Evaluation of right adrenal vein cannulation by computed tomography angiography in 140 consecutive patients undergoing adrenal venous sampling.

OBJECTIVE: As it is now known that primary aldosteronism (PA) is more prevalent than was previously recognized, and is a potentially curable cause of hypertension and related cardiovascular diseases, the search for a safe and effective means of its diagnosis has reemerged as a topic of interest. Adrenal venous sampling is the gold standard for diagnosis of PA, but the technique is challenging and the small right adrenal vein can be particularly difficult to cannulate. Our objective was to evaluate the usefulness of computed tomography during angiography (angio-CT) in increasing the success of adrenal venous sampling and to identify factors associated with cannulation failure. DESIGN: Retrospective review. METHODS: A total of 140 consecutive patients with suspected PA except Cushing's syndrome treated at a single hospital from June 2008 to May 2013 were included. Catheter misplacement and correct cannulation rates before angio-CT and success rate of sampling after angio-CT were calculated. Univariate analysis for factors related to incorrect cannulation included gender, age, height, weight, BMI, and adrenal nodules. Successful sampling was biochemically defined according to cortisol concentrations in the venous blood samples. RESULTS: Angio-CT detected misplaced catheters in 13 patients (9.3%). The calculated correct cannulation rate of adrenal vein sampling increased from 86.4% before angio-CT to 95.7% after CT (P<0.001, McNemar's test). Univariate analysis showed a tendency for a higher rate of failure of right adrenal venous sampling in taller patients (P=0.052, Mann-Whitney's U test). CONCLUSION: Angio-CT improved success of adrenal venous sampling.

Association of glycated albumin with the presence of carotid plaque in patients with type 2 diabetes.

AIMS/INTRODUCTION: Postprandial hyperglycemia is a potent risk factor for cardiovascular disease. Serum glycated albumin (GA) has been reported to reflect postprandial blood glucose fluctuations. In the present study, we assessed the possible correlation of GA with the presence of carotid plaque to evaluate the potential clinical usefulness of GA for predicting atherosclerotic cardiovascular complications in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with type 2 diabetes (n = 236) admitted to Nippon Medical School Hospital (Tokyo, Japan) for glycemic control (aged 19-86 years, 81 females and 155 males) were examined. Clinical measurements were taken on admission. The presence of carotid plaque was assessed by ultrasonography. RESULTS: In patients with carotid plaque (n = 154), GA (P = 0.023) was higher than those without carotid plaque (n = 82). In contrast, neither fasting plasma glucose (P = 0.48) nor glycated hemoglobin (P = 0.41) was significantly different between the groups. The results of logistic regression analysis showed that GA (age- and sex-adjusted odds ratio [95% confidence interval], 1.05 [1.01-1.09]; P = 0.017) and glycated hemoglobin (1.17 [1.01-1.37]; P = 0.036) were significantly associated with the presence of carotid plaque. CONCLUSIONS: The positive correlation of serum GA with the presence of carotid plaque in type 2 diabetes suggests that GA will serve as a useful clinical marker for predicting diabetic cardiovascular complications.

Identical germline mutations in the TMEM127 gene in two unrelated Japanese patients with bilateral pheochromocytoma.

OBJECTIVE: Recently, TMEM127 was shown to be a new pheochromocytoma susceptibility gene; this is consistent with its function as a tumour suppressor gene (Journal of Clinical Endocrinology and Metabolism, 2009, 94, 2817). Most pheochromocytomas arise from the adrenal medulla, and in approximately half of the cases, the tumours are bilateral (Journal of Clinical Endocrinology and Metabolism, 2009, 94, 2817; Journal of the American Medical Association, 2004, 292, 943; Human Mutation, 2010, 31, 41; Science, 2009, 325, 1139). The aim of the present study was to determine whether TMEM127 mutations are involved in the pathogenesis of pheochromocytomas/paragangliomas in Japanese subjects. PATIENTS AND METHODS: For this study, 74 unrelated patients with pheochromocytoma/paraganglioma who tested negative for mutations and deletions in RET, VHL, SDHB and SDHD were recruited through a multi-institutional collaborative effort in Japan. The TMEM127 gene sequence was determined in their germline DNA, and tumour DNA was analysed for the loss of heterozygosity. In addition, their TMEM127 gene sequences were compared with sequences from 114 normal healthy, ethnically matched controls. RESULTS: Among the 74 eligible patients, two unrelated patients (2·7%) with bilateral adrenal pheochromocytoma were found to have an identical germline TMEM127 mutation (c.116_119delTGTC, p.Ile41ArgfsX39) associated with 2q deletion loss of heterozygosity, which was also previously described in a Brazilian case (Journal of the American Medical Association, 2004, 292, 943). We also determined that none of the 114 normal healthy controls had this deletion mutation. CONCLUSION: This is the first report showing that TMEM127 mutation plays a pathological role in pheochromocytoma in an Asian population. Although our surveillance is limited, the prevalence and the phenotype of this gene mutation appear to be similar to those reported in previous studies.

