Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are significant causes of chronic liver disease worldwide. Both are characterized by histological lesions that can include ...steatosis, and each can lead to cirrhosis. It might be possible for pathologists to identify lesions and patterns of ALD and NAFLD; we review these lesions and propose methods to distinguish between the disorders. Any form of ALD can lead to end-stage liver disease, according to long-term studies of biopsy specimens and patient outcomes. Although steatosis can be a significant cofactor in progression of established chronic liver disease, or even development of hepatocellular carcinoma, only steatohepatitis indicates the presence of progressive liver disease in patients with NAFLD. Pediatric and adolescent NAFLD differ from adult nonalcoholic steatohepatitis and should be recognized as distinct conditions. Benign and malignant liver tumors have been more frequently reported with the increasing prevalence of obesity and diabetes. Histological scoring systems for ALD and NAFLD have been proposed to monitor efficacy in clinical trials and serve as prognostic factors. We review what we have learned from pathological analyses about the development of these disorders and how this information might be used to detect and treat them.
Accurate estimates of childhood cancer incidence are important for policy makers to inform priority setting and planning decisions. However, many countries do not have cancer registries that quantify ...the incidence of childhood cancer. Moreover, even when registries do exist, they might substantially underestimate the true incidence, since children with cancer might not be diagnosed. We therefore aimed to provide estimates of total childhood cancer incidence accounting for underdiagnosis.
We developed a microsimulation model to simulate childhood cancer incidence for 200 countries and territories worldwide, taking into account trends in population growth and urbanicity, geographical variation in cancer incidence, and health system barriers to access and referral that contribute to underdiagnosis. To ensure model results were consistent with epidemiological data, we calibrated the model to publicly available cancer registry data using a Bayesian approach in which the observed data are fixed and the model parameters (cancer incidence and probabilities of health system access and referral) are random variables. We estimated the total incidence of childhood cancer (diagnosed and undiagnosed) in each country in 2015 and projected the number of cases from 2015 to 2030.
Our model estimated that there were 397 000 (95% uncertainty interval UI 377 000–426 000) incident cases of childhood cancer worldwide in 2015, of which only 224 000 (95% UI 216 000–237 000) were diagnosed. This finding suggests that 43% (172 000 of 397 000) of childhood cancer cases were undiagnosed globally, with substantial variation by region, ranging from 3% in western Europe (120 of 4300) and North America (300 of 10 900) to 57% (43 000 of 76 000) in western Africa. In south Asia (including southeastern Asia and south-central Asia), the overall proportion of undiagnosed cases was estimated to be 49% (67 000 of 137 000). Taking into account population projections, we estimated that there will be 6·7 million (95% UI 6·3–7·2) cases of childhood cancer worldwide from 2015 to 2030. At current levels of health system performance, we estimated that 2·9 million (95% UI 2·7–3·3) cases of childhood cancer will be missed between 2015 and 2030.
Childhood cancer is substantially underdiagnosed, especially in south Asia and sub-Saharan Africa (including western, eastern, and southern Africa). In addition to improving treatment for childhood cancer, health systems must be strengthened to accurately diagnose and effectively care for all children with cancer. As countries expand universal health coverage, these estimates of total incidence will hopefully help guide efforts to appropriately increase health system capacity to ensure access to effective childhood cancer care.
Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard T H Chan School of Public Health, Harvard Medical School, National Cancer Institute, SickKids, St Jude Children's Research Hospital, and Union for International Cancer Control.
Liver injury triggered by immune checkpoint inhibitors has been increasingly seen in clinical practice, and the incidence is likely to rise further in the next several years because of expanded ...indications for cancer immunotherapy. Tissue damage driven by disrupted immune tolerance against self-antigens is called an immune-related adverse event (irAE). irAEs in the liver histologically presents panlobular hepatitis (∼70%), isolated central zonal necrosis (∼20%), primarily granulomatous hepatitis (∼5%), and other minor forms of tissue injury (∼5%). Infiltrating cells are mainly lymphocytes and occasional eosinophils. Unlike classic autoimmune hepatitis (AIH), plasma cell infiltration is not conspicuous. Immunostaining reveals a large number of CD8+ T lymphocytes and a markedly smaller number of CD4+ cells or CD20+ B lymphocytes. The unique CD3+/CD20+ and CD4+/CD8+ ratios shifted in favor of CD8+ cytotoxic T lymphocytes are helpful to discriminate irAEs from other conditions (e.g., AIH, idiosyncratic drug-induced liver injury). Another hepatobiliary manifestation of irAEs is sclerosing cholangitis clinically characterized by elevations of biliary enzymes, diffuse duct wall thickening, and duct dilatation. Lymphocytic infiltration can be observed by endoscopic biopsies from the thick extrahepatic bile ducts, and liver needle biopsies may also show severe lymphocytic cholangitis resembling primary biliary cholangitis. An important differential diagnosis of irAEs is previously asymptomatic or subclinical liver disease unmasked by cancer immunotherapy, which is often challenging and requires close clinicopathological correlations.
