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Background: Intraoperative parathyroid hormone (ioPTH) levels are not monitored routinely in thyroid surgery, although they are used widely during parathyroidectomy as an indicator of parathyroid gland function. This prospective study evaluated the occurrence of hypoparathyroidism after thyroid surgery and the use of ioPTH levels to predict the need for postoperative vitamin D supplementation., Methods: Seventy-two patients underwent thyroidectomy or neck dissection by 1 surgeon. Forty-five patients had a total thyroidectomy, 16 patients had a hemithyroidectomy, 9 patients had a completion thyroidectomy, and 2 patients had a neck dissection alone for recurrent thyroid cancer. ioPTH and serum calcium (SCa) levels were obtained during the course of surgery and 1 month after surgery. Levels from these time points were compared, and correlated with the need for vitamin D supplementation at the 1-month follow-up evaluation using the Fisher exact test., Results: Of the 72 patients, 14 had an ioPTH level less than 10 pg/mL at closure. At the 1-month evaluation, 11 of these 14 patients required vitamin D supplementation because of persistent hypoparathyroidism or hypocalcemia (P <.001). The remaining 3 of the 14 patients with ioPTH levels less than 10 pg/mL at closure did not require vitamin D supplementation at the 1-month evaluation because they were asymptomatic and their PTH and SCa levels had normalized. None of the 58 patients with an ioPTH level greater than 10 pg/mL at closure needed vitamin D supplementation at the 1-month follow-up evaluation., Conclusions: An ioPTH level less than 10 pg/mL at closure is a strong predictor of hypoparathyroidism after thyroid surgery. Patients with ioPTH levels less than 10 pg/mL at closure should be placed on vitamin D supplementation after surgery to anticipate decreased parathyroid gland function and to avoid symptomatic hypocalcemia.

Background: Ductal carcinoma in situ of the breast (DCIS) forms a heterogeneous group of lesions with varying invasive potential. This study tested whether heparanase-1 (HPR1), an endoglycosidase that specifically degrades the heparan sulfate (HS) proteoglycans in the breast extracellular matrix, was associated with the most aggressive DCIS subtypes., Study Design: Fifty-seven DCIS specimens and 10 normal breast specimens were examined for HPR1 expression using immunohistochemical staining. Twenty-seven arbitrarily selected specimens were also examined for HS deposition by immunofluorescence staining, confirming HPR1 activity. Patient medical records were obtained to explore a possible association between biologic potential using Van Nuys Prognostic Index (VNPI) and HPR1 expression., Results: Twenty-one (75%) of 28 comedo and microinvasive DCIS specimens stained HPR1 positive; 4 (14%) of 29 other subtypes (papillary, cribriform, and solid subtypes) stained HPR1 positive on immunohistochemistry (p = 0.003). Among 27 DCIS stained for HS, we found that 8 (67%) of 12 HPR1-negative DCIS had intact HS deposition in the extracellular basement membrane; none of the 15 HPR1-positive DCIS stained HS positive. Six (86%) of seven DCIS with VNPI scores 8 to 9 and 14 (50%) of 28 DCIS with VNPI scores 5 to 7 were HPR1 positive; only 3 (17%) of 18 DCIS with VNPI scores 3 to 4 were HPR1 positive. Median VNPI score in patients with HPR1-positive DCIS was 7 (range 3 to 9), compared with 4.5 (range 3 to 7) in patients with HPR1-negative DCIS (p < 0.001)., Conclusions: HPR1 was expressed at a significantly higher frequency in the invasive comedo and DCIS with microinvasion subtypes than in the noninvasive subtypes. HPR1 expression was inversely associated with HS deposition in the extracellular basement membrane of the DCIS. HPR1 expression was associated with a higher VNPI score. These observations suggest that HPR1 expression in DCIS can play an important role in development of DCIS into an invasive breast cancer.

Background: Intraoperative parathyroid hormone (IOPTH) monitoring in parathyroidectomy for multigland disease is less clear than for single-gland disease. This study assesses the role of IOPTH for hyperplasia., Methods: A prospective database revealed 45 patients with hyperplasia undergoing parathyroidectomy utilizing IOPTH from February 1999 to August 2003., Results: Twenty-six females and 19 males had a mean age of 55 years. Twenty-two patients underwent total parathyroidectomy. Twenty-three patients underwent subtotal parathyroidectomy. Twenty-seven patients (60%) had a drop of IOPTH greater than 50% at 10 minutes after removal of all presumably abnormal parathyroid tissue. Nine additional patients (20%) had an IOPTH drop greater than 50%, but continued exploration revealed more abnormal tissue. Nine patients failed to decrease greater than 50%, and exploration was continued. A final IOPTH less than 35 pg/mL or a greater than 90% decrease from baseline was predictive of a successful operation in 40 patients. The 5 patients who did not meet this criteria remained hyperparathyroid., Conclusions: IOPTH identifies sporadic hyperplasia and guides completeness of resection for patients with known hyperplasia. However, more rigid criteria are required than for adenomas. Failure to achieve appropriate decreases in IOPTH should prompt further neck exploration or a search for a mediastinal gland.

Hypothesis: Minimally invasive parathyroidectomy (MIP) depends on accurate preoperative localization of abnormal parathyroid glands. If the findings of a technetium Tc 99m sestamibi-labeled single-photon emission computed tomography (SPECT) (hereafter referred to as sestamibi SPECT or scan) are negative or ambiguous, cervical ultrasonography (CUS) may increase the success of preoperative gland localization and MIP, avoiding bilateral neck exploration., Design: We collected data regarding preoperative sestamibi SPECT and CUS for parathyroid gland localization and intraoperative findings., Setting: Tertiary care university hospital., Patients: From August 1, 2000, through January 31, 2003, 71 patients (12 men and 59 women; mean age, 59 years) with primary hyperparathyroidism underwent preoperative sestamibi SPECT and CUS. Patients with prior or concurrent thyroid surgery, reoperative parathyroid disease, secondary/tertiary hyperparathyroidism, or studies performed at outside hospitals, were excluded. The MIP was performed by 1 surgeon with a 2- to 3-cm incision made on the side of the neck where the abnormal gland was preoperatively located., Main Outcome Measurements: Operative findings were compared with results of preoperative studies to determine the accuracy of sestamibi SPECT and CUS for successful MIP., Results: All 71 patients underwent preoperative sestamibi SPECT and CUS. Sestamibi scanning was accurate in 53 (75%) of 71 patients, whereas CUS was accurate in 40 (56%) in determining the side where the glands were located. Sestamibi scan and CUS findings were negative in 5 patients. These patients underwent planned bilateral neck exploration. Of the remaining 66 patients, MIP was successfully performed in 60 (91%). The CUS was complementary to sestamibi scanning in 9 (15%) of these 60 patients, allowing them to avoid bilateral neck exploration., Conclusions: A positive sestamibi scan finding is the only preoperative requirement for most patients with primary hyperparathyroidism for MIP. If the sestamibi scan findings are negative or ambiguous, preoperative CUS can localize an additional 14% of enlarged parathyroid glands, further facilitating an MIP in these patients.

