Visible Lesions Research Articles

Evaluation of HPV infection helps to direct ALA-PDT of condyloma acuminata

Background and objectivesAminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) is increasingly applied for the treatment of condyloma acuminata (CA). However, the determinants for the sessions and end points of ALA-PDT treatment remains unclear. Here, we recorded HPV screening, evaluated the frequency and efficacy of ALA-PDT in different types of CA, in order to individualize ALA-PDT treatment to CA. MethodsA total of 227 CA patients with HPV infection and visible warts were recruited. Prior to PDT, visible lesions were removed by radio frequency or microwave. HPV DNA detection were performed before each PDT treatment and at follow-up. Treatment was ended after two consecutive negative HPV DNA detection. ResultsOf the 227 patients, 119 patients received ALA-PDT and 116 patients completed all treatments. We found that CA patients with multiple-site infection, intra-luminal infection or multiple-type of HPV infection required more sessions of ALA-PDT. The recurrence rate was 8.62% (10/116). Viral load was significantly lower after six PDT treatments compared to viral load after three PDT treatments. Gender, HPV subtypes and warts location had no significant effect on the recurrence rate. ConclusionComprehensive evaluation of HPV infection state helps to individualize ALA-PDT treatment scheme for CA patients and predict the therapeutic efficacy.

Cytomorphometric analysis of buccal mucosal cells in iron deficiency anemia: A cross-sectional study.

Worldwide, at any given moment, more individuals have iron deficiency anemia (IDA) than any other health problems. Very few studies have been conducted to evaluate changes in oral mucosa in IDA. The present study is undertaken for cytomorphometric analysis of buccal mucosal cells in IDA. Nuclear diameter (ND), cell diameter (CD), nuclear area (NA), cell area (CA), and nuclear-cytoplasmic ratio (N/C) are measured and compared in buccal mucosal cells of IDA patients and controls. To evaluate cytomorphometric changes in epithelial cells of oral mucosa in IDA and to compare these changes with the controls. A cross-sectional study. Forty cases of IDA and forty cases of control group were selected for the study. IDA cases were diagnosed with decreased Hb level, MCV, MCH, MCHC and confirmed by decreased serum iron and increased total iron-binding capacity levels. Cytomorphometric analysis of buccal mucosa was performed to study CA, CD, NA, ND, and N/C ratio. Statistical analysis was done using t- test in SPSS software version 4. Results of our study showed increased cell area, cell diameter, nuclear area, nuclear diameter, and nuclear-cytoplasmic ratio in anemic group as compared to controls. The study suggests that individuals with IDA regardless of clinically visible oral lesions show cytological changes in oral mucosal epithelium. Knowledge of quantitative alterations in oral epithelial cells of IDA patients is important as these alterations are similar to those seen in precancerous and radiation-induced changes. Cytomorphometry is an efficient tool to understand the extent of cellular changes that occur in oral epithelial cells in IDA.

High Proportions of Newly Detected Visible Lesions and Pathology Grade Change Among Patients with Barrett's Esophagus Referred to Expert Centers.

Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is increasingly being performed at tertiary and community centers. While it has been suggested that these patients should be evaluated at expert centers, the impact of this practice has not been evaluated. We aimed to assess the impact of referral of BE-related neoplasia patients to expert centers by assessing the proportion of patients with change in pathological diagnosis and visible lesions detected. Multiple databases were searched until December 2021 for studies of patients with BE referred from the community to expert center. The proportions of pathology grade change and newly detected visible lesions at expert centers were pooled using a random-effects model. Subgroup analyses were performed based on baseline histology and other relevant factors. Twelve studies were included (1630 patients). The pooled proportion of pathology grade change after expert pathologist review was 47% (95% CI 34-59%) overall and 46% (95% CI 31-62%) among patients with baseline low-grade dysplasia. When upper endoscopy was repeated at an expert center, the pooled proportion of pathology grade change was still high 47% (95% 26-69%) overall and 40% (95% CI 34-45%) among patients with baseline LGD. The pooled proportion of newly detected visible lesions was 45% (95% CI 28-63%) and among patients referred with LGD was 27% (95% CI 22-32%). An alarmingly high proportion of newly detected visible lesions and pathology grade change were found when patients were referred to expert centers supporting the need for centralized care for BE-related neoplasia patients.