Localization of the most severely dysplastic/invasive lesions and mucin phenotypes in intraductal papillary mucinous neoplasm of the pancreas.

OBJECTIVE: The aim of this study was to define the relevance of mural nodules (MNs) as a "direct" indicator of malignancy of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Thirty-nine surgically resected IPMNs excluding obviously invasive carcinomas were examined. The distribution of the most severely dysplastic lesions was mapped on specimens. Immunohistochemical analysis for MUC1 and MUC2 was performed on sections containing the histologically predominant lesions and the most severely dysplastic areas. RESULTS: The presence of MNs correlated well with the histological grade of IPMN (P < 0.01); however, the most severely dysplastic lesions were associated with a flat/nonelevated area rather than MNs (78.9%). In the MUC1-positive subgroup, minimally invasive carcinoma was colocalized to MNs, whereas most severely dysplastic foci including minimally invasive carcinoma with components of mucinous and tubular adenocarcinoma were observed in the areas apart from MNs in the MUC2-positive and MUC1/2-negative subgroups, respectively. CONCLUSIONS: Although our data support the concept that MNs represent areas of higher-grade dysplasia within IPMN, development of invasive lesions from MNs may be limited to cases that are MUC1-positive. Careful attention should be paid to the emergence of invasive IPMN from flat foci in MUC2-positive and MUC1/2-negative cases.

Practical dietary calorie management, body weight control and energy expenditure of diabetic patients in short-term hospitalization.

AIM: We investigated how dietary management affected body weight (BW) reduction and energy expenditure in obese and normal-weight type 2 diabetic patients. METHODS: Type 2 diabetic patients who were hospitalized for diabetic control (93 men and 51 women) were checked for resting energy expenditure (REE). Subjects were divided into the two groups according to body mass index (BMI): obese (BMI > or = 25), and normal-weight (BMI <25). Following the recommendations by JDS, JAS and JASSO, ideal body weight was calculated as [IBW=height (m) x height (m) x 22 (kg/m(2))], and dietary calorie (kcal/day) was determined as 25 kcal/kg IBW. RESULTS: Dietary calorie intake during hospitalization was similar in both groups. REE was greater in obese than in normal-weight patients. The difference between the calorie intake and energy expenditure (Deltacalorie) was -222+/-26 kcal in obese patients and 69+/-27 kcal in normal-weight patients. Obese patients therefore had larger BW decreases than normal-weight patients (-171+/-12 vs. -92+/-11 g/day, p<0.005). In the obese group, a positive correlation was found between the change of BW and Deltacalorie. This correlation remained after adjusting for age, BMI, gender, and respiratory quotient. Serum lipid profiles were significantly improved in both groups. CONCLUSION: These diet instructions showed the appropriate calorie restriction depending on the BMI and induced reasonable BW reduction in both obese and normal-weight subjects. The dietary program recommended by JDS, JAS and JASSO is practically useful for BW control and for improving lipid metabolism in type 2 diabetic patients.

Comparison of pituitary-adrenal responsiveness between insulin tolerance test and growth hormone-releasing peptide-2 test: a pilot study.

Insulin tolerance test (ITT) is the gold standard for assessing the hypothalamic-pituitary-adrenal (HPA) function. GH-releasing peptide (GHRP)-2, which has a strong GH-stimulating activity, is useful for diagnosing GH deficiency as well as ITT. Additionally, GHRP-2 is also known to activate HPA axis. There have been no comparative studies of pituitary-adrenal responsiveness between GHRP-2 test and ITT in patients with hypothalamic/pituitary disease. To assess whether GHRP-2 test could be an alternative to ITT for diagnosing HPA axis failure, both ITT and GHRP-2 test were performed in 15 patients suspected of hypopituitarism. A 100mug dose of GHRP-2 was administered intravenously and plasma ACTH and serum cortisol concentrations were measured. In ITT, a peak cortisol value over 18mug/dl is considered normal. Nine patients were diagnosed as HPA axis failure by ITT. Their median peak cortisol in GHRP-2 test was 11.4mug/ml. In 6 patients diagnosed as normal HPA axis status by ITT, their median peak cortisol in response to GHRP-2 test was 21.4mug/dl, significantly higher (p=0.0032) than seen in patients diagnosed as HPA axis failure. There was a strong correlation between the peak cortisol in GHRP-2 test and ITT (r=0.817; p<0.0001). When the cut-off value for the peak cortisol in GHRP-2 test was set to 13-14mug/dl for diagnosing HPA axis failure, the specificity and sensitivity were 100% and 88.9%, respectively. Although further studies that include normal subjects are needed, these preliminary results suggest the possibility that GHRP-2 test may be an alternative to ITT for assessing HPA axis function.

