Association between polymorphism of beta3-adrenoceptor gene and overactive bladder.

AIMS: In human urinary bladder, beta3-ARs play an important role in promoting detrusor relaxation during the storage phase of the micturition cycle. The present study investigated whether a Trp64Arg polymorphism of the gene encoding the beta3-AR is associated with overactive bladder (OAB) syndrome. METHODS: This study involved 100 women with OAB and 101 healthy control women without OAB. Hair root samples were obtained from all subjects and used for beta3-AR gene analysis. Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis was performed to analyze a polymorphism in the gene of Trp64Arg. RESULTS: The overall frequency of the 64Arg variant (heterozygous plus homozygous) in OAB patients was 47% and significantly higher than the frequency of 22.8% found in non-OAB control women. Within OAB patients, numbers of micturitions per day, urgency episodes per day, and urgency incontinence episodes per day in the 64Arg variant carriers were not significantly different from those in the normal gene carriers. CONCLUSIONS: This study shows that the Trp64Arg polymorphism in the beta3-AR gene is weakly but significantly associated with OAB syndrome.

The effect of atherosclerosis-induced chronic bladder ischemia on bladder function in the rat.

AIMS: To develop a rat model of atherosclerosis-induced chronic bladder ischemia and investigate the effect of chronic bladder ischemia on voiding behavior and bladder function. METHODS: Adult male rats were divided into three groups. The arterial injury (AI) group underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet. The sham group underwent sham operation and received a 2% cholesterol diet. The control group received a regular diet. After 8 weeks, a metabolic cage study and cystometry were performed without anesthesia. Bladder blood flow was measured using a laser Doppler blood flowmeter. Histological examination of the iliac arteries and the bladder was performed. The bladder was also processed for immunohistochemical staining of oxidative stress markers. RESULTS: The metabolic cage study showed that in the AI group, voiding frequency significantly increased while voided volume significantly decreased. Cystometry showed that the frequency of reflex bladder contractions was significantly higher in the AI group. Filling-induced decrease in bladder blood flow was the greatest in the AI group. Histological study showed that in the AI group alone, atherosclerotic occlusion occurred in the iliac arteries as well as in the downstream bladder microvessels. Oxidative stress marker positive cells were more prevalent in the AI bladder than in the other bladders. CONCLUSIONS: Combined with a high-cholesterol diet, endothelial injury of iliac arteries induced arterial occlusive disease in the downstream vessels and consequent bladder ischemia in rats. This model of chronic bladder ischemia showed detrusor overactivity manifested as an increase in voiding frequency.

The Association between Severity of Atherosclerosis and Lower Urinary Tract Function in Male Patients with Lower Urinary Tract Symptoms.

OBJECTIVES: The present study was undertaken to investigate the association between the severity of atherosclerosis and lower urinary tract function in male patients with lower urinary tract symptoms. METHODS: Male patients with lower urinary tract symptoms were examined with routine investigation. The severity of atherosclerosis was assessed by ultrasound examination of carotid artery. Patients were divided into two groups: control group and atherosclerosis group. The voiding function and storage function were compared between the two groups. RESULTS: A total of 50 men (69.9 ± 9.1 years [mean ± standard deviation]) entered the study. There was no significant difference in age distribution (control group: 68.7 ± 7.6 years; atherosclerosis group: 72.5 ± 9.7 years) and prostate volume (control group: 26.5 ± 17.3 mL; atherosclerosis group: 22.2 ± 11.0 mL) between the two groups. In the voiding parameters, maximum flow rate in the atherosclerosis group (13.4 ± 5.5 mL/s, P < 0.05) was significantly lower than that in the control group (16.7 ± 7.7 mL/s). Postvoid residual urine volume showed no significant difference between the two groups. In the storage parameters, voided volume was significantly reduced in the atherosclerosis group (161.8 ± 46 mL, P < 0.05), as compared to control group (201.1 ± 78 mL). Moreover, daytime frequency was 7.13 ± 3.02 times in the control group, and significantly higher in the atherosclerosis group (8.75 ± 2.50 times, P < 0.05). CONCLUSION: Development of atherosclerosis impairs both voiding and storage function independently of age, suggesting atherosclerosis leads to lower urinary dysfunction.