Added value of zoomed-echo-planar imaging diffusion-weighted imaging for evaluation of periampullary carcinomas.

To assess the image quality feasibility and diagnostic value of zoomed diffusion-weighted imaging (z-EPI DWI) using echo-planar imaging (EPI) compared with conventional DWI (c-EPI DWI) in patients with periampullary disease. Thirty-six patients with periampullary carcinomas and fifteen with benign periampullary disease were included in this study. All the subjects underwent MR cholangiopancreatography (MRCP), c-EPI DWI, and z-EPI DWI. Two radiologists independently assessed image quality of the two image sets, including overall image quality and lesion conspicuity. In addition, signal intensity and ADC measurements of DWIs in the periampullary lesions were conducted. Diagnostic accuracies of the combined image sets of MRCP and z-EPI DWI were compared with those of a combined set of MRCP and c-EPI DWI. z-EPI DWI showed significantly better image quality scores (anatomic structure visualization, 2.94 ± 0.24; overall image quality, 2.96 ± 0.17) compared to that with c-EPI DWI (anatomic structure visualization, 2.02 ± 0.22; overall image quality, 2.04 ± 0.24) (both P < 0.01). For all the periampullary malignant lesions and small lesions (≤20 mm), there was better delineation of lesion conspicuity and the lesion margin, as well as diagnostic confidence with z-EPI DWI (all P<0.05). The rate of periampullary malignancy's hyperintense signal on z-EPI DWI was increased to 91.7% (33/36) compared to c-EPI DWI (69.4% (25/36)) (P = 0.023). For all malignant lesions and small lesions, the diagnostic accuracy scores were increased using the MRCP and z-EPI DWI combined set, compared to the MRCP and c-EPI DWI combined set (P<0.05). Diagnostic accuracy for detection and differentiation of malignant lesions from benign lesions significantly improved for the MRCP and z-EPI DWI combined set compared with MRCP and c-EPI DWI combined set (P<0.05). There were no significant differences between c-EPI DWI and z-EPI DWI in the ADC values of periampullary malignant and benign lesions (P>0.05). z-EPI DWI has an advantage that could lead to remarkable image quality improvements and enhanced lesion visualization of periampullary carcinomas. z-EPI DWI was superior to c-EPI DWI for detecting, delineating, and diagnosing the lesions, particularly for small challenging lesions.

Recurrence-free survival and prognosis after adjuvant therapy with radioactive iodine-131 in patients with differentiated thyroid carcinoma

This study aimed to assess recurrence-free survival (RFS) rates and recurrence-related factors of patients who received adjuvant therapy (AT) with radioactive iodine (RAI) for differentiated thyroid cancer (DTC) following thyroidectomy. We evaluated 284 patients who underwent AT between January 2011 and July 2020 at our hospital. Recurrence was defined as visible recurrent lesions on image analysis or need for repeat surgery with pathologically confirmed recurrent lesions. RFS rate and prognostic factors were statistically evaluated. The median observation period was 30.2 months (range, 5.7–294 months). Overall, 192 patients were female and 92 were male, and the median age was 54 years (range, 9–85 years). Initial assessment revealed 39 recurrence cases. The 3-year RFS rate was 85.8% (95% confidence interval: 81.1–90.9%). Univariate analysis revealed that histology (except for papillary carcinoma), Tg level > 4 ng/dL before AT, and AT result significantly exacerbated the RFS rate. In multivariate analysis, histology and AT result were also important contributors to the worsening RFS rate. Results of AT can be determined relatively early and are important in predicting future recurrence in patients with DTC. Increasing the success rate of AT may lead to an improved prognosis.

