Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas.

Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number of familial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes 1p and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes 1p (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on 1p and urinary excretion of metanephrine by these patients (P = 0.02). LOH on 1p, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes 1p and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma.

Inappropriate medicine prescribing in older South Africans: A cross-sectional analysis of medicine claims data.

BACKGROUND: Prescribing for older patients is a well-recognised problem, and inappropriate items are prescribed frequently. Several tools and criteria are available to promote rational prescribing in older patients. OBJECTIVE: To determine the prevalence of potentially inappropriate prescriptions (PIPs) in older South African patients. METHODS: A retrospective drug utilisation review was conducted using medicine claims data over a 1-year period. Patients aged ≥65 years with at least one paid claim for any medicine item during this period were included. The prevalence of PIPs was identified by applying the 2012-Beers criteria list. RESULTS: A total of 103 420 patients, mean age 74.0 years (standard deviation 6.7), 57.1% female, were included in the analysis. The number of PIPs identified was 562 852 in 71 206 patients (68.9%). The most common medicines inappropriately prescribed were oestrogen (oral and patch formulations only) (12.4%), meloxicam (7.3%), amitriptyline and combinations thereof (6.5%), diclofenac (6.4%), ibuprofen (6.1%), alprazolam (5.3%), meprobamate and combinations thereof (5.0%), sliding-scale insulin (3.3%), amiodarone (3.1%) and doxazosin (2.6%). Medicines were inappropriately prescribed to women statistically significantly more often than to men (1.9:1; p<0.001), although this difference was not of practical significance (Cramér's V=0.06). CONCLUSIONS: Medicine use in older patients must be appropriate and evaluated regularly. According to explicit criteria, PIPs were found to be common in older patients registered on the database. Monitoring of PIPs may increase the quality of prescribing, but explicit criteria cannot substitute for clinical judgement based on the individual patient.

Management of thyroid nodules in pregnancy.

BACKGROUND: Disorders of the thyroid are common in pregnancy. In particular, a thyroid nodule is frequently discovered before or during pregnancy. OBJECTIVE: To develop guidelines for the management of thyroid nodules during pregnancy. METHODS: We reviewed the cases of 40 pregnant patients with thyroid nodules evaluated during a 10-year period Cytological findings were compared with available histological findings, and concordance rates were determined. The rank sum test was used for statistical analysis. RESULTS: Fine-needle aspirations of thyroid nodules in 62% of patients were benign cytologically (25 patients). Of 8 patients with negative cytological results who had thyroidectomy, all had benign disease histologically (100% concordance rate). Cytological findings of papillary cancer (3 patients) strongly correlated with final histological diagnosis (100% concordance rate), whereas papillary cancer was confirmed histologically in only 2 of 4 patients with cytological findings suspicious for this disease (50% concordance rate). All 3 nodules with cytological findings suspicious for follicular neoplasm were benign adenomas histologically. Of 2 nodules suspicious for Hürthle cell neoplasm, l was Hürthle cell adenoma and the other was Hürthle cell carcinoma (100% concordance rate). Thyroidectomy during the second trimester of pregnancy or the early postpartum period was successful. CONCLUSIONS: The approach to thyroid nodules in pregnancy should be similar to that for nonpregnant patients. Thyroidectomy should be performed (1) during the second trimester for malignant lesions and cytological findings suspicious for papillary cancer and (2) in the postpartum period for cytological findings suspicious for follicular neoplasm.

Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients.