Hypothesis: Laparoscopic adrenalectomy (LA) is most commonly performed for pheochromocytomas (PHEs) and aldosteronomas (ALDs). We hypothesize that LA for these differing tumor types is associated with different operative courses and outcomes., Design: Retrospective study of a 10-year experience with LA., Setting: University teaching hospital., Patients: Laparoscopic adrenalectomy was performed on 149 patients. During data analysis, the initial 35 LAs performed for various adrenal lesions were excluded to account for the learning curve. Twenty-six of 30 PHEs and 34 of 45 ALDs were included., Main Outcome Measures: Analysis of variance was used to compare operative time, tumor size, estimated blood loss, and postoperative length of hospital stay between the PHE and ALD groups and subsets of these groups. chi(2) Analysis was used to compare tumor location, transfusion requirements, conversion to open procedures, and incidence of major complications., Results: Right-sided lesions occurred in 19 of 26 PHEs, and left-sided lesions occurred in 28 of 34 ALDs (P <.001). Mean +/- SD tumor size of PHEs (4.9 +/- 1.8 cm) was larger than that of ALDs (2.7 +/- 1.7 cm) (P <.001). Mean +/- SD operative time for PHEs vs ALDs was 191 +/- 49 vs 162 +/- 48 minutes (P =.02). Mean +/- SD estimated blood loss was greater for PHEs (276 +/- 298 mL) than for ALDs (196 +/- 324 mL) (P =.33). Subset analysis revealed that the mean +/- SD size of right-sided PHEs (5.3 +/- 1.8 cm) was significantly larger than that of right-sided ALDs (3.0 +/- 1.5 cm) (P=.001). Mean +/- SD operative time for right-sided PHEs (198 +/- 44 minutes) was longer than that for right-sided ALDs (145 +/- 37 minutes) (P=.005). Six PHE patients required blood transfusions vs 2 ALD patients (P =.05). Two LAs, 1 PHE and ALD, were converted to open procedures. Mean +/- SD length of hospital stay was longer for PHE patients vs ALD patients (4 +/- 4 vs 2 +/- 3 days; P =.08). Six PHE patients had complications vs 3 ALD patients (P =.13)., Conclusions: For PHEs, LA was associated with the removal of more right-sided lesions, larger tumors, longer operative times, and more complications. Trends toward greater estimated blood losses and longer hospital stays were observed for PHEs vs ALDs. Despite the advanced skills of an experienced surgeon, LA for PHEs is associated with a more complex course than for ALDs. Surgeons should begin performing LA for ALD early in their experience to avoid the potential pitfalls associated with PHEs.

While primary hyperparathyroidism (primary HPT) is recognized as a correctable cause of nephrolithiasis and osteoporosis, its role as an organic cause of major depression is less clear. The rate of major depression in primary HPT, response of symptoms to parathyroidectomy, and potential cost benefits were reviewed. From August 1994 to September 2002, 360 patients underwent parathyroidectomy for primary HPT. Thirty-five patients met Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM IV-TR) criteria for major depression. Postoperatively, a modified form of the Outcomes Institutes Health Status Questionnaire 2.0 was used to evaluate patient mood and continued need for antidepressant medication (ADM). Cost analysis of ADM use was performed. Thirty-five of 360 patients (10%) with primary HPT met criteria for major depression. Thirteen of 35 (37%) required ADM preoperatively. Postoperatively, 29/35 (83%) patients responded to a phone survey: 90 per cent stated depression no longer impacted their ability to work or activities of daily living; 52 per cent reported an improved quality of life; 27 per cent discontinued preoperative ADM; and 27 per cent reduced their ADM dose. Reduction in ADM resulted in a savings of dollars 700 to dollars 3000 per patient per year. Major depression occurs in 10 per cent of patients undergoing parathyroidectomy for primary HPT. Parathyroidectomy reduces symptoms of major depression, improves quality of life, and can eliminate or reduce the need for antidepressant medication in up to 54 per cent of patients.

Objective: To report the complementary use of video-assisted thoracoscopic surgery (VATS) and intraoperative 99mTc-sestamibi scanning for persistent secondary hyperparathyroidism due to a mediastinal supernumerary parathyroid gland., Methods: We describe a patient with recurrent secondary hyperparathyroidism attributable to a mediastinal parathyroid gland who underwent parathyroidectomy with use of VATS, intraoperative 99mTc-sestamibi scanning (gamma probe), and intraoperative monitoring of intact parathyroid hormone (iPTH)., Results: A 32-year-old man with chronic renal failure who had undergone a 4-gland parathyroidectomy with autotransplantation 14 years previously presented with symptomatic hypercalcemia. A preoperative single-photon emission computed tomographic (SPECT) sestamibi scan revealed a focus of mediastinal uptake, suggestive of an intrathymic gland. The patient underwent a cervical exploration, and the previously reimplanted parathyroid gland and the thymus were resected. iPTH levels failed to normalize, and the operation was terminated. A repeated SPECT scan again revealed an area of mediastinal uptake. Computed tomographic scan of the chest showed a mediastinal gland adjacent to the aortic arch. VATS and intra-operative sestamibi scanning aided in localization of the ectopic parathyroid gland. After removal of the hyperplastic gland, iPTH levels decreased appropriately., Conclusion: In reoperative parathyroidectomy involving mediastinal glands, VATS, complemented by gamma probe localization and iPTH monitoring, may be used to minimize the operative dissection needed to cure hyperparathyroidism.

Purpose: Heparanase-1 (HPR1) is an endoglycosidase that degrades the side chains of heparan sulfate proteoglycan (HSPG), a key component in cell surfaces, the extracellular matrix (ECM), and the basement membrane (BM). The purpose of this study was to evaluate HPR1 expression in thyroid neoplasms and its effect in degrading the HSPG substrates in the ECM and BM and to determine its role in thyroid tumor metastasis., Experimental Design: HPR1 mRNA expression was analyzed by using in situ hybridization with a digoxigenin-labeled antisense RNA probe on paraffin-embedded tumor sections and reverse transcription-PCR (RT-PCR) in fresh tumor tissues. HPR1 protein expression was analyzed by using immunohistochemical staining with an anti-HPR1 rabbit antiserum and immunofluorescence (IF) with an anti-HPR1 monoclonal antibody. The effect of HPR1 expression in thyroid neoplasms was analyzed by examining the presence and integrity of the HSPG substrates in the ECM and BM using IF staining with a specific monoclonal antibody against heparan sulfate. The relationship of HPR1 expression in papillary thyroid carcinomas (PTCs) with various clinicopathological parameters was analyzed statistically. The role of HPR1 in thyroid tumor metastasis was further examined by comparing HPR1 levels in 10 thyroid tumor cell lines to their invasive and metastatic potential., Results: In situ hybridization analysis of 81 tumor samples (62 papillary carcinomas and 19 follicular adenomas) revealed that HPR1 was expressed at a much higher frequency in PTCs than in follicular adenomas (P<0.05). RT-PCR analyses of fresh tumor tissues revealed that HPR1 mRNA could be detected in primary and metastatic thyroid papillary carcinomas. HPR1 expression was confirmed at the protein level by immunohistochemical staining and IF stainings. IF analysis of HSPG revealed that HS was deposited abundantly in the BM of normal thyroid follicles and benign follicular adenomas but was absent in most thyroid papillary carcinomas. A lack of heparan sulfate in PTCs inversely correlated with HPR1 expression. Clinicopathological data analyses revealed that PTCs with local and distant metastases scored HPR1 positive at a significantly higher frequency than nonmetastatic thyroid cancers (P=0.02). To further explore the role of HPR1 in tumor metastases, we characterized HPR1 expression in 10 thyroid tumor cell lines using RT-PCR and Western blot and measured HPR1 enzymatic activity using a novel ELISA. HPR1 was differentially expressed in different types of cell lines; overexpression of HPR1 in two tumor cell lines led to a dramatic increase of their invasive potential in vitro in an artificial BM., Conclusions: Our study suggests that HPR1 expressed in papillary carcinomas is functional and that HPR1 expression is associated with thyroid tumor malignancy and may significantly contribute to thyroid tumor metastases.

