Buddhist Tzu Chi General Hospital Research Articles

Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan

RASopathies are developmental diseases caused by mutations in rat sarcoma-mitogen-activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS-related disorders (NSRD), including cardio-facio-cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. A retrospective study was conducted at the Mackay Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu-Chi General Hospital, Chang-Gung Memorial Hospital, Taichung Veterans General Hospital, and Chung Shan Medical University Hospital from January 2007 to December 2018. We reviewed the clinical records of 76 patients with a confirmed molecular diagnosis of RASopathies, including NS, CS, CFC syndrome, and NSML. We evaluated the demographic data and medical records with clinical phenotypes of cardiac structural anomalies using cross-sectional and color Doppler echocardiography, electrocardiographic findings, and follow-up data. A total of 47 (61.8%) patients had cardiac abnormalities. The prevalence of cardiac lesions according to each syndrome was 62.7, 50.0, 60.0, and 66.7% in patients with NS, CFC syndrome, CS, and NSML, respectively. An atrial septal defect was usually combined with other cardiac abnormalities, such as pulmonary stenosis (PS), HCMP, ventricular septal defect, or patent ductus arteriosus. Patients with NS most commonly showed PS. In patients with NSRD and cardiac abnormalities, HCMP (29.4%) was the most commonly observed cardiac lesion. PTPN11 was also the most frequently detected mutation in patients with NS and NSRD. Cardiac abnormalities were the most common symptoms observed in patients with RASopathies at the time of their first hospital visit. Performing precise analyses of genotype-cardiac phenotype correlations in a larger cohort will help us accurately diagnose RASopathy as soon as possible.

Diagnostic diversity among patients with cognitive complaints: A 3-year follow-up study in a memory clinic.

To describe the distribution and estimate the mortality risks of degenerative dementias and nondegenerative conditions in a memory clinic. We enrolled 727 consecutive patients with cognitive complaints who visited the memory clinic in Buddhist Tzu Chi General Hospital during 2013 to 2016. Three main diagnostic groups were defined: pure type dementia, in which only one type of dementia was diagnosed, such as Alzheimer disease (AD), vascular dementia (VaD), Parkinson disease with dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD); mixed type dementia; and nondegenerative conditions. We described the frequency of different diagnoses and employed Cox proportional hazards regression models to examine the mortality risks for each diagnostic group after adjusting for age, sex, education, and cognitive status. All patients alive on or after September 30, 2018, were censored in the analysis. Two-thirds of patients (n = 496, 68.2%) were diagnosed with degenerative dementias. Pure type to mixed type dementia ratio was about 2: 1. AD remained the most common pure dementia subtype, followed by VaD and PDD. Among all nondegenerative conditions, depression/anxiety and subjective cognitive decline were the most common diagnoses. During a mean follow-up of 3.4 years, 150 deaths were documented, and the mortality risk was 61 deaths/1000 person-years. Mortality risks were associated with age, sex, education, and cognitive function at diagnosis but did not differ by diagnostic group. Clinical diagnoses for patients with cognitive complaints are diverse, and nearly one-third are of nondegenerative conditions. Baseline cognitive function is a stronger predictor for survival than clinical diagnosis.

IGF-axis confers transformation and regeneration of fallopian tube fimbria epithelium upon ovulation.

