Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies.

Chromogranin-A (CgA) is an acidic soluble protein with a virtually ubiquitous occurrence in normal human neuroendocrine tissues. Of the many potential tissue sources of CgA immunoreactivity, which contribute to basal (unstimulated) circulating CgA? To explore this question we studied the effects of selective and nonselective suppression of secretion at several sites within the neuroendocrine system. Selective disruption of sympathetic outflow by trimethaphan decreased basal CgA by 25%, suggesting that sympathetic neurons contribute to circulating CgA. Plasma CgA in patients with unilateral and bilateral adrenalectomy fell within the range observed in normal subjects, weighing against the adrenal medulla as a major source of basal circulating CgA. Selective suppression of a variety of anterior and posterior pituitary cell types decreased plasma levels of the usual resident peptide hormones, but left plasma CgA unperturbed. After propranolol treatment, plasma CgA remained unaltered. Secretin suppressed plasma PTH and calcitonin, but did not alter plasma CgA levels. On the other hand, widespread nonselective suppression of a variety of neuroendocrine secretory cells by somatostatin decreased plasma CgA by 48%. Plasma catecholamines were unaltered by somatostatin infusion, suggesting that somatostatin inhibited CgA release from nonsympathoadrenal sources. During the infusion of somatostatin, the plasma epinephrine increment in response to insulin-induced hypoglycemia was maintained, and plasma CgA did not fall, nor did it rise after somatostatin cessation. Taken together, these findings suggest that somatostatin did not inhibit transport of stimulation-released CgA from the adrenal medulla to the circulation. In conclusion, although the adrenal medulla is the major tissue source of CgA immunoreactivity in man, other neuroendocrine sites, including sympathetic axons and multiple endocrine glands, appear to influence the basal circulating concentration of CgA.     

Changes in arterial ketone body ratio after transcatheter arterial embolization for hepatocellular carcinoma-clinical and experimental studies

Arterial ketone body ratio (AKBR) were examined in 114 cases of hepato-biliary tract diseases. AKBR of the normal control was 1.47 +/- 0.38, while it remained less than 0.7 in liver cirrhosis, hepatocellular carcinoma (HCC), alcoholic liver diseases and malignant biliary tract obstruction. AKBR correlated well with serum albumin and cholinesterase. Thirty five cases of HCC were treated with transcatheter arterial embolization (TAE), 20 cases with gelatin sponge and 15 cases without gelatin sponge. In cases with gelatin sponge AKBR decreased significantly immediately after TAE and recovered gradually during 24 hours. Without gelatin sponge AKBR decreased slightly and remained unchanged until 24 hours later. Concerning the prognosis after TAE, AKBR recovered well in cases with good prognosis, while in poor prognosis AKBR progressively decreased to below 0.3. In experimental TAE with gelatin sponge using rabbit VX2-induced liver tumor, AKBR decreased significantly. In fatal rabbit group after TAE, AKBR decreased progressively. Plasma endotoxin was also measured in TAE with experimental rabbit, AKBR and endotoxin showed reverse correlation. From these results it was suggested that the measurement of AKBR is very useful for the evaluation of efficacy and prognosis of TAE in primary liver cancer.     

Effective TAE therapy using Lipiodol with epirubicin for liver metastases of nonfunctioning islet cell carcinoma of the pancreas

We report the response of two patients with advanced nonfunctioning islet cell carcinoma of the pancreas with liver metastases treated with a combination of surgi-cal resection and transarterial embolization (TAE), using Lipiodol with epirubicin. After pretreatment evaluation, the two patients were diagnosed with nonfunctioning islet cell carcinoma of the pancreas with liver metastases. Preoperatively, in both patients, TAE was performed through the hepatic arteries, using Lipiodol and sponzel plus epirubicin. Surgical resection of the primary tumor (radical distal pancreatectomy and pancreaticoduodenectomy) was performed. After surgical resection and evaluation of the malignant histopathological features of the neoplasms, chemotherapy, which included oral 5-fluorouracil (FU), and transarterial infusion therapy, using Lipiodol with epirubicin, was administered to the patients. Follow-up evaluation of the two patients by computerized tomography (CT) scan showed a reduction in the size of the metastatic hepatic masses after several chemoembolizations through the hepatic arteries. This combined treatment modality may be an effective therapeutic strategy for improved management of patients with advanced nonfunctioning islet cell carcinoma of the pancreas with liver metastases.     

