What we still do not know about adrenal vein sampling for primary aldosteronism.

During the last two decades, primary aldosteronism has emerged as the most common cause of secondary hypertension, and advances in the diagnosis and treatment of this condition have improved patient care substantially. A major stumbling block in the evaluation and management of these patients, which ultimately guides treatment and prognosis, is answering the question, "Which adrenal gland(s) produce aldosterone?" Adrenal vein sampling has emerged as the only reliable method to determine the answer to this question; however, the methodology and criteria for lateralization have been determined empirically with little prospective data. The major remaining controversies surrounding adrenal vein sampling include: who should perform and who should undergo the procedure; what criteria should be used to define a successful study and lateralization of aldosterone production; whether cosyntropin should be infused during the procedure and how; and what to do when results are ambiguous? This article reviews some of the advances in the execution of this procedure, the variations in procedure, the data that fuel the controversies, and the issues that need to be resolved in the future.

The many faces of pheochromocytoma.

OBJECTIVE: To recognize and manage pheochromocytomas in unusual settings. METHODS: Three case reports are presented with clinical, biochemical, imaging, and operative findings. The pitfalls in diagnosis of pheochromocytomas and management are addressed. RESULTS: We begin with a 27-yr-old gravida 2, para 1 Caucasian woman with unexplained tachycardia and hypertension during a routine pre-natal visit at 30 weeks estimated gestational age. Urinary studies revealed elevated catecholamines. Magnetic resonance imaging localized a 6.6-cm right adrenal mass with features consistent with a pheochromocytoma. She was medically managed with phenoxybenzamine and propranolol until 35 weeks, after which she underwent a combined Cesarean section, and open right adrenalectomy. Another patient, a 36-yr-old African-American woman presented to a hospital in cardiac arrest, with elevated serum troponins, and underwent cardiac catheterization, which revealed normal coronary arteries. A computed tomography (CT) scan revealed a left adrenal mass and CT-guided biopsy was consistent with a pheochromocytoma, although prior studies were negative. Finally, we present a 49-yr-old Caucasian woman who had a right adrenalectomy 10 yr prior and presented to the clinic with fluctuating blood pressures, headaches, and palpitations. Further testing revealed she had a recurrent metastatic pheochromocytoma. The challenges behind treating these patients are further explored. CONCLUSION: Antenatal diagnosis of pheochromocytoma, though challenging, is associated with lower maternal and fetal morbidity and mortality. The differential diagnosis for cardiac arrest in the presence of normal coronary arteries should include a pheochromocytoma. Finally, treatment with iodinated metaiodobenzylguanidine may be a therapeutic option for those patients with metastatic pheochromocytomas.

Radiologic characterization of adrenal masses: the role of computed tomography--derived attenuation values.

BACKGROUND: Recent studies suggest that low computed tomography (CT) attenuation values can be used to differentiate benign adrenal adenomas from non-adenomas. We examined the utility of non-enhanced CT attenuation values of

Improving operative performance using a laparoscopic hernia simulator.

BACKGROUND: Traditionally, the acquisition of surgical skill has occurred entirely in the operating room. To meet the expanding challenges of cost containment and patient safety, novel methods of surgical training utilizing ex-vivo workstations are being developed. The purpose of our study was to evaluate the impact of a laparoscopic training curriculum on surgical residents' operative performance. METHODS: Twenty-one surgery residents completed baseline laparoscopic total extraperitoneal (TEP) hernia repairs. Operative performance was evaluated using a validated global assessment tool. Each resident was then randomized to a control group or a trained group. A CD ROM, video, and simulator were used for training. At the end of the study, each resident's operative performance was again evaluated. RESULTS: Improvement was significantly greater in the trained group in five of the eight individual global assessment areas as well as the composite score (P <0.05). Questionnaire data suggested that training resulted in improved understanding of the TEP hernia repair (P = 0.01) and an increased willingness to offer the operation to patients with nonrecurrent unilateral hernias (P = 0.02). CONCLUSIONS: A multimodality laparoscopic TEP hernia curriculum improves residents' knowledge of the TEP hernia repair and comfort in performing the procedure, and may also improve actual operative performance.

Burn-activated neutrophils and tumor necrosis factor-alpha alter endothelial cell actin cytoskeleton and enhance monolayer permeability.

