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Introduction: Use of antipsychotic drugs, especially second-generation agents, has been suggested to cause acute pancreatitis in multiple case reports; however, such an association has not been corroborated by larger studies. This study examined the association of antipsychotic drugs with risk of acute pancreatitis. Methods: Nationwide case–control study, based on data from several Swedish registers and including all 52,006 cases of acute pancreatitis diagnosed in Sweden between 2006 and 2019 (with up to 10 controls per case; n = 518,081). Conditional logistic regression models were used to calculate odds ratios (ORs) in current and past users of first-generation and second-generation antipsychotic drugs (dispensed prescription

Head and neck cancers (HNCs) include various malignant tumors of the upper aerodigestive tract. Due to their anatomical location, HNCs can cause obstruction, odynophagia, or trismus, leading to dysphagia. In addition, this patient group may be vulnerable to treatment side effects both by surgery and oncological treatment, exposing the patients to an even higher risk of malnutrition. The risk of malnourishment is often resolved by applying a feeding gastrostomy tube. The present study aims to identify complication rates after percutaneous endoscopic gastrostomy (PEG) and open gastrostomy (OG) in patients treated for HNC in a high-volume center.Retrospective cohort study.A retrospective cohort study of all patients treated for a new diagnosis of HNC at the Department of Otorhinolaryngology and Head and Neck Surgery at Karolinska University Hospital between January 1, 2000 and December 31, 2018 in whom gastrostomy was performed.Regarding tumor location, 165 (56.7%) were in the pharynx, 68 (23.4%) in the oral cavity, 57 (19.6%) in the larynx, and 1 (0.3%) in the nasal cavity. PEG was performed in 240 (82.5%) and OG in 51 (17.5%) patients. The overall complication rate was 28.2%: 64 (26.7%) among PEG patients and 18 (35.3%) among OG patients. The incidence of major complications was 3.1%.Our study confirms that enteral feeding via gastrostomy is a safe method, regardless of the technique used (PEG or OG), with a low rate of major complications and no mortality linked to the procedure.3 Laryngoscope, 132:1778-1784, 2022.

Summary Background/objective Gastric outlet obstruction can have a large impact on quality of life for patients with upper gastrointestinal cancer or benign obstruction. Partial stomach-partitioning gastrojejunostomy has previously shown promising outcomes compared to conventional gastrojejunostomy in terms of reduced delayed gastric emptying. The objective of the current study was to present outcomes of partial stomach-partitioning gastrojejunostomy in a single high-volume center for upper gastrointestinal cancer. Methods A retrospective cohort study including all consecutive patients who underwent partial stomach-partitioning gastrojejunostomy from 2013 to 2020. The primary outcome was oral intake tolerance. A subgroup analysis was performed in all patients with manifest gastric outlet obstruction comparing partial stomach-partitioning gastrojejunostomy to conventional gastrojejunostomy. Results Partial stomach-partitioning gastrojejunostomy was performed in 32 patients and laparoscopic technique was used in 19 patients (59%). The procedure improved oral intake tolerance defined by gastric outlet obstruction scoring system by 0.63 points on average (P = 0.041). No postoperative complications related to the procedure were observed. Recurrence of gastric outlet obstruction developed in six patients (19%), four patients (13%) required endoscopic reintervention but no patient required surgical reintervention. A comparison between partial stomach-partitioning gastrojejunostomy and conventional gastrojejunostomy showed no statistically significant differences regarding postoperative nutritional status, length of hospital stay, recurrence or reintervention. Conclusion The results of the study show that partial stomach-partitioning gastrojejunostomy can be an effective surgical treatment for patients suffering from gastric outlet obstruction and that the procedure can be safely performed with laparoscopic technique.

Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

Background Population-based patient reported outcome data in oesophageal cancer are rare. The main purpose of this study was to describe health-related quality of life (HRQOL) 1 year after the diagnosis of oesophageal cancer, comparing subgroups of curatively and palliatively managed patients. Methods This is a nationwide population-based cohort study, based on the Swedish National Registry for Oesophageal and Gastric Cancer (NREV) with prospectively registered data, including HRQOL instruments from the European Organisation for Research and Treatment of Cancer including the core and disease specific questionnaires (EORTC QLQ-C30 and QLQ-OG25). Patients diagnosed with oesophageal cancer between 2009 and 2016 and with complete HRQOL data at 1 year follow-up were included. HRQOL of included patients was compared to a reference population matched by age and gender to to a previous cohort of unselected Swedish oesophageal cancer patients. Linear regression was performed to calculate mean scores with 95% confidence intervals (CI) and adjusted linear regression analysis was used to calculate mean score differences (MD) with 95% CI. Results A total of 1156 patients were included. Functions and global health/quality of life were lower in both the curative and palliative cohorts compared to the reference population. Both curatively and palliatively managed patients reported a severe symptom burden compared to the reference population. Patients who underwent surgery reported more problems with diarrhoea compared to those treated with definitive chemoradiotherapy (dCRT) (MD -14; 95% CI − 20 to − 8). Dysphagia was more common in patiens treated with dCRT compared to surgically treated patients (MD 11; 95% CI 4 to 18). Those with palliative intent due to advanced tumour stage reported more problems with dysphagia compared to those with palliative intent due to frailty (MD -18; 95% CI − 33 to − 3). Conclusions One year after diagnosis both curative and palliative intent patients reported low function scores and severe symptoms. Dysphagia, choking, and other eating related problems were more pronounced in palliatively managed patients and in the curative intent patients treated with dCRT.

Time to surgery after termination of neoadjuvant chemoradiotherapy for esophageal cancer has traditionally been 4–6 weeks. Observational studies have suggested that delay of surgery for up to three months may lead to improved tumor regression and better outcomes. NeoRes II is the first randomized trial to address this in esophageal cancer. No difference in surgical morbidity or mortality between early and delayed surgery was reported in a previous publication from the trial. A multicenter clinical trial with randomized 1:1 allocation of standard time to surgery of 4–6 weeks, or delay of surgery to 10–12 weeks, after termination of chemoradiotherapy. The primary endpoint was complete histological tumor regression in patients with adenocarcinoma. Secondary endpoints included tumor regression grade, tumor free resection margins and overall survival in all patients, and stratified by histological subtype. In total 249 patients were randomized, 204 with adenocarcinoma and 45 with squamous cell carcinoma. There was no significant difference in histological complete response between adenocarcinoma patients allocated to standard time to surgery (20.6%) compared to delayed (25.6%) surgery (P = 0.18). Tumor free resection margin was achieved in 97.4% after standard time to surgery and 97.1% after delayed surgery (P = 1.0). The median follow-up time for survival was 51 months. Delayed time to surgery was associated with a 35% higher overall mortality, hazard ratio 1.35 (95% CI:0.94–1.95), (P = 0.11). No significant difference in complete histological tumor regression or tumor free resection margins comparing standard and delayed time to surgery after chemoradiotherapy was observed. There was a non-significant trend towards inferior overall survival after delayed surgery, suggesting caution in delaying surgery for more than 6 weeks after neoadjuvant chemoradiotherapy.

Benign oesophageal strictures (BES) are often easily treated but around 30% progress into recurrent or refractory benign oesophageal strictures (RBES), that need repetitive dilatations. Difficulties of RBES have been widely discussed in the literature, but there is not a well-established consensus regarding the definition of RBES. In this study we wanted to develop a simple definition in relation to aetiology and number of dilatation sessions per stricture. A retrospective study on 242 BES-patients treated with endoscopic dilatation was performed. The primary endpoint was need of further dilatation per procedure, based on total number of dilatation sessions performed and stricture ethology. Univariate and multivariable regression analysis were performed to assess risk factors for RBES. Among 242 patients, 76 had RBES. The need of further dilatation increases with 13% at fifth dilation session and keeps a continuous mean value at 81%. Investigating some aetiologies separately, the point where need increases does vary. The risk of having RBES decreased for distal (Odds Ratio (OR) 0,25 (Confidence interval (CI) 95% 0,09-0,65)) and middle (OR 0,35 (CI 95% 0,13-0,88)) location of the stricture compared to proximal strictures. We propose that a stricture can be defined as RBES when reaching the fifth dilatation session. At that point we also suggest that clinicians should consider additional treatment, in addition to dilatation, in order to resolve the stricture.

