The role of radioactive iodine in the management of patients with differentiated thyroid cancer - An oncologic surgical perspective.

With improved understanding of the biology of differentiated thyroid carcinoma its management is evolving. The approach to surgery for the primary tumour and elective nodal surgery is moving from a "one-size-fits-all" recommendation to a more personalised approach based on risk group stratification. With this selective approach to initial surgery, the indications for adjuvant radioactive iodine (RAI) therapy are also changing. This selective approach to adjuvant therapy requires understanding by the entire treatment team of the rationale for RAI, the potential for benefit, the limitations of the evidence, and the potential for side-effects. This review considers the evidence base for the benefits of using RAI in the primary and recurrent setting as well as the side-effects and risks from RAI treatment. By considering the pros and cons of adjuvant therapy we present an oncologic surgical perspective on selection of treatment for patients, both following pre-operative diagnostic biopsy and in the setting of a post-operative diagnosis of malignancy.

Pediatric endocrine surgery: a 20-year experience at the Mayo Clinic.

CONTEXT: Surgically managed endocrinopathies are rare in children. Most surgeons have limited experience in this field. Herein we report our operative experience with pediatric patients, performed over two decades by high-volume endocrine surgeons. SETTING: The study was conducted at the Mayo Clinic (a tertiary referral center). PATIENTS: Patients were <19 years old and underwent an endocrine operation (1993-2012). MAIN OUTCOME MEASURES: Demographics, surgical procedure, diagnoses, morbidity, and mortality were retrospectively reviewed. RESULTS: A total of 241 primary cases included 177 thyroid procedures, 13 neck dissections, 24 parathyroidectomies, 14 adrenalectomies, 7 paragangliomas, and 6 pancreatic procedures. Average age of patients was 14.2 years. There were 133 total thyroidectomies and 40 hemithyroidectomies. Fifty-three cases underwent a central or lateral neck dissection. Six-month follow-up was available for 98 total thyroidectomy patients. There were four cases of permanent hypoparathyroidism (4%) and no permanent recurrent laryngeal nerve (RLN) paralyses. Sequelae of neck dissections included temporary RLN neurapraxia and Horner's syndrome. Parathyroidectomy was performed on 24 patients: 20 with primary hyperparathyroidism (HPT), three with tertiary HPT, and one with familial hypocalciuric hypocalcemia. Three patients (16%) had recurrent HPT, all with multiglandular disease. One patient had temporary RLN neurapraxia. We performed seven bilateral and seven unilateral adrenalectomies; eight were laparoscopic. Indications included pheochromocytoma, Cushing's syndrome, adrenocortical carcinoma, congenital adrenal hyperplasia, and ganglioneuroma. One death was due to adrenocortical carcinoma. Five paraganglioma patients had succinate dehydrogenase subunit B mutations, and one recurred. Six patients with insulinoma underwent enucleation (n = 5) or distal pancreatectomy (n = 1). A single postoperative abscess was managed nonoperatively. CONCLUSION: Pediatric endocrine procedures are uncommon but can be safely performed with complication rates comparable to those of the adult population. It is imperative that these operations be performed by high-volume surgeons.

[Papillary thyroid carcinoma: clinical manifestations, recurrences and prognosis].

Papillary carcinoma was detected in 2512 cases out of 3048 patients with differentiated thyroid carcinoma who underwent surgery during a 61-year period at the Mayo Clinic. The clinical picture of papillary carcinoma was shown to be interrelated with the appearance of recurrences, metastases and with prognosis for life. Lethality and survival were estimated within 5, 10, 20, 30 and 40 years depending on the stage of the disease that allowed a separation and comparison of groups of low and high risk in connection with the further prognosis. Median follow-up was 14 +/- 0.9 years and the longest follow-up was 60 years. It was shown that if the tumor was confined to the neck and the tumor was grossly resected the survival rate did not differ from the level predicted by an actuarial curve, and the appearance of metastases in regional lymph nodes represented no real threat in low-risk patients.

Percutaneous ethanol injection for treatment of cervical lymph node metastases in patients with papillary thyroid carcinoma.