Paragangliomas are rare tumors that arise from extraadrenal chromaffin cells. We examined the clinical characteristics, location, treatment, and outcome of 236 patients (141 females, 60%) with 297 benign paragangliomas evaluated at the Mayo Clinic during 1978-1998. The mean age (+/-SD) at diagnosis was 47 +/- 16 yr. Of the 297 paragangliomas, 205 were in the head and neck region, and 92 were below the neck. Paragangliomas were discovered and diagnosed incidentally on imaging studies in 9% of patients. Biochemical screening was performed in 128 patients; 40 patients (17% of the total and 31% of those screened) had hyperfunctional tumors. Of the 40 patients with tumoral catecholamine excess, 38 had documented hypertension. In patients identified with catecholamine-secreting paragangliomas, the sensitivities achieved by measurements in the 24-h urine collection were 74% for total metanephrines, 84% for norepinephrine, 18% for dopamine, and 14% for epinephrine. Multiple imaging modalities were used for tumor localization. The false negative rates were 0% for magnetic resonance imaging, 5.8% for computed tomography, 3.4% for angiography, 10.7% for ultrasonography, and 39% for radioactive iodine-labeled metaiodobenzylguanidine scintigraphy. Of 192 patients (81.4%) with follow-up data (mean, 43.9 months; range, 0.5-240), operative cure was achieved in 133 (69%). Of the 59 patients without cure, 23 had persistent disease, 5 had recurrent disease, 16 had multiple persistent synchronous tumors, and 15 subsequently developed metachronous tumors. In conclusion, most paragangliomas are nonhypersecretory and located in the head and neck region. Magnetic resonance imaging was associated with the lowest false negative rate, and metaiodobenzylguanidine was the least sensitive imaging study. A significant proportion of patients (31%) has persistent or recurrent disease, and long-term follow-up is important.

Laparoscopic adrenalectomy for adrenocorticotropin-dependent Cushing's syndrome.

Bilateral adrenalectomy is indicated for the treatment of ACTH-dependent Cushing's syndrome when the tumorous source of ACTH hypersecretion cannot be identified or removed. Potential advantages of laparoscopic over open adrenalectomy include shorter hospitalization, decreased requirement for postoperative analgesia, and decreased postoperative morbidity due to incisional complications. Bilateral laparoscopic adrenalectomy performed for the treatment of ACTH-dependent Cushing's syndrome was attempted in 19 patients at our institution between 1995 and 1998. Conversion to an open procedure was required in three patients. All patients who underwent bilateral laparoscopic adrenalectomy were subsequently followed to assess the outcome of this intervention. Twelve patients with pituitary-dependent Cushing's syndrome and four with ectopic ACTH syndrome underwent successful bilateral laparoscopic adrenalectomy. All patients experienced resolution of the signs and symptoms (e.g. proximal myopathy, hirsutism, and emotional lability) of Cushing's syndrome as well as weight loss, improved glucose tolerance, and improved control of blood pressure. No residual cortisol secretion was detected in the patients. Bilateral laparoscopic adrenalectomy is a safe and effective treatment for Cushing's syndrome when the ACTH-secreting neoplasm cannot be removed.

Cushing's syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization.

Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 micro g/d), epinephrine (66 micro g/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 micro g/dl and decreased to 12.9 and 4.5 micro g/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was -4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 micro g/d), epinephrine (0 micro g/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing's syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.

Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter.