Detection of Ectoparasites in Farmed Striped Catfish (Pangasius hypophthalmus) in Karangpilang, Surabaya, Indonesia

This research aimed to identify ectoparasites infecting farmed striped catfish in Karangpilang Surabaya, Indonesia. Individual catfishes with visible lesions on the body surface and abnormal behaviors were included in the study. Mucilage samples of 90 fishes were examined under a microscope for the presence of ectoparasite on the body surface of the fish, in the area of gills, skins, fins, and tails. Gills were cut with scissors and combed with a tweezer. Skin and fin were also scrapped with a sterile scalpel. The mucus obtained was put on an object glass and was observed under the microscope. The fish pond water was analysed for Oxygen Demand (DO), pH and temperature three times two weeks apart, starting from the day of fish sampling. Results showed that 42.2% (n=90) of samples were infected by ectoparasites. The ectoparasites identified were Gyrodactylus sp., Dactylogyrus sp., Trichodina sp. and Chilodonella sp. Fish pond water in the study site was of suitable quality for the growth of catfish. This study suggested that pathogens other than ectoparasites play roles in the development of pathologic conditions of stripped catfishes in the study area.

Low-field magnetic resonance image enhancement via stochastic image quality transfer.

Low-field (<1T) magnetic resonance imaging (MRI) scanners remain in widespread use in low- and middle-income countries (LMICs) and are commonly used for some applications in higher income countries e.g. for small child patients with obesity, claustrophobia, implants, or tattoos. However, low-field MR images commonly have lower resolution and poorer contrast than images from high field (1.5T, 3T, and above). Here, we present Image Quality Transfer (IQT) to enhance low-field structural MRI by estimating from a low-field image the image we would have obtained from the same subject at high field. Our approach uses (i) a stochastic low-field image simulator as the forward model to capture uncertainty and variation in the contrast of low-field images corresponding to a particular high-field image, and (ii) an anisotropic U-Net variant specifically designed for the IQT inverse problem. We evaluate the proposed algorithm both in simulation and using multi-contrast (T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR)) clinical low-field MRI data from an LMIC hospital. We show the efficacy of IQT in improving contrast and resolution of low-field MR images. We demonstrate that IQT-enhanced images have potential for enhancing visualisation of anatomical structures and pathological lesions of clinical relevance from the perspective of radiologists. IQT is proved to have capability of boosting the diagnostic value of low-field MRI, especially in low-resource settings.

Screening of Ophidiomyces ophidiicola in the free-ranging snake community annually harvested for the popular ritual of San Domenico e dei Serpari (Cocullo, AQ, Italy)

In the Abruzzi village of Cocullo (Italy), each year, on May 1st, local snake hunters (known as Serpari) display colubrids, captured in the wild, to commemorate the ancient ritual of San Domenico. The ascomycete Ophidiomyces ophidiicola (Oo) is the causative agent of ophidiomycosis, an emerging disease with sublethal effects. Skin lesions, such as dysecdysis, edematous, crusty or necrotic scales, swellings, nodules, and ulcers, are the most common clinical manifestation of the disease. The pathogen and its associated disease are well characterized in wild snakes in North America, whereas broad screenings of free ranging wild ophidians in Europe are rare. In 2019, as part of a multi-year snake health monitoring project, all the Cocullo ophidians were carefully examined for integumentary affections and those showing signs consistent with ophidiomycosis were dry swabbed on the skin and on any visible cutaneous lesions with a single applicator. The extracted DNA underwent a broad-range panfungal PCR targeting the D1-D2 region, as well as two conventional PCRs specific to the ITS2 and IGS regions of Oo DNA. Twenty-three out of 129 snakes (13/82 Elaphe quatuorlineata; 7/31 Hierophis viridiflavus; 3/15 Zamenis longissumus; 0/1 Natrix helvetica) resulted clinically affected, but no specific Oo genomic DNA was detected by PCR. The Cocullo ritual celebration provided a unique opportunity for the first systematic testing of a large sample size of a local snake community for the monitoring of this pathogen in Italy.

