Recurrent renal hyperparathyroidism and DNA analysis of autografted parathyroid tissue

In spite of recent therapeutic advances, severe overt secondary hyperparathyroidism due to chronic renal failure necessitates parathyroidectomy and recurrent hyperparathyroidism is one of the most significant problems in this patient population. In the present study, the incidence of recurrent hyperparathyroidism was evaluated in relation to the histopathological features. Image cytometric DNA analysis was performed to estimate the proliferative potential of parathyroid tissue. The study comprised 248 patients who underwent parathyroidectomy from 1973 to 1991. The frequency of recurrent hyperparathyroidism after subtotal parathyroidectomy was 4 (21.1%) of 19 patients, the rate of graft-dependent recurrence after removal of residual parathyroid tissue with forearm autograft was 2 (50%) of 4 patients. The frequency of graft-dependent recurrence after total parathyroidectomy with forearm autograft was 16 (7.5%) of 212 patients. The frequency of recurrence was significantly higher (p<0.01) when nodular hyperplastic parathyroid tissue was autografted (17 of 68 patients, 25%) than when diffuse-hyperplastic tissue was grafted (1 of 105 patients, <1%). All 58 specimens subjected to image cytometric DNA analysis showed a diploid nuclear pattern cytometrically. However, the relative number of scattered cells that displayed cytometric nuclear DNA values outside the main diploid histogram peak was significantly greater (p<0.01) in nodular hyperplastic tissue before being autografted and in parathyroid tissue removed at re-operation performed for recurrence than in diffuse hyperplastic tissue. These clinical findings and results of DNA analysis clearly indicated that nodular hyperplastic parathyroid tissue has a higher growth potential, and it is concluded that to prevent graft-dependent recurrence, the nodular type of hyperplastic tissue should not be autografted.

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Resumen A pesar de recientes avances terapéuticos, el hiperpatiroidismo secundario a falla renal severa hace necesaria la paratiroidectomía, pero el hiperparatiroidismo recurrente constituye uno de los problemas más significativos. En el presente estudio se analizó la incidencia de hiperpatiroidismo recurrente en relación con los hallazgos histopatológicos. Se practicó análisis de DNA por citometría de imagen con el fin de estimar el potencial de proliferación del tejido paratiroideo. El estudio comprendió 248 pacientes sometidos a paratiroidectomía entre 1973 y 1991. La frecuencia hiperparatiroidismo recurrente después de paratiroidectomía subtotal fue 4/19 (21.1%), y la tasa de recurrencia dependiente del injerto, después de la resección paratiroidea con autoinjerto en el antebrazo, fue de 2/4 (50%). La frecuencia de recurrencia dependiente del injerto después de paratiroidectomía total con autoinjerto en el antebrazo fue de 16/212 (7.5%). La frecuencia de recurrencia apareció significativamente mayor (p<0.01) cuando se autotrasplantó tejido hiperplásico nodular (17/68; 25%) que cuando se autotrasplantó tejido hiperplásico difuso (1/105; <1%). La totalidad de los 58 especímenes sometidos a análisis de DNA por citometría de imagen exhibió un patrón nuclear diploide. Sin embargo, el número de células dispersas que exhibieron valores citométricos de DNA nuclear por fuera del pico principal del histograma diploide fue significativamente mayor (p<0.01) en el tejido hiperplásico nodular antes de ser autoinjertado y en el tejido paratiroideo resecado en el curso de la reoperación realizada por recurrencia, que en el tejido hiperplásico difuso. Estos hallazgos clínicos y los resultados del análisis de DNA indican claramente que el tejido paratiroideo hiperplásico nodular posee un mayor grado de potencial de crecimiento, y se llega a la conclusión que para prevenir la recurrencia dependiente del injerto no se debe autoinjertar el tipo nodular de tejido hiperplásico.

