[The long-term efficacy of metformin in megestrol acetate-based fertility-sparing treatment for patients with endometrial atypical hyperplasia and endometrioid endometrial cancer].

Objective: To assess the long-term efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC). Methods: The randomized controlled trail study was conducted from October 2013 to October 2017 in the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. Patients with EAH or EEC were firstly stratified according to pathology, and randomized to receive MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day) or MA (160 mg orally, daily). Baseline data between two groups of patients were compared. Estimates of time to complete remission (CR) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. Cox proportional-hazards regression model was used to estimate hazard ratios (HR) of related factors for recurrence-free survival. Quantitative data were represented by M (Q1, Q3). Results: A total of 150 patients were included, and 76 patients were allocated to receive MA plus metformin with the age of 32.5 (28.0, 36.0), while 74 patients received MA alone with the age of 32.0 (28.0, 36.0). By the end of follow-up period, 96.7% (n=145) of patients achieved complete remission, with a median follow-up time of 57.7 (26.7, 70.5) months. The median CR time for the MA plus metformin group and the MA alone group were 6.3 (3.5, 8.3) months and 6.8 (4.0, 9.3) months, respectively (P=0.193), with 2-year cumulative CR rate of 98.6% and 98.5%, respectively (P=0.879). The median time of RFS was 28.1 (12.5, 57.3) months for the MA plus metformin group and 33.3 (14.1, 62.5) months for the MA alone group (P=0.213), with a cumulative RFS rate of 61.9% and 65.8%, respectively (P=0.560). In the subgroup of non-obese (body mass index<28 kg/m2) patients with EAH, the median RFS times were 25.7 (7.6, 60.3) months and 47.3 (17.5, 64.8) months for the MA plus metformin group and the MA alone group, respectively (P=0.033), with a cumulative RFS rate of 57.5% and 80.6%, respectively (P=0.029). According to Cox proportional hazards regression analysis, undergoing assisted reproductive treatment (HR=2.358, 95%CI: 1.069-5.204, P=0.034) was identified as an independent risk factor for recurrence-free survival after complete remission of endometrial lesions. Conclusion: The long-term follow-up outcome indicates that there is no significant difference in CR time and RFS time between MA plus metformin therapy and MA alone therapy for patients with EAH or EEC.

Severe Anemia from Multiple Gastric Hyperplastic Polyps in a Hemodialysis Patient after Long-term Use of a Proton-pump Inhibitor.

A 90-year-old man on maintenance hemodialysis was admitted due to severe symptomatic anemia. Biopsies under esophagogastroduodenoscopy demonstrated that the cause of anemia was intermittent blood oozing from multiple gastric hyperplastic polyps. Even after successful eradication of Helicobacter pylori, he showed hypergastrinemia (480 pg/mL) owing to esomeprazole (proton-pump inhibitor) therapy for the past 4.5 years to treat reflux esophagitis. Seven months after we switched esomeprazole to famotidine (H2-receptor antagonist), those gastric polyps and anemia were remarkably ameliorated with lowered gastrin levels. This case indicates that long-term use of a proton-pump inhibitor triggers chronic hypergastrinemia, leading to gastric hyperplastic polyps and subsequent severe anemia.

Drug-coated balloon therapy for in-stent restenosis in patients with iliofemoral deep vein thrombosis: A single-arm observational study.

BACKGROUND: Iliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in-stent restenosis (ISR) has become an emerging non-negligible problem. METHODS: To evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug-coated balloon (DCB) on venous ISR lesions, we conducted a single-center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel-coated balloon dilatation. RESULTS: We found a collagen-rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow-up (p < 0.0001). During follow-up, the VEINES-QOL scores (p < 0.0001), VEINES-Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed. CONCLUSIONS: The use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.

Comparison between combination of tamsulosin and Pentoxifylline versus tamsulosin alone in the treatment of lower urinary tract symptoms due to benign prostate hyperplasia: A preliminary study.

