Search

Supplementary Data from Homozygous Deletion of MTAP Gene as a Poor Prognosticator in Gastrointestinal Stromal Tumors

Purpose: Chromosome 9 is frequently deleted in high-risk gastrointestinal stromal tumors (GISTs), whereas its specific tumor suppressor genes (TSGs) are less understood. We did an integrative study of MTAP gene at 9p21 to analyze its implication in GISTs.Experimental Design: To search TSGs on chromosome 9, we used ultrahigh-resolution array comparative genomic hybridization to profile DNA copy number alterations of 22 GISTs, with special attention to MTAP gene. MTAP immunoexpression was assessable for 306 independent GISTs on tissue microarrays, with 146 cases analyzed for MTAP homozygous deletion, 181 for mutations of KIT and PDGFRA receptor tyrosine kinase genes, and 7 for MTAP hypermethylation.Results: Array comparative genomic hybridization identified 11 candidate TSGs on 9p and six on 9q. MTAP and/or CDKN2A/CDKN2B at 9p21.3 were deleted in one intermediate-risk (11) and seven high-risk (70) GISTs with two cases homozygously codeleted at both loci. MTAP homozygous deletion, present in 25 of 146 cases, was highly associated with larger size and higher mitotic rate, Ki-67 index, and risk level (all P < 0.01) but not with receptor tyrosine kinase genotypes. Whereas MTAP homozygous deletion correlated with MTAP protein loss (P < 0.001), 7 of 30 GISTs without MTAP expression did not show homozygous deletion, including three MTAP-hypermethylated cases. MTAP homozygous deletion was univariately predictive of decreased disease-free survival (P < 0.0001) and remained multivariately independent (P = 0.0369, hazard ratio = 2.166), together with high-risk category (P < 0.0001), Ki-67 index >5 (P = 0.0106), and nongastric location (P = 0.0416).Conclusions:MTAP homozygous deletion, the predominant mechanism to deplete protein expression, is present in 17 of GISTs. It correlates with important prognosticators and independently predicts worse outcomes, highlighting the role in disease progression. (Clin Cancer Res 2009;15(22):696372)

Summary Background Chronic kidney disease-mineral and bone disorder (CKD-MBD) has more influence in the elderly. Parathyroidectomy remains the golden standard for this situation but has tended to be excluded for older patients for many reasons. This study aimed to evaluate the efficacy and safety of the surgery in the elderly population. Methods 156 patients were included and arranged into younger (≦65 years of age, n = 139) and elderly (>65 years of age, n = 17) groups. The change of bone mineral density (BMD) data, recovery potential {[(postoperative BMD) – (preoperative BMD)]/(preoperative BMD) ∗ 100%}, surgical successful rate and related complications were collected. Results Both groups exhibited significant postoperative improvement on the BMD results. The recovery potential of the elderly was not lower than the younger group. High success rate and none of persistent vocal palsy, hypocalcemia or any sequela were also observed in the elderly. Conclusions Parathyroidectomy is an effective and safe intervention for the CKD-MBD in the elderly.

BACKGROUND Thyroid incidentalomas are typically nonpalpable thyroid nodules discovered during radiographic evaluation for a non-thyroid issue. Thyroid incidentalomas visualized by computed tomography (CT) and ¹⁸F-flurodeoxyglucose (FDG) positron emission tomography (PET) before living donor liver transplantation (LDLT) are rare. The aim of the study was to analyze the clinical impact of thyroid incidentalomas discovered prior to transplantation. MATERIAL AND METHODS This retrospective study recruited 1010 patients undergoing LDLT between 2010 and 2019. CT was performed on each patient, whereas PET was performed on randomized patients (n=498). RESULTS The prevalence and malignant risk of thyroid incidentaloma on CT was 2.3% (23/1010) and 13.0% (3/23), respectively. The prevalence of thyroid incidentaloma on PET was 3.0% (15/498). Approximately half of the FDG uptake on PET was diffuse uptake (n=7), whereas the other half was focal uptake (n=8). The malignant risk of PET incidentaloma with focal FDG uptake was 37.5% (3/8). Four asymptomatic thyroid cancers were identified incidentally. After total thyroidectomy followed by LDLT, these patients maintained cancer-free status. CONCLUSIONS Thyroid incidentalomas occurred at a rate of 2-3% in LDLT candidates. The malignant risk was 13.0% on CT incidentaloma, and 37.5% on PET incidentaloma with focal FDG uptake. Curative treatment of incidental thyroid cancer followed by LDLT without delay can achieve a favorable prognosis.

Transoral endoscopic parathyroidectomy vestibular approach for secondary hyperparathyroidism (SHPT) is controversial with regard to the time consumed, safety, and feasibility. We present our initial experience with modified transoral endoscopic parathyroidectomy vestibular approach (m-TOEPVA) procedure for SHPT using total parathyroidectomy with autotransplantation.We retrospectively reviewed 10 patients with SHPT who underwent the m-TOEPVA procedure from December 2017 to April 2018 at our center.There were a total of 6 male individuals and 4 female individuals with a median age of 58.5 years. Among whom, 5 were on hemodialysis and 5 on peritoneal dialysis. The median length of hospital stay and operative time was 5 (4, 5) days, and 321.5 (302.75, 362.25) minutes, respectively. Successful removal of 4 parathyroid glands was achieved in 8 of 10 patients (80%) and, in 8 patients (8/10, 80%), the intact parathyroid hormone successfully dropped to300 pg/mL at 3 months postoperatively. Two patients with ectopic parathyroid gland in the superior mediastinum were noted preoperatively by MIBI scan and subsequently had successful removal. Except for 1 patient with prolonged hospital stay (11 d) due to hungry bone syndrome, there were no other major complications.m-TOEPVA by total parathyroidectomy with autotransplantation for SHPT is feasible, safe, and offers optimal cosmetic results. The most valuable part is that m-TOEPVA provides direct visualization and successful removal of the ectopic parathyroid glands in the superior mediastinum.

