sueco de Cáncer de Esófago y Estómago (National Register for Oesophageal and Gastric Cancer, NREV), se identificaron los pacientes diagnosticados de cáncer de esófago y de la GOJ entre 2006-2015. El NREV se cruzó con otros registros nacionales para obtener información adicional. Se calculó la proporción anual de pacientes tratados con intención curativa o mediante resección quirúrgica en cada una de las áreas territoriales de los condados y se categorizaron en baja, intermedia y alta. El tratamiento con intención curativa se definió como la quimiorradioterapia definitiva (definitive chemoradiation therapy, dCRT) o la cirugía, con o sin tratamiento oncológico neoadyuvante. Se analizó la supervivencia global con un modelo multinivel basado en el condado de residencia en el momento del diagnóstico. RESULTADOS: Se incluyeron 5.959 pacientes, de los que 1.503 (25,2%) fueron tratados quirúrgicamente. La mediana de supervivencia global después del tratamiento con intención curativa fue de 7,7, 8,8 y 11,1 meses para los condados de volumen bajo, intermedio y alto. Para el grupo de cirugía fue de 7,4, 9,3 y 11,0 meses, respectivamente. En el análisis multivariable, una mayor tasa de tratamiento con intención curativa y una mayor tasa de resección se asociaron con una mejor supervivencia (tiempo ganado 1,17; i.c. del 95% 1,05-1,30, P < 0,001 y tiempo ganado 1,24; i.c. del 95% 1,12-1,37, P < 0,001) después del ajuste para los factores principales de confusión. CONCLUSIÓN: Los pacientes diagnosticados en condados con tasas altas de tratamiento con intención curativa y de cirugía tuvieron una mejor supervivencia.

Improvements in esophageal and gastric cancer care in Sweden-population-based results 2007-2016 from a national quality register.

The Swedish National Register for Esophageal and Gastric cancer was launched in 2006 and contains data with adequate national coverage and of high internal validity on patients diagnosed with these tumors. The aim of this study was to describe the evolution of esophageal and gastric cancer care as reflected in a population-based clinical registry. The study population was 12,242 patients (6,926 with esophageal and gastroesophageal junction (GEJ) cancers and 5,316 with gastric cancers) diagnosed between 2007 and 2016. Treatment strategies, short- and long-term mortality, gender aspects, and centralization were investigated. Neoadjuvant oncological treatment became increasingly prevalent during the study period. Resection rates for both esophageal/GEJ and gastric cancers decreased from 29.4% to 26.0% (P = 0.022) and from 38.8% to 33.3% (P = 0.002), respectively. A marked reduction in the number of hospitals performing esophageal and gastric cancer surgery was noted. In gastric cancer patients, an improvement in 30-day mortality from 4.2% to 1.6% (P = 0.005) was evident. Overall 5-year survival after esophageal resection was 38.9%, being higher among women compared to men (47.5 vs. 36.6%; P < 0.001), whereas no gender difference was seen in gastric cancer. During the recent decade, the analyses based on the Swedish National Register for Esophageal and Gastric cancer database demonstrated significant improvements in several important quality indicators of care for patients with esophagogastric cancers. The Swedish National Register for Esophageal and Gastric cancer offers an instrument not only for the control and endorsement of quality of care but also a unique tool for population-based clinical research.

Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study.

The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64-1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41-0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21-4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery.

Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer: international expert consensus based on a modified Delphi process.

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.

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.

Effects of neoadjuvant chemoradiotherapy vs chemotherapy alone on the relief of dysphagia in esophageal cancer patients: secondary endpoint analysis in a randomized trial.

Dysphagia is the most significant symptom in patients with esophageal cancer. There are different therapeutic interventions designed to relieve dysphagia, but few studies have addressed the effects of neoadjuvant therapy. The aim of this study is to compare the effects on dysphagia of neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) and further to study the association between dysphagia response and histological response. Patient reported swallowing function was a secondary endpoint in the NeoRes trial, in which patients were randomized between neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. Patients completed dysphagia questionnaires before the start and after neoadjuvant therapy, using the European Organization for Research and Treatment of Cancer (EORTC) esophageal cancer modules QLQ-OES24/OG25. Chirieac tumor regression grade (TRG) was used to assess the histological response. Out of 181 patients were randomized, of whom 87% completed the dysphagia questionnaires before and 73% after neoadjuvant treatment. Patient characteristics were similar between the treatment arms. Among patients reporting dysphagia at baseline, neoadjuvant therapy improved dysphagia in both arms. The mean dysphagia score after neoadjuvant treatment was significantly lower after nCT compared to after nCRT (P = 0.022). The reported dysphagia did not differ between those with a complete histological response (TRG 1) and those without any response at all (TRG 4) (P = 0. 583).

