David Stewart Morrison

Background & Aims: After decades of steep increases, primary liver cancer (PLC) incidence in Scotland was known to have plateaued between 2014 and 2017, while mortality continued to rise. More recent data are needed to understand if incidence trends were sustained and then began to affect mortality. Methods: Incidence and mortality data (1997–2023) from the Scottish Cancer Registry and National Records of Scotland, respectively, were linked to perform incidence-based mortality analysis. Temporal trends by PLC overall, and by subtypes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), were evaluated using Joinpoint regression. PLC subtypes, sex, age groups, deprivation quintiles, and histologic verification were compared across identified turning points. Results: 12,720 PLC incidence and 11,423 PLC mortality records were included. The plateau in overall PLC incidence continued from 2014 to 2023. PLC mortality rate increased from 5.4 in 1997 to 11.7 in 2017, then plateaued at 11.5 per 100,000 population through 2023. Incidence and mortality of iCCA continued to rise throughout. Conclusions: Sustained plateauing of HCC incidence in Scotland has led to levelling-off of mortality rates. These may be attributable to public health interventions and improved management of risk factors. Further work is needed to understand continued increases in iCCA rates.

Background: Cancer is a major contributor to morbidity following kidney transplantation. This study examines the incidence of cancer in kidney transplant recipients (KTRs) in Scotland, compares this to the general population, and identifies factors associated with cancer development. Methods: This nationwide cohort study utilised data from the Scottish Renal Registry, Scottish Cancer Registry and hospitalisation records. Standardised incidence rate ratios (SIRs) compared cancer incidence to the general population. Cox proportional hazards models identified factors associated with post-transplant cancer. Results: Between 1997-2021, 4033 patients ≥18 years received a first kidney transplant. 770 developed cancer versus 194 expected (SIR 3.9, 95% CI 3.7–4.2). Site-specific SIRs were greatest for non-melanomatous skin cancer, lymphoma and kidney cancer. Cancer incidence was 7-times that of the general population in kidney transplant recipient (KTR) under 40, the increased incidence fell to 3-times for KTRs over 60. Consistent differences in the incidence of the most common cancers in the general population (colorectal, lung breast, prostate) were not detected in this population. Conclusions: There is an increased risk of cancer in KTRs, particularly younger individuals. Non-melanomatous skin cancers remain the most frequent cancer in a population with low natural UV exposure. Tailored counselling and surveillance strategies are needed to improve patient outcomes.

Objective: To provide contemporary data on cancer mortality rates within the context of incidence in the population with intellectual disabilities. Methods: Scotland’s 2011 Census was used to identify adults with intellectual disabilities and controls with records linked to the Scottish Cancer Registry and death certificate data (March 2011–December 2019). The control cohort without intellectual disabilities and/or autism were used for indirect standardisation and calculation of crude incident rates/crude mortality rates, and age–sex standardised incident rate ratios/standardised mortality ratios (SIR/SMR), with 95% CIs. Results: Adults with intellectual disabilities were most likely diagnosed cancers of digestive, specifically colorectal (14.2%), lung (9.3%), breast (female 22.9%), body of the uterus (female 9.3%) and male genital organs (male 17.6%). Higher incident cancers included metastatic cancer of unknown primary origin (female SIR=1.70, male SIR=2.08), body of uterus (female SIR=1.63), ovarian (female SIR=1.59), kidney (female SIR=1.85) and testicular (male SIR=2.49). SMRs were higher, regardless of a higher, similar or lower incidence (female SMR=1.34, male SMR=1.07). Excess mortality risk was found for colorectal (total SMR=1.54, male SMR=1.59), kidney (total SMR=2.01 u, female SMR=2.85 u), female genital organs (SMR=2.34 (ovarian SMR=2.86 u, body of uterus SMR=2.11), breast (female SMR=1.58) and metastatic cancer of unknown primary origin (female SMR=2.50 u, male SMR=2.84). Conclusions: Adults with intellectual disabilities were more likely to die of cancer than the general population. Reasons for this may include later presentation/diagnosis (so poorer outcomes), poorer treatment/compliance or both. Accessible public health approaches are important for people with intellectual disabilities, and healthcare professionals need to be aware of the different cancer experiences faced by this population.

