Clinical Presentation of Paraovarian Cysts.

BACKGROUND: A paraovarian cyst (POC) is located between the ovary and the fallopian tube. In many cases POCs are diagnosed and managed as ovarian cysts. But since POC are a distinct entity in their clinical presentation and surgical intervention, they should be better defined. OBJECTIVES: To describe the clinical perioperative and operative characteristics of patients with POCs in order to improve pre-operative diagnosis and management. METHODS: A retrospective cohort study of patients with an operative diagnosis of POC between 2007 and 2019 in a single university-affiliated tertiary care medical center was included. Demographic characteristics as well as symptoms, sonographic appearance, surgery findings, and histology results were retrieved from electronic medical records. RESULTS: During the study period 114 patients were surgically diagnosed with POC, 57.9% were in their reproductive years and 24.6% were adolescents. Most presented with abdominal pain (77.2%). Preoperative sonographic exams accurately diagnosed POC in only 44.7% of cases, and 50.9% underwent surgery due to suspected torsion, which was surgically confirmed in 70.7% of cases. Among women with confirmed torsion, 28.9% involved the fallopian tube without involvement of the ipsilateral ovary. Histology results showed benign cysts in all cases, except two, with a pathological diagnosis of serous borderline tumor. CONCLUSIONS: POC should always be part of the differential diagnosis of women presenting with lower abdominal pain and sonographic evidence of adnexal cysts. If POC is suspected there should be a high level of suspicion for adnexal torsion and low threshold for surgical intervention, especially in adolescent, population who are prone to torsion.

Association between thyroid cysts and hypertension by atherosclerosis status: a cross-sectional study.

Our recent studies indicate that thyroid cysts have clinical implications. Thyroid cysts could have a positive effect on the supply of thyroid hormones. Both hyperthyroidism and hypothyroidism cause hypertension. Hypothyroidism, but not hyperthyroidism, is a risk factor for atherosclerosis. Therefore, thyroid cysts could be associated with hypertension, and atherosclerosis might influence the association between thyroid cysts and hypertension. To evaluate the clinical significance of thyroid cysts, a cross-sectional study was conducted with 1801 Japanese aged 40-74 years. Thyroid cysts were significantly positively associated with hypertension in participants without atherosclerosis. However, there was a significant inverse association in those with atherosclerosis. The potential confounding factor adjusted odd ratios and 95% confidence intervals (95% CIs) were 1.49 (95% CI 1.17-1.90) for participants without atherosclerosis and 0.49 (95% CI 0.24-0.98) for those with atherosclerosis. The present study demonstrates that thyroid cysts have clinical implications because thyroid cysts support thyroid hormone activity. Our findings provide sufficient evidence to develop a risk assessment for hypertension for the general population, even though further research is required.

Response patterns in adventitial layer of Echinococcus granulosus sensu stricto cysts from naturally infected cattle and sheep.

Cystic echinococcosis is a zoonotic disease caused by the metacestode of Echinococcus granulosus sensu lato. The disease is characterized by the development of cystic structures inside viscera of the intermediate host, mainly liver and lungs. These cysts are formed by three layers: germinal, laminated, and adventitial layer, the latter being the local host immune response. Metacestodes that develop protoscoleces, the infective stage to the definitive host, are termed fertile, whereas cysts that do not produce protoscoleces are termed non-fertile. Sheep usually harbor fertile cysts while cattle usually harbor non-fertile cysts. Adventitial layers with fibrotic resolution are associated to fertile cysts, whereas a granulomatous reaction is associated with non-fertile cysts. The aim of this study was to analyze cellular distribution in the adventitial layer of fertile and non-fertile E. granulosus sensu stricto cysts found in liver and lungs of cattle and sheep. A total of 418 cysts were analyzed, 203 from cattle (8 fertile and 195 non-fertile) and 215 from sheep (64 fertile and 151 non-fertile). Fertile cysts from cattle showed mixed patterns of response, with fibrotic resolution and presence of granulomatous response in direct contact with the laminated layer, while sheep fertile cysts always displayed fibrotic resolution next to the laminated layer. Cattle non-fertile cysts display a granulomatous reaction in direct contact with the laminated layer, whereas sheep non-fertile cysts display a granulomatous reaction, but in direct contact with the fibrotic resolution. This shows that cattle and sheep cystic echinococcosis cysts have distinct local immune response patterns, which are associated to metacestode fertility.