Outcome of neoadjuvant therapies for cancer of the oesophagus or gastro-oesophageal junction based on a national data registry.

BACKGROUND: Randomized trials have shown that neoadjuvant treatment improves survival in the curative treatment of oesophageal and gastro-oesophageal junction cancer. Results from population-based observational studies are, however, sparse and ambiguous. METHODS: This prospective population-based cohort study included all patients who had oesophagectomy for cancer in Sweden, excluding clinical T1 N0, recorded in the National Register for Oesophageal and Gastric Cancer, 2006-2014. Patients were stratified into three groups: surgery alone, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy. RESULTS: Neoadjuvant treatment was given to 521 patients (51·1 per cent) and 499 (48·9 per cent) received surgery alone. Neoadjuvant chemotherapy increased the risk of postoperative surgical complications compared with surgery alone (adjusted odds ratio 2·01, 95 per cent c.i. 1·24 to 3·25; P = 0·005). Postoperative mortality was significantly increased after neoadjuvant chemoradiotherapy compared with surgery alone (odds ratio 2·37, 1·06 to 5·29; P = 0·035). Survival improved in patients with squamous cell carcinoma after neoadjuvant chemotherapy, whereas after neoadjuvant chemoradiotherapy survival was significantly improved only in the subgroup with the highest performance status and without known co-morbidity. In adenocarcinoma there was a trend towards improved overall survival after neoadjuvant chemotherapy, but neoadjuvant chemoradiotherapy did not offer a survival benefit. Stratified analysis including only patients with adenocarcinoma in the highest performance category without known co-morbidity showed a strong trend towards improved survival after neoadjuvant chemotherapy compared with surgery alone (adjusted hazard ratio 0·47, 0·21 to 1·04; P = 0·061). CONCLUSION: For patients with squamous cell carcinoma of the oesophagus or gastro-oesophageal junction, neoadjuvant treatments seemed to increase long-term survival, but also the risk of postoperative morbidity and mortality, compared with surgery alone. Neither neoadjuvant treatment option seemed to improve survival significantly among patients with adenocarcinoma, compared with surgery alone.

Validation of data quality in the Swedish National Register for Oesophageal and Gastric Cancer.

BACKGROUND: The Swedish National Register for Oesophageal and Gastric Cancer (NREV) was launched in 2006. Data are reported at diagnosis (diagnostic survey), at the time of surgery (surgical survey) and at first outpatient follow-up (follow-up survey). The aim of this study was to evaluate data originating from NREV in terms of comparability, completeness, accuracy and timeliness. METHODS: Coding routines were compared with international standards and completeness was evaluated by means of a 5-year (2009-2013) comparison with mandatory national registers. Validity was tested by comparison with reabstracted data from source medical records in 400 patients chosen randomly with stratification for hospital size and catchment area population. Timeliness of registration was described. RESULTS: Coding routines followed national and international guidelines. Compared with the Swedish Cancer Registry from 2009 to 2013, 6069 (95·5 per cent) of 6354 patients were registered in NREV at the time of data extraction. Of 60 variables investigated, 10 966 of 12 035 original entries were correct in the reabstraction, resulting in an exact agreement of 91·1 per cent in the register. There were 782 (6·5 per cent) incorrect and 287 (2·4 per cent) missing entries. Median time to registration was 3·9, 3·4 and 4·1 months for diagnostic, surgical and follow-up surveys respectively. CONCLUSION: NREV has reached a position with good coverage of those with the relevant diagnoses, and contains comparable and valid data. Quality data on each variable are available. Timeliness is an area with potential for improvement.

Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction.