BACKGROUND: This study examined the hypothesis that exposure of an endothelial cell (EC) monolayer to tumor necrosis factor-alpha (TNF-alpha) and that burn-activated neutrophils alter EC actin cytoskeleton and enhance the permeability of the monolayer. METHODS: Neutrophils were harvested from rats that had undergone a 45% surface area burn (BURN-neutrophil) or uninjured control rats. ECs were grown on polyester filters or fibronectin-coated glass slides and exposed for 4 hours to media, TNF-alpha (100 ng/mL), or TNF-alpha plus BURN-neutrophil or uninjured control rats (10(7) cells). Monolayer permeability was assessed by measuring the flux of albumin across the cells. EC surface area and microfilament number and length were determined by the staining of actin microfilaments with rhodamine phalloidin followed by fluorescent microscopy. RESULTS: The amount of albumin that moved across the monolayer in response to TNF-alpha plus BURN-neutrophil was twice that of media alone (P <.05) or TNF-alpha alone (P <.05). The number and length of actin microfilaments in ECs exposed to TNF-alpha plus BURN-neutrophil were significantly less than that of cells exposed to media alone or TNF-alpha alone. CONCLUSIONS: These data are consistent with a hypothesis that TNF-alpha plus BURN-neutrophil affect endothelial monolayer permeability by altering EC actin cytoskeletal organization.

A clinical pathway for inguinal hernia repair reduces hospital admissions.

BACKGROUND: Clinical pathways have been advocated as a means to improve and standardize patient care while reducing costs through improved efficiency. This study examines the hypothesis that development of a clinical pathway reduces hospital admissions in a Veterans Affairs (VA) medical center. MATERIALS AND METHODS: For the year prior to June 1997, 168 elective inguinal herniorrhaphies were performed. This constituted the prepathway (pre-P) group. One hundred ninety-six elective inguinal herniorrhaphies were performed during the year following institution of the clinical pathway-the postpathway (post-P) group. RESULTS: Hospital admissions were compared between the two groups. In the pre-P group 61 of the 168 patients (36%) were admitted while 29 of the 196 patients (15%) in the post-P group were admitted (P < 0.001). In the pre-P group 27 of the 53 patients reviewed (51%) had either no justification or inadequate justification for admission. In the post-P group 8 of the 29 patients admitted (28%) had inadequate justification (pre-P vs post-P, P = 0.124). Common reasons for admission included pain, perioperative complications, and concurrent medical problems or surgical procedures. The most common single cause other than pain was urinary retention. The average age of patients requiring admission was greater both pre-P and post-P. CONCLUSIONS: We conclude that institution of a clinical pathway for inguinal herniorrhaphy decreased hospital admissions. The reasons for this decrease are probably multifactorial and include improvements in physician and staff awareness. The decrease in unnecessary admissions should result in more efficient use of hospital resources.

Effect of diabetes mellitus on endotoxin-induced lung injury.

OBJECTIVE: To examine the effects of diabetes mellitus on lipopolysaccharide (LPS)-induced pulmonary edema and alveolar neutrophil recruitment and activation. HYPOTHESIS: Zucker diabetic fatty rats are resistant to the effects of intratracheal LPS on the extravasation of plasma proteins into the lungs. DESIGN: Zucker diabetic fatty (ZDF) rats (genotype fa/fa) were used as a model of diabetes mellitus, while their normoglycemic heterozygous littermates served as controls. Lipopolysaccharide (Escherichia coli 0111: B4; 100-200 microg) or vehicle (0.25 mL of isotonic sodium chloride solution) was instilled into the airways of ZDF and control rats. Four hours later, pulmonary microvascular dysfunction was assessed by measuring the extravasation of Evans blue dye into the lung. Lipopolysaccharide-induced neutrophil recruitment was assessed by counting the number of neutrophils within the bronchoalveolar lavage fluid and measuring their expression of CD11b/CD18 by fluorescence-activated cell analysis sorting. RESULTS: The LPS (200 microg) induced a 32% increase in Evans blue dye extravasation into the lungs of controls (P = .008) but had no such effect in diabetic animals. Pulmonary extravasation of Evans blue dye in controls was greater than that of ZDF rats both at baseline (P = .002) and in response to 200 microg of LPS (P<.001). The LPS upregulated neutrophil CD11b/CD18 expression in diabetic and nondiabetic groups and induced a greater than 50-fold increase in the number of neutrophils within the airways of both control and diabetic groups (P<.001). CONCLUSION: Despite the recruitment of a large number of neutrophils into the lung, the LPS-induced change in pulmonary microvascular permeability in diabetic animals is substantially less than that of nondiabetic controls.