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Résumé Malgré des progrès thérapeutiques récents, l-hyperparathyroïdie secondaire en rapport avec l'insuffisance rénale nécessite une parathyroïdectomie. L'hyperparathyroïdie récidivante est un des problèmes les plus importants. Dans cette étude, l'incidence de la récidive de l'hyperparathyroïdie a été évaluée par rapport à des données d'anatomie pathologique. L'analyse par cytométrie de flux de l'AND a été réalisée pour évaluer le pouvoir de prolifération du tissu parathroïde. Deux cent quarante huit patients ayant eu une parathyroïdectomie entre 1973 et 1991 ont été étudiés. La fréquence de la récidive de l'hyperparathyroïdie après parathyroïdectomie subtotale était de 4/19 (21.1%), celle de récidives du greffon après exérèse du tissu résiduel et autotransplantation à l'avant-bras était de 2/4 (50%). La fréquence de récidive du greffon après parathyroïdectomie totale et autotransplantation à l'avant-bras a été de 16/212 (7.5%). La fréquence de récidive était plus élevée (p<0.01) lorsque le tissu greffé était de siège d'une hyperplasie nodulaire (17/68; 25%) que lorsque le greffon etait le siège d'une hyperplasie diffuse (1/105; <1%). Les 58 échantillons étudiés an cytométrie de flux ont montré une diploïdie d'ADN. Le nombre de cellules dispersées ayant une disposition non diploïde était plus important (p<0.01) en cas d'hyperplasie nodulaire avant l'autotransplantation et en cas d'exérèse de tissu parathyroïde pour récidive qu'en cas d'hyperplasie diffuse. Ces données cliniques et les résultats d'analyse cytométrique indiquent clairement que le tissu parathyroïde hyperplasique a une puissance de croissance élevée et, pour éviter les récidives du greffon, il ne faut pas autotransplanter de tissu hyperplasique.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Raman spectroscopy of parathyroid tissue pathology

Primary hyperparathyroidism (HPT) in 80% of patients is due to a solitary parathyroid adenoma, while in 20% multigland pathology exists, usually hyperplasia [Scott-Coombes, Surgery, 21(12):309–312, 2003]. Despite recent advances in minimally invasive parathyroidectomy, better preoperative localisation techniques and intraoperative parathyroid hormone (PTH) monitoring, a 4% failure rate [Grant CS, Thompson G, Farley D, Arch Surg, 140:47–479, 2005] persists making accurate differentiation between adenomas and hyperplasia of prime importance. We investigated the ability of Raman spectroscopy to accurately differentiate between parathyroid adenomas and hyperplasia. Raman spectra were measured at defined points on the parathyroid tissue sections using a bench-top microscopy system. Multivariate analysis of the spectra was carried out to construct a diagnostic algorithm correlating spectral results with the histopathological diagnosis. A total of 698 spectra were analysed. Principal-component (PCA)-fed linear discriminant analysis (LDA) used to construct a diagnostic algorithm. Detection sensitivity for parathyroid adenomas was 95% and hyperplasia was 93%. These preliminary results indicate that Raman spectroscopy is potentially an excellent tool to differentiate between parathyroid adenomas and hyperplasia.     

DNA patterns in parathyroid disease predict postoperative parathyroid hormone secretion

Flow cytometric analysis of the nuclear deoxyribonucleic acid (DNA) content of parathyroid glands excised from patients with hypercalcemic hyperparathyroidism has identified three distinct DNA patterns. The most frequent pattern showed a high percentage of cells with tetraploid DNA, which indicated an increase in the G2 and M phase of the cell cycle. Thirty-four patients were found to have abnormal tetraploid DNA content. One patient had a normal diploid pattern, and seven were found to have an aneuploid DNA population in their excised parathyroid glands. This unexpected finding of aneuploid DNA appears to be an unique feature of these endocrine glands because they have no histologic or clinical characteristics of malignant change. All patients have remained normocalcemic and clinically well after excision of only grossly enlarged glands. Postoperative parathyroid hormone (PTH) levels were correlated in 17 patients with DNA analyses of biopsy specimens from 30 normal-sized glands which were left in situ. Seven patients with elevated PTH postoperatively had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had been taken. In 10 patients with normal PTH levels, six had normal diploid patterns, whereas four had high tetraploid DNA in their gland biopsy specimens. DNA content present in biopsy specimens of normal-sized, in situ glands was predictive (p less than 0.042) of parathyroid gland secretory activity. These findings suggest that the stimulus for parathyroid gland hyperfunction often affects more than a single enlarged gland and persists after clinical cure, as shown by a more rapid cell turnover in some remaining glands and continued hypersecretion of hormone.     

