Point-of-care lung ultrasound predicts hyperferritinemia and hospitalization, but not elevated troponin in SARS-CoV-2 viral pneumonitis in children.

SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.

Epidemiology and management of oral cavity squamous cell carcinoma in Ireland.

INTRODUCTION: The epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014. RESULTS: A total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215). CONCLUSION: Primary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.

Unified chromatography in drug development: Exploiting chaotropic/kosmotropic salts for an accelerated method development.

Recent trends in supercritical fluid chromatography (SFC) introduced an innovative gradient profile called Unified Chromatography (UC), which pushes the amount of liquid modifier up to 80-100 % of the total mobile phase composition. These new conditions allow the full transition from a supercritical to a liquid state, unifying the benefits of both SFC and liquid chromatography. However, to facilitate the use of UC for industrial drug development, a stronger effort is needed to streamline and simplify its method development and optimization. In this work, a quick and novel method development procedure for UC is introduced, enabled by the first-time use of novel additives in SFC/UC that exploit chaotropic/kosmotropic properties. A comprehensive view on some fundamental properties, such as the amount of liquid modifier blended with supercritical CO2 (scCO2) and the percentage of water added in the mobile phase is given, to clarify the benefits of using either a chaotropic salt (NaClO4), kosmotropic (HCOONa) or salt with mixed properties (NaOMs - sodium methanesulfonate). With this expanded knowledge, challenging separations of nucleosides, nucleotide, indoles, triazoles and related derivates have been accomplished with UC. Finally, we provide an example of UC delivering a faster and better method for an AbbVie pipeline compound under accelerated stability study. The combined use of scCO2-based chromatography and the novel additive NaClO4 ensures the retention and elution of all degradation species generated at different conditions, where RP-HPLC failed to provide satisfactory performance.

Survival in an era of organ preservation: an update on laryngeal cancer in Ireland.

BACKGROUND: Laryngeal cancer epidemiology has changed in recent years, with falling incidence observed internationally. Organ preservation therapies have revolutionised management, though some patients may be unsuitable and survival was noted to fall in the 2000s. This study examines trends in laryngeal cancer in Ireland. METHODS: A retrospective cohort study of National Cancer Registry of Ireland data from 1994 to 2014. RESULTS: From a cohort of 2651, glottic disease was most common (62%, n = 1646). Incidence rose to 3.43 cases/100,000/year for 2010-2014. 5-year disease-specific survival (DSS) was 60.6% and did not change significantly over time. Overall survival (OS) for T3 disease managed with primary radiotherapy was similar to primary surgery (HR 0.98, p = 0.9). DSS for T3 disease improved with primary radiotherapy (HR 0.72, p = 0.045). CONCLUSION: Incidence of laryngeal cancer in Ireland rose despite international trends, while survival changed little. Radiotherapy improves DSS for T3 disease but does not improve OS, possibly secondary to poor organ function post-radiotherapy.

Impact of the COVID-19 pandemic on cancer care in Ireland - Perspectives from a COVID-19 and Cancer Working Group.

Upon the COVID-19 pandemic onset in Ireland, cancer service disruptions occurred due to prioritisation of COVID-19 related care, redeployment of staff, initial pausing of screening, diagnostic, medical and surgical oncology procedures, staff shortages due to COVID-19 infection and impacts on the physical and mental health of cancer healthcare workers. This was coupled with reluctance among people with symptoms suspicious for cancer to attend for clinical evaluation, due to concerns of contracting the virus. This was further compounded by a cyber-attack on national health service IT systems on May 14th 2021. The Irish Cancer Society, a national cancer charity with a role in advocacy, research and patient supports, convened a multi-disciplinary stakeholder group (COVID-19 and Cancer Working Group) to reflect on and understand the impact of the pandemic on cancer patients and services in Ireland, and discuss potential mitigation strategies. Perspectives on experiences were gathered across domains including timeliness of data acquisition and its conversion into intelligence, and the resourcing of cancer care to address cancer service impacts. The group highlighted aspects for future research to understand the long-term pandemic impact on cancer outcomes, while also highlighting potential strategies to support cancer services, build resilience and address delayed diagnosis. Additional measures include the need for cancer workforce recruitment and retention, increased mental health supports for both patients and oncology professionals, improvements to public health messaging, a near real-time multimodal national cancer database, and robust digital and physical infrastructure to mitigate impacts of the current pandemic and future challenges to cancer care systems.

Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

Age Alone Is Not a Barrier to Concurrent Chemoradiotherapy for Advanced Head and Neck Cancer.

BACKGROUND: Head and Neck Cancer (HNC) is associated with significant morbidity and mortality, especially when high stage disease is present. There exists a range of options for the management of locoregionally advanced HNC, though doubt remains as to the optimal strategy in the elderly population. AIMS: To evaluate the benefits imparted by concurrent chemoradiotherapy (CCRT) to the elderly population of HNC patients in Ireland. METHODS: A retrospective cohort study was conducted using 20 years of cancer registry data provided by the National Cancer Registry of Ireland. Cox multivariate regression analysis was applied to test for the benefits of CCRT in HNC. RESULTS: Survival analysis showed an overall benefit to the use of CCRT in patients with advanced disease over 70 years, particularly when used for hypopharyngeal, oropharyngeal, and laryngeal malignancy. There was a benefit to cancer-specific but not all-cause mortality in those over 75 years, and no benefit was observed to the addition of chemotherapy in those over 80 years; only 8 patients over 80 received CCRT. There was no statistically significant difference in the benefits derived by those over 70 years relative to those under 70 years. CONCLUSION: CCRT confers significant survival benefits to appropriately selected elderly HNC patients and should therefore not be withheld solely on the basis of age.

Photo-Oxidation Mechanisms in Liquid Pharmaceutical Formulations: The Overlooked Role of Singlet Oxygen Presented as a Case Study.

PURPOSE: Oxidation is one of the most common degradation pathways for active pharmaceutical ingredients (APIs) in pharmaceutical formulations, mostly involving 1-electron processes via peroxy radicals and 2-electron processes by peroxides. In liquid pharmaceutical formulations, several factors can impact oxidative instabilities including pH, excipient impurities, headspace oxygen, and the potential for photo-oxidation. Photo-oxidation can be particularly challenging to characterize given the number of oxidative mechanisms which can occur. This was observed during formulation development of a new chemical entity, MK-1454, where a degradation peak was observed during photostability studies which was not previously observed during peroxide and peroxyradical forced stress studies. METHODS: To gain a fundamental understanding of reactive oxygen species generation and its role in degradation of MK-1454, experiments were performed with materials which either generate or measure reactive oxygen species including organic hydroperoxides, singlet oxygen, and superoxide to fundamentally understand a photodegradation mechanism which was observed in the original formulation. LC-MS experiments further elucidated the structure and mechanism of this observed degradation pathway. RESULTS: A clear relationship between the decrease in dissolved oxygen after light exposure and the loss of MK-1454 was established. The data indicate that singlet oxygen is the most likely contributor of a particular photodegradation product. The singlet oxygen was generated by the inactive ingredients in the formulation, and LC-MS confirm this as the most likely pathway. CONCLUSION: This work highlights the importance of understanding photochemical degradation of APIs in solution formulations and provides approaches which can better elucidate those mechanisms and thereby control strategies.

Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

Lung ultrasound allows for earlier diagnosis of bronchiolitis than auscultation: an animal experiment and human case series.

