Kosuke Tobita

Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan pancreas society.

Objective: The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs). Materials and Methods: We performed a multi-institutional, retrospective study on a collected series of patients with MCN pathologically defined by ovarian-type stroma. Clinicopathological features and prognosis were investigated. Result: Mucinous cystic neoplasm was confirmed in 156 cases, including 129 adenomas (82.7%) and 21 noninvasive (13.4%) and 6 invasive carcinomas (3.9%). Patients with MCN were exclusively women (98.1%) with the mean age of 48.1 years. All but 1 MCN were in the pancreatic body/tail region with a mean size of 65.3 mm. Communication between the cyst and the pancreatic duct was found in 18.1%. The 3-, 5-, and 10-year survival rates were 97.6%, 96.6%, and 96.6%, respectively. A significant difference in the survival rates was observed between adenomas and carcinomas and between minimally invasive carcinomas and invasive carcinomas. Cyst diameter and presence of mural nodule were predictive of malignant MCN. Conclusions: Mucinous cystic neoplasm is a rare but distinctive pancreatic cystic neoplasm with a favorable overall prognosis. All MCNs should be resected to prevent malignant changes but can be observed for an appropriate time when the lesion is small without the presence of mural nodules.

Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: a multicenter study in Japan.

Objective: The aim of this study was to evaluate the long-term follow-up results of patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) without mural nodules (MNs) at 10 representative institutions in Japan. Methods: We analyzed 349 follow-up BD-IPMN patients who had no MNs on endoscopic ultrasonography at initial diagnosis. Results: Observation periods ranged from 1 to 16.3 years (median, 3.7 years). Sixty-two (17.8%) patients exhibited disease progression during follow-up. Twenty-two underwent surgery, leading to a pathological diagnosis of carcinoma in 9 and adenoma in 13. Although the remaining 287 (82.2%) showed no changes, 7 underwent surgery because of symptoms (n = 2), choice (n = 2), or development of pancreatic ductal adenocarcinoma (n = 3); all of them were diagnosed pathologically as adenomas. Of the 29 patients undergoing surgery, all 9 with carcinoma exhibited signs of progression, such as increased main pancreatic duct diameter and/or appearance of MNs. Pancreatic ductal adenocarcinomas and additional BD-IPMNs developed in 7 (2.0%) and 13 (3.7%), respectively. Overall, 320 (91.7%) patients were followed without surgery. Conclusions: Most BD-IPMN patients who had no MNs on endoscopic ultrasonography could be managed without surgery. However, careful attention should be paid to disease progression and the development of pancreatic ductal adenocarcinomas during follow-up.Abbreviations: IPMN - intraductal papillary mucinous neoplasm, BD-IPMN - branch duct intraductal papillary mucinous neoplasm, MD-IPMN - main duct intraductal papillary mucinous neoplasm, MN - mural nodule, MPD - main pancreatic duct, PDA - pancreatic ductal adenocarcinoma, US - ultrasonography, ERCP - endoscopic retrograde cholangiopancreatography, MRCP - magnetic resonance cholangiopancreatography, EUS - endoscopic ultrasonography, CT - computed tomography

Multicenter study of serous cystic neoplasm of the Japan pancreas society.

Objectives There have been only a few reports on follow-up results of serous cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical indication of SCN are not determined yet. Methods In this multi-institutional study of the Japan Pancreas Society, a total of 172 patients with SCN were enrolled. The mean follow-up period was 4.5 years. Surgical resection was performed in 90 patients, whereas the remaining 82 were simply observed. Results Of all patients, 20% were symptomatic. The tumor was located in the pancreatic head (39%), body (35%), and tail (22%). The mean diameter of the tumor was 4.1 cm. None of the patients showed distant or lymph node metastasis except for liver metastasis found in 2 patients (1.2%). No patient died during the follow-up. The preoperative diagnosis did not correctly identify SCN in 57 (63%) of 90 resected cases. A honeycomb appearance, which is one of the most characteristic findings of SCN, could be diagnosed better by endoscopic ultrasonography than by other imaging diagnostic modalities. Conclusions Surgical resection should be considered only when clear distinction from other surgical diseases is difficult, when symptoms or mass effects are present, and when the tumor size is large.

Visualization of penetrating transmural arteries in situ by monochromatic synchrotron radiation.

