Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of hepatocellular carcinoma (HCC). In order to assess the relative contribution of HBV and HCV to HCC worldwide, and identify ...changes over time, we conducted a systematic review of case series published up to the year 2014. Eligible studies had to report seroprevalence of both hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti‐HCV), alone and in combination, for at least 20 adult HCC cases. Studies using a first‐generation enzyme‐linked immunosorbent assay test for HCV were excluded. A total of 119,000 HCC cases in 260 studies were included from 50 countries. Most European and American countries show a preponderance of HCV over HBV and a substantial fraction of viral marker–negative cases. Asian and African countries generally show a predominance of HBV. The fraction of HCV‐positive HCC cases is substantial in Taiwan, Mongolia, Japan, and Pakistan as well as in Western‐Central Asia and Northern Africa. No eligible studies were available in Oceania, large parts of Africa, Eastern Europe, and Central Asia. The United States, Brazil, and Germany show evidence of higher prevalence of HCV in HCC since the year 2000. Conversely, Japan and Italy show a decline in the proportion of HCV‐positive HCC. Conclusion: HBV and HCV are predominant causes of HCC in virtually all world areas, with a growing fraction of HCC cases in several countries attributable to HCV. (Hepatology 2015;62:1190‐1200)
High‐quality data on liver cancers by probable cause are scarce in many regions of the world. The United Nations recently set a goal of eliminating viral hepatitis as a major public health threat by ...2030. We aimed to estimate the number of new cases of cancers attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) at a global, regional and country level, and by development status. We used data on the prevalence of HBV and HCV in hepatocellular carcinoma from a systematic review including 119,000 cases in 260 studies covering 50 countries. A statistical model was constructed to extrapolate empirical data to countries without prevalence data. Country‐specific numbers of liver cancer cases attributable to HBV and HCV were calculated using data from GLOBOCAN 2012. Globally, 770,000 cases of liver cancer occurred worldwide in 2012, of which 56% (95% CI: 52–60) were attributable to HBV and 20% (95% CI: 18–22) to HCV. Currently, HBV causes approximately two out of three cases of liver cancer in less developed countries but one in four cases in more developed countries and shows a much higher degree of geographical aggregation in Eastern Asia and sub‐Saharan Africa than HCV. These estimates help set priorities for liver cancer prevention. High‐coverage HBV vaccination will be transformational in HBV‐endemic countries but the prevention of HCV transmission and the treatment of chronic carriers of both viruses requires new scalable solutions.
What's new?
To facilitate priority setting for liver cancer prevention, more data are needed on attributable causes of liver malignancy. Here, the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in hepatocarcinoma was determined based on systematic review of data from 50 countries, with liver cancer cases attributable to the viruses calculated using GLOBOCAN 2012 data. The results show that of 770,000 liver cases reported in 2012, more than half were attributed to HBV, while one‐fifth were associated with HCV. The contribution of the two viruses to liver cancer varied significantly by development status and region.
Abstract Objectives Compare the area under the receiver operating characteristic curve (AUC) vs. the area under the precision–recall curve (AUPRC) in summarizing the performance of a diagnostic ...biomarker according to the disease prevalence. Study Design and Setting A simulation study was performed considering different sizes of diseased and nondiseased groups. Values of a biomarker were sampled with various variances and differences in mean values between the two groups. The AUCs and the AUPRCs were examined regarding their agreement and vs. the positive predictive value (PPV) and the negative predictive value (NPV) of the biomarker. Results With a disease prevalence of 50%, the AUC and the AUPRC showed high correlations with the PPV and the NPV ( ρ > 0.95). With a prevalence of 1%, small PPV and AUPRC values (<0.2) but high AUC values (>0.9) were found. The AUPRC reflected better than the AUC the discriminant ability of the biomarker; it had a higher correlation with the PPV ( ρ = 0.995 vs. 0.724; P < 0.001). Conclusion In uncommon and rare diseases, the AUPRC should be preferred to the AUC because it summarizes better the performance of a biomarker.
In patients who have chronic heart failure with reduced left ventricular ejection fraction, severe secondary mitral-valve regurgitation is associated with a poor prognosis. Whether percutaneous ...mitral-valve repair improves clinical outcomes in this patient population is unknown.
We randomly assigned patients who had severe secondary mitral regurgitation (defined as an effective regurgitant orifice area of >20 mm
or a regurgitant volume of >30 ml per beat), a left ventricular ejection fraction between 15 and 40%, and symptomatic heart failure, in a 1:1 ratio, to undergo percutaneous mitral-valve repair in addition to receiving medical therapy (intervention group; 152 patients) or to receive medical therapy alone (control group; 152 patients). The primary efficacy outcome was a composite of death from any cause or unplanned hospitalization for heart failure at 12 months.