The role of chromogranin A in the management of patients with phaeochromocytoma

OBJECTIVE: Chromogranin A (CgA) is the most accurate general marker of neuroendocrine tumours. Supranormal CgA concentrations have been recorded in patients with tumours of neuroectodermal origin such as phaeochromocytoma and paraganglioma. DESIGN: The present study was performed to assess the role of CgA determination in the management of patients with phaeochromocytoma, in comparison with urinary catecholamines and their metabolites. PATIENTS: The patients studied included 22 cases with phaeochromocytoma at initial presentation or at relapse some years after surgical cure or during follow-up of a malignant phaeochromocytoma. Seventeen patients were evaluated before and after surgical removal of phaeochromocytoma. To assess the specificity of the hormonal parameters, 20 subjects were enrolled as controls; they were from a group of patients referred to our observation for possible phaeochromocytoma and who were subsequently proven not to have the disease. RESULTS: Urinary epinephrine and norepinephrine were supranormal in 82% and 77% of patients, respectively. Urinary metanephrines and normetanephrines were supranormal in 84% and 89% of patients, respectively. The combination of urinary metanephrine and normetanephrine had a sensitivity of 100% in identifying a phaeochromocytoma. CgA was supranormal in 91% of patients. Combining the results of CgA and urinary catecholamines (epinephrine and norepinephrine), the sensitivity for diagnosis of phaeochromocytoma was 100%. Urinary catecholamines, metabolites (metanephrine and normetanephrine) and CgA levels in patients with malignant phaeochromocytoma did not differ significantly from those of patients with benign lesions. In most cases, CgA normalized after surgery. CONCLUSIONS: Our results indicate that CgA is a good marker of phaeochromocytoma; measurement of CgA could have a role in the follow-up of patients operated on for phaeochromocytoma.     

Plasma chromogranin A levels are increased in a small portion of patients with hereditary head and neck paragangliomas

Context The majority of patients with head and neck paragangliomas (HNPGL) have biochemically silent tumours. Chromogranin A (CgA) is a tumour marker for neuroendocrine tumours. Objective To assess the role of CgA as a tumour marker in patients with hereditary HNPGL. Patients and Methods We included 95 consecutive patients with hereditary HNPGL for screening of plasma CgA levels and catecholamine excess by measurement of 24‐h urinary excretion of (nor)metanephrine, (nor)adrenaline, VMA, dopamine and 3‐methoxytyramine. In all patients with catecholamine excess, abdominal/intrathoracic paragangliomas were excluded by ¹²³I‐MIBG scintigraphy, MRI and/or CT. Results Plasma CgA levels were increased in only 15 of 95 patients (16%). Thirty‐three of the 95 patients (35%) had increased urinary excretion rates of catecholamines. Six of these 33 patients (18%) had increased plasma CgA levels. Nine of the 62 patients (15%) with a biochemically silent tumour, i.e. no increased urinary excretion of catecholamines or their metabolites, had increased CgA levels. Increased plasma CgA levels were positively correlated with urinary excretion rates of noradrenaline (r = 0·68, P = 0·005) and normetanephrine (r = 0·68, P = 0·005). There was a positive correlation between maximal HNPGL diameter and plasma CgA levels in the 57 patients with a single HNPGL (r = 0·57, P = 0·001). Conclusions Plasma CgA levels are increased in only a small portion of patients with hereditary HNPGL and have limited additional value to the combination of radiological and routine biochemical assessment of patients with HNPGL. Increased plasma CgA levels are associated with increased noradrenergic activity and tumour size in patients with a single HNPGL.     

Malignant pheochromocytoma with multiple hepatic metastases treated by chemotherapy and transcatheter arterial embolization.

A 62-year-old Japanese male developed multiple hepatic metastases two years after resection of pheochromocytoma of the right adrenal gland. Transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastases resistant to 27 cycles of combined chemotherapy consisting of cyclophosphamide, vincristine, and dacarbazine. After TAE, the hepatic metastatic lesions decreased in size and hypertension passed its crisis. The present case suggests the utility of TAE for multiple hepatic metastases under careful blood pressure monitoring.     