Introduction: Pancreatoblastoma (PB) is a rare pancreatic neoplasm that occurs most in pediatric patients. Here, we report a rare case of adult PB with liver metastasis and review the literature in order to assist clinicians in the management of the disease. Case Presentation: A 27-year-old female patient suffered from postprandial fullness, anorexia, and weight loss in the past 3 months. An abdominal ultrasound and contrast-enhanced computed tomography scans confirmed right abdominal mass with compression of major liver vessels, as well as the P-duct and biliary ducts and causing mild dilatation. Pancreatoduodenectomy was performed and pathologic findings showed typical squamoid corpuscles, which confirmed the diagnosis of PB. The patient was alive and disease-free for 1 year and 10 months until a new metastatic lesion was found. Radiofrequency ablation was arranged as a curative treatment, and no viable tumor or sign of recurrence was found until this paper was submitted. Based on a review of previous case reports, we found adult PB patients with only liver metastasis presented with a smaller tumor size (P = 0.031), more frequent pancreatic head origin (P = 0.043), and decreased 1-year mortality (P = 0.009) compared with patients with other distal metastases. Therefore, we assumed that PB with liver metastasis might present favorable outcome by complete surgical resection or other curative treatment. Conclusion: PB patients with liver metastasis are more likely to show a pancreatic head origin, smaller tumor size, and more favorable outcomes compared with other sites of metastasis. PB should be treated aggressively with surgical resection or other curative treatment as opposed to chemotherapy alone.

Patients with end-stage renal disease (ESRD) may demonstrate secondary hyperparathyroidism (SHPT), characterized by parathyroid hormone oversecretion in response to electrolyte imbalance (e.g., hypocalcemia and hyperphosphatemia). Moreover, this electrolyte imbalance may affect vocal cord muscle contraction and lead to voice change. Here, we explored the effects of SHPT on the voices of patients with ESRD. We used data of 147,026 patients with ESRD from the registry for catastrophic illness patients, a sub-database of Taiwan National Health Insurance Research Database. We divided these patients into 2 groups based on whether they had hyperparathyroidism (HPT) and compared vocal dysfunction (VD) incidence among them. We also prospectively included 60 ESRD patients with SHPT; 45 of them underwent parathyroidectomy. Preoperatively and postoperatively, voice analysis was used to investigate changes in vocal parameters. In the real-world database analysis, the presence of HPT significantly increased VD incidence in patients with ESRD (p = 0.003): Cox regression analysis results indicated that patients with ESRD had an approximately 1.6-fold increased VD risk (p = 0.003). In the clinical analysis, the “jitter” and “shimmer” factors improved significantly after operation, whereas the aerodynamic factors remained unchanged. In conclusion, SHPT was an independent risk factor for VD in patients with ESRD, mainly affecting their acoustic factors.

Severe hypocalcemia is a serious complication occurring after parathyroidectomy for secondary hyperparathyroidism. Totally, 322 patients who were successfully treated with total parathyroidectomy and bilateral thymectomy plus autotransplantation were studied. Group A (247 patients) developed mild hypocalcemia. Group B (75 patients) who had post-operative serum Ca levels 4 g of intravenous (i.v.) Ca gluconate to keep Ca levels ≥6.5 mg/dL developed severe hypocalcemia. Preoperatively, patient age was recorded, and serum Ca, P, alkaline phosphatase (Alk-ptase), and intact parathyroid hormone (iPTH) levels were checked. These serum levels were checked again 18 h post-operatively. The algorithm showed that i.v. Ca gluconate 8 g/150 dL (5% glucose)/day was administered for Ca levels

BACKGROUND With growing literature, the feasibility of transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been confirmed as a valid method for managing differentiated thyroid cancer. Completion thyroidectomy (CT) is recommended in patients who have been diagnosed with differentiated thyroid cancer after unilateral lobectomy by TOETVA. In this retrospective study, the authors addressed the critical questions of how and when to do the second operation of CT to avoid a neck scar. MATERIALS AND METHODS The authors retrospectively reviewed our patients who had received TOETVA in our hospital from August 2016 to December 2019. Those who received CT after initial TOETVA as cTOETVA were further separated according to the approaching methods. Demographic data, operative variables, and postoperative variables were collected and analyzed. RESULTS A total of 97 patients were enrolled using TOETVA. Malignancies were present in 42 patients (43.3%) using TOETVA. There were 3 approaching methods of cTOETVA and separated into reopen transcervical approach (re-TCA), retransoral TOETVA (re-TOETVA), and transaxillary approach (TAA) groups. There were no significant complications among patients for cTOETVA. Of the 8 patients for the cTOETVA, 3 received re-TCA, 3 re-TOETVA, and 2 TAA. CONCLUSIONS The outcomes are encouraging and demonstrate the feasibility of scarless completion thyroidectomy after initial TOETVA. The re-TOETVA procedure should be completed within 14 days after the initial TOETVA procedure, TAA beyond 14 days, and re-TCA may be completed at any time. The cTOETVA techniques using re-TOETVA or TAA have better cosmetic results than re-TCA in oncological equivalency.

Inadvertent recurrent laryngeal nerve (RLN) injury is a major complication of thyroidectomy. This study aimed to investigate the association between preoperative clinical parameters and RLN size prediction. Total thyroidectomy and thyroid lobectomy data were collected between January 2014 and April 2017. Routine identification of the recurrent laryngeal nerves was performed, while intraoperative findings (nerve diameter, thyroid gland weight, intraoperative neuromonitoring (IONM) use, and signal recording) and demographic data were collected for analysis. A total of 848 patients with 1357 RLNs at risk were enrolled in this study. RLN diameter was thinner in females, those with body height

Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (AR) gene expression on the clinical features and progression of PTC. The levels of AR mRNA and protein in frozen, formalin-fixed, paraffin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between AR expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the effects of AR on the regulation of cell migration, and key epithelial&ndash, mesenchymal transition (EMT) markers. AR mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in AR mRNA expression diminished during PTC tumorigenesis, as AR mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women. AR mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of AR in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of N-cadherin, Snail1, Snail2, Vimentin, and TWIST1 and up-regulating E-cadherin gene expression. These results suggest that suppression of the androgen&ndash, AR axis may lead to aggressive tumor behavior in patients with PTC.