Endoscopic resection for local residual or recurrent cancer after definitive chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma

Chemoradiotherapy (CRT) and radiotherapy (RT) are treatment options for esophageal squamous cell carcinoma (ESCC), but local residual/recurrent cancer after CRT/RT is a major problem. Endoscopic resection (ER) is an effective treatment option for local residual/recurrent cancer. To ensure the efficacy of ER, complete removal of endoscopically visible lesions with cancer-free vertical margins is desired. This study aimed to identify the endoscopic parameters associated with the complete endoscopic removal of local residual/recurrent cancer. In this single-center, retrospective study, we used a prospectively maintained database to identify esophageal lesions that were diagnosed as local residual/recurrent cancer after CRT/RT and treated by ER between January 2012 and December 2019. We evaluated the associations of endoscopic R0 resection with findings on conventional endoscopy and endoscopic ultrasonography (EUS). In total, 98 lesions (83 cases) were identified from our database. The rate of endoscopic R0 resection was higher for flat lesions (100% versus 77%, P = 0.00014). EUS was performed for 24 non-flat lesions, and endoscopic R0 resection was achieved for 94% of lesions with an uninterrupted fifth layer. Flat lesions on conventional endoscopy and lesions with an uninterrupted fifth layer on EUS are good candidates for ER.

Improving Visualization of Osteochondritis Dissecans Using Delay-Multiply-and-Sum Reconstruction

Osteochondritis dissecans (OCD) of the capitellum is a joint defect that is common among adolescent athletes. It is important to diagnose OCD as early as possible, because early-stage OCD lesions have a high rate of spontaneous healing with rest. Medical ultrasound could potentially be used as a screening tool for OCD but is limited by the use of delay-and-sum (DAS) reconstruction. In this study, we tested conventional delay-multiply-and-sum (DMAS) and novel low-pass DMAS reconstruction algorithms for better visualization of OCD lesions. We created phantom and cadaveric OCD models that simulated a range of OCD lesion severities and stabilities. We also imaged an in vivo case of OCD in a patient study. In the reconstructed images, several profiles were taken to measure OCD lesion contrast, cartilage contrast, crack thickness error and bone interface clarity. In the phantom and cadaveric OCD models, we found that histogram-matched conventional DMAS reconstruction improved lesion contrast by up to 16%, cartilage contrast by 26% and bone interface clarity by 15% on average compared with DAS reconstruction. Histogram-matched low-pass DMAS reconstruction improved lesion contrast by up to 22%, cartilage contrast by 45%, and bone interface clarity by 29% on average compared with DAS reconstruction. In the in vivo case of OCD, we found that histogram-matched conventional and low-pass DMAS reconstruction improved lesion contrast by 22% and 26%, respectively. The application of DMAS reconstruction improved the ability of medical ultrasound to detect OCD lesions of the capitellum when compared with DAS reconstruction.

Comparing 12-core and 20-core biopsy for prostate cancer diagnosis with transperineal MR/US fusion biopsy: assessing the effective number of systemic cores using propensity score matching.

