Ethnicity and socio-economic status affects the incidence and survival of hepatosplenic T-cell lymphoma.

To address the lack of contemporary population-based epidemiological studies of hepatosplenic T-cell lymphoma (HSTCL), we undertook a population-based study of ICD-O-3-coded HSTCL in England. We used the National Cancer Registration Dataset and linked datasets on hospital admissions, Systemic Anti-Cancer Therapy, socio-demographics, comorbidities and death, identifying cases from 1 January 2013 to 31 December 2019 with survival data up to 5 January 2021. Crude and directly age-standardised incidence rates per million persons per year were calculated. Crude and adjusted incidence rate ratios compared incidence between groups using Poisson regression. A Cox proportional hazards model estimated mortality risks adjusted for age, sex, ethnicity, deprivation and allogenic stem cell transplant (allo-SCT; time varying). We identified 44 patients, mean age 42 years. Median survival was 11 months, and 1 and 5 year survivals were 48% (95% CI 29%-43%) and 22% (95% CI 12%-42%) respectively. The age-standardised incidence was 0.1 per million/year. Incidence was higher in areas with greater deprivation (0.15 per million/year), and more cases than expected were in non-White patients (39%). Non-Whites had a twofold increased risk of death (adjusted hazard ratio 2.21 [95% CI 1.03-4.78]) even after adjusting for deprivation, younger age and allo-SCT. In conclusion, ethnicity and socio-economic status affect both the incidence and survival of HSTCL.

Smoking is a Risk Factor for Autoimmune Hepatitis: An English Registry-Based Case-Control Study.

Purpose: Smoking is a risk factor for some autoimmune diseases, but its association with autoimmune hepatitis remains unknown. We conducted a population-based matched case-control study to examine the association between tobacco smoking and the risk of autoimmune hepatitis in England. Patients and Methods: From the Clinical Practice Research Datalink and linked Hospital Episode Statistics, 2005-2017, we included 987 cases diagnosed with autoimmune hepatitis after age 18 years and up to 10 frequency-matched population controls per case. We used multiple logistic regression to estimate the odds ratio of autoimmune hepatitis in ever-smokers vs never-smokers, adjusting for sex, age, general practice, calendar time of registration with the general practice, and socioeconomic status. Results: The autoimmune hepatitis cases were more likely to be ever-smokers than the controls (44% vs 37%). The ever-smokers had an increased risk of autoimmune hepatitis compared with the never-smokers (adjusted odds ratio = 1.20, 95% confidence interval 1.03-1.39). Conclusion: Smoking was associated with an increased risk of autoimmune hepatitis.

Cause-specific mortality in patients with alcohol-related liver disease in Denmark: a population-based study.

BACKGROUND: Increased knowledge of the causes of death will be essential to prevent premature death in alcohol-related liver disease. We examined cause-specific mortality, including death due to specific cancers, in the 15 years after diagnosis of alcohol-related liver disease. METHODS: We used nationwide health registries to identify patients (aged ≥18 years) with a first diagnosis of alcohol-related liver disease between Jan 1, 2002, and Dec 31, 2017, in Denmark and followed up patients for their underlying cause of death up to Dec 31, 2019. We estimated the cause-specific mortality and investigated whether the cause-specific mortality differed by sex, age (<50, 50-59, and ≥60 years), alcohol-related liver disease severity at diagnosis (decompensated cirrhosis, compensated cirrhosis, alcoholic hepatitis, and steatosis or unspecified liver disease), and presence of diabetes. FINDINGS: The study included 23 385 patients with incident alcohol-related liver disease. Patients had a median age of 58 years (IQR 51-65), 15 819 (68%) were men and 7566 (32%) were women, and 15 358 (66%) had cirrhosis. During 111 532 person-years of follow-up, 15 692 (67%) patients died. Liver disease was the leading cause of death. In the first 5 years after alcohol-related liver disease diagnosis, liver disease caused almost half of all deaths, and the 5-year risk of death due to liver disease was 25·8% (95% CI 25·3-26·4). Beyond 5 years, causes other than liver disease combined became more common; of these extrahepatic causes, cancer, cardiovascular disease, and alcohol use disorder were the most common. Hepatocellular carcinoma was the dominant cause of cancer death (10-year risk of 2·5%, 95% CI 2·3-2·7), followed by lung cancer (1·9%, 1·7-2·1). The 10-year risk of death due to liver disease (around 30%) was similar for patients in all age groups and independent of sex and diabetes but was three times higher for those with decompensated cirrhosis (46·7%, 44·8-48·4) than steatosis or unspecified liver disease (16·2%, 15·3-17·2). INTERPRETATION: Patients diagnosed with alcohol-related liver disease were at high risk of dying from liver disease many years after diagnosis, irrespective of age and sex. Death due to specific cancers, including hepatocellular carcinoma, each contributed minimally to the total mortality in patients with alcohol-related liver disease. FUNDING: TrygFonden and the Novo Nordisk Foundation.