Toxic multinodular goiter (TMNG) represents a frequent cause of endogenous hyperthyroidism, affecting 5-15% of such patients (with higher frequencies reported in iodine-deficient areas of the world). Although mutations of human TSH receptor (hTSHR) have been described in autonomously functioning thyroid nodules (AFTN), the role of such mutations in the pathogenesis of TMNG remains unclear. To search for alterations of hTSHR in AFTN and TMNG, we performed bidirectional, dye primer automated fluorescent DNA sequencing of the entire transmembrane domain and cytoplasmic tail of hTSHR (TMD+CT-hTSHR) using DNA extracted from nodular regions of 24 patients with TMNG and 7 patients with AFTN. Eight of the 24 patients (33.3%) showed heterozygote polymorphism of codon 727 on the cytoplasmic tail of hTSHR with an amino acid substitution of aspartic acid to glutamic acid. Three of 24 (12.5%) patients with TMNG were found to carry a heterozygote mutation of codon 703, resulting in substitution of alanine with glycine. One patient had multiple heterozygote mutations including I606M (Ile to Met), A703G (Ala to Gly), Q720E (Gln to Glu), and D727E (Asp to Glu). Two patients exhibited silent polymorphism of codons 460 and 618. We found no mutation of the TMD+CT-hTSHR in 7 patients with AFTN, except for a silent polymorphism of codon 460 in 1. DNA fingerprinting of codon 727 using restriction enzyme NlaIII and genomic DNA confirmed the sequencing results in all cases, indicating that the sequence alterations were not somatic in nature. This technique was also used to examine peripheral blood genomic DNA from 52 normal individuals and 49 patients with Graves' disease; 33.3% of TMNG (P = 0.019 vs. normal subjects), 16.3% of Graves' disease patients (P = 0.10 vs. normal subjects), and 9.6% of normal individuals were heterozygous for the D727E polymorphism. Expression of the D727E hTSHR variant in eukaryotic cells (COS-7) resulted in an exaggerated cAMP response to TSH stimulation compared to that of the wild-type hTSHR. These findings indicate that a germline polymorphism of codon D727E of hTSHR is associated with TMNG, suggesting that its presence is an important predisposing genetic factor in the pathogenesis of TMNG.

Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes.

In adults, endogenous hyperinsulinemic hypoglycemia is almost invariably due to insulinoma. In these patients with insulinoma, neuroglycopenic episodes exclusively after meal ingestion and negative 72-h fasts are extraordinarily rare. We describe five adults with neuroglycopenic episodes from hyperinsulinemic hypoglycemia within 4 h of meal ingestion and negative 72-h fasts. Each had negative transabdominal ultrasonography, spiral computed tomographic scanning, and celiac axis angiography of the pancreas. However, all showed positive selective arterial calcium stimulation tests indicative of pancreatic beta-cell hyperfunction. At pancreatic exploration, no insulinoma was detected by intraoperative ultrasonography and complete mobilization and palpation of the pancreas. Moreover, the resected pancreata showed islet hypertrophy and nesidioblastosis, but no insulinoma. No definite disease-causing mutation was detected in Kir6.2 and SUR1 genes, which encode the subunits of the pancreatic ATP-sensitive potassium channel responsible for glucose-induced insulin secretion. Four patients who underwent gradient-guided partial pancreatectomy have been free of hypoglycemic symptoms for up to 3 yr follow-up; the other, who underwent a limited distal pancreatectomy, has had brief recurrence of symptoms. The unique clinical features and responses to dynamic testing in these adults with hyperinsulinemic hypoglycemia in the absence of insulinoma may constitute a new syndrome of postprandial hypoglycemia from diffuse beta-cell hyperfunction.

Advances and controversies in the diagnosis and management of medullary thyroid carcinoma.

Recent advances in the diagnosis and treatment of medullary thyroid carcinoma (MTC) have been significant, but some issues remain controversial. MTC may occur either as a hereditary or a nonhereditary entity. Hereditary MTC can occur either alone--familial MTC (FMTC)--or as the thyroid manifestation of multiple endocrine neoplasia type 2 (MEN 2) syndromes (MEN 2A and MEN 2B). These hereditary disorders are due to germline mutations in the RET proto-oncogene. Early diagnosis and treatment considerably improve the prognosis in patients with MTC. Genetic testing can identify almost all affected individuals with hereditary disease and permits early thyroidectomy in gene carriers. Plasma CT is an excellent marker for postoperative follow-up. Imaging studies help delineate recurrent or metastatic lesions. Treatment of recurrent or metastatic disease is primarily surgical, including either palliative or microdissective surgery. Radiation therapy is reserved for skeletal metastasis or nonresectable metastatic MTC. Efficacy of current chemotherapy programs is not well established. Overall, the 10-year survival rates are approximately 65%.

Results of subtotal parathyroidectomy in hemodialysis patients.