Biliary stricture and duodenal obstruction have been increasingly recognized as complications of chronic pancreatitis. The anatomical relationship of the distal common bile duct and the duodenum with the head of the pancreas is the main factor for their involvement in chronic pancreatitis. In hospitalized patients with pancreatitis, the incidence of biliary stricture and duodenal obstruction is reported to be about 6% and 1.2%, respectively. For patients requiring an operation for chronic pancreatitis the incidence increases to 35% for biliary stricture and 12% for duodenal obstruction. Fibrosis around the distal common bile duct can cause stenosis with obstruction of bile flow. Clinically, the presentation of these patients ranges from being asymptomatic with elevated alkaline phosphatase or bilirubin, or both, to being septic with cholangitis. Jaundice, cholangitis, hyperbilirubinemia, and persistent elevation of serum alkaline phosphatase occur more frequently in patients with pancreatitis with a biliary stricture. A twofold elevation of alkaline phosphatase is a marker of possible common duct stenosis in patients with chronic pancreatitis. The incidence of both biliary cirrhosis and cholangitis in these patients is about 10%. ERCP reveals a characteristic long, smoothly tapered stricture of the intrapancreatic common bile duct. In duodenal obstruction, the factors that convert self-limiting edema to chronic fibrosis and stricture formation are unknown, but ischemia superimposed on inflammation may be the major cause. These patients present with a prolonged history of nausea and vomiting. Barium studies typically show a long constricting lesion of the duodenum, and endoscopy reveals reactive inflammatory changes in a narrowed duodenum. Operation is indicated in patients with common bile duct strictures secondary to chronic pancreatitis when there is evidence of cholangitis, biliary cirrhosis, common duct stones, progression of stricture, elevation of alkaline phophatase and/or bilirubin for over a month, and an inability to rule out cancer. The operation of choice is either choledochoduodenostomy or choledochojejunostomy. A cholecystoenterostomy is less favored because of its higher failure rate (23%). Endoscopic stenting plays a role in patients who are unfit for surgery, but it is not recommended as definitive therapy. For duodenal obstruction, failure to resolve the obstruction with 1-2 weeks of conservative therapy is an indication for bypass. The operation of choice is a gastrojejunostomy. Not uncommonly, combined obstruction of the pancreatic duct, common bile duct, and duodenum will develop. Combined drainage procedures or resection are used to manage these problems.

Background: Interest in general surgery has declined among US medical students, with the increasing number of female medical students being cited as a causative factor. This study evaluates factors related to choosing a general surgery career and determines if they differ between men and women., Methods: A survey assessing factors that contributed to career choice was distributed to a 2002 graduating medical school class to be returned with their match lists. Students were asked, from a given list, which factors influenced their career choice. Those students who did not pursue a career in general surgery were asked what factors contributed to that decision. The results were stratified by gender., Results: Of 120 surveys, 54 women and 48 men responded (response rate=85%). The reason most commonly cited for a particular career choice by both men and women was the intellectual challenge of the field, chosen by 41 men (85%) and 46 women (85%). The two next most common reasons cited by male students were an elective in the field and practice lifestyle (40 of 48 respondents, or 82%, for each). Practice lifestyle was a contributing factor for 37 of the 54 women, or 69% (P=.132). The other reasons most commonly cited by women were an elective and faculty in the chosen field (46 of 54, or 85%, and 38 of 54, or 70%). Thirty-seven of the 48 men, or 77% (P=.588), felt that faculty in the field contributed to their career choice. The most commonly cited reasons for not choosing general surgery--residency lifestyle, practice lifestyle, and length of training--were the same for both groups., Conclusions: Fewer women than men considered practice lifestyle in choosing their medical career. However, both men and women considered lifestyle, elective in the field of choice, and faculty important in career choice. In 2002, men and women had the same reasons for pursuing a career in general surgery or seeking another specialty.

Background: Hyperparathyroidism is associated with subjective feelings of fatigue and depression as well as limitations in physical activity from musculoskeletal complaints. These quality of life symptoms are not widely accepted as an indication for parathyroidectomy. This study quantifies and compares subjective symptoms of patients with hyperparathyroidism before and after surgery., Methods: Between February 2001 and June 2002, 61 patients (14 males and 47 females, mean age of 60.8+/-14.4 years) underwent parathyroidectomy. There were 45 patients with single-gland adenomas, 9 patients with double adenomas, 3 patients with primary hyperparathyroidism from 4-gland hyperplasia, 3 patients with secondary hyperparathyroidism, and 1 patient with tertiary hyperparathyroidism. Patients filled out a 53-question survey based on the Health Outcomes Institute Health Status Questionnaire 2.0 before surgery, 1 month postoperatively, and 3-24 months postoperatively. The survey included questions on overall health, daily activities, mood, and medical conditions. Surveys were analyzed for changes in symptoms attributable to parathyroidectomy. Serum calcium and intact parathyroid hormone levels were obtained preoperatively and at 1- and 3-month follow-up visits., Results: At both postoperative evaluations, patients' perception of general health, muscle strength, energy level, and mood significantly improved (P<.05). Moreover, there was a significant correlation between the changes in serum calcium and intact parathyroid hormone levels and improvement in symptoms., Conclusions: Parathyroidectomy for hyperparathyroidism is associated with significant improvement in patient quality of life. These subjective symptoms represent a valid indication for parathyroidectomy.

Entrapment neuropathy is a group of clinical disorders involving compression of a peripheral nerve and interference with nerve function mostly through traction injury. We have investigated the chronic compression of peripheral nerves as an experimental procedure for detecting changes in ultrastructural nerve morphology. Adult hamsters (Mesocricetus auratus, N = 30) were anesthetized with a 25% pentobarbital solution and received a cuff around the right sciatic nerve. Left sciatic nerves were not operated (control group). Animals survived for varying times (up to 15 weeks), after which they were sacrificed and both sciatic nerves were immediately fixed with a paraformaldehyde solution. Experimental nerves were divided into segments based upon their distance from the site of compression (proximal, entrapment and distal). Semithin and ultrathin sections were obtained and examined by light and electron microscopy. Ultrastructural changes were qualitatively described and data from semithin sections were morphometrically analyzed both in control and in compressed nerves. We observed endoneurial edema along with both perineurial and endoneurial thickening and also the existence of whorled cell-sparse structures (Renaut bodies) in the subperineurial space of compressed sciatic nerves. Morphometric analyses of myelinated axons at the compression sites displayed a remarkable increase in the number of small axons (up to 60%) in comparison with the control axonal number. The distal segment of compressed nerves presented a distinct decrease in axon number (up to 40%) comparatively to the control group. The present experimental model of nerve entrapment in adult hamsters was shown to promote consistent histopathologic alterations analogous to those found in chronic compressive neuropathies.

