Incidence Of Hyperplasia Research Articles

Ethnic and National Differences in Congenital Adrenal Hyperplasia Incidence: A Systematic Review and Meta-Analysis

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of cortisol, aldosterone, or both. The most common type is the 21-hydroxylase enzyme deficiency in approximately 95% of cases resulting from CYP21A2 gene mutations or deletions. Objectives: This study aimed to systematically review the national differences in CAH incidence and analyze the pooled results to determine disparities and whether ethnicity can predispose people to develop CAH. Methods: PubMed, Scopus, and LILACS were used to achieve results until June 22, 2018. Study eligibility criteria included availability of full-text; English, Spanish, or Portuguese languages; incidence or number of new cases; and number of live births or sample population. Only the classic CAH type (salt-wasting and simple-virilizing) was considered, and no distinction was made between the enzyme deficiency types. Results: This study summarizes the findings of 58 studies and 31 countries (from 1969 to 2017), in which the overall CAH incidence was 1:9,498 (95% confidence interval: 1:9,089, 1:9,945). Countries from the Eastern Mediterranean and Southeast Asia revealed the highest CAH incidence. The lowest incidence was reported in countries of the Western Pacific of Asia. No remarkable difference was observed in the Hispanics/Latino and White groups. However, they manifested a higher incidence of CAH than people identified as Black or of African descent. Published studies on CAH incidence in the sub-Saharan African region and parts of Europe were insufficient. Conclusions: This study highlights the at-risk population for CAH and regions that need monitoring for CAH. The highest CAH incidence could be attributed to higher consanguinity, less genetic diversity, or other genetic causes since CAH is an inherited genetic disorder. Cultural practices in some places regarding consanguineous unions or geographic isolation may directly affect the incidence. Newborn screening for CAH may be unavailable in many developing countries, thereby affecting the actual CAH incidence. Therefore, healthcare workers should be trained to recognize CAH at an early stage to reduce its complications and mortality.

The influence of electromagnetic fields of industrial frequency on the male reproductive system

Introduction. The safety of exposure to the population of a growing number of sources of electromagnetic fields everywhere, both in work and at home, has become a public health problem. This article presents the results of research on the study of the potentially adverse effects of electromagnetic fields of industrial frequency on the reproductive system of personnel of energy supply institutions. The aim of the study is to explore the possible adverse effects of electromagnetic fields of industrial frequency on the male reproductive system. Materials and methods. The object of the study was 144 employees engaged in the repair and operation of power grid facilities and 40 employees who are not exposed to electromagnetic fields of industrial frequency. To assess laboratory parameters, blood samples were taken, followed by determination of the levels of total testosterone, free testosterone and globulin binding sex hormones. Results. The subjects of the main group revealed a high incidence of prostatic hyperplasia and chronic prostatitis. The employees of the main group had lower concentrations of sex hormones (p<0.05) in relation to similar indicators of the control group. A negative correlation was revealed between the levels of total, free testosterone and sex hormone binding globulin with experience (r=-0.36 p=0.009; r=-0.264 p=0.06; r=-0.349 p=0.01, respectively). Limitations of the study. The study is limited by the number of highly trained workers exposed to electromagnetic fields of industrial frequency. Conclusions. The results of the study indicate the negative impact of electromagnetic fields of industrial frequency on the reproductive system of employees engaged in the repair and operation of power grid facilities. With an increase in the length of service of employees, a decrease in the concentration of globulin binding sex hormones, total and free testosterone was found. Among workers exposed to electromagnetic fields of industrial frequency, a high prevalence of prostate pathologies was revealed.

Abstract 706: Efficacy evaluation of BR-9001, a SMEDDS formulation of 3,3’-diindolylmethane, as an inhibitor of preneoplastic and neoplastic lesion development in the prostate of Hi-Myc mice