For transperineal (TP) prostate biopsy, target biopsy for visible lesions on MRI is important, but there is no consensus of the number of systemic biopsy cores. Our study aimed to confirm the diagnostic efficiency of 20-core systemic biopsy by comparison with 12-core using propensity score matching (PSM). The 494 patients conducted the naive TP biopsy were retrospectively analyzed. There were 293 patients with 12-core biopsy and 201 patients with 20-core biopsy. PSM was performed for minimizing confounding variables, and the established effects' value was analyzed for 'index-positive or negative' clinically significant prostate cancer (csPCa) (Index means PIRADS Score ≥ 3 on multiparametric prostate MRI). At 12-core biopsy, there were 126 cases of prostate cancer (43.0%), and 97 cases of csPCa (33.1%). At 20-core biopsy, there were 91 cases (45.3%) and 63 cases (31.3%). After propensity score matching, for index-negative csPCa, the estimated odds ratio was 4.03 (95% CI 1.35-12.09, p value 0.0128), and for index-positive csPCa, the estimated odds ratio was 0.98 (95% CI 0.63-1.52, p value 0.9308). The 20-core biopsy did not show a higher detection rate for csPCa in comparison with the 12-core biopsy. However, when MRI did not show a suspicious lesion, 20-core biopsy showed higher odd ratio in comparison with 12-core biopsy. Therefore, if there is a suspicious lesion in MRI, 20-core biopsy is excessive and 12-core biopsy is sufficient. Whereas if there is no suspicious lesion in MRI, it is better to proceed with 20-core biopsy.

Artificial Intelligence for Automated DWI/FLAIR Mismatch Assessment on Magnetic Resonance Imaging in Stroke: A Systematic Review.

We conducted this Systematic Review to create an overview of the currently existing Artificial Intelligence (AI) methods for Magnetic Resonance Diffusion-Weighted Imaging (DWI)/Fluid-Attenuated Inversion Recovery (FLAIR)-mismatch assessment and to determine how well DWI/FLAIR mismatch algorithms perform compared to domain experts. We searched PubMed Medline, Ovid Embase, Scopus, Web of Science, Cochrane, and IEEE Xplore literature databases for relevant studies published between 1 January 2017 and 20 November 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Five studies fit the scope of this review. The area under the curve ranged from 0.74 to 0.90. The sensitivity and specificity ranged from 0.70 to 0.85 and 0.74 to 0.84, respectively. Negative predictive value, positive predictive value, and accuracy ranged from 0.55 to 0.82, 0.74 to 0.91, and 0.73 to 0.83, respectively. In a binary classification of ±4.5 h from stroke onset, the surveyed AI methods performed equivalent to or even better than domain experts. However, using the relation between time since stroke onset (TSS) and increasing visibility of FLAIR hyperintensity lesions is not recommended for the determination of TSS within the first 4.5 h. An AI algorithm on DWI/FLAIR mismatch assessment focused on treatment eligibility, outcome prediction, and consideration of patient-specific data could potentially increase the proportion of stroke patients with unknown onset who could be treated with thrombolysis.

Early lesion visualization after catheter ablation for atrial fibrillation: rationale and preliminary results of the CALAMARI study

Abstract Funding Acknowledgements Type of funding sources: None. Background Incomplete atrial lesion is related to high atrial fibrillation (AF) recurrence after Pulmonary vein antrum isolation (PVAI). Objectives The CALAMARI study is a single-center, prospective, observational study with a longitudinal design. The primary aim is to assess PVAI lesion and its development over time using cardiovascular magnetic resonance (CMR). The secondary objective is to identify possible predictors of AF recurrence. Methods 96 consecutive patients undergoing PVAI for paroxysmal AF will undergo four sequential CMR: 1) pre-PVAI CMR 2) post-PVAI CMR, immediately after the ablation 3) CMR one-day or one-week post-PVAI 4) CMR 3-months post-PVAI. Dark-blood short-inversion-time recovery (DB-STIR) will identify oedema. Pre- and post-contrast prepped inversion-recovery with long inversion time (IR-prep) and three-dimensional late gadolinium enhancement (3D-LGE) images will be used to visualize atrial lesion (AL). Qualitative and quantitative assessments of AL will be performed. Patients will be followed-up for 2 years to identify AF recurrence. Preliminary results Ten patients (63.1±5.7 years old, 80% male) completed a pre-PVAI CMR and a post-PVAI-CMR. The AL post-PVAI was visible in 9 patients (90%) using post-contrast IR-prep sequences and in 6 patients (60%) using pre-contrast IR-prep and 3D-LGE. Microvascular obstruction was identified in 7 (70%) patients using IR-prep-post-contrast. On DB-STIR, edema was visualized in all patients with a significant increase in the left atrium wall thickening in CMR post-PVAI vs. pre-PVAI CMR (6.4±2.9 vs. 3.4±1.5, p = 0.09). Conclusion Post-PVAI AL visualization with CMR is feasible in most patients. The CALAMARI study will better understand the AL modifications over time.