Effect of long-term prazosin and yohimbine administration on c-Fos expression in spinal neurons: inhibitory effect of alpha-1 and alpha-2 adrenoceptors on afferents from the lower urinary tract.

INTRODUCTION: To investigate the effects of long-term administration of the α(1)-adrenoceptor antagonist prazosin and the α(2)-adrenoceptor antagonist yohimbine on afferent inputs from the lower urinary tract by evaluating c-Fos expression in the spinal cord. MATERIALS AND METHODS: Prazosin or yohimbine was administered for 4 weeks in rats using an osmotic pump. Effects of these agents on urodynamic parameters were determined by continuous cystometry in conscious rats. After cystometry, c-Fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. RESULTS: The administration of prazosin (0.12 mg/kg/day) or yohimbine (0.10 mg/kg/day) significantly increased micturition interval and bladder capacity, but did not affect micturition pressure and residual urine volume. The numbers of c-Fos-positive neurons in the dorsal horn were significantly lower in rats that received prazosin than in controls. Yohimbine reduced the number of c-Fos-positive neurons in part of the dorsal horn. CONCLUSIONS: Long-term administration of prazosin and yohimbine at clinically recommended doses can exert inhibitory effects on afferent pathways from the lower urinary tract during the storage phase. These reductions of the afferent input result in the increased bladder capacity and increased micturition interval.

Alpha1-adrenoceptor antagonists improve bladder storage function through reduction of afferent activity in rats with bladder outlet obstruction.

AIMS: Using a rat BOO model, we determined whether α1-adrenoceptor (AR) antagonists (silodosin, prazosin) improve the bladder storage function by reducing afferent input from the lower urinary tract. MATERIALS AND METHODS: Male rats received partial bladder outlet obstruction or sham surgery were used. Four weeks following surgery, their voiding behavior was measured in a metabolic cage. BOO-rats were administered silodosin, prazosin or vehicle for 2 weeks subcutaneously using osmotic pump. At the post-drug condition, voiding behavior was measured again. The L6 spinal cord was removed and immunostained using anti c-Fos antibody. The rats were also performed continuous cystometry with saline without anesthesia or restraint at the pre- and post-drug conditions. RESULTS: Metabolic cage study showed the voiding behavior of BOO-rats was characterized by increase in frequency of urination and decrease in volume voided. Cystometric evaluation also showed the significant increase both in the number of successive voiding contraction and in contraction pressure. The administration of silodosin or prazosin significantly decreased urinary frequency and the number of micturition reflex but affected neither bladder contraction pressure nor residual volume. The number of c-Fos-positive cell significantly increased in BOO-rats, while significantly decreased in those receiving αl-AR antagonists. CONCLUSIONS: The present study demonstrates that α1-AR antagonists silodosin and prazosin have an inhibitory effect on afferent input from the lower urinary tract independently of reducing urethral resistance, and thereby reduce the storage dysfunction secondary to BOO. This result suggests that αl-AR, particularly αlA-AR, may play an important role in the activation of the afferent pathway.

Suppression of SOCS3 increases susceptibility of renal cell carcinoma to interferon-α.

Interferon (IFN)-α is one of the most commonly used agents in immunotherapy for patients with advanced stage renal cell carcinoma. However, because of the drug resistance to IFN-α, its benefits are limited. In this study, we examined whether repression of suppressor of cytokine signaling (SOCS) proteins, which are involved in the IFN-induced signaling pathway, can overcome the IFN resistance of renal cell carcinoma. The effect of IFN-α on SOCS3 expression and cell proliferation was examined using IFN-resistant 786-O and IFN-sensitive ACHN cell lines. The effects of SOCS3-targeted siRNA on 786-O xenografts were determined by SOCS3 expression, morphological observation, and tumor volume. The SOCS3 mRNA expression level was significantly increased by IFN-α stimulation in 786-O, but not in ACHN cells. The overexpression of SOCS3 by gene transfection in ACHN cells significantly inhibited the growth-inhibitory effect of IFN-α. Suppression of SOCS3 expression in 786-O cells by siRNA activated the IFN signaling pathway through signal transducer and activator of transcription 1 phosphorylation and recovered sensitivity to IFN-α. An in vivo study indicated that co-administration of SOCS3-targeted siRNA promoted IFN-α-induced cell death and growth suppression in 786-O cell xenograft in nude mice. Morphological observation of the tumors revealed the inhibition of SOCS3-induced apoptosis, invasion of inflammatory cells and fibrosis. SOCS3 could be a key component in the resistance to IFN treatment of renal cell carcinoma. Silencing SOCS3 gene expression could be an effective strategy to enhance the antitumor effect of IFN in human renal cell carcinoma cells.