Abstract Self-Microemulsifying Drug Delivery Systems (SMEDDS) can greatly increase the bioavailability of agents with limited solubility. Studies were performed to characterize the efficacy of BR-9001, a SMEDDS formulation of 3,3’-diindolylmethane (DIM), in preventing preneoplastic and neoplastic prostate lesion development in Hi-Myc mice. Beginning at age 8 weeks, groups of 105 male Hi-Myc mice received twice daily oral (gavage) administration of BR-9001 (BioResponse LLC, Boulder, CO) at DIM-equivalent doses of 0 (vehicle control), 200, or 400 mg/kg/dose. At ages 4 months, 5.5 months, and 7 months, cohorts of 35 mice/group were euthanized and necropsied; at each time point, tissues were collected from 25 mice/group for pathology; 5 mice/group for analysis of DIM levels in the plasma and prostate; and 5 mice/group for biomarker analysis. Prostate lesion development in pathology cohorts was determined by microscopic evaluation of step sections through the entire accessory sex gland block. Plasma and prostate levels of DIM were quantitated by LC-MS/MS; biomarkers were analyzed by RT-PCR. Administration of BR-9001 produced dose-related levels of DIM in the plasma and prostate at all time points. However, BR-9001 provided at most limited protection against prostate lesion development. Most lesions were identified in the lateral prostate (LP), where statistically significant reductions in incidences of murine prostatic intraepithelial neoplasias (mPIN) were seen in 4-month-old mice receiving the high dose of BR-9001 and in 5.5-month-old and 7-month-old mice receiving the low dose of BR-9001. Reductions in mPIN incidence in groups receiving BR-9001 were due to lower incidences of small mPIN lesions; incidences of large mPIN were significantly increased at 5.5 months in both groups receiving BR-9001. BR-9001 had no statistically significant effect on % occupancy of the LP by mPIN, the incidence of microinvasive mPIN in the LP, or cancer incidence in the LP. In the anterior prostate (AP), incidences of atypical hyperplasia were similar in all groups. However, at all necropsy time points, mice receiving the high dose of BR-9001 demonstrated significant increases in the incidences of moderate to marked AP atypia; these increases were accompanied by decreases in the incidence of mice with slight to moderate AP atypia. None of 22 potential molecular biomarkers were found to be clearly linked to development and progression of prostate lesions in Hi-Myc mice. Despite the presence of measurable concentrations of DIM in the plasma and prostate in mice in both treated groups at all time points, BR-9001 demonstrated equivocal efficacy in preventing the development of preneoplastic and neoplastic lesions in the Hi-Myc mouse model of prostate cancer. [Supported by NCI HHSN261201500042I/HHSN26100003.] Citation Format: Genoveva Murillo, Gina Qualter, Xinjian Peng, Miguel Muzzio, Elizabeth R. Glaze, Altaf Mohammed, Maarten C. Bosland, David L. McCormick. Efficacy evaluation of BR-9001, a SMEDDS formulation of 3,3’-diindolylmethane, as an inhibitor of preneoplastic and neoplastic lesion development in the prostate of Hi-Myc mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 706.

Microsurgical Anterolateral Thigh Flap for Reconstruction of Extremity Soft Tissue Defects in Pediatric Patients.

The anterolateral thigh flap is one of the most widely used flaps because it has the advantages of less damage to the donor site, no sacrifice of main blood vessels, and abundant soft tissue. However, the application of anterolateral thigh flap in children is relatively rare because of small blood vessels and rapid physiological changes. The aim of this study was to explore the effectiveness and characteristics of free anterolateral thigh flaps for the reconstruction of extremity soft tissue defects in pediatric patients. This study included 26 pediatric patients, with an average age of 6.7 years (range, 2-13 years). There were 5 cases of upper limb defects and 21 cases of lower limb defects, all of which were accompanied by exposed bones or tendons. The causes of defects included traffic injury in 9 cases, mechanical injury in 7 cases, collision injury in 4 cases, spoke injury in 3 cases, cicatricial contracture in 2 cases, and fibroma in 1 case. All defects were reconstructed with free anterolateral thigh flaps. Twenty-six anterolateral thigh flaps were harvested, including 15 fasciocutaneous flaps and 11 musculocutaneous flaps. The mean size of the flap was 73.4 cm 2 (range, 4 × 3 to 24 × 8 cm). The donor sites were sutured directly in 19 cases and underwent split-thickness skin grafting in 7 cases. There were 3 cases of vascular crisis, 3 cases of flap edge necrosis, 3 cases of infection, 1 case of pressure ulcer, and 1 case of dehiscence after surgery. Eleven patients had scar hyperplasia in the donor site. A total of 34 reoperations were performed, including 14 flap debulking, 7 debridement, 4 skin graft, 3 vascular crisis re-exploration, and 6 other procedures. Free anterolateral thigh flap was a safe and reliable option for reconstructing soft tissue defects of extremities in pediatric patients. Notably, the incidence of scar hyperplasia in the donor site and the possibility of reoperation in pediatric patients were higher than those in adult patients.

Mechanically reinforced biotubes for arterial replacement and arteriovenous grafting inspired by architectural engineering.