Association of serum apolipoprotein B48 level with the presence of carotid plaque in type 2 diabetes mellitus.

AIMS: The atherogenicity of chylomicron remnants has been discussed. We examined whether serum apoB48 level is associated with the presence of carotid plaque in type 2 diabetic patients. METHOD: Forty type 2 diabetic patients (21 males and 19 females, 52.8+/-11.8 years old; mean+/-S.D.) were divided into two groups by the presence or absence of carotid plaque. The diurnal change of serum apoB48 level was measured by enzyme-linked immunosorbent assay. RESULTS: Fasting serum apoB48 level was higher in the subjects with carotid plaque than those without (6.5+/-3.8vs. 4.1+/-1.9 microg/ml, p=0.01). Age- and gender-adjusted analysis showed that the presence of carotid plaque was associated with fasting apoB48 (OR 1.43; 95% CI, 1.07-2.09, p=0.04) and triglyceride (OR 1.14; 95% CI, 1.02-1.32, p=0.04) levels. In normal LDL-cholesterol (<140 mg/dl) subjects, the presence of carotid plaque was associated with fasting apoB48 level (OR 2.16; 95% CI, 1.22-5.32, p=0.04), but not associated with fasting triglyceride level (OR 1.11; 95% CI, 0.99-1.30, p=0.13). CONCLUSIONS: Serum apoB48 level was strongly associated with the presence of carotid plaque in type 2 diabetic patients.

[Two cases of pancreatic tumor with von Hippel-Lindau disease].

Von Hippel-Lindau disease (VHL disease) is an inherited neoplasia syndrome. VHL disease which frequently complicates pancreatic lesions is rarely diagnosed by existence of pancreatic involvements. We report two cases of VHL disease with pancreatic lesions. The first patient was a 40-year-old woman. Adrenal pheochromocytoma, spinal hemangioblastoma and pancreatic endocrine tumor were resected. The second case was a 68-year-old woman with past surgical histories included cerebellar and spinal hemangioblastoma. Subtotal pancreatectomy was performed for multiple serous cystadenoma. IPMN which has been never reported as pancreatic involvement of VHL disease were documented by imaging diagnosis in the first case, and by histological examination in the second case. We considered VHL disease from coexistent multiple tumors include pancreatic involvements and finally diagnosed by genetic examination in both cases. Care should be taken regarding the patient's right for treatment against for the genetic disease. We hold a genetic conference composed of multidisciplinary team. Consequently we detected another VHL disease patient from patient's family.

Mucinous carcinoma of Vater's ampulla with a unique extension along the main pancreatic duct.

We report a case of mucinous carcinoma of Vater's ampulla with a unique extension along only the main pancreatic duct (MPD) and microinvasion to the pancreas. A 52-year-old man was referred to our hospital for the evaluation and treatment of acute pancreatitis. Abdominal computed tomography (CT) demonstrated swelling in the head of the pancreas with a mass in the duodenum. Hypotonic duodenography and endoscopic examination revealed a well-defined mass, measuring about 25 mm in size, in Vater's ampulla. A biopsy specimen of the tumor showed moderately differentiated adenocarcinoma. A pylorus-preserving pancreaticoduodenectomy with a regional lymphadenectomy was performed, under a preoperative diagnosis of adenocarcinoma of Vater's ampulla with direct invasion into the head of the pancreas. The resected specimen of the duodenum confirmed the presence of the mass, which measured 22 x 15 mm in size, in Vater's ampulla. Microscopically, the tumor consisted of two components: moderately differentiated adenocarcinoma in the peripheral region of the tumor Vater's papilla and mucinous carcinoma in the central region of the tumor. The mucinous carcinoma component uniquely extended along only the MPD with microinvasion to the pancreas. Immunohistochemically, both the moderately differentiated adenocarcinoma and the mucinous carcinoma were positive for cytokeratin 20 (CK20) and negative for cytokeratin 7 (CK7) which is the pattern of intestinal-type carcinoma of Vater's ampulla. We concluded that the original site of this tumor may have been the duodenal epithelium of Vater's ampulla originally moderately differentiated adenocarcinoma-which subsequently changed to mucinous carcinoma that extended along only the MPD with microinvasion to the pancreas.