OBJECTIVE: The objective of this study was to evaluate the technique, efficacy, and side effects of percutaneous ethanol injection in patients with limited cervical nodal metastases from papillary thyroid carcinoma. SUBJECTS AND METHODS: Fourteen patients who had undergone thyroidectomy for papillary thyroid carcinoma presented with limited nodal metastases (one to five involved nodes) in the neck between May 1993 and April 2000. All patients had received previous iodine-131 ablative therapy with a mean total dose per patient of 7,548 MBq. Ten of the patients either were considered poor surgical candidates or preferred not to have surgery, and all were unresponsive to iodine-131 therapy. Each metastatic lymph node was treated with percutaneous ethanol injection, and patients received both clinical and sonographic follow-up. RESULTS: Twenty-nine metastatic lymph nodes in our 14 patients were injected. Mean sonographic follow-up was 18 months (range, from 2 months to 6 years 5 months). All treated lymph nodes decreased in volume from a mean of 492 mm(3) before percutaneous ethanol injection to a mean volume of 76 mm(3) at 1 year and 20 mm(3) at 2 years after treatment. Six nodes were re-treated 2-12 months after initial percutaneous ethanol injection because of persistent flow on color Doppler sonography (n = 4), stable size (n = 1), or increased size (n = 1). Two patients developed four new metastatic nodes during the follow-up period that were amenable to percutaneous ethanol injection. Two patients developed innumerable metastatic nodes that precluded retreatment with percutaneous ethanol injection. No major complications occurred. All patients experienced long-term local control of metastatic lymph nodes treated by percutaneous ethanol injection. In 12 of 14 patients, percutaneous ethanol injection was successful in controlling all known metastatic adenopathy. CONCLUSION: Sonographically guided percutaneous ethanol injection is a valuable treatment option for patients with limited cervical nodal metastases from papillary thyroid cancer who are not amenable to further surgical or radioiodine therapy.

Anaplastic thyroid carcinoma: a 50-year experience at a single institution.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive of human malignancies. However, there have been few large studies of histologically well-defined ATC. We report the results of a 50-year experience of this lethal malignancy. METHODS: We reviewed all cases of ATC managed in this institution between 1949 and 1999. One pathologist (J.R.G.) reviewed all pathologic material. Clinical details were obtained from medical records, and current status of all patients was determined. RESULTS: There were 134 cases, with a female-to-male ratio of 1.5:1 and a mean age of 67 years. Benign thyroid disease was present in 27 cases (20%) and well-differentiated thyroid carcinoma in 31 (23%). Sixty-two patients (46%) had distant metastases at diagnosis, and 98% of the tumors were locally invasive. Primary treatment was surgical for 96 patients (72%). Complete resection was achieved in 29 cases (30%), with "minimal residual disease" in 25. Neither extent of operation nor completeness of resection affected survival (P > .4). Postoperative radiotherapy gave slightly longer median survival (5 vs 3 months), which was not significant (P < .08). Multimodal therapy, including operation, chemotherapy, and radiotherapy, did not improve survival. CONCLUSIONS: The outlook for patients with ATC remains grim. Novel treatments for ATC are desperately needed.

Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake.

The ability of thyroid cancers to concentrate radioiodine (RAI) is dependent, in part, upon the expression and functional integrity of the sodium iodide symporter (NIS). However, some differentiated thyroid carcinomas (DTCs) and most undifferentiated thyroid carcinomas lack the ability to concentrate iodide and are thereby insensitive to 131I therapy. Variation of NIS protein expression may be an important factor in this behavior. We wished to determine whether NIS protein expression in primary DTC tumors correlated with the subsequent RAI uptake by metastatic lesions in the same patients. We obtained paraffin-embedded tissue specimens from 60 patients with metastatic thyroid cancer who had undergone total or near-total thyroidectomy at the Mayo Clinic for DTC and had known presence or absence of RAI uptake in their tumor deposits determined by total body scanning after thyroid hormone withdrawal. Tissue sections from the primary intrathyroidal tumors were subjected to immunostaining (IS) using a monoclonal antibody against human NIS. Slides were subsequently examined for specific IS by two independent reviewers. For each patient, whole body scan (WBS) uptake was recorded, and correlation between results of IS and WBS was analyzed. Of 43 patients with a positive WBS, 37 also had positive IS of their tumors. In six patients with negative IS, a positive WBS was documented, and in three of these cases TSH at the time of surgery was less than 0.3 mIU/liter. Of the 17 patients with negative WBS, 10 were also negative on IS. Positive IS accurately predicted a positive scan in our study in 84% of cases; the ability of the IS to detect all cases with a positive scan was 86%, and it increased to 90% when patients who were receiving thyroid hormone therapy at the time of surgery were excluded from the analysis. Overall, the results of our retrospective study suggest that NIS IS of the thyroidal primary tumor in patients with papillary and follicular thyroid cancers has substantial ability to predict the behavior of subsequent deposits of metastatic and recurrent cancer with respect to iodine trapping and concentration. Our findings require confirmation in prospective studies to more accurately determine the predictive ability of the test and its role in the postoperative management of patients with DTC. If confirmed, NIS IS of DTC primary lesions may prove useful in the management of patients with known or suspected metastatic thyroid cancer.

Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis.

BACKGROUND: Papillary thyroid cancer (PTC) in young patients may rarely be encountered with pulmonary metastases. Previous studies have suggested that, in the pediatric population, this may not portend a lethal outcome. Our present study, children with pulmonary metastases, was designed to clarify this issue. METHODS: Fourteen children and young adolescents (mean age, 13.5 years; range, 9.8-17 years) with PTC and pulmonary metastases were treated at our institution between 1937 and 1998. Surgical treatment consisted of total thyroidectomy (n = 10 patients), subtotal thyroidectomy (n = 3 patients), and a biopsy only procedure (n = 1 patient). All patients who underwent thyroidectomy also underwent a variety of cervical lymph node dissections, and all patients proved to have regional nodal disease. After the operation, 12 patients were treated with ablative doses of (131)I, 1 patient was treated with external beam irradiation, and all patients were placed on suppressive thyroid hormone therapy. The mean length of follow-up was 19.3 years (range, 1-45 years). RESULTS: Regional recurrent disease developed in 2 patients (15%). No patient experienced the development of worsening pulmonary disease or extra-pulmonary metastases. All patients with recurrent disease underwent selective nodal resections. No patient died of metastatic PTC. Seven patients (50%) remain completely free of disease and are probably cured; 7 patients (50%) are asymptomatic with residual pulmonary disease. CONCLUSIONS: A stepwise treatment approach allows long-term survival and frequent cure for young patients with PTC and concomitant pulmonary metastases.

A multidisciplinary study of the 'yips' phenomenon in golf: An exploratory analysis.

BACKGROUND: The 'yips' is a psychoneuromuscular impediment affecting execution of the putting stroke in golf. Yips symptoms of jerks, tremors and freezing often occur during tournament golf and may cause performance problems. Yips-affected golfers add approximately 4.7 strokes to their scores for 18 holes of golf, and have more forearm electromyogram activity and higher competitive anxiety than nonaffected golfers in both high and low anxiety putting conditions. The aetiology of the yips is not clear. OBJECTIVE: To determine whether the yips is a neurological problem exacerbated by anxiety, or whether the behaviour is initiated by anxiety and results in a permanent neuromuscular impediment. METHODS: In phase I, golf professionals assisted investigators in developing a yips questionnaire that was sent to tournament players (<12 handicap) to establish the prevalence and characteristics of the yips. Phase II measured putting behaviour in scenarios that contribute to the yips response. Four self-reported yips and 3 nonaffected golfers putted 3 scenarios using an uncorrected grip and a standard length putter. Heart rate was superimposed on the videotape and the putter grip was instrumented with strain gauges to measure grip force. Electromyograms and relative putting performance were also measured. RESULTS: The questionnaire was sent to 2,630 tournament players, of whom 1,031 (39%) responded (986 men and 45 women). Of these, 541 (52%) perceived they experienced the yips compared with 490 (48%) who did not. Yips-affected golfers reported that the most troublesome putts were 3, 4 and 2 feet (0.9, 1.2 and 0.6 metres) from the hole. Fast, downhill, left-to-right breaking putts and tournament play also elicited the yips response. Golfers affected by the yips had a faster mean heart rate, increased electromyogram activity patterns and exerted more grip force than nonrffected golfers and had a poorer putting performance. CONCLUSIONS: For <10 handicap male golfers and <12 handicap female golfers, the prevalence of the yips is between 32.5% and 47.7%, a high proportion of serious golfers. This high prevalence suggests that medical practitioners need to understand the aetiology of the yips phenomenon so that interventions can be identified and tested for effectiveness in alleviating symptoms. Although previous investigators concluded that the yips is a neuromuscular impediment aggravated but not caused by anxiety, we believe the yips represents a continuum on which 'choking' (anxiety-related) and dystonia symptoms anchor the extremes. The aetiology may well be an interaction of psychoneuromuscular influences. Future research to test the effect of medications such as beta-blockers should assist in better identifying the contributions these factors make to the yips phenomenon.

Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)].