Nuclear DNA analysis of hyperplastic parathyroid glands in multiple endocrine neoplasia type I.

Twenty-four hyperplastic parathyroid glands from 11 patients with multiple endocrine neoplasia type I (MEN-I), and 36 hyperplastic parathyroid glands in 15 patients with sporadic primary hyperparathyroidism, ie, not associated with MEN, were analyzed for DNA by flow cytometry. Sixteen of 24 hyperplastic parathyroid glands from patients with MEN-I were DNA diploid, and eight were DNA aneuploid. Thirty-three of 36 hyperplastic parathyroid glands from patients without MEN were DNA diploid, and only three were DNA aneuploid. The mean percentage of 4c level (a measure of the G2M phase of the cell cycle) of DNA diploid hyperplastic parathyroid glands taken from patients with MEN-I was 8.1% +/- 4.5%, which is significantly higher than the 3.5% +/- 3.4% for those taken from patients without MEN. Our results show that there is a difference in nuclear DNA content between hyperplastic parathyroid glands in patients with MEN-I and those in patients without MEN.     

Thallous chloride uptake and DNA profile in parathyroid adenomas

Thallium isotope scintigraphy is used to localize parathyroid adenomas but the mechanism underlying the technique is poorly understood. While larger adenomas are reliably localized the results are less certain for small tumours. This study explores the relationship between cellular DNA profile and thallium uptake (localization accuracy) in 24 parathyroid adenomas. The DNA profile was assessed using flow cytometry and standard subtraction thallium scintigraphy was performed before surgery. Fifteen of the 24 adenomas demonstrated excessive mitotic activity and 13 of these glands were accurately localized. Of the remaining nine glands, only five were localized accurately (P less than 0.01, chi 2 test including Yates' correction). This difference in thallium uptake could not be accounted for on the basis of gland weight. Thallium localization of parathyroid adenomas is related to mitotic activity. This may explain some of the limitations of this technique.     

The use of radioiodinated toluidine blue for preoperative localization of parathyroid pathology

The efficiency of preoperative radioactive toluidine blue (RTB) scintigraphy for the localization of parathyroid pathology was evaluated prospectively in 69 patients (age range, 15 to 81 years; mean, 56 years) with primary hyperparathyroidism. Four patients have previously undergone negative exploratory surgery. Patients underwent preoperative dual radionuclide parathyroid-RTB/technetium 99m (Tc 99m)-thyroid scintigraphies with a computer-interfaced gamma-camera with a pinhole collimator. Computer-acquired scintigraphic data were analyzed for parathyroid localizations by an RTB-parathyroid/thyroid superposition technique. At surgery, parathyroid adenomas were found in 64 patients (single adenomas in 60 patients; two adenomas in four patients), nine of these adenomas were mediastinal. Four patients had parathyroid hyperplasia. One patient had no parathyroid pathology (negative exploratory surgery). Correlation between the surgical-pathologic findings and the scintigraphic RTB localization studies disclosed a sensitivity of 87%, with a specificity of 94%, and an overall accuracy of 92%. The routine use of preoperative scintigraphic parathyroid-RTB/Tc 99m-thyroid localization has proved to be highly effective, enabling detection of small hyperfunctioning parathyroid glands in normal and ectopic locations in a wide range of weights. In this series a success rate of 98% was achieved on initial and reexploratory surgery for primary hyperparathyroidism.     