BACKGROUND: In older adults, bladder outlet obstruction (BOO) is prevalent, primarily due to benign prostatic hyperplasia (BPH). These patients' lower urinary tract symptoms can be treated surgically and with medical therapy. Compared to standard treatment with tamsulosin, Pentoxifylline, a phosphodiesterase inhibitor, could benefit patients with BOO due to its properties on microcirculatory blood flow and oxygenation of ischemic tissues. Hence, this trial intended to study the efficacy of Pentoxifylline combined with tamsulosin in treating BOO patients. MATERIALS AND METHODS: This randomized, double-blind clinical trial recruited 60 patients with BPH from a single center in 2022. Upon consent of patients meeting the eligibility criteria, they were randomly allocated to intervention (Pentoxifylline + tamsulosin) and control (placebo + tamsulosin) groups. The patients were evaluated for international prostate symptom score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax ) by uroflowmetry, and post-void residual volume (PVR) by abdominal sonography at the onset of the study and after the 12th week. RESULTS: Patients who used the combination therapy had significantly better results of prostate symptoms and quality of life improvement (IPSS: -36.6%, QoL: -45.3%) compared to patients who received tamsulosin alone (IPSS: -21.2%, QoL: -27.7%) (p < .001). Also, this study shows that the improvement in maximum urinary flow rate and residual volume by combination therapy is significantly higher (Qmax : +42.5%, PVR: -42.6%) compared to monotherapy (Qmax : +25.1%, PVR: -26.1%) (p < .001). CONCLUSION: When combined with tamsulosin, Pentoxifylline could significantly improve the lower urinary symptoms of BPH patients. It is well tolerated, and the treatment outcomes are better in patients who receive the combination of Pentoxifylline and tamsulosin than those who only receive tamsulosin.

Disturbed bone marrow adiposity in patients with Cushing's syndrome and glucocorticoid- and postmenopausal- induced osteoporosis.

Background: Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O). Methods: Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated. Results: Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (<100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (>100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar>100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events. Conclusion: Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases.

Modified Estrogen-Progesterone Induction Method of Mammary Gland Hyperplasia in Rats.

In female Wistar rats, mammary gland hyperplasia (MGH) was modeled according to a modified protocol involving estrogen-progesterone induction and taking into account the duration of the estrous cycle of this animal species. MGH was induced over four 7-day cycles; each cycle included subcutaneous administration of 17ß-estradiol (0.5 mg/kg) for 4 days, injection of progesterone (5 mg/kg) on day 5, then 2 days without injections. In females with MGH, a significant increase in the height and diameter of the nipples of the mammary glands was recorded, two types of changes were observed in the gland tissue: tubuloalveolar and lobuloalveolar hyperplasia. The study confirmed the development of MGH in rats by a modified method.

A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia.

Lower urinary tract symptoms (LUTS) secondary to benign prostrate hyperplasia (BPH) are common geriatric diseases, and its incidence rises with age. The treatment of BPH and LUTS is becoming a burden for health care. The meta-analysis was performed to evaluate the efficacy and safety of combination therapy (tamsulosin plus tadalafil) compared with tamsulosin alone in treatment of males with LUTS/BPH. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were utilized to conduct this study. There were several databases available for literature retrieval, including Medline, Embase, PubMed, Scopus, Web of Science databases, and Cochrane Controlled Trials Register. To improve the comprehensiveness of the search, related references were also searched. Finally, six randomized controlled trials including 441 patients were included. The combination therapy had significant improvements in total International Prostate Symptom Score (p < .0001), quality of life score (p = .003), maximum urine flow rate (p < .00001), and International Index of Erectile Function (p < .00001) compared with the tamsulosin monotherapy, but there was no obvious difference in postvoid residual volume (p = .06). In terms of safety, the combination group had comparable rates of discontinuation due to adverse events (p = .19) than the monotherapy group except for pain symptoms (p < .0001). The combination of tamsulosin and tadalafil provided a preferable therapeutic effect compared with the tamsulosin alone in treating males with BPH/LUTS, and both therapy regimens were well tolerated by the patients.

Cyclosporine induced generalized hyperkeratosis in a dog.