BackgroundThe fallopian tube fimbria is regarded as the main tissue of origin and incessant ovulation as the main risk factor of ovarian high-grade serous carcinoma. Previously, we discovered the tumorigenesis activity of human ovulatory follicular fluid (FF) upon injection to the mammary fat pad of Trp53-null mice. We also found a mutagenesis activity of FF-ROS and a apoptosis-rescuing activity of Hb from retrograde menstruation. However, neither of them can explain the tumorigenesis activities of FF.MethodsFrom two cohorts of ovulatory FF retrieved from IVF patients, the main growth factor responsible for the transformation of human fimbrial epithelial cells was identified. Mechanism of activation, ways of signal transduction of the growth factor, as well as the cellular and genetic phenotypes of the malignant transformation was characterized.FindingsIn this study, we showed that insulin-like growth factor (IGF)-axis proteins, including IGFBP-bound IGF2 as well as the IGFBP-lytic enzyme PAPP-A, are abundantly present in FF. Upon engaging with glycosaminoglycans on the membrane of fimbrial epithelial cells, PAPP-A cleaves IGFBPs and releases IGF2 to bind with IGF-1R. Through the IGF-1R/AKT/mTOR and IGF-1R/AKT/NANOG pathways, FF-IGF leads to stemness and survival, and in the case of TP53/Rb or TP53/CCNE1 loss, to clonal expansion and malignant transformation of fimbrial epithelial cells. By depleting each IGF axis component from FF, we proved that IGF2, IGFBP2/6, and PAPP-A are all essential and confer the majority of the transformation and regeneration activities.InterpretationThis study revealed that the FF–IGF axis functions to regenerate tissue damage after ovulation and promote the transformation of fimbrial epithelial cells that have been initiated by p53- and Rb-pathway disruptions.FundThe study was supported by grants of the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-303-001-MY2; MOST 105-2314-B-303-017-MY2; MOST 107-2314-B-303-013-MY3), and Buddhist Tzu Chi General Hospital, Taiwan (TCMMP104-04-01).

Cutaneous malignant melanoma in Eastern Taiwan: Clinicopathologic analysis of 56 cases

Background: The incidence, histological subtypes, and tumor behaviors of cutaneous malignant melanoma are quite different in Asian and Western countries. Objectives: Our purpose was to define the epidemiology, tumor behaviors, and possible prognostic predictors of cutaneous melanomas based on an Eastern Taiwanese population. Methods: We conducted a retrospective study to collect cases of cutaneous melanoma at Buddhist Tzu-Chi General Hospital, Hualien, Taiwan, from May 1, 2003, to August 31, 2017. We analyzed mean age at onset, gender, primary tumor locations, histological subtypes, Breslow's thickness, Clark's level, ulceration, lymph nodes, and distant metastatic status. Univariate and multivariate analyses for survival were performed by means of Cox proportional hazard model. Survival curves were plotted by Kaplan–Meier method. Results: A total of 56 cases of cutaneous melanoma were recorded. The male-to-female ratio was 3.67:1. The median survival was 2.82 years (0.63–5.00 years). Acral melanoma (AM) accounts for 69.6% of cases, and feet are the most common location (62.5%). Acral lentiginous melanoma (ALM) is the most common histological type (44.6%), followed by nodular melanoma (33.9%). Poor prognostic factors include older age (≧65 years), male gender, Breslow's thickness >4 mm, distant metastasis, and head-and-neck location. Conclusion: AM is the most common location, and ALM is the most common histological type of cutaneous melanoma in Eastern Taiwan. Melanoma in Eastern Taiwan tends to be delay diagnosed with advanced stage and thicker tumors than Western Taiwan. Prudent palm and sole examinations, improved medical accessibility, and more public educational programs may help encourage the early detection of melanoma.

Neurosurgery for sinusitis-related and sinusitis-unrelated intracranial abscess

Background: Sinusitis-related intracranial abscess (ICA) is a rare but serious complication and is different from those of sinusitis-unrelated ICA. Purpose: This study aimed to analyze the differences in bacteriology, host factors, presentations, and prognoses between cases of sinusitis-related and sinusitis-unrelated ICA. Methods: This retrospective study was conducted at Buddhist Tzu Chi General Hospital (Hualien, Taiwan), during January 2010–August 2014, and enrolled patients with pathologically proven postsurgery ICA. P Results: The number of patients with sinusitis-related and sinusitis-unrelated ICA was 10 and 17, respectively. Compared with sinusitis-unrelated ICA patients, significantly more patients with sinusitis-related ICA experienced cirrhosis, ophthalmic abnormalities, and frontal and cavernous sinus involvement. Among all ICA patients, diabetes mellitus (DM) was associated with an increased mortality risk. Patients with DM exhibited the highest positive culture rates for Klebsiella pneumoniae. Conclusion: Frontal sinusitis is associated with an increased risk of intracranial invasion. DM and liver cirrhosis patients exhibited the highest mortality rates among all ICA patients. Patient comorbidity should be considered when prescribing antibiotics for treatment.

