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Rayan Nikkilä,1– 4 Elli Hirvonen,1 Janne Pitkäniemi,1,5,6 Jari V Räsänen,7 Nea K Malila,1 Antti Mäkitie2,3,8 1Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; 2Department of Otorhinolaryngology, Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 3Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 4Päijät-Häme Joint Authority for Health and Wellbeing, Department of Oral and Maxillofacial Surgery, Lahti Central Hospital, Lahti, 15850, Finland; 5Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland; 6Department of Public Health, University of Helsinki, Helsinki, Finland; 7Department of General Thoracic and Oesophageal Surgery, Heart and Lung Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 8Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska Hospital, Stockholm, SwedenCorrespondence: Antti Mäkitie, Helsinki University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery, P.O.Box 263, FI-00029 HUS, Helsinki, Finland, Tel +358-50-428 6847, Email antti.makitie@helsinki.fiPurpose: The occurrence of a second primary cancer (SPC) after primary esophageal carcinoma (EC) or gastric cardia carcinoma(GCC) is well acknowledged. However, previous research on the risk of SPC among these patients has been predominantly conducted in Asian countries. Yet, notable population-dependent variation in histological types and risk profiles exists. This register-based study assesses the histology-specific risk of SPC among individuals initially diagnosed with a first primary EC or GCC.Patients and Methods: We obtained data on 7197 patients diagnosed with EC/GCC in Finland between 1980 and 2022 from the Finnish Cancer Registry. Standardized incidence ratios (SIR) of SPC were subsequently calculated relatively to the cancer risk of the general population.Results: The average and median follow-up times were 2.8 years and 10.5 months. Adenocarcinomas and squamous cell carcinomas comprised 57.8% (n = 4165) and 36.6% (n = 2631) of all cases, respectively. An increased SIR was noted among EC/GCC patients after 15– 20 years of follow-up (SIR 1.49, 95% CI: 1.01– 2.11). Among adenocarcinoma patients, an increased SIR for SPCs of the digestive organs was seen in the 40– 54-year-old group (SIR 9.86, 95% CI: 3.62– 21.45). Squamous cell carcinoma patients displayed increased SIRs for cancer of the mouth/pharynx (SIR 3.20, 95% CI: 1.17– 6.95) and respiratory organs (1.77, 1.07– 2.76).Conclusion: Healthcare professionals should be aware of the increased risk of SPCs occurring in the mouth/pharynx, respiratory and digestive organs in survivors of EC/GCC. Patients should be advised about this risk and remain alert for symptoms, even beyond the standard 5-year follow-up period.Keywords: esophageal squamous cell carcinoma, adenocarcinoma, gastric cardia carcinoma, tumor, second primary cancer

Background: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for102 patients (33.9 per cent). Median disease-free survival (DFS) after firstresection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates. [ABSTRACT FROM AUTHOR]

Background: In the photodynamic therapy (PDT) of non‐aggressive basal cell carcinomas (BCCs), 5‐aminolevulinic acid nanoemulsion (BF‐200ALA) has shown non‐inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL‐PDT in the treatment of BCCs. Objectives: To compare the histological clearance, tolerability (pain and post‐treatment reaction) and cosmetic outcome of MAL, BF‐200 ALA and low‐concentration HAL in the PDT of non‐aggressive BCCs. Methods: Ninety‐eight histologically verified non‐aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED‐PDT in two repeated treatments with MAL, BF‐200 ALA or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post‐treatment reactions fluorescence and photobleaching were evaluated. Results: According to intention‐to‐treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9–98.3) for MAL, 90.9% (95% CI = 76.4–96.9) for BF‐200 ALA and 87.9% (95% CI = 72.7–95.2) for HAL, with no differences between the arms (P = 0.84). There were no differences between the arms as regards pain, post‐treatment reactions or cosmetic outcome. Conclusions: Photodynamic therapy with low‐concentration HAL and BF‐200 ALA has a similar efficacy, tolerability and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration. [ABSTRACT FROM AUTHOR]