There is a lack in clinically-suitable vascular grafts. Biotubes, prepared using in vivo tissue engineering, show potential for vascular regeneration. However, their mechanical strength is typically poor. Inspired by architectural design of steel fiber reinforcement of concrete for tunnel construction, poly(ε-caprolactone) (PCL) fiber skeletons (PSs) were fabricated by melt-spinning and heat treatment. The PSs were subcutaneously embedded to induce the assembly of host cells and extracellular matrix to obtain PS-reinforced biotubes (PBs). Heat-treated medium-fiber-angle PB (hMPB) demonstrated superior performance when evaluated by in vitro mechanical testing and following implantation in rat abdominal artery replacement models. hMPBs were further evaluated in canine peripheral arterial replacement and sheep arteriovenous graft models. Overall, hMPB demonstrated appropriate mechanics, puncture resistance, rapid hemostasis, vascular regeneration, and long-term patency, without incidence of luminal expansion or intimal hyperplasia. These optimized hMPB properties show promise as an alternatives to autologous vessels in clinical applications.

383. Unscheduled bleeding on hormone replacement therapy: is it a cause for concern?

Introduction and aims of the study: Bleeding within the first 3-6months after commencing Hormone Replacement Therapy (HRT) requires reassurance but after 6 months warrants further assessment. Evidence suggests that the risk of endometrial hyperplasia/malignancy associated with sequential HRT over 3 years is around 2.7-5% and <1% with Continuous combined HRT.The aims of this study were to establish the incidence of hyperplasia/ malignancy in our population and to guide the referral system for such patients.

Atypical Hyperplasia Found Incidentally during Routine Breast Reduction Mammoplasty: Incidence and Management.

Background:Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) of the breast are premalignant lesions. Although the literature on ADH and ALH as a whole is well-developed, research on ADH and ALH incidentally discovered during breast reduction is less robust.Methods:In this study, 355 patients undergoing bilateral reduction mammoplasty at West Virginia University were retrospectively reviewed. A variety of demographic and clinicopathologic variables were collected for each patient, and the incidence of atypical hyperplasia was calculated. Four patients (1.13%) were found to have atypical hyperplasia, three ALH, and one ADH, which is within the range reported in the literature. For patients incidentally found to have atypical hyperplasia, an in-depth analysis of postoperative management was performed.Results:Of the four patients with atypical hyperplasia, three were referred to a cancer center, and one patient followed only with plastic surgery. The three patients who were referred to a cancer center saw a breast surgeon, whereas the patient followed only by plastic surgery did not. None of the four patients received anti-estrogen therapy, but each patient who followed with a cancer center was offered treatment and declined.Conclusions:As a relatively uncommon finding with complex management guidelines, atypical hyperplasia discovered on breast reduction should be referred to a cancer center for long-term follow-up and management when possible. Further research is needed to assess if the management of atypical hyperplasia discovered incidentally after routine reduction should mimic treatment of atypical hyperplasia found after biopsy for suspicion of malignancy.

The Efficacy and Safety of PD-1 Inhibitors Combined with Nab-Paclitaxel Plus Gemcitabine versus Nab-Paclitaxel Plus Gemcitabine in the First-Line Treatment of Advanced Pancreatic Cancer: A Retrospective Monocentric Study.

PurposeThe purpose of this study was to evaluate the efficacy and safety of PD-1 inhibitor combined with nab-paclitaxel plus gemcitabine (AG) chemotherapy versus AG chemotherapy in the first-line treatment of advanced pancreatic cancer.Patients and MethodsThis study included the application of AG treatment and PD-1 combined with AG treatment with advanced pancreatic ductal adenocarcinoma at the Affiliated Hospital of Qingdao University from September 2018 to July 2020. Clinical information and next-generation sequencing (NGS) reports of patients were collected to compare the effectiveness and adverse events of the two treatments and analyze the risk factors affecting the prognosis of patients.ResultsThere was no difference in PFS between the AG group and the PD-1+AG group (4.9 months vs 5.0 months, P = 0.154), but the difference in OS was statistically significant (9.3 months vs 12.1 months, P < 0.001). Compared with the AG group, the PD-1+AG group reduced the risk of death about 20.0% (HR = 0.203, 95% CI, 0.090−0.459, P < 0.001). In terms of safety, the incidence of hypothyroidism and reactive skin capillary hyperplasia in PD-1 + AG group was higher than that in AG group (P < 0.050) in grade 1–2; grade 3–4 adverse reactions were mainly hematologic AEs and abnormal liver function. The incidence of grade 3–4 adverse reactions in the two groups was 38.7% (95% CI, 20.5–56.9%) and 35.3% (95% CI, 10.0–60.6%), respectively. In addition, PD-1+ AG regimen improved the OS of patients with KRAS and TP53 co-mutations (8.0months vs 10.2 months, P = 0.004).ConclusionPD-1 inhibitors combined with AG chemotherapy have shown good efficacy and safety in the first-line treatment of patients with advanced pancreatic ductal adenocarcinoma. This regimen similarly improved OS in patients with KRAS and TP53 co-mutations.

