Thompson, Geoffrey B.

Background: Historical outcomes in anaplastic thyroid carcinoma (ATC) are poor, with a median survival of only 5 months and <20% of patients surviving 1 year from diagnosis. We hypothesized that survival in newly diagnosed patients with stages IVA and IVB locoregionally confined ATC might be improved by utilizing an aggressive therapeutic approach, prioritizing both the eradication of disease in the neck and preemptive treatment of occult metastatic disease. Methods: Between January 1, 2003, and December 31, 2007, 25 new ATC patients were evaluated at our institution. Of these 25 patients, 10 (40%) had metastatic disease at diagnosis and therefore underwent palliative treatment, whereas 5 (20%) had regionally confined disease and desired treatment at their local medical facilities. The remaining 10 consecutive patients (40%) had regionally confined ATC and elected aggressive therapy combining individualized surgery (where feasible), intensity-modulated radiation therapy (IMRT), and radiosensitizing + adjuvant chemotherapy intending four cycles of docetaxel + doxorubicin. Outcomes were assessed on an intention to treat basis. Results: There were no deaths from therapy, but hospitalization was required in two patients (20%) because of treatment-related adverse events. Five patients (50%) are alive and cancer-free, all having been followed >32 months (range: 32–89 months; median: 44 months) with a median overall Kaplan–Meier survival of 60 months. Overall survival at 1 and 2 years was 70% and 60%, respectively, compared to <20% historical survival at 1 year in analogous patients previously treated with surgery and conventional postoperative radiation at our and other institutions. Conclusions: Although based upon a small series of consecutively treated patients, an aggressive approach combining IMRT and radiosensitizing plus adjuvant chemotherapy appears to improve outcomes, including survival in stages IVA and IVB regionally confined ATC, but remains of uncertain benefit in patients with stage IVC (metastatic) disease. Also uncertain is the optimal chemotherapy regimen to use in conjunction with IMRT. Further multicenter randomized trials are required to define optimal therapy in this rare but deadly cancer.

Abstract Background Controversy exists regarding the aggressiveness of initial therapy in childhood papillary thyroid cancer (PTC). Few studies with long‐term outcome exist and second primary malignancies have rarely been analyzed. Methods We studied 215 PTC patients younger than 21 years old managed during 1940 through 2008. The patients were aged 3–20 year old (median age = 16 years); the median follow‐up was 29 years. Recurrence and mortality details were taken from a computerized database. Results Median primary tumor size was 2.2 cm. Six percent had distant metastases at presentation, 5% had incomplete tumor resection, 86% had nodes removed at initial surgery, and 78% had nodal metastases. After complete surgical resection, PTC recurred in 32% by 40 years. At 20 years, the recurrence rates at local, regional, and distant sites were 7, 21, and 5%, respectively. During 1940–1969, local and regional recurrence rates after unilateral lobectomy (UL) were significantly ( P < 0.001) higher than after bilateral lobar resection (BLR). During 1950–2008 radioiodine remnant ablation (RRA) was administered within 18 months to 32%; it did not diminish the 25‐year regional recurrence rate of 16% seen after BLR alone ( P = 0.86). Only two fatal events from PTC occurred at 28 and 30 years, for a cause‐specific mortality at 40 years of only 2%. All‐causes mortality rates did not exceed expectation through 20 years, but from 30 through 50 years, the number of deaths was significantly ( P < 0.001) higher than predicted. Fifteen of 22 deaths (68%) resulted from nonthyroid malignancy. Conclusion Survival from childhood PTC should be expected, but later death from nonthyroid malignancy is disconcerting. Seventy‐three percent of those who died from nonthyroid malignancy had received postoperative therapeutic irradiation.

AbstractBackgroundIntense disease surveillance and frequent lymph node metastases (LNMs) in papillary thyroid cancer (PTC) have resulted in increased locoregional recurrences. We examined the safety and efficacy of an optimized surgical approach including preoperative ultrasonograpy (US), bilateral thyroidectomy, routine compartment VI dissection, and lateral neck dissection for LNM.MethodsDuring 1999–2006, a total of 420 patients underwent optimized primary surgery; 291(69%) females, median age 46 years; follow‐up 98%, median 4.4 years. Patients were reviewed for tumor characteristics, pattern of LNM, staging, and outcomes.ResultsTotal or near‐total thyroidectomy was performed in 212 (51%) and 208 (49%) patients, respectively. Tumors were multicentric, 40% (average 1.7 cm); were bilateral, 30%; and showed extrathyroidal extension, 17%. Overall, 223 (53%) patients had LNMs: 213 (51%) were central and 85 (20%) were lateral jugular. pTNM staging: I, 258 (61%); II, 35 (8%); III, 88 (21%); IV, 39 (9%). AGES (age, grade, extension, and size—thyroid tumor; and MACIS (metastasis, age, completeness of resection, invasion, and size) prognostic scores were low risk in 362 (86%) and 352 (84%), respectively. Relapse developed in 57 (14%) patients: LNM in 44, soft tissue local recurrence (LR) in 5, distant metastases (DM) in 8. Hypoparathyroidism occurred in 5 (1.2%) patients and 1 had unintentional laryngeal nerve damage. Relapse with LNM occurred in previously operated fields in 19 (5%) patients, 11(3%) from disease virulence (LR or DM), preoperative false‐negative (FN) US in 12 (3%), and combination of FN‐US and recurrence in the operated field in 5 (1%) patients.ConclusionsRecurrence was limited to 5% of patients when the extent of disease was accurately defined and potentially curable. This optimized surgical strategy is relatively safe.