Cyst formation in proximal renal tubules caused by dysfunction of the microtubule minus-end regulator CAMSAP3.

Epithelial cells organize an ordered array of non-centrosomal microtubules, the minus ends of which are regulated by CAMSAP3. The role of these microtubules in epithelial functions, however, is poorly understood. Here, we show that the kidneys of mice in which Camsap3 is mutated develop cysts at the proximal convoluted tubules (PCTs). PCTs were severely dilated in the mutant kidneys, and they also exhibited enhanced cell proliferation. In these PCTs, epithelial cells became flattened along with perturbation of microtubule arrays as well as of certain subcellular structures such as interdigitating basal processes. Furthermore, YAP and PIEZO1, which are known as mechanosensitive regulators for cell shaping and proliferation, were activated in these mutant PCT cells. These observations suggest that CAMSAP3-mediated microtubule networks are important for maintaining the proper mechanical properties of PCT cells, and its loss triggers cell deformation and proliferation via activation of mechanosensors, resulting in the dilation of PCTs.

Ultra-Small Lung Cysts Impair Diffusion Without Obstructing Air Flow in Lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare lung disease found primarily in women of childbearing age, characterized by the formation of air-filled cysts, which may be associated with reductions in lung function. An experimental, regional ultra-high resolution CT scan identified an additional volume of cysts relative to standard chest CT imaging, which consisted primarily of ultra-small cysts. RESEARCH QUESTION: What is the impact of these ultra-small cysts on the pulmonary function of patients with LAM? STUDY DESIGN AND METHODS: A group of 103 patients with LAM received pulmonary function tests and a CT examination in the same visit. Cyst score, the percentage lung volume occupied by cysts, was measured by using commercial software approved by the US Food and Drug Administration. The association between cyst scores and pulmonary function tests of diffusing capacity of the lungs for carbon monoxide (Dlco) (% predicted), FEV1 (% predicted), and FEV1/FVC (% predicted) was assessed with statistical analysis adjusted for demographic variables. The distributions of average cyst size and ultra-small cyst fraction among the patients were evaluated. RESULTS: The additional cyst volume identified by the experimental, higher resolution scan consisted of cysts of 2.2 ± 0.8 mm diameter on average and are thus labeled the "ultra-small cyst fraction." It accounted for 27.9 ± 19.0% of the total cyst volume among the patients. The resulting adjusted, whole-lung cyst scores better explained the variance of Dlco (P < .001 adjusted for multiple comparisons) but not FEV1 and FEV1/FVC (P = 1.00). The ultra-small cyst fraction contributed to the reduction in Dlco (P < .001) but not to FEV1 and FEV1/FVC (P = .760 and .575, respectively). The ultra-small cyst fraction and average cyst size were correlated with cyst burden, FEV1, and FEV1/FVC but less with Dlco. INTERPRETATION: The ultra-small cysts primarily contributed to the reduction in Dlco, with minimal effects on FEV1 and FEV1/FVC. Patients with lower cyst burden and better FEV1 and FEV1/FVC tended to have smaller average cyst size and higher ultra-small cyst fraction. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00001465; URL: www.clinicaltrials.gov.

LINEZOLID-INDUCED MITOCHONDRIAL TOXICITY PRESENTING AS RETINAL NERVE FIBER LAYER MICROCYSTS AND OPTIC AND PERIPHERAL NEUROPATHY IN A PATIENT WITH CHRONIC GRANULOMATOUS DISEASE.

PURPOSE: To report a case with unique changes in the retinal nerve fiber layer observed on optical coherence tomography in a 22-year-old patient on chronic linezolid therapy for recurrent pyogenic liver abscesses with underlying chronic granulomatous disease. METHODS: History and clinical examination, laboratory evaluation, fluorescein angiography, and optical coherence tomography. RESULTS: The patient presented with best-corrected visual acuity of 20/200 in the right eye and 20/125 in the left eye. He had moderate optic disk edema and superotemporal field defects bilaterally. Swept-source optical coherence tomography revealed the presence of retinal nerve fiber layer microcystic spaces. Laboratory tests showed no positive findings except for an elevated lactic acid level. Linezolid-induced optic neuropathy was suspected, and the drug was discontinued. Six weeks after termination of oral linezolid therapy, the optic disk edema and the microcystic spaces in the retinal nerve fiber layer resolved, and the best-corrected visual acuity improved to 20/50 in the right and 20/40 in the left eye, respectively. CONCLUSION: Linezolid is a widely used antibiotic with broad-spectrum action. However, chronic use can lead to mitochondrial toxicity that may have protean manifestations. Ocular examination, particularly of the optic nerve and nerve fiber layer using multimodal imaging, is critical in diagnosing such toxicity.