Analysis of clinical features of myasthenia gravis complicated with hyperthyroidism.

Objectives:To investigate the clinical features of patients with myasthenia gravis complicated with and without hyperthyroidism.Methods:A total of 2083 patients with myasthenia gravis (MG) admitted in Center of Treatment of Myasthenia Gravis Hebei Province between January 2013 and July 2020 were retrospectively analyzed and divided into two groups: Group-A and Group-B, with 108 MG patients complicated with hyperthyroidism in Group-A and 1975 MG patients without thyroid disease in Group-B. The age of onset, gender, Osserman classification, acetylcholine receptor antibody and thymus status of the two groups were analyzed in the two groups. Independent-sample t test was used for intra-group comparison, and χ2 test was utilized for comparison of enumeration data. P<0.05 indicates a statistically significant difference.Results:The age of onset in Group-A was significantly lower than that in Group-B (p=0.000), the number of female patients was significantly higher than that in Group-B (p=0.037), and the level of Achrabs titer was significantly lower than that in Group-B (p=0.000). The incidence of thymoma in Group-A was significantly lower than that in Group-B (p=0.012), while the incidence of thymic hyperplasia was significantly higher than that in Group-B (p=0.000).Conclusion:Patients with MG complicated with hyperthyroidism are mainly female, with a lower age of onset, a lower level of acetylcholine receptor antibody, a lower incidence of thymoma, and a higher incidence of thymic hyperplasia. The clinical features of such patients are remarkably different from those of MG without thyroid disease.

Морфологическая характеристика фоновчых патологиеских процессов в слизистой оболочке, прилежащей к опухолевому узлу, при раке желудка кишечного типа

Introduction. Many fundamental and practical problems associated with pre-tumor changes in the stomach have not been sufficiently studied, which indicates the relevance of their study both at the stages of carcinoma development and in the mucous membrane adjacent to the tumor. The study aimed to detect the incidence, severity, and interconnections of background pathological processes in the gastric mucosa at different distances from the tumor node in gastric carcinomas of the intestinal type. Materials and methods. The surgical material of 43 patients with gastric carcinomas of the intestinal type after gastrectomy and resection of the stomach (626 tissue samples) from the tumor node and adjacent gastric mucosa at a distance from 1 cm to the resection lines was investigated. We assessed the frequency of occurrence, severity, and correlation relationships of the background pathological processes, i.e.,epithelial hyperplasia, intestinal metaplasia, and inflammatory and atrophic changes. Results. In the mucous membrane adjacent to the tumor, we revealed epithelial hyperplasia, intestinal metaplasia, and inflammatory and atrophic changes. There was a significant decrease in the number of cases of hyperplasia and intestinal metaplasia of the epithelium at the distance from the tumor. Moreover, we detected a decrease in the severity of all studied pathological processes. Positive moderate correlations were revealed between the parameters characterizing pathological processes at different distances from the tumor. Conclusion. The incidence and severity of background pathological processes, i.e., epithelial hyperplasia, intestinal metaplasia, and inflammatory and atrophic changes, detected in the mucous membrane in intestine type of gastric carcinoma decrease with distance from the tumor node. The results of the correlation analysis indicate the possibility of a functional relationship of such processes as epithelial hyperplasia, intestinal metaplasia and atrophy, as well as their important role in gastric carcinogenesis. The detection of these changes in the material obtained from the areas of the resection lines indicates the need for further study of their clinical significance. Keywords: gastric cancer, epithelial hyperplasia, intestinal metaplasia, inflammatory infiltration, atrophy

Focal Segmental Glomerulosclerosis Superimposed on Transplant Glomerulopathy: Implications for Graft Survival