Splenomegaly with sea-blue histiocytes is not associated with dyslipidemia, except in severe cases of hypertriglyceridemia, Tangier disease, or lecithin cholesterol acyltransferase deficiency. We describe two kindreds in which the sea-blue histiocyte syndrome was associated with an apoE variant in the absence of severe dyslipidemia. Both patients presented with mild hypertriglyceridemia and splenomegaly. After splenectomy both patients developed severe hypertriglyceridemia. Pathological evaluation of the spleen revealed the presence of sea-blue histiocytes. A mutation of apoE was demonstrated, with a 3-bp deletion resulting in the loss of a leucine at position 149 in the receptor-binding region of the apoE molecule [apoE (delta149 Leu)]. Although both probands were unrelated, they were of French Canadian ancestry, suggesting the possibility of a founder effect. In summary, we describe two unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. In addition, we provide evidence linking the syndrome to an inherited dominant mutation in the apoE gene, a 3-bp deletion on the background of an apoE 3 allele that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia.

Are posttherapy radioiodine scans informative and do they influence subsequent therapy of patients with differentiated thyroid cancer?

UNLABELLED: Posttherapy scans (PTS) with a gamma camera are typically used after therapeutic doses of 131I to visualize metastases that may not be seen with lower dose diagnostic scans. During a 16-month period, we studied 81 patients (64 with papillary thyroid cancer and 17 with follicular thyroid cancer), who had both a diagnostic whole-body scan (131I dose 3 mCi) and a PTS. A total of 117 PTS were evaluated. At the time of PTS, clinical or radiologic evidence of metastatic or residual disease was present in 68 patients (84%). The anatomic sites of known disease included, neck (63), mediastinum (23), lung (35), bone (14), trachea (16), esophagus (5), and brain (2). PTS showed focal areas of abnormal uptake not seen in diagnostic scans in 15 scans (13%). Areas with abnormal new uptake included: neck (5), lung (5), mediastinum (4), bone (2), and adrenal (1). In 7 patients (9%) the PTS results impacted future decisions regarding plans for subsequent diagnostic scanning and 131I therapy or changed the patient's risk group category. IN CONCLUSION: (1) 13% of 117 PTS demonstrated abnormal foci of 131I uptake not seen on pretherapy scans and (2) PTS changed management strategy in 9% of the studied patients.

FHIT and TSG101 in thyroid tumours: aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance.

OBJECTIVE: The chromosomal regions containing the two putative tumour suppressors, fragile histidine triad gene (FHIT) and tumour suppressor gene 101 (TSG101), are deleted frequently in thyroid tumours. We therefore analysed FHIT and TSG101 transcripts in a group of advanced thyroid tumours to establish their role in thyroid tumorigenesis. DESIGN: Retrospective analysis of FHIT and TSG101 mRNA transcripts and genomic DNA from cryo-preserved thyroid tumours. TP53, previously shown at the genomic level not to be mutated in this cohort of tumours, served as a control. PATIENTS: We analysed nine follicular thyroid carcinomas (FTC), six papillary thyroid carcinomas and six follicular adenomas (FA) and histologically normal thyroid tissue from four of the FA patients. MEASUREMENTS: Single stage and nested reverse transcription polymerase chain reaction (RT-PCR) products of FHIT, TSG101, and TP53 were analysed by agarose or polyacrylamide gel electrophoresis and sequenced. Genomic DNA was also analysed by polymerase chain reaction and sequencing (FHIT) or by Southern blotting (TSG101). Clinical data were correlated with the results of the mutation analysis. RESULTS: Truncated FHIT transcripts were observed frequently alongside full length transcripts with nested RT-PCR, most often in FTC, while single stage RT-PCR revealed only normal length transcripts in all tumours. Similar results were obtained for TP53, while abnormal TSG101 transcripts were detectable by single stage RT-PCR. Sequence analysis of the truncated FHIT and TSG101 transcripts revealed mainly exon skipping and alternate RNA processing events. Only a single point mutation (of TSG101) was found. Southern blotting for the TSG101 gene, and PCR amplification and sequencing of the FHIT gene showed no evidence of genomic abnormalities in either case, and there was no evidence of splice site mutations in the FHIT gene, suggesting that the truncated transcripts result from altered RNA processing. There was no relationship between tumour stage, grade or survival and the presence of FHIT or TSG101 abnormalities. CONCLUSIONS: Truncated FHIT and TSG101 transcripts in thyroid tumours reflect alternate mRNA splicing events, rather than genomic deletions. Such abnormal RNA processing seems to be common and widespread in thyroid neoplasms, as similar results were obtained by analysis of transcripts of TP53, which we had previously shown not to be mutated in these specimens. Although a pathogenetic role for these aberrant transcripts remains possible, no correlation was found with stage, histological grade or outcome in this small group of advanced thyroid malignancies. Relaxation of mRNA splice control appears to be a feature of follicular cell-derived thyroid neoplasms.