The Red River shear zone (RRSZ) is a major left‐lateral strike‐slip shear zone, containing a ductilely deformed metamorphic core bounded by brittle strike‐slip and normal faults, which stretches for ...>1000 km from Tibet through Yunnan and North Vietnam to the South China Sea. The RRSZ exposes four high‐grade metamorphic core complexes along its length. Various lithologies from the southernmost core complex, the Day Nui Con Voi (DNCV), North Vietnam, provide new constraints on the tectonic and metamorphic evolution of this region prior to and following the initial India–Asia collision. Analysis of a weakly deformed anatectic paragneiss using P–T pseudosections constructed in the MnO–Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–TiO2–O (MnNCKFMASHTO) system provides prograde, peak and retrograde metamorphic conditions, and in situ U–Th–Pb geochronology of metamorphic monazite yields texturally controlled age constraints. Tertiary metamorphism and deformation, overprinting earlier Triassic metamorphism associated with the Indosinian orogeny and possible Cretaceous metamorphism, are characterized by peak metamorphic conditions of ~805 °C and ~8.5 kbar between c. 38 and 34 Ma. Exhumation occurred along a steep retrograde P–T path with final melt crystallizing at the solidus at ≥~5.5 kbar at ~790 °C. Further exhumation at ~640–700 °C and ~4–5 kbar at c. 31 Ma occurred at subsolidus conditions. U–Pb geochronological analysis of monazite from a strongly deformed pre‐kinematic granite dyke from the flank of the DNCV provides further evidence for exhumation at this time. Magmatic grains suggest initial emplacement at 66.0 ± 1.0 Ma prior to the India–Asia collision, whereas grains with metamorphic characteristics indicate later growth at 30.6 ± 0.4 Ma. Monazite grains from a cross‐cutting post‐kinematic dyke within the core of the DNCV antiform provide a minimum age constraint of 25.2 ± 1.4 Ma for the termination of fabric development. A separate and significant episode of monazite growth at c. 83–69 Ma is suggested to be the result of fluid‐assisted recrystallization following the emplacement of magmatic units.
The Seebeck coefficient, a defining parameter for thermoelectric materials, depends on the contributions to conductivity of charge carriers at energies away from the Fermi level. Highly conductive ...materials tend to exhibit conductivity from carriers close to the Fermi level. In this article, we propose polymer blends in which ground state hole carriers, created by doping a minor additive component, are mainly at an orbital energy set below the hole energy of the major component of the blend. Transport, however, is expected to occur through the major component. This leads to a regime in which hole conductivity and Seebeck coefficient may be increased in parallel. While the absolute conductivity of the composite, and thus ZT, are not particularly high, this work demonstrates a route for designing thermoelectric materials in which increases in Seebeck coefficient and conductivity do not cancel each other.
Summary
Background
Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects ...survival after HCC diagnosis.
Methods
This was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.
Results
Approximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).
Conclusions
Anti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
To evaluate the effectiveness and feasibility of implementing a linguistically and culturally tailored Diabetes Prevention Program among Chinese immigrants with prediabetes living in New York City.
A ...total of 60 Chinese immigrants with prediabetes were randomized into either a Diabetes Prevention Program lifestyle intervention (n = 30) consisting of 12 bi-weekly core sessions and six monthly post-core sessions or the control intervention (n = 30), consisting of quarterly mailing of diabetes prevention information. Each Diabetes Prevention Program intervention session lasted 1.5-2 h and covered topics such as healthy eating, physical activity, stress reduction and problem-solving skills. Outcomes such as percent change in weight, BMI, and HbA1c concentration were assessed at baseline, 6 and 12 months. A mixed-effects linear regression was applied to test the intervention effect at months 6 and 12. Data were collected in the period 2012-2013 and analysed in 2014.
The participant attrition rate was < 5% (2 out of 60) at 12 months. There was a significantly greater percent weight loss in the intervention group (-3.5 vs. -0.1%; P = 0.0001) at 6 months, which was largely maintained at 12 months (-3.3 vs. 0.3%; P = 0.0003).
Participants in a Diabetes Prevention Program-based intervention achieved greater weight loss and improvements in HbA1c concentration than control participants. Evaluation of the Chinese Diabetes Prevention Program curriculum in a larger trial is warranted.
Cholangiocarcinoma represents the second most frequent type of primary liver cancer that develops through a multistep histopathologic sequence. Dysplasia in the biliary tract epithelium is a ...precursor lesion of cholangiocarcinoma. This review provides a practical overview of bile duct dysplasia in relation to invasive carcinoma, covering clinicopathological features, diagnostic criteria, differential diagnosis, useful testing modalities, and challenges in daily practice. The key features of biliary intraepithelial neoplasia, intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, and mucinous cystic neoplasm are described. Important differential diagnoses are included. Common pitfalls in histopathologic interpretation of bile duct biopsies and frozen sections are discussed.
•Dysplasia in the bile duct is a precursor lesion of cholangiocarcinoma.•Four types of biliary precancerous lesions are currently recognized.•Accurate diagnosis of bile duct dysplasia relies on careful histopathology evaluation and ancillary tests.
The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This ...Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.
Combined hepatocellular‐cholangiocarcinoma is a rare primary neoplasm in the liver. It has gained increasing recognition recently, which in part may be due to more extensive sampling of the explants ...and surgical resection specimens, the diagnostic challenges encountered in the clinical practice, and the yet to be determined clinical outcome, but partly may be attributed to its intriguing histogenesis/cells of origin. This review aims to update combined hepatocellular‐cholangiocarcinoma with an emphasis on the pathological diagnosis, including the differential diagnosis and its diagnostic pitfalls, the possible cell of origin of this neoplasm, and its clinical outcome.
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