甲状旁腺损伤相关的临床解剖学研究与原因分析

随着甲状腺癌发病率的升高,随之开展的甲状腺手术也越来越多。甲状旁腺与甲状腺关系紧密复杂且位置多变、血供脆弱,其损伤所带来的甲状旁腺功能减退成为了术后常见并发症之一。甲状旁腺损伤或功能障碍的原因是多方面的,既有解剖学因素,包括形态、颜色、数量、位置和血供上的变异,也与术者操作技巧或能量器械的运用有关,而血供的破坏与组织的...     

Rapid parathyroid hormone analysis during venous localization

OBJECTIVE: To determine the usefulness of the rapid parathyroid hormone (PTH) assay during venous localization for primary hyperparathyroidism (1 degrees HPTH). SUMMARY BACKGROUND DATA: Remedial exploration for persistent 1 degrees HPTH poses a significant challenge when noninvasive preoperative localization studies are negative. Based on experience with the intraoperative rapid PTH assay, this technique was extrapolated to the interventional radiology suite and generated near real-time data for the interventional radiologist employing on-site hormone analysis, with a 12-minute turnaround time from blood sampling to assay result. METHODS: Between November 1997 and July 2002, 446 patients with 1 degrees HPTH were referred for treatment. Of these, 56 (12.5%) represented remedial patients who had each undergone one or more previous cervical explorations. Noninvasive imaging studies were positive for or suggestive of localized disease in 49/56 (87.5%) of these patients, who therefore proceeded directly to surgical exploration. Seven patients with persistent 1 degrees HPTH and negative noninvasive studies underwent selective venous sampling employing a rapid PTH assay in the interventional suite. RESULTS: Venous localization demonstrated an apparent PTH gradient in six of the seven patients. In three, a subtle gradient demonstrated in near real-time prompted additional sampling, which confirmed an unequivocal hormone gradient. In an additional case, the absence of a gradient on initial sampling prompted further sampling, which was positive. All of the patients were explored, and in five of the six patients with a positive PTH gradient, a parathyroid adenoma (mean weight 636 +/- 196 mg) was resected from a location predicted by venous localization. In the sixth patient with a positive gradient, parathyroid tissue was not identified; however, there was a significant fall in the intraoperative PTH values, and immediate postoperative and follow-up laboratory data at 1 month are indicative of a cure. In the one patient with negative localization, abnormal parathyroid tissue could not be located during surgical exploration. CONCLUSIONS: The rapid PTH assay is a major adjunct for obtaining informative venous localization in patients with persistent 1 degrees HPTH. This information is extremely helpful to the surgeon in this challenging group of patients and resulted in a 100% cure rate when a venous gradient was demonstrated. The authors now employ this technique routinely in remedial patients with negative noninvasive imaging studies.     

DNA histogram of parathyroid tissue in determining extent of parathyroidectomy

In an attempt to better define hyperplasia from adenoma and for more accurate discernment of grossly normal but histologically abnormal presumed hyperfunctioning gland, parathyroid tissue obtained at operation was subjected to flow cytometric analysis producing DNA histogram. Seventeen abnormal specimens and seven normal specimens obtained from parathyroidectomy cases were placed in RPMI 1640 culture medium, treated to produce a monodispersed cell suspension, and stained with propidium iodide fluorescent dye to provide a measure of DNA content that could be graphically demonstrated. All cell cycles for affected cell populations could be demonstrated on DNA histogram in the G0G1, S, and G2M phases. Proliferative index was arbitrarily derived by combining percentages of G2M plus S phases. It was apparent that the value so derived showed a tendency for higher value for the abnormal parathyroid tissue but the overlap was sufficient so that no specific discriminating value could be placed on DNA histogram. While flow cytometry may not be of significant use in intraoperative identification of abnormal parathyroid tissue, the values obtained may indicate that a spectrum of activity occurs in hyperparathyroidism that cannot be fully appreciated at the present time and that may in the light of incomplete knowledge manifest itself in the clinical state of hyperparathyroidism and hypercalcemia. The findings of our flow cytometry study may indeed lend credence to the view that all hyperparathyroidism represents a four-gland hyperfunction although this does not support as a consequence routine subtotal parathyroidectomy but should stimulate further inquiry into the pathogenesis of primary hyperparathyroidism.     

