Background Human papillomavirus vaccination and cervical screening are lacking in most lower resource settings, where approximately 80% of more than 500 000 cancer cases occur annually. Visual inspection of the cervix following acetic acid application is practical but not reproducible or accurate. The objective of this study was to develop a “deep learning”-based visual evaluation algorithm that automatically recognizes cervical precancer/cancer. Methods A population-based longitudinal cohort of 9406 women ages 18–94 years in Guanacaste, Costa Rica was followed for 7 years (1993–2000), incorporating multiple cervical screening methods and histopathologic confirmation of precancers. Tumor registry linkage identified cancers up to 18 years. Archived, digitized cervical images from screening, taken with a fixed-focus camera (“cervicography”), were used for training/validation of the deep learning-based algorithm. The resultant image prediction score (0–1) could be categorized to balance sensitivity and specificity for detection of precancer/cancer. All statistical tests were two-sided. Results Automated visual evaluation of enrollment cervigrams identified cumulative precancer/cancer cases with greater accuracy (area under the curve [AUC] = 0.91, 95% confidence interval [CI] = 0.89 to 0.93) than original cervigram interpretation (AUC = 0.69, 95% CI = 0.63 to 0.74; P < .001) or conventional cytology (AUC = 0.71, 95% CI = 0.65 to 0.77; P < .001). A single visual screening round restricted to women at the prime screening ages of 25–49 years could identify 127 (55.7%) of 228 precancers (cervical intraepithelial neoplasia 2/cervical intraepithelial neoplasia 3/adenocarcinoma in situ [AIS]) diagnosed cumulatively in the entire adult population (ages 18–94 years) while referring 11.0% for management. Conclusions The results support consideration of automated visual evaluation of cervical images from contemporary digital cameras. If achieved, this might permit dissemination of effective point-of-care cervical screening.

(Abstracted from J Natl Cancer Inst 2019; doi: 10.1093/jnci/djy225) Ninety-nine percent of cervical cancers cases are caused by infections with a human papillomavirus (HPV). This cancer can be prevented in most women by cervical cancer screening and HPV vaccination.

Context and Objectives Urinary bladder paraganglioma (UBPGL) is rare. We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL. Methods We conducted a multi-center study of consecutive patients with pathologically-confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality. Results 110 patients (56, 51% women) were diagnosed with UBPGL at a median age of 50 years (IQR, 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after initial diagnosis. Development of metachronous metastases was associated with younger age (Hazard ratio, HR 0.97, 95%CI 0.94-0.99), UBPGL size (HR of 1.69, 95%CI of 1.31-2.17), and a higher degree of catecholamine excess (HR of 5.48, 95%CI of 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR of 20.80, 95%CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality. Conclusions Only a minority of patients were diagnosed before biopsy/surgery, reflecting the need of better diagnostic strategies. All patients with UBPGL should be monitored life-long for development of recurrence and metastases.

Background: Cushing's syndrome has been described as a complex endocrine disorder characterized with high cortisol concentration. Correct and early diagnosis of Cushing's syndrome is challenging. According to the latest guideline, bilateral inferior petrosal sinus sampling (BIPSS) is considered to be the gold standard for the differential diagnosis. However, in some unusual cases, this method may be false positive. Here, we presented a rare case of orbital neuroendocrine tumor secreting adrenocorticotrophic hormone with false positive inferior petrosal sinus sampling. Case presentation: A 48-year-old woman was admitted to West China Hospital of Sichuan University, presenting with fatigue, whole body edema for 1 year, alopecia and skin pigmentation for 5 months. Hormonal profiles including plasma cortisol and adrenocorticotrophic hormone (ACTH) measurements and low-dose dexamethasone inhibition test suggested that the patient had Cushing's syndrome. However, during tumor location phase, the results of high-dose dexamethasone inhibition test (HDDST) contradicted desmopressin (DDAVP) stimulation test. Thus, BIPSS was employed, and its results indicated a pituitary origin. Interestingly, MRI of sellar region showed an innocent pituitary but caught a serendipitous lesion in the lateral rectus muscle of left eye, which was later proved to be an orbital neuroendocrine tumor secreting ACTH by pathological and immunohistochemical results. ACTH level of the patients was < 0.1 ng/L and cortisol level was 51.61 nmol/L 1 week after surgery. At 24 months followup, the patient appeared stable with no complaints nor any symptoms of Cushing's syndrome, including moon face, purple striate and central obesity. The patient's life quality also improved significantly. Conclusion: We reported a rare case of endogenous Cushing's syndrome due to ectopic ACTH secreting from an orbital neuroendocrine tumor. This unique case of orbital EAS suggests that orbital venous blood backflow, owning to abnormal anatomic structures, may possibly lead to false positive BIPSS results.