Rapid and complete workup of esophageal cancer is vital for a timely and individual treatment strategy. The aim of this study is to uncover potential delay, inefficiencies and non-contributing investigations in the diagnostic process. This retrospective cohort study included all esophageal cancer patients referred to or diagnosed in the Amsterdam UMC or Karolinska Institutet between July 2020 and July 2021. Radiology, pathological assessment and MDT meeting reports were reviewed. To assess time interval from diagnosis to treatment, information on date of diagnosis, admittance to referral hospital, MDT and start treatment was collected. This study included 252 esophageal cancer patients, 187 were treated with curative intent. Curative patients had a median age of 68, were predominantly male (74.9%) with adenocarcinoma (71.4%). Patients had a median of 34 days (IQR:27-43) between diagnosis and start treatment and a median time to referral of 6 days (IQR:0-11). Main denominators for prolonged time between diagnosis and treatment was need for additional diagnostics (45.5%) and local protocol (Amsterdam UMC 39 days vs Karolinska 27 days). However, for 33 out of 77 patients (42.9%), no other than logistical reasons could be found. Differences in time between diagnosis and treatment in the centers can be explained by variations in workup protocol, MDT regulations and the need for additional diagnostics.

The Nordic countries have similar health care systems and registries simplifying epidemiological research and the treatment of esophageal cancer is largely centralized. However, differences in treatment traditions can hamper the possibility to assess results and harmonize control arms in joint randomized trials. In setting up a Nordic multi-center randomized trial regarding the use of nasogastric tube (NG-tube) decompression, we aimed to investigate differences in perioperative routines after esophageal resection at Nordic University hospitals. All Nordic University Hospitals with an upper gastrointestinal cancer center (UGC) were contacted regarding a Nordic randomized controlled trial exploring the effects and complications associated with the use of NG-tube after esophagectomy for cancer. Those who chose to join the trial were sent a questionnaire regarding surgical volumes and practices including mean annual number of esophagectomies, surgical method/access, and routine use of pyloric drainage and jejunostomy. In addition, the current standard postoperative use of NG-tube and routine X-ray/CT evaluation, along with postoperative traditions regarding the start of liquid diet was enquired. High volume centers were defined as performing >20 procedures/year. Thirteen of 17 centers with a combined catchment area of 16 million inhabitants and an annual volume of 445 esophagectomies joined the trial network. All, but one center used a total minimally invasive- or hybrid surgical approach but otherwise, the routine use of pyloric drainage and jejunostomy varied widely without being statistically different. All 13 centers reported routine use of NG-tube and 4 employed continuous suction. The NG-tube was removed between 3 and 7 days postoperatively, but also strategies between the centers (suction on NG-tube, start of liquid diet, routine X-ray/CT evaluation) varied without being statistically significant Firm adherence to standardized operations and safety protocols are implemented in Nordic UGCs to reduce the potential consequences of complications. However, the results find the differences in perioperative care after esophagectomy apparent, highlighting the need for high-level evidence regarding these practices. A unified approach may facilitate clinical trial initiatives. There is a paucity of evidence regarding optimal NG-tube use after esophagectomy for cancer and a randomized trial (kiNETiC ISRCTN39935085) investigating this issue is underway.

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. 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. The study included 119 patients of whom 112 (94.1%) completed an upper gastrointestinal contrast study. The results showed that 8 (7.1%) patients had no emptying of contrast from the gastric conduit, partial emptying was seen in 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 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 can improve postoperative outcomes.