Background: Intraoperative intact parathyroid hormone (iPTH) monitoring is useful in the operative management of hyperparathyroidism. Recent studies suggest that measurement of intraoperative total serum calcium (TSC) levels may be a more cost effective and readily available method of intraoperative guidance during neck dissection than iPTH levels, the gold standard. We compared the accuracy of intraoperative TSC to iPTH in predicting surgical cure during parathyroidectomy., Patients and Methods: From September 1, 2001 to October 31, 2002, 88 parathyroidectomies were performed. iPTH and TSC were measured at the start of the operation, and at 5 and 10 min after gland removal. Data were compared, and trends were analyzed with respect to removal of abnormal parathyroid tissue as confirmed by pathology. One-way analysis of variance was used to determine if decreases in TSC were significant., Results: The mean baseline iPTH level (418 +/- 610 pg/ml) dropped by 70% 5 min after removal of the abnormal glands (86 +/- 102 pg/ml) and by 85% at 10 min (39 +/- 39 pg/ml). The mean baseline TSC level (10.0 +/- 0.8 mg/dl) dropped by 4% at 5 min after removal of the abnormal glands (9.6 +/- 0.9 mg/dl) and remained at 4% at 10 min (9.6 +/- 0.8 mg/dl). iPTH dropped by > or =50% in 73 patients (83%) at 5 min and in 87 patients (99%) at 10 min after gland resection. TSC decreased below baseline at 5 min and remained below baseline at 10 min in only 47 patients (54%). In the remaining patients, intraoperative TSC changes were less predictable and did not respond consistently to resection of abnormal glands., Conclusions: The decreases in TSC during parathyroidectomy, if present, are minimal. Unlike iPTH levels, TSC levels do not consistently decrease at 5 and 10 min after gland resection. While attractive in terms of cost and availability, intraoperative TSC levels are not clinically reliable in confirming removal of abnormal parathyroid tissue.

The RAS-RAF-MEK-ERK-MAP kinase pathway mediates the cellular response to extracellular signals that regulate cell proliferation, differentiation, and apoptosis. Mutation of the RAS proto-oncogene occurs in various thyroid neoplasms such as papillary thyroid carcinomas (PTCs), follicular thyroid adenomas and carcinomas. A second genetic alteration frequently involved in PTC is RET/PTC rearrangements. Recent studies have shown that BRAF, which is a downstream signaling molecule of RET and RAS, is frequently mutated in melanomas. This study tests whether BRAF is also mutated in thyroid tumors and cell lines. We analyzed BRAF gene mutation at codon 599 in thyroid tumors using mutant-allele-specific PCR and in 10 thyroid tumor cell lines by DNA sequencing of the PCR-amplified exon 15. We found that BRAF was mutated in 8 of 10 thyroid tumor cell lines, including 2 of 2 papillary carcinoma cell lines, 4 of 5 anaplastic carcinoma cell lines, 1 of 2 follicular carcinoma cell lines, and 1 follicular adenoma cell line. BRAF mutation at codon 599 was detected in 21 of 56 PTC (38%) but not in 18 follicular adenomas and 6 goiters. BRAF mutation occurred in PTC at a significantly higher frequency in male patients than in female patients. To test whether BRAF mutation may cooperate with RET/PTC rearrangements in the oncogenesis of PTC, we tested whether BRAF-mutated PTCs were also positive for RET/PTC rearrangements. Immunohistochemical staining was conducted to evaluate RET/PTC rearrangements by using two different anti-RET antibodies. Surprisingly, we found that a large number of BRAF-mutated PTCs (8 of 21) also expressed RET, indicating that the RET proto-oncogene is rearranged in these BRAF-mutated PTCs. These observations suggest that mutated BRAF gene may cooperate with RET/PTC to induce the oncogenesis of PTC.

Central pancreatectomy is an uncommonly performed procedure that may be particularly useful for the removal of benign and low malignant potential lesions in the neck and body of the pancreas. This procedure may have fewer major complications and better preserve endocrine and exocrine function than the more commonly performed pancreaticoduodenectomy or distal pancreatectomy. We report our recent experience with central pancreatectomy and review the literature on this topic.

An 18-year-old woman presented with a 6-month history of amenorrhoea and hyperandrogenism. Three months later she developed several episodes of fasting hypoglycaemia and was subsequently diagnosed with an insulinoma. Hyperinsulinaemia was observed in association with an elevated serum testosterone level. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS). Polycystic ovarian syndrome is unusual in a patient having an insulinoma. The rarity of this association may be the result of the late age of onset of this type of tumour, intermittent secretion of excessive insulin by the tumour, the degree of hyperinsulinism or other factors extrinsic to the insulin receptor that may facilitate insulin activity. However, we could not discover how our patient differs in having had PCOS from the majority of women with insulinoma who do not. If other patients with insulinoma are subsequently found to have hyperandrogenism, then this tumour might be added to the differential diagnosis of causes of anovulatory cycles and hyperandrogenaemia, although rare the association would be uncommon.

Managing cervical lymph node metastases in well-differentiated thyroid cancer with either "berry picking" (BP) or anatomic neck dissection (AND) has not been shown to alter survival. Nevertheless local control of thyroid cancer is important. The purpose of this study is to determine whether the local recurrence rate of well-differentiated thyroid cancer is equivalent with BP versus AND. A retrospective analysis revealed 41 patients with well-differentiated thyroid cancer and cervical node metastases seen by a single surgeon from 1985 to 2002. A total of 83 initial and repeat neck operations were performed (nine BPs, 30 central neck dissections, and 44 modified radical neck dissections). Recurrence of cancer, intervention for recurrence, and complications of the BP and AND groups were evaluated. All nine (100%) patients undergoing a limited BP operation had local recurrence of cancer. Only three of the 32 (9%) patients undergoing an initial formal neck operation had local recurrence of tumor. The recurrences after BP (100%) were significantly greater than the recurrences after AND (9%) (P < 0.001). The incidence of surgical complications with BP and AND was not different. Six of 32 (19%) initial formal neck dissection patients and four of nine (44%) BP patients had surgical complications. We conclude that BP is associated with greater local recurrence of thyroid cancer. Patients with nodal metastases should be managed with ANDs.

Introduction: Extracellular matrix (ECM) degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the ECM. Previous studies have demonstrated HPR expression in various malignancies and that there is differential HPR expression between benign and malignant tumors. Currently, there is no technique that can reliably predict the malignant behavior of some pheochromocytomas. This study tests whether HPR is differentially expressed in malignant and benign pheochromocytomas., Methods: Paraffin-embedded specimens from 29 pheochromocytomas were evaluated. The tissues were collected from surgical specimens over a 10-year period from 26 patients (8 males, 18 females) with a mean age of 47 years (range 19-78 years, median 47 years). One female patient underwent 3 separate operations for malignant pheochromocytoma and thus provided 3 specimens. Another female patient had both the primary tumor and a liver metastasis processed, and therefore provided 2 specimens. Patient charts and pathology reports were reviewed to classify the pheochromocytomas as either benign or malignant. Based on clinical behavior and/or pathological evidence of metastasis or invasion into surrounding tissues, 10 specimens were malignant and 19 had benign behavior. As a control, normal adrenal tissue from 3 nephrectomy specimens was included in the study, as was tissue from 1 adrenocortical adenoma. All 33 specimens were tested for HPR gene expression by in situ hybridization (ISH) with an antisense RNA probe and immunohistochemistry (IHC) with an anti-HPR antibody. Statistical analysis was done using the chi(2) test of proportions to determine if HPR expression correlated with malignancy using ISH, IHC, or both tests together., Results: Using ISH, the percentage of HPR expression in the malignant pheochromocytomas was 50% while HPR expression in the benign tumors was 21% (P = 0.11). Using IHC, the percentage of HPR expression in the malignant pheochromocytomas was 80% while HPR expression in the benign tumors was 32% (P = 0.01). Considering both tests cumulatively, all 10 malignant pheochromocytomas stained positive for HPR by ISH and IHC, while only 37% of the benign tumors were positive for HPR expression (P = 0.001). The one adrenal adenoma and the 3 normal adrenal glands processed stained negative for HPR expression by both ISH and IHC., Conclusions: HPR expression is higher in malignant pheochromocytomas than in benign pheochromocytomas or normal tissue. HPR may contribute to the invasive characteristics of malignant pheochromocytomas and might be used as a marker to distinguish malignant from benign pheochromocytomas. HPR expression might also be used as a prognostic tool in guiding long-term patient follow-up.