Place of overactive bladder in male lower urinary tract symptoms.

Lower urinary tract symptoms (LUTS) are highly prevalent in older men and women. Overactive bladder symptom syndrome (OAB) comprises the storage subset of LUTS and, in both sexes, is the most bothersome. The management of male LUTS has however, been disproportionately dominated in the past by an emphasis on prostatic pathology (bladder outlet obstruction (BOO) and prostatic enlargement). Pharmacotherapy that targets the prostate (e.g., α1-adrenoceptor antagonists) often fails to alleviate OAB symptoms, while many studies suggest that antimuscarinic therapy alone, or in combination with α1-adrenoceptor antagonists, can improve OAB symptoms in men with and without BOO. Recent studies suggest that arterial obstructive disease, such as atherosclerosis, may cause OAB in both men and women via ischemia, hypoxia and oxidative stress in the bladder. In this context, the use of phosphodiesterase inhibitors has been suggested to be a potential pharmacotherapy for men with LUTS. This article provides a review of the place of OAB in male LUTS and its treatment and provides an opportunity to draw data from a number of sources into one manuscript for critical review.

Association between antibody response against cytomegalovirus strain-specific glycoprotein H epitopes and HLA-DR.

The gH of CMV is a major target for strain-specific neutralizing antibodies. To verify whether there is a correlation between HLA-DR type and strain-specific antibodies, antibodies against CMV gH in potential donors and recipients for renal transplantation were investigated. Among 471 subjects, 404 (86%) showed reactivity to CMV gH, but no antibodies against gH were detected in 67 (14%) subjects. The positive rates were over 80% in most HLA subpopulations. Fewer subjects with HLA-DR10 and DR11 had antibodies to CMV gH than did those without HLA-DR10 and DR11. HLA-DR10 and DR11 may be associated with fewer/non-responders for strain-specific neutralizing antibodies.

Obstruction alters muscarinic receptor-coupled RhoA/Rho-kinase pathway in the urinary bladder of the rat.

AIMS: The present study investigated the effects of the bladder outlet obstruction (BOO) on the muscarinic receptor (MR)-coupled RhoA/Rho-kinase (ROK) pathway in the detrusor smooth muscle of the rat. METHODS: Detrusor muscle samples were obtained from bladders after 4 weeks of BOO and also from sham-operated control rats. Contractile responses to electrical field stimulation (EFS) and 1 microM carbachol (Cch) were determined in isolated detrusor strips. The effects of the ROK inhibitor Y-27632 on the Cch-induced phasic and sustained contractions were evaluated. Western blotting was used to determine the relative levels of RhoA expression and ROK isoform expression. RESULTS: Bladder weight increased significantly after 4 weeks of BOO. Contractile responses to EFS decreased significantly in detrusor muscle from the obstructed bladder. Cch (1 microM) induced a biphasic response consisting of an initial phasic contraction followed by a sustained contraction. Y-27632 attenuated the phasic and sustained contractions induced by Cch in both control and obstructed bladders. However, BOO caused a significant increase in contractile force during the sustained phase of the contractions induced by Cch. An inhibitory effect of Y-27632 on the sustained responses to Cch was significantly enhanced in the obstructed bladder. In accordance with the functional study, the expression of RhoA and ROK isoforms (both alpha and beta) at the protein level significantly increased in the obstructed bladder. CONCLUSIONS: These results suggest that the enhanced MR-coupled RhoA/ROK pathway contributes to the maintenance of contractile force in the obstructed bladder, as a compensatory mechanism for expelling the urine against the obstruction.

Effect of long-term oxybutynin administration on c-Fos expression in spinal neurons: inhibition of antimuscarinics on bladder afferents in conscious rats.