PURPOSE: Early diagnosis of bronchiolitis in infants allows for risk stratification for central apnea, and, when available, the timely initiation of antiviral treatment. An animal model could demonstrate if earlier diagnosis is possible with ultrasound than with clinical exam. Even if possible, translating this to pediatrics would require observations from undifferentiated human infants. METHODS: We used serial daily clinical and lung ultrasound exams in a bovine calf model (Bos taurus) of respiratory syncytial virus bronchiolitis. Ultrasound and clinical examiners were blinded to each other's findings and the treatments used in 24 calves. Time to diagnosis was compared using Kaplan-Meier curves. A case series of human infants with upper respiratory tract infections, without clinical signs of bronchiolitis, and in whom lung ultrasound was performed, was extracted from hospital records. RESULTS: In the bovine model, lung ultrasound findings emerged earlier and lasted later than auscultatory findings. Relying on auscultation, 5/24 (21%) of animals were diagnosed by post-inoculation day 5 whereas 24/24 (100%) were diagnosed by ultrasound. We identified seven infants in whom lung ultrasound was used to diagnose bronchiolitis before adventitial lung sounds emerged. Three of these subsequently developed typical clinical findings of bronchiolitis in the hospital. Two had alternative explanations for their abnormal lung ultrasounds (both required surgical intervention). Two were discharged and required no further medical attention. CONCLUSION: Lung ultrasound allowed earlier diagnosis of bronchiolitis than clinical exam in the bovine model. In the human case series this was also true, but alternative causes of abnormal ultrasound were frequent.

Validating a bovine model for lung ultrasound of bronchiolitis.

PURPOSE: Bronchiolitis is a very common acute lung disease in infants caused commonly by respiratory syncytial virus (RSV). Point-of-care lung ultrasound is increasingly used in clinical care but proof that ultrasound reflects histological disease is lacking. Bovine calves are a good model for RSV bronchiolitis. We answered the following two questions: (1) does point-of-care lung ultrasound reflect lung pathology at the histological level in a bovine calf model of bronchiolitis? and (2) are point-of-care lung ultrasound images in human infants similar to those obtained in calves? METHODS: We experimentally infected 24 five to six-week-old bovine calves with RSV and compared six window lung ultrasound with lung histology10 days after inoculation. The calves were treated with antivirals and antipyretics leading to variable severity of illness. We used canonical discriminant analysis to determine if abnormal lung ultrasound findings reflected different histological findings. We compared the ultrasounds obtained from the calves with ultrasounds obtained from 10 human infants who were diagnosed clinically with bronchiolitis. RESULTS: Canonical discriminant analysis generally demonstrated good class separation based on the maximal severity of ultrasound finding in each acoustic window. Lung ultrasound performed poorly at detecting bronchopneumonia. Bovine ultrasounds looked similar to human infant lung ultrasounds. CONCLUSION: Point-of-care lung ultrasound abnormalities reflect lung pathology at the histological level in a bovine calf model of bronchiolitis. Point-of-care lung ultrasound images in human infants are similar to those obtained in calves.

Social inequalities in treatment receipt for childhood cancers in Ireland: A population-based analysis.

Treatment advances over the past five decades have resulted in significant improvements in survival from childhood cancer. Although survival rates are relatively high, social disparities in outcomes have been sometimes observed. In a population-based study, we investigated social inequalities by sex and deprivation in treatment receipt in childhood cancer in Ireland. Cancers incident in people aged 0 to 19 during 1994 to 2012 and treatments received were abstracted from the National Cancer Registry Ireland. Multivariable modified Poisson regression with robust error variance (adjusting for age, and year) was used to assess associations between sex and deprivation category of area of residence at diagnosis and receipt of cancer-directed surgery, chemotherapy or radiotherapy. Three thousand seven hundred and four childhood cancers were included. Girls were significantly less likely than boys to receive radiotherapy for leukemia overall (relative risk [RR] = 0.70; 95% confidence interval [CI] = 0.50-0.98), and acute lymphoblastic leukemia specifically (RR = 0.54; 95% CI = 0.36-0.79), and surgery for central nervous system (CNS) overall (RR = 0.83; 95% CI = 0.74-0.93) and other CNS (RR = 0.76; 95% CI = 0.60-0.96). Girls were slightly less likely to receive chemotherapy for non-Hodgkin lymphoma and surgery for Hodgkin lymphoma (HL), but these results were not statistically significant. Children residing in more deprived areas were significantly less likely to receive chemotherapy for acute myeloid leukemia or surgery for lymphoma overall and HL, but more likely to receive chemotherapy for medulloblastoma. These results may suggest social inequalities in treatment receipt for childhood cancers. Further research is warranted to explore whether similar patterns are evident in other childhood cancer populations and to better understand the reasons for the findings.