Introduction: Transplant glomerulopathy (TG) is a morphological lesion resulting from chronic glomerular endothelium injury, and it is strongly associated with poor graft survival. TG coexisting with focal segmental glomerulosclerosis (FSGS) can be found in renal allograft biopsies, but few related studies are available. Methods: Consecutive kidney transplant recipients with biopsy-proven TG were studied retrospectively. Patients concomitant with FSGS were identified and compared with those without FSGS. The influence of FSGS on allograft outcomes was assessed using univariate and multivariate Cox regression models. Results: Of the 66 patients with TG, 40 (60.6%) had concomitant FSGS. TG patients with FSGS had higher proteinuria (median, 2.6 vs. 0.8 g/24 h, p < 0.001) and serum creatinine levels (median, 2.5 vs. 2.1 mg/dL, p = 0.04), lower serum albumin levels, higher chronic glomerulopathy (cg) score, larger glomerular tuft area, lower number of podocytes, and higher incidences of podocyte hyperplasia, pseudotubule formation, and diffuse foot process effacement than those without FSGS (all p < 0.05). The kidney allograft loss rate of patients with FSGS was higher than that of patients without FSGS (65.7% vs. 37.5%, p = 0.03). The presence of FSGS was independently associated with allograft loss in TG (hazard ratio (HR) = 3.42, 95% confidence interval (CI): 1.30–8.98, p = 0.01). Other independent predictors were proteinuria (HR = 1.18, 95% CI: 1.02–1.37, p = 0.02), estimated glomerular filtration rate (HR = 0.94, 95% CI: 0.91–0.97, p < 0.001), and panel reactive antibody (HR = 3.99, 95% CI: 1.14–13.99, p = 0.03). Moreover, FSGS (odds ratio (OR) = 4.39, 95% CI: 1.29–14.92, p = 0.02) and cg (OR = 5.36, 95% CI: 1.56–18.40, p = 0.01) were independent risk factors for proteinuria. Conclusion: In this cohort of patients with TG, the presence of FSGS was strongly associated with more severe clinicopathological features and worse allograft survival.

Long-term Follow-up of a Randomized Trial of Tacrolimus or Cyclosporine A Microemulsion in Children Post Liver Transplantation.

Background.The aim of this study was to determine the long-term efficacy and safety of tacrolimus (Tac) and cyclosporine immunosuppression in pediatric liver transplantation (LTx).Methods.One hundred fifty-six patients who had taken part in a multicenter, randomized, open, parallel study of Tac and corticosteroids versus cyclosporine A microemulsion (CyA-ME), corticosteroids, and azathioprine. Patients were assessed at regular intervals up to 14 y after LTx. Analysis was conducted descriptively.Results.In a long-term follow-up, there was a similar incidence of acute rejection (Tac versus CyA-ME, 5 versus 8) and graft loss (5 versus 10). There were 11 deaths in the cohort, which were from infectious complications/malignancy in the Tac group (n = 2/5) and from chronic rejection/liver failure in the CyA-ME group (n = 3/6). A similar incidence of Epstein-Barr virus and posttransplant lymphoproliferative disease was observed (8 versus 8, 3 versus 3). However, there was a greater incidence of cosmetic adverse events in the CyA-ME cohort, with higher incidences of hypertrichosis (8 versus 27) and gum hyperplasia (20 versus 6). Growth improved equally in both groups. Overall, 81% of patients randomized to Tac remained on Tac therapy at study end, compared with 31% of patients randomized to CyA-ME. Common reasons for switching from CyA-ME included steroid-resistant/acute rejection (n = 12/8) and cosmetic changes (n = 8).Conclusions.This study is the first prospective, observational follow-up study of pediatric patients randomized to Tac and CyA-ME to evaluate long-term outcomes. Our analysis was limited by the degree of switchover between the cohorts; however, there were fewer deaths from chronic rejection/liver failure and reduced adverse events with Tac. Long-term use of Tac and Tac combination therapy appears to be safe and effective immunosuppression for pediatric LTx recipients.

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17-β estradiol.

The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-β estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.

Abstract 2661: Role of NKX2-1 in thyroid neoplasms induced by iodine-deficiency and radiation