Intraoperative parathyroid hormone assay and parathyroid reoperations

BACKGROUND: The purpose of this study was to determine whether intraoperative parathyroid hormone (IOPTH) assay improved results of reoperations. METHODS: One hundred two patients with persistent/recurrent sporadic primary hyperparathyroidism underwent 108 reoperations (1996-2002). IOPTH was not used (n=58) from 1996-1998 (group 1). IOPTH was used (n=50) from 1999-2002 (group 2). Sensitivity and positive predictive value of IOPTH and its influence on surgical strategy were analyzed. A 50% decrease occurring 10 minutes after removal of parathyroid tumor was used to determine if all abnormal tissue had been removed. RESULTS: Groups 1 (58 patients) and 2 (50 patients) were comparable except for duration of follow-up. The cure rate was 84% (group 1, 87%; group 2, 82%, P=0.7). Hypocalcemia developed in 20 patients (permanent in 2 patients). There was 1 permanent vocal cord paralysis and 1 patient died of toxic shock syndrome. IOPTH successfully predicted cure in 44 of 49 patients (sensitivity, 90%); the positive predictive value was 90%. Values for parathyroid hormone level and the ratio parathyroid hormone/calcium at day 1 were at least as accurate as IOPTH in predicting cure. IOPTH was helpful in 1 patient but misleading in 4 patients. It failed to modify intraoperative strategy in most other patients. CONCLUSIONS: IOPTH testing was relatively reliable in patients with persistent or recurrent sporadic primary hyperparathyroidism, but the test unfortunately failed to improve the overall success rate at reoperation.     

肾源性腺瘤临床病理学分析

目的 探讨肾源性腺瘤临床病理学特点.方法经病理确诊的肾源性腺瘤患者11例.男5例,女6例.平均年龄56(37～78)岁.对肿瘤进行临床病理学观察并复习文献.结果 11例肿瘤发生于输尿管2例,膀胱9例.9例膀胱肾源性腺瘤中行膀胱部分切除术1例,行经尿道膀胱肿瘤电切术8例.发生于输尿管2例分别行右输尿管镜检术及左输尿管切开取石术.患者术后病理确诊为肾源性腺瘤8例,非典型性肾源性腺瘤2例,肾源性腺瘤恶变1例.镜下肾源性腺瘤表现为典型的肾小管样形态;非典型性肾源性腺瘤细胞核大、深染、核仁明显及核分裂象;肾源性腺瘤恶变者局部瘤细胞保持典型肾源性腺瘤的基本组织结构,周围同种形态的细胞失去细胞间黏附力,呈弥漫实性生长并侵犯浅肌层.非典型性及恶变者3例分别定期行羟喜树碱、吡柔比星及表柔比星膀胱内灌注治疗.11例患者平均随访46(24～104)个月.复发1例,死于其他疾病1例,未复发9例.结论肾源性腺瘤临床少见,临床症状及膀胱镜检查均无特异性;病理形态学与肌浸润行为证据上提示肾源性腺瘤可以恶变;治疗以局部切除为主,非典型性和恶变者进一步行膀胱内定期灌注治疗;肾源性腺瘤术后需长期密切随访.