Seprafilm® Application Method in Laparoscopic Surgery.

Background and Objectives:Postoperative adhesions occur less often in laparoscopies than in laparotomies, but the incidence can be reduced further. Seprafilm, a sodium hyaluronate/carboxymethylcellulose absorbable barrier, was developed to prevent adhesions after abdominal surgery, and is approved for postoperative adhesion prevention. However, Seprafilm is seldom used in laparoscopic surgery because of its tendency to break apart when it is inserted into the abdominal cavity through a trocar, resulting in a high placement failure rate. We propose a better method for applying the adhesion barrier Seprafilm in single- or multiport gynecologic surgery.Methods:This is a retrospective analysis of patients who underwent multi- or single-port gynecologic laparoscopies from December 2014 through January 2016 in Buddhist Tzu Chi General Hospital, Hualien, 46 patients received Seprafilm (Genzyme Corp., Cambridge, MA, USA) via the proposed method. A piece of Seprafilm was cut into quarters. To moisten and soften the Seprafilm, each piece was placed on a wet wrung gauze until it became naturally curled. Two pieces of the film were rolled up with the backing paper that came from the package of Seprafilm. Holding the rolled Seprafilm with a grasper, the surgeon delivered it into the abdomen through a 11-mm trocar.Results:The success rates of Seprafilm insertion and correct placement were 100% (46/46) and 95.7%, respectively. In 2 single-port (2/26) laparoscopic surgeries, the placement of the film failed; all placements in the multiport laparoscopic surgeries were successful (20/20). The average time required for placement of pieces of Seprafilm per surgery was 4.0 ± 1.47 minutes among all surgeries; significantly more time was needed in the single-port surgeries (mean, 4.4 ± 1.59 minutes) than in the multiport surgery (mean, 3.4 ± 1.13 minutes) (P < .05).Conclusions:This method of Seprafilm placement is a simple technique that does not need special equipment and ensures a high success rate. The placement of the film takes longer in single-port surgeries than in multiport surgeries.

Two-phase laparoendoscopic single-site cervical ligament-sparing hysterectomy: An initial experience.

Objective:To report our initial experience with and the short-term outcomes of two-phase laparoendoscopic single-site cervical ligament-sparing hysterectomy (LESS-CLSH).Materials and Methods:A retrospective case study included 40 women who underwent LESS-CLSH from January 2014 to December 2016 at Buddhist Tzu Chi General Hospital. Uterine specimens were extracted through contained manual morcellation with a tissue pouch. The first phase was LESS supracervical hysterectomy and conization of the internal orifice of the cervix. The second phase was transvaginal cervical conization and cylinderization. Women with a uterus diameter of >12 cm, a broad ligament myoma, or severe pelvic adhesion were categorized into a difficult group, and others were categorized into a nondifficult group.Results:The difficult group required more time and had more blood loss than the nondifficult group. The mean surgical time was 187.2 ± 33.9 and 139.1 ± 20.7 min, and the mean blood loss was 533.3 ± 333.3 and 225.3 ± 168.2 mL in the difficult and nondifficult groups, respectively. The overall visual analog scale (VAS) pain scores at 0–4, 24, and 48 h after surgery were 7.1 ± 1.9, 4.2 ± 1.6, and 2.3 ± 1.5, respectively; no difference in the VAS pain scores, pain relief score, and hospitalization duration was observed between the two groups. Minor surgical complications or adverse events on follow-up were noted. Three months after surgery, the diameter and thickness of the cervix were decreased by approximately 0.5 and 1.0 cm, respectively.Conclusion:LESS-CLSH is a minimally invasive, safe, and feasible approach, even for difficult laparoscopic hysterectomy. Contained manual morcellation enables more controlled specimen removal than morcellation only.

Incidence and characteristic analysis of in-hospital falls after anesthesia.