The validity of quick intraoperative parathyroid hormone assay: an evaluation in seventy-two patients based on gross morphologic criteria.

BACKGROUND: Parathyroidectomy for primary hyperparathyroidism has conventionally required identification of all parathyroid glands with excision of grossly abnormal glands. Using this approach, cure rates exceed 95%. Directed cervical exploration has been advocated using quick intraoperative parathyroid hormone (QPTH) assay with preoperative localization. Adoption of this approach requires validation of the accuracy of QPTH assay. METHODS: Patients with primary hyperparathyroidism undergoing bilateral neck exploration during a 31-month period were reviewed. Uniglandular (UGD) or multiglandular (MGD) disease was determined by gross morphologic criteria. QPTH assays were performed before skin incision and at 5, 10, and 20 minutes after excision of each abnormal gland. A 10-minute QPTH decrease of 50% from baseline levels indicated curative excision. These data were not used to guide extent of exploration or tissue resection. RESULTS: Of 72 patients, 55 (76%) had UGD and 17 (24%) had MGD. QPTH assay accurately predicted the disease state in 89%. Four (7%) UGD patients did not have an appropriate QPTH decline at 10 minutes. Four (24%) MGD patients had an inappropriate QPTH decline at 10 minutes. CONCLUSIONS: Using QPTH guided exploration, 6% (4 of 72) of patients would undergo unnecessary extended exploration and 6% (4 of 72) (95% CI, 1% to 13%) may require reoperation for unidentified MGD. These results validate the accuracy of QPTH assay.

Sentinel lymph node biopsy, an alternative to elective axillary dissection for breast cancer.

BACKGROUND: Axillary metastases remain an important prognostic indicator in breast cancer. Axillary lymphadenectomy (ALND) carries significant morbidity and is unnecessary in most patients with early breast cancer; thus, sentinel lymph node (SLN) biopsy has been advocated for axillary staging. We studied the SLN identification rate and its accuracy in predicting axillary metastases. METHODS: One hundred nineteen women with breast carcinoma underwent SLN and ALND. Lymphoscintigraphy was performed using Technetium99 sulfur colloid supplemented by Isosulfan blue dye. Hematoxylin/eosin-stained lymph node sections were examined by light microscopy. RESULTS: The SLN identification rate was 81%. One SLN was negative (1%) in a patient with axillary disease. SLN histology correctly predicted the absence of axillary disease in 98.6%. Sensitivity, specificity, and positive and negative predictive values were 96%, 100%, 100%, and 99%, respectively. CONCLUSIONS: Sentinel lymph node biopsy accurately predicts total axillary status and is valuable in the surgical staging of breast cancer.

The effect of antimicrobial agents on the induction of tumour necrosis factor by alveolar macrophages in vitro in response to endotoxin.

Alveolar macrophages from New Zealand white rabbits were incubated with twice the MIC of amikacin, ciprofloxacin, aztreonam, ceftazidime and imipenem and exposed to either 10(4), 10(5) or 10(6) cfu/mL live Pseudomonas aeruginosa ATCC 27853 or 0.1, 1 or 10 mg/L purified lipopolysaccharide (LPS) derived from P. aeruginosa to determine the effects of different classes of antimicrobial agent on production of tumour necrosis factor (TNF). Incubation of macrophages with ciprofloxacin and amikacin resulted in less TNF activity after exposure to live P. aeruginosa than was found for saline, aztreonam, ceftazidime or imipenem (P < 0.05). However, no significant differences were found between any of the agents after macrophages had been exposed to purified LPS. Different antimicrobial agents therefore appear to exert different effects in vitro on the TNF response of macrophages to bacterial stimulation.

Effect of a bradykinin antagonist on the local inflammatory response following thermal injury.