Abstract：

Objective To investigate the clinical and pathological characteristics of nephrogenic adenoma. Methods Eleven patients were diagnosed as nephrogenic adenoma including 5 men and 6 women, aged 37-78 years (56 on average). The pathological findings in all cases of nephrogenic adenoma were presented with a review of the literature. Results Eleven cases of nephrogenic adenomas were evaluated, 2 cases were in ureter and 9 cases were in the bladder. Eight of the 9 bladder cases underwent TUR-BT surgery in continuous epidural anesthesia, 1 case underwent partial cystectomy with general anesthesia. A right ureteroscopy and left ureterolithotomy were performed respectively in continuous epidural anesthesia for the 2 cases in ureter. The final diagnosis was based on histopathological findings. For all of cases, 8 cases were diagnosed as nephrogenic adenomas, 2 cases as atypical nephrogenic adenoma and 1 case as nephrogenic adenoma with malignant transformation. The microscopic appearance of nephrogenic adenoma demonstrated that morphology closely resembled aberrant tubules of the kidney. In addition, atypical nephrogenic adenomas appeared as the presence of cytologic atypia, including nuclear enlargement, nuclear hyperchromasia and prominent nucleoli. The morphologic changes of nephrogenic adenomas with malignant transformation were that tumor cells retained the basic structural characteristics of typical nephrogenic adenomas, and the similar morphological cells lost adhesion ability among cells and presented diffuse solid growth in the surrounding area.Intravesical perfusion was further performed for treating the patients with atypical nephrogenic adenomas or nephrogenic adenomas with malignant transformation. The mean patient follow up was 46 months (range, 24- 104 months), and there was only 1 case of recurrence. Conclusions Nephrogenic adenoma is an uncommon benign lesion of the urinary tract. The symptoms and cystoscopic manifestations are not unique. We reported one patient of nephrogenic adenomas with malignant transformation and provided some evidence for malignant alteration in morphology and invasive behavior. All patients underwent local excision of the lesions. Intravesical perfusion was further performed for treating the patients of atypical nephrogenic adenomas or nephrogenic adenomas with malignant transformation. Whether it is nephrogenic adenoma or atypical nephrogenic adenoma, long-term follow-up after treatment is necessary.     

甲状旁腺病变的超声诊断及多种影像学对比分析

评价超声在甲状旁腺疾病诊断中的价值及多种影像学检查技术在甲状旁腺疾病诊断中的对比分析。方法回顾性分析于我院行甲状旁腺手术切除患者94例,共104个病灶。观察病变的声像图特征,对比分析多种影像学检查结果。结果不同甲状旁腺病变的超声声像图特征具有差异性,超声诊断甲状旁腺病变的敏感度为82.69%(86/104),对于直径1cm的病变,超声诊断的敏感度明显高于其他检查单独使用,而对于合并甲状腺结节的病变超声的敏感度低于核素显像及超声联合核素检查(P均0.05)。结论超声可作为甲状旁腺病变诊断的首选检查方法,联合运用各种影像学检查,可更好地进行病变的术前定位及诊断。     

Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma

BACKGROUND: Distinction of parathyroid cancer from atypical parathyroid adenoma (APA) at operation is difficult. The aim of this study was to determine whether parathyroid cancer and APA have different operative findings and long-term outcomes. METHODS: A retrospective review was undertaken of patients with suspicious or malignant parathyroid tumours treated between 1974 and 2005. Parathyroid cancer was defined as a lesion with vascular or tissue invasion, and APA as a neoplasm with broad fibrous bands, trabecular growth, mitosis and nuclear atypia. RESULTS: Twenty-seven patients with suspicious or malignant parathyroid tumours were identified. After histological review, parathyroid cancer was confirmed in 11 patients (group 1) and 16 tumours were classified as APA (group 2). The clinical presentation and operative findings of the two types of tumour were indistinguishable. At initial surgery, seven patients in group 1 underwent en bloc resection, and four had parathyroidectomy. Four of the seven patients who had en bloc resection had recurrences. No recurrences were observed in the other seven patients in group 1 at a median follow-up of 65 months. In group 2, eight patients had en bloc resection and eight had parathyroidectomy; no patient had recurrence at a median follow-up of 91 months. CONCLUSION: Operative findings cannot distinguish APA from parathyroid cancer reliably. Without evidence of macroscopic local invasion, the value of en bloc resection at initial surgery remains debatable.     