The changing face of Irish head and neck cancer epidemiology: 20 years of data.

BACKGROUND: Head and neck cancer (HNC) is associated with significant morbidity and mortality, especially when high stage disease is present. The epidemiology and prognosis of HNC has changed considerably over the last 20 years. AIMS: This study aimed to examine the epidemiological trends in HNC patients over a prolonged period in Ireland. METHODS: We conducted a retrospective cohort study using 20 years of cancer registry data provided by the National Cancer Registry of Ireland. Baseline characteristics and survival statistics were thereby generated. RESULTS: 10,148 patients were identified. There is a growing population of young (< 50 years) and very old (> 85 years) HNC patients; 48.15% of the population was elderly (> 65 years). Oral cavity (29.8%) and laryngeal cancer (28.1%) remain the most prevalent subsites, though oral cavity cancer prevalence declined from 35.9% in 1994 to 27.5% in 2014. Oropharyngeal cancer prevalence increased from 13.6 to 22.2% over the same period. Overall 5-year survival has improved significantly to 56.8% in 2010 but there remains a disparity between the elderly and adult cohorts (42.0% vs 60.7%). 5-year survival for hypopharyngeal and oropharyngeal cancers has improved from 11.8% and 33.3% to 22.2% and 44.8%, respectively, while laryngeal and oral cavity cancer survival remains approximately stable at 58.7% and 61.5%, respectively. CONCLUSION: HNC survival in Ireland has improved in line with increasing recognition of the value of multidisciplinary assessment, subspecialisation in cancer care, and targeted therapies based on tumour subsites. Survival in the elderly cohort remains poor despite increasing recognition of the challenges such cases pose.

International differences in lung cancer survival by sex, histological type and stage at diagnosis: an ICBP SURVMARK-2 Study.

INTRODUCTION: Lung cancer has a poor prognosis that varies internationally when assessed by the two major histological subgroups (non-small cell (NSCLC) and small cell (SCLC)). METHOD: 236 114 NSCLC and 43 167 SCLC cases diagnosed during 2010-2014 in Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK were included in the analyses. One-year and 3-year age-standardised net survival (NS) was estimated by sex, histological type, stage and country. RESULTS: One-year and 3-year NS was consistently higher for Canada and Norway, and lower for the UK, New Zealand and Ireland, irrespective of stage at diagnosis. Three-year NS for NSCLC ranged from 19.7% for the UK to 27.1% for Canada for men and was consistently higher for women (25.3% in the UK; 35.0% in Canada) partly because men were diagnosed at more advanced stages. International differences in survival for NSCLC were largest for regional stage and smallest at the advanced stage. For SCLC, 3-year NS also showed a clear female advantage with the highest being for Canada (13.8% for women; 9.1% for men) and Norway (12.8% for women; 9.7% for men). CONCLUSION: Distribution of stage at diagnosis among lung cancer cases differed by sex, histological subtype and country, which may partly explain observed survival differences. Yet, survival differences were also observed within stages, suggesting that quality of treatment, healthcare system factors and prevalence of comorbid conditions may also influence survival. Other possible explanations include differences in data collection practice, as well as differences in histological verification, staging and coding across jurisdictions.

International variation in oesophageal and gastric cancer survival 2012-2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study).

OBJECTIVE: To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. METHODS: As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012-2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. RESULTS: Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. CONCLUSION: Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.

A way to explore the existence of "immortals" in cancer registry data - An illustration using data from ICBP SURVMARK-2.

