Biomedical subjects

Gerard M Doherty

Publications and source records attributed to Gerard M Doherty.

30 records · Page 2Linked to original sources

PubMed2004

The surgical management of MEN-1 pancreatoduodenal neuroendocrine disease.

BACKGROUND: The management of multiple endocrine neoplasia, type 1 (MEN-1) pancreatoduodenal neuroendocrine neoplasms (NENs) is controversial. An aggressive surgical approach is intended to control the functional syndromes and malignant potential for nodal or distant metastasis. METHODS: The results of treating 39 patients with MEN-1 pancreatoduodenal NENs over a 35-year period are available from chart reviews and patient interviews. This study focuses on pattern of disease, disease recurrence, and long-term functional outcomes. RESULTS: Between 1967 and 2003, 39 patients ages 19 to 58 years (mean age, 37) had abdominal operations for their pancreatoduodenal NENs: 26 with Zollinger-Ellison syndrome, 4 with hypoglycemia, 3 with both Zollinger-Ellison syndrome and hypoglycemia, and 6 with nonfunctional neoplasms. Fifteen of these 39 patients had malignant disease on initial abdominal operation; 24 of 39 patients have not required abdominal reoperation, 17 of whom have available follow-up data. Of these 17 patients, 11 have biochemical evidence of disease recurrence (increased serum concentrations of gastrin, insulin, or pancreatic polypeptide), while 6 have no biochemical evidence of recurrence. A total of 30 abdominal reoperations were performed in 15 patients; 14 of 15 patients undergoing 1 or more reoperations developed evident malignant disease by their most recent operation. Nine of 13 reoperative patients with follow-up data have evidence of disease recurrence. Functional outcomes available in 20 patients showed that 10 patients require insulin and that 6 require oral hypoglycemic medications. Ninety percent have no abdominal pain or nausea/vomiting, while 4 are unable to return to work secondary to this disease. CONCLUSIONS: Treatment of MEN-1 pancreatoduodenal NENs is met with frequent recurrence and some treatment-related morbidity and mortality. Most patients (22 of 39) eventually demonstrated malignant growth, but, with this strategy, few died of this disease.

Adult↗

PubMed2004

Laparoscopic adrenalectomy for malignant disease.

Malignant tumours of the adrenal gland are uncommon but are associated with substantial mortality. For most tumours resection is the only opportunity for cure. Advances in diagnostic and surgical techniques have improved the detection and treatment of these tumours. Further advances need new ways to make decisions about the use of laparoscopic resection for malignant, or potentially malignant, adrenal tumours. We review studies on the outcome of laparoscopic adrenalectomy for primary adrenal cancer as well as studies on metastatic disease to the adrenal glands. There are few prospective data because of the rarity of this condition. Careful individual judgment by the surgeon remains the cornerstone of safe and complete resection for adrenal malignant disease.

Adrenal Gland Neoplasms↗

PubMed2004

Pleomorphic rhabdomyosarcoma of the anterior abdominal wall following multimodality treatment for carcinoma of the rectum.

Postradiation sarcomas are rare, and the most commonly reported ones are malignant fibrous histiocytoma, osteosarcoma, angiosarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor, and high-grade pleomorphic sarcoma, not otherwise specified. There are a few case reports of postradiation rhabdomyosarcomas following treatment of retinoblastoma, breast cancer, endometrial adenocarcinoma, and Hodgkin's disease. Secondary neoplasms following radiation and surgical treatment of rectal adenocarcinomas have not been reported in the English literature. We report a case of pleomorphic rhabdomyosarcoma of the anterior abdominal wall following treatment of rectal carcinoma, and we review the literature.

Abdominal Wall↗

PubMed2003

Is preoperative iodine 123 meta-iodobenzylguanidine scintigraphy routinely necessary before initial adrenalectomy for pheochromocytoma?

BACKGROUND: Iodine 123 meta-iodobenzylguanidine (MIBG) scintigraphy has been used in patients with clinical suspicion of pheochromocytoma to confirm the nature of an adrenal or extraadrenal mass or to identify occult disease. Additionally, it may be used to identify unsuspected bilaterality or metastases in the setting of a known unilateral adrenal mass before operation. We sought to determine the role of (123)I MIBG scintigraphy in this apparently routine preoperative setting. Our hypothesis was that (123)I MIBG would provide additional preoperative information that could modify operative intervention. METHODS: All patients undergoing (123)I MIBG scintigraphy at our institution between 1992 and 2002 were identified. MIBG results, operative procedures and findings, and pathologic findings were retrospectively reviewed and compared. RESULTS: The (123)I MIBG scintigraphy was performed in a total of 315 patients. Of these, 48 were patients with an initial biochemical diagnosis of pheochromocytoma and a unilateral adrenal mass. 47 of the 48 (98%) primary scans were positive for a single focus of activity concordant with anatomic imaging data from computed tomography or magnetic resonance imaging and operative findings. The (123)I MIBG did not reveal unsuspected metastatic or bilateral disease in any patient. CONCLUSION: In this large series of patients undergoing (123)I MIBG scintigraphy, the test served only to confirm diagnostic impressions and corroborate anatomic imaging. The (123)I MIBG did not alter the operative management of any patient with a solitary adrenal lesion in the clinical context of biochemically-proven catecholamine excess.