Gallbladder carcinoma associated with occult pancreatobiliary reflux in the absence of pancreaticobiliary maljunction.

We herein report a case of gallbladder carcinoma associated with occult pancreatobiliary reflux (PR) in the absence of pancreatobiliary maljunction. A 67-year-old woman was referred to our hospital for the evaluation and treatment of a gallbladder tumor. Ultrasonography and computed tomography showed a nodular lesion in the fundus of the gallbladder, indicating the possibility of a gallbladder carcinoma. Endoscopic ultrasonography showed the nodular tumor and thickness of the surrounding epithelium. Endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction without the common channel and a slight dilatation of the common bile duct (15 mm in diameter). An open cholecystectomy and partial resection of the liver bed of the gallbladder with regional lymphadenectomy was performed. A C-tube was inserted from the cut end of the cystic duct into the common bile duct to prevent bile stasis. Biliary amylase and lipase levels sampled in the gallbladder were 2604 IU/l and 775 IU/l, respectively. Biliary amylase level in the bile collected from the C-tube in the common bile duct was 119 550 IU/l on postoperative day (POD) 6 and 22 265 IU/l on POD 12. These observations suggested that PR was present in this patient. The histopathological findings of the resected specimen showed a well-differentiated adenocarcinoma of the gallbladder with invasion to the muscle layer and no metastasis of the resected lymph nodes. A high index of nuclear staining for MIB-I in the cancer cells (about 10%) was exhibited, and a few cells in the normal epithelium also stained positive.

Pylorus-preserving total pancreatectomy for an intraductal papillary-mucinous neoplasm of the pancreas.

BACKGROUND/PURPOSE: Total pancreatectomy (TP) is rarely performed to treat invasive ductal carcinoma of the pancreas, due to the associated markedly impaired quality of life and poor prognosis after the resection. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is characterized by extensive intraductal spread and a favorable outcome even when presenting at an invasive stage. We herein reappraise the role of pylorus-preserving total pancreatectomy (PPTP) as a viable alternative pancreatic resection modality for borderline and malignant IPMN. METHODS: A total of five patients with IPMN underwent PPTP and their clinical follow-up data were reviewed. RESULTS: TP was performed due to recurrent IPMN in the remnant pancreas after distal pancreatectomy in three patients and due to massive involvement of the entire pancreas in the others. All patients were treated by the pylorus-preserving method, while the spleen was also preserved in one patient. The surgical margins were negative and no metastasis to the resected lymph nodes was evident, based on histological examinations. One patient underwent a re-operation due to postoperative intraabdominal bleeding, while another patient required tubedrainage for left pleural effusion. Three of the four patients who underwent PPTP with a splenectomy experienced postoperative gastric ulcer, which were controlled by medication. One patient died due to suicide 16 months after the PPTP. All the others were doing well without recurrence at periods of 62 to 127 months after the PPTP. CONCLUSIONS: PPTP is therefore considered to be indicated as an effective treatment for borderline or malignant IPMN with extensive involvement, when the patient's condition permits, in order to achieve complete resection of the IPMN.

A malignant nonfunctioning pancreatic endocrine tumor with a unique pattern of intraductal growth.

The intraductal growth of nonfunctioning pancreatic endocrine tumors (NFPTs) is considered to be rare, and in our survey of the English-language literature, we found only three cases to have been described previously. We herein report the case of a 36-year-old man with a malignant NFPT that uniquely grew within the lumen of the main pancreatic duct (MPD) and completely obstructed the MPD, as shown by endoscopic retrograde pancreatography (ERP). Endoscopic ultrasonography clearly detected the tumor with intraductal growth. In addition, positron emission tomography (PET), using 18F-fluorodeoxyglucose (FDG) and computed tomography (CT) with the same scanner (FDG-PET/CT) showed enhanced uptake of FDG in the tumor. A pylorus-preserving pancreaticoduodenectomy and regional lymphadenectomy were performed under the preoperative diagnosis of an NFPT. Microscopically, positive immunoreactions for synaptophisin and vasoactive intestinal peptide indicated neuroendocrine differentiation of the tumor, while in addition, metastasis to a lymph node along the common hepatic artery was also observed. The patient has survived for 6 months after the surgery without any evidence of recurrence or metastasis. Both ERP and FDG-PET/CT were thus found to be useful for predicting the malignant potential of an NFPT in the preoperative diagnosis.