INTRODUCTION: Cyclosporine is a potent immunosuppressive agent used in veterinary medicine to treat a variety of inflammatory or immune mediated conditions. Many adverse effects are associated with this medication, however most of them rarely occur. A 5-year-old, female intact French bulldog was presented with multiple, multifocally distributed, severe hyperkeratotic and papillomatous/verrucous plaques. The dog was on long-term immunosuppressive treatment with cyclosporine for meningoencephalitis of unknown origin (MUO). It had an history of atopic dermatitis and calcinosis cutis. A papillomavirus infection was excluded by polymerase chain reaction (PCR), and histopathologic analysis revealed a chronic lymphoplasmacytic non-specific dermatitis, perifolliculitis and periadnexitis and focal folliculitis with papillomatous epidermal hyperplasia and orthokeratotic hyperkeratosis. The diagnosis of "cyclosporine-induced epidermal hyperplasia with secondary pyoderma" was made. Cyclosporine was discontinued and as an alternative mycophenolate mofetil was started to control the MUO. An antimicrobial treatment was prescribed for three weeks. After four months, the skin lesions had healed completely. To date after 2 years, the dog is still in remission. The occurrence of hyperplastic lesions associated with cyclosporine therapy have already been described in previous reports. Most of them resemble those of psoriasiform lichenoid dermatitis, although papilloma virus may be detected in some instances. The dog of the present case showed some peculiarities in the histopathological findings, and a papillomavirus involvement was ruled out with PCR. Like observed in a previous report, there was no correlation between cyclosporine blood level and the severity of dermatological changes. A discontinuation of cyclosporine resulted in complete healing in 4 months. This case highlights the importance of regular monitoring and follow-ups in patients on immunosuppressive therapy. Even rare side effects should always be considered in these cases.

INTRODUCTION: La cyclosporine est un puissant agent immunosuppresseur utilisé en médecine vétérinaire pour traiter une variété de conditions inflammatoires ou à médiation immunitaire. De nombreux effets indésirables sont associés à ce médicament, mais la plupart d'entre eux se produisent rarement. Un bouledogue français intact, âgé de 5 ans, a été présenté avec de multiples plaques hyperkératosiques et papillomateuses/verruqueuses sévères, réparties de manière multifocale. Le chien suivait un traitement immunosuppresseur à long terme à base de cyclosporine pour une méningo-encéphalite d'origine inconnue (MUO). Il avait des antécédents de dermatite atopique et de calcinosis cutis. Une infection à papillomavirus a été exclue par réaction en chaîne par polymérase (PCR) et l'analyse histopathologique a révélé une dermatite chronique lymphoplasmocytaire non spécifique, une périfolliculite et une périannexite ainsi qu'une folliculite focale avec hyperplasie épidermique papillomateuse et hyperkératose orthokératosique. Le diagnostic d'¼hyperplasie épidermique induite par la cyclosporine avec pyodermie secondaire¼ a été posé. La cyclosporine a été stoppée et on a commencé à administrer du mycophénolate mofétil comme alternative pour contrôler l'OMU. Un traitement antimicrobien a été prescrit pendant trois semaines. Après quatre mois, les lésions cutanées étaient complètement guéries. À ce jour, après deux ans, le chien est toujours en rémission. L'apparition de lésions hyperplasiques associées au traitement par la cyclosporine a déjà été décrite dans des rapports précédents. La plupart d'entre elles ressemblent à celles de la dermatite lichénoïde psoriasiforme, bien que le virus du papillome puisse être détecté dans certains cas. Le chien du cas présent présentait quelques particularités dans les résultats histopathologiques et une implication du papillomavirus a été exclue par PCR. Comme observé dans un rapport précédent, il n'y avait pas de corrélation entre le taux sanguin de cyclosporine et la sévérité des altérations dermatologiques. L'arrêt de la cyclosporine a permis une guérison complète en 4 mois. Ce cas souligne l'importance d'une surveillance et d'un suivi réguliers des patients sous traitement immunosuppresseur. Les effets secondaires, même rares, doivent toujours être pris en compte dans ces cas.

[Dasatinib-induced follicular lymphoid hyperplasia, an entity to know]. / Hyperplasie lymphoïde folliculaire induite par la prise de dasatinib, une entité à connaître.

