Adenocarcinoma arising in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor therapy.

We report a case of developing multiple adenocarcinoma foci in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor (PPI) therapy. A 57-year-old man, who was undergoing hemodialysis for chronic renal failure, underwent an upper gastrointestinal endoscopy to elucidate the cause of anemia. Atrophic gastritis with H. pylori infection and multiple adenocarcinoma foci in multiple hyperplastic polyps were found in the endoscopic and histological examinations. Enterochromaffin-like micronests and parietal cell protrusion in the background of the polyps suggested the existence of hypergastrinemia. The serum gastrin level was markedly high-10,206 pg/ml (normal range 37-172 pg/ml). The cause of this marked hypergastrinemia was not autoimmune gastritis and gastrinoma. After discontinuing PPI therapy and successful eradication of H. pylori, the serum gastrin level decreased to normal range. These findings indicate that hypergastrinemia may be caused by long-term PPI therapy in patients with H. pylori infection. This case suggests that hypergastrinemia may mediate gastric carcinogenesis in patients with H. pylori infection.

Severe erosive esophagitis developing after gastric ulcer formation.

A 90-year-old woman visited to our institute due to postprandial obstructive sensation of the esophagus. She had suffered from ischemic heart disease and diabetes mellitus, and taken low-dose aspirin for prophylaxis. She also had a history of a large ulcer located on the upper gastric body at 81 years-old. Esophago-gastric junction was normal excepting mild hiatal hernia at that time. The esophagogastroduodenoscopy showed a lump of food at the lower esophagus with severe stricture and mucosal injury. Rabeprazole 20 mg per day was given, and both the inflammatory change and the symptoms improved after the prescription. A probable reason of the development is impaired gastroesophageal motility and acid regurgitation induced by gastric deformity caused after ulcer formation.

Metronidazole-induced neurotoxicity developed in liver cirrhosis.

A 68 year-old-male with hepatitis C-positive liver cirrhosis was admitted because of liver abscess. After metronidazole was initiated against the infection, mental disturbance appeared. Hepatic encephalopathy was suspected at first, however, the brain MRI showed hyperintense lesion of the bilateral basal dendric nuclei which indicated metronidazole-associated encephalopathy. The symptoms became well after cessation of the drug. Metronidazole is a widely used medicine against various infections. Recent case reports describe that this medicine can induce reversible encephalopathy. However, there have been few reports regarding metronidazole-induced encephalopathy occurred in patients with cirrhosis. Here we report on a case of hepatic cirrhosis and abscess in which reversible metronidazole-induced encephalopathy developed.

Gastric emptying in patients with autoimmune pancreatitis.

OBJECTIVES: Autoimmune pancreatitis (AIP) and its extrapancreatic lesions seem to be clinical manifestations of organs involved in IgG4-related systemic disease. To clarify whether the stomach is a target organ, gastric function was evaluated in patients with AIP. METHODS: In 6 patients with AIP, gastric emptying was assessed by Carbon 13 (¹³C) acetate breath test before and after steroid therapy. Based on 4-hour breath samples, the half ¹³CO2 excretion time (T(1/2)) and the time of maximal excretion (T(max)) were calculated as gastric emptying parameters. Data of 20 healthy volunteers were used as controls. The number of IgG4-positive plasma cells in gastrofiberscopic biopsy specimens was counted before and after steroid therapy. RESULTS: Both T(1/2) and T(max) in patients with AIP decreased significantly after steroid therapy (T(1/2): 1.89 ± 0.21 hours vs 1.69 ± 0.15 hours, P = 0.046; and T(max): 1.1 ± 0.2 hours vs 0.96 ± 0.2 hours, P = 0.027), and became similar to those of the controls (T(1/2): 1.69 ± 0.32 hours and T(max): 0.98 ± 0.2 hour). The number of IgG4-positive plasma cells infiltrating the gastric mucosa decreased after steroid therapy. CONCLUSIONS: Gastric emptying was impaired in patients with AIP and improved to the reference range after steroid therapy. The stomach may be a target organ of IgG4-related systemic disease.

Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

BACKGROUND/AIMS: Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. METHODOLOGY: The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. RESULTS: Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). CONCLUSIONS: Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

[A case of fulminant ulcerative colitis initially presenting as fever of unknown origin].

A 40's man was referred to our hospital for the investigation of fever of unknown origin lasting for a month. The laboratory data showed a prominent inflammatory reaction and a high titer of PR3-ANCA. Despite the various imaging studies and bacteriological examinations, the cause of the fever could not be detected until he complained of abdominal pain with bloody stool that appeared during hospitalization and which prompted colonoscopy, resulting in the diagnosis of moderate ulcerative colitis of the descending colon. Although temporal improvement was achieved by mesalazine administration, the symptom exacerbated again. Then, a combination of steroid administration and the leukocytapheresis (LCAP) was performed, but it was also not effective. His rapidly deteriorating condition with the lesion extending to whole colon necessitated subtotal colectomy. He has been afebrile and in good condition since the operation, which indicates the cause of the fever was due to ulcerative colitis.

Predictors of malignancy and natural history of main-duct intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVES: Because the prevalence of carcinoma is high in main-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, surgical resection is recommended for all main-duct type IPMNs. This study aimed to investigate the clinical predictors of malignancy and natural history of main-duct IPMNs. METHODS: Preoperative clinical characteristics reliably correlated with malignancy in 26 surgically resected patients with main-duct IPMN, and long-term outcome in 20 conservatively followed patients with main-duct IPMN was examined. RESULTS: Age at diagnosis was significantly older in conservatively followed IPMN patients than in surgically resected IPMN patients. Main pancreatic duct (MPD) dilatation 10 mm or greater and mural nodules were significantly more frequent in malignant IPMNs. Obvious progression of dilatation of the MPD was detected in all 4 conservatively followed patients who developed invasive pancreatic carcinoma. The histology of IPMN at autopsy of 4 conservatively followed patients who died of other causes 21 to 120 months later was adenoma. Seven conservatively followed without malignant findings did not show obvious progression of MPD dilatation. CONCLUSIONS: Although surgical resection is indicated for many main-duct IPMNs, conservative follow-up may be an option for elderly asymptomatic patients with main-duct IPMNs with the MPD less than 10 mm, no obvious mural nodule, and negative cytology.

Endoscopic approach for diagnosing autoimmune pancreatitis.

It is of utmost importance to differentiate autoimmune pancreatitis (AIP) from pancreatic cancer (PC). Segmental AIP cases are sometimes difficult to differentiate from PC. On endoscopic retrograde cholangiopancreatography, long or skipped irregular narrowing of the main pancreatic duct (MPD), less upstream dilatation of the distal MPD, side branches derived from the narrowed portion of the MPD, absence of obstruction of the MPD, and stenosis of the intrahepatic bile duct suggest AIP rather than PC. Abundant infiltration of IgG4-positive plasma cells is frequently and rather specifically detected in the major duodenal papilla of AIP patients. IgG4-immunostaining of biopsy specimens obtained from the major duodenal papilla is useful for supporting a diagnosis of AIP with pancreatic head involvement. On endoscopic ultrasonography (EUS), hyperechoic spots in the hypoechoic mass and the duct-penetrating sign suggest AIP rather than PC. EUS and intraductal ultrasonography sometimes show wall thickening of the common bile duct even in the segment in which abnormalities are not clearly observed with cholangiography in AIP patients. EUS-guided fine needle aspiration, especially EUS-guided Tru-Cut biopsy, is useful to diagnose AIP, as well as to exclude PC.

Endoscopic hemostasis techniques for upper gastrointestinal hemorrhage: A review.

Upper gastrointestinal hemorrhage (UGIH) is an urgent disease that is often encountered in daily medical practice. Endoscopic hemostasis is currently indispensable for the treatment of UGIH. Initially, when UGIH is suspected, a cause of UGIH is presumed from the medical interview and physical findings. After ample primary treatment, urgent endoscopy is performed. Many methods of endoscopic hemostasis are in wide use, including hemoclip, injection and thermo-coagulation methods. Although UGIH develops from a wide variety of diseases, such as esophageal varices and gastric and duodenal ulcer, hemostasis is almost always possible. Identification of the causative diseases, primary treatment and characteristic features of endoscopic hemostasis are needed to allow appropriate treatment.