Oral HPV Infection in Women with HPV-Positive Cervix Is Closely Related to Oral Sex.

The oral transmission of HPV and, consequently, the risk of oral cancer has increased in the last years. Oral sex has often been implicated among the risk factors for oral HPV infections, however, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. The present study aimed to evaluate the coexistence of papilloma virus, at the levels of the oral and genital mucosa, in women with a histologically confirmed HPV lesions (and a positive HPV test) at the genital level and a negative HPV control group. We also evaluated how some risk factors, such as smoking, the number of partners, age, and sexual habits can influence the possible presence of the virus itself in the oropharynx of the same women. In total, 117 unvaccinated women aged between 18 and 52 were enrolled. We found that the prevalence of oral HPV infection was high among the women with concomitant genital HPV infection (22%) compared to the HPV-negative women (0%), and the estimated odds ratio was 17.36 (95% CI: 1.02, 297.04). In none of the women with oral HPV did we find any relevant clinical lesions. The potential risk factors for HPV infections in the oropharynx and genitals were analyzed based on questionnaire responses. A multivariate analysis showed that genital HPV infections were significantly associated with a number of sexual partners > 10 (OR 138.60, 95% CI: 6.04-3181.30, p < 0.001), but the data also referred to having between 3-5 or 6-10 partners as being significant, as were a high level of education (OR 6.24, 95% CI: 1.67-4.23.26 p = 0.003), a frequency of sexual intercourse >10 (OR 91.67 95% CI: 3.20-2623.52, p = 0.004), oral sex (OR 6.16, 95% CI: 1.22-31.19, p = 0.014), and >20 cigarettes/day (OR 6.09 95% CI: 1.21-30.61, p = 0.014). Furthermore, being "separate" and having multiple sexually transmitted diseases were also significantly associated with genital HPV infection. In contrast, oral HPV infections were significantly associated with women aged 36 to 50 years (OR 27.38, 95% CI: 4.37-171.37; p = 0.000202) and oral sex (OR 95.5, 95% CI: 5.13-1782.75, p = 0.001126).Additionally, being separate, being cohabitant, lifetime sexual partners of >10, 3-5 lifetime sexual partners, <20 years of age, >10 sexual intercourse per month, occasional and regular anal sex, >20 cigarettes per day, a history of sexually transmitted disease (herpes and multiple), and having a history of genital warts were significant. Screening and early diagnosis are considered to be practically unfeasible for this category of cancer, given the lack of visible lesions; the 9-valent HPV vaccine remains the only means that could help to successfully counter the growing incidence of oral squamous cell carcinoma.

Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya.

Globally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies. Healthy women ages 18-34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition. Among 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36-90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded >2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was <10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and -27.1% to -20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased >50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively). TFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR. NCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382].

Evolving best practices in the surgical management of endometriosis - examining the evidence and expert opinion.

Endometriosis is a common and often debilitating condition, with multiple theories of pathogenesis. Despite the prevalence of endometriosis, the optimal surgical management remains unclear. Laparoscopy is the gold standard for the diagnosis of endometriosis, with biopsy confirmation more accurate than visual diagnosis alone. It is not clear from the existing data whether excision of endometriosis is superior to ablation. Improvement in pain has been documented following peritonectomy, however, controlled trials are lacking. It is not clear whether concomitant hysterectomy improves pain associated with endometriosis, although hysterectomy may reduce reoperation rate. Bilateral oophorectomy performed for the treatment of endometriosis may not be curative without simultaneous excision of all visible lesions, and the risks of surgical menopause should be considered. The rate of appendiceal endometriosis is higher than previously suspected, and may not correlate with intraoperative visual findings, suggesting appendectomy should be considered during surgical treatment of endometriosis. Despite the prevalence of endometriosis, there is a paucity of data to guide optimal surgical management. More high-quality studies are needed.