OBJECTIVES: To investigate the effect of long-term administration of oxybutynin on afferent input from the bladder by evaluating c-Fos expression in the spinal cord. METHODS: Using an osmotic pump, long-term administration of oxybutynin (4 weeks) was performed in the rat. The effects of oxybutynin (2 doses) on the urodynamic parameters were determined by continuous cystometry in conscious rats. After cystometry, c-Fos expression in the spinal cord was measured by immunohistochemistry. RESULTS: The long-term administration of low-dose oxybutynin (0.36 mg/kg/d) significantly increased the micturition interval and bladder capacity, but it did not affect micturition pressure. However, administration of high-dose oxybutynin (3.6 mg/kg/d) significantly decreased the micturition pressure and increased the residual volume. In the rats that received low-dose oxybutynin, the number of c-Fos-positive neurons in the spinal cord was significantly lower than that in controls. CONCLUSIONS: Administration of low-dose oxybutynin decreased the c-Fos expression induced by continuous infusion of saline into the bladder. This result suggests that the antimuscarinic drug oxybutynin at clinically recommended doses can exert an inhibitory effect on afferent input from the bladder during the storage phase without affecting detrusor contractions.

Strain-specific seroepidemiology and reinfection of cytomegalovirus.

Although there have been some reports describing the serostatus of cytomegalovirus, strain-specific antibody responses and their distribution remain unknown. In this study, ELISA using fusion proteins encompassing epitope of glycoprotein H from both AD169 and Towne strains was used to test 352 blood donors. Of these 352 donors, 207 were analyzed for strain-specific glycoprotein H antibodies. Of the 44 donors whose serum contained antibodies against both AD169 and Towne, 27 (60%) were aged 50 years or over (p = 0.0003). This may indicate serological evidence of reinfection with cytomegalovirus in the elder population. The nucleotide sequence analysis of cytomegalovirus glycoprotein H from the peripheral blood of the cytomegalovirus-positive renal transplant recipients showed that our strain-specific ELISA can reveal cytomegalovirus reinfection after transplantation.

Influence of pelvic floor muscle contraction on the profile of vaginal closure pressure in continent and stress urinary incontinent women.

PURPOSE: We characterized the vaginal pressure profile as a representation of closure forces along the length and circumference of the vaginal wall. Vaginal pressure profile data were used to test the hypothesis that the strength of pelvic floor muscle contractions differs significantly between continent women and women with stress urinary incontinence. MATERIALS AND METHODS: Vaginal pressure profile recordings were made in 23 continent subjects and in 10 patients with stress urinary incontinence. The recordings characterized closure forces along the entire length of the vagina and identified differences among the anterior, posterior, left and right sides of the vaginal wall. Using a novel, directionally sensitive vaginal probe we made vaginal pressure profile measurements with the women at rest and during pelvic floor muscle contraction while supine. RESULTS: The nature of the vaginal pressure profile was characterized in terms of force distribution in the anterior and posterior vaginal walls, which was significantly greater than that on the left and right sides. The continent group had significant greater maximum pressure than the stress urinary incontinence group on the posterior side at rest (mean +/- SE 3.4 +/- 0.3 vs 2.01 +/- 0.36 N/cm(2)) and during pelvic floor muscle contraction (4.18 +/- 0.26 vs 2.25 +/- 0.41 N/cm(2)). The activity pressure difference between the posterior and anterior vaginal walls in the continent group was significantly increased when the pelvic floor muscles contracted vs that at rest (3.29 +/- 0.21 vs 2.45 +/- 0.26 N/cm(2)). However, the change observed in the stress urinary incontinence group was not significant (1.85 +/- 0.38 vs 1.35 +/- 0.27 N/cm(2)). CONCLUSIONS: The results demonstrate that the voluntary pelvic floor muscles impose significant closure forces along the vaginal wall of continent women but not in women with stress urinary incontinence. The implication of these findings is that extrinsic urethral closure pressure is insufficiently augmented by pelvic floor muscle contraction in women with stress urinary incontinence.

High resolution regional elasticity mapping of the human prostate.