There are differences in esophageal cancer care across different counties in Sweden. According to national guidelines, all patients should be offered equal care which should be administrated by regional multidisciplinary cancer conferences (MCCs). The aim of the study was to investigate differences between the six regional MCCs in Sweden regarding clinical stageing and recommended treatment. Ten consecutive cases per participating center, 60 cases in total, were planned for inclusion. After anonymization the radiological investigations were presented, along with the original case-specific medical history, anew at the six regional MCCs. Estimation of clinical TNM and treatment allocation (curative, palliative or best supportive care) were compared between MCCs as well as with the original assessment. Interim analysis was performed in April 2022 when ten cases had been presented at five of the six regional MCCs. All available cases were assessed at five MCCs in addition to the previous original assessment (60 assessments). The mean age for the first ten cases was 74.8 years (SD ± 9.8 years). Eight out of ten cases were men. In estimations of T- and N-stage the MCCs agreed in only one out of ten cases. In half of the cases more than three different estimations of N-stage were made. For clinical M-stage there was exact agreement in three cases. In determination of recommended treatment, all five MCCs were in agreement on half of the cases. Preliminary data show striking differences, both in assessment of TNM as well as treatment recommendation at different MCCs. One patient, recommended curative treatment by one MCC could be allocated to palliative care by another. Inclusion is ongoing and further analysis of these differences are warranted to achieve more equal care for esophageal cancer patients in Sweden. MCC_fig1.jpg (could not be inserted).

The advantages of multidisciplinary treatment conferences (MDT) are advocated in staging and treatment of esophageal cancer. Improved timeliness to surgery, adherence to guidelines, increased probability of complete clinical staging and allocation to curative treatment have all been attributed to the introduction of MDTs but there are few studies published in support of MDTs positive effect on outcomes. The aim is to investigate the association between MDT and survival in esophageal cancer. All patients diagnosed with esophageal cancer in the Swedish Registry for Esophageal and Gastric Cancer between 2006-2018 were included in this retrospective cohort study. Patients were grouped according to whether or not they had been discussed at an MDT as part of their staging process. The cohort was followed until death, emigration, or end of follow-up. Factors possibly affecting group allocation was explored with multivariable logistic regression and the impact of MDT on survival was studied with Cox-regression and the Kaplan–Meier method. Of 6607 patients diagnosed with esophageal cancer, 1338 (20%) were not discussed at an MDT. Median survival was 10.7 months with MDT and 4.4 months without MDT. Age above 80, OR 0.29 (0.18-0.47 95%CI), Charlson Comorbidity Index>2, OR 0.79 (0.66-0.96) and clinical stage IVb, OR 0.66 (0.44-0-97) all decreased the probability of being presented at an MDT, whereas squamous cancer, OR 1.45 (1.18-1.77) and later year of diagnosis OR 1.33 (1.30-1.37 per year) increased the probability of an MDT. Adjusted for the well-established prognostic factors above, the MDT was still an independent predictor of survival, HR 0.63 (0.58-0.69 95%CI). The role of the MDT in the staging and treatment of patients with esophageal cancer is, in the present study, clearly associated with improved survival. Older, more comorbid patients with advanced disease are at a disadvantage since they are not consistently discussed in a multidisciplinary setting. Whether the survival benefit is due to the MDT alone or lack of ambition in what appears to be non-curable cases is yet to be determined.

In autumn 2019, the Public Health Agency of Sweden identified a cluster of

In autumn 2019, the Public Health Agency of Sweden identified a cluster of Salmonella Newport cases by whole genome sequencing (WGS). Cases’ distribution in place and time indicated a nation-wide ongoing outbreak. An investigation was initiated to identify the source and prevent further cases. We conducted a case–case study based on notified salmonellosis cases and a Salmonella trawling questionnaire, comparing 20 outbreak cases and 139 control cases. Food exposures were compared by adjusted odds ratios (aOR) with 95% confidence interval (CI) using logistic regression. Implicated foods were sampled. Outbreak cases were more likely to have consumed crayfish (aOR = 26; 95% CI: 6.3–105). One specific brand of imported frozen, pre-cooked whole crayfish in dill brine was identified as the source. Salmonella Newport was later detected in different batches from retail and in one sample from border control. Isolates from food samples clustered with the human outbreak strain by WGS. Although the retailer made a complete recall, two more cases were identified long afterwards. This investigation demonstrated the successful use of a case–case study and targeted microbiological testing to identify the source. The immediate action taken by the retailer was important to confirm the source and stop the outbreak.