Background: Early survival after pancreaticoduodenectomy has improved, but its morbidity remains high. The purpose of this study is to determine how the intra-operative (OR) occurrence of major vascular complications affects the outcome of pancreaticoduodenectomy., Methods: The medical records of 180 consecutive patients having pancreaticoduodenectomy from 1991 to 2001 were reviewed. Vascular complications were defined as "an unanticipated injury or thrombosis of a major vessel necessitating intervention." Age, sex, type of pancreaticoduodenectomy, tumor size, estimated blood loss, OR time, time in intensive care, post-OR hospitalization, and survival were compared., Results: Eighteen vascular complications were identified. Differences in age, sex, and type of resection between patients with or without vascular complications were not significant. OR time, estimated blood loss, blood transfusions, tumor size, time in intensive care, and post-OR hospitalization were all significantly greater in patients with vascular complications. Median survival for patients with vascular complications was significantly shorter than for patients without vascular complications. Thirty-day mortality was greater in patients with vascular complications., Conclusion: Vascular complications significantly affect the outcome of pancreaticoduodenectomy increasing OR time, estimated blood loss, blood transfusion requirements, time in intensive care, post-OR hospitalization, and mortality.

Background: Reoperation for recurrent thyroid cancer poses an increased risk of complications, including thoracic duct fistula. Treatment of this complication is controversial. A survey of thoracic literature reports the use of somatostatin analog, whereas no cases have reported the use of this therapy in cases arising from neck dissection., Methods: We report a 16-year-old girl with recurrent papillary thyroid cancer who had a persistent lymphatic-cutaneous fistula develop after repeat modified left neck dissection. Despite conservative management, drainage persisted for 2 months. A regimen was begun that included TPN and injections of a somatostatin analog., Results: Treatment with a somatostatin analog resulted in an immediate attenuation of drainage and subsequent closure of the fistula after 16 days of treatment., Conclusion: The use of somatostatin analog can increase the success of conservative management of thoracic duct fistulae., (Copyright 2002 Wiley Periodicals, Inc.)

Background: Metastasis of malignant breast cells is in part mediated through degradation of the extra-cellular matrix by proteolysis, enabling malignant cells to migrate through the surrounding stroma. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate (HS) moiety of proteoglycans, a component of the extracellular matrix and basement membrane., Methods: Fifty-one primary breast tumors, 13 lymph node metastases, 4 ductal carcinoma in situ, 7 benign, and 5 normal specimens were examined for HPR1 expression using immunohistochemical staining. The functional role of HPR1 expression was determined by examining HS deposition using immunofluorescence staining., Results: Sixteen of 30 breast carcinomas (53%) with sentinel node metastasis expressed HPR1. In contrast, only 5 of 21 nonmetastatic primary breast carcinomas (23%) were HPR1 positive. Eighteen of 30 breast carcinomas between 1 and 5 cm expressed HPR1, compared with 3 of 21 HPR1-positive specimens in tumors < or =1 cm. Statistical analysis revealed that HPR1 expression was associated with breast tumor metastases (P =.04) and primary tumors between 1 and 5 cm (P =.002). Ninety percent of HPR1-positive tumors lacked HS deposition, suggesting an inverse correlation between HPR1 expression and HS deposition., Conclusions: HPR1 expression correlates with the lack of HS deposition and with the metastatic potential of breast cancers. The frequency of HPR1 is significantly higher in breast tumors between 1 and 5 cm than in tumors < or =1 cm.

Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate chains of proteoglycan, a component of blood vessel walls and the extracellular matrix. Recent studies demonstrated that HPR1 expression is increased in a variety of malignancies and may play a critical role in tumor metastases. The HPR1 gene and its genomic structure have been recently cloned and characterized. To understand the mechanisms of HPR1 gene expression and regulation, we first mapped the transcription start site of the HPR1 gene and found that HPR1 mRNA was transcribed from the nucleotide position 101 bp upstream of the ATG codon. A 3.5-kb promoter region of the HPR1 gene was cloned. Sequence analysis revealed that the TATA-less, GC-rich promoter of the HPR1 gene belongs to the family of housekeeping genes. This 3.5-kb promoter region exhibited strong promoter activity in two thyroid tumor cell lines. Truncation analysis of the HPR1 promoter identified a minimal 0.3-kb region that had strong basal promoter activity. Truncation and mutational analysis of the HPR1 promoter revealed three Sp1 sites and four Ets-relevant elements (ERE) significantly contributing to basal HPR1 promoter activity. Binding to the Sp1 sites by Sp1 and to the ERE sites by GA-binding protein (GABP) was confirmed by electrophoretic mobility shift assay and competition and supershift electrophoretic mobility shift assays. Cotransfection of Sp- and GABP-deficient Drosophila SL-2 cells with the HPR1 promoter-driven luciferase construct plus the expression vector encoding the Sp1, Sp3, or GABP gene induced luciferase gene expression. Mutation or truncation of the Sp1 or ERE sites reduced luciferase expression in both SL-2 cells and thyroid tumor cell lines. Coexpression of GABPalpha/beta and Sp1 or Sp3 further increased luciferase reporter gene expression. Our results collectively suggest that Sp1 cooperates with GABP to regulate HPR1 promoter activity.

Laparoscopic adrenalectomy has been recommended as the standard method for removing an aldosteronoma. To assess our surgical experience with primary hyperaldosteronism in the era of laparoscopic adrenalectomy a 6-year retrospective review of 30 consecutive patients was done. The 20 men and 10 women ranged in age from 35 to 78 with a mean of 51.2 years. All patients were hypertensive and hypokalemic with a mean serum potassium of 2.9 +/- 0.32 (standard deviation) mmol/L. Serum aldosterone was elevated in 28 of 30 (94%) patients and normal in the remaining two. Serum renin was suppressed in all patients. CT correctly localized the tumor in all 30 patients. Twenty-eight patients had histologically documented adenomas and two had associated cortical hyperplasia on pathology. Mean adenoma size was 2.0 +/- 1.12 cm. Twenty-four patients underwent left laparoscopic adrenalectomies, whereas right laparoscopic adrenalectomies were performed in five. One was converted to an open left adrenalectomy. Mean operative time was 183 minutes. The mean hospital stay for laparoscopic adrenalectomy was 2.2 days. The patients were followed from one to 63 months (mean 26.1 months). Twenty-nine of 30 (95%) patients were rendered normokalemic. The remaining patient takes a potassium-wasting diuretic. Persistent hypertension was present in 10 of 30 (33%) patients. Blood pressure in nine of 10 patients was controlled with less medical therapy. The other patient's blood pressure remained difficult to control despite multiple medications. Duration of hypertension before surgery was a significant risk factor for persistent hypertension (P < 0.05). Gender (P > 0.05) and age (P > 0.05) at the time of surgery were not statistically significant predicators for persistent hypertension. There were two reported trocar site hernias. We conclude that primary hyperaldosteronism due to aldosterone-producing tumors can be diagnosed and accurately localized with preoperative measurements of serum aldosterone, renin, and CT scanning. Laparoscopic adrenalectomy is safe and effective for the treatment of primary hyperaldosteronism with minimal associated morbidity and a short hospital stay. Hypokalemia may be cured by surgical treatment, although persistent hypertension still occurs. Duration of hypertension before surgery is a risk factor for persistent hypertension whereas age and sex are not.