RESUMO Objetivo: Determinar se a admissão em terapia intensiva está associada à progressão subsequente da doença em pacientes com tumores sólidos não metastáticos. Métodos: Trata-se de estudo de coorte observacional de participantes do Biobanco do Reino Unido que identificou aqueles diagnosticados com tumores sólidos e que sobreviveram à hospitalização. Duas coortes foram formadas a partir da admissão em terapia intensiva e de uma nova doença metastática, conforme relatado nas consultas de seguimento do Biobanco do Reino Unido, ou foram comparados os registros de Atenção Primária ou Secundária. Utilizou-se a análise de riscos proporcionais de Cox para levar em conta os possíveis fatores de confusão na análise multivariada. Resultados: Identificaram-se 1.854 pacientes com tumores sólidos, dos quais 453 (24,4%) foram admitidos em terapia intensiva. As taxas não ajustadas de doença metastática e morte foram maiores na coorte de terapia intensiva com menor intervalo livre de progressão. Em 5 anos, 25% dos sobreviventes da terapia intensiva e 14% dos sobreviventes hospitalizados tinham desenvolvido doença metastática (p < 0,001), com taxa de intervalo livre de progressão equivalente de 65% versus 81% (p < 0,001). Após o ajuste para fatores de confusão, a razão de risco de intervalo livre de progressão entre os sobreviventes de terapia intensiva e a coorte hospitalizada foi de 1,69 (IC95% 1,31 - 2,18; p < 0,001). Conclusão: Pacientes com tumores sólidos internados no hospital dentro de 2 anos após o diagnóstico teriam intervalo livre de progressão subsequente mais baixo se tivessem passado por uma internação em terapia intensiva. Essa observação se manteve após o ajuste para variáveis de confusão.

Objective: To determine whether admission to critical care is associated with subsequent disease progression in patients with non-metastatic solid tumors. Methods: This observational cohort study of UK Biobank participants identified those diagnosed with solid tumors and survived hospitalization. Two cohorts were identified based on critical care admission and new metastatic disease as reported at UK Biobank follow-up visits, or primary or secondary care records were compared. Cox proportional hazards analysis was used to account for potential confounders in the multivariate analysis. Results: A total of 1,854 solid tumor patients were identified, of whom 453 (24.4%) experienced critical care admission. Unadjusted rates of metastatic disease and death were higher for the critical care cohort with lower progression-free survival. At five years, 25% of the critical care survivors and 14% of the hospitalized survivors had developed metastatic disease (p < 0.001), with a corresponding progression-free survival rate of 65% versus 81% (p < 0.001). After adjustment for confounders, the hazard ratio for progression-free survival between critical care survivors and the hospitalized cohort was 1.69 (95%CIs 1.31 - 2.18; p < 0.001). Conclusion: Solid tumor patients admitted to the hospital within 2 years of diagnosis had poorer subsequent progression-free survival if they had experienced a critical care admission. This observation was maintained after adjustment for confounding variables.

The coronavirus pandemic has disrupted cancer screening programmes. Kregting and colleagues’ microsimulation models indicate that attempting to quickly catch up with missed screens while simultaneously restarting the ongoing programme would achieve better outcomes but require substantial increases in normal screening capacity that may not be feasible.