Prognostic indicators in differentiated thyroid carcinoma.

BACKGROUND: Thyroid cancer ranges from well-differentiated lesions with an excellent prognosis to anaplastic carcinoma, which is almost uniformly fatal. Thus, methods to assess the behavior of thyroid malignancies are necessary to arrive at appropriate treatment decisions. METHODS: We discuss the factors that affect the prognosis of patients with well-differentiated thyroid malignancies, including papillary, follicular, Hürthle cell, and medullary thyroid carcinomas. We also review the presentation, therapy, and outcome of patients seen at our center over a span of 50 years. These data have identified those prognostic factors that are predictive of survival and recurrence in differentiated thyroid cancer. RESULTS: Several classifications with different variables have been developed to define risk-group categories. Three widely used systems, in addition to the TNM staging system, include AGES, AMES, and MACIS. CONCLUSIONS: A better understanding of independently important prognostic variables will result in improved patient care and treatment.

Treating the patient with differentiated thyroid cancer with thyroglobulin-positive iodine-131 diagnostic scan-negative metastases: including comments on the role of serum thyroglobulin monitoring in tumor surveillance.

Differentiated thyroid cancer (DTC) patients, especially the 10% to 15% at high risk of cancer-related death, should have long-term monitoring for detection of recurrence or metastasis. Conventional radiologic and ultrasonographic imaging is useful for localization of recurrent or persistent disease. For patients who have had ablation of residual thyroid tissue, measurement of serum thyroglobulin (Tg) levels and radioactive iodine (RAI) imaging provide highly sensitive tools for early detection. Serum Tg is reliable only in the absence of Tg autoantibodies. Sensitivity increases with TSH stimulation, either by withdrawal of thyroxine (T4) therapy, or administration of recombinant TSH (rTSH). In some patients, serum Tg levels are positive but the RAI whole body scan (WBS) is negative. In these patients, either the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between Tg synthesis and the iodine-trapping mechanism. Recent literature suggests that empiric high-dose RAI therapy of Tg-positive diagnostic scan-negative patients may result in a high rate of visualization of uptake in posttherapy scans (PTS). Evidence for subsequent improvement of parameters of disease activity has also been presented. Almost all such reported cases had micrometastases that were not visualized by conventional imaging. In our experience, aggressive macrometastases with negative diagnostic WBS do not show significant uptake after therapeutic doses of RAI. The small size of micrometastases in the first group of patients and a possible defect of the iodine-trapping mechanism in the second group may explain this apparent discrepancy. Based on presently available information, a generalized recommendation for RAI therapy of Tg-positive, diagnostic scan-negative patients should await further studies. Meanwhile, in some high-risk patients, in the absence of alternative therapies, empiric RAI therapy is justified.

Impact of primary surgery on outcome in 300 patients with pathologic tumor-node-metastasis stage III papillary thyroid carcinoma treated at one institution from 1940 through 1989.

BACKGROUND: The pathologic tumor-node-metastasis (pTNM) system is universally used to define the extent of disease in human malignancies. This study evaluated the impact of initial therapy on cause-specific mortality (CSM) rates and recurrence rates in pTNM stage III papillary thyroid carcinoma. METHODS: Three hundred patients (median age, 58 years) were followed on average for 14 postoperative years. Of these, 246 patients (82%) had complete primary tumor resection; 208 patients (69%) had nodal metastases; 161 (54%) had locally invasive primary tumors; 45 patients (15%) underwent initial unilateral lobectomy (UL). Bilateral lobar resection (BLR) accounted for 242 patients (near-total, 54%; total thyroidectomy, 23%). RESULTS: The 30-year rates for CSM, distant metastases, nodal metastases, and local recurrence (LR) were 29%, 22%, 19%, and 16%, respectively. The 20-year rates for CSM were significantly higher (50% vs 14%) when primary tumor was incompletely resected (P = .0001). After complete resection, 20-year rates for CSM and LR after BLR were 12% and 10%, respectively, which were significantly lower (P < .05) than the 23% and 26% rates seen after UL. There were no significant differences in nodal metastases or distant metastases rates between UL and BLR (P > .4). The 20-year LR rate after total thyroidectomy (13%) was not different (P = .5) from the 11% seen after near-total thyroidectomy. CONCLUSIONS: In this nonrandomized evaluation of patients with pTNM stage III papillary thyroid carcinoma, the extent of primary thyroid resection appeared to significantly impact CSM and LR but did not apparently influence regional or distant metastasis.

Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma?

BACKGROUND: Controversy continues regarding the optimal extent of primary thyroid resection in most patients with papillary thyroid carcinoma (PTC), who are at minimal risk of cause-specific mortality (CSM). This study was designed to compare CSM and recurrence rates after either unilateral lobectomy (UL) or bilateral lobar resection (BLR) in patients with PTC considered low risk by AMES criteria. METHODS: Outcome was studied in 1685 patients initially treated during 1940 through 1991 and followed for up to 54 postoperative years (mean, 18 years). One thousand six hundred fifty-six patients (98%) had complete primary tumor resection; 634 (38%) had involvement of regional nodes. One hundred ninety-five patients (12%) had UL; BLR accounted for 1468 (near-total 60%; total thyroidectomy 18%). RESULTS: Thirty-year rates for CSM and distant metastasis were 2% and 3%, respectively. Twenty-year rates for local recurrence and nodal metastasis were 4% and 8%, respectively. There were no significant differences in CSM or distant metastasis rates between UL and BLR (P > .2). After UL, 20-year rates for local recurrence and nodal metastasis were 14% and 19%, significantly higher (P = .0001) than the 2% and 6% rates seen after BLR. CONCLUSIONS: UL was not associated with higher CSM rates, but it was associated with a significantly higher risk of locoregional recurrence. Thus BLR probably represents a preferable initial surgical approach to patients with low-risk PTC.

Indications, technique, and efficacy of alcohol injection of enlarged parathyroid glands in patients with primary hyperparathyroidism.

BACKGROUND: Percutaneous alcohol ablation of the parathyroid gland (PAAP) has been proposed as an alternative treatment for primary hyperparathyroidism in patients unsuitable for surgery. The current study aimed to determine the (1) selection criteria, (2) associated morbidity, and (3) efficacy of PAAP. METHODS: From 1987 to 1998, 36 patients with primary hyperparathyroidism (mean age 65 years) underwent PAAP. The indications for PAAP were (1) medical comorbidity, (2) technically unsafe reoperative surgery, (3) partial ablation of a single remaining gland, and (4) patient choice. RESULTS: There were no long-term complications. Two patients had temporary recurrent laryngeal nerve injury and 4 had temporary hypocalcemia. Over a median follow-up of 16 months, 12 (33%) of the patients remained eucalcemic. For analysis purposes patients were separated into 2 separate groups: 29 with attempted complete ablation and 7 with partial ablation of a single remaining gland only. Ten of the complete ablation group (34%) remained eucalcemic. In the partial ablation group only 2 remained eucalcemic, but all had adequately controlled serum calcium levels. CONCLUSION: PAAP should be considered for hyperparathyroid patients with excessive reoperative morbidity or prohibitive medical comorbidity or those in whom the intent is to partially ablate a single remaining enlarged gland. In these patients close follow-up of serum calcium is required, and repeat treatments may be necessary because recurrence of hypercalcemia is likely.

Differential loss of heterozygosity at 7q31.2 in follicular and papillary thyroid tumors.

We analysed 42 differentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary thyroid cancers (PTC) and 14 follicular thyroid carcinomas (FTC) with 13 microsatellite markers specific for the long arm of human chromosome 7 within 7q31; this region is deleted frequently in several other tumor types. Overall, 20 of the 42 samples analysed (48%) displayed LOH with one or more of the markers tested. LOH was detected most frequently (78%) in FTC, the most malignant of the thyroid tumors. A smallest common deleted region (SCDR) was defined in this tumor type flanked by markers D7S480 and D7S490. This SCDR is distinct from D7S522, the most commonly deleted locus in many other tumors, which was deleted in only one FTC. D7S522 did show LOH in two of six informative PTCs. None of the PTC and only two of the FAs showed LOH in the FTC SCDR. Since FA is considered a premalignant stage of FTC, our results suggest that inactivation of a putative tumor suppressor at 7q31.2 may be acquired during adenoma to carcinoma progression. The absence of LOH at this locus amongst PTC suggests that inactivation of this tumor suppressor is specific for FTC. In conclusion, LOH at 7q31 is a frequent event in differentiated thyroid cancer, and we have defined a 2 cM SCDR specific for FTC.