Follicular lymphoid hyperplasia induced by dasatinib is an entity recently described. It is sometimes difficult to rule out the diagnostic of small B-cell lymphoma. Usually, the node is swollen, with follicular architecture conserved, composed by germinal centers with variable size and shape, with a hight number of mitoses and tingible bodies macrophages inside. Follicular lymphoid hyperplasia is isolated or associated with multiple reactive patterns. The immunohistochemical profil of germinal centers is CD20+, CD10+, BCL6+, BCL2-. Swollen node disappears in a short time after dasatinib discontinuation. Clinicians and pathologists need to be aware of this entity, so as not to avoid mistakenly suspect lymphoma when lymphadenopathy occurs in a patient with chronic myeloid leukemia treated with dasatinib.

Complications Following Facial Injection of Growth Factor Solution.

OBJECTIVE: Topical injection of growth factor (GF) for facial rejuvenation is unauthorized, but it is commonly performed in China, leading to emerging and challenging complications. The purpose of this study is to investigate the clinical, imaging, and histopathologic characteristics of complications caused by facial GF injection, as well as their treatments and outcomes. METHODS: We performed a retrospective single-centered case series study on consecutive patients who were treated for complications following facial injection of GF. The primary outcome was the recurrence over follow-up period. The secondary outcomes were the subjective evaluations of the facial aesthetic, symptomatic, and psychological improvements using the Global Aesthetic Improvement Scale (GAIS) and a patient-reported outcome measurement (PROM). Kaplan-Meier analysis and log-rank test were performed to investigate the recurrence. RESULTS: A total of 32 females with an average age of 42.6 ± 9.4 years were included. Most patients received GF injections in non-medical institutes such as beauty spas and presented with uncontrollable soft tissue hyperplasia, diffuse subcutaneous swelling, and skin redness. Ultrasonography showed heterogeneous hypoechoic or echogenic areas in a thickened and disorganized subcutaneous tissue hierarchy. MRI showed flaky isointensive or hypointensive signals on T1WI and hyperintensive signals on T2WI. 37.5% patient underwent triamcinolone acetonide injection, whereas 62.5% patients underwent surgical interventions. Lipoma-like hyperplastic tissue was found during surgery. HE staining confirmed intramuscular lipoma and fibrolipomatous tissue hyperplasia. Recurrence was found in 37.5% patients over a median follow-up of 6 months. KM curves and log-rank test demonstrated no significant difference in the recurrence between patients who underwent nonsurgical or surgical interventions (p = 0.77). GAIS and PROM scores indicated substantial aesthetic, symptomatic, and psychological improvements in 70%, 91.7%, and 75% patients, respectively. CONCLUSIONS: Both surgical and nonsurgical interventions are feasible and effective treatment options for GF-induced complications. Although recurrence rate was relatively high, aesthetic, symptomatic, and psychological improvements were achieved in most patients. We developed a workflow that might help diagnose and treat complications following unknown dermal filler injections. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Rare case of coexisting ovarian Brenner tumour and ovarian stromal hyperplasia presenting with persistent endometrial hyperplasia following treatment with levonorgestrel-intrauterine system.

Endometrial hyperplasia (EH) is a precursor of endometrial cancer. It arises in an environment of unopposed oestrogen. Treatment is based on a combination of weight management, diet and exercise, and the use of progestogens either via a levonogestrel-intrauterine system (LNG-IUS) or orally. The LNG-IUS is the first-line recommendation for EH without atypia. Recurrences are rare, and any recurrences despite prolonged treatment and control of risk factors necessitate a thorough consideration of other oestrogenic sources. This case report presents a rare case of a coexisting ovarian Brenner tumour and ovarian stromal hyperplasia in a menopausal patient in her 50s with recurrent EH despite earlier regression. The above histology may have provided the additional oestrogenic influence. This patient subsequently underwent a definitive hysterectomy and bilateral salpingo-oophorectomy (BSO). It is important to maintain a high index of suspicion for potential oestrogenic influences in cases of refractory EH that are not identifiable on imaging. BSO should be considered at the time of hysterectomy in such cases of unidentified oestrogenic foci.

Abnormal hyperplasia of chondrocytes in a rat model of glucocorticoid-induced osteonecrosis of the femoral head.