Partial and full thickness burns with intervening zones of stasis were created on the backs on New Zealand White rabbits (n = 23). Either saline or the bradykinin receptor antagonist, NPC 17731, was administered. Skin blood flow was measured hourly using a laser Doppler blood flowmeter. After 4 h skin samples were harvested for assessment of tissue oedema (wet/dry weights) and leucocyte accumulation (immunohistochemistry). Statistical analysis was performed using Analysis of variance (ANOVA) and Mann-Whitney U test with a level of significance at P < 0.05. It was found that blood flow was decreased postburn in all groups. Bradykinin antagonist resulted in increased blood flow in partial thickness burns and zones of stasis compared to saline-treated animals (P < 0.05). Pretreatment with bradykinin antagonist showed reduced tissue oedema in full thickness burns (P < 0.05). No significant difference was observed in leucocyte accumulation between both groups. These data suggest a role for bradykinin in the pathogenesis of postburn microvascular changes which is independent of leucocyte-mediated injury.

Inhibition of selectin- and integrin-mediated inflammatory response after burn injury.

Inflammation and microvascular injury in the areas adjacent to burn wounds produces extension of postburn tissue necrosis. Leukocytes are potent mediators of the local inflammatory response preceding tissue necrosis, and the selectin and integrin adhesion molecules have been implicated in leukocyte-mediated tissue destruction. We sought to examine the role of L-selectin (CD62-L) and CD18 in leukocyte accumulation and tissue necrosis following burn injury. New Zealand White rabbits (n = 36) were subjected to burn injury and were randomized to treatment with saline (control) or monoclonal antibodies to L-selectin or CD18. Animals given the anti-L-selectin antibody demonstrated reduced immunohistochemical evidence of leukocyte accumulation at 24 hr postinjury but did not show improved wound perfusion or reduced tissue necrosis. Animals in the anti-CD18 group showed significantly improved tissue survival and improved tissue perfusion but had grades of leukocyte accumulation similar to those in the control group. These observations suggest that leukocyte accumulation is partially L-selectin dependent and that leukocyte accumulation alone is not sufficient to cause changes in blood flow and tissue destruction, both of which appear to be largely CD18 mediated.

Role of CD14 in hemorrhagic shock-induced alterations of the monocyte tumor necrosis factor response to endotoxin.

OBJECTIVE: To determine if the shock-induced alterations in whole blood monocyte tumor necrosis factor (TNF) response are mediated by the CD14 receptor. DESIGN: Prospective controlled animals experiments. MATERIALS AND METHODS: New Zealand White rabbits (n = 15) were subjected to hemorrhage and resuscitation. Blood samples obtained before shock and 24, 72, and 120 hours after shock were stimulated with lipopolysaccharide in the presence or absence of the anti-CD14 monoclonal antibody, 63D3. Tumor necrosis factor was assayed using L929 cells. MEASUREMENTS AND MAIN RESULTS: There are no detectable TNF activity in unstimulated blood. The CD14 inhibition resulted in a 55% reduction in baseline TNF activity. After shock, there was a marked increase in TNF activity with lipopolysaccharide stimulation. Addition of 63D3 resulted in a dose-dependent 95% reduction in TNF activity at 24 and 72 hours after shock, (p < 0.05). CONCLUSION: The enhanced whole blood monocyte TNF response after hemorrhage is CD14 dependent.

Is octreotide beneficial following pancreatic injury?

BACKGROUND: Pancreatic injury is often associated with multiple complications related to uncontrolled pancreatic exocrine secretion, including pancreatic fistula, pseudocyst, and intra-abdominal abscesses. Somatostatin analogues such as octreotide have been shown to decrease pancreas-related morbidity following major pancreatic resection in patients with pancreatic neoplasms and acute severe pancreatitis. This study was conducted to determine whether or not the administration of octreotide influences the incidence and severity of abdominal complications following pancreatic injury. PATIENTS AND METHODS: Patients with intraoperative diagnosis of pancreatic injury over a 6-year period were studied retrospectively. Specific complications assessed include abdominal abscesses, pseudocyst, pancreatitis, and pancreatic fistula. Statistical analysis of qualitative variables was by chi-square analysis, and analysis of quantitative variables by Student's t-test (P < 0.05). RESULTS: Injury to the pancreas was identified in 96 patients. Sixteen early deaths (< 48 hours) and one late death occurred, for a mortality of 18%, leaving 80 patients as the study population; 21 patients received octreotide and 55 patients did not. Pancreatic fistula occurred in 32 patients (40%). When stratified by pancreatic injury severity, there was no significant difference in complication rates, although patients treated with octreotide had a higher rate of fistula formation (48% versus 40%), longer duration of fistula drainage, and longer hospital stay compared with untreated patients. CONCLUSION: Although adverse patient selection may be a factor in this retrospective survey, the magnitude of observed differences raises concerns regarding the empiric administration of octreotide to such patients pending prospective study.