What is it that the clinician "feels" during a digital rectal examination? To answer this question, it is necessary to measure the elastic properties of the prostate and verify the stiffness values with histological examination. Therefore, we devised an Elasticity Mapping System to evaluate the elastic properties of various histopathological grades of prostate cancer in relation to benign prostatic hyperplasia (BPH) and normal tissue. The system consists of a micro tactile sensor, a three-axis (XYZ) with one (fine Z) micromanipulation stage, a stereoscope camera and a measurement chamber. Using this methodology we mapped the elasticity of human prostate cancer (CaP) and it was obviously observed that the node was significantly harder than surrounding normal tissues and had some textures.

Spatial distribution of vaginal closure pressures of continent and stress urinary incontinent women.

Clinically the strength of the contraction of the female pelvic floor is qualitatively evaluated by vaginal tactile palpation. We therefore developed a probe to enable the quantitative evaluation of the closure pressures along the vagina. Four force sensors mounted on the four orthogonal directions of an intra-vaginal probe were used to measure the vaginal pressure profile (VPP) along the vaginal wall. Clinical experiments on 23 controls and 10 patients with stress urinary incontinence (SUI) were performed using the probe to test the hypothesis that the strength of pelvic floor muscle (PFM) contractions, imposed by voluntary contraction, is related to urinary continence. The results show that VPPs, characterized in terms of pressure distribution on the anterior and posterior vaginal walls, are significantly greater than those in the left and right vaginal walls. When the PFM contracted, the positions of the maximum posterior pressures in continent females and SUI patients were 0.63+/-0.15 cm and 1.19+/-0.2 cm proximal from their peak points of anterior pressure, which are 1.52+/-0.09 cm and 1.69+/-0.13 cm proximal from the introitus of vagina, respectively. The statistical analysis shows that the maximum posterior vaginal pressures of the controls were significantly greater than those of the SUI patients both at rest (continent: 3.4+/-0.3 N cm(-2), SUI: 2.01+/-0.36 N cm(-2), p<0.05) and during PFM contraction (continent: 4.18+/-0.26 N cm(-2), SUI: 2.25+/-0.41 N cm(-2), p<0.01). In addition, the difference between the posterior and anterior vaginal walls is significantly increased when the controls contract the PFM. By contrast, there are no significant differences in the SUI group. The results show that the VPP measured by the prototype probe can be used to quantitatively evaluate the strength of the PFM, which is a clinical index for the diagnosis or assessment of female SUI.

Defining overactive bladder as hypersensitivity.

Overactive bladder (OAB), according to the International Continence Society (ICS) definition, is a symptom syndrome, with urgency as the cornerstone symptom. However, the word 'urgency' and its definition continue to be the subject of much debate and confusion. It is generally difficult for patients to differentiate urgency from normal urge, particularly when the desire to void is strong. To investigate the micturition behavior associated with OAB, we conducted a Patient Trust Study in 21 intelligent (i.e., to be 'trusted') female patients who could clearly and accurately discriminate between urgency and urge. The results showed that in 43% of patients seeking medical care, urgency episodes occurred less than once/day, and some patients had days without urgency. Our patients deferred voiding until bladder sensation was relatively strong, suggesting that coping was not common among these patients. Four of the 21 patients studied experienced spontaneous resolution of several urgency episodes. At volumes exceeding 40% of the maximum bladder volume (MBV), urgency episodes occurred frequently and independently of the bladder volume, indicating that 40% of the MBV may be a threshold of bladder volume to induce urgency. A linear relationship was observed between bladder volume and increasing bladder sensation. However, compared with normal subjects, urge sensation increased markedly at any given bladder volume among patients with OAB in our study. This hypersensitivity was observed in our patients regardless of urgency episodes. We therefore hypothesized that OAB may be more accurately defined as a hypersensitivity disorder rather than a syndrome characterized by urgency.

The effects of ovariectomy and estrogen replacement on acetylcholine release from nerve fibres and passive stretch-induced acetylcholine release in female rat bladder.