Objective To examine 5-year survival in esophageal cancer after minimally invasive esophagectomy (MIE) compared to open esophagectomy (OE). Summary background data MIE is becoming an increasingly common approach in the surgical treatment of esophageal cancer. A recent meta-analysis suggested 18% lower 5-year all-cause mortality after MIE compared to OE, but the quality of the included studies was limited. Methods Population-based cohort study including almost all patients who underwent elective esophagectomy for esophageal cancer in Sweden or Finland in 2010-2016, with follow-up until 2020. Cox regression was used to provide hazard ratios (HRs) with 95% confidence intervals (CIs) of all-cause 5-year mortality (main outcome) after MIE (hybrid or total) versus OE. Adjustments were made for age, sex, comorbidity, pathological tumor stage, histological tumor type, neoadjuvant chemo(radio)therapy, country, and annual hospital volume of esophagectomy. Results Among all 1,264 patients, 470 (37.2%) underwent MIE and 794 (62.8%) underwent OE. MIE was associated with an 18% decreased risk of all-cause 5-year mortality, compared to OE (adjusted HR 0.82, 95% CI 0.67-1.00 [P = 0.048]). The HR of all-cause 5-year mortality was seemingly lower after total MIE compared to OE (adjusted HR 0.77, 95% CI 0.60-0.98) than after hybrid MIE compared to OE (adjusted HR 0.87, 95% CI 0.68-1.11). Conclusions This bi-national study indicates that MIE is associated with a higher 5-year survival than OE in patients with esophageal cancer, and that the survival benefit is greater after total MIE than hybrid MIE.

Background Accumulating evidence suggests a survival benefit after curative oesophageal cancer surgery in women compared with men. The aim of this study was to explore sex disparities in survival after surgery with curative intent in patients with oesophageal cancer. Methods This was a population-based cohort study, including all patients with oesophageal or gastric cancer who underwent surgery with a curative intent between 2006 and 2017 in Sweden. Female versus male mortality rate ratio (MRR) and excess mortality rate ratio (EMRR) were used as measures of survival. Two different parametric models were designed to account for potential confounders. Patients with gastric cancer were used as a comparison group as no differences in survival between sexes were expected among these patients. Results A total of 1301 patients underwent resection for oesophageal adenocarcinoma and 305 patients for oesophageal squamous cell carcinoma. Women had a lower EMRR (0.76, 95 per cent c.i. 0.58 to 1.01, P = 0.056; 0.52, 95 per cent c.i. 0.32 to 0.84, P = 0.007 respectively) in both histological subtypes. The effect was more profound in early clinical stages, in patients receiving neoadjuvant treatment, and without postoperative complications. No sex-related difference was observed in survival of patients with gastric cancer. Conclusions Women undergoing resection for oesophageal carcinoma have better survival compared with men.