BackgroundIn-hospital falls may result in serious clinical adverse consequences, but the effects of anesthesia in the occurrence of postoperative falls are still undetermined. Anesthesia may theoretically cause postoperative falls due to the residual pharmacologic and neuromuscular blocking effects of anesthetics. We retrospectively reviewed events of in-hospital falls occurred after anesthesia management to identify the incidence and risk factors of postanesthesia falls.MethodsWe reviewed the postanesthesia visit of patients received anesthesia in the Hualien Buddhist Tzu Chi General Hospital from January 2009 to December 2013. Falls happened within 24 h after anesthesia were recorded. The Poisson regression model was used for simultaneous analysis of the association between incidence proportion of postanesthesia falls and the potential risk factors.ResultsA total of 60,796 inpatients received anesthesia management over the past 5 years, and ten patients fell within 24 h after anesthesia. All cases happened in the general wards. Falls occurred more often at the bedside, presence of caregivers, and during the daytime. Patients underwent regional anesthesia, and old age significantly increased the risk of postanesthesia falls, while differences in gender and ASA physical status did not affect the occurrence of postanesthesia falls.ConclusionsThe overall incidence proportion of postanesthesia falls is 1.6 cases per 10,000 patients (95 % CI 0.006 to 0.026 %) over a 24-h observation period. Falls are more commonly happened during the less expected periods after operation and are increased in the elderly and patients received regional anesthesia. This study highlights that more comprehensive clinical practice guidelines for postoperative care should be exercised to prevent the in-hospital falls.

The impact of pseudephedrine on lower urinary tract symptoms in male patients without concomitant voiding dysfunction

The impact of pseudephedrine on lower urinary tract symptoms in male patients without concomitant voiding dysfunction

Long-term outcome of Gamma Knife radiosurgery in patients with tiny intracanalicular vestibular schwannomas detected by three-dimensional fast imaging employing steady-state acquisition magnetic resonance

ObjectiveTo evaluate the effectiveness and long-term outcome of Gamma Knife radiosurgery (GKRS) for tiny vestibular schwannomas (VSs) detected by three-dimensional fast imaging employing steady-state acquisition magnetic resonance (3D-FIESTA MR). Materials and methodsBetween January and December 2004, 3D-FIESTA MR of the brain was performed in patients who had physical health examinations at the Buddhist Tzu Chi General Hospital (Hualien, Taiwan). Tiny intracanalicular VSs (defined as a tumor volume < 0.5 cm2) was detected in 13 patients (8 women and 5 men). The mean age of the patients was 60 years (range, 45–84 years). Hearing function was graded using the Gardner–Robertson (GR) classification. Dose planning was performed on intraoperative stereotactic contrast-enhanced images using multiple 4-mm isocenters. The mean tumor volume was 0.098 cm2 (range, 0.013–0.4 cm2). The mean margin dose was 12.4 Gy (range, 11–14 Gy), and the isodose line was set at a mean of 53.8% (range, 50–70%). ResultsTwelve patients had GR Grade I or II hearing before GKRS, and GR I or II hearing was maintained in 11 patients. Facial and trigeminal nerve functions were preserved in all patients. The tumor control rate was 100% at a mean follow-up period of 9.8 ± 1.1 years (range, 76–126 months). One patient developed acute vertigo 1 day after GKRS, which subsided after short-term use of steroids and did not recur. ConclusionWith the application of 3D-FIESTA, tiny VSs can be detected early. Because low-dose (12–14 Gy) GKRS is safe and effective for long-term control of the growth of tumors with acceptable preservation rate of hearing function, it may be worthwhile to use 3D-FIESTA to detect tiny VSs and treat the patients using GKRS.