BackgroundPenetrating transmural arteries with a diameter of <500 μm are considered to be a critical vascular component that causes a transmural variation of myocardial blood flow under various pathophysiological conditions. However, the conventional coronary angiographic system is not oriented to the visualization of such small arteries as these. Methods and ResultsWe magnified and monochromatized the inherently narrow beam (3 mm along the vertical direction) of synchrotron radiation by using an asymmetrically cut silicon crystal with 311 reflecting planes to obtain a monochromatic x-ray with relatively large beam size (60×25 mm) and with an energy of just above (+130 eV) the K-absorption edge of the contrast materials (33.17 and 37.41 keV for iodine and barium, respectively). We irradiated dogs or excised hearts with the monochromatic x-ray and obtained coronary angiograms using an image intensifier and video system with a spatial resolution of 170 μm. In the anesthetized dog experiments, we visualized the transmural penetrating arteries (5 to 15 μm in length) arising every 4 to 7 mm from the epicardial branch. Visualization of these arteries filled with heavy element- loaded microspheres (15 gm in diameter) in the excised- heart experiments, in which the monochromatic x-ray was irradiated to the hearts through a 10- to 20-cm acrylic plate, indicated that this system could be used for human patients, in whom body absorption of x-ray is substantial. ConclusionsCoronary angiogram by means of monochromatic x-ray is useful for a precise evaluation of coronary circulation, both in clinical settings and in physiological animal experiments.

Coronary vasoconstrictive effects of neuropeptide Y and their modulation by the ATP-sensitive potassium channel in anesthetized dogs.

OBJECTIVES This study examined the coronary vasoconstrictive action of endogenous neuropeptide Y (NPY) during sympathetic nerve stimulation and its modulation by the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel in vivo. BACKGROUND Exogenous NPY was characterized by its potent vasoconstrictive effect. However, endogenous NPY has failed to show any vasoconstrictive activity in vivo. METHODS We studied 70 anesthetized dogs with vagotomy under beta-adrenergic blockade. Ansae subclaviae stimulation and intracoronary administration of the neurotransmitters (NPY and norepinephrine) were done with or without alpha-adrenergic blockade, NPY antagonist BIBP3226 or KATP channel acting agents. We measured coronary vascular resistance (CVR) and the neurotransmitter levels in systemic arteries and the great cardiac vein, and the amount of overflow (venoarterial difference times myocardial blood flow). RESULTS During nerve stimulation, NPY levels correlated significantly with CVR at the highest r value (r = 0.850, p < 0.0001) obtained for the venous level under alpha-blockade, but norepinephrine showed no correlation. Treatment with BIBP3226 abolished the correlation between NPY level and CVR under alpha-blockade. Without alpha-blockade, norepinephrine levels correlated significantly with CVR; however, NPY showed no correlation. The amount of NPY overflow during the stimulation was nearly 1,000-fold lower than norepinephrine overflow. Exogenous NPY had a 100-fold more potent coronary vasoconstrictive action than that of norepinephrine. The KATP channel antagonist glibenclamide enhanced vasoconstriction of NPY, and the agonist pinacidil suppressed it with a predominant effect in the subepicardial region. CONCLUSIONS During sympathetic nerve stimulation, the vasoconstrictive actions of NPY are masked by norepinephrine under intact alpha-adrenoceptor conditions, manifest during alpha-blockade and modulated by KATP channel activity.

Clinical significance of wall invasion pattern of subserosa-invasive gallbladder carcinoma.

We have previously classified wall invasion patterns of gallbladder carcinoma (GBC) cases into two groups, i.e., the infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor differentiation, aggressive infiltration and decreased postoperative survival in terms of its histological differentiation, lymphatic invasion, venous invasion, lymph node status, neural invasion and mode of subserosal infiltration. In the present study, we analyzed 42 surgically-resected subserosal invasive gallbladder adenocarcinomas, invading the perimuscular connective tissue (pT2). The cumulative 5-year survival rate in the series was 48.7%. Lymphatic invasion (p=0.021), venous invasion (p=0.020), mode of subserosal infiltration (p<0.001), histological differentiation (p=0.030) and biliary infiltration (p=0.007) were noted, respectively, at a significantly higher incidence in more aggressive infiltration or poor differentiation in the DG type. The cumulative 5-year survival rate of curative resection cases was lower in patients with the DG type than in those with the IG type (68.9 versus 20.2%, respectively, p=0.006, log-rank test). On Cox’s proportional hazard regression modeling, the low degree of venous/perineural invasion and IG type of wall invasion pattern were associated with a significant improvement in overall survival. Our data suggest that the wall invasion pattern is an independent predictor of survival in subserosal invasive GBC. Regarding the clinical application of our concept, on the classification of patients with subserosal invasive GBC based on a combination of the wall invasion pattern and lymph node status, the overall survival rate in patients with the DG type and/or N2 metastasis (n=21) was lower than in patients with the IG type and N0, 1 metastasis (n=21) (p=0.0023, log-rank test). The wall invasion pattern could contribute to decision-making concerning curative resection for subserosal invasive GBC.