Does a patent accessory pancreatic duct prevent acute pancreatitis?

BACKGROUND AND AIM: The role of the accessory pancreatic duct (APD) in pancreatic pathophysiology has been unclear. We previously examined the patency of the APD in 291 control cases who had a normal pancreatogram in the head of the pancreas by dye-injection endoscopic retrograde pancreatography (ERP). APD patency was 43% and was closely related with the shape of the terminal portion of the APD. The present study aimed to clarify the clinical implications of a patent APD. METHODS: Based on the underlying data, the patency rate of the APD was estimated from the terminal shape of the APD on ERP in 167 patients with acute pancreatitis. RESULTS: In patients with acute pancreatitis, stick-type APD, spindle-type APD, and cudgel-type APD, which showed a high patency, were rare, and branch-type APD and halfway-type or no APD, which showed quite low patency, were frequent in acute pancreatitis patients. Accordingly, the estimated patency of the APD in acute pancreatitis patients was only 21%. There was no significant relationship between the estimated APD patency and etiology or severity of acute pancreatitis. CONCLUSIONS: The terminal shapes of the APD with low patency were frequent in acute pancreatitis patients, and estimated APD patency was only 21% in acute pancreatitis. A patent APD may function as a second drainage system to reduce the pressure in the main pancreatic duct and prevent acute pancreatitis.

FDG-PET/CT findings of autoimmune pancreatitis.

BACKGROUND/AIMS: This study aimed to evaluate the clinical utility in Fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET)/ computed tomography (CT) in the management of patients with autoimmune pancreatitis (AIP), with special emphasis on differentiating AIP from pancreatic cancer (PC). METHODOLOGY: FDG-PET/CT findings of 10 AIP patients were compared with those of 14 PC patients. RESULTS: There were no significant differences between AIP and PC in early and delayed maximum standardized uptake value (SUV(max)), and in the ratio of delayed to early SUV(max). Abnormal extrapancreatic FDG uptake was observed in 5 AIP patients, in the hilar lymph nodes (n = 4), mediastinal lymph nodes (n = 2), abdominal lymph nodes (n = 2), and bilateral salivary glands (n = 2). After steroid therapy, the abnormal FDG uptake in the pancreas disappeared almost completely in two patients, and the FDG uptake in the hilar, mediastinal and abdominal lymph nodes decreased in one patient. CONCLUSIONS: FDG-PET/CT may be helpful to differentiate AIP from PC by assessing FDG-uptake patterns in the pancreas and extrapancreatic lesions, it may have the potential to assess the disease activity of AIP and its extrapancreatic lesions, and it may be useful as a monitoring marker for tapering or stopping steroid therapy.

Juxtapapillary duodenal diverticula and pancreatobiliary disease.

Juxtapapillary duodenal diverticula (JPD) are observed in around 10-20% of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). They are acquired extraluminal outpouchings of the duodenal wall through 'locus minoris resistance' and their incidence increases with age. They have been studied mainly with regard to their association with pancreatobiliary disease. Choledocholithiasis is considered to be strongly associated with JPD, but the role of JPD in the development of cholecystolithiasis and pancreatitis is still disputable. Since JPD are located in the vicinity of the papilla of Vater, they not only cause mechanical compression of the bile duct but also induce dysfunction of the sphincter of Oddi. They are considered to lead to bile stasis and to allow reflux from the duodenum into the bile duct, which results in an ascending infection of beta-glucuronidase-producing bacteria. The ERCP procedure can be hampered by JPD, although recent papers have reported no difference in the successful cannulation rate or complications between patients with JPD and those without JPD. Disorders caused by JPD are amenable to appropriate therapy, e.g. endoscopic sphincterotomy and surgical intervention.

A patent accessory pancreatic duct prevents pancreatitis following endoscopic retrograde cholangiopancreatography.