Laparoendoscopic single-site hysterectomy with Ligasure is better than conventional laparoscopic assisted vaginal hysterectomy

Objective: To determine an ideal route and device in hysterectomy by comparing laparoendoscopic single-site (LESS) hysterectomy with conventional laparoscopic-assisted vaginal hysterectomy (LAVH). Methods: This is a computed clinical pathway based caseecontrol study performed in the Buddhist Tzu Chi General Hospital, Hualien, Taiwan. Seventy-two patients (36 LESS hysterectomies and 36 LAVH) from May 2011 to August 2013 were included. The choice of route of hysterectomy and Ligasure use during the operation were made by the patient or by economic considerations. Perioperative outcomes, including postoperative visual analog scale for pain and analgesic pain-relief score were compared. Results: Surgical time and length of hospital stay were shorter in LESS hysterectomy than in LAVH (126 ± 47.7 minutes vs. 158 ± 60.7 minutes and 4.7 ± 0.8 days vs. 5.4 ± 0.8 days, respectively). The visual analog scale pain scores at 0e2 hours and 24 hours postoperation were significantly lower in LESS hysterectomy than in LAVH (5.68 ± 2.11 vs. 8.14 ± 1.46 and 3.75 ± 1.61 vs. 5.04 ± 1.28, respectively). Overall, the pain score decreased by 30%, 26%, and 12% at 0e2 hours, 24 hours, and 48 hours, respectively, after the operation. The total pain-relief score was 38.2% lower in LESS hysterectomy than in LAVH (1.15 ± 0.44 vs. 1.86 ± 0.33; p < 0.001). There were comparable adverse events in both groups. Conclusion: This study demonstrated that LESS hysterectomy with Ligasure is superior to conventional LAVH.

A rapid and accurate technique for the identification of the recurrent laryngeal nerve.

We studied the anatomic relationship between the recurrent laryngeal nerve (RLN) and the third tracheal ring, which was very important for rapid identification of RLN in our hands. This study was initially performed using 8 fresh cadavers (4 female and 4 male). The transverse nerve location from the third trachea and the depth from its anterior surface were measured. We further observed the topography of RLN in relation to the trachea in 60 patients, between November 2008 and January 2011, at the Tri-Service General Hospital and Buddhist Tzu Chi General Hospital, Taipei Branch, Taiwan, with 46 lobo-isthmectomies and 14 total thyroidectomies. The time spent in identifying the RLN was also recorded. Among cadaver groups, the transverse distance (width) and the vertical distance (depth) averaged 3.3 and 17.6 mm, respectively. Among the clinical cases, the width and depth averaged 4.4 and 14.6 mm, respectively. The depth measured in males was significantly deeper than that in females (22.3 vs 13.2 mm) (P < .05). The time spent in identifying the RLN after starting dissection in the RLN triangle was not statistically significantly different between the cadaver group and the clinical group (10.6 ± 5.7 seconds and 15.5 ± 17.7 seconds, respectively; P > .05). The median time was 9 and 10 seconds, respectively. There was no statistically significant side-to-side difference in terms of the time spent in searching for the RLN. Using the third ring as guidance, our inferior-superior technique offers an extra benefit in identifying the RLN safely and quickly, as compared to the conventional inferior approach.

