Biomedical subjects
Publications and source records attributed to Gerard M Doherty.
Duodenopancreatic endocrine tumors are the most frequently lethal part of MEN-1. The management of these patients is complicated by the variable hormonal function of the tumors, and the often indolent but occasionally lethal nature of the tumors. This article reviews our current approach to the diagnosis, surveillance and management of these patients.
OBJECTIVES: This analysis was performed to evaluate the influence of clinical and treatment factors on local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma. METHODS: The records of 56 children and adolescents with papillary and follicular carcinoma of the thyroid were reviewed. They ranged in age from 4 to 20 years. There were 43 females and 13 males. At diagnosis, 15 (27%) patients had disease confined to the thyroid, 34 (60%) had additional lymph node metastasis to the neck or upper mediastinum, and 7 (13%) also had lung metastasis. Treatment consisted of a total thyroidectomy in 48 patients, a subtotal thyroidectomy in 4 patients, and a lobectomy in 4 patients. All 56 patients received postoperative thyroid hormone suppressive therapy. (131)I was administered to 82% (46 of 56) of patients after their initial surgery. RESULTS: The overall survival rate was 98% with a follow-up of 0.6-30.7 years (with a median follow-up of 11.0 years). The one death that occurred in this patient population was the result of a congenital heart defect and was unrelated to thyroid carcinoma. The 10-year progression-free survival rate was 61%. Nineteen patients (34%) experienced a recurrence of their thyroid carcinoma. The time to first recurrence of disease ranged from 8 months to 14.8 years (mean, 5.3 years). None of those with disease confined to the thyroid developed recurrent disease. The recurrence rate was 50% (17 of 34) in patients with lymph node metastasis and 29% (2 of 7) in patients with lung metastasis (P = 0.02). Tumor characteristics were evaluated for time to first recurrence utilizing the logistic likelihood ratio test to predict disease recurrence. Thyroid capsule invasion (P = 0.02), soft tissue invasion (P = 0.03), positive margins (P = 0.006), and tumor location at diagnosis (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02) were significant for developing recurrent disease. Patients younger than 15 years old at diagnosis were more likely to have more extensive tumor at diagnosis than patients who were 15 years and older (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02). CONCLUSION: Carcinoma of the thyroid in children and adolescents has little risk of mortality but a high risk of recurrence. Younger patients present with a more advanced stage of disease and are more likely to have disease recurrence. Total thyroidectomy and lymph node dissection, followed by postoperative (131)I therapy, thyroid hormone replacement (suppressive) administration, and diligent surveillance are warranted.
OBJECTIVE: To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. SUMMARY BACKGROUND DATA: The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems. METHODS: From 83 families with MEN 2A, eight patients with HD were identified (MEN 2A-HD). These and all patients with MEN 2B followed at the authors' institution (n = 53) were sent questionnaires to describe the onset and type of gastrointestinal symptoms and treatment they had before the diagnosis of MEN 2. Records of all patients responding were reviewed, including radiographic imaging, histology, surgical records, and genetic testing. RESULTS: Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28) to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to 63 years before being diagnosed with MEN 2. All patients responding were underweight as infants and had symptoms of abdominal pain, distention, and constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal biopsies with a diverting colostomy as the initial surgical procedure. This was followed by a colostomy takedown and pull-through procedure at a later interval. Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%). Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had radiographic imaging, 32% were admitted to the hospital, and 29% underwent surgery. CONCLUSIONS: Patients with MEN 2A-HD had a typical HD presentation and always required surgery. Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management.
OBJECTIVE: To report the results of treatment of patients with familial pheochromocytomas in the laparoscopic era. SUMMARY BACKGROUND DATA: The optimal surgical management of pheochromocytomas that arise in familial neoplasia syndromes may be complicated by bilateral involvement and associated endocrinopathies. METHODS: Twenty-one patients with familial pheochromocytomas (15 with multiple endocrine neoplasia [MEN] 2A, 4 with MEN 2B, 1 each with von Hippel-Lindau and neurofibromatosis type 1) underwent adrenalectomy between December 1993 and July 2001. Clinical, biochemical, and pathologic data were obtained by retrospective review of perioperative medical records, postoperative biochemical testing, and patient questionnaire. RESULTS: Mean age at diagnosis was 37 +/- 11 years. Twenty of the 21 patients had elevated urine catecholamines, and all had radiographic evidence of an adrenal tumor or tumors. Pheochromocytoma-related symptoms were present in 11 patients (52%). One patient with MEN 2B underwent open adrenalectomy due to previous adrenal surgery and megacolon. Laparoscopic adrenalectomy was attempted in the remaining 20 patients (9 right, 11 left, 2 bilateral). Two patients (9.1%) were converted to open adrenalectomy. Intraoperative hypertensive episodes occurred in 15 patients (71%) and were easily controlled medically. Mean operative time was 216 +/- 57 minutes, mean postoperative length of stay was 3.1 +/- 1.3 days, and mean tumor size was 3.1 +/- 1.0 cm. Minor complications occurred in three patients (14.3%) and major complications in two patients (9.5%). During a mean follow-up of 57 months, a contralateral pheochromocytoma developed in four patients with MEN 2 (33%); three of them underwent adrenalectomy. There have been no long-term complications related to hypertension or adrenalectomy. CONCLUSIONS: This study is the largest series of patients with familial pheochromocytoma undergoing adrenalectomy during the laparoscopic era. The results suggest that the laparoscopic approach is safe and effective for managing unilateral or bilateral adrenal medullary disease in this population.
Approximately 90% of patients with primary hyperparathyroidism (PHPT) are cured by parathyroidectomy at the initial neck exploration. Those not cured either remain hypercalcemic in the immediate postoperative period or develop hypercalcemia after a long period of normocalcemia. Almost all cases of hypercalcemia after neck exploration for PHPT are evident early in the postoperative period and are caused either by an overlooked parathyroid adenoma or an incomplete resection of hyperplastic parathyroid tissue. Less commonly, the surgeon has failed to recognize, and adequately treat, parathyroid carcinoma, or the diagnosis of PHPT was incorrect and there is another cause of the hypercalcemia. A successful neck exploration for PHPT is primarily dependent on the experience of the operating surgeon, the anatomic location of the parathyroid glands, either in "normal" or "ectopic" sites, and the presence of a single enlarged parathyroid gland as opposed to multiglandular disease or parathyroid carcinoma. In cases where an enlarged parathyroid gland is not identified at operation, noninvasive or invasive radiographic imaging procedures are useful in localizing the gland. Currently, the most reliable and practical procedure is technetium 99m sestamibi scanning. This technique identifies an enlarged parathyroid gland in 65-80% of cases. Single photon emission computed tomography (SPECT) in association with sestamibi scanning increases the sensitivity of the procedure to 85%. These imaging procedures are least reliable in patients with multiglandular disease. Ultrasound and computed tomographic scanning are less sensitive; however, they are commonly used as confirmatory tests in association with sestamibi scanning. When noninvasive imaging procedures fail to identify an enlarged parathyroid gland, invasive procedures, such as selective arteriography, are performed. Whereas invasive procedures are useful, they are associated with significant morbidity. Reoperations for persistent or recurrent hyperparathyroidism, compared with the initial operations, are associated with higher complication rates. In 90% of cases, the abnormal pathology can be reached through a cervical incision. The success rate of the reoperation depends primarily on the results of the localization procedure and whether the patient has a single enlarged parathyroid gland or multiglandular disease. Resection of a single enlarged gland is curative in virtually all patients. If, however, the patient has multiple gland disease, the operation is successful less often, especially in those with certain familial endocrinopathies.