At 12 months, the rate of the primary outcome was 54.6% (83 of 152 patients) in the intervention group and 51.3% (78 of 152 patients) in the control group (odds ratio, 1.16; 95% confidence interval CI, 0.73 to 1.84; P=0.53). The rate of death from any cause was 24.3% (37 of 152 patients) in the intervention group and 22.4% (34 of 152 patients) in the control group (hazard ratio, 1.11; 95% CI, 0.69 to 1.77). The rate of unplanned hospitalization for heart failure was 48.7% (74 of 152 patients) in the intervention group and 47.4% (72 of 152 patients) in the control group (hazard ratio, 1.13; 95% CI, 0.81 to 1.56).
Among patients with severe secondary mitral regurgitation, the rate of death or unplanned hospitalization for heart failure at 1 year did not differ significantly between patients who underwent percutaneous mitral-valve repair in addition to receiving medical therapy and those who received medical therapy alone. (Funded by the French Ministry of Health and Research National Program and Abbott Vascular; MITRA-FR ClinicalTrials.gov number, NCT01920698 .).
Background
The Net Benefit (Δ) is a measure of the benefit‐risk balance in clinical trials, based on generalized pairwise comparisons (GPC) using several prioritized outcomes and thresholds of ...clinical relevance. We extended Δ to N‐of‐1 trials, with a focus on patient‐level and population‐level Δ.
Methods
We developed a Δ estimator at the individual level as an extension of the stratum‐specific Δ, and at the population‐level as an extension of the stratified Δ. We performed a simulation study mimicking PROFIL, a series of 38 N‐of‐1 trials testing sildenafil in Raynaud's phenomenon, to assess the power for such an analysis with realistic data. We then reanalyzed PROFIL using GPC. This reanalysis was finally interpreted in the context of the main analysis of PROFIL which used Bayesian individual probabilities of efficacy.
Results
Simulations under the null showed good size of the test for both individual and population levels. The test lacked power when being simulated from the true PROFIL data, even when increasing the number of repetitions up to 140 days per patient. PROFIL individual‐level estimated Δ were well correlated with the probabilities of efficacy from the Bayesian analysis while showing similarly wide confidence intervals. Population‐level estimated Δ was not significantly different from zero, consistently with the previous Bayesian analysis.
Conclusion
GPC can be used to estimate individual Δ which can then be aggregated in a meta‐analytic way in N‐of‐1 trials. GPC ability to easily incorporate patient preferences allow for more personalized treatment evaluation, while needing much less computing time than Bayesian modeling.
Objective
To evaluate the surgical and functional outcomes of urethral reconstruction associated with phalloplasty, depending on the surgical techniques and patient history.
Materials and Methods
We ...conducted a single‐centre retrospective study including 89 patients who underwent phalloplasty with urethral reconstruction between 2007 and 2018. Patients included were trans‐male patients undergoing gender‐affirming surgery and cis‐male patients undergoing penile reconstruction after trauma, congenital malformation, or cancer. Urethral reconstructions were performed by free flap or skin graft (total or thin). Secondary urethroplasty may include direct vision urethrotomy, excision‐anastomosis, or augmentation urethroplasty (skin graft, buccal mucosa graft). Patient demographics, medical history, peri‐ and postoperative data were collected from patient files. Functional results were evaluated using individual questionnaires.
Results
The mean (±sd) follow‐up duration was 5.5 (±3.7) years. No significant difference was found for total urethral complication rate (fistula and/or stricture) according to type of urethral construction (70.9% for free flap urethra vs 73.5% for skin graft urethra; P = 0.911), nor according to the patient's grounds for surgery (72.7% for cis‐male vs 71.8% for trans‐male patients; P = 1). A total of 36 patients (40.5%) answered the functional questionnaire, of whom 80.5% reported usually voiding while standing and 47.5% were comfortable with urinating in public.
Conclusions
Urethral construction in phalloplasty is associated with a high complication and revision rate regardless of the type of urethral reconstruction. Voiding in a standing position is generally possible but should not conceal feeble functional results.
Women with gestational trophoblastic tumors (GTT) resistant to single-agent chemotherapy receive alternative chemotherapy regimens, which, although effective, cause considerable toxicity. All GTT ...subtypes express programmed death-ligand 1 (PD-L1), and natural killer (NK) cells are involved in trophoblast immunosurveillance. Avelumab (anti-PD-L1) induces NK cell-mediated cytotoxicity. The TROPHIMMUN trial assessed avelumab in women with chemotherapy-resistant GTT.
In this phase II multicenter trial (ClinicalTrials.gov identifier: NCT03135769), women with GTT who experienced disease progression after single-agent chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. Rate of hCG normalization was the primary endpoint (2-step Simon design).
Between December 2016 and September 2018, 15 patients were treated. Median age was 34 years; disease stage was I or III in 53.3% and 46.7% of women, respectively; and International Federation of Gynecology and Obstetrics (FIGO) score was 0-4 in 33.3%, 5-6 in 46.7%, and ≥ 7 in 20% of patients. Prior treatment included methotrexate (100%) and actinomycin D (7%). Median follow-up was 25 months, and median number of avelumab cycles was 8 (range, 2-11). Grade 1-2 treatment-related adverse events occurred in 93% of patients, most commonly (≥ 25%) fatigue (33.3%), nausea/vomiting (33.3%), and infusion-related reaction (26.7%). One patient had grade 3 uterine bleeding (treatment unrelated). Eight patients (53.3%) had hCG normalization after a median of 9 avelumab cycles; none subsequently relapsed. Probability of normalization was not associated with disease stage, FIGO score, or baseline hCG. One patient subsequently had a healthy pregnancy. In avelumab-resistant patients (46.7%), hCG was normalized with actinomycin D (42.3%) or combination chemotherapy/surgery (57.1%).