In 61 hemodialysis patients undergoing subtotal parathyroidectomy, there was a good correlation between the preoperative serum immunoreactive parathyroid hormone value (iPTH) and the weight of parathyroid tissue removed surgically (p less than or equal to 0.001). Postoperatively, iPTH decreased rapidly from an initial mean (+/- SD) of 2,928 +/- 1,600 muleq/ml and remained at 365 +/- 296 muleq/ml at last follow-up of patients still undergoing hemodialysis (normal, less than 50 muleq/ml). Of six patients who had recurrent hyperparathyroidism (10 percent of total), three required a second subtotal parathyroidectomy. Aluminum-related osteomalacia eventually developed in six patients with bone biopsy-proven hyperparathyroidism before parathyroidectomy. Nine patients with severe fracturing bone disease and hypercalcemia preoperatively but without clear evidence of hyperparathyroidism did not show a favorable response to subtotal parathyroidectomy (high mortality within 28 months, persistence of hypercalcemia, and symptomatic bone disease). Thus, subtotal parathyroidectomy can benefit patients with clearly established severe progressive hyperparathyroidism not responsive to medical therapy but is contraindicated in patients with low iPTH values and no bone biopsy evidence of severe hyperparathyroidism.

Patterns of failure in grossly resected pancreatic ductal adenocarcinoma treated with adjuvant irradiation +/- 5 fluorouracil.

PURPOSE: Analyze patterns of failure, survival, and tolerance in patients with totally resected ductal adenocarcinoma of the pancreas treated with adjuvant irradiation alone or combined with chemotherapy. METHODS AND MATERIALS: The records of 29 patients treated with radiotherapy following curative resection of pancreas cancer at the Mayo Clinic were retrospectively reviewed. Twenty-two (76%) patients underwent a subtotal pancreatectomy (Whipple procedure), six (21%) a total pancreatectomy, and one (3.5%) a distal pancreatectomy. Twenty-six (90%) had lesions located in the head of the pancreas and three (10%) were located either in the body or tail. Twelve (41%) of the tumors were histologic Grade 3, 15 (52%) Grade 2, and two Grade 1. Contiguous invasion of adjacent tissues or organs was found in fifteen patients (52%) and seventeen (59%) had lymph node involvement. Greater than 75% of patients received more than 45 Gy, with a median dose of 54 Gy, and twenty-seven (93%) patients received concomitant 5-fluorouracil chemotherapy. RESULTS: The median survival was 22.8 months and the 2-year survival 48%. When survival was compared with that achieved with surgery alone in our institution, data suggested a doubling in both median and long-term survival with the addition of adjuvant treatment. Eighty-three percent of patients experienced tumor relapse with seventeen of 29 (59%) developing either liver metastases or peritoneal spread. In three patients, tumors recurred locally; one of one with microscopic residual disease after resection and two of 28 (7%) with negative margins (one of the two was treated with inadequate radiation portals). Patients tolerated adjuvant treatment with minimal acute toxicity consisting mostly of vomiting or nausea which, were controlled with medication in all patients. Chronic toxicity was acceptable; while 5 of 29 (17%) developed some form of possible treatment related complication, only one patient (3.5%) developed a small bowel obstruction. CONCLUSION: These results corroborate data in previous studies which have shown a survival benefit when adjuvant irradiation plus 5-fluorouracil is used in patients with completely resected ductal adenocarcinoma of the pancreas. The patterns of failure indicate that post-operative adjuvant treatment can effectively control disease locally but that future survival improvements will be achieved only by reducing the incidence of liver and peritoneal metastases.

Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein.