Dysphagia is the main symptom of cancer of the esophagus and gastroesophageal junction and causing nutritional problems and weight loss, often counteracted by insertion of self-expandable metal stents or nutrition via an enteral route. Clinical observations indicate that neoadjuvant therapy may effectively and promptly alleviate dysphagia, making such nutrition supportive interventions redundant before surgical resection. The objective of the current study was to carefully study the effects of induction neoadjuvant therapy on dysphagia and its subsequent course and thereby investigate the actual need for alimentary gateways for nutritional support. Thirty-five consecutive patients scheduled for neoadjuvant therapy were recruited and assessed regarding dysphagia and appetite at baseline, after the first cycle of preoperative treatment with either chemotherapy alone or with chemoradiotherapy and before surgery. Platinum-based therapy in combination with 5-fluorouracil was administered intravenously days 1-5 every 3 weeks and consisted of three treatments. Patients receiving combined chemoradiotherapy started radiotherapy on day one of second chemotherapy cycle. They received fractions of 2 Gy/day each up to a total dose of 40 Gy. Watson and Ogilvie dysphagia scores were used to assess dysphagia, while appetite was assessed by the Edmonton Assessment System Visual analogue scale-appetite questionnaire. Patients were evaluated at regular outpatient clinic visits or by telephone. The histological tumor response in the surgical specimen was assessed using the Chirieac scale. Ten patients scheduled for neoadjuvant chemotherapy and 25 patients scheduled for chemoradiotherapy were included in the analysis. There was a significant improvement in dysphagia in both treatment groups, according to both scales, already from baseline to the completion of the first chemotherapy cycle which remained to the end of the neoadjuvant treatment (P < 0.001). Appetite also improved after the first chemotherapy cycle (P = 0.03). Body weight did not change during any type of neoadjuvant therapy. We were unable to demonstrate any association between relief of dysphagia and the degree of histological response to neoadjuvant therapy in the surgical specimen. The present study shows that a platin - 5FU-based neoadjuvant chemotherapy, with or without concomitant radiotherapy, effectively and promptly relieves dysphagia in patients presenting with cancers of the esophagus or gastroesophageal junction already after the first cycle.

Predicting the concentration of verotoxin-producing Escherichia coli bacteria during processing and storage of fermented raw-meat sausages.

A model to predict the population density of verotoxigenic Escherichia coli (VTEC) throughout the elaboration and storage of fermented raw-meat sausages (FRMS) was developed. Probabilistic and kinetic measurement data sets collected from publicly available resources were completed with new measurements when required and used to quantify the dependence of VTEC growth and inactivation on the temperature, pH, water activity (aw), and concentration of lactic acid. Predictions were compared with observations in VTEC-contaminated FRMS manufactured in a pilot plant. Slight differences in the reduction of VTEC were predicted according to the fermentation temperature, 24 or 34°C, with greater inactivation at the highest temperature. The greatest reduction was observed during storage at high temperatures. A population decrease greater than 6 decimal logarithmic units was observed after 66 days of storage at 25°C, while a reduction of only ca. 1 logarithmic unit was detected at 12°C. The performance of our model and other modeling approaches was evaluated throughout the processing of dry and semidry FRMS. The greatest inactivation of VTEC was predicted in dry FRMS with long drying periods, while the smallest reduction was predicted in semidry FMRS with short drying periods. The model is implemented in a computing tool, E. coli SafeFerment (EcSF), freely available from http://www.ifr.ac.uk/safety/EcoliSafeFerment. EcSF integrates growth, probability of growth, and thermal and nonthermal inactivation models to predict the VTEC concentration throughout FRMS manufacturing and storage under constant or fluctuating environmental conditions.

Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers.