In patients with single-agent chemotherapy-resistant GTT, avelumab had a favorable safety profile and cured approximately 50% of patients. Avelumab could be a new therapeutic option, particularly in patients who would otherwise receive combination chemotherapy.
We evaluated mortality rates and underlying causes of death among French decedents with sarcoidosis from 2002 to 2011.We used data from the French Epidemiological Centre for the Medical Causes of ...Death to 1) calculate sarcoidosis-related mortality rates, 2) examine differences by age and gender, 3) determine underlying and nonunderlying causes of death, 4) compare with the general population (observed/expected ratios), and 5) analyse regional differences.1662 death certificates mentioning sarcoidosis were recorded. The age-standardised mortality rate was 3.6 per million population and significantly increased over the study period. The mean age at death was 70.4 years (versus 76.2 years for the general population). The most common underlying cause of death was sarcoidosis. Sarcoidosis decedents were more likely to be males when aged <65 years. When sarcoidosis was the underlying cause of death, the main other mentions on death certificates were chronic respiratory and cardiovascular diseases. The overall observed/expected ratio was >1 for infectious disease, tuberculosis and chronic respiratory disease, and <1 for neoplasms. We observed a north-south gradient of age-standardised mortality ratio at the country level.Despite the limitation of possibly capturing the more severe cases of sarcoidosis, this study may help define and prioritise preventive interventions.
The annual prevalence of metastatic neuroendocrine tumours (mNETs) is rising, leading to significant healthcare costs. The present study aimed to describe healthcare resource use (HRU) and the ...corresponding costs among patients with mNETs, according to primary tumour location, functioning status and type of treatments. The LyREMeNET study included consecutive mNET patients with a diagnosis performed between January 2010 and December 2017, who were seen at least once in the ENETS center of excellence in Lyon. The median HRU and costs per patient were estimated, up to 3 years before and after the diagnosis. The Cancer database of the center was linked to the French national health data system. HRU and related costs were described per person per month (PPPM). Among 316 patients presenting with a mNET, 48.4% had a small‐intestinal mNET, 32.3% had a pancreatic mNET and 39.2% had carcinoid syndrome. The mean overall cost increased from €615 to €2875 PPPM between the years preceding and following the diagnosis, and remained above €2500 in the two subsequent years. The two main cost drivers of total healthcare expenditure were drugs (€1161) and hospital stay (€662). Median costs of mNETs arising from pancreas and small intestine were €2325 and €2540 PPPM, respectively. Costs were higher in patients with a functional mNET (€2807 PPPM for carcinoid syndrome) and during peptide receptor radionuclide therapy (PRRT) (€8835 PPPM). The highest overall cost was found during the first year following the diagnosis. Cost of care was higher for small intestine mNETs, for functional mNETs and during peptide receptor radionuclide therapy.
The highest overall cost was found during the first year following the diagnosis of metastatic neuroendocrine tumour (mNET). Cost of care was higher for small intestine mNETs, for functional mNETs and during the PRRT.
Aims
Subclassification of large B cell lymphoma (LBCL) is challenging due to the overlap in histopathological, immunophenotypical and genetic data. In particular, the criteria to separate diffuse ...large B cell lymphoma (DLBCL) and high‐grade B cell lymphoma (HGBL) are difficult to apply in practice. The Lunenburg Lymphoma Biomarker Consortium previously reported a cohort of over 5000 LBCL that included fluorescence in‐situ hybridisation (FISH) data. This cohort contained 209 cases with MYC rearrangement that were available for a validation study by a panel of eight expert haematopathologists of how various histopathological features are used.
Methods and results
Digital whole slide images of haematoxylin and eosin‐stained sections allowed the pathologists to visually score cases independently as well as participate in virtual joint review conferences. Standardised consensus guidelines were formulated for scoring histopathological features and included overall architecture/growth pattern, presence or absence of a starry‐sky pattern, cell size, nuclear pleomorphism, nucleolar prominence and a range of cytological characteristics. Despite the use of consensus guidelines, the results show a high degree of discordance among the eight expert pathologists. Approximately 50% of the cases lacked a majority score, and this discordance spanned all six histopathological features. Moreover, none of the histological variables aided in prediction of MYC single versus double/triple‐hit or immunoglobulin‐partner FISH‐based designations or clinical outcome measures.
Conclusions
Our findings indicate that there are no specific conventional morphological parameters that help to subclassify MYC‐rearranged LBCL or select cases for FISH analysis, and that incorporation of FISH data is essential for accurate classification and prognostication.
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