The histologic spectrum of proliferative parathyroid lesions (hyperplasia, adenoma, and carcinoma) often overlap, and differentiation between these lesions may at times be difficult. p27kip1 (p27) is a cyclin-dependent kinase inhibitor that helps regulate the transition from the G1 to the S phase of the cell cycle. Significantly higher levels of p27 expression have been detected in some normal tissues than in their neoplastic counterparts. The authors analyzed a series of parathyroid lesions to determine if expression of this cell cycle protein may be useful in distinguishing between parathyroid hyperplasia, adenomas, and carcinomas. Formalin-fixed paraffin-embedded tissues from randomly selected patients (22 histologically normal parathyroid glands, 33 cases of hyperplasia, 43 adenomas, and 17 carcinomas) were analyzed for expression of p27 by immunostaining. All cases were also immunostained for Ki67 with antibody MIB-1. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI). In situ hybridization (ISH) for p27 mRNA was done using a cRNA probe with 30 of these cases. Normal parathyroid glands had the highest p27 LI (89.6 +/- 1.4), followed by hyperplasia (69.6 +/- 7.5), adenomas (56.8 +/- 3.4), and carcinomas (13.9 +/- 2.6). ISH showed no differences in p27 mRNA, indicating that the expression of the p27 gene was controlled at a posttranslational level in parathyroid tissues. Ki67 expression was significantly higher in carcinomas (LI = 8.4 +/- 1.9) than in adenomas (LI = 2.7 +/- 0.2) and hyperplasia (LI = 3.3 +/- 0.4). These results suggest that both p27 and Ki67 may be helpful in the diagnosis of histologically difficult parathyroid lesions.

Surgery of the liver, biliary tract, and pancreas.

Biliary, hepatic, and pancreatic surgery at the Mayo Clinic during 1973 was retrospectively examined. A total of 1,137 operations were performed in the 12-month period, with an overall hospital mortality of 2.6%. The operative mortality for 586 elective cholecystectomies for chronic cholecystitis with cholelithiasis was 0.3%--for acute cholecystitis 1.5% and for elective common duct exploration 2.9%. The present review is compared with prior reports in which similar methodology permitted comparisons. Improvement in operative mortality was noted in surgery for cholecystitis and pancreatic and hepatic lesions. The figures drawn from this and previous reports represent more than 10,000 operations on the liver, biliary tract, and pancreas performed at the Mayo Clinic.

Surgical management of hepatic hydatid disease.

The use of conservative or radical surgical procedures in the management of hepatic echinococcosis is controversial. A review of data on 23 patients with hydatid cysts of the liver that were diagnosed between 1935 and 1990 at our institution was undertaken to determine the safety and efficacy of various surgical procedures. In eight patients (group 1), the cysts were treated conservatively by instillation of a scolicidal agent followed by evacuation of the cyst, drainage, or omentoplasty of the residual cyst cavity. Thirteen patients (group 2) underwent radical excision of the cyst by either pericystectomy or hepatic resection. In addition, two patients were treated by combined techniques. Scolicidal agents were used in 18 patients (78%) and apparently resulted in caustic biliary injury and death in 2 patients. Group 1 and group 2 patients had similar complication rates (62% and 54%, respectively) and mean hospital stay (24 and 23 days, respectively). Recurrent cysts, however, were detected in three of six patients who underwent a conservative surgical procedure and participated in follow-up, whereas no patients treated by a radical procedure had a recurrence. Because pericystectomy and hepatic resection resulted in a low rate of recurrence and eliminated the need for use of potentially toxic scolicidal agents, these procedures may be the preferred method for the surgical management of hepatic hydatid disease.

Pyloric antral mucosal webs.

The current literature on pyloric antral mucosal webs was reviewed. In addition, seven patients in the Mayo Clinic experience with pyloric antral mucosal webs are reported on. In recent years, four patients with significant obstructive symptoms thought to be caused by a mucosal web have had the diagnosis confirmed at surgery and have had excellent results from a variety of surgical procedures.

Vagotomy and pyloroplasty in the treatment of duodenal ulceration. Long-term results.