Dietary therapy for a patient affected with 3-hydroxy-3-methylglutaric aciduria

3-Hydroxy-3-methylglutaric aciduria (OMIM 246450) is an extremely rare genetic metabolic disorder of leucine caused by deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase). Affected patients present with life-threatening metabolic acidosis, hyperammonemia, and nonketotic hypoglycemia. Optimal outcome for patients depends on early diagnosis and treatment, prompt management of acute metabolic decompensation during the chronic stage, and long-term interprofessional health care programs. Nutritionists play a pivotal role in the care of metabolic disorders throughout the rest of a patient’s life. A 4-year-old intubated Bunun tribe female patient was admitted to the pediatric intensive care unit of the Buddhist Tzu Chi General Hospital (Hualien, Taiwan) due to status epilepticus, hypoglycemia, and severe metabolic acidosis. Results of urine gas chromatography with mass spectrometry revealed markedly elevated 3-methylglutaric acid, 3-hydroxy-3-methylglutaryl-CoA, and 3-hydroxyisovaleric acid, a finding consistent with a diagnosis of HMG-CoA lyase deficiency. She received an interdisciplinary health care program after acute management. Dietary therapy was the major part of the transdisciplinary health delivery process. Total daily calories were increased from 1400 kcal/day (targeted 60e80%) to 2100e2200 kcal/day (targeted 100%). The ratio of protein lipid and carbohydrate was 13%:24%:63% as recommended for healthy children. Lifelong protein restriction was essential. Total daily protein was given at a dose of 1.5e2 g/kg/day (target: above 50 g/day after the age of 4 years) and was administered at different growth and developmental stages. The daily leucine dose was 1000 mg (suggested dose ¼ 700e900 mg/day), 1.5% of the total protein amount was designed for her. Because leucine is an essential amino acid, close monitoring of optimal serum levels through blood sampling should be reached for better growth and development. Food avoidance was a major focus on restriction of protein from milk, meat, cheese, fish, poultry (including egg), beans, and nutlets, and even any foods containing milk and egg. Partial limited foods included sprouts (alfalfa, clover), radish, red bean, and murgbean. Unlimited fruits included vegetables and low protein starch such as green bean noodles, rice flour, pearl sago, lotus root powder, cornstarch, and corn flour, and low leucine foods such as potato powder were advised. The patient’s major protein source was from a special formula (I-Valex I and II; Abbott, Chicago, USA). Other nutrients such as multivitamins and minerals were prescribed. Daily oral L-carnitine was also prescribed to increase excretion of organic acid. The ability to recognize food labeling was taught to the parents, the patient, and school nurses. Servings for daily dietary content (Table 1) and sample meal plans were designed (Table 2).

Visceral Hypersensitivity in Non-erosive Reflux Disease: Neurogenic Overwhelming in Esophagus?

The mechanism underlying the pathogenesis of heartburn and chest pain in gastro-esophageal reflux disease (GERD) has not been clearly established. An important advance in understanding how heartburn is experienced has been accomplished with the reporting of dilated intracellular spaces (DIS) in the esophageal mucosa of patients with erosive GERD and non-erosive reflux disease (NERD) [1]. Although the presence of DIS provides a theoretical pathway for direct entry of hydrogen ions into the mucosa [2], its relationship to esophageal barrier function is still controversial since there are no direct measurements of esophageal acid permeability in vivo to support its contribution to barrier function. Another important breakthrough is the detection of transient receptor potential vanilloid subfamily member-1 receptors (TRPV1) in the esophageal mucosa [3], which may potentially contribute to visceral hypersensitivity as one of the important mechanisms in patients with NERD [4]. This notion is supported by the observation that perception of heartburn and esophageal sensitization can be induced by TRPV1 activation after the exposure to capsaicin and related TRPV1 activators such as heat and acid [5]. TRPV1 activation has also been hypothesized to induce neurogenic inflammation by the release of substance P and calcitonin-gene-related peptide (CGRP) in primary afferent neurons [6]. These neuropeptides mediate nociception and neurogenic inflammation via neurokinin 1 receptor (NK1R) for substance P and receptor activity-modifying protein 1 (RAMP1) for CGRP [7–9]. Therefore, the upregulation of TRPV1 expression in the esophageal mucosa is likely explanation for the phenomenon of visceral sensitization in NERD. Moreover, an induction of proteinase-activated receptor-2 (PAR-2) expression was reported in the esophageal mucosa of GERD patients, which correlated well with mucosal inflammatory changes and elevated tissue interleukin (IL)-8 concentrations, providing a possible mechanism for proinflammatory changes in GERD [10]. Furthermore, PAR-2 also mediates nociception via the release of substance P [11]. Finally, although anion-sensing ion channels (ASICs) have been implicated in the chemosensitivity in primary afferent fibers [12], its clinical implication is yet unclear in GERD and is thought to be more likely referred to the mechanosensitivity of the esophagus. In this issue of Digestive Diseases and Sciences [13], Yoshida et al. test the hypothesis regarding the role of nociceptors and neuropeptides in the pathogenesis of visceral hypersensitivity of NERD by examining the expression of acid-sensitive nociceptors including TRPV1, ASIC3, PAR-2, and neuropeptides such as substance P and CGRP with their cognate receptors NK1R and RAMP1 in the esophageal mucosa of NERD patients as compared with age-matched healthy controls. Not surprisingly, increased mRNA expression for TRPV1 and PAR-2 was present in the esophageal mucosa of NERD patients accompanied by a similar increase in substance P protein level and mRNA of its receptor NK1R. They also reported the presence of substance P-positive and CGRP-positive nerves in lamina propria of the esophageal mucosa of their patients by immunohistochemistry. They reported a positive correlation between substance P protein level and acid reflux score. Their data suggest that visceral hypersensitivity in NERD patients appears to be related to nociception and neurogenic inflammation, which supports their hypothesis C.-L. Chen (&) Department of Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 970, Taiwan e-mail: harry.clchen@msa.hinet.net