Summary: Background: Primary hyperparathyroidism (PHPT) can occur at any age. This study aimed to compare the necessity, feasibility, safety, and outcomes of parathyroidectomy in the management of minor-symptomatic or asymptomatic PHPT patients according to age (young vs. old). Methods: We retrospectively reviewed the medical records of 146 consecutive patients who underwent surgery for PHPT from January 2005 to June 2016 in our institution. The patients ranged in age from 12 to 85 years. For the analysis, the included patients (n = 137) were separated into young (age

Summary: Background: To evaluate the value of preoperative dipyridamole thallium-201 scintigraphy for reducing cardiovascular complication in secondary hyperparathyroidism (SHPTH) patients. Methods: Thallium scintigraphy was arranged for all dialysis patients who underwent parathyroidectomy from Jan 2011 to July 2015. Management of defects on thallium scintigraphy included cardiac catheterization and ultrasonography. Analysis includes 30-day mortality, morbidity and the predicting factors for thallium scintigraphy defect. Results: Of 249 patients with SHPTH, 19 (7.6%) had defects on thallium scintigraphy, 15 (88%) of whom had coronary artery disease on angiography. History of acute coronary syndrome (ACS, p

Neoadjuvant chemotherapy (NAC) is a widely‑used treatment for breast cancer, as it may render unresecta-ble breast tumors to become resectable. In addition, NAC provides the unique opportunity to assess response to treatments within months rather than years of follow‑up. However, predictive markers of tumor response to NAC are lacking. Therefore, the present study aimed to investigate the expression of endoglin, a marker of angiogenesis, and its association with pathologic responses to NAC. Samples from 34 breast cancer patients were obtained prior to and following NAC treatment. Immunohistochemical staining for endoglin and the mechanistic target of rapamycin (mTOR) was performed, and the correlation between the expression of these markers and pathologic response was examined. The overall response rate to NAC of these 34 patients was 67.6%. A mean microvascular density value of 14 served as a threshold score for the increased expression of endoglin. Increased expression of endoglin in primary tumors prior to NAC correlated with improved response in primary tumors (P=0.019) or in primary tumors and regional lymph nodes (P=0.014), when compared with reduced expression of endoglin. Increased expression of mTOR following NAC was additionally correlated with improved response to NAC. The results of the present study demonstrated that the expression of endoglin in breast tumor samples prior to NAC may be a predictor of treatment response. Long‑term follow‑up of clinical outcome is required to explain the elevation of mTOR expression levels following NAC treatment in responsive tumors.

Background We investigated factors associated with all-cause mortality and cardiovascular disease (CVD)-associated mortality after parathyroidectomy (PTX) in patients on maintenance hemodialysis (HD). Methods Our study population consisted of 161 consecutive HD patients who underwent PTX before 2009 and 354 consecutive HD patients without PTX as controls from those visiting the Kaohsiung Chang Gung Memorial Hospital, Taiwan between 2009 and 2013. All-cause and CVD mortality with clinical variables were compared in PTX and non-PTX HD patients. Results PTX patients had significantly lower all-cause and CVD mortality than controls. Multivariate logistic regression analyses showed PTX patients had a lower odds ratio for all-cause mortality than those without (odds ratio=.35, 95% confidence interval=.16 to .74). Association analysis based on clinical variables revealed patients with higher hemoglobin, albumin, creatinine, and HD adequacy index-Kt/V levels had significantly decreased risk of all-cause mortality. Conclusions PTX in HD patients reduces the risk of death.

Highlights • The mean NGA during inspiration in patients with dyspnea was less than that in patients without. • The mean age of patients with dyspnea was greater than that of patients without. • Dyspnea that occurred at 0–8 days post operation recovered within 3–17 days after BiPAP., Introduction Dyspnea due to bilateral vocal cord palsy after total thyroidectomy (BVCPATT) is a life-threatening complication; nevertheless, we try to avoid tracheotomy. Methods Using normalized glottal area (NGA), we retrospectively studied 14 patients with BVCPATT. Nine patients without dyspnea were treated conservatively, while five with dyspnea received immediate bilevel positive air-way pressure (BiPAP) treatment. Both right and left recurrent nerves were grossly intact during surgery. Results The mean NGA during inspiration of five patients with dyspnea was less than that of nine patients without (6.21 ± 1.57 (mean ± standard deviation) vs. 20.5 ± 9.5; p = 0.001). The mean age of patients with dyspnea was more than that of patients without (61.6 ± 15.6 vs. 38 ± 10.2; p = 0.007). Five patients with dyspnea that occurred at 0–8 days post operation recovered within 3–17 days after BiPAP. Conclusion Dyspnea occurred in patients with BVCPATT who were relatively older. The mean NGA during inspiration in patients with dyspnea was less than that in patients without. BiPAP might be a new treatment for dyspnea.

Background Changes of calcification scores of the abdominal aorta (CSAA) after total parathyroidectomy plus autotransplantation (TPX + AT) for symptomatic secondary hyperparathyroidism (SSHP) have never been reported. Methods Forty-nine patients who successfully underwent TPX + AT for SSHP were enrolled; 13 patients who had regular hemodialysis were enrolled as controls. Preoperatively, patients' age, gender, and duration of dialysis were recorded. Serum Ca, P, alkaline phosphatase (Alk-ptase), intact parathyroid hormone (iPTH), vitamin D, FGF23, and Klotho levels, and CSAA were measured. One year postoperatively, these data were measured again. In the control group, these data were recorded and measured before and one year later. Results Serum iPTH, Alk-ptase and FGF23 levels and CSAA of the study group were significantly higher than those of the control group. One year postoperatively, serum Ca, P, Alk-ptase, iPTH, and FGF23 levels and CSAA were significantly lower than those before surgery. Except for FGF23 levels, other items of the control group did not change significantly one year later, whereas the study group decreased CSAA more than the control group. Conclusion One year postoperatively, CSAA decreased.

Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) is a novel technique with better cosmetic results. However, extraction of a large malignant thyroid nodule from the central incision of TOETVA necessitates breaking it into pieces to avoid mental nerve injury, a situation that may violate a proper oncological surgery. In this study, we sought the appropriate nodular diameter in thyroid cancer to be removed in an intact status through the central incision of the TOETVA technique. A total of 27 cases of thyroid nodules were operated using the TOETVA technique from Aug 2016 to July 2017. Excluding 10 benign goiters, the specimens of 17 thyroid cancer cases were divided into intact (group T, n=7) and fragmented (group F, n=10), with a median nodular diameter of 18.35 and 30.30 mm, respectively. Receiver operating characteristic (ROC) curve analysis revealed that the safest nodular diameter is 20 mm, with 100% sensitivity and 87.5% specificity.