OBJECTIVE: The aim of our study was to determine whether abnormal hyperplasia of chondrocytes occurs in glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) using a well-established rat model. MATERIALS AND METHODS: Rats were injected with lipopolysaccharide and methylprednisolone to induce GC-ONFH, while control animals were injected with saline (12 animals per group). Establishment of the disease model was confirmed using micro-computed tomography and hematoxylin-eosin (HE) staining of femoral head tissue sections. Chondrocyte hyperplasia was detected using HE staining and semi-quantitated using toluidine blue and saffron O staining. Expression of the autophagy marker LC3B was assessed in cartilage tissues of femoral head using immunohistochemistry. RESULTS: GC-ONFH animals showed significantly greater area of abnormal chondrocyte hyperplasia in femoral head tissue sections than control animals. They also showed significantly higher expression of LC3B in articular cartilage of the femoral head. CONCLUSIONS: GC-ONFH may be associated with abnormal chondrocyte hyperplasia in articular surface cartilage, which may be related to glucocorticoid-induced overactivation of autophagy.

Juvenile arsenic exposure aggravates goblet cell hyperplasia and airway mucus secretion in ovalbumin-sensitized mice.

Gestational arsenic (As) exposure has been associated with adverse developmental outcomes. The purpose of this study was to explore the impacts of As exposure in different periods on susceptibility to allergic asthma. In model 1, dams were administered with NaAsO2 (0.1 or 1 ppm) by drinking water throughout pregnancy and lactation. In model 2, newly weaned pups were exposed to NaAsO2 (1 ppm) through drinking water. Pups were sensitized and challenged with ovalbumin (OVA). Inflammatory cell infiltration and pulmonary T helper 2 (Th2) cytokine upregulation were shown in OVA-sensitized and challenged pups. Goblet cell hyperplasia and airway mucus secretion were observed in OVA-sensitized and challenged pups. Maternal As exposure throughout pregnancy and lactation did not aggravate inflammatory cell infiltration, airway mucus secretion and pulmonary Th2 cytokine upregulation in OVA-sensitized and challenged pups. Although airway hyperreactivity, inflammatory cell infiltration and Th2 cytokine weren't influenced, OVA-evoked Goblet cell hyperplasia and airway mucus secretion were aggravated in pups who were exposed to NaAsO2 after weaning. In conclusion, juvenile As exposure increases susceptibility to allergic asthma through aggravating Goblet cell hyperplasia and airway mucus secretion. The impacts of maternal As exposure during pregnancy and lactation on susceptibility to allergic asthma needs to be further evaluated in other animal experiments.

Endometrial Cancer Following Levonorgestrel-Releasing Intrauterine System Insertion in Young Women with Atypical Hyperplasia: Two Case Reports and Literature Review.

Levonorgestrel-releasing intrauterine system (LNG-IUS) insertion is the first-line treatment for atypical hyperplasia (AH) in young women who wish to retain their fertility. However, the procedure is not always effective, and may allow AH to progress to endometrioid endometrial cancer (EEC). Two young women with AH who wished to preserve their fertility developed EEC following 52-mg LNG-IUS in insertion at our institution. One was a 34-year-old woman diagnosed with endometrial cancer 2 years after LNG-IUS insertion. The second was a 30-year-old woman diagnosed 17 months after LNG-IUS insertion. Proactive molecular risk classification for endometrial cancer (ProMisE) classification revealed that the first and second patients had p53-abnormal (p53abn) EEC and mismatch repair deficient (MMR-d) EEC, respectively. MMR-d and p 53abn were frequently observed in both AH and EEC specimens. Studies suggest that MMR-d and p53abn are predictors of the occurrence adverse effects after fertility-preserving treatment for EEC. AH is a precursor of EEC. Therefore, p53 and mismatch repair (MMR) mutation may be used to identify women with AH who will not likely benefit from progestin therapy. Molecular assays in women with AH will likely be useful for identifying novel predictive biomarkers of progestin resistance and to improve the safety of conservative treatment. Combined assessment of progesterone receptor (PR) with these predictive molecular markers may improve the predictive ability.

Enterochromaffin-like Cell Hyperplasia-Associated Gastric Neuroendocrine Tumors May Arise in the Setting of Proton Pump Inhibitor Use.