Positive immunostaining of thyroid transcription factor-1 in primary nasopharyngeal papillary adenocarcinoma

Department of Otolaryngology, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan Department of Pathology, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan c Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan Department of Otolaryngology, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung, Taiwan f School of Medicine, Tzu Chi University, Hualien, Taiwan

Intravesical Botulinum Toxin A Injections Do Not Benefit Patients with Ulcer Type Interstitial Cystitis

Background: Ulcer type and non-ulcer type interstitial cystitis/bladder pain syndromes (IC/BPS) are considered different disease entities. Thus, intravesical botulinum toxin A (BoNT-A) treatment outcomes could differ for each entity. Objectives: To evaluate and compare the treatment outcomes of BoNT-A injections for treatment of each IC/BPS type. Study Design: Prospective interventional study. Setting: Tertiary medical center affiliated with Buddhist Tzu Chi General Hospital and Tzu Chi University, Taiwan. Methods: Forty-four consecutive patients with IC/BPS for whom conventional treatments failed were prospectively enrolled in this study. Patients were classified as having ulcer (n = 10) or non-ulcer (n = 30) IC/BPS based on their previous cystoscopic findings. Intervention: All patients received 4 sets of intravesical BoNT-A injections (100 U in 40 suburothelial injections) every 6 months. The primary end-point was the global response assessment (GRA) 6 months after the fourth set of BoNT-A injections. Secondary end-points included the O’Leary-Sant score (OSS) including symptom indexes (ICSI) and problem indexes (ICPI), visual analog scale (VAS) pain score, voiding diary, and urodynamics variables. Results: After 4 sets of BoNT-A injections, 15 patients with non-ulcer IC/BPS had GRA scores ≥ 2, while the other 15 had GRA scores &lt; 2. All 10 patients with ulcer IC/BPS had GRA scores &lt; 2 at the study end-point (treatment failure). At baseline, patients with ulcer IC/BPS had significantly higher daytime frequency, nocturia, smaller functional bladder capacity, smaller voided volume, greater VAS, smaller maximal bladder capacity, and greater glomerulation grade than did patients with non-ulcer IC/BPS. After 4 sets of BoNT-A injections, patients with non-ulcer IC/BPS and GRA scores ≥ 2 or &lt; 2 all had significantly decreased ICSI, ICPI, OSS, VAS pain scores, frequency episodes, and increased functional bladder capacity. However, patients with ulcer IC/BPS showed no significant change in any clinical or urodynamic variable. After failure of repeated BoNT-A injections, all 10 patients with ulcer IC/ BPS underwent transurethral electrocauterization of their ulcers, which resulted in immediate pain relief. Limitations: Lack of a control arm in this study. Conclusion: Repeated intravesical BoNT-A injections provided effective treatment outcomes at the end-point in half of the patients with non-ulcer IC/BPS, but did not benefit any patient with ulcer type IC/BPS. Ulcer type IC/BPS should be treated as a different disease than non-ulcer IC/BPS. Institutional Review: This study was approved by the Institutional Review Board of the Tzu-chi General Hospital (TCGH 100-06). Key words: Botulinum toxin, interstitial cystitis, bladder pain syndrome, intravesical treatment, Hunner’s ulcer