Leiomyosarcoma of the pancreas: Report of a case

Leiomyosarcoma of the pancreas is a rare neoplasm, with only 34 reported cases in the literature. We encountered a rare case of leiomyosarcoma of the pancreas, treated successfully by surgery. A 41-year-old woman was referred to our hospital for further examinations of a pancreatic tumor. Imaging studies demonstrated a solid and lobular mass, about 4 cm in diameter, in the body of pancreas. This mass had a nonuniform content and was encapsulated. We performed distal pancreatectomy and splenectomy for an assumed diagnosis of invasive ductal carcinoma. Macroscopically, a sagittal section of the operative specimen showed a well-circumscribed yellowish-white mass without any cystic changes. Immunohistological examination revealed that α-smooth muscle actin, desmin, and vimentin were positive, and the labeling index of MIB-1 was 50% or more. Based on these findings, we confirmed a diagnosis of leiomyosarcoma originating from the pancreas. During 14 months of follow-up to date, there has not been any evidence of local recurrence or distant metastasis.

An annular pancreas associated with carcinoma of the papilla of Vater: report of a case

An annular pancreas is an uncommon congenital anomaly that usually presents early in childhood. Malignancy in the setting of an annular pancreas is unusual. We herein report a case of annular pancreas with carcinoma of the papilla of Vater. A 59-year-old man presented with epigastric discomfort and was referred to us after gastroduodenal endoscopy showed a tumor of the papilla of Vater. Preoperative imaging showed the pancreatic parenchyma encircling the descending duodenum and a tumor at the papilla of Vater. A pancreaticoduodenectomy was performed for the annular pancreas and the ampullary tumor. Histological examination confirmed a complete annular pancreas and carcinoma in situ of the papilla of Vater. We also provide a review of the reported cases of an annular pancreas with periampullary neoplasms and discuss the clinical characteristics of this anomaly.

Hepatobiliary and pancreatic: Hepatic adenoma, focal nodular hyperplasia and congenital absence of the portal vein.

A young woman, aged 18, was investigated because of chronic diarrhea. She was a twin and had a previous history of a ventricular septal defect that closed spontaneously. On physical examination, she had a mass in the right iliac fossa. Blood tests revealed iron deficiency anemia. Liver function tests were normal and serological tests for hepatitis B and C were negative. An ultrasound study was consistent with an ovarian neoplasm. However, a contrastenhanced computed tomography scan with reformatted images (coronal and sagittal) showed that the mass was attached to the left lobe of the liver and that a vein within the stalk drained into the left hepatic vein (Fig. 1). In addition, intrahepatic portal veins were not seen and there was an abnormal vessel adjacent to a dilated inferior vena cava. These findings were consistent with congenital absence of the portal vein. A magnetic resonance imaging scan with a T2-weighted image (Fig. 2) showed central necrosis within the mass consistent with an hepatic adenoma as well as a decreased signal intensity in the periphery of the mass after the administration of superparamagnetic iron oxide. The latter is consistent with focal nodular hyperplasia. Angiography showed that the blood supply to the mass arose from the left hepatic artery and, in the portal phase, there was a connection between the anastomosis of the superior mesenteric and splenic veins and a dilated inferior vena cava. The tumor was removed at laparoscopy and the pathological diagnosis was that of an hepatic adenoma within focal nodular hyperplasia. Atresia or agenesis of the portal vein is a rare congenital anomaly that is often associated with anomalies of the systemic vasculature. In addition, patients appear to be at high risk for a variety of liver lesions including focal nodular hyperplasia, adenomas, hepatoblastomas and hepatocellular carcinomas. These lesions may develop in response to changes in the hepatic vasculature or to changes in the composition of hepatic blood. The development of an adenoma within an area of focal nodular hyperplasia may not have been reported previously.

Nonfunctioning pancreatic endocrine tumor with extension into the main pancreatic duct: Report of a case

Pancreatic endocrine tumors (PETs) rarely involve the main pancreatic duct. We report a case of malignant nonfunctioning pancreatic endocrine tumor (NFPET) with prevalent intraductal growth. A 47-year-old woman was referred to us after ultrasonography at a routine health check showed diffuse swelling of the pancreas. Preoperative imaging showed a solid mass in the tail of the pancreas and a bulging intraductal mass in the main pancreatic duct. We performed total pancreatectomy because the tumor occupied almost the entire lumen of the main pancreatic duct. Histological examination confirmed well-differentiated endocrine carcinoma. We review reported cases of the intraductal growth of NFPETs and discuss the pathogenesis of these unusual tumors.