CONTEXT.­: Hypergastrinemia states such as achlorhydria from gastric mucosal atrophy or a gastrin-producing tumor in humans have been associated with the development of enterochromaffin-like (ECL) cell hyperplasia and gastric neuroendocrine tumors (GNETs). Whether drugs that can elevate serum gastrin levels, such as proton pump inhibitors (PPIs), can produce the same tissue effect is not known, and there is no concrete evidence linking the use of PPIs to GNETs outside animal models and case reports. OBJECTIVE.­: To explore the clinicopathologic association for GNETs of presumed ECL cell origin that cannot be reliably placed into any of the 3 established categories currently recognized by the World Health Organization. DESIGN.­: This is a retrospective clinicopathologic study of GNETs in the body/fundus during a period of 15 years (2005-2019). RESULTS.­: Of a total of 87 cases, 57 (65.5%) were associated with atrophic gastritis, 2 (2.3%) were associated with Zollinger-Ellison syndrome, and 28 (32.2%) were unclassified. Of the latter, 11 were consistent with true sporadic/type 3 GNETs, while 17 had background mucosal changes of parietal cell and ECL cell hyperplasia but without underlying detectable gastrinoma, and 88.2% (15 of 17) of patients from this group had documented long-term PPI use. This subtype of GNETs was more commonly multifocal and of higher grade (P = .03) than "true" sporadic GNETs. CONCLUSIONS.­: A subset of GNETs arises in the background of gastric mucosal changes suggestive of hypergastrinemia, but without underlying gastrinoma, and could be linked to long-term PPI use.

Amlodipine Induced Gum Hypertrophy: A Rare Case Report.

BACKGROUND: DIGO or drug-induced gingival overgrowth occurs as a side effect of certain drugs. Until now, the etiology of drug-induced gingival overgrowth is not clearly understood. Among the calcium channel blockers, nifedipine has been shown to be most frequently associated with drug-induced gingival hyperplasia. Amlodipine is a comparatively newer calcium channel blocker that with a longer duration of action and lesser side effects as compared to nifedipine. There are only certain case reports of amlodipine-induced gum hyperplasia. CASE PRESENTATION: We report a case of amlodipine-induced gum hyperplasia in a 66-year-old hypertensive patient taking amlodipine at a dose of 5 mg once a day. There was significant regression of gum hypertrophy after substitution of amlodipine by Losartan. CONCLUSION: Amlodipine is one of the commonly prescribed antihypertensive drugs, and gingival hyperplasia is one overlooked side effect in patients taking amlodipine. Awareness of this potential side effect of amlodipine may be helpful to reduce the anxiety of patients and the cost of diagnostic procedures.

Effects of chronic exposure to nonylphenol at environmental concentration on thyroid function and thyroid hyperplasia disease in male rats.

The aim of this work was to determine whether chronic exposure to nonylphenol (NP), a representative substance of environmental endocrine disruptors (EEDs), at environmental concentration would have toxic effects on thyroid function and thyroid hyperplasia disease. Two hundred SPF Sprague-Dawley rats were divided into five groups (n = 40 per group): blank control group (corn oil), low-dose NP exposure group (0.4 mg/kg/d), medium-dose NP exposure group (4 mg/kg/d), high-dose NP exposure group (40 mg/kg/d), and estradiol control group (E2: 30 µg/kg/d). The rats were treated by gavage for 34 weeks, which were sampled twice (17 weeks and 34 weeks respectively). NP accumulation in the thyroid tissue (F = 52.93, P < 0.001) and serum (F = 5.54, P = 0.00) continuously increased in a significant dose-effect relationship. After NP exposure, the serum FT3 levels exhibited a dose-dependent increasing trend (F = 4.68, P = 0.01), while the serum FT4 level showed an opposite trend (F = 3.93, P= 0.01). Compared with the control group, hyperechoic areas (i.e., calcification points) were observed in the high-dose group. Follicular epithelial stratification was extremely severe, the monolayer cubic epithelial cells became flat, and the area of single follicles was even smaller in the high-dose group. In the high-dose NP group, there were numerous mitochondria that were severely swollen. The rough endoplasmic reticulum was abundant, with obvious expansion and vesiculation. The relative expression of ERα (F = 5.29, P = 0.00), ERß (F = 10.17, P = 0.00), TRα (F = 7.71, P = 0.00), TRß (F = 3.52.17, P = 0.02) and HMGB1 (F = 10.16, P = 0.01) proteins in the thyroid tissue in each NP exposure group was increased compared with the control group, and the relative expression of proteins increased if the exposure time was prolonged under the same exposure dose. Chronic exposure to NP at environmental concentration could have toxic effects on thyroid function, and induce thyroid hyperplasia disease in male rats.