Background Fundoplication is an essential step in para-oesophageal hernia (POH) repair, but which type minimizes postoperative mechanical complications is controversial. Methods This was a randomized, double-blind clinical trial conducted between May 2009 and October 2018. Patients with symptomatic POH were allocated to either a total (Nissen) or a posterior partial (Toupet) fundoplication after hernia reduction and crural repair. The primary outcome was dysphagia (Ogilvie dysphagia scores) at 6 months postoperatively. Secondary outcomes were peri- and postoperative complications, swallowing difficulties assessed by the Dakkak dysphagia score, gastro-oesophageal reflux, quality of life (QoL), and radiologically confirmed hernia recurrence. Results A total of 70 patients were randomized to a Nissen (n = 32) or a Toupet (n = 38) fundoplication. Compared with baseline, Ogilvie dysphagia scores were stable at the 3- and 6-month follow-up in the Nissen group (P = 0.075 and 0.084 respectively) but significantly improved in the Toupet group (from baseline mean (s.d.): 1.4 (1.1) to 0.5 ( 0.8) at 3 months, and 0.5 (0.6) at 6 months; P = 0.003 and P = 0.001 respectively). At 6 months, Dakkak dysphagia scores were significantly higher in the Nissen group than in the Toupet group (mean (s.d.): 10.4 (7.9) versus 5.1 (7.2); P = 0.003). QoL scores improved throughout the follow-up. However, at 3 and 6 months postoperatively, the absolute median improvement (⍙) from preoperative values in the mental component scores of the Short Form-36 QoL questionnaire was significantly higher in the Toupet group (median (i.q.r.): 7.1 (−0.6 to 15.2) versus 1.0 (−5.4 to 3.3) at 3 months, and 11.2 (1.4 to 18.3) versus 0.4 (−9.4 to 7.5) at 6 months; (P = 0.010 and 0.003 respectively)). At 6 months, radiologically confirmed POH recurrence occurred in 11 of 24 patients (46 per cent) of the Nissen group and in 15 of 32 patients (47 per cent) of the Toupet group (P = 1.001). Conclusions A partial posterior wrap (Toupet fundoplication) showed reduced obstructive complications and improved QoL compared with a total (Nissen) fundoplication following POH repair. Registration number: NCT04436159 (http://www.clinicaltrials.gov)

Objectives The aim of this study was to investigate the sentinel lymph node biopsy (SLNB) method in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) guided by preoperative hybrid single-photon emission tomography/computed tomography (SPECT/CT) lymphoscintigraphy. Methods Thirty-nine patients with stage T1-T3, any N-stage, M0 cancer of the oesophagus or GOJ planned for curatively intended esophagectomy underwent preoperative SPECT/CT lymphoscintigraphy following endoscopically guided submucosal injection of radiocolloid and intraoperative radio-guided SLNB using a hand-held gamma scintillation device. Results The detection rate in preoperative SPECT/CT imaging was 88%. The median number of detected SLN stations in preoperative imaging was 1 (range 0-4). At least one suspected SLN was identified in all intraoperative SLNP procedures. In six cases, no lymph nodes were identified in the SLNB. In six cases, the SLNB was false negative. The sensitivity for successful SLNB procedures was 20%, the specificity was 100% and the accuracy was 75%. Conclusions Preoperative SLN mapping using SPECT/CT yields a high number of detected SLN stations compared to previous studies using planar imaging. The accuracy of the SLNB method in patients with predominantly ≥T3-stage tumours and with a history of previous neoadjuvant treatment is poor, and the method is not recommended in these patient groups.

Contains fulltext : 225948.pdf (Publisher’s version ) (Open Access) 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.

Background Gastrectomy including D2 lymphadenectomy is regarded as the standard curative treatment for advanced gastric cancer in Asia. This procedure has also been adopted gradually in the West, despite lack of support from RCTs. This study sought to investigate any advantage for long‐term survival following D2 lymphadenectomy in routine gastric cancer surgery in a Western nationwide population‐based cohort. Methods All patients who had a gastrectomy for cancer in Sweden in 2006–2017 were included in the study. Prospectively determined data items were retrieved from the National Register of Oesophageal and Gastric Cancer. Extent of lymphadenectomy was categorized as D1+/D2 or the less extensive D0/D1 according to the Japanese Gastric Cancer Association classification. Overall survival was analysed and, in addition, a variety of possible confounders were introduced into the Cox proportional hazards regression model. Results A total of 1677 patients underwent gastrectomy, of whom 471 (28·1 per cent) were classified as having a D1+/D2 and 1206 (71·9 per cent) a D0/D1 procedure. D1+/D2 lymphadenectomy was not associated with higher 30‐ or 90‐day postoperative mortality. Median overall survival for D1+/D2 lymphadenectomy was 41·5 months with a 5‐year survival rate of 43·7 per cent, compared with 38·5 months and 38·5 per cent respectively for D0/D1 (P = 0·116). After adjustment for confounders, in multivariable analysis survival was significantly higher after D1+/D2 than following D0/D1 lymphadenectomy (hazard ratio 0·81, 95 per cent c.i. 0·68 to 0·95; P = 0·012). Conclusion This national registry study showed that long‐term survival after gastric cancer surgery was improved after gastrectomy involving D1+/D2 lymphadenectomy compared with D0/D1 dissection., A nationwide prospective register‐based study examined the extent of lymphadenectomy in curative gastric cancer surgery and its effects on long‐term survival. More evidence in favour of thorough lymphadenectomy