BACKGROUND/AIM: Pancreatitis is the most common and feared complication of endoscopic retrograde cholangiopancreatography (ERCP). We previously examined patency of the accessory pancreatic duct (APD) by dye injection endoscopic retrograde pancreatography (ERP). APD patency was found in 43% of 291 control cases who had no particular changes in the head of the pancreas compared to only 6% in patients with acute pancreatitis. APD patency was closely related with the shape of the terminal portion of the APD. This study aimed to clarify whether patency of the APD prevents post-ERCP pancreatitis. METHODS: We examined retrospectively the terminal shape of the APD by ERP in 34 patients with post-ERCP pancreatitis. Based on these data, patency of the APD was estimated from its terminal shape in patients with post-ERCP pancreatitis. RESULTS: The stick-type APD (p < 0.01), which indicated high patency, was less frequent, and the branch-type APD (p < 0.01) and halfway-type APD, or no APD (p < 0.01), which showed quite low patency, were more frequent in patients with post-ERCP pancreatitis compared with controls. Accordingly, the estimated patency of the APD in post-ERCP pancreatitis patients was only 16%, which was significantly lower than the 43% in controls. There was no significant relationship between the estimated APD patency and the severity of post-ERCP pancreatitis. CONCLUSIONS: The estimated APD patency was significantly lower in patients with post-ERCP pancreatitis. A patent APD may function as a second drainage system to reduce the pressure in the main pancreatic duct and prevent post-ERCP pancreatitis.

Utility of narrow band imaging for identification of the orifice of the bile duct during ERCP.

Exact identification of the orifice of the bile duct in the major duodenal papilla is required for selective cannulation during endoscopic retrograde cholangiopancreatography (ERCP). However, there are some cases in which the orifice is unclear. The narrow band imaging (NBI) system is an endoscopic imaging technique based on modification of spectral features that enhances visualization of the vascular network. On NBI, bile appears as a bright red fluid, and it is enhanced in the digestive tract. We report two cases in which the NBI was useful for identification of the orifice of the bile duct during ERCP. We recommend the NBI technique before cannulation in cases where the orifice is unclear on the standard image.

Metachronous extrapancreatic lesions in autoimmune pancreatitis.

OBJECTIVE: Autoimmune pancreatitis (AIP) is frequently associated with various extrapancreatic lesions. The distribution and frequency of extrapancreatic lesions preceding or subsequent to AIP are unknown. The aim of this study was to investigate metachronous extrapancreatic lesions of AIP. PATIENTS AND METHODS: Extrapancreatic lesions were examined clinically, radiologically, and histologically in 56 AIP patients. RESULTS: Extrapancreatic lesions were associated in 25 (45%) of 56 AIP patients. Twenty-nine extrapancreatic lesions were detected synchronously with AIP in 18 patients, and 18 lesions were detected metachronously in 11 AIP patients. Fourteen patients had more than 2 extrapancreatic lesions. There was no significant difference in serum IgG4 levels between AIP patients with preceding extrapancreatic lesions and synchronous extrapancreatic lesions. Extrapancreatic lesions preceding AIP were sclerosing sialadenitis (n=8), cervical lymphadenopathy (n=4), swelling of the lacrimal glands (n=2), retroperitoneal fibrosis (n=1), and hilar lymphadenopathy (n=1). Retrospective histopathological examination confirmed that these lesions were compatible with IgG4-related sclerosing disease. Steroid therapy was not given for these initial lesions, and AIP occurred 3 to 48 months after these initial lesions. Swelling of the preceding extrapancreatic lesions persisted when AIP occurred. Extrapancreatic lesions subsequent to AIP were retroperitoneal fibrosis (n=1) and systemic lymphadenopathy (n=1), both of which occurred during follow-up of AIP without steroid therapy. All extrapancreatic lesions improved after steroid therapy. CONCLUSION: Swelling of salivary or lacrimal glands, lymphadenopathy, and retroperitoneal fibrosis can precede AIP. Lymphadenopathy and retroperitoneal fibrosis can occur subsequent to AIP. Recognition of these findings will aid in the correct diagnosis of AIP.

