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Biomedical subjects

Samuel A Wells

Publications and source records attributed to Samuel A Wells.

15 recordsLinked to original sources
PubMed2007

The multiple endocrine neoplasia syndromes.

Multiple endocrine neoplasia (MEN) type 1 and type 2 exhibit an autosomal dominant pattern of inheritance. In the past two decades the germline mutations that cause these inherited syndromes have been identified. The large majority of patients with MEN1 have mutations in the menin gene. Mutations in the REarranged during Transfection (RET) gene cause MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). Specific codon mutations within RET correlate with disease phenotype and severity. Also, children from families with MEN2A, MEN2B, or FMTC, who are found to have inherited a mutated RET allele, can be managed by prophylactic thyroidectomy, thus preventing the development of medullary thyroid carcinoma (MTC), the dominant endocrinopathy in patients with these hereditary syndromes. New insights into the molecular pathway of RET signal transduction are leading to novel targeted therapies in patients with locally advanced or metastatic hereditary MTC.

Humans↗
PubMed2006

Medullary thyroid cancer.

The goal in managing patients who have MTC is to detect and surgically remove disease at an early stage. Tumor marker-based biochemical screening and DNA-based genetic screening have created the opportunity for effective prophylactic surgery in patients at risk for hereditary MTC. Complete surgical resection is critical for cure because cervical reoperation for persistent or recurrent disease benefits only select patients. With the advent of therapies that target the RET-activated pathways, new hope may be emerging for patients who have locally advanced or metastatic disease.

Calcitonin↗
PubMed2005

Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A.

BACKGROUND: Medullary thyroid carcinoma is the most common cause of death in patients with multiple endocrine neoplasia (MEN) type 2A (MEN-2A) or type 2B or familial medullary thyroid carcinoma. We sought to determine whether total thyroidectomy in asymptomatic young members of kindreds with MEN-2A who had a mutated allele of the RET proto-oncogene could prevent or cure medullary thyroid carcinoma. METHODS: A total of 50 patients 19 years of age or younger who were consecutively identified through a genetic screening program as carriers of a RET mutation characteristic of MEN-2A underwent total thyroidectomy. Five to 10 years after the surgery, each patient was evaluated by physical examination and by determination of plasma calcitonin levels after stimulation with provocative agents. RESULTS: In 44 of the 50 patients, basal and stimulated plasma calcitonin levels were at or below the limits of detection of the assay (proportion, 0.88; 95 percent confidence interval, 0.76 to 0.95). Two patients had basal and stimulated plasma calcitonin levels above the normal range. Stimulated plasma calcitonin levels had increased but remained within the normal range in four patients. The data suggest that there was a lower incidence of persistent or recurrent disease in children who underwent total thyroidectomy before eight years of age and in children in whom there were no metastases to cervical lymph nodes. CONCLUSIONS: In this study, young patients identified by direct DNA analysis as carriers of a RET mutation characteristic of MEN-2A had no evidence of persistent or recurrent medullary thyroid carcinoma five or more years after total thyroidectomy. A longer period of evaluation will be necessary to confirm that they are cured.

Adolescent↗
PubMed2005

Long-term functionality of cryopreserved parathyroid autografts: a 13-year prospective analysis.