Background Laparoscopic gastrectomy (LG) for cancer has been introduced in institutions worldwide in an effort to minimize surgical trauma, while aiming to provide comparable oncological outcomes to conventional open gastrectomy (OG). The aim of this study was to present our results during the period of implementation of the laparoscopic technique. Materials and methods In 2012, LG for the treatment of gastric cancer was introduced at our institution. The results presented are based on a retrospective analysis of data from a cohort of all patients treated with curative intent over the period 2010-2018. Results During the study period, 206 patients underwent surgery for gastric cancer: 129 patients (62.6%) had an OG and 77 patients (37.4%) an LG. The conversion rate due to technical reasons was 2.6%. LG was associated with significantly less intraoperative blood loss [mean (mL), OG 544 versus LG 176] and shorter hospital stay than OG [mean (d), OG 12 versus LG 8], fewer severe complications (Clavien-Dindo grade ≥ IIIb) [OG 29 (22.5%) versus LG 9 (11.7%), P = 0.081], significantly lower anastomotic leak rate [OG 18 (14.0%) versus LG 1 (1.3%)] and no 90-day mortality. The percentage of R0 resections was similar between the two groups (OG 82.2% versus LG 85.7%, P = 0.507), while the mean number of resected lymph nodes was significantly higher in the laparoscopic group [OG 34 versus LG 39, P = 0.030]. Conclusions Our data suggest that similar and, in some aspects, better short-term outcomes can be achieved with LG with maintained oncological quality.

In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients.

Oesophageal cancer management requires extensive in-hospital care. This cohort study aimed to quantify in-hospital care for esophageal cancer patients in relation to intended treatment and to analyze factors associated with risk of spending a large proportion of survival time in hospital. Methods All patients with oesophageal cancer in three nationwide registers over a ten-year period, were included. In-hospital care during the first year after diagnosis was evaluated and the proportion of survival time spent in hospital, stratified for intended treatment (curative, palliative or best supportive care) calculated. Associations of relevant factors to a greater proportion of survival time in hospital was analyzed by multivariable logistic regression. Results In-hospital care was provided for a median time of 39, 26 and 15 days the first year after diagnosis of oesophageal cancer for curative, palliative and best supportive care groups respectively. Patients receiving curatively intended treatment spent a median of 12% of their survival time in hospital during the first year after diagnosis, while palliative or best supportive care patients spent 19% and 23% respectively. Factors associated with more in-hospital care included higher age, female sex, being unmarried and chronic obstructive pulmonary disease (COPD). Conclusion The burden of in-hospital care during the first year after diagnosis of oesophageal cancer was substantial. Important clinical and socioeconomic factors were identified that predisposed to a greater proportion of survival time spent in hospital.

Accumulating evidence points to a better survival in female patients after a curative oesophageal cancer surgery. However, there is a need for more well-designed and sufficiently powered studies for limitations in previous studies. Better understanding of sex differences in the postoperative survival may be helpful for a sex-specific treatment. Methods This is a population-based cohort study including all patients in Sweden with oesophageal cancer that underwent a curative surgical treatment between 2006 and 2017. Sex difference in postoperative survival was explored with excess mortality rate ratio (EMRR) and absolute difference of excess mortality rate along the whole follow-up time, using flexible parametric model. Age at the time of surgery, Charlson comorbidity index, ASA score, tumor stage, post-operative complications, marital status, education level and hospital volume were considered as covariates in the analysis model. Stratification analysis by clinical stages, perioperative neoadjuvant treatment and post-operative complications was also performed. Results In all, there were 1301 patients resected for oesophageal adenocarcinoma and 305 patients for oesophageal squamous cell carcinoma. For both oesophageal adenocarcinoma and oesophageal squamous cell carcinoma, female patients had a lower excess mortality rate than males (adjusted EMRR: 0.77, 95% CI: 0.58–1.01, P = 0.059; 0.53, 95% CI: 0.33–0.85, P = 0.009, respectively). This sex difference was particularly strong shortly after surgery then gradually decreased over the ensuing years (Figure) and was more profound in the early clinical stages, and in patients receiving neoadjuvant treatment and without post-operative complications. Conclusion Female patients seem to have a better survival shortly after esophagectomy for patients with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma, and the sex difference thereafter weakened. Our results may imply a different response to oesophageal cancer surgery between the sexes, and associated pre- and post-operative treatment, thus a sex-specific strategy may be considered in further work.