Abstract The multi-step carcinogenesis model, including the adenoma-carcinoma sequence, has been proposed in many cancers including those of colon, pancreas, and thyroid. BRAF activation is among the reported gene mutations important for thyroid carcinogenesis. However, the role of NKX2-1, a master regulator of thyroid development and function, in thyroid carcinogenesis remains elusive. In this study, we investigated the role of NKX2-1 in thyroid neoplasm formation using thyroid-specific Nkx2-1 conditional KO mice, Nkx2-1(fl/fl);TPO-Cre (cKO mice). Nkx2-1(fl/fl) (WT) and cKO mice were each allotted to four groups: 1. Control Diet, 2. Control Diet + Radiation, 3. Low Iodine Diet (LID), 4. LID + Radiation. Whole body gamma-irradiation (2 Gy, 3 times every other day) was carried out at 4-8 weeks of age, followed by switching the diet to either Control Diet or LID. Thyroid histology was examined at 1.1-1.3 years after the start of the diet. In both WT and cKO mice, iodine-deficiency, regardless of radiation, induced diffuse hyperplasia (goiter) in more than 50% of the mice, and increased the incidence of focal hyperplasia considered as a preneoplastic lesion. Adenoma formation was only observed in LID-treated mice regardless of radiation, suggesting that iodine-deficiency, but not radiation, is a key factor for mouse thyroid adenoma formation. The incidence of adenoma formation was significantly higher in cKO mice than WT mice in LID + Radiation group (14% for WT vs 52% for cKO, in progress). In addition, carcinoma formation was observed only in LID + Radiation-treated mice, suggesting that radiation is necessary to proceed from adenoma to cancer in thyroid carcinogenesis. Further, there is a tendency for higher incidence of carcinoma in LID + Radiation-treated cKO mice (4% for WT vs 11% for cKO, in progress). These results suggest that the loss of Nkx2-1 can promote adenoma formation induced by iodine-deficiency, and possibly facilitate carcinogenesis induced by LID + Radiation. In summary, our results suggest that NKX2-1 may function as a tumor suppressor in thyroid carcinogenesis. We are now trying to investigate the molecular mechanisms by which loss of NKX2-1 affects thyroid proliferation and facilitates neoplasm formation by examining the molecular profiles of mouse thyroids after LID and/or radiation treatment. Citation Format: Yo-Taro Shirai, Yoshinori Takizawa, Manabu Iwadate, Jorge Paiz, Shigetoshi Yokoyama, Masaaki Miyakoshi, Jerrold M. Ward, Shioko Kimura. Role of NKX2-1 in thyroid neoplasms induced by iodine-deficiency and radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2661.

CLINICAL-STATISTICAL STUDY ON THE FREQUENCY AND ETIOLOGICAL FACTORS OF GINGIVAL HYPERPLASIA

Introduction. Gum hyperplasia is clinically translated by growth in gum size, edema and bleeding (over-normal bags). The gum may be thin or fibrous, firm (in pseudotumor forms). In the absence of proper treatment, it will be associated with the bone resorption of the alveolar process, leading to different degrees of dental mobility. Purpose. Through this clinical-statistical study, we aim to analyze patients diagnosed with gum hyperplasia by age, gender, type of gum hyperplasia, etiology and localization. Also, by observing in surgical practice more and more cases of gum hyperplasia in patients with orthodontic treatment, through this clinical-statistical study, we aim to quantify the incidence of gingival hyperplasia in orthodontic treatments carriers and its distribution by gender. Material and method. The study is retrospective type, performed on 172 patients with the diagnosis of gum hyperplasia (K06.1), treated in the Oro-maxillo-facial surgery Clinic in Targu Mures, during Jan.2015-march 2021. Hypocrate concept 3 was used to access patient observation sheets. Results and discussions. Analyzing the descriptive statistical data of this retrospective clinical-statistical study, it is observed that the average age of the subjects is 58 years, the distribution by sex favors the female gender (59%), generally occurs in adults, has affinity for the right hemimaxilla, approx. 25% of patients have gingival hyperplastic lesions caused by orthodontic appliances and mobile/mobilizable prostheses. These types of lesions represent a ratio of 2/1 in favor of females, which indicates that the aesthetic requirements for females are much higher compared to males. Also, interpreting, from a medical point of view, the statistical conclusions of this study, we find that the patient's gender does not influence the location and appearance of the hyperplasic lesion, instead the age of the patients influences the occurrence of the hyperplastic lesion. Conclusion. Orthodontic therapy should be indicated after a correct evaluation of periodontal tissues, quantification of periodontal indices and detection of risk factors.

The Angiopoietin-like protein 4: a promising biomarker to distinguish brucella spondylitis from tuberculous spondylitis