Vascular risk factors for optical coherence tomography-detected macular cysts: The Maastricht Study.

PURPOSE: To investigate whether higher blood pressure and greater arterial stiffness are associated with the presence of macular cysts and whether this association is already present in the absence of micro-aneurysms in individuals with and without type 2 diabetes. METHODS: Using spectral domain optical coherence tomography (OCT), we performed a macular volume scan in 2647 individuals (mean age 60 ± 8 years, 50% men, 27% type 2 diabetes). The association between macular cysts and 24-hour systolic and diastolic blood pressure, pulse pressure, mean arterial blood pressure, carotid-femoral pulse wave velocity and carotid distensibility was assessed by use of logistic regression. RESULTS: Twenty-four hours systolic blood pressure was associated with the presence of macular cysts [OR = 1.03 (95% CI 1.00-1.05) per 1 mmHg, p = 0.03]. 24 hr pulse pressure [OR = 1.61 (95% CI 1.11-2.34) per 10 mmHg, p = 0.01] and carotid-femoral pulse wave velocity [OR = 1.16 (95% CI 1.02-1.32) per 1 m/s, p = 0.02] were associated with macular cysts, while carotid distensibility was not [OR = 1.03 (95% CI 0.96-1.11) per 1.0*10-3 /kPa, p = 0.45]. Associations were similar in individuals with and without type 2 diabetes and were already present in the absence of micro-aneurysms. CONCLUSION: Twenty-four hours systolic blood pressure, 24 hr pulse pressure and carotid-femoral pulse wave velocity are associated with the presence of OCT-detected macular cysts in individuals with and without type 2 diabetes, even in the absence of micro-aneurysms. Therefore, blood pressure and aortic stiffness are potential factors contributing to macular cysts.

High Activation of the AKT Pathway in Human Multicystic Renal Dysplasia.

Multicystic renal dysplasia is a congenital cystic anomaly of the kidney caused by abnormal metanephric differentiation with immature tubules. It is surrounded by mesenchymal collars and islands of immature mesenchyma present between the cysts. The PI3K-AKT-mTOR signaling pathway is a key regulator involved in cell growth, proliferation, motility, survival, and apoptosis. Activation of the PI3K-AKT-mTOR pathway results in the survival and proliferation of tumor cells in many cancers. The aim of this study is to analyze the topographic expression of phospho-AKT, phospho-mTOR, and phospho-70S6K in renal development and in the multicystic dysplastic kidney (MCDK). A total of 17 fetal kidneys of development age from the first to the third trimester and 13 cases of pathological kidneys with MCDK were analyzed by immunohistochemistry in order to evaluate the expression of phospho-AKT (S473), phospho-mTOR, and phospho-70S6K. Phospho-AKT and phospho-mTOR were expressed early in renal development and in an identical manner for every structure derived from the ureteric bud, such as collecting ducts and urothelium. Phospho-p70S6K was expressed early in the urothelium and in glomerular mesangial cells. Later, their expressions differed according to the needs of cell proliferation and differentiation over time by becoming more selective. In MCDK, phospho-AKT, phospho-mTOR, and phospho-70S6K have the same profile: a high cytoplasmic expression in cystic epithelium, loose mesenchyma, and primitive tubes. This study demonstrates the essential and specific role of the PI3K-AKT-mTOR pathway in the formation of cysts in multicystic renal dysplasia.

Combined Preparation of Human Olfactory Ensheathing Cells in the Therapy of Post-Traumatic Cysts of the Spinal Cord.

In experiments on rats, co-transplantation of olfactory ensheathing cells of the human olfactory mucosa and neural stem/progenitor cells from the same source into post-traumatic cysts of the spinal cord led to improvement of the motor activity of the hind limbs and reduced the size of the cysts in some animals by 4-12%. The transplantation of a combination of the olfactory mucosa cells is effective and can be used in preclinical trials for the treatment of spinal cord injuries.