Outcomes after emergency appendicectomy in patients with liver cirrhosis: a population-based cohort study from England.

INTRODUCTION: The mortality risk after appendicectomy in patients with liver cirrhosis is predicted to be higher than in the general population given the associated risk of perioperative bleeding, infections and liver decompensation. This population-based cohort study aimed to determine the 90-day mortality risk following emergency appendicectomy in patients with cirrhosis. METHODS: Adult patients undergoing emergency appendicectomy in England between January 2001 and December 2018 were identified from two linked primary and secondary electronic healthcare databases, the clinical practice research datalink and hospital episode statistics data. Length of stay, re-admission, case fatality and the odds ratio of 90-day mortality were calculated for patients with and without cirrhosis, adjusting for age, sex and co-morbidity using logistic regression. RESULTS: A total of 40,353 patients underwent appendicectomy and of these 75 (0.19%) had cirrhosis. Patients with cirrhosis were more likely to be older (p < 0.0001) and have comorbidities (p < 0.0001). Proportionally, more patients with cirrhosis underwent an open appendicectomy (76%) compared with 64% of those without cirrhosis (p = 0.03). The 90-day case fatality rate was 6.67% in patients with cirrhosis compared with 0.56% in patients without cirrhosis. Patients with cirrhosis had longer hospital length of stay (4 (IQR 3-9) days versus 3 (IQR 2-4) days and higher readmission rates at 90 days (20% vs 11%, p = 0.019). Most importantly, their odds of death at 90 days were 3 times higher than patients without cirrhosis, adjusted odds ratio 3.75 (95% CI 1.35-10.49). CONCLUSION: Patients with cirrhosis have a threefold increased odds of 90-day mortality after emergency appendicectomy compared to those without cirrhosis.

Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in England.

BACKGROUND: A faecal immunochemical tests (FIT) cut-off of ≥10 µg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%. AIMS: To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata. METHODS: A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017-2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates. RESULTS: In total, 514 (1.5%) CRCs were diagnosed following 33,694 index FIT requests. Individuals with a FIT ≥ 10 µg Hb/g faeces had a >3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% [95% CI: 0.03%-2.86%]). Non-anaemic patients with a FIT < 100 µg Hb/g faeces had a CRC risk of <3%, except those between the age of 70 and 85 years (5.26% 95% CI: 2.72%-7.73%). Using a ≥3% CRC threshold in patients <55 years calculated using FIT, age and anaemia might allow 160-220 colonoscopies per 10,000 FITs to be re-purposed, at a cost of missing 1-2 CRCs. CONCLUSIONS: FIT alone with a single cut-off is unlikely to be a panacea for optimising CRC diagnosis, as risk varies by FIT, age and anaemia when faecal haemoglobin levels are below 100 µg Hb/g. Tailored FIT cut-offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.

1-year survival in haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018.

Haemophagocytic lymphohistiocytosis (HLH) is a lethal syndrome of excessive immune activation. We undertook a nationwide study in England of all cases of HLH diagnosed between 2003 and 2018, using linked electronic health data from hospital admissions and death certification. We modelled interactions between demographics and comorbidities and estimated one-year survival by calendar year, age group, gender and comorbidity (haematological malignancy, auto-immune, other malignancy) using Cox regression. There were 1628 people with HLH identified. Overall, crude one-year survival was 50% (95% Confidence interval 48-53%) which varied substantially with age (0-4: 61%; 5-14: 76%; 15-54: 61%; > 55: 24% p < 0.01), sex (males, 46%, worse than females, 55% p < 0.01) and associated comorbidity (auto-immune, 69%, haematological malignancy 28%, any other malignancy, 37% p < 0.01). Those aged < 54 years had a threefold increased risk of death at 1-year amongst HLH associated with malignancy compared to auto-immune. However, predicted 1-year survival decreased markedly with age in those with auto-immune (age 0-14, 84%; 15-54, 73%; > 55, 27%) such that among those > 55 years, survival was as poor as for patients with haematological malignancy. One-year survival following a diagnosis of HLH varies considerably by age, gender and associated comorbidity. Survival was better in those with auto-immune diseases among the young and middle age groups compared to those with an underlying malignancy, whereas in older age groups survival was uniformly poor regardless of the underlying disease process.

Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials.

BACKGROUND AND AIMS: Observational studies have shown an association between statin or aspirin use and a decreased risk of HCC, but the effects of a well-defined treatment strategy remain unknown. We emulated trials of the effects of continuous statin or aspirin use on HCC risk in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis). APPROACH AND RESULTS: We specified target trials for statins and, separately, aspirin and emulated them using Danish health care registries. All eligible patients with ALD cirrhosis diagnosed in 2000-2018 were included in either an exposed or an unexposed arm. Patients were followed until HCC or death without HCC. The 5-year risk of HCC was estimated using marginal structural models with inverse probability weighting. Using statins continuously for 5 years compared with not using statins resulted in a relative risk (RR) of HCC of 0.67 (95% CI: 0.45-0.91). The RR of death without HCC was 0.69 (95% CI: 0.65-0.77). For aspirin, the RR was 1.05 (95% CI: 0.60-1.42) for HCC and 1.02 (95% CI: 0.95-1.09) for death without HCC. CONCLUSIONS: In patients with ALD cirrhosis, 5 years of continuous statin use resulted in a 33% RR reduction of HCC (number needed to treat = 94) and a 31% RR reduction of death without HCC (number needed to treat = 7). Such strong causal effects are implausible and best explained by uncontrollable confounding, highlighting the need for randomized trials. Aspirin use likely does not affect the risk of HCC or death without HCC.

Long-term adverse effects and healthcare burden of rectal cancer radiotherapy: systematic review and meta-analysis.

BACKGROUND: As rectal cancer survival increases, more patients survive with potentially severe, long-term gastrointestinal and genitourinary complications from radiotherapy. The burden of these complications for patients and healthcare services is unclear, which this review aims to quantify. METHODS: Systematic search of Medline and Embase for randomized-controlled trials (RCTs) and multicentre observational studies published since 2000, reporting hospitalization/procedural intervention for long-term (>6 months post-treatment) gastrointestinal or genitourinary complications after radiotherapy and surgery for rectal cancer. Prevalence values were pooled in a meta-analysis assuming random effects. Organ-preservation patients were excluded. RESULTS: 4044 records screened; 24 reports from 23 studies included (15 RCTs, 8 Observational), encompassing 15 438 patients. Twenty-one studies (median follow-up 60 months) reported gastrointestinal complications post-radiotherapy: pooled prevalence 11% (95% confidence interval (95% CI) 8-14%). Thirteen reported small bowel obstruction: prevalence 9% (95% CI 6-12%), a 58% increased risk compared with surgery alone (RR 1.58, 95% CI 1.26-1.98, n = 5 studies). Seven reported fistulas: prevalence 1% (95% CI 1-2%). Thirteen reported genitourinary complications: prevalence 4% (95% CI 1-6%); RR 1.10 (95% CI 0.88-1.38, n = 3 studies) compared with surgery alone. CONCLUSIONS: Over 10% of patients are hospitalized for long-term complications following rectal cancer radiotherapy. Serious gastrointestinal complications are commonplace; late small bowel obstruction is more common in patients having radiotherapy and surgery compared with surgery alone. Patients and clinicians need to be aware of these risks.

Temporal Trends in the Incidence of Hemophagocytic Lymphohistiocytosis: A Nationwide Cohort Study From England 2003-2018.

Hemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality, and is increasingly being diagnosed. We aimed to quantify the incidence of diagnosed HLH and examine temporal trends in relation to age and associated diseases. Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between January 1, 2003, and December 31, 2018. We calculated incidence rates of diagnosed HLH per million population by calendar year, age group, sex, and associated comorbidity (hematological malignancy, inflammatory rheumatological or bowel diseases [IBD]). We modeled trends in incidence and the interactions between calendar year, age, and associated comorbidity using Poisson regression. There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (incidence rate ratio [IRR] 2018 compared to 2003: 3.88, 95% confidence interval [CI] 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11, 95% CI 1.09 to 1.12). There was a transition across age groups with greater increases in those aged 5-14 years of HLH associated with rheumatological disease/IBD compared with hematological malignancy, with similar increases in HLH associated with both comorbidities for those 15-54, and greater increases in HLH associated with hematological malignancies for those 55 years and older. The incidence of HLH in England has quadrupled between 2003 and 2018. Substantial variation in the incidence occurred with inflammatory rheumatological diseases/IBD-associated HLH increasing more among the younger age groups, whereas in older age groups, the largest increase was seen with hematological malignancy-associated HLH.

Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.

The Duration and Magnitude of Postdischarge Venous Thromboembolism Following Colectomy.

OBJECTIVE: To assess the impact of current guidelines by reporting weekly postoperative postdischarge venous thromboembolism (VTE) rates. SUMMARY BACKGROUND DATA: Disparity exists between the postoperative thromboprophylaxis duration colectomy patients receive based on surgical indication, where malignant resections routinely receive 28 days extended thromboprophylaxis into the postdischarge period and benign resections do not. METHODS: English national cohort study of colectomy patients between 2010 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type and surgical indication, absolute incidence rates (IRs) per 1000 person-years and adjusted incidence rate ratios (aIRRs) for postdischarge VTE were calculated for the first 4 weeks following resection and postdischarge VTE IRs for each postoperative week to 12 weeks postoperative. RESULTS: Of 104,744 patients, 663 (0.63%) developed postdischarge VTE within 12 weeks after colectomy. Postdischarge VTE IRs per 1000 person-years for the first 4 weeks postoperative were low following elective resections [benign: 20.66, 95% confidence interval (CI): 13.73-31.08; malignant: 28.95, 95% CI: 23.09-36.31] and higher following emergency resections (benign: 47.31, 95% CI: 34.43-65.02; malignant: 107.18, 95% CI: 78.62-146.12). Compared with elective malignant resections, there was no difference in postdischarge VTE risk within 4 weeks following elective benign colectomy (aIRR=0.92, 95% CI: 0.56-1.50). However, postdischarge VTE risks within 4 weeks following emergency resections were significantly greater for benign (aIRR=1.89, 95% CI: 1.22-2.94) and malignant (aIRR=3.13, 95% CI: 2.06-4.76) indications compared with elective malignant colectomy. CONCLUSIONS: Postdischarge VTE risk within 4 weeks of colectomy is ∼2-fold greater following emergency benign compared with elective malignant resections, suggesting emergency benign colectomy patients may benefit from extended VTE prophylaxis.

Time trends in the incidence rates of venous thromboembolism following colorectal resection by indication and operative technique.

AIM: It is important for patient safety to assess if international changes in perioperative care, such as the focus on venous thromboembolism (VTE) prevention and minimally invasive surgery, have reduced the high post colectomy VTE risks previously reported. This study assesses the impact of changes in perioperative care on VTE risk following colorectal resection. METHOD: This was a population-based cohort study of colectomy patients in England between 2000 and 2019 using a national database of linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Within 30 days following colectomy, absolute VTE rates per 1000 person-years and adjusted incidence rate ratios (aIRRs) using Poisson regression for the per year change in VTE risk were calculated. RESULTS: Of 183 791 patients, 1337 (0.73%) developed 30-day postoperative VTE. Overall, VTE rates reduced over the 20-year study period following elective (relative risk reduction 31.25%, 95% CI 5.69%-49.88%) but not emergency surgery. Similarly, yearly changes in VTE risk reduced following minimally invasive resections (elective benign, aIRR 0.93, 95% CI 0.90-0.97; elective malignant, aIRR 0.94, 95% CI 0.91-0.98; and emergency benign, aIRR 0.96, 95% CI 0.92-1.00) but not following open resections. There was a per year VTE risk increase following open emergency malignant resections (aIRR 1.02, 95% CI 1.00-1.04). CONCLUSION: Yearly VTE risks reduced following minimally invasive surgeries in the elective setting yet in contrast were static following open elective colectomies, and following emergency malignant resections increased by almost 2% per year. To reduce VTE risk, further efforts are required to implement advances in surgical care for those having emergency and/or open surgery.

The risk of unexpected hospital admissions and primary care visits after an elective day-case gastroscopy: a cohort study within England.