ObjectiveThe Angiopoietin-like protein 4 (ANGPTL-4) has been proved to be a protein associated with multiple inflammatory responses. Nevertheless, whether it contributes to distinguishing brucella spondylitis (BS) from tuberculous spondylitis (TS) remains an open question. Our study aim is to explore the capability of the ANGPTL-4 to differentiating BS from TS.Materials and methodIn our study, 53 patients were screened out according to the criteria precisely in Xinjiang Medical University Affiliated of the First Hospital from 1 January, 2016, to 31 December, 2018. Their clinical data were retrospectively reviewed. All of them underwent pathological biopsy and magnetic resonance imaging examination. All the frozen tissue sections were stained for testing ANGPTL-4.ResultAmong the 53 patients, BS had 26 patients, and TS had 27 patients. There was no significant difference between the baseline (P = 0.682) between the two groups. The positive rate of ANGPTL-4 in TS patients (24/27, 88.89%) was higher than that in BS patients (17/26, 65.83%) (P < 0.05). The incidence of microangiopathy and fibrous connective tissue hyperplasia in patients with BS was distinctly higher than those in the TS (P = 0.001, P = 0.008, respectively). Patients of TS frequently presented more granuloma, caseous necrosis, epithelial-like reaction, interleukin 6 (IL-6), and C-reactive protein (CRP) than those of BS.ConclusionOur study provided novel insights into distinguishing BS from TS using the ANGPTL-4 combining with histopathology, which may become new supporting evidence.Key Points• Brucella spondylitis and tuberculous spondylitis are a significant public health concern and even have prolonged damage, contributing to severe health and economic outcomes in Xinjiang of China.• The granuloma, caseous necrosis, epithelioid reaction, microangiosis, and fibrous connective tissue of pathological tissue might play a critical significance for distinguishing brucella spondylitis from tuberculous spondylitis patients.• ANGPLT-4 may become new supporting evidence identify brucella spondylitis and tuberculous spondylitis which is implicated in inflammation angiogenesis-related disorders.

Unlikely Coexistence of Sporadic Pheochromocytoma and Bilateral Macronodular Adrenal Hyperplasia: A Challenge to Manage

Background: The incidence of bilateral macronodular adrenal hyperplasia (BMAH) is unknown, but growing in an era of increased utilization of imaging. Coexistence of BMAH and pheochromocytoma has not previously been reported.Clinical Case: A 63-year man presented with enlarging left chest-wall mass found to have a poorly differentiated sarcoma. Staging PET/CT identified a hypermetabolic 2.0 cm left adrenal nodule with SVU of 16.6 concerning for metastasis. Hormonal evaluation included dexamethasone suppression test with 7AM serum cortisol of 24.7 ug/dL (<1.8 ug/dL) without dexamethasone level, serum ACTH <5.0 pg/mL (7.2–63 pg/mL), plasma metanephrine of <0.20 nmol/L (0–0.49 nmol/L), and plasma normetanephrine of 0.76 nmol/L (0.00–0.89 nmol/L). Biopsy of this left adrenal nodule was consistent with pheochromocytoma. By history, he lacked any classical symptoms of pheochromocytoma. Repeat testing demonstrated only slight elevations in normetanephrine (1.3 nmol/L and 1.2 nmol/L); he remains asymptomatic at follow-up 4 months later. However, history and exam revealed central obesity, thin skin, type 2 diabetes mellitus on insulin, and hypertension controlled on three agents concerning for Cushing’s. Repeat evaluation showed AM cortisol of 17.9 ug/dL (<1.8 mcg/dL) with dexamethasone level of 917 ng/dL (180–550 ng/dL), ACTH of 6.4 pg/mL with concordant cortisol of 23.1 ug/dL, and 24 hour urine collection with 0.98 L volume, creatinine of 0.58 g/24h (1–2 g/24hr), and urinary free cortisol of 67 ug/24h (3.5–45) altogether suggesting ACTH-independent hypercortisolism. On review of CT abdomen, he has bilateral adrenal nodules measuring >1cm with bilateral gland enlargement consistent with BMAH. Resection of his left adrenal gland was not pursued due to cormorbidities as well as biochemically-silent nature of his pheochromocytoma. To manage his hypercortisolism, he was recently initiated on osilodrostat after completing radiation therapy for his chest-wall sarcoma.Conclusion: This is the first case demonstrating clinical, biochemical, and imaging results consistent with bilateral macronodular adrenal hyperplasia and hypercortisolism also found to have a clinically and biochemically silent, biopsy proven pheochromocytoma. This is also a unique use of osilodrostat to manage BMAH.

Incidence of Neo-Intimal Hyperplasia in Anterior Circulation Aneurysms Following Pipeline Flow Diversion