Objective Thyroid surgery is generally a safe surgery but its complications are still common. We wish to identify preoperative factors that predict postoperative complications. Methods A nationwide survey was conducted by senior surgeons from 16 medical centers and 5 regional hospitals in Taiwan to thyroid operations performed over 3 years. 3846 cases were retrospectively examined to identify factors influencing complications: indication for surgery, preoperative evaluation, such as ultrasonography, chest X-ray, computed tomography and magnetic resonance imaging, isotope scanning, fine-needle aspiration cytology (FNAC) and thyroid function test, and patient characteristics. Results Eighty-four percent of patients were female. Seven percent of the patients had immediate postoperative hypocalcemia (mild and severe) and 2.3%, hoarseness (recurrent laryngeal nerve (RLN) injury, temporary/permanent). Logistic regression analysis identified an association between hypocalcemia and RLN injury with age, hospital category, surgical procedure types (total thyroidectomy, unilateral, bilateral subtotal or total resection). A lower incidence of hypocalcemia was related to preoperative neck ultrasound and FNAC analysis (the odds ratio (OR) = 0.5 and 0.65, [95% confidence interval (CI) 0.331–0.768 and 0.459–0.911], P = 0.0014 and 0.0127, respectively), while RLN injury was not associated with any preoperative evaluation. The ORs of hypocalcemia and RLN injury for patients older than 50 years were 0.55 and 2.15, [0.393–0.763 and 1.356–3.4], P, Highlights • Thyroid surgery depends on careful preoperative planning. • Evaluation for lesions, adjuvant devices, and surgical modalities are important. • Preoperative evaluation affects the hypocalcemia. • Intraoperative monitor may reduce RLN injury.

// Chien-Feng Li 1,2,3,4 , Li-Tzong Chen 2,3,5,6 , Jui Lan 7 , Fong-Fu Chou 8 , Ching-Yih Lin 9,10 , Yen-Yang Chen 11 , Tzu-Ju Chen 1 , Shau-Hsuan Li 11 , Shih-Chen Yu 7 , Fu-Ming Fang 12 , Hui-Chun Tai 13 and Hsuan-Ying Huang 7 1 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan 2 National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan 3 Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan 5 Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Institutes of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan 7 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 9 Department of Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan 10 Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan 11 Division of Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 12 Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 13 Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan Correspondence: Hsuan-Ying Huang, email: // Keywords : GIST, 5p, AMACR, amplification, proliferation Received : August 13, 2014 Accepted : October 18, 2014 Published : October 18, 2014 Abstract Non-random gains of chromosome 5p have been observed in clinically aggressive gastrointestinal stromal tumors, whereas the driving oncogenes on 5p remain to be characterized. We used an integrative genomic and functional approach to identify amplified oncogenes on 5p and to evaluate the relevance of AMACR amplification at 5p13.3 and its overexpression in gastrointestinal stromal tumors. Thirty-seven tumor samples, imatinib-sensitive GIST882 cell line, and imatinib-resistant GIST48 cell line were analyzed for DNA imbalances using array-based genomic profiling. Forty-one fresh tumor samples of various risk categories were enriched for pure tumor cells by laser capture microdissection and quantified for AMACR mRNA expression. AMACR- specific fluorescence in situ hybridization and immunohistochemistry were both informative in tissue microarray sections of 350 independent primary gastrointestinal stromal tumors, including 213 cases with confirmed KIT / PDGFRA genotypes. To assess the oncogenic functions of AMACR, GIST882 and GIST48 cell lines were stably silenced against their endogenous AMACR expression. In 59% of cases featuring 5p gains, two major amplicons encompassed discontinuous chromosomal regions that were differentially overrepresented in high-risk cases, including the one harboring the mRNA-upregulated AMACR gene. Gene amplification was detected in 19.7% of cases (69/350) and strongly related to protein overexpression (p

INTRODUCTION Parathyroid Hormone (PTH) is an effective therapeutic agent for osteoporosis, but the treatment requires long-term daily injections. Oral gene delivery is a less invasive alternative to daily injections. OBJECTIVE The aim of this study is to investigate the effect of orally administered nonionic polymeric micelles of plasmid cDNA containing human cytomegalovirus promoter (PCMV)-PTH (1-34) plus EDTA on body mineral density and bone microstructure in ovariectomized rats. MATERIAL AND METHODS A total of 27 Spraque-Dawley female rats were subjected to a bilateral ovariectomy. One month following the ovariectomy, they were randomly assigned to three groups: (1) (PCMVPTH (1-34) cDNA in polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) polymeric micelle formations plus EDTA); (2) PCMV-PTH (1-34) cDNA and (3) drinking water. The treatment was administered by oral gavage on day 1, 2, 7, 14, and 21 at 8-hour intervals. Body mineral density, bone volume fraction, and trabecular thickness of the lumbar spine and femoral neck were examined with peripheral quantitative computed tomography at pre- and post-intervention (3 months after the start of the intervention) and analyzed using two-way repeated measures analysis of variance. RESULTS Results showed that bone mineral density, bone volume fraction and trabecular thickness were significantly increased in Group 1 over time, compared with those in Group 2 and Group 3. CONCLUSION In conclusion, significantly improved bone mineral density and bone microstructure were observed in ovariectomized rats treated with PTH (1-34) cDNA delivered by nonionic polymeric micelles.

SummaryFollicular thyroid carcinoma (FTC) with sternum metastasis is rarely reported. Conservative treatments always result in a poor prognosis. We report two cases of FTC presenting with a large symptomatic solitary metastatic lesion in the sternum. Surgical intervention included total thyroidectomy, combined with wide composite resection of the sternal manubrium, as well as the adjacent clavicular head and ribs. A large defect with exposed pericardium and great vessels was found post resection in both cases. Because the ipsilateral vessels were sacrificed, a contralateral extended pedicled pectoralis major adipofascial flap was designed and transposed to cover the underlying vital organs. The patients received both adjuvant I-131 and radiotherapy postoperatively. The treatment was uneventful, and the patients are well and asymptomatic 5 years after the treatment. Wide composite resection and appropriate adjuvant therapies may offer a survival benefit in patients with advanced FTC with sternum metastasis.

Background. To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-2 and N1 disease. Patients and methods. A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling. Results. With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI. Conclusions. For patients with T1-2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.

Context: MicroRNA (miR)-146b is overexpressed in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal invasion, advanced tumor stage, and poor prognosis. However, the underlying mechanism of miR-146b in relation to its oncogenic behavior in PTC and its putative targets remain unknown. Objective: The purpose was to investigate IL-1 receptor-associated kinase 1 (IRAK1) as the potential miR-146b target gene and its involvement in PTC. Design: We used genome-wide microarray, computational analysis, and 3′ UTR reporter gene assays to identify IRAK1 as a miR-146b target gene. In vitro gain/loss-of-function experiments were further performed to determine the effects of IRAK1 on proliferation, colony formation, and wound-healing in PTC cancer cell lines. Expression levels of miR-146b and IRAK1 of 50 cases of PTC and its adjacent normal thyroid specimens were assessed via qRT-PCR. Results: Microarray expression profile revealed that the mRNA level of IRAK1 gene was down-regulated by miR-146b. The 3′ UTR of IRAK1 mRNA was found to be a molecular target of miR-146b posttranscriptional repression in BCPAP cells by reporter gene assays. MiR-146b promoted the migration and proliferation of PTC cells by down-regulating IRAK1 expression, whereas restoration of IRAK1 expression reversed this effect. In addition, the expression of IRAK1 mRNA was significantly lower in PTC clinical tissue samples than normal adjacent thyroid specimens and showed a strong inverse correlation with the expression of miR-146b in PTC specimens. Conclusion: Our results demonstrated that IRAK1 is a direct target of miR-146b and has functional roles to inhibit various aggressive PTC cell activities. In conjunction with current therapeutic regimens, targeting the miR-146b-IRAK1 axis may provide a potential approach for PTC management.