Context. Coronal mass ejections (CMEs) are large eruptions of magnetised plasma from the Sun that are often accompanied by solar radio bursts produced by accelerated electrons. Aims. A powerful source for accelerating electron beams are CME-driven shocks, however, there are other mechanisms capable of accelerating electrons during a CME eruption. So far, studies have relied on the traditional classification of solar radio bursts into five groups (Type I–V) based mainly on their shapes and characteristics in dynamic spectra. Here, we aim to determine the origin of moving radio bursts associated with a CME that do not fit into the present classification of the solar radio emission. Methods. By using radio imaging from the Nançay Radioheliograph, combined with observations from the Solar Dynamics Observatory, Solar and Heliospheric Observatory, and Solar Terrestrial Relations Observatory spacecraft, we investigate the moving radio bursts accompanying two subsequent CMEs on 22 May 2013. We use three-dimensional reconstructions of the two associated CME eruptions to show the possible origin of the observed radio emission. Results. We identified three moving radio bursts at unusually high altitudes in the corona that are located at the northern CME flank and move outwards synchronously with the CME. The radio bursts correspond to fine-structured emission in dynamic spectra with durations of ∼1 s, and they may show forward or reverse frequency drifts. Since the CME expands closely following an earlier CME, a low coronal CME–CME interaction is likely responsible for the observed radio emission. Conclusions. For the first time, we report the existence of new types of short duration bursts, which are signatures of electron beams accelerated at the CME flank. Two subsequent CMEs originating from the same region and propagating in similar directions provide a complex configuration of the ambient magnetic field and favourable conditions for the creation of collapsing magnetic traps. These traps are formed if a CME-driven wave, such as a shock wave, is likely to intersect surrounding magnetic field lines twice. Electrons will thus be further accelerated at the mirror points created at these intersections and eventually escape to produce bursts of plasma emission with forward and reverse drifts. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether a nationwide prenatal anomaly screening programme improves detection rates of univentricular heart (UVH) and transposition of great arteries (TGA), and whether maternal risk factors for severe fetal heart disease affect prenatal detection.Design: Population-based cohort study.Setting: Nationwide data from Finnish registries 2004-14.Population: A total of 642 456 parturients and 3449 terminated pregnancies due to severe fetal anomaly.Methods: Prenatal detection rates were calculated in three time periods (prescreening, transition and screening phase). The effect of maternal risk factors (obesity, in vitro fertilisation, pregestational diabetes and smoking) was evaluated.Main Outcome Measures: Change in detection rates and impact of maternal risk factors on screening programme efficacy.Results: In total, 483 cases of UVH and 184 of TGA were detected. The prenatal detection rate of UVH increased from 50.4% to 82.8% and of TGA from 12.3% to 41.0% (P < 0.0001). Maternal risk factors did not affect prenatal detection rate, but detection rate differed substantially by region.Conclusions: A nationwide screening programme improved overall UVH and TGA detection rates, but regional differences were observed. Obesity or other maternal risk factors did not affect the screening programme efficacy. The establishment of structured guidelines and recommendations is essential when implementing the screening programme. In addition, a prospective screening register is highly recommended to ensure high quality of screening.Tweetable Abstract: Implementation of a nationwide prenatal anomaly screening improved detection rates of UVH and TGA. [ABSTRACT FROM AUTHOR]

Background: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. Methods: Patients with oesophageal cancer were randomized to a home‐based IMT programme before surgery or usual care. IMT included the use of a flow‐resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. Results: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). Conclusion: Despite an increase in preoperative inspiratory muscle function, home‐based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 ( https://www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Evidence suggests that structured training programs for laparoscopic procedures can ensure a safe standard of skill acquisition prior to independent practice. Although minimally invasive esophagectomy (MIO) is technically demanding, no consensus on requirements for training for the MIO procedure exists. The aim of this study is to determine essential steps required for a structured training program in MIO using the Delphi consensus methodology. Eighteen MIO experts from 13 European hospitals were asked to participate in this study. The consensus process consisted of two structured meetings with the expert panel and two Delphi questionnaire rounds. A list of items required for training MIO were constructed for three key domains of MIO, including (1) requisite criteria for units wishing to be trained and (2) to proctor MIO and (3) a framework of a MIO training program. Items were rated by the experts on a scale 1-5, where 1 signified 'not important' and 5 represented 'very important.' Consensus for each domain was defined as achieving Cronbach alpha ⩾0.70. Items were considered as fundamental when ⩾75% of experts rated it important (4) or very important (5). Both Delphi rounds were completed by 16 (89%) of the 18 invited experts, with a median experience of 18 years with minimally invasive surgery. Consensus was achieved for all three key domains. Following two rounds of a 107-item questionnaire, 50 items were rated as essential for training MIO. A consensus among European MIO experts on essential items required for training MIO is presented. The identified items can serve as directive principles and core standards for creating a comprehensive training program for MIO. [ABSTRACT FROM AUTHOR]

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2, 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. [ABSTRACT FROM AUTHOR]

SUMMARY To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection. [ABSTRACT FROM AUTHOR]

SUMMARY We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning. [ABSTRACT FROM AUTHOR]

Cortical thickness analysis has been proposed as a potential diagnostic measure in memory disorders. In this retrospective study, we compared the cortical thickness values of 24 patients with frontotemporal dementia (FTD) to those of 25 healthy controls, 45 symptomatic subjects with stable mild cognitive impairment (S-MCI), 15 subjects with progressive mild cognitive impairment (P-MCI), and 36 patients with Alzheimer's disease (AD). The patterns of regions of thinning in FTD when compared to controls and also S-MCI patients showed similar trends; thinning of the bilateral frontal poles and bilateral medial temporal lobe structures, especially the anterior part of the gingulum, the uncus, and parahippocampal gyri. Cortical thinning in FTD was also found on the boundary regions of parietal and occipital lobes. In the P-MCI group compared to FTD, the trend of thinning in small distinct areas of the parietal and occipital lobes was observed. The FTD and AD groups did not differ statistically, but we found trends toward thinning in FTD of the left cingulate gyrus, and the left occipitotemporal gyri, and in AD of the inferior parietal, occipitoparietal, and the pericalcarine regions, more in the right hemisphere. In FTD, increased slowness in the executive test (Trail-Making A) correlated with the thinner cortex, whereas the language tests showed the lower scores, the thinner cortex in the left hemisphere. Cortical thickness might be a tool for detecting subtle changes in brain atrophy in screening of dementia prior to the development of diffuse or lobar atrophies. [ABSTRACT FROM AUTHOR]

Background: The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication. Methods: Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively. Results: There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038). Conclusions: Proliferative activity after fundoplication increased in the long term in the distal esophagus despite a normal fundic wrap and healing of GERD. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The ultimate purpose of the transport system is to serve the needs and expectations of the end users, who in turn shape the system by their own behaviour, actions and investments. This work examines, within the framework of the Large Technological Systems theory the possibility to categorise users of the transport system into homogeneous segments on the basis of their differences in daily mobility and transportation of goods. Furthermore, the potential to deepen this segmentation to describe the needs of, but later in the policy process also the social acceptance by, different user groups for new transport technology or policy, is examined. [ABSTRACT FROM AUTHOR]