BACKGROUND: The functional results of cryopreserved heterotopic parathyroid autotransplantation (CHPA) are not well defined. The authors evaluated the outcomes of delayed CHPA for the treatment of surgically induced hypoparathyroidism. METHODS: Since November 1991, 448 parathyroid samples from 436 patients were cryopreserved at our institution. Of these, 29 patients underwent 34 CHPA procedures, with placement of 20 to 25 pieces of parathyroid tissue (approximately 50 to 75 mg) into the forearm. Outcomes were determined based on peripheral parathyroid hormone (PTH) levels and, where available, PTH gradients between grafted and nongrafted arms. Graft function results were defined as completely functional (patients with normal PTH and calcium levels off all calcium/vitamin D supplementation), partially functional (normal PTH levels and mild hypocalcemia on calcium supplementation), or nonfunctional (low PTH levels and dependent on calcium/vitamin D supplementation). RESULTS: Of the 29 patients with CHPA, prospective data were available for 26 patients undergoing 30 CHPA procedures (9 patients with MEN 1, 4 with MEN 2A, 1 with MEN 2B, and 12 with sporadic hyperparathyroidism). The mean follow-up interval was 2 years. Twelve of 26 patients (46%) had completely functional grafts, 6 patients (23%) had partially functional grafts, and the remaining 8 patients (31%) had nonfunctional grafts. No patient with CHPA had graft-dependent recurrent hyperparathyroidism. Of the 14 patients (15 autografts) with MEN, 7 patients (50%) had fully functional grafts, and 2 patients (14%) had partially functional grafts. The mean cryopreservation period was 7.9 months (range, 1 week to 22 months) for functional autografts and 15.3 months (range, 2 weeks to 106 months) for nonfunctional autografts (P < .01). CONCLUSIONS: Based on these data and those in previous studies, approximately 60% of delayed, cryopreserved parathyroid autografts are functional. In this study 40% autografts (46% of patients) achieved full competency off supplements. Some patients have evidence of graft function with normal PTH levels but are not normocalcemic. Results were similar for patients with MEN and nonhereditary hyperparathyroidism. The duration of cryopreservation was a significant indicator of graft failure, and no functional autograft was observed beyond 22 months of preservation. CHPA is a useful treatment modality for patients with postoperative hypocalcemia after thyroid or parathyroid surgery, who do not respond to immediate parathyroid autotransplantation.

Adolescent↗
PubMed2004

A report on accrual rates for elderly and minority-ethnicity cancer patients to clinical trials of the American College of Surgeons Oncology Group.

BACKGROUND: Incidence and mortality rates for cancers vary by ethnic background and patient age. Accrual of diverse patient populations to cancer clinical trials is essential in order to ensure that findings related to new management strategies can be generalized. The goal of this study was to evaluate accrual patterns for patients participating in the American College of Surgeons Oncology Group (ACOSOG) cancer protocols. Ethnic diversity among clinical trial investigators may also influence accrual patterns, so the ethnic background of the ACOSOG membership was also evaluated. STUDY DESIGN: Demographics for the patients registered on ACOSOG breast, thoracic, and colorectal clinical trials were evaluated and compared with data on the general population and the cancer population in the United States. Accrual patterns for patients from other reported cancer clinical trials were also presented, and the self-reported ethnic distribution of the ACOSOG membership was analyzed. RESULTS: Distribution of African Americans, Hispanic Americans, and Asian Americans to the ACOSOG breast and colorectal clinical trials was relatively proportionate to the cancer population. African Americans were underrepresented in the thoracic clinical trials, and this disparity was partially offset by data on the proportion of African Americans with stage-eligible lung cancer. Accrual rates for patients age 65 years and older were better than those reported by most other clinical trialists. CONCLUSIONS: Elderly patients are successfully recruited into surgical clinical trials, and this will provide important data for future analyses regarding cancer outcomes in this growing population of cancer patients. Aggressive outreach to minority-ethnicity cancer patients for accrual into clinical trials should continue.

Age Factors↗
PubMed2004

Hereditary medullary thyroid carcinoma in patients greater than 50 years old.

BACKGROUND: Despite near complete penetrance and frequent early evaluation of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia 2 (MEN 2) variants, a significant minority of patients are evaluated later in life. METHODS: With the aim of characterizing the expression of hereditary MTC in an older cohort, MEN 2 patients from our institutional database who were evaluated after age 50 years were identified, and clinical data were reviewed. RESULTS: Thirty-nine patients (36 MEN 2A, 3 FMTC, and no MEN 2B) who were evaluated after age 50 years were identified; they represented 9% of all MEN 2 patients who were enrolled in our program. Most of the patients (79%) had abnormal screening examinations, and the AJCC staging was significantly higher in this cohort compared with younger patients. Overall, 43% of the patients had normal calcitonin levels after operation. There were 3 observed MTC-related deaths, all from distant metastases; the overall survival rate was 86% at 5 years and 74% at 10 years. The distribution of RET mutations in this cohort was similar to younger patients. CONCLUSIONS: These results suggest the presence of modifiers of MTC expression. Despite the tendency of older patients with hereditary MTC to have advanced stage disease at evaluation, they have high rates of biochemical cure, and the overall survival is excellent.

Age Factors↗
PubMed2002

Gastrointestinal manifestations of multiple endocrine neoplasia type 2.

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.

Adolescent↗
PubMed2002

Recurrent or persistent hyperparathyroidism.

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.

Choristoma↗