Extracellular matrix degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the extracellular matrix. HPR1 is not expressed in normal epithelial cells but can be detected in a variety of malignancies. In the present study, we examined HPR1 expression in pancreatic cancer by using in situ hybridization and tested whether HPR1 expression correlated with any clinicopathlogic parameters. HPR1 was not detected in the ductal cells of normal pancreas samples obtained from 10 patients at autopsy. However, HPR1 was detected in 77 (78%) of 99 pancreatic adenocarcinomas. Among them, 69 (78%) of 89 primary pancreatic adenocarcinomas and 8 (80%) of the 10 metastases were HPR1 positive. Age, sex, tumor stage, and lymph node status were not predictive of HPR1 expression. Log-rank test of the Kaplan-Meier survival curves revealed that HPR1 expression in early-stage tumors was associated with decreased survival. HPR1 expression was frequent in pancreatic adenocarcinomas and was associated with decreased survival in early-stage tumors. This suggests that HPR1 may contribute to the highly invasive and early metastatic behavior of pancreatic cancer.

This study tests whether exposure to cigarette smoke alone or combined with cellophane wrapping of the pancreas increases the development of microscopic abnormalities in the pancreas of Syrian golden hamsters. Ninety hamsters were randomly divided into 4 groups. Thirty-five hamsters were exposed to 3 continuous hours of cigarette smoke daily for 3 months following celiotomy to cellophane wrap the gastric lobe of the pancreas (group 1). Thirty-two hamsters were not exposed to continuous cigarette smoke and had the wrap surgery alone (group 2). Twelve hamsters were exposed to cigarette smoke and had no surgery (group 3). Eleven hamsters had no exposure to cigarette smoke and no surgery (group 4). All of the hamsters were sacrificed after 3 months. The gastric (wrapped) and splenic (unwrapped) lobes of the pancreas were reviewed grossly and histologically. In all 4 groups, there were no gross abnormalities in either lobe of the pancreas. Histopathologic evaluation of the gastric lobes from group 1 showed that 13 of 35 lobes (37%) had pancreatitis (11 chronic, 1 acute, and 1 both). In group 2, 12 of 32 (38%) gastric lobes had pancreatitis (10 chronic, 2 acute). The incidence of pancreatitis in groups 1 and 2 was significantly higher than in groups 3 (0/12; p < 0.04) and 4 (0/11; p < 0.03), respectively. A significantly lower incidence of pancreatitis was found in the splenic lobes of all 4 groups when compared to gastric lobes in groups 1 and 2. Three of the 67 cellophane-wrapped glands had ductal hyperplasia. The effects of cellophane wrapping of the pancreas, both in the wrapped and unwrapped areas, induced changes of pancreatitis and hyperplasia that may be preneoplastic. Cigarette smoking, alone or combined with cellophane wrapping, did not cause these changes. Longer exposure to cigarette smoke may be needed to cause premalignant changes in the hamster pancreas., (Copyright 2002 S. Karger AG, Basel and IAP)

The infrequent occurrence of benign epithelial cysts of the pancreas is the reason why little is known regarding their clinical relevance and surgical management. We report the case of a 38-year-old woman with a benign epithelial cyst that was resected by the rarely performed central pancreatectomy. The presentation, evaluation, and differences between this and other cystic lesions of the pancreas are discussed. The benefits of central pancreatectomy for this benign lesion are reviewed.

Background: Acute pancreatitis (AP) initiates a generalized inflammatory response that increases intestinal permeability and promotes bacterial translocation (BT). Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon-like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the intestinal mucosa by stimulating epithelial growth. The purpose of this study was to determine whether GLP-2 decreases intestinal permeability and BT in AP., Methods: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied. AP was induced in group I and group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II rats received a similar volume of normal saline as a placebo postoperatively for 3 days. Group III and group IV received GLP-2 analog and placebo, respectively. At 72 hours postoperatively, blood was drawn for culture of gram-negative organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum were harvested for culture of gram-negative bacteria. Intestinal resistance as defined by Ohm's law was determined using a modified Ussing chamber to measure transepithelial current at a fixed voltage. A point scoring system for five histologic features that include intestinal edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and ileum were taken for pathology., Results: All group I and group II rats had AP. The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas, and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%, 30%, and 20% translocation in group II., Conclusion: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis.

Hypothesis: Use of intraoperative measurement of intact parathyroid hormone (iPTH) to confirm complete excision of hyperfunctioning parathyroid tissue does not improve overall operative success rates., Design: Case series of patients undergoing parathyroidectomy with or without intraoperative iPTH measurement., Setting: University teaching hospital., Patients and Interventions: Fifty patients undergoing parathyroidectomy before our institution of intraoperative iPTH sampling in March 1999 (group 1) were compared with 50 patients undergoing parathyroidectomy after this technique was adopted (group 2). Overall, 100 patients underwent operation between December 1996 and May 2000. Serum calcium and iPTH levels were measured at 1- and 3-month intervals. Intraoperative frozen sections and operative times were also analyzed., Results: Mean preoperative calcium levels were 2.85 and 2.82 mmol/L (11.4 and 11.3 mg/dL) in groups 1 and 2, respectively. One-month postoperative calcium values were identical in both groups at 2.35 mmol/L (9.4 mg/dL) (group 1 SD = 0.18 [0.74], group 2 SD = 0.20 [0.82]). At 1 month, all but 1 patient in group 1 had normalized calcium values (2% failure rate), while 3 patients in group 2 (6%) remained hypercalcemic. All 3 patients in group 2 had intraoperative iPTH levels that returned to normal. There was a significant difference in the number of intraoperative frozen sections between groups, with a mean (SD) of 3.4 (1.7) in group 1 and 2.0 (1.6) in group 2 (P<.01). There was no significant difference in operative times between groups., Conclusions: Use of intraoperative iPTH sampling did not significantly affect the overall success of parathyroidectomy, as determined by postoperative normocalcemia. There was, however, a significant decrease in the number of frozen sections sent at operation.

Background: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values., Methods: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals., Results: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values., Conclusions: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.

Background: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations., Patients and Methods: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay., Results: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels., Conclusions: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.

Background: Bacterial translocation from the gut to mesenteric lymph nodes and other extraintestinal sites is an important source of infection in acute pancreatitis. Impaired host immunity is known to promote bacterial translocation. Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reaction, and hematopoiesis., Methods: Twenty-four mongrel dogs (18-29 kg) were studied in four equal groups. In Groups I and II, acute pancreatitis was induced by direct pressure injection of 4% taurocholate and trypsin into the pancreatic duct at laparotomy. Groups III and IV had only laparotomy. Group I and III dogs were given IL-6 (50 microg/kg/d, sq) daily starting 24 h after operation and Group II and IV dogs received an equal volume of saline administered at similar time. All animals had blood drawn for culture, complete blood count (CBC), platelets, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and amylase on d 0, 1, 4, and 7. On d 7, mesenteric lymph nodes (MLN), spleen, liver, pancreas, and cecum were harvested for pathology study and for cultures of aerobic and anaerobic bacteria. Quantitative cecal cultures of aerobic and anaerobic bacteria were obtained., Results: All Group I and Group II dogs had severe pancreatitis. The increase of plasma CRP in Group I was sustained throughout treatment (1.3+/-0.3 on d 0 vs 3.1+/-0.3*, 3.0+/-0.3*, and 2.9+/-0.3* on d 1,4, and 7, respectively). Plasma CRP was increased in Group II on d 1 and d 4 (1.3+/-0.3 mg/dL on d 0 vs 3.6+/-0.3* mg/dL on d 1, and 3.1+/-0.3* on d 4, *p < 0.05). There were no differences in white blood cell (WBC) count, differential, platelets, and ESR between Groups I and II. Bacterial translocation to MLN was lower in Group I (1/6) than in Group II (6/6) (p < 0.05). All 6 dogs in Group II had bacterial spread to distant sites compared to 2 of 6 dogs in Group I (p = 0.066). Both MLN and other distant organ cultures were negative in Group III and only 1 of 6 MLN cultures was positive in Group IV., Conclusions: IL-6 treatment decreases bacterial translocation to MLN and may be beneficial in reducing septic complications in acute pancreatitis.