甲状旁腺腺瘤合并甲状腺结节34例临床分析

目的探讨甲状旁腺腺瘤合并甲状腺结节的诊断及外科治疗方法。方法回顾性分析我院收治的34例甲状旁腺腺瘤合并甲状腺结节的临床诊治经验。结果甲状旁腺腺瘤单侧单发多见(3l/34),单侧甲状旁腺腺瘤合并同侧甲状腺结节多见(25/31)。甲状腺结节病变性质主要为结节性甲状腺肿(27/34)。34例均行外科手术治疗。术后早期有8例患者出现短时的低钙血症,余无明显并发症。术后随访26例,全部患者甲状旁腺腺瘤均无明显复发迹象,结节性甲状腺肿患者有2例术后复查再次发现甲状腺结节,均予以动态观察,未行进一步手术切除,其余病例甲状腺结节均无复发。结论手术切除是治疗甲状旁腺腺瘤合并甲状腺结节的最有效的方法,最常用手术方式为单侧颈部探查术,术前定性及定位诊断结合术中诊断是手术成功的关键。     

Modern parathyroid surgery: a cost-benefit analysis of localizing strategies

HYPOTHESIS: Preoperative and intraoperative localizing techniques are more cost-effective than a nondirected bilateral neck exploration in the initial treatment of primary hyperparathyroidism (HPT). DESIGN: A clinical outcome model was developed to simulate the surgical management of primary HPT. Clinical scenarios modeled included a nondirected bilateral neck exploration and surgery using the following localizing strategies: preoperative technetium Tc 99m sestamibi scanning, intraoperative "quick" intact parathyroid hormone assay, or intraoperative radioguidance. Average total charges based on intent to treat were estimated from our practice and from the literature. MAIN OUTCOME MEASURES: Average total charges per patient (for the primary operation and for reexploration for persistent HPT, if needed), incidence of surgical failure (ie, persistent HPT), and risk of recurrent laryngeal nerve injury (cumulative risk of the primary procedure and a subsequent operation for persistent HPT). RESULTS: The use of any localizing strategy reduced total charges, risk of persistent HPT, and cumulative risk of recurrent laryngeal nerve injury compared with a nondirected bilateral neck exploration. The greatest cost savings and the lowest risk of recurrent laryngeal nerve injury were achieved when technetium Tc 99m sestamibi scanning was combined with intraoperative radioguidance. The lowest rate of persistent HPT was found when technetium Tc 99m sestamibi scanning was combined with an intraoperative parathyroid hormone assay. CONCLUSIONS: Limited parathyroid surgery using any localizing strategy is cost-effective, safe, and efficacious in the management of primary HPT. The cost benefit was primarily achieved by reduced operative charges and immediate hospital discharge rather than a lower need for reexploration for persistent HPT.     

Cytogenetic analysis of the pathology of frozen shoulder

Background:

Frozen shoulder (FS) is a debilitating musculoskeletal condition with an uncertain etiology and pathogenic mechanism. The aim of this study was to investigate the hypothesis that an alteration in the level of cytokines may disrupt the normal inflammatory and tissue healing process in the shoulder, leading to the development of FS.

Materials and Methods:

A prospective case–control study was undertaken, analyzing patients undergoing arthroscopic treatment of FS and control patients being treated for subacromial bursitis. Synovial biopsies were taken from all subjects. Synovial RNA levels were analyzed using quantitative polymerase chain reaction (qPCR)

Results:

Thirteen patients with FS were recruited, four of whom were diagnosed with diabetes mellitus, along with 10 control patients. Cytogenetic analysis using qPCR revealed both fibrogenic cytokine matrix metalloproteinase 3 (MMP 3) (1.98×10 ⁵ vs. 755.0, P=0.068) and inflammatory cytokine interleukin 6 (IL 6) (1679.2 vs. 372.8, P=0.062) to be elevated in FS cases as compared to controls. Comparison between diabetic and non-diabetic patients revealed a decrease in the level of expression of inflammatory cytokine, monocyte colony stimulating factor (M-CSF) (12,496 vs. 305.1, P=0.04) in diabetic FS patients.

Conclusions:

The results demonstrate that levels of inflammatory and fibrogenic cytokines are elevated in the synovium of patients with FS compared with controls. This indicates that altered levels of inflammatory cytokines may be associated with the pathogenesis of inflammation evolving into fibrosis, which is the characteristic feature of FS. We have also shown the opposite to be the case in patients with diabetic FS.