There is an unexplained male predominance in the incidence of esophageal (EAC) and non-cardia gastric adenocarcinoma (GAC) which cannot be explained by known risk factors. Differences in the exposures to sex hormones may play a part in the observed sex difference. This study aimed to test the hypothesis that androgens increase the risk of EAC, cardia GAC, and non-cardia GAC. We analysed a matched cohort based on a national Swedish database of prostate cancer patients. Methods Prostate cancer patients receiving androgen deprivation therapy (ADT) were the exposed group. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed control group. The participants were followed until a diagnosis of esophageal or gastric cancer, death, emigration, or end of the study period. The risk of esophageal adenocarcinoma, cardia gastric adenocarcinoma, non-cardia gastric adenocarcinoma, and esophageal squamous-cell carcinoma among ADT-exposed compared to unexposed was calculated by multivariable Cox proportional hazard regression. The hazard ratios and 95% confidence intervals were adjusted for confounders. Results There was a risk reduction of non-cardia gastric adenocarcinoma among ADT-users compared to non-users (HR 0.49 [95% CI 0.24–0.98]). No such decreased risk was found for esophageal adenocarcinoma (HR 1.17 [95% CI 0.60–2.32]), cardia gastric adenocarcinoma (HR 0.99 [95% CI 0.40–2.46]), or esophageal squamous cell carcinoma (HR 0.99 [95% CI 0.31–3.13]). Conclusion This study indicates that androgen deprivation therapy decreases the risk of non-cardia gastric adenocarcinoma, while no decreased risk was found for esophageal adenocarcinoma, cardia gastric adenocarcinoma, or esophageal squamous-cell carcinoma.

The operating surgeon’s assessment of surgical radicality following esophagectomy is reported to the Swedish National Registry for Esophageal and Gastric cancer(NREV). The variable provides means to identify risk factors for non-curative resections and study whether the surgeon’s assessment independently prognosticates survival. Methods All patients in NREV undergoing esophagectomy between 2006–2018 was grouped according to the surgeon’s assessment of radicality: Curative-, Borderline-curative- and Palliative resection. The cohort was followed until death, emigration or end of follow-up. Factors affecting group allocation was studied with multivariable logistic regression and survival with cox-regression and the Kaplan–Meier method. Results Of 1860 resected patients, esophagectomy was deemed curative in 1515(81%), borderline-curative in 179(10%), palliative in 63(3%) and missing in 103(6%). Median survival was 44.6, 20.0, 11.5 and 29.6 months respectively. Advanced stage (e.g., stage IVa), OR 7,37 (1,93–28,1 95%CI) and blood-loss >1000 mL, OR 1.90 (1,17-3,08), increased the risk of borderline-curative resection. Minimally invasive surgery and multidisciplinary treatment decision (MDT) decreased the risk of borderline-curative resection, OR 0.42 (0,23-0,77) and OR 0.41 (0,22-0,77). Adjusted for well-established prognostic factors, e.g. age, p-TNM and R1-resection, the surgeon’s assessment was an independent variable for survival; borderline-curative HR 1,38 (1,11-1,72), palliative HR 1,91 (1,38-2,63). Conclusion The surgeon’s operative assessment of radicality following esophagectomy appears to independently prognosticate survival. Advanced stage and large-volume intraoperative blood loss increases the risk while minimally invasive surgery and MDT decreases the risk for borderline-curative resection.