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLNs) and other extra intestinal organs is an important source of infection in acute pancreatitis (AP). Lexipafant (BB-882) is a potent platelet-activating factor receptor antagonist that has an anti-inflammatory effect. To examine whether BB-882 could affect BT in acute necrotizing pancreatitis, 48 male Sprague Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mL/kg of body weight). Group I rats received BB-882 (10 mg/kg, i.p. qd) and Group II rats received a similar volume of normal saline as a placebo postoperatively for 2 days. Group III and Group IV received BB-882 and placebo, respectively, after an exploratory laparotomy. At 48 hours postoperatively, blood was drawn for culture, serum amylase, and tumor necrosis factor (TNF)-alpha determinations. Specimens from MLNs, spleen, liver, pancreas, and cecum were harvested for culture of gram-positive, gram-negative, and anaerobic bacteria. Quantitative cecal cultures of gram-positive, gram-negative, and anaerobic bacteria were obtained. A point scoring system for five histological features that include interstitial edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. There was no difference in serum amylase levels (2415 +/- 127 IU/L versus 2476 +/- 170 IU/L), serum TNF-alpha levels (7820 +/- 1396 pg/mL versus 7318 +/- 681 pg/mL), and the mean pancreatic histology score (5.9 +/- 1.2 versus 6.5 +/- 1.1) between Group I and Group II, respectively (P > 0.05). Seven of 12 Group I rats had BT to MLNs, compared with 11 of 12 rats in Group II (P > 0.05). Five of 12 Group I rats had BT to distant sites such as pancreas, spleen, liver, and/or blood, compared with 11 of 12 rats in Group II (P < 0.05). BB-882 treatment decreases bacterial spread to distant sites, but does not reduce serum amylase levels and serum TNF-alpha levels or ameliorate pancreatic damage in rats with AP.

A retrospective study of patients with surgically resectable adenocarcinoma of the pancreatic head was undertaken to determine which prognostic factors are independently associated with improved survival. Thirty-four men and 41 women (mean age, 61.9 years) had resection for adenocarcinoma of the pancreatic head between 1980 and 1997 at Rush-Presbyterian-St. Luke's Medical Center. Surgical resections included 15 total pancreatectomies, 43 pyloric-preserving procedures, and 17 standard Whipple procedures. Thirty-six patients received adjuvant radiation and/or chemotherapy. Overall median survival was 13 months, with a 5-year survival of 17 per cent. Thirty-day surgical mortality was 1.3 per cent. Significant factors that negatively influenced survival using univariate Kaplan-Meier analysis were: positive resection margin (P = 0.01), intraoperative blood transfusion (P = 0.01), and lymph node metastases (P = 0.01). Presenting signs and symptoms, patient demographics, operative procedure, tumor size, histologic differentiation, and adjuvant therapy did not have a significant impact on survival. Using multivariate Cox regression analysis, the only significant independent factors improving survival were the absence of intraoperative blood transfusion (P = 0.02) and a negative resection margin (P = 0.04). Performing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas with negative microscopic margins of resection and without intraoperative transfusion significantly improves survival.

Advances in minimally invasive surgery have made it possible to remove solid organs such as the adrenal gland laparoscopically. Several studies have shown that when applied to appropriate operative candidates, laparoscopic adrenalectomy is a safe alternative to conventional open surgery with real advantages in terms of decreasing postoperative pain and length of hospital stay and allowing earlier return to normal activity. The indications for laparoscopic adrenalectomy are essentially the same as those described for open adrenalectomy. We do not recommend laparoscopic adrenalectomy for known primary or metastatic malignant tumors of the adrenal glands, because of the risk of tumor implantation that might compromise the patient's chance for cure, nor do we recommend it for lesions larger than 6 to 8 cm where the chance of malignancy is high. The preoperative preparation, laparoscopic instruments, operative techniques, and potential complications and their treatments are described in this review. Laparoscopic adrenalectomy is becoming the preferred method of surgically treating many adrenal problems. Although conventional surgical approaches will undoubtedly be required to treat certain adrenal lesions, surgeons with an interest in treating patients with adrenal disorders must become proficient in the technique of laparoscopic adrenalectomy. This will allow them to select the most appropriate operative approach for their patients' individual problems.

Objective: To describe a patient with systemic calciphylaxis., Methods: We present a case of a 26-year-old woman with end-stage renal disease taking intramuscular injections of erythropoietin in whom systemic calciphylaxis subsequently developed. Both clinical and laboratory findings are reviewed., Results: In a 26-year-old woman with end-stage renal disease who was taking erythropoietin intramuscularly, multiple, superficial ulcerative lesions developed on both lower extremities. Despite aggressive treatment, new lesions subsequently developed. Laboratory values showed an increased calcium-phosphate product and a normal parathyroid hormone level. A skin biopsy specimen showed necrotic skin and subcutaneous fat with foci of calcification around the vessels, findings that confirmed the diagnosis of calciphylaxis. The patient then underwent subtotal parathyroidectomy and responded with initial improvement; however, her condition later deteriorated, and she died of uncontrolled pulmonary hemorrhage., Conclusion: Systemic calciphylaxis is a rare but devastating complication of end-stage renal disease. This condition mimics many different disorders; therefore, a high index of suspicion is essential for early recognition and diagnosis, which is assisted by biopsy specimens of skin lesions. Treatment includes subtotal or total parathyroidectomy in conjunction with autotransplantation, administration of phosphate binders, aggressive treatment with antibiotics, and lowering of the calcium-phosphate product. Even though a successful outcome is possible when this disease is recognized early and treated aggressively, the morbidity and mortality associated with systemic calciphylaxis still remain high.

There are a number of different approaches available to surgically remove the adrenal gland. These can be broadly classified into two general categories, open and laparoscopic. There is no one best method for all patients. Surgeons, skilled in all aspects of adrenal surgery, should choose an approach for adrenalectomy based on patient and tumor related factors. Once advantages and disadvantages of a specific procedure, with these factors in mind, are weighed, the best approach for the individual patient should be chosen.

Thyroid reoperations can be technically difficult and associated with an increased risk of complications. To determine the indications for reoperations and the risk of postoperative complications with these procedures, records of 362 patients undergoing thyroidectomy by a single surgeon (R.A.P.) were reviewed. Thirty-two patients had a reoperation. The group consists of 21 women and 11 men with an average age of 55 years (range, 31-79). Twenty-four patients had 1 prior operation, and 8 patients had 2 or more. We performed 4 of the initial operations, and 28 were done by surgeons at other centers. Fourteen reoperations were done for symptomatic multinodular goiter (MNG), and 5 because of a change in the histologic diagnosis from benign to cancerous. The remainder were for further treatment of malignancy. The most common operation was completion thyroidectomy (31). In 3 patients, either unilateral or bilateral modified radical neck exploration was performed. One patient required median sternotomy. One subtotal thyroidectomy was also performed. Recurrent laryngeal nerve injury occurred in 2 patients. It resolved in 1 patient but was permanent in another, who had 3 operations for MNG. One of the 2 patients with preoperative unilateral vocal cord paralysis had return of function after removal of a substernal goiter. The other had a permanent nerve injury from the original surgery. Three patients had postoperative hypocalcemia (calcium <8.0 mg/dL). This resolved in all patients within 1 to 6 months. One patient who had a third operation for MNG had postoperative hemorrhage necessitating tracheostomy for airway control. Another patient developed a seroma that resolved within 2 months. We conclude that reoperations are indicated for both benign and malignant thyroid disease. Because they carry a higher risk of complications, every effort should be made to avoid them by performing definitive initial treatment.