BACKGROUND: Accurately recorded vital status of individuals is essential when estimating cancer patient survival. When deaths are ascertained by linkage with vital statistics registers, some may be missed, and such individuals will wrongly appear to be long-term survivors, and survival will be overestimated. Interval-specific relative survival that levels off above one indicates that the survival among the cancer patients is better than expected, which could be due to the presence of immortals. METHODS: We included colon cancer cases diagnosed in 1995-1999 within the 19 jurisdictions in seven countries participating in ICBP SURVMARK-2, with follow-up information available until end-2015. Interval-specific relative survival was estimated for each year following diagnosis, by country and age group at diagnosis. RESULTS: The interval-specific relative survival levels off at 1 for all countries and age groups, with two exceptions: for the age group diagnosed at age 75 years and above in Ireland, and, to a lesser extent, in New Zealand. CONCLUSION: Overall, a subset of immortals are not apparent in the early years within the ICBP SURVMARK-2 study, except for possibly in Ireland. We suggest this approach as one strategy of exploring the existence of immortals, and to be part of routine checks of cancer registry data.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

PURPOSE: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes. METHODS: This was a national, multi-site, retrospective observational study, including PABC patients treated in 12 oncology institutions from August 2001 to January 2020. Data extracted included information on patient demographics, tumour biology, staging, treatments, and maternal/foetal outcomes. Survival data for an age-matched breast cancer population over a similar time period was obtained from the National Cancer Registry of Ireland (NCRI). Standard biostatistical methods were used for analyses. RESULTS: We identified 155 patients-71 (46%) were gp-PABC and 84 (54%) were pp-PABC. The median age was 36 years. Forty-four patients (28%) presented with Stage III disease and 25 (16%) had metastatic disease at diagnosis. High rates of triple-negative (25%) and HER2+ (30%) breast cancer were observed. We observed an inferior 5-year overall survival (OS) rate in our PABC cohort compared to an age-matched breast cancer population in both Stage I-III (77.6% vs 90.9%) and Stage IV disease (18% vs 38.3%). There was a low rate (3%) of foetal complications. CONCLUSION: PABC patients may have poorer survival outcomes. Further prospective data are needed to optimise management of these patients.

A randomized controlled trial comparing non-steroidal anti-inflammatory and fusion protein inhibitors singly and in combination on the histopathology of bovine respiratory syncytial virus infection.

Bovine respiratory syncytial virus (RSV) has substantial morbidity in young calves, and closely parallels human RSV in infants. We performed a randomized controlled trial in five to six-week-old Holstein calves (Bos taurus). comparing fusion protein inhibitor (FPI) and non-steroidal anti-inflammatory drug (NSAID) singly and in combination at three and five days after experimental BRSV infection. Thirty-six calves received one of six treatments; Ibuprofen started on day 3, Ibuprofen started on day 5, FPI started on day 5, FPI and Ibuprofen started on day 3, FPI and Ibuprofen started on day 5, or placebo. We have previously reported significant clinical benefits when combined FPI and NSAID treatment was started at three and five days after bovine RSV infection. Necropsy was performed on Day 10 following infection and hematoxylin and eosin staining was performed on sections from each lobe. Histology was described using a four-point scale. We performed canonical discrimination analysis (CDA) to determine the structural level where differences between treatments occurred and mixed effects regression to estimate effect sizes. Separation from placebo was maximal for dual therapy at the levels of the alveolus, septum, and bronchus in CDA. We found that the clinical benefits of combined FPI and NSAID treatment of BRSV extend at least partially from histopathological changes in the lung when treatment was started three days after infection. We found decreased lung injury when ibuprofen was started as monotherapy on day 3, but not day 5 following infection. Combined therapy with both an FPI and ibuprofen was always better than ibuprofen alone. We did not prove that the clinical benefits seen starting FPI and ibuprofen five days after infection can be solely explained by histopathological differences as identified on H&E staining.