Differentiation of autoimmune pancreatitis from pancreatic cancer by diffusion-weighted MRI.

OBJECTIVES: We sought to clarify the clinical utility of diffusion-weighted magnetic resonance imaging (DWI) for differentiating autoimmune pancreatitis (AIP) from pancreatic cancer. METHODS: Thirteen AIP patients underwent DWI before therapy, and six of them underwent DWI after steroid therapy. The extent and shape of high-intensity areas were compared with those of 40 pancreatic cancer patients. Apparent diffusion coefficient (ADC) values were calculated in the AIP area before and after steroid therapy in pancreatic cancer patients and in a normal pancreatic body. RESULTS: On DWI, AIP and pancreatic cancer were detected as high-signal intensity areas. The high-intensity areas were diffuse (n=4), solitary (n=6), and multiple (n=3) in AIP patients, but all pancreatic cancer patients showed solitary areas (P<0.001). A nodular shape was significantly more frequent in pancreatic cancer, and a longitudinal shape was more frequently found in AIP (P=0.005). ADC values were significantly lower in AIP (1.012+/-0.112 x 10(-3) mm(2)/s) than in pancreatic cancer (1.249+/-0.113 x 10(-3) mm(2)/s) and normal pancreas (1.491+/-0.162 x 10(-3) mm(2)/s) (P<0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.075 x 10(-3) mm(2)/s to distinguish AIP from pancreatic cancer. After steroid therapy, high-intensity areas on DWI disappeared or were markedly decreased, and the ADC values of the reduced pancreatic lesions increased almost to the values of normal pancreas. CONCLUSIONS: DWI is useful for detecting AIP and for evaluating the effect of steroid therapy. ADC values were significantly lower in AIP than in pancreatic cancer. An ADC cutoff value may be useful for distinguishing AIP from pancreatic cancer.

Pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a junction of the pancreatic and bile ducts located outside the duodenal wall, usually forming a markedly long common channel. In PBM patients, this anomaly allows regurgitation between the pancreatobiliary and biliopancreatic tract. Since hydrostatic pressure within the pancreatic duct is usually higher than that in the common bile duct, pancreatic juice frequently refluxes into the bile duct. As a result, pancreatic enzyme levels are generally very high in the bile and there is a related high incidence of biliary cancer. PBM can be divided into PBM with biliary dilatation (congenital choledochal cyst [CCC]) and PBM without biliary dilatation (maximal diameter of the bile duct

Allergic manifestations in autoimmune pancreatitis.

OBJECTIVE: Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. However, target antigens for AIP have not been detected. Furthermore, its preponderant occurrence in elderly men and the very dramatic response with no major residual deformity to oral steroid therapy within 2 weeks suggest that the pathogenesis of AIP might not involve autoimmune mechanism. Recently, it was reported that the immune reaction closely involved in the pathogenesis of allergic disorders was upregulated in the affected tissues of AIP. This study aimed to examine the allergic manifestations in AIP patients. METHODS: This case series consisted of 45 AIP patients. Present and/or past histories of allergic diseases, clinical findings, and laboratory data were reviewed. RESULTS: Twenty patients (allergic-type AIP) had histories of allergic diseases, such as acute allergic rhinitis (n= 11), including rose and hay fever, atopic dermatitis (n= 5), bronchial asthma (n= 3), drug allergy (n= 2), and hypersensitivity pneumonitis (n= 1). Serum IgE levels were elevated in only 12 allergic-type AIP patients, and they were significantly higher in allergic-type AIP patients than in AIP patients without allergic manifestations (P = 0.0001). The peripheral eosinophil count was significantly elevated in allergic-type AIP patients (P =0.048). With respect to initial symptoms, obstructive jaundice was less frequent in allergic-type AIP patients (P = 0.012), and abdominal pain was detected in only five patients with allergic-type AIP (P = 0.013). Allergic-type AIP occurred predominantly from September to February in 19 of 20 patients (P = 0.001). CONCLUSION: Allergic manifestations were detected in about half of the AIP patients, and allergic mechanisms may be related to the occurrence of AIP in these patients.