Arterial chemotherapy of 5—fluorouracil and mitomycin Cin the treatment of liver metastases of colorectal cancer

AIM：Regional chemotherapy using hepatic artery catheters is a good method of treating patients with colorectal cancer liver metastases.We investigated the survival of patients with liver metastases from colorectal cancer using 5-fluorouracil(5-FU)and mitomycin C Cthrough implantable hepatic arterial infusion port.METHODS:Seventy-five patents with inoperable liver metastases forom colorectal cancer were included between March,1992 and November,2001,We placed implantable hepatic arterial cathter(HAC)port by laparotomy,5-FU,1000mg/m^2/d continuors infusion for five days every four weeks,was delivered in the hepatic arterial catheter through the port.Mitomycin C,30mg/m^2/d infusion in the first day every cycel through the port.Response to the treatment was evaluated by serial determinations of plasma CEAand imaping techniques consisting of computerized tomography and sonography of liver.RESULTS:Sixty-eight were performed hepatic artery chemotherapy and fifty-six were followed up among seventy-five HAC patients.Twenty-six patients(46.4%)have responded and4complete remission were achieved.Eight patients(14.3%)had stable liver metastases.Twenty-two patients(39.3%)were progressed with increased tumor size and number.Twenty-nine patients(51.8%)had a decreased serum CEAlevel.while10patients(17.9%) were stable and 17patients(30.4%)had an increased serum CEAlevel.There were no operative death in this serise.Complications,which occurred in 18patients(32.1%),were as followed:hepatic artery thrombosis in11,Upper gastric and intestinal bleeding in3,liver abscess in1,pocket infection in1,cholangitis in1,and hepatic artery pseudo-aneurysm in one patient.CONCLUSION:Combined infusion of 5-FU and mitomycin C by hepatic artery catheter port is an effective treatment for liver metastases from colorectal cancer.The high response and lower complication rater prove the adjuvant treatment of colorectal cancer with this treatment.     

Chromogranin A as tumor marker in medullary thyroid carcinoma.

We measured plasma levels of chromogranin A (CgA) and calcitonin (CT) in 61 patients with surgically confirmed medullary thyroid carcinoma (MTC). CT was elevated in 46 patients, whereas CgA was elevated in 14 patients. Plasma levels of CgA and CT were moderately correlated (r = 0.87), but CgA became elevated in most patients only in advanced disease. Patients with high plasma CT values (greater than 10 micrograms/L) also had elevated CgA in 83% of cases. An elevated plasma CgA level despite normal CT levels was found in only 1 patient. In 8 MTC patients with moderately elevated basal CT levels, pentagastrin as a secretagogue usually was not able to release detectable amounts of CgA from MTC tissue. In 2 MTC patients, i.v. catheter sampling gave sharp gradients for CT concentrations (greater than 2.7-fold peak to peripheral ratios) and, therefore, precise MTC tissue localization, whereas no gradients were demonstrable for CgA (less than 1.2-fold). One patient with MTC and elevated CgA reached normal CgA plasma levels within 8 days after thyroidectomy. In metastatic tissue from 8 patients with MTC, CgA and CT were detectable immunohistologically in all cases, but plasma CgA was elevated only in 2 and CT in 7 of them. Plasma CgA levels in patients with MTC usually became elevated only in advanced disease and were not able to detect early disease stages, were correlated with CT levels, were not useful in stimulation tests or venous localization studies, and probably resulted from the release from MTC tissue as the major tissue source, as shown in the sporadic cases.     

Plasma methionine-enkephalin and leucine-enkephalin in normal subjects and patients with pheochromocytoma

Plasma methionine-enkephalin-like and leucine-enkephalin-like immunoreactivity (met-enkephalin-LI and leu-enkephalin-LI, respectively) in six normal subjects and six patients with pheochromocytoma were determined. The contents of met-enkephalin-LI and leu-enkephalin-LI in two of six pheochromocytomas were 40- to 50-fold higher and those in the other four pheochromocytomas were less than those in normal human adrenal medulla. The former two patients showed high plasma met-enkephalin-LI and leu-enkephalin-LI levels. As plasma catecholamines levels returned to the normal range after extirpation of tumors, met-enkephalin-LI and leu-enkephalin-LI in plasma became undetectable in these patients. In contrast, neither met-enkephalin-LI nor leu-enkephalin-LI was detected in plasma from the latter four patients. Met-enkephalin-LI and leu-enkephalin-LI concentrations were higher in the adrenal vein than in the peripheral vein in three patients. Plasma met-enkephalin-LI and leu-enkephalin-LI increased concomitantly with catecholamines after glucagon stimulation and during a spontaneous attack in a patient with pheochromocytoma. Plasma met-enkephalin-LI changed in parallel with leu-enkephalin-LI in all cases. High performance liquid chromatography coupled with RIAs has shown that met-enkephalin and leu-enkephalin circulate in plasma from a patient with pheochromocytoma as intact pentapeptides. None of normal subjects showed detectable concentrations of met-enkephalin-LI and leu-enkephalin-LI in plasma (more than 5 pg/ml and 3 pg/ml, respectively). It is concluded that met-enkephalin and leu-enkephalin are released concomitantly with catecholamines from pheochromocytomas.     