Background. We examined the changes in circulating fibroblast growth factor 23 (FGF23) and Klotho concentrations in hemodialysis patients after parathyroidectomy (PTX). Methods. We enrolled a cohort of hemodialysis patients who received PTX. Postoperatively, patients received calcium supplements and/or vitamin D analogue (calcitriol) to maintain serum calcium within 7.0–8.0 mg/dL. Information on clinical parameters including bone-mineral metabolic variables was collected pre-PTX and on days 5 and 90 after PTX. Concomitantly, serum full-length FGF23 and α-Klotho levels were measured. The relationship between FGF23 and clinical parameters was analyzed by single linear regression. Results. Forty-six participants (33 women; 13 men) were enrolled in the study. Their mean age was 56.49 years. Serum FGF23 and α-Klotho concentrations were elevated on days 5 and 90 after PTX compared to baseline (p>0.05). Serum FGF23 concentrations negatively correlated with serum calcium concentrations pre-PTX (Beta -0.31; R2 0.0949; p=0.040), day 5 post-PTX (Beta -0.31; R2 0.0982; p=0.036), and day 90 post-PTX (Beta -0.39; R2 0.1528; p=0.008). Conclusions. There was no change in circulating FGF23 and Klotho concentrations after PTX in hemodialysis patients given postoperative calcium supplements and/or vitamin D analogue. Serum FGF23 concentrations pre-PTX and at days 5 and 90 after PTX were inversely related to serum calcium concentrations.

To report our experience with targeted-ultrasound in assessing 142 cases with clustered microcalcifications of intermediate concern detected on digital mammography. All cases had histopathologically-proven microcalcifications within the biopsied or surgical specimens. There were 30%[43/142] breast cancers and 70%[99/142] benign lesions. Only 26%[37/142] of clustered microcalcifications were identified on targeted-ultrasound and other findings including negative study (n = 33), anechoic ducts or cysts (n = 70), dilated ducts with echogenic content (n = 13) and hypoechoic nodules (n = 26). There was no statistical difference of the frequency of negative ultrasound between benign and malignant microcalcifications (P = 0.071). However, only 7.1%[5/70] cases with anechoic ducts or cysts were proven to be breast cancer. The frequencies of depiction of dilated ducts with echogenic foci or hypoechoic nodules were significantly higher for malignant microcalcifications (P < 0.001). Ultrasound was significantly more sensitive for the identification of malignant cases but biopsy of clustered microcalcifications is still warranted when targeted-ultrasound revealed negative findings.

Papillary thyroid carcinoma (PTC) are clinicopathogenetically heterogeneous. Micro-RNAs (miRNAs) are involved in the pathogenesis of diverse human cancers, including PTC. Information regarding associations between clinicopathological features of PTC with the expression of specific miRNAs, however, is sparse. In this study, we compared expression of deregulated miRNAs in PTCs to assess this was associated with selected clinicopathogenetic features.We analyzed the expression levels of three reported deregulated miRNAs (miR-221, miR-222, and miR-146b) using quantitative real-time polymerase chain reaction in 100 cases of PTCs with distinct clinicopathogenetic characteristics and 16 paired normal controls. The tumor samples were categorized into low- and high-risk groups on the basis of the tumor-node-metastasis staging system.The expression levels of miR-221, miR-222, and miR-146b were significantly associated with extrathyroidal invasion (p = 0.013, 0.05, and 0.003, respectively). The expression levels of miR-221 and miR-146b were significantly higher in the high-risk PTC group (p = 0.01 and 0.042, respectively). The miR-146b expression levels in PTCs with BRAF mutation were significantly higher than those without this mutation (p0.0001). There were no other associations between the expression of these miRNAs and other clinicopathological parameters.Our results show the potential importance of miR-221, miR-222, and miR-146b in determining the aggressive properties of PTCs and highlight the need to identify the gene targets of these miRNAs.

Purpose: Chromosome 9 is frequently deleted in high-risk gastrointestinal stromal tumors (GISTs), whereas its specific tumor suppressor genes (TSGs) are less understood. We did an integrative study of MTAP gene at 9p21 to analyze its implication in GISTs. Experimental Design: To search TSGs on chromosome 9, we used ultrahigh-resolution array comparative genomic hybridization to profile DNA copy number alterations of 22 GISTs, with special attention to MTAP gene. MTAP immunoexpression was assessable for 306 independent GISTs on tissue microarrays, with 146 cases analyzed for MTAP homozygous deletion, 181 for mutations of KIT and PDGFRA receptor tyrosine kinase genes, and 7 for MTAP hypermethylation. Results: Array comparative genomic hybridization identified 11 candidate TSGs on 9p and six on 9q. MTAP and/or CDKN2A/CDKN2B at 9p21.3 were deleted in one intermediate-risk (11) and seven high-risk (70) GISTs with two cases homozygously codeleted at both loci. MTAP homozygous deletion, present in 25 of 146 cases, was highly associated with larger size and higher mitotic rate, Ki-67 index, and risk level (all P < 0.01) but not with receptor tyrosine kinase genotypes. Whereas MTAP homozygous deletion correlated with MTAP protein loss (P < 0.001), 7 of 30 GISTs without MTAP expression did not show homozygous deletion, including three MTAP-hypermethylated cases. MTAP homozygous deletion was univariately predictive of decreased disease-free survival (P < 0.0001) and remained multivariately independent (P = 0.0369, hazard ratio = 2.166), together with high-risk category (P < 0.0001), Ki-67 index >5 (P = 0.0106), and nongastric location (P = 0.0416). Conclusions: MTAP homozygous deletion, the predominant mechanism to deplete protein expression, is present in 17 of GISTs. It correlates with important prognosticators and independently predicts worse outcomes, highlighting the role in disease progression. (Clin Cancer Res 2009;15(22):696372)