BACKGROUND: The long-term survival benefits of neoadjuvant chemotherapy (NAC) and chemoradiotherapy (NACR) for oesophageal carcinoma are well established. Both are burdened, however, by toxicity that could contribute to perioperative morbidity and mortality. METHODS: MEDLINE, the Cochrane Library and Embase were searched to capture the incidence of any postoperative complications, cardiac complications, respiratory complications, anastomotic leakage, postoperative 30-day mortality, total postoperative mortality and treatment-related mortality in randomized clinical trials comparing NAC or NACR with surgery alone, or NAC versus NACR. Meta-analyses comparing NAC and NACR were conducted by using adjusted indirect comparison. RESULTS: Twenty-three relevant studies were identified. Comparing NAC or NACR with surgery alone, there was no increase in morbidity or mortality attributable to neoadjuvant therapy. Subgroup analysis of NACR for squamous cell carcinoma (SCC) suggested an increased risk of total postoperative mortality and treatment-related mortality compared with surgery alone: risk ratio 1·95 (95 per cent confidence interval 1·06 to 3·60; P = 0·032) and 1·97 (1·07 to 3·64; P = 0·030) respectively. A combination of direct comparison and adjusted indirect comparison showed no difference between NACR and NAC regarding morbidity or mortality. CONCLUSION: Neither NAC nor NACR for oesophageal carcinoma increases the risk of postoperative morbidity or perioperative mortality compared with surgery alone. There was no clear difference between NAC and NACR. Care should be taken with NACR in oesophageal SCC, where an increased risk of postoperative mortality and treatment-related mortality was apparent.

Staging laparoscopy with peritoneal lavage to identify peritoneal metastases and free intraperitoneal cancer cells in the management of locally advanced gastric cancer.

INTRODUCTION: Gastric cancer often presents in advanced stage with a significant risk for peritoneal dissemination. Staging laparoscopy can be used to detect peritoneal carcinomatosis (PC+) and free cancer cells in peritoneal lavage cytology (CY+). The current study aimed to present the outcomes of staging laparoscopy and the prognosis of PC+ and CY+ in a Swedish high-volume center. MATERIALS AND METHODS: A cohort study including all consecutive patients with locally advanced gastric cancer who underwent staging laparoscopy between February 2008 and October 2022. The laparoscopy findings were categorized as PC+, PC-CY+ (positive cytology without peritoneal carcinomatosis) or negative laparoscopy (PC-CY-). The primary endpoint was overall survival (OS) stratified by laparoscopy findings. The secondary endpoint was OS within each laparoscopy finding group stratified by subsequent treatment. RESULTS: Among 168 patients who underwent staging laparoscopy, 78 patients (46%) had PC-CY-, 29 patients (17%) had PC-CY+ and 61 patients (36%) had PC+. Decreased OS was observed for both PC-CY+ patients (aHR 2.14, 95% CI 1.13-4.06) and PC+ patients (aHR 5.36, 95% CI 3.21-8.93), compared to PC-CY-. Patients with PC-CY+ who converted to PC-CY- after chemotherapy and underwent tumor resection seemed to have a better prognosis compared to patients with persisting PC-CY+. CONCLUSIONS: Staging laparoscopy is an important tool in the staging of locally advanced gastric cancer. Tumor resection for patients with PC-CY+ who convert to PC-CY- may lead to improved survival for these patients.

Diagnostic workup for esophageal cancer patients can be improved with checklists and clearer protocols; a comparative study between two tertiary centers in Europe.

BACKGROUND: Rapid and complete workup of newly diagnosed esophageal cancer is vital for a timely, individual and high-quality treatment strategy. The aim of this study was to uncover potential delay, inefficiencies and non-contributing investigations in the diagnostic process in two tertiary referral centers. METHODS: This retrospective cohort study included all newly diagnosed esophageal cancer patients referred to or diagnosed in the Amsterdam UMC and Karolinska University Hospital between July 2020 and July 2021. Radiology, pathological assessment and multidisciplinary team meeting reports were reviewed. To assess time interval from diagnosis to treatment, dates of diagnosis, admittance to referral hospital, MDT meeting and start of treatment were collected. RESULTS: In total, 252 esophageal cancer patients were included, 187 were treated with curative intent. Curatively treated patients had a mean age of 66 years, were predominantly male (74.9 %) with an adenocarcinoma (71.1 %). Curatively treated patients had a median time from diagnosis to referral of seven days (IQR:0-11) and of 35 days (IQR:28-45) between diagnosis and start of treatment. Main reasons for the significant (P < 0.001) differences in time between diagnosis and treatment between centers, Amsterdam UMC (39 days) vs Karolinska (27 days), were need for additional diagnostics (47.8 %) and differences in referral routine. Gastroscopy was repeated in 32.2 % of patients, mainly for further anatomical mapping. CONCLUSION: Significant time differences between centers in the path from diagnosis to start treatment can be explained by differences in workup approach, referral routines and MDT meeting regulations. Repeat of gastroscopy can be prevented with clearer endoscopy guidelines.