Evaluation of video-assisted thoracoscopic surgery in the diagnosis of diaphragmatic injuries.

BACKGROUND: Injury to the diaphragm from penetrating or blunt thoracoabdominal trauma is notoriously difficult to diagnose. Chest radiography, computed tomography scan, contrast studies, diagnostic peritoneal lavage, and laparoscopy are inadequate; thus, celiotomy is commonly performed in patients with suspected diaphragmatic injury. We compared the diagnostic accuracy of video-assisted thoracoscopic surgery (VATS) with that of exploratory celiotomy in the evaluation of diaphragmatic and thoracoabdominal injury. PATIENTS AND METHODS: Hemodynamically stable patients admitted to a level I trauma center with blunt or penetrating injury to the lower chest or abdomen underwent VATS and subsequent celiotomy under the same general anesthetic. Intraoperative thoracoscopic findings were blinded to the abdominal surgeons. RESULTS: Twenty-six patients were enrolled in the study over a 12-month period. Diaphragmatic injuries were identified in 8 patients (31%). Videothoracoscopy identified all eight injuries in these patients. Six of the 8 patients (75%) with diaphragmatic injuries sustained associated injury to intrathoracic or intra-abdominal organs. There was no mortality and no procedure-related morbidity. There were no missed injuries in patients who underwent VATS. CONCLUSIONS: Video-assisted thoracoscopy is a safe, expeditious, and accurate method of evaluating the diaphragm in injured patients, and is comparable in diagnostic accuracy to exploratory celiotomy.

Alterations in alveolar macrophage tumor necrosis factor (TNF) response following hemorrhagic shock.

The purpose of this study was to determine if hemorrhagic shock alters the alveolar macrophage (M phi) tumor necrosis factor (TNF) response to lipopolysaccharide (LPS) stimulation. New Zealand White rabbits underwent hemorrhage and resuscitation. At 1, 2, 3, 5, and 7 days post-shock, both M phis and peripheral whole blood monocytes were incubated in vitro with saline or Escherichia coli LPS. The supernatants were assayed for TNF activity using the L929 bioassay. Alveolar M phis from hemorrhaged animals showed reduced TNF activity during the first 5 days post-hemorrhage. Maximal depression of TNF activity was observed on days 3 and 5 post-hemorrhage (p < .05). In comparison, peripheral whole blood monocytes showed an increased TNF response on post-shock days 2 and 3. These results suggest that hemorrhagic shock and resuscitation differentially affect TNF response in alveolar and peripheral blood M phi populations.

Alterations in leukocyte adhesion molecule expression after burn injury.

OBJECTIVE: To determine if thermal injury alters the expression of leukocyte adhesion molecules. DESIGN: This is a controlled experimental animal study. MATERIALS AND METHODS: Partial thickness burns were created on the backs of New Zealand White rabbits. At 30 minutes, 2 hours, 4 hours, and 24 hours after burn, skin was harvested for immunohistochemistry. Monoclonal antibodies were used to study changes in intercellular adhesion molecule 1 (ICAM-1), E-selectin, and leukocyte CD11a. Staining was graded on a scale of 0 to 4. MEASUREMENTS AND MAIN RESULTS: ICAM-1 was significantly decreased at 24 hours after burn (p < 0.007, Wilcoxon signed rank test). CD11a was increased at 30 minutes (p < 0.02), 2 hours (p < 0.02), and 24 hours (p < 0.006). E-selectin was increased at 2 hours (p < 0.03). CONCLUSION: Thermal injury alters the expression of leukocyte adhesion molecules.