3-Iodobenzylguanidine↗

PubMed2003

Who performs endocrine operations in the United States?

BACKGROUND: Endocrine surgery is a discipline that is dedicated to high-quality care of patients with endocrine surgical disease. The relationship between its "identity" as a separate field and clinical practice patterns is not known. METHODS: The National Inpatient Sample was searched by the International Classification of Diseases-9th revision-Clinical Modification codes for parathyroidectomy, thyroidectomy, and adrenalectomy for the years 1988 through 2000. The surgeons who performed these operations were profiled by 2 methods: Method A, by the percentage of the total primary International Classification of Diseases-9th revision-Clinical Modification procedure codes that were the selected endocrine procedures; method B, by absolute number of index endocrine procedures performed per year. Only patients with complete coding data for the surgeons were included. RESULTS: In this sample, surgeons whose practice was comprised of 25% or less of these endocrine procedures performed 11,071 parathyroidectomies (78% of total), 46,210 thyroidectomies (82% of total), and 4209 adrenalectomies (94% of total). In contrast, surgeons whose practice was comprised of more than 75% of these endocrine procedures performed 769 parathyroidectomies (5% of total), 1560 thyroidectomies (3% of total), and 128 adrenalectomies (3% of total). CONCLUSION: If these data can be extrapolated to indicate generalized practice patterns, the majority of common operations for endocrine disease are performed by surgeons whose practice is not focused on endocrine surgery. However, much of this effect is due to the fact that non-endocrine surgeons far outnumber endocrine surgeons. This understanding of clinical practice patterns will be important to consider during future studies that seek to determine the relationship between surgeon volume and patient outcomes.

Adrenalectomy↗

PubMed2003

Multiple endocrine neoplasia type 1: duodenopancreatic tumors.

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.

Duodenal Neoplasms↗

PubMed2003

Localization of IFN-gamma-activated Stat1 and IFN regulatory factors 1 and 2 in breast cancer cells.

The aim of the present work was to evaluate the induction and localization of Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-gamma exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20. Results from growth assays, Western staining, electrophoretic mobility shift assay (EMSA), and immunohistochemical staining were collated to test our hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would provide additional information about the functionality of the IFN-gamma signaling pathway in human tumor lines. EMSA results showed that in each of four cell lines, Stat1 expression was increased and demonstrated functional activity after IFN-gamma stimulation. Western and EMSA analysis showed upregulation of IRF-1 but not IRF-2 in each cell line. Confocal microscopy of cells stained for Stat1, IRF-1, and IRF-2 confirmed the results and also provided novel information about the intracellular localization of proteins and intercellular variations in responses. The proportion of cells with IRF-1 stimulation and translocation was positively correlated with the IFN-gamma growth suppression in vitro. In conclusion, using four independent assays, we have demonstrated that heterogeneity in IFN-gamma-mediated upregulation of signal transduction proteins can be detected in vitro and that these differences can explain distinct cellular growth effects.

Antibodies, Monoclonal↗

PubMed2003

The role of interferon regulatory factor-1 and interferon regulatory factor-2 in IFN-gamma growth inhibition of human breast carcinoma cell lines.

Interferon (IFN) regulatory factor-1 (IRF-1) and IRF-2 play opposing roles in the regulation of many IFN-gamma-inducible genes. To investigate the signal transduction pathway in response to IFN-gamma in light of differences in growth effects, we selected four human breast carcinoma cell lines based on a spectrum of growth inhibition by IFN-gamma. MDA468 growth was markedly inhibited by IFN-gamma, and it showed substantial induction of IRF-1 mRNA but little IRF-2 induction. SKBR3 showed little growth inhibition and little induction of IRF-1 mRNA but significant induction of IRF-2 mRNA. HS578T and MDA436 growth inhibition and IRF-1/IRF-2 induction were intermediate. All four cell lines showed intact receptor at the cell surface and Stat1 translocation to the nucleus by immunostaining. By EMSA, there were marked differences in the induced ratio of IRF-1 and IRF-2 binding activity between the cell lines that correlated with growth inhibition. Finally, antisense oligonucleotides specific for IRF-1 attenuated IFN-gamma growth inhibition in MDA436 and MDA468, confirming the direct role of IRF-1 in IFN-gamma growth inhibition. Induction of IRF-1 causes growth inhibition in human breast cancer cell lines, and induction of IRF-2 can oppose this. The relative induction of IRF-1 to IRF-2 is a critical control point in IFN-gamma response.

Breast Neoplasms↗

PubMed2002

Childhood and adolescent thyroid carcinoma.

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.

Adolescent↗

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

Adrenalectomy for familial pheochromocytoma in the laparoscopic era.

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.

Adrenal Gland Neoplasms↗

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↗