IntroductionFlow diversion of the distal anterior circulation cerebral vasculature may be used for management of wide necked aneurysms not amenable to other endovascular approaches. Follow-up angiography sometimes demonstrates neo-intimal hyperplasia within or adjacent to the stent, however there is limited evidence in the literature examining the incidence in MCA and ACA aneurysms. We present our experience with flow diversion of the distal vasculature and evaluate the incidence of neo-intimal hyperplasia. Materials and methodsRetrospective review of patients who underwent Pipeline embolization device (PED) treatment for ruptured and unruptured anterior circulation aneurysms. ResultsA total of 251 anterior circulation aneurysms were treated by pipeline flow diversion, of which 175 were ICA aneurysms, 14 were ACA aneurysms and 18 were MCA aneurysms. 6-month follow-up angiography was available in 207 patients. The incidence of neo-intimal hyperplasia was 15.9%, 21.4%, and 61.1% in ICA, ACA, and MCA aneurysms, respectively. MCA-territory aneurysms developed neo-intimal hyperplasia at a significantly higher rate than aneurysms in other vessel territories. Rates of aneurysmal occlusion did not significantly differ from those patients who did not exhibit intimal hyperplasia on follow-up angiography. ConclusionIn our experience, flow diversion of distal wide-necked MCA and ACA aneurysms is a safe and effective treatment strategy. The presence of neo-intimal hyperplasia at 6-month angiography is typically clinically asymptomatic. Given the statistically higher rate of neo-intimal hyperplasia in MCA aneurysms at 6-month angiography, we propose delaying initial follow-up angiography to 12-months and maintaining dual antiplatelet therapy during that time.

Prevention of mammary carcinogenesis in MMTV-neu mice by targeting RLIP.

The overexpression and amplification of the protooncogene neu (ERBB2) play an important role in the development of aggressive breast cancer (BC) in humans. Ral-interacting protein (RLIP), a modular stress-response protein with pleiotropic functions, is overexpressed in several types of cancer, including BC. Here, we show that blocking RLIP attenuates the deleterious effects caused by the loss of the tumor suppressor p53 and inhibits the growth of human BC both in vitro and in vivo in MMTV-neu mice. In addition, we show that treatment with the diet-derived, RLIP-targeting chemotherapeutic 2'-hydroxyflavanone (2HF), alone or in combination with RLIP-specific antisense RNA or antibodies, significantly reduced the cumulative incidence and/or burden of mammary hyperplasia and carcinoma in MMTV-neu mice. 2HF treatment correlated with reduced tumor cell proliferation and increased apoptosis, and the average number of Ki67-positive (proliferating) cells was significantly lower in the tumors of 2HF-treated mice than in the tumors of control mice. Furthermore, targeting RLIP also resulted in the overexpression of E-cadherin and the infiltration of CD3+ T cells into mammary tumors. Taken together, these results underscore the translational potential of RLIP-targeting agents and provide a strong rationale to validate them in the clinic.

CLINICAL, MORPHOLOGICAL, AND EPIDEMIOLOGICAL CHARACTERISTICS OF ENDOMETRIAL HYPERPLASTIC PROCESSES IN SUMY REGION

Endometrial hyperplastic processes take an important place among the gynecological diseases in women of various ages and are one of the most common reasons for admission at inpatient gynecology departments. The urgency of the pathology is due to the significant prevalence of endometrial hyperplastic processes, high incidence of malignancy, prolonged relapsing course, and decreased reproductive function, since these diseases are one of the most common causes of infertility in women of childbearing age. The statistics related to the incidence of endometrial hyperplastic processes in Ukraine is not available. An analysis of case histories and medical records showed that in 40% of cases, endometrial hyperplastic processes were asymptomatic. In 60% of cases, the clinical manifestations of endometrial hyperplastic processes were menstrual disorders, such as dysmenorrhea, oligomenorrhea, menorrhagia, and metrorrhagia. In 30% of cases, endometrial hyperplastic processes were recurrent. The most common concomitant pathologies of the pelvic organs were uterine leiomyoma and endometriosis; the most common concomitant extragenital diseases were hypertension and obesity. Our study and data analysis showed that there is an increasing trend in the incidence of endometrial hyperplastic processes in Sumy region in 2011–2020. The maximum incidence was in 2016. A correlation was found between hyperplasia incidence and age. Thus, the largest number of non-atypical and atypical endometrial hyperplasia cases was observed in women aged 45–55 years. The lowest number of non-atypical endometrial hyperplasia cases was registered in women aged 66+, while atypical hyperplasia cases – in women under 30 years of age. Glandular polyps of the endometrium were most often diagnosed at the age of 31–44; the lowest number of these was found in women over 66 years. Most glandular-fibrous endometrial polyps were observed in women aged 45–55 years, while women under 30 presented with the fewest cases. Fibrous endometrial polyps were most common in older age groups – 66+; the lowest number of such endometrial polyps was found in women under 30 years. We attributed the decreased incidence of endometrial hyperplastic processes in 2020 to the quarantine measures introduced, which, as a consequence, led to the decreased number of diagnosed cases, since they are often asymptomatic.