AIMS: The present study investigated the effects of ovariectomy and estrogen replacement on the release of acetylcholine (Ach) from cholinergic neurons as well as on the tetrodotoxin (TTX)-insensitive stretch-induced Ach release in isolated rat detrusor. In addition, the above effects on rat micturition characteristics were also studied. METHODS: Thirty female rats randomly received a sham operation, ovariectomy, or ovariectomy plus estrogen replacement. Using metabolic cages, micturition parameters were recorded. Then, in vitro functional experiments that included the measurements of nerve-mediated detrusor muscle contraction, Ach release from nerve fibres, and stretch-induced TTX-insensitive Ach release were performed. Ach release was measured using microdialysis and high-performance liquid chromatography. RESULTS: Ovariectomized rats showed a significant decrease in voided volume and significant increase in 24-hr frequency of voiding. Ovariectomy caused the significant increase in both TTX-insensitive basal Ach release and TTX-insensitive stretch-induced Ach release. On the other hand, ovariectomy caused a significant decrease in Ach release from nerve fibres, resulting in the decrease in the contractile responses of detrusor muscle to electrical nerve stimulation. Estrogen replacement restored these alterations induced by ovariectomy. CONCLUSIONS: Our findings showed that as a results of estrogen deficiency, Ach release from nerve fibres decreased, suggesting that this reduction of Ach released from cholinergic nerves may cause the decrease in detrusor contractility. Furthermore, this study also demonstrated that stretch-induced TTX-insensitive Ach release was increased by ovariectomy. This may be a contributing factor to the development of overactive bladder in elderly women.

Ultrasound evaluation of dynamic responses of female pelvic floor muscles.

Ultrasound imaging of the pelvic floor carries diagnostically important information about the dynamic response of the pelvic floor muscles (PFM) to potentially incontinence-producing stress, which cannot be readily captured and assimilated by the observer during the scanning process. We presented an approach based on motion tracking quantitatively to analyze the dynamic parameters of PFM on the ano-rectal angle (ARA). Perineal ultrasonography was performed on 22 asymptomatic females and nine stress urinary incontinent (SUI) patients with a broad age distribution and parity. The ventral-dorsal and cephalad-caudad movements of the ARA were resolved and kinematic parameters, in terms of displacement, trajectory, velocity and acceleration, were analyzed. The results revealed the possible mechanisms of PFM responses to prevent the urine from incontinence in fast and stress events such as coughs. The statistical analyses showed that the PFM responses of the healthy subjects and the SUI patients are significantly different in both the supine and standing experiments.

Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors.

We investigated the cAMP-dependent and -independent mechanisms of relaxation via beta-adrenoceptor in rat detrusor muscle with and without pre-contraction. A microdialysis technique was used to measure detrusor tension and cAMP level on the same detrusor tissue. In non-contracted tissue, isoproterenol, clenbuterol (beta2-adrenoceptor agonist) and FR165101, ((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)oxy]acetic acid hydrochloride (beta3-adrenoceptor agonist) relaxed detrusor muscle and cAMP levels also increased in a concentration dependent manner. SQ22536 (adenylyl cyclase inhibitor) markedly suppressed relaxation, suggesting that beta-adrenoceptor-mediated relaxation may be attributed mainly to cAMP-dependent mechanism. In high K+ pre-contracted tissue, although relaxation advanced in a concentration dependent manner, cAMP production reached a plateau at concentrations of more than 10(-7) M. SQ22536 had only a small inhibitory effect. However, large-conductance, Ca2+-activated K+ (BK(Ca)) channel inhibitors, charybdotoxin and iberiotoxin markedly suppressed relaxation. These results suggest that in addition to cAMP-dependent pathway, BK(Ca) channels are involved in the beta-adrenoceptor agonists-induced relaxation in pre-contracted detrusor muscle.

[Retroperitoneal bronchogenic cyst: a case report].

A rare case of retroperitoneal bronchogenic cyst is presented. A 50-year-old man was referred to our hospital for an investigation of a retroperitoneal mass. Computed tomography and magnetic resonance imaging confirmed a retroperitoneal mass, about 4 cm in diameter, adjacent to the left kidney and spleen. On the basis of these imaging modalities, a definitive diagnosis of this mass could not be made. So, resection of the mass was performed. The removed mass was an unilocular cyst and filled with mucinous fluid. Histopathologically, the cyst wall was composed of a fibrovascular connective tissue containing mucus-secreting glands and cartilages and was lined by ciliated pseudostratified columnar epitherium. Thus, a diagnosis of bronchogenic cyst was made. Bronchogenic cysts are rare congenital anomalies of the primitive foregut and usually develop in the mediastinum and lung.