Epineurial Pseudocyst of the Intratemporal Facial Nerve: A Case Series Study.

OBJECTIVES: The goal of this case series was to describe the clinical and radiological characteristics of epineurial pseudocysts of the intratemporal facial nerve (EPIFs) and to discuss the relevance in clinical practice. MATERIALS AND METHODS: A retrospective case series of 10 consecutive patients with EPIFs identified through computed tomography (CT), between 2009 and 2018. Morphological characteristics, coexisting pathology, facial nerve function, and evolution over time were analyzed. RESULTS: A unilateral EPIF was found in 5 patients (50%) and a bilateral EPIF was found in the other 5 (50%). The largest dimensions were observed in the coronal plane, with an average craniocaudal length of 6.0 mm (range, 3-9 mm). None of the patients presented with facial nerve dysfunction. Growth could not be observed in any of the patients. In 5 cases (33.3%), CT imaging showed a reduced transmastoid access to the facial recess caused by the EPIF. CONCLUSION: All EPIFs in this study were incidental findings. Facial nerve function was normal in all patients. Knowledge of EPIFs is important to perform safe cholesteatoma and cochlear implant surgery and to prevent unnecessary follow-up imaging.

Retrorectal cyst: proteus in the backyard-case series and literature review.

Retrorectal cysts are cystic lesions located in the retrorectal space and are a distinct subset of retrorectal tumours, which are often misdiagnosed due to their rarity and mimicry of symptoms caused by common diseases. We have described the presentation and management of four patients who were diagnosed with retrorectal cysts from a 10-year retrospective chart review at our institute, a tertiary care centre. In middle-aged women, the following should raise suspicion of retrorectal cyst: gastrointestinal or urinary obstructive features, mass or fullness palpable on the posterior wall on digital rectal examination, presacral dimple, perianal fistula and/or recurrent disease. Such features should prompt an MRI evaluation of the pelvis for definitive diagnosis.

Magentic Resonance Imaging Evaluation of Regional Lung Vts in Severe Neonatal Bronchopulmonary Dysplasia.

Rationale: Bronchopulmonary dysplasia is a heterogeneous lung disease characterized by regions of cysts and fibrosis, but methods for evaluating lung function are limited to whole lung rather than specific regions of interest.Objectives: Respiratory-gated, ultrashort echo time magnetic resonance imaging was used to test the hypothesis that cystic regions of the lung will exhibit a quantifiable Vt that will correlate with ventilator settings and clinical outcomes.Methods: Magnetic resonance images of 17 nonsedated, quiet-breathing infants with severe bronchopulmonary dysplasia were reconstructed into end-inspiration and end-expiration images. Cysts were identified and measured by using density threshold combined with manual identification and segmentation. Regional Vts were calculated by subtracting end-expiration from end-inspiration volumes in total lung, noncystic lung, total-cystic lung, and individual large cysts.Measurements and Main Results: Cystic lung areas averaged larger Vts than noncystic lung when normalized by volume (0.8 ml Vt/ml lung vs. 0.1 ml Vt/ml lung, P < 0.002). Cyst Vt correlates with cyst size (P = 0.012 for total lung cyst and P < 0.002 for large cysts), although there was variability between individual cyst Vt, with 22% of cysts demonstrating negative Vt. Peak inspiratory pressure positively correlated with total lung Vt (P = 0.027) and noncystic Vt (P = 0.015) but not total lung cyst Vt (P = 0.8). Inspiratory time and respiratory rate did not improve Vt of any analyzed lung region.Conclusions: Cystic lung has greater normalized Vt when compared with noncystic lung. Ventilator pressure increases noncystic lung Vt, but inspiratory time does not correlate with Vt of normal or cystic lung.

New insights into targeting hepatic cystogenesis in autosomal dominant polycystic liver and kidney disease.