Ezrin, a member of the ezrin–radixin–moesin family, acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling. It implicates tumor progression, metastatic dissemination, and adverse outcomes in several cancer types, including pediatric and adult sarcomas. Although ezrin upregulation was shown by cDNA expression profiling, no study has systematically evaluated the significance of ezrin expression in a large cohort of gastrointestinal stromal tumors (GISTs). Ezrin immunostaining was carried out on tissue microarrays of primary GISTs and assessable in 347 cases, 188 of which were successfully evaluated for mutation variants of KIT and PDGFRA receptor tyrosine kinase (RTK) genes by sequencing with or without screening by denatured high-performance liquid chromatography. These GISTs with known RTK genotypes were dichotomized into two prognostically different groups. The endogenous expression and phosphorylation of ezrin in GIST cell lines were analyzed by western blotting. By immunohistochemistry, ezrin overexpression was present in 66% of GISTs and significantly associated with the non-gastric location (P=0.002) and decreased disease-free survival (P=0.032, univariately). However, it was not related to the National Institute of Health (NIH) risk category, Ki-67 labeling index, RTK genotypes, and other variables. In multivariate analyses, ezrin overexpression remained independently predictive of adverse outcome (P=0.008, risk ratio=2.363), together with Ki-67 labeling index >5% (P

Background With combination of intraoperative ultrasound and palpation, more than 90-95% of all insulinomas will be found during exploration. But even in experienced hands some are not detected. When a familial multiple endocrine neoplasia type 1 (MEN-1) has been excluded, the question arises intraoperatively, whether we just failed to find an insulinoma or whether another illness is causing the disease. The latter may be a noninsulinoma pancreatic hypoglycemia caused by focal hyperplastic of islets or by neoplastic isleta with or without microadenomas (synonymous: “adult nesidioblastosis” or “insulinomatosis” by pathologists and “NIPHS” by clinicians). Our own experience with 20 out of 125 patients with pancreatic hyperinsulinism is demonstrated, where we did not find an insulinoma intraoperatively. In some of them operative flaws led to this result and in the majority preoperative diagnosis of NIPHS was confirmed. Thus NIPHS accounts for 16% of all forms of sporadic pancreatic hyperinsulinism and has to be integrated into our daily preoperative work-up and intraoperative management. Patients and methods The charts of 125 adult patients with documented endogenous hyperinsulinemic hypoglycemia were extracted, operated on between 1986 and 2008. All patients with benign or malignant solid insulinoma and all patients with familial MEN-1 were excluded, leaving 20 patients (xx%) with sporadic disease, in whom no insulinoma was detected during exploration. These were 4 men and 16 women with a mean age of 45.4 ± 14.8 years (range 18 to 76 years). Results Eleven patients underwent operation for a presumed insulinoma, of which the final diagnoses were insulinoma in 4 (three at the head and one at the tail of pancreas) and NIPHS in 7, respectively. The other 9 patients underwent operation for preoperatively diagnosed NIPHS and were all proven to have NIPHS, postoperatively. Patients with insulinoma were all cured by removal of their tumors. The 11 patients with NIPHS were treated by a partial or subtotal pancreatectomy and none had reported further episodes of neuroglycopenia after 77 months of follow-up. Three of them developed postoperative insulin-dependent diabetes mellitus. Conclusion When a circumscribed insulinoma cannot be detected by preoperative localization studies in patients with proven endogenous hyperinsulinimic hypoglycemia the biochemical results of oral glucose tolerance test (OGTT) and 72 hours fast should be reassessed, carefully. When the data clearly point to an insulinoma, a thorough surgical examination undertaken, with special focus of attention on the head and uncinate process of the pancreas. If still no tumor is found, the operation should be terminated. When results of OGTT and 72 hours fast assume NIPHS a selective arterial calcium stimulation test is indicated, since the necessary 70-80% pancreatectomy can be guided by results of the stimulated insulin gradient. Following these principles all 20 patients were cured in a mean follow-up of 7.5 years. In 2 patients (10%), however, extensive partial pancreatectomy resulted in a mild insulin dependent diabetes mellitus. Altogether sixteen out of 20 patients (%) with sporadic endogenous pancreatic hyperinsulinemia and failed demonstration of a single tumor proved to have NIPHS. Even when an insulinoma is suspected after biochemical analysis and preoperative localization study as well as intraoperative findings failed to show a tumor (n = 11) 7 patients (%) demonstrated to have NIPHS.

Introduction: Constitutively activated signal transducers and activators of transcription (STAT) proteins are found in various types of tumors. However, there is still very limited information about the role of STATs in breast cancer. The power of tissue microarray technique is the capability of doing a series of analyses of thousands specimens in a parallel fashion with minimal damage to the origin blocks. This study was designed with the application of tissue microarray to analyze the STAT3 status in breast cancer. Materials and Methods: Archival tissue specimens from 102 patients with primary invasive breast cancer were selected, and STAT3 expression was analyzed by immunohistochemical staining with tissue microarray. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histologic grading, and tumor-node-metastasis staging were also collected. Results: By multivariate analysis, the STAT3 expression turned out to be significantly related to the overall 5-year survival rate (P = 0.024). Conclusion: Immunohistochemical staining with tissue microarray was convenient and feasible for the analysis of STAT3 expression status in breast cancer. Our preliminary results are promising and deserve further evaluation. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2286–90)

Cognitive impairment was frequently reported in uremic patients with dialysis, but improvements of cognition after parathyroidectomy for symptomatic secondary hyperparathyroidism have never been reported before.Thirty-nine patients, who were successfully operated on with total parathyroidectomy plus autotransplantation were enrolled. Twenty-three dialysis patients, age50 years, who had a serum level of intact parathyroid hormone (iPTH) greater than 650 pg/ml, and who did not undergo parathyroidectomy were selected as the control group. The mini-mental state examination (MMSE) and the clinical dementia rating (CDR) test were administered to all patients. Before the operation, educational level, symptoms of bone pain, skin itching, general weakness and insomnia were recorded and serum levels of calcium, phosphorus, alkaline phosphatase (Alk-ptase), iPTH, aluminum, and hemoglobin were measured in the study and control groups. At 12-week postoperatively, serum levels of calcium, phosphorus, Alk-ptase, iPTH, and aluminum were measured again and at 16-week postoperatively, the MMSE and the CDR test were administered again. In the control group, both MMSE and CDR test were administered again after the period or 16-week.Serum calcium level was only significant difference (p = 0.002), whereas clinical symptoms, gender, etiologies of secondary hyperparathyroidism, duration of dialysis, educational level, age, and serum levels of phosphorus, Alk-ptase, iPTH, aluminum, and hemoglobin were not significantly different between the two groups. The educational level was the only factor affecting MMSE scores (p = 0.003). In the study group, at 12-week postoperatively, symptoms improved significantly, serum levels of calcium, phosphorus, Alk-ptase, iPTH, and aluminum decreased significantly, and at 16-week postoperatively, MMSE scores increased from 25 +/- 5 (mean +/- SD) to 26 +/- 5 (p0.001) and CDR scales decreased significantly (p0.001). Neither MMSE scores nor CDR scales of the control group changed significantly after the 16-week period.Parathyroidectomy for symptomatic secondary hyperparathyroidism can improve cognition.