Attenuation of hyperplasia in lung parenchymal and colonic epithelial cells in DMBA-induced cancer by administering Andrographis paniculata Nees extract using animal model.

OBJECTIVES: This study was designed to evaluate the potential of Andrographis paniculata ethanolic extract to inhibit the increase in proliferation and induction of abnormal cell death. METHODS: The hyperplasia stage as an early stage of cancer development was induced by oral administration of 20 mg/Kg BW DMBA to SD rats twice a week for 5 weeks. There were five groups in this study include negative control, positive control, and treatment groups of DMBA induction followed by administration of A. paniculata ethanolic extract in doses equivalent to 10, 30 or 100 mg/Kg BW andrographolide once per day for 6 consecutive weeks. On the last day, rats were sacrificed, lung and colon tissues were collected. Histological examination by HE staining and immunohistochemistry using p53, telomerase, and caspase-3 antibodies were aimed at observing hyperplasia state in these tissues. RESULTS: DMBA induction to SD rats was able to produce hyperplasia in lung parenchymal and colon epithelial tissue. This can be showed by the increasing number of proliferated cells and as indicated by the number of brown-colored nuclei with sharper intensity. As well telomerase appears to be overexpressed strongly, while p53 and caspase-3 show low intensity. The administration of A. paniculata extract for 6 weeks showed a decrease in the number of cells that actively proliferate, a decrease in telomerase activity, and an increase in caspase-3 levels which indicate cellular death activity. CONCLUSIONS: A. paniculata ethanolic extract can inhibit the development of cancer at the hyperplasia stage by reducing telomerase activity and increasing apoptosis, marked by an increase of caspase-3 expressions.

Capsaicin attenuates imiquimod-induced epidermal hyperplasia and cutaneous inflammation in a murine model of psoriasis.

Psoriasis is one of the most common chronic inflammatory diseases that is characterized by well-defined erythematous plaques, with typical histopathological findings of lymphocytic infiltration and epidermal hyperplasia. Topical treatments of psoriasis are either associated with limited response or with side effects. Up to date, topicals targeting neuroimmune axis in psoriasis or psoriasiform dermatitis have not been explored. Here, we investigated whether percutaneous delivery of capsaicin could attenuate the pathological change of psoriasiform inflammation. Imiquimod-induced psoriasis-like murine model was used to evaluate therapeutic effects from topical application of capsaicin. An additional model of psoriasiform dermatitis induced by direct IL-23 injection was used to identify the level of action from capsaicin in this neuroimmune axis. Cutaneous inflammation was assessed by erythema level and ear thickness change. Key cytokines, infiltrating cells in the skin, and draining lymph node cells were investigated. The results showed that capsaicin administration obstructed the activation of IL-23/IL-17 pathway induced by imiquimod, presenting with significantly reduced psoriasiform dermatitis both in gross appearance and microscopic features. Tissue gene expression of psoriatic core cytokines induced by imiquimod (including IL-23, IL-17A, IL-22, TNF-α, and IL-6) were greatly decreased by capsaicin application. This protective effect from capsaicin could be hampered by direct intradermal injection of IL-23. CONCLUSION: Epicutaneous delivery of capsaicin on imiquimod-treated murine skin could significantly decrease expression of multiple inflammatory cytokines and the severity of prototypic change of psoriasiform inflammation. The beneficial effect imposed by capsaicin reinforces the neuroimmune contribution towards psoriasiform inflammation and provides a potential non-steroidal therapeutic alternative for topical treatment of psoriasiform dermatitis.