Introduction: Polycystic liver disease (PLD) is a rare disease defined by the growth of hepatic cysts and occurs either isolated or as an extrarenal manifestation of polycystic kidney disease. While surgery has been the mainstay in treatment of symptomatic PLD, recently discovered regulatory mechanisms affecting hepatic cystogenesis provide potential new therapies to reduce hepatic cyst burden.Areas covered: This review summarizes intracellular pathways and therapeutic targets involved in hepatic cystogenesis. While drugs that target cAMP, mTOR and bile acids were evaluated in clinical trials, investigation in autophagy, Wnt and miRNA signaling pathways are still in the pre-clinical phase. Recent epidemiological data present female hormones as a promising therapeutic target. Additionally, therapeutic advances in renal cystogenesis are reviewed for their potential application in treatment of hepatic cysts.Expert opinion: Further elucidation of the pathophysiology of hepatic cystogenesis is needed to provide additional targets and improve the efficacy of current treatments. The most promising therapeutic target in PLD is the female hormone pathway, given the increased severity in women and the harmful effects of exogenous estrogens. In addition, combining current pharmaceutical and surgical therapies can lead to improved outcomes. Lastly, the rarity of PLD creates the need to share expertise internationally.

Life Cycle and Lensing of a Macular Microcyst.

INTRODUCTION: Microscopic details about retinal conditions can provide insight into pathological mechanisms, but these are ordinarily difficult to obtain in situ. We demonstrate how high-resolution imaging and optical modeling can be combined to reveal morphological features of a macular microcyst, offering insight into microcyst formation. OBJECTIVE: To use adaptive optics scanning laser ophthalmoscopic (AOSLO) images to track a transient retinal microcyst and derive its 3-dimensional shape. METHODS: A series of AOSLO images were gathered before, during, and after a transient retinal microcyst developed in an otherwise normal healthy 26-year-old male subject. Optical coherence tomography (OCT) independently confirmed the location of the microcyst. Optical modeling was conducted to quantify the lensing effect of the optically uniform microcyst and to determine its 3-dimensional shape. Increment threshold sensitivity, targeted within and around the microcyst, was tested to see if cone photoreceptor function was affected. RESULTS: A transient microcyst appeared as a 50 µm diameter circle in AOSLO images, localized to the inner nuclear layer. Based on image distortion of the photoreceptor mosaic, optical modeling suggests that the microcyst had the shape of an aspherical lens, distinguishable from a spherical, cylindrical, or elliptical shape, indicative of an edematous expansion of laminar tissue. The microcyst spontaneously resolved about 30 days after first discovery. No changes to the photoreceptor mosaic ensued from the presence of the microcyst, and functional testing of the photoreceptors below the microcyst indicated no loss of light sensitivity. CONCLUSIONS: Microcysts have been associated with numerous subtypes of optic nerve degeneration, including multiple sclerosis and various inherited neuropathies. This microcyst appeared in a healthy individual and resolved without intervention. Lensing effects can be used to determine microcyst shape, which cannot be resolved by OCT imaging, and to help infer etiology.

A Functional Parathyroid Cyst from the Hemorrhagic Degeneration of a Parathyroid Adenoma.

A 77-year-old man with a history of hypertension, prostate hyperplasia, and urolithiasis was admitted for acute kidney injury caused by hypercalcemia. Neck ultrasonography showed a large cyst adjacent to the right lower thyroid lobe. Although a 99mtechnetium sestamibi scan was negative, an extremely high intracystic intact parathyroid hormone level suggested that the cyst had a parathyroid origin and that a functional parathyroid cyst was present. Immunohistochemical staining for the calcium-sensing receptor (CaSR) after right lower parathyroidectomy revealed CaSR-positive cells lining the cyst, indicating that the functional parathyroid cyst had originated from the hemorrhagic degeneration of a parathyroid adenoma.

In vitro 3D phenotypic drug screen identifies celastrol as an effective in vivo inhibitor of polycystic kidney disease.

Polycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative treatments. The signaling rewiring in PKD that drives cyst formation is highly complex and not fully understood. As a consequence, the effects of drugs are sometimes difficult to predict. We previously established a high throughput microscopy phenotypic screening method for quantitative assessment of renal cyst growth. Here, we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules, including approved drugs. We identified 81 active molecules that inhibit cyst growth. Multi-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological properties. Celastrol, a triterpenoid from Tripterygium Wilfordii, was identified as a potent inhibitor of cyst growth in vitro. In an in vivo iKspCre-Pkd1lox,lox mouse model for PKD, celastrol inhibited the growth of renal cysts and maintained kidney function.