Purpose: To describe the relationship between comorbidities and survival following admission to the intensive care unit. Methods: Retrospective observational study using several linked routinely collected databases from 16 general intensive care units between 2002 and 2011. Comorbidities identified from hospitalisation in the five years prior to intensive care unit admission. Odds ratios for survival in intensive care unit, hospital and at 30 days, 180 days and 12 months after intensive care unit admission derived from multiple logistic regression models. Results: There were 41,230 admissions to intensive care units between 2002 and 2011. Forty-one percent had at least one comorbidity – 24% had one, 17% had more than one. Patients with comorbidities were significantly older, had higher Acute Physiology and Chronic Health Evaluation II scores and were more likely to have received elective rather than emergency surgery compared with those without comorbidities. After excluding elective hospitalisations, intensive care unit and hospital mortality for the cohort were 24% and 29%, respectively. Asthma (odds ratio 0.79, 95% confidence interval 0.63–0.99) and solid tumours (odds ratio 0.74, 0.67–0.83) were associated with lower odds of intensive care unit mortality than no comorbidity. Intensive care unit mortality was raised for liver disease (odds ratio 2.98, 2.43–3.65), cirrhosis (odds ratio 2.61, 1.9–3.61), haematological malignancy (odds ratio 2.29, 1.85–2.83), chronic ischaemic heart disease (odds ratio 1.53, 1.19–1.98), heart failure (odds ratio 1.79, 1.35–2.39) and rheumatological disease (odds ratio 1.53, 1.18–1.98). Conclusions: Comorbidities affect two-fifths of intensive care unit admission and have highly variable effects on subsequent outcomes. Information on the differential effects of comorbidities will be helpful in making better decisions about intensive care unit support and understanding outcomes beyond surviving intensive care unit.

Background: Strategies for breast cancer prevention are informed by assessing whether incidence differs by tumour biology. We describe temporal trends of breast cancer incidence by molecular subtypes in Scotland. Methods: Population-based cancer registry data on 72,217 women diagnosed with incident primary breast cancer from 1997 to 2016 were analysed. Age-standardised rates (ASR) and age-specific incidence were estimated by tumour subtype after imputing the 8% of missing oestrogen receptor (ER) status. Joinpoint regression and age- period- cohort models were used to assess whether significant differences were observed in incidence trends by ER status. Results: ER positive tumour incidence steadily increased particularly for women of screening age 50 to 69 years from 1997 till around 2011 (1.6%/year, 95%CI: 1.2 to 2.1). ER negative incidence decreased among all ages at a consistent rate of −0.7%/year (95%CI: −1.5, 0) from around 2000-2016. Compared to the 1941-1959 central birth cohort, women born 1912-1940 had lower incidence rate ratios (IRR) for ER+ tumours and women born 1960- 1986 had higher IRR for ER- tumours. Conclusions: We show evidence of aetiologic heterogeneity of breast cancer. Future incidence and survival reporting should be monitored by molecular subtypes.

Insomnia in cancer patients is prevalent, persistent and confers risk for physical and psychological disorder. We must better understand how insomnia develops in cancer patients and explore the main contributors to its chronicity so that insomnia management protocols can be integrated more effectively within cancer care. This study monitors the etiology of insomnia in breast cancer patients and identifies risk factors for its persistence. 173 females with newly diagnosed, non-metastatic breast cancer were tracked from diagnosis for 12-months. Participants completed monthly sleep assessments using the Insomnia Severity Index (ISI) and 3-monthly health-related quality-of-life assessments using the European Organisation for Research and Treatment of Cancer - Breast (EORTC QLQ-C30-BR23) scale. Clinical data on disease status and treatment regimens were also assessed. Prior to diagnosis, 25% of participants reported sleep disturbance, including 8% with insomnia syndrome (IS). Prevalence increased at cancer diagnosis to 46% (18% IS) and remained stable thereafter at around 50% (21% IS). We also explored sleep status transitions. The most common pattern was to remain a good sleeper (34%-49%) or to persist with insomnia (23%-46%). 77% of good sleepers developed insomnia during the 12-month period and 54% went into insomnia remission. Chemotherapy (odds ratio=0·08, 95% ci 0·02-0·29, p<·001) and pre-diagnosis ISI scores (odds ratio=1·13/unit increase in pre-diagnosis sleep score, 95% ci 1·05-1·21, p=·001) were identified as the main risk factors for persistent insomnia. These data advance our understanding of insomnia etiology in cancer patients and help identify those who should be prioritised for insomnia management protocols.