Intravenous (i.v.) calcium chloride is usually given to treat symptomatic hypocalcemia; however, the extravasation of calcium solution may cause soft tissue and skin necrosis. After parathyroidectomy and autotransplantation for secondary hyperparathyroidism associated with end-stage renal failure, i.v. calcium infusion is often necessary to treat severe postoperative hypocalcemia. We reviewed 371 patients who underwent parathyroidectomy for secondary hyperparathyroidism between January 2000 and June 2005, 96 of whom received i.v. calcium postoperatively for symptomatic hypocalcemia. We report the cases of three (3%) of our own patients and of one patient referred to our hospital, who suffered skin necrosis after i.v. calcium solution administration. These reports show that i.v. calcium should be administered into large veins, or via a central line, and diluted in an appropriate volume of solution. Moreover, the calcium solution infusion should be ceased if the patient complains of tenderness over the injection site. If skin necrosis develops, we suggest early debridement and a simple split thickness skin graft to repair the skin defect. We report our experience to remind surgeons of the danger of calcium chloride injection and to discuss ways of preventing and treating this complication.

To investigate the usefulness of whole body scan (WBS) and serum thyroglobulin (Tg) measurement after thyroxine withdrawal during sequential follow-ups in patients with differentiated thyroid cancer (DTC).Two hundred and sixty-five consecutive DTC patients were enrolled. They were previously treated with near-total thyroidectomy and I-131 remnant ablation, without initial metastases or Tg antibodies. All had the first follow-up WBS and serum Tg measurement 6-12 months after initial treatment, and 165 patients received the second follow-up without further therapy. Positive/negative predictive values (PPV/NPV) were calculated by the outcome of patients being followed up for more than 8 years (mean+/-SD: 133+/-26 months).Serum Tg levels while the patients were off thyroxine therapy decreased spontaneously in 39.3% of the cases without further therapy. The NPV of the first follow-up serum Tg level was excellent:2 microg/L and0.5 microg/L were 95.1% and 98.2%, respectively. However, the PPV of the first follow-up serum Tg level was low:10 microg/L and 2-10 microg/L were 40% and 9.6%, respectively. The trend of Tg levels was more informative; the PPV was 62.5% in cases with an increase of serum Tg of10 microg/L and 16.6% with an increase of5 microg/L. However, decreasing Tg levels may associate with rapid deterioration of disease, in which cases decrease of Tg indicated dedifferentiation of the tumor. The diagnostic WBS showed the same picture in 91.5% of the patients. Only one patient (0.6%) turned from negative study to positive during the follow-up. In the meanwhile his serum Tg levels increased from 0.56 to 13.6 microg/L.It is most informative when both the trend and the levels of Tg during sequential follow-up are considered. The diagnostic WBS may be performed for selected patients with indication based on Tg levels to localize the disease.

To reduce the chance of recurrent hyperthyroidism, two methods of subtotal thyroidectomy were performed and compared. From January 1998 to December 2002, 340 patients were operated on with subtotal thyroidectomy. They were prospectively randomized into two groups. Group A included 166 patients and group B 174 patients. Group A patients had a 2.5 x 1 x 1 cm thyroid remnant on each side and group B patients had a 2.5 x 1 x 1 cm remnant on one side plus total lobectomy on the other side. Thyroid function tests including T(3), T(4), TSH, and antimicrosomal antibody (AMA) were checked preoperatively and in the follow-up period of 3 months, and later up to 26.4 +/- 1.1 months (mean +/- SE). The age, sex, duration of oral medicine, and blood loss of the two groups were not significantly different during surgery and the follow-up period. The operative time was less in group A (113 +/- 3.3 minutes) than that in group B (131 +/- 3.2 minutes) (p0.001). In the long-term follow-up period, recurrent hyperthyroidism was noted in 15 patients in group A and 3 patients in group B. The difference was significant (p = 0.003). Hypothyroidism was noted in 35 of the group A patients and in 46 of the group B patients. The differences between the two groups regarding hypothyroidism was not significant (p = 0.181). Multivariate logistic regression analysis revealed preoperative titers of AMAor = 6400, which was the only factor affecting the incidence of hypothyroidism in the later follow-up period. In consideration of hypothyroidism, recurrent hyperthyroidism, and postoperative complications, subtotal thyroidectomy with total lobectomy plus subtotal lobectomy provides a better outcome than bilateral subtotal lobectomy.

Previous studies have demonstrated that point mutations in all three ras genes (H-ras, K-ras, and N-ras) may occur in thyroid neoplasia. However, the overall incidence of ras mutations in thyroid tumors and their frequency in specific histologic types varies widely in different series. Many earlier studies have chosen allele-specific oligonucleotide hybridization approaches to examine ras mutations without further confirmation of the positive samples by DNA sequencing. In this study, mutational hot spots in exon 1 (codons 12/13) and exon 2 (codon 61) of the H-ras, K-ras, and N-ras were polymerase chain reaction (PCR) amplified and sequenced with an automatic sequencer. ras mutations were detected in 4 of 89 (4.5%) benign and malignant thyroid tumors. Three of 8 follicular carcinomas exhibited mutations in codon 61 of H-ras, K-ras, and N-ras, respectively, and mutation at codon 61 of N-ras was found in 1 of 12 follicular adenomas. No mutations were observed in the other tumors, which included 20 nodular goiters, 5 Hürthle cell adenomas, 42 papillary carcinomas, and 2 undifferentiated carcinomas. Our results, obtained by the direct sequencing technique, indicate a lower overall prevalence of ras oncogenes in thyroid tumors than reports in earlier series. However, the frequency of ras mutations in specific histotype of thyroid tumors and their exclusive involvement of codon 61 in our series are similar to those studies utilizing DNA sequencing to detect or to confirm ras gene alterations. The selective occurrence of ras mutations in benign and malignant follicular neoplasms indicates that ras gene alterations have a specific and early role in the development of follicular type of thyroid tumors in Taiwan.