Location and appearance of dysplastic Barrett’s esophagus recurrence after endoscopic eradication therapy: no additional yield from random biopsy sampling neosquamous mucosa

Surveillance after complete remission of intestinal metaplasia (CRIM) is essential. Current recommendations are to sample visible lesions first, followed by random 4-quadrant biopsy sampling of the original Barrett's esophagus (BE) length. To inform post-CRIM surveillance protocols, we aimed to identify the anatomic location, appearance, and histology of BE recurrences. We performed an analysis of 216 patients who achieved CRIM after endoscopic eradication therapy for dysplastic BE at a Barrett's Referral Unit between 2008 and 2021. The anatomic location, recurrence histology, and endoscopic appearance of dysplastic recurrences were evaluated. After a median of 5.5 years (interquartile range, 2.9-7.2) of follow-up after CRIM, 57 patients (26.4%) developed nondysplastic BE (NDBE) recurrence and 18 patients (8.3%) developed dysplastic recurrence. From 8158 routine surveillance biopsy samplings of normal-appearing tubular esophageal neosquamous epithelium, the yield for recurrent NDBE or dysplasia was 0%. One hundred percent of dysplastic tubular esophageal recurrences were visible and in BE islands, whereas 77.8% of gastroesophageal junction dysplastic recurrences were nonvisible. Four distinct endoscopic features suspicious for recurrent advanced dysplasia or neoplasia were identified: buried or subsquamous BE, irregular mucosal pattern, loss of vascular pattern, and nodularity or depression. The yield of routine surveillance biopsy sampling of normal-appearing tubular esophageal neosquamous epithelium was zero. BE islands with indistinct mucosal or loss of vascular pattern, nodularity or depression, and/or signs of buried BE should raise clinician suspicion for advanced dysplasia or neoplasia recurrence. We suggest a new surveillance biopsy sampling protocol with a focus on meticulous inspection, followed by targeted biopsy sampling of visible lesions and random 4-quadrant biopsy sampling of the gastroesophageal junction.

Ultrafast DCE-MRI for discriminating pregnancy-associated breast cancer lesions from lactation related background parenchymal enhancement.

To investigate the utility of ultrafast dynamic-contrast-enhanced (DCE) MRI in visualization and quantitative characterization of pregnancy-associated breast cancer (PABC) and its differentiation from background-parenchymal-enhancement (BPE) among lactating patients. Twenty-nine lactating participants, including 10 PABC patients and 19 healthy controls, were scanned on 3-T MRI using a conventional DCE protocol interleaved with a golden-angle radial sparse parallel (GRASP) ultrafast sequence for the initial phase. The timing of the visualization of PABC lesions was compared to lactational BPE. Contrast-noise ratio (CNR) was compared between the ultrafast and conventional DCE sequences. The differences in each group's ultrafast-derived kinetic parameters including maximal slope (MS), time to enhancement (TTE), and area under the curve (AUC) were statistically examined using the Mann-Whitney test and receiver operator characteristic (ROC) curve analysis. On ultrafast MRI, breast cancer lesions enhanced earlier than BPE (p < 0.0001), enabling breast cancer visualization freed from lactation BPE. A higher CNR was found for ultrafast acquisitions vs. conventional DCE (p < 0.05). Significant differences in AUC, MS, and TTE values were found between the tumor and BPE (p < 0.05), with ROC-derived AUC of 0.86 ± 0.06, 0.82 ± 0.07, and 0.68 ± 0.08, respectively. The BPE grades of the lactating PABC patients were reduced as compared with the healthy lactating controls (p < 0.005). Ultrafast DCE MRI allows BPE-free visualization of lesions, improved tumor conspicuity, and kinetic quantification of breast cancer during lactation. Implementation of this method may assist in the utilization of breast MRI for lactating patients. The ultrafast sequence appears to be superior to conventional DCE MRI in the challenging evaluation of the lactating breast. Thus, supporting its possible utilization in the setting of high-risk screening during lactation and the diagnostic workup of PABC. • Differences in the enhancement slope of cancer relative to BPE allowed the optimal visualization of PABC lesions on mid-acquisitions of ultrafast DCE, in which the tumor enhanced prior to the background parenchyma. • The conspicuity of PABC lesions on top of the lactation-related BPE was increased using an ultrafast sequence as compared with conventional DCE MRI. • Ultrafast-derived maps provided further characterization and parametric contrast between PABC lesions and lactation-related BPE.