Effects of the Calcium Antagonist Felodipine on the Sympathetic and Renin-Angiotensin-Aldosterone Systems in Essential Hypertension

ABSTRACT Studies were performed in 10 male patients with untreated essential hypertension, WHO grade I-II, aged 25–62 years, to explore the acute (single dose) and long-term (8 weeks) effects of felodipine on sympathetic activity—evaluated by plasma and urinary catecholamines—as related to blood pressure, heart rate and the activity in the renin-angiotensin-aldosterone system. The patients were hospitalized for 8 (acute) and 6 (long-term) days and were maintained on a standardized daily intake of sodium (150 mmol), potassium (75 mmol) and water (2500 ml). Acute felodipine administration (10 mg) significantly reduced blood pressure and increased heart rate. Plasma and urinary noradrenaline, plasma renin activity and angiotensin II increased, whereas plasma and urinary adrenaline, dopamine, aldosterone and plasma vasopressin were unaltered. Long-term felodipine treatment, 10 mg twice daily, reduced blood pressure to a similar extent as acute felodipine administration, but heart rate was not significantly changed. Plasma noradrenaline 3 and 12 hours after the last dose and urinary noradrenaline were increased, whereas plasma and urinary adrenaline and dopamine were unchanged. Plasma renin activity and angiotensin II were increased 3 hours, but unchanged 12 hours after the last dose. Plasma aldosterone was unchanged but urinary aldosterone increased. Plasma vasopressin was unchanged. The changes in plasma noradrenaline as related to blood pressure, heart rate, plasma renin activity and angiotensin II during long-term felodipine treatment may reflect decreased cardiac and renal β-adrenoceptor-mediated responses. Increased renal clearance of aldosterone could partly explain the unaltered plasma aldosterone level in spite of increased plasma angiotensin II following long-term felodipine treatment.     

Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005

The First International Symposium on Pheochromocytoma, held in October 2005, included discussions about developments concerning these rare catecholamine-producing tumors. Recommendations were made during the symposium for biochemical diagnosis, localization, genetics, and treatment. Measurement of plasma or urinary fractionated metanephrines, the most accurate screening approach, was recommended as the first-line test for diagnosis; reference intervals should favor sensitivity over specificity. Localization studies should only follow reasonable clinical evidence of a tumor. Preoperative pharmacologic blockade of circulatory responses to catecholamines is mandatory. Because approximately a quarter of tumors develop secondary to germ-line mutations in any one of five genes, mutation testing should be considered; however, it is not currently cost effective to test every gene in every patient. Consideration of tumor location, presence of multiple tumors, presence of metastases, and type of catecholamine produced is useful in deciding which genes to test. Inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for malignancy are important problems requiring further resolution.     

Hepatic artery embolisation--new approach for treatment of malignant carcinoid syndrome

A transcatheter embolisation was carried out for treatment of a patient suffering from hepatic metastases of a malignant carcinoid tumour. Recurrent and very severe carcinoid symptoms could be observed; a bronchial carcinoid supposingly the primary tumour without characteristic symptoms was removed six years before. The carcinoid symptoms became resistant to pharmacological agents and finally ended in life-threatening clinical complications. The transcatheter hepatic artery embolisation was successfully performed and repeated three months later. After embolisation relief of carcinoid symptom and a significant decrease in 5-hydroxyindole acetic acid (5-HIAA) urinary excretion lasting for eight months could be observed. There were no serious complications with adequate pharmacological cover, however, a transient fever, leucocytosis, abdominal pain and an increase in serum transaminase activities occurred after the procedure. The transcatheter hepatic artery embolisation should be a method of choice for treatment of patients with carcinoid metastases producing severe carcinoid symptoms resistant to pharmacological agents.     