Background: The goal of this study was to evaluate the safety and efficacy of total thyroidectomy performed for benign thyroid disease., Methods: A total of 106 consecutive patients undergoing total thyroidectomy for benign disease from October 1982 to July 1995 were reviewed. The 33 men and 73 women had an average age of 46 years (range, 16 to 82 years). Indications for total thyroidectomy were a thyroid nodule with the history of head and neck radiation in 36 patients, bilateral thyroid nodules in 35, needle biopsy of a follicular neoplasm or frozen section diagnosis of a possible malignancy in 18, and toxic goiter in 17. Total thyroidectomy was performed as the primary operation in 98 patients, and 8 patients had a completion reoperation for recurrent disease., Results: Pathology findings revealed benign nodular goiter in 49 patients, follicular adenoma in 26, hyperplasia in 19, and Hashimoto's thyroiditis in 12. Postoperative hemorrhage requiring operative hemostasis occurred in two patients (1.9%). Two patients had unilateral recurrent laryngeal nerve (RLN) palsy before operation (1.9%). Three patients had unilateral postoperative RLN palsy (2.8%). Two cases resolved in 3 and 4 months. The only permanent RLN injury occurred in a patient reoperated for a compressive goiter. Early postoperative hypocalcemia (8.0 mg/dl or less) was found in nine patients (8.5%). No patient had permanent hypoparathyroidism at long-term follow-up evaluation., Conclusions: Total thyroidectomy for benign thyroid disease can avoid reoperation for nodular goiter and hyperthyroidism and eliminate any subsequent risk of malignant change in radiated thyroid glands. A low complication rate can be achieved with meticulous surgical technique. Total thyroidectomy can be performed safely for bilateral benign thyroid disease.

Background: This study evaluates the indication for frozen section (FSx) in the management of the solitary thyroid nodule given the increasing use of fine-needle aspiration biopsy (FNAB)., Methods: The charts of 561 patients who underwent thyroidectomy for a solitary nodule were reviewed. Each patient underwent either FNAB, FSx, or both. Results were compared to the final diagnosis to evaluate their effectiveness in predicting malignancy., Results: The sensitivity and specificity for FNAB alone (162 patients) were 86% and 91%, respectively, and for FSx (494 patients) 79% and 99%, respectively. The routine use of FSx with diagnostic FNABs did not improve the accuracy over either test alone. Sensitivity, specificity, and accuracy were essentially unchanged when the use of FSx was limited to just atypical FNAB but dropped significantly when FSx was not used., Conclusions: When results of FNAB and FSx are interpreted as benign or malignant, both are highly accurate predictors of malignancy. Routine use of FSx and FNAB does not improve the sensitivity or specificity in the detection of malignancy over that of either examination alone. FSx proved useful in determining the extent of operation only when results of the FNAB were atypical.

Solitary, palpable thyroid nodules are common, but only a small percentage are malignant. It is important to evaluate these nodules in a cost-efficient manner that avoids missing a cancer. Historically, radioisotope imaging has played a major role in the workup of thyroid nodules; however, with the advent of fine needle aspiration biopsy (FNAB), this role has become less clear. From 1974 to 1994, 770 patients with a solitary nodule underwent thyroidectomy. Preoperatively, 471 had thyroid scans, and 149 had FNAB. The incidence of carcinoma in nodules excised on the basis of thyroid scan was 23 per cent, whereas the incidence of carcinoma was 37 per cent when FNAB was used (P = 0.003). Fine needle aspiration was a significantly better predictor of malignancy than thyroid scan and resulted in a smaller proportion of excisions for benign nodules. Thyroid scan provided little additional information in those patients who underwent FNAB. Because thyroid scans add little in determining which nodules require surgical excision, they should no longer be a routine part of the evaluation of a solitary thyroid nodule.

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLN) and other extraintestinal organs is an important source of infection in acute pancreatitis (AP). Epidermal growth factor (EGF), a peptide hormone with trophic effects on gut mucosa, has decreased intestinal mucosal injury in septic rats and decreased burn-induced BT in mice. The purpose of this study is to examine whether EGF could affect BT in acute necrotizing pancreatitis. Forty-eight male Sprague-Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the biliopancreatic duct (1 ml/kg of body weight). Group III and Group IV underwent laparotomy without induction of acute pancreatitis. Group I rats received human recombinant EGF (100 micrograms/kg, subcutaneously twice daily) and Group II rats received a similar volume of 0.1% bovine serum albumin as a placebo postoperatively. Group III and Group IV received EGF and placebo, respectively. At 48 hr postoperatively, blood was drawn for culture and amylase determinations. Jejunum and ileum were obtained to measure mucosal protein content, mucosal thickness, villus height, and crypt depth. Specimens from MLN, spleen, liver, pancreas, and cecum were harvested for pathology and culture of gram positive (G+), gram negative (G-), and anaerobic bacteria. Ileal mucosal protein levels were increased significantly in Group I (1.96 +/- 0.14 mg/cm) compared to Group II (0.95 +/- 0.15 mg/cm intestinal segment) (P < 0.01). Jejunal and ileal mucosal thickness, villus height, and crypt depth in Group I were significantly increased when compared to Group II (P < 0.05). All 12 rats in Group II had BT to MLN compared to 58% (7 of 12 rats) in Group I (P < 0.05). Thirty-three percent (4 of 12 rats) had BT to distant sites such as pancreas, spleen, liver, and/or blood in Group I vs 83% (10 of 12 rats) in Group II (P < 0.05). EGF treatment minimizes intestinal damage, decreases BT to MLN and bacterial spread to distant sites, and may be beneficial in preventing septic complications in AP.

Background: Angiogenesis correlates with growth and likely metastases in several tumors. To determine whether it has a similar role in pheochromocytomas, immunohistochemical staining of factor VIII was done on the tumor tissue of 42 patients., Methods: Formalin-fixed, paraffin-embedded tissue was obtained from 29 women and 13 men with 24 primary adrenal and 18 extraadrenal pheochromocytomas. Patients were divided into two groups. Group 1 included 32 patients with benign pheochromocytomas, and group 2 included 10 patients with malignant tumors evidenced by capsular or vascular invasion (six), liver metastases (three), or periaortic lymph node metastases (one). Blood vessels highlighted by factor VIII staining of endothelial cells with labeled streptavidin-biotin were counted under light microscopy. Mean vessel count within a 10 mm2 micrometer disk was calculated under x100, x200, and x400 magnification fields., Results: There were no significant differences in patient age or clinical symptoms between the groups. The mean tumor size in group 2 of 8.8 +/- 5.3 cm was larger than the mean of 4.8 +/- 2.8 cm in group 1 (p < 0.005). The mean counts of vessels in the x100, x200, and x400 magnification fields were 102 +/- 48, 40 +/- 18, and 19 +/- 9 in group 1, and 203 +/- 77, 73 +/- 28, and 37 +/- 15 in group 2. The number of blood vessels in group 2 was significantly higher than in group 1 (p < 0.001) in each studied field., Conclusions: In this study the number of tumor blood vessels correlated with the invasive behavior of pheochromocytomas. Tumor angiogenesis may be useful in determining the likelihood of malignant behavior in pheochromocytomas.