To investigate the relationship between parathyroid hormone (PTH) gene polymorphisms and secondary hyperparathyroidism in Chinese hemodialysis (HD) patients.210 patients in one HD unit were enrolled as the study group and 203 age-matched health subjects were enrolled as controls. PTH genotypes were determined by polymerase chain reaction and restricted fragment length polymorphisms (RFLPs) of BstBI and DraII. B and b or D and d were indicated by the presence or absence, respectively, of BstBI and DraII at restriction sites on the PTH gene. Serum iPTH levels and serum total calcium (Sca), phosphate (Sp), bone-specific alkaline phosphatase (bAlk), and aluminum (Al) levels across different genotypes were compared.When polymorphisms at the BstBI the restriction site were investigated, the patients' BB, Bb, and bb genotype frequencies were 62%, 37%, and 1%, respectively. At the DraII restriction site, the patients' DD, Dd, and dd genotype frequencies were 78%, 17%, and 5%, respectively. No significant differences were found across the three genotypes, BB, Bb, and bb, in serum Sca, Sp, bAlk, Al and iPTH levels. DraII cleavage PTH gene polymorphisms displayed a similar pattern. Patients with BBDD haplotype were not found to have significantly higher serum iPTH levels than those with other haplotypes.Our study appears to indicate that PTH gene polymorphisms do not influence serum iPTH levels in Chinese HD patients.

Background It has been controversial to anastomose the severed recurrent laryngeal nerve after transection because when severed recurrent nerves are directly anastomosed, the vocal cords do not regain normal movements and are fixed in the median. The objective of this study was to learn whether direct neurorrhaphy is necessary if the recurrent laryngeal nerve is severed during thyroid or parathyroid surgery. Study design From 1998 to 2001, 12 patients who had a complete recurrent laryngeal nerve injury during thyroid or parathyroid surgery were enrolled into this study. Eight had primary repair of the nerve; four did not have repair because of cancer invasion. Patients were followed with laryngoscopic or laryngovideostroboscopic examination at 3 months and 6 months postoperatively. Subjective ratings of aspiration and voice quality were based on patient reports. Perceptual voice quality was rated according to grade, roughness, breathiness, asthenia, and strain (GRBAS) scales. If a patient's voice quality, aspiration, and GRBAS scales did not improve at 6 months postoperatively, medialization laryngoplasty was considered. Results Eight patients with immediate repair showed improved voice quality, aspiration, GRBAS scales, and maximum phonation time at 6 months after surgery. A significant decrease of glottal gap was also noted in patients with neurorrhaphy but not in four patients without neurorrhaphy. Medialization laryngoplasty was performed in all four patients without neurorrhaphy in the followup period. Immobilization of the vocal cord was noted in all of them, but only one in the neurorrhaphy group had an atrophy of the cord; all four patients without neurorrhaphy had atrophy. Conclusions Neurorrhaphy of the recurrent laryngeal nerve is a simple and effective procedure to improve voice quality, aspiration, GRBAS scales, glottal gap, and maximum phonation time by preventing atrophy of the vocal cord.

Background The changes in spermatogenesis after parathyroidectomy in patients with symptomatic secondary hyperparathyroidism have not been reported before. Study design Nineteen men with symptomatic secondary hyperparathyrodism were enrolled in our study. Their ages ranged from 29 to 50 years and duration of dialysis from 72 to 168 months. Before operation, serum levels of calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, prolactin, luteinizing homone, follicle-stimulating hormone, and testosterone were checked routinely in association with semen analysis. Those data were checked again 3 months after successful operation. Finally, 15 patients had total parathyroidectomy with subcutaneous autotransplantation of 60 or 90 mg of tissue and complete postoperative data was available for 13 patients. The semen analysis included sperm density, volume of semen, motility index, percentage of active motility, and percentage of normal morphology. Results Ten patients had normal sperm density (≥20 × 10 6 /mL), and nine patients had oligospermia ( 6 /mL) (n = 4) or azoospermia (n = 5). The ages of patients, duration of dialysis, and weight of removed parathyroid glands were quite similar between the two groups. The serum levels of calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and testosterone were not significantly different between the group with normospermia and the group with oligospermia or azoospermia. Three months after total parathyroidectomy with autotransplantation, the serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were markedly decreased; the percentage of active motility and motility index were markedly improved; the serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, and testosterone had no significant changes; and the volume of semen, sperm density, and percentage of normal morphology had no significant improvements. One patient, who had oligospermia with primary infertility, had paternity 6 months after parathyroidectomy, though his oligospermia remained unchanged at that time. Conclusion After parathyroidectomy, the sperm motility index and percentage of active motility can be improved. We speculate that increases in fertilization and paternity in uremic male patients can be expected after surgery.

Aims: Secondary hyperparathyroidism (HPT) worsens anemia and may cause hyporesponsiveness to recombinant human erythropoietin therapy (r-HuEPO). To investigate the effect of parathyroidectomy (PTX) on iron homeostasis and erythropoiesis, we conducted a prospective study in chronic hemodialysis patients who underwent PTX. Methods: Thirty-two patients were enrolled in this study. Based on the increases in hemoglobin level after PTX, patients were divided into responders and nonresponders. Iron homeostasis and erythropoiesis were assessed before and 1 and 3 months after PTX, hemoglobin and parathyroid hormone levels were monitored until 6 months after PTX. Results: In the responders, increased hemoglobin levels were observed in 15 patients at 1 and 3 months after PTX (8.0 ± 0.8 g/dl vs. 9.2 ± 1.3 and 10.1 ± 0.9 g/dl, p < 0.05). The nonresponders had higher pre-PTX hemoglobin levels than the responders (10.3 ± 1.6 g/dl vs. 8.0 ± 0.8 g/dl, p < 0.05). There was no further increase in hemoglobin at 6 months compared to 3 months after PTX in both groups. In neither group did PTX affect serum ferritin, transferrin saturation and serum erythropoietin level. Serum soluble transferrin receptor (sTfR) concentration was found to be higher in responders than in nonresponders (3.32 ± 1.28 mg/l vs. 1.70 ± 0.31 mg/l, p < 0.05). Conclusions: We conclude that PTX can improve anemia in hemodialysis patients with severe hyperparathyroidism and greater resistance to r-HuEPO therapy. The reversing of anemia does not involve altering iron mobilization. Pre-PTX hemoglobin and serum sTfR levels can predict the effect of PTX on correcting anemia.