AIM: To determine the excess of acute medical contacts following a day-case diagnostic gastroscopy. METHODS: Cohort study using English linked primary, secondary care and death registry electronic health data. We included 277,535 diagnostic day-case gastroscopies in 225,304 people between 1998 and 2016 and followed up for 30 days. 1,383,535 30-day periods without a gastroscopy within 991,249 people frequency matched on year, gender and decade of birth. Non-cancer deaths, emergency non-cancer admissions and cardio, vascular or respiratory (CVR) primary care consultations were identified and adjusted for each other as competing risks. Outcomes related to possible indications for gastroscopy were censored. RESULTS: 5.1% of day-case diagnostic gastroscopies were followed by emergency hospital admission, 0.4% for a CVR diagnosis. Adjusted for age, sex, morbidity, time trends, indications and competing risks, there was a 0.1% excess of CVR-related hospital admissions compared to controls. This reduced to 0.05% (95% confidence interval 0.04-0.06%) in people under 40 years without morbidity and increased to 1.1% (0.6%-1.6%) in people over 90 years with high comorbidity. Similarly, by 30 days, 3.8% had a primary care consultation for a CVR problem, with an excess after adjustment ranging from 0.13% (0.11%-0.16%) to 0.31% (0.14%-0.50%). Overall numbers needed to harm ranged from 1 in 294 gastroscopies to 1 in 67 gastroscopies. CONCLUSIONS: There was an excess of vascular and respiratory events associated with a diagnostic gastroscopy. In younger patients, this risk manifested as an increase in primary care consultations while in older patients there was an increase in emergency hospital admissions.

Mortality Following Appendicectomy in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: With the global prevalence of liver cirrhosis rising, this systematic review aimed to define the perioperative risk of mortality in these patients following appendicectomy. METHODS: Systematic searches of Medline, EMBASE, Cochrane Library databases, ICTRP, and Clinical trials.gov were undertaken to identify studies including patients with cirrhosis undergoing appendicectomy, published since database inception to March 2021. Studies had to report mortality. Two review authors independently identified eligible studies and extracted data. Pooled analysis of in-patient and 30-day mortality was performed. RESULTS: Of the 948 studies identified, four were included and this comprised three nationwide database studies (USA and Denmark) and one multi-centre observational study (Japan). A total of 923 patients had cirrhosis and 167,211 patients did not. In-patient mortality ranged from 0 to 1.7% in patients with cirrhosis and 0.17 to 0.3% in patients without. 30-day mortality was 9% in patients with cirrhosis compared to 0.3% in those without. One study stratified cirrhotic patients into compensated and decompensated groups. In patients with compensated cirrhosis, mortality following laparoscopic appendicectomy (0.5%) was significantly lower than open appendicectomy (3.2%). The meta-analysis highlighted a tenfold increase in perioperative mortality in cirrhotic patients (OR 9.92 (95% CI 4.67 to 21.06, I2 = 28%). All studies reported an increased length of stay in patients with cirrhosis. CONCLUSION: This review suggests that appendicectomy in the cirrhotic population is associated with increased mortality. LA may be safer in this population. Lack of information on cirrhosis severity and failure to control for age and co-morbidities make the results difficult to interpret. Further large population-based studies are required.

Incidence and survival of haemophagocytic lymphohistiocytosis: A population-based cohort study from England.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory condition with poor outcomes. OBJECTIVES: Few population-based estimates of the incidence and survival in adults exist. We aimed to provide these data for England. METHODS: We used population-based linked data from primary care, secondary care, cancer registries and mortality databases in England to identify people diagnosed with HLH between 1 January 2000 and 31 December 2016. We calculated annual incidence rates by age and sex, modelled change in incidence over time with Poisson regression, calculated overall 1-year survival using Kaplan-Meier methods and estimated adjusted hazard ratios (HRs) of death using a Cox proportional hazards model. RESULTS: We identified 214 patients with HLH. The reported age and sex-adjusted incidence increased twofold over the period, from around one to around two per million. Incidence was highest in those below 1 year (14.6 per million) and ≥75 years (2.2 per million), and lowest in those aged 15-44 years (0.8 per million). One-year survival varied by age and sex from 77% (95% confidence interval [CI] 63%-86%) in those <15 years to 30% (95% CI 14%-49%) in those ≥75. In patients with haematological cancer, the adjusted HR for death was 2.60 (95% CI 1.45-4.66) compared to patients with no malignant or rheumatological disease. CONCLUSION: The incidence of HLH diagnosis in England has increased between 2000 and 2016 and occurs in all ages with varying underlying diseases. One-year survival varies substantially, being particularly poor in those aged over 75 years and those with haematological malignancy.