Discrepancy of Cytogenetic Analysis in Western and Eastern Taiwan

This study aimed at investigating the results of second-trimester amniocyte karyotyping in western and eastern Taiwan, and identifying any regional differences in the prevalence of fetal chromosomal anomalies. From 2004 to 2009, pregnant women who underwent amniocentesis in their second trimester at three hospitals in western Taiwan and at four hospitals in eastern Taiwan were included. All the cytogenetic analyses of cultured amniocytes were performed in the cytogenetics laboratory of the Genetic Counseling Center of Hualien Buddhist Tzu Chi General Hospital. We used the chi-square test, Student t test, and Mann-Whitney U test to evaluate the variants of clinical indications, amniocyte karyotyping results, and prevalence and types of chromosomal anomalies in western and eastern Taiwan. During the study period, 3573 samples, 1990 (55.7%) from western Taiwan and 1583 (44.3%) from eastern Taiwan, were collected and analyzed. The main indication for amniocyte karyotyping was advanced maternal age (69.0% in western Taiwan, 67.1% in eastern Taiwan). The detection rates of chromosomal anomalies by amniocyte karyotyping in eastern Taiwan (45/1582, 2.8%) did not differ significantly from that in western Taiwan (42/1989, 2.1%) (p=1.58). Mothers who had abnormal ultrasound findings and histories of familial hereditary diseases or chromosomal anomalies had higher detection rates of chromosomal anomalies (9.3% and 7.2%, respectively). The detection rate of autosomal anomalies was higher in eastern Taiwan (93.3% vs. 78.6%, p=0.046), but the detection rate of sex-linked chromosomal anomalies was higher in western Taiwan (21.4% vs. 6.7%, p=0.046). We demonstrated regional differences in second-trimester amniocyte karyotyping results and established a database of common chromosomal anomalies that could be useful for genetic counseling, especially in eastern Taiwan.

Brain Morphology Changes in a Remitted Patient With Late-Onset, Drug-Naïve, Non-Psychotic Major Depressive Disorder After Amisulpride Monotherapy

Brain Morphology Changes in a Remitted Patient With Late-Onset, Drug-Naïve, Non-Psychotic Major Depressive Disorder After Amisulpride Monotherapy

A Kind of D-Amino Acid Oxidase Inhibitor, Sodium Benzoate, Might Relieve Panic Symptoms in a First-Episode, Drug-Naïve Panic-Disorder Patient

A Kind of D-Amino Acid Oxidase Inhibitor, Sodium Benzoate, Might Relieve Panic Symptoms in a First-Episode, Drug-Naïve Panic-Disorder Patient

Superior antidepressant effect occurring 1 month after rTMS: add-on rTMS for subjects with medication-resistant depression

Depression is a major psychiatric disorder. The standard treatment for depression is antidepressant medication, but the responses to antidepressant treatment are only partial, even poor, among 30%–45% of patients. Refractory depression is defined as depression that does not respond to antidepressant therapy after 4 weeks of use. There is evidence that repetitive transcranial magnetic stimulation (rTMS) may exert effects in treating psychiatric disorder through moderating focal neuronal functions. High-frequency rTMS on the left prefrontal area and low-frequency rTMS on the right prefrontal area were shown to be effective in alleviating depressive symptoms. Given the statistically significant antidepressant effectiveness noted, the clinical application of rTMS as a depression treatment warrants further studies. Application of rTMS as an add-on therapy would be a practical research model. High-frequency (5–20 Hz) rTMS over the left dorsolateral prefrontal cortex was found to have a significant effect on medication-resistant depression. In the present study, we not only measured the acute antidepressant effect of rTMS during treatment and immediately after its completion but also evaluated participants 1 month after completion of the treatment protocol. Study participants were divided into two groups: an active rTMS group (n = 10) and a sham group (n = 10). The active rTMS group was defined as participants who received the rTMS protocol, and the sham group was defined as participants who received a sham rTMS procedure. A significant Hamilton Depression Rating Scale score reduction was observed in both groups after the fifth and tenth treatments. However, those in the active rTMS group maintained their improvement as measured one month after completion of the rTMS protocol. Participants who received active rTMS were more likely to have persistent improvement in depression scores than participants who received sham rTMS.