Rationale:Langerhans cell histiocytosis (LCH) is characterized by clonal proliferation of immature dendritic cells, mainly affects children. LCH in adult sellar region is extremely rare. In literature, optimal treatments remain unclear and only a few cases of LCH were treated using surgery. Here, we present a rare case of isolated hypothalamic-pituitary LHC in female adult. We focused on elucidating the clinical manifestations and immunohistochemical features of LCH, and exploring the proper treatment in adults.Patient concerns:A 50-year-old woman was admitted to our hospital, presenting with polydipsia and polyuria for over 3 months.Diagnoses:Radiological studies revealed lesions (0.5 × 0.9 × 0.4 cm) on posterior pituitary and enlarged pituitary stalk, which was moderately enhanced on contrast magnetic resonance imaging (MRI) of sellar region. In biopsy, pathological examination of Langerhans cells were observed with positive S-100 protein and Ki-67 antigen markers, findings were sufficient to establish a diagnosis of central nervous system (CNS) LCH.Interventions:The patient with LCH restricted in the sellar region received both surgery and chemotherapy. Gamma knife radiosurgery was performed after diagnosed as central diabetes insipidus (CDI) induced by pituitary lesion. And tumorectomy was performed 5 years later. However, in the latest MRI in 2017, the nodular shadow became larger (about 1.4 cm), chemotherapy and further systemic therapy were given.Outcomes:At 12-month follow-up, no local reoccurrence was noticed.Lessons:For LCH, though difficult to be diagnosed and none defined standard therapeutic approach to adults, surgery should be considered if there are neurological symptoms or histological diagnosis. The present study showed that some manifestations can be meaningful when central nervous system (CNS) is involved. For complex diseases in the sellar region, multi-disciplinary team (MDT) model of diagnosis and treatment should be helpful for better clinical efficacy.

Objective: The procedure for the captopril challenge test (CCT) in diagnosing primary aldosteronism (PA) is not standardized. We performed a meta-analysis to evaluate the controversial diagnostic value and influential factors of the post-captopril aldosterone/renin ratio (ARR). Methods: We searched literature in databases for eligible studies (until October 1, 2020). We extracted information regarding study and patient characteristics, CCT methods, outcome data. We pooled studies using the random-effect model. We performed meta-regression and six pre-specified subgroup analyses to explore heterogeneity. Results: Nineteen studies involving 4568 subjects were included. The pooled sensitivity and specificity were 0.825 (95% CI 0.804–0.844) and 0.919 (95% CI 0.908–0.928). The area under the summary receiver operating characteristic curve was 0.9487 (95% CI 0.9207–0.9767). Meta-regression revealed that heterogeneity might derive from time interval ( p = 0.0117) and study population ( p = 0.0033). Subgroup analyses showed significant differences between the subgroups stratified by the dose, posture, study region, time interval, cut-off value and study population for sensitivity and/or specificity ( p < 0.05). Conclusion: Post-captopril ARR is comparably valuable for diagnosing PA at cut-offs from 12.0 to 50.0. Conducting the CCT in the supine position with 25 mg of captopril may attain greater sensitivity. Conducting the CCT in the seated position with 50 mg of captopril may attain greater specificity. A 90-min time interval may perform best in both the sensitivity and specificity.

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Background and purpose To develop and validate a risk model (Extracranial Carotid Artery Stenosis score, ECAS score) to predict moderate and severe ECAS. Furthermore, we compared discrimination of the ECAS score and three existing models with regard to both moderate and severe ECAS. Methods The ECAS score was developed based on the Renqiu Stroke Screening Study (RSSS), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. ECAS was diagnosed by carotid duplex ultrasound according to the published criteria. Independent predictors of moderate (≥50%) and severe (≥70%) ECAS were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow test were used to assess model discrimination and calibration. Results A total of 5010 participants were included and the mean age was 64.3. The proportion of ECAS of < 50%, 50-69%, 70-99% and occlusion was 4.4, 0.5, 0.4, and 0.4%, respectively. The ECAS score was developed from sets of predictors of moderate and severe ECAS. The ECAS score demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.785-0.846). The Hosmer-Lemeshow tests of ECAS score for moderate and severe ECAS were not significant in the derivation and validation cohorts (all P > 0.05). When compared to the three existing models, the ECAS score showed significantly better discrimination for both moderate and severe ECAS (all P < 0.001). Conclusion The ECAS score is a valid model for predicting moderate and severe ECAS. Further validation of the ECAS score in different populations and larger samples is warranted.