AbstractBackgroundToxic multinodular goiter (Plummer’s disease) has posed challenges to surgeons, endocrinologists, and radiation oncologists since its description in 1913. A literature review with evidenced‐based methodology has not yet been reported.MethodsA systematic review of the English literature from 1950 to 2007 and report of Mayo Clinic experience since 1950 was undertaken to establish evidence‐based recommendations for management.ResultsSurgery and radioactive iodine (RI) are both supported by level IV evidence in the treatment of solitary toxic nodules and toxic multinodular goiter, and treatment is determined by symptoms and co‐morbidities. No evidence suggests a difference in treatment outcome based on pretreatment clinical or subclinical hyperthyroidism. Level IV evidence supports thyroidectomy over RI for large goiters. When compressive symptoms are present, level IV evidence supports thyroidectomy for maximal symptom relief in patients at moderate risk. Occult malignancies are found in 2–3% of thyroidectomy specimens for Plummer’s disease. Despite technical reports of RI dose considerations, there are no prospective studies validating a dose formula. Ethanol ablation of toxic nodules in patients unfit for surgery is supported by level III evidence. Level V data suggest a cost benefit favoring surgery.ConclusionsTreatment of Plummer’s disease with antithyroid medications, ethanol ablation, RI ablation, or surgery must balance the goals of therapy, durability of cure, relief of symptoms, risk of malignancy, and risk of complications. Between 1950 and 2006, 948 (70%) of 1,356 patients with Plummer’s disease have been treated surgically at Mayo Clinic.

AbstractBackgroundPatients with papillary thyroid carcinoma (PTC) may suffer recurrence despite thyroidectomy and complete radioiodine (RAI) ablation. Reoperation is vitally dependent on accurate and complete disease localization, typically utilizing cervical ultrasonography (US) and/or computed tomography. Our aim was to determine the comparative value of F18‐fluorodeoxyglucose positron emission tomography (PET) to US for localization of locoregional recurrence in patients who underwent reoperation for recurrent PTC.MethodsFrom 1999 to 2004, 30 patients who underwent re‐exploration and 100 nonoperated patients who were investigated with PET for possible recurrent PTC were reviewed. The surgical group [9 males, 21 females; mean age = 50 years (range = 18–84 years)] all had received RAI ablation. Preoperative thyroid‐stimulating hormone (TSH), thyroglobulin (Tg), and location of metastasis were recorded for each imaging study and surgical exploration. All separate sites that contained disease pathologically must have been identified by imaging for a patient to be considered true positive (TP).ResultsPET scans were TP in 43%, false positive in 7%, false negative (FN) in 50%, and had a sensitivity of 46%. Comparable US results were 86%, 10%, 3%, and 96%. Of the 15 patients with FN PET scans, 13 had lymph node metastasis less than 2 cm in diameter, 11 had Tg ≤ 10 μg/L, and the TSH < 20 in 13. In only 3 of the 30 (10%) patients was PET deemed to add value.ConclusionsAt least with suppressed TSH, PET scanning in reoperative PTC patients appears to offer modest benefit beyond high‐resolution US.

Laparoscopic adrenalectomy is one of the most clinically important advances in the past 2 decades for the treatment of adrenal disorders. When compared to open adrenalectomy, laparoscopic adrenalectomy is equally safe, effective, and curative; it is more successful in shortening hospitalization and convalescence and has less long-term morbidity. The laparoscopic approach to the adrenal is the procedure of choice for the surgical management of cortisol-producing adenomas and for patients with corticotropin (ACTH) dependent Cushing's syndrome for whom surgery failed to remove the source of ACTH. The keys to successful laparoscopic adrenalectomy are appropriate patient selection, knowledge of anatomy, delicate tissue handling, meticulous hemostasis, and experience with the technique of laparoscopic adrenalectomy.

AbstractBackgroundCushing’s syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10‐year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management.Materials and MethodsFrom 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five‐year survival rates were calculated where applicable by the Kaplan‐Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC).ResultsTwo‐hundred thirty‐one patients (78%) had ACTH‐dependent CS and 67 patients (22%) had ACTH‐independent CS. One‐hundred ninety‐six patients (66%) had pituitary‐dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty‐four patients (18%) had cortisol‐secreting adenomas, 10 patients (3%) had cortisol‐producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five‐year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively.ConclusionsSurgery for CS is highly successful for pituitary‐dependent CS and most ACTH‐independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross‐sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today’s management of the complex patient with CS.