Hepatic blood flow during reduced liver grafting in pigs

Intraoperative changes in portal venous and hepatic arterial flow were compared in porcine recipients of reduced liver grafts with recipients of intact grafts and sham-operated controls. Control animals showed no significant changes in hepatic blood flow (measured with perivascular ultrasonic cuffs), heart rate, mean arterial pressure, cardiac output, acid/base balance, plasma sodium, potassium, glucose, or catecholamines. Recipients of intact or reduced grafts showed hypotension, reduced cardiac output, tachycardia, and increased systemic vascular resistance during the anhepatic phase, which lasted approximately 30 min. These changes returned to normal in recipients of intact grafts but in recipients of reduced grafts, levels returned only to 50–60% of baseline. After intact grafting, total liver blood flow and the portal and arterial components returned to baseline within 2 hr of revascularization, but after reduced grafting, hepatic arterial flow values remained depressed to 50–60% of baseline. Plasma epinephrine and norepinephrine were unaltered during control operation but increased 4- to 20-fold in recipients of all grafts. These returned towards baseline in all except recipients of reduced grafts, in which norepinephrine levels remained significantly elevated for the 4 hr of postoperative study. These data highlight persistent elevation of plasma norepinephrine after reduced liver grafting, which may have contributed to the diminished hepatic arterial flow. These results need to be confirmed in adult recipients of split liver grafts in whom grafts are comparatively small. In such patients receiving donor livers which have undergone prolonged storage, the effects of increased plasma norepinephrine levels upon donor agonal arterial spasm may be significant.Surgical assistance was given by Messrs H. Naki, E. Henry, D. Tango, T. Magxala, and H. Arendse.Financial assistance for this project was received from the Staff Research Fund of the University of Cape Town and the Mauerberger Foundation Fund.     

Rupture of hepatocellular carcinoma after transcatheter arterial embolization: an unusual case

Rupture of hepatocellular carcinoma (HCC) as a complication of transcatheter arterial embolization (TAE) is very rare. An unusual rupture of HCC after TAE was treated with successful surgical resection. A 65 year-old woman with liver cirrhosis developed multiple HCC in both lobes of the liver. TAE was attempted for the HCCs, but the original left hepatic artery, obliterated due to the previous repeated TAEs, was replaced by the left gastric artery. Right hepatic arteries were embolized while preserving the replaced left hepatic artery. Nine days after TAE, the patient presented a rupture of HCC in the left lateral segment of the liver, in which no deposit of Lipiodol was recognized. Since additional TAE to achieve hemostasis failed, left lateral segmentectomy was carried out with concern for the poor hepatic functional reserve. The patient was discharged 3 weeks after surgery without any complication. This is the first case of ruptured HCC in the non-embolized part of the liver after TAE, which was resected successfully.     

Nisoldipine--effects on the renin-angiotensin-aldosterone system and catecholamines. Studies in normotensive and hypertensive subjects

We have studied the effects of nisoldipine, a new calcium channel antagonist, on the renin-angiotensin-aldosterone system and on plasma catecholamines in 10 healthy volunteers and in 29 patients with primary essential hypertension. Of these 29 patients, thirteen had normal renin hypertension (NRH), and sixteen had low renin hypertension (LRH). Eight healthy volunteers received placebo. Short-term (24 h) effects were measured in all subjects and long-term (up to 6 months) effects of 10-40 mg nisoldipine daily were monitored in the 29 hypertensive patients. Plasma renin activity (PRA) increased slightly, although this rise was not statistically significant, 1 h after the first dose of nisoldipine in both normotensive subjects and hypertensive patients. After 2 h PRA had returned to the pre-treatment level. No change in PRA was observed after administration of placebo. Plasma angiotensin II (AII) levels showed considerable variation after nisoldipine administration. Plasma aldosterone levels decreased despite the increase in PRA and AII concentrations. However, no concomitant reduction in urinary aldosterone excretion was observed. Plasma noradrenaline levels increased slightly 2-4 h after administration of nisoldipine, and decreased again thereafter, but no changes in plasma adrenaline levels were seen. Nisoldipine had no long-term effects on the renin-angiotensin-aldosterone system or on serum catecholamine levels.     

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.     

Adrenal metastasis from hepatocellular carcinoma (HCC): report of 3 cases.