Investigation of Spotty Liver Disease and Campylobacter hepaticus in Layer Flocks-A Field Study.

Campylobacter hepaticus (C. hepaticus) was recently discovered as the causative agent of Spotty Liver Disease (SLD). SLD affects laying hens and causes significant economic losses in egg production in several countries throughout the world. Field observations reveal that cases of SLD appear with a high risk of reoccurrence, specifically in free-range and organic brown-feathered layer lines. Possible factors contributing to the development of SLD still have to be elucidated. In this field study, one free range (Flock 1) and one organic flock (Flock 2) of brown laying hens kept on farms with a history of clinical SLD were monitored for C. hepaticus colonization, clinical signs, and egg production from 16 to 79 wk of age on the first farm and from 17 to 83 wk of age on the other. The flocks showed a significant drop in egg production at 32 to 39 or 56 wk of age, respectively, which was associated with macroscopically visible liver lesions typical for SLD. Interestingly, in both cases observed clinical disease was linked to a stressful event: heat stress for Flock 1 and respiratory symptoms for Flock 2. C. hepaticus was detected by PCR during the acute phase of the disease in Flock 1. At 50 wk after the initial clinical outbreak had waned, C. hepaticus was still able to be isolated by culture in this flock. This clearly demonstrates that C. hepaticus persists either in the birds or their environment. We speculate that this long persistence may favor chronic SLD in affected flocks and the reoccurrence of SLD in subsequent flocks. Clinically less severe SLD outbreaks may be observed after re-exposure of clinically recovered flocks.

Radionuclide-Labeled Microspheres for Radio-Immunotherapy of Hepatocellular Carcinoma.

Brachytherapy, including radioactive seed implantation (RSI) and transarterial radiation therapy embolization (TARE), is an important treatment modality for advanced hepatocellular carcinoma (HCC), but the inability of RSI and TARE to treat tumor metastasis and recurrence limits their benefits for patients in the clinic. Herein, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors-loaded alginate microspheres (IMs) are developed as radionuclide carriers with immunomodulatory functions to achieve effective radio-immunotherapy. The size and swelling properties of IMs can be facilely tailored by adjusting the calcium source during emulsification. Small/large IMs(SIMs/LIMs) are biocompatible and available for RSI and TARE, respectively, after 177 Lu labeling. Among them, 177 Lu-SIMs completely eliminated subcutaneous HCC in mice after intratumoral RSI. Moreover, in combination with anti-PD-L1, 177 Lu-SIMs not only eradicate primary tumors by RSI but also effectively inhibit the growth of distant tumors, wherein the potent abscopal effect can be ascribed to the immune stimulation of RSI and the modulation of the tumor immune microenvironment (TIME) by IDO1 inhibitors. In parallel, LIMs demonstrate excellent embolization efficiency, resulting in visible necrotic lesions in the central auricular artery of rabbits, which are promising for TARE in future studies. Collectively, a versatile therapeutic agent is provided to synchronously modulate the TIME during brachytherapy for efficient radio-immunotherapy of advanced HCC.