In the years 1960 through 1966, vagotomy and pyloroplasty was performed for duodenal ulceration in 182 patients. Elective operation was performed in 84% of cases, and intractability of symptoms was the major indication. For emergency operations, bleeding was the main indication. Eight of 182 patients died in the postoperative period (operative mortality 4.4%--3.3% elective, 10.3% emergency). Follow-up of 1 to 17 years has been obtained in 154 of 182 patients (96% of these from 5 to 17 years). Ulcer recurred in 12.3% of cases (13.6% elective, 4.5% emergency); the average time to recurrence was 4.8 years. Fully 37% of recurrent ulcers were documented 6 years or more postoperatively. Morbidity was significant; diarrhea and "dumping" were the most noteworthy sequelae, and these occurred in 16.2% and 7.8% of cases, respectively. "Postgastrectomy sequelae" occurred in 61 of 154 patients. It is concluded from this study that vagotomy and phyloroplasty, as currently practiced and used in the elective surgical treatment of chronic duodenal ulceration, does not sufficiently protect against recurrence of ulcer.

Biliary bypass for ductal adenocarcinoma of the pancreas: Mayo Clinic experience, 1970-1975.

During a recent 6-year period at the Mayo Clinic, 151 biliary bypass procedures for ductal adenocarcinoma of the pancreas were done, with operative mortality of 6.0% and an acceptable operative morbidity. Relief of jaundice was universal among survivors. Median survival was 6.0 months, and 3-year survival was 2%. These figures are compared with those for resective procedures.

Subclavian vein. A golden route.

Percutaneous access to the subclavian vein provides a route for the insertion of a variety of devices necessary in the management of severely ill patients. As described in this article, the technique can be easily and safely performed. Special emphasis is given to the more recent applications of the technique in the placement of Swan-Ganz catheters, cardiac pacemakers, and hemodialysis cannulas. With familiarity of the anatomy, careful attention to details, and an awareness of the potential complications, this technique can become a useful tool for the practicing physician in various disciplines.

Are concomitant surgical procedures acceptable in patients undergoing cervical exploration for primary hyperparathyroidism?

Cervical exploration for primary hyperparathyroidism is an extremely safe procedure with essentially no operative mortality or morbidity and with success rates approaching 98%. These results have encouraged experienced surgeons to perform other surgical procedures concomitantly with cervical exploration with use of the same general anesthetic agent. This retrospective study was performed to assess the safety and efficacy of this practice. At our institution, 117 patients underwent cervical exploration for primary hyperparathyroidism in combination with an additional surgical procedure, including breast (25), biliary (21), gynecologic (19), intra-abdominal (18), and cardiothoracic (6) operations. The mean operative time was 155 minutes, and the mean duration of hospitalization was 7.6 days. Postoperatively, 115 patients (98%) were normocalcemic. Nine complications (mostly minor), which occurred in eight patients, related primarily to the concomitant surgical procedure. No operative mortality occurred. If performed by experienced surgeons in carefully selected patients, cervical exploration for primary hyperparathyroidism in combination with another elective operation is safe and cost-effective.

Classification of hepatic venous outflow obstruction: ambiguous terminology of the Budd-Chiari syndrome.

Severe hepatic venous outflow obstruction and its manifestations often are recorded under the label "Budd-Chiari syndrome." Unfortunately, this label is ambiguous; it does not clearly identify the site of the lesion (hepatic veins versus inferior vena cava), its morphologic features (thrombotic versus nonthrombotic), or its cause. In the literature, implied or expressed definitions vary. Use of a standardized topographic and pathogenetic classification of hepatic venous outflow obstruction would enable investigators to group patients with comparable conditions, as required for therapeutic trials, prognostic evaluations, and studies of pathogenetic pathways. Review of our own cases revealed that hepatic venous outflow obstruction involving large hepatic veins is usually thrombotic and that isolated obstruction of the inferior vena cava or of small hepatic veins is usually nonthrombotic. Application of such a classification seems feasible and may yield useful results.