Although autopsy reports show that the adrenal gland is the second most common organ of hematogeneous metastasis from hepatocellular carcinoma (HCC), paradoxically there is found to be a very scarce number of the adrenal metastasis in clinical practice. We have recently experienced rare patients with right adrenal metastasis from HCC. Case 1: A 51 year-old man with a 5-year history of chronic hepatitis was admitted with hematemesis to Nippon Medical School Hospital. CT revealed a main tumor associated with a few daughter tumors in the hepatic posterior segment and in addition another tumor located between the right hepatic lobe and right kidney. The diagnosis of HCC with a right adrenal gland metastasis was made, and hepatectomy and right adrenalectomy was performed. Twenty months after operation he was alive and free of disease. Case 2: A 78 year-old man underwent resection of the lateral segment of the left hepatic lobe for HCC. Twelve months later, recurrent foci in the residual liver were found and those were treated with transarterial embolization (TAE). Right adrenal metastasis was found on CT 26 months after hepatectomy. TAE was done for the hepatic recurrent tumors and adrenal metastasis. Twelve months after, he survived in good condition. Case 3: A 47 year-old man presented with liver cirrhosis with a long history. He was diagnosed as having HCC with multiple intrahepatic metastases and was treated with TAE 4 times. Follow-up CT revealed right adrenal metastasis. TAE was done for hepatic recurrent tumor and right adrenal metastasis. Three months later the patient died of liver failure.     

Plasma and tissue chromogranin in patients with adrenocortical adenomas

Adrenal adenomas frequently arise from cortical islets in the medulla, and these islets seem to present a greater risk for pathological growth than cortical cells within the adrenal cortex. Chromogranin A (CgA), a glycoprotein co-stored in secreting granules and co-released with resident hormones of chromaffin cells, behaves as a prohormone, generating several biologically active peptides capable of influencing growth, morphogenesis and progression of endocrine tumors. The aim of our study was to investigate whether chromaffin cells may be involved in the development and growth of adrenocortical adenomas. We enrolled 19 patients (12 females and 7 males, mean+/-SD age 54.9+/-11.2 yr, age range 34-75 yr) with incidental, non-functioning, benign adrenocortical adenomas, and measured circulating levels of CgA, catecholamines and creatinine before and 2 months after surgery. Plasma CgA was evaluated by immunoradiometric assay. Testing for CgA immunoreactivity in the removed tissues was performed by immunohistochemical analysis. Mean plasma CgA did not significantly change following surgery (before 73.7+/-15.2 ng/ml; after 68.9+/-14.8 ng/ml). Individual CgA values indicated that 4 patients had plasma CgA levels above our cut-off of normality. After mass removal, CgA further increased in 2 cases, decreased in 1 and normalized in 1. No variation in CgA levels was found in the other patients. No correlation was observed between CgA and the variables measured, except between CgA and plasma creatinine (r=0.472, p<0.05). Histopathological evaluation revealed adrenocortical adenomas in all cases and immunohistochemical analysis detected no CgA immunoreactivity in any specimen. Our results show that in human adrenocortical adenomas CgA is not expressed and that removal of the mass does not modify plasma CgA levels. For these reasons the endocrine involvement of local CgA in adrenocortical tumorigenesis is unlikely.     

Plasma human atrial natriuretic peptide levels in patients with liver cirrhosis

Plasma levels of human atrial natriuretic peptide (hANP) were investigated in patients with liver cirrhosis, and the relationships between plasma hANP levels and the following factors were studied: presence of ascites, serum and urine electrolytes, plasma renin activity, angiotensin I and II, aldosterone, catecholamines, prostaglandin derivatives, conventional liver function tests and circulating blood volume. Plasma hANP level was significantly (P less than 0.05) elevated in patients with ascites (mean = 58.6 pg/mL, s.e.m. = 8.8) compared with cases without ascites (mean = 36.6 pg/mL, s.e.m. = 2.6). With the disappearance of ascites, the level fell to normal in most cases. Urine sodium excretion was positively correlated with plasma hANP in patients without ascites, but not in patients with ascites. The plasma hANP level was disproportionately high for the rate of urinary Na excretion in cirrhotics with ascites. The plasma hANP level was not correlated with any of the other factors such as blood volume, renin-angiotensin-aldosterone levels, catecholamines and liver function tests. These results suggest that plasma hANP levels are elevated in cirrhotic patients especially with ascites, but the natriuretic response of the kidney to this raised hANP level can be impaired in patients with liver cirrhosis and ascites.     

Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery

AIM： To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery.
METHODS： We reviewed 9 patients who underwent transcatheter arterial embolization （TAE） for the ruptured hepatic artery pseudoaneurysm following major hepatobiliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arterial collaterals to the liver which may affect post-TAE liver damage and patient outcome.
RESULTS： The underlying diseases were all malignancies, and the surgical procedures included hepatopancreatoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenectomy in 2. A total of 11 pseudoaneurysm developed： 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful hemostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arterial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic artery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE.
CONCLUSION： When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral pathways to the liver created by the primary surgical procedure and a short postoperative interval may lead to an unfavorable ou