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.

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.

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.

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.

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.

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

The natural course of autoimmune pancreatitis.

BACKGROUND/AIMS: Since autoimmune pancreatitis (AIP) responds dramatically to steroid therapy, most AIP patients are promptly treated with steroids when the diagnosis of AIP is made. Therefore, the natural course of AIP is unclear. This study aimed to evaluate the clinical course of AIP patients without steroid therapy and assess the indications for steroid therapy in these patients. METHODOLOGY: Clinical features were retrospectively assessed in 12 patients who were followed for more than 6 months after the diagnosis of AIP without steroids. RESULTS: Six patients were later treated with steroids due to exacerbation of AIP. Five of them developed obstructive jaundice due to bile duct stenosis. Segmental enlargement progressed to diffuse enlargement in 4 patients. Serum IgG and/or IgG4 levels increased with AIP progression. In 4 patients, swelling of the salivary glands preceded AIP. Radiological and clinical features responded well to steroid therapy. Spontaneous improvement occurred in 3 patients. Four asymptomatic patients with segmental pancreatic enlargement have demonstrated no changes without steroid therapy until now. CONCLUSIONS: About half of the segmental AIP cases progressed and needed steroid therapy, which was effective. Asymptomatic segmental AIP cases without biliary lesions may be followed without steroid therapy with periodic laboratory and imaging studies.

Biliary lesions associated with autoimmune pancreatitis.

BACKGROUND/AIMS: Characteristic radiological features of biliary lesions in patients with autoimmune pancreatitis (AIP) have not yet been identified. METHODOLOGY: Bile duct lesions and their relationships to other clinical findings were assessed in 43 AIP patients. RESULTS: Of the 43 AIP patients, 34 (79%) had bile duct stenosis. In all the 34 patients, the lower bile duct was involved; in 21 of these, only the lower bile duct was involved, and in 13 patients, there was widespread wall thickening of the middle and upper bile duct where stenosis was not obvious on cholangiography. Furthermore, 4 patients with extensive bile duct involvement also had stenosis of the intrahepatic bile duct. All patients with bile duct involvement had involvement of the head portion of the main pancreatic duct. None of the 6 patients with involvement of only the body and/or tail portion of the main pancreatic duct had bile duct involvement. Gallbladder wall thickening was more frequently noted in patients with extensive bile duct involvement (p < 0.01). Serum IgG4 levels were significantly more elevated in patients with extensive bile duct involvement (p < 0.05). CONCLUSIONS: AIP patients with extensive bile duct involvement characterized by widespread wall thickening of the bile duct may have more active disease.

Diagnosis and clinical implications of pancreatobiliary reflux.

The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts and regulates the outflow of bile and pancreatic juice. A common channel can be so long that the junction of the pancreatic and bile ducts is located outside of the duodenal wall, as occurs in pancreaticobiliary maljunction (PBM); in such cases, sphincter action does not functionally affect the junction. As the hydropressure within the pancreatic duct is usually greater than in the bile duct, pancreatic juice frequently refluxes into the biliary duct (pancreatobiliary reflux) in PBM, resulting in carcinogenetic conditions in the biliary tract. Pancreatobiliary reflux can be diagnosed from elevated amylase level in the bile, secretin-stimulated dynamic magnetic resonance cholangiopancreatography, and pancreatography via the minor duodenal papilla. Recently, it has become obvious that pancreatobiliary reflux can occur in individuals without PBM. Pancreatobiliary reflux might be related to biliary carcinogenesis even in some individuals without PBM. Since few systemic studies exist with respect to clinical relevance and implications of the pancreatobiliary reflux in individuals with normal pancreaticobiliary junction, further prospective clinical studies including appropriate management should be performed.

No relationship between plasma desacyl-ghrelin levels and rabeprazole-related delay in gastric emptying : controlled study in healthy volunteers.

BACKGROUND AND OBJECTIVE: Recent studies have indicated that rabeprazole, a proton pump inhibitor, delays gastric emptying. However, the mechanism of action remains unclear. We conducted this study to clarify whether desacyl-ghrelin (the inactive form of the endogenous growth hormone secretagogue receptor ghrelin) is involved in rabeprazole-induced changes in gastric motor function. METHODS: Twelve healthy males underwent (13)C-acetate breath tests to evaluate gastric emptying of a liquid meal twice after administration of rabeprazole 20 mg/day for 3 days or no medication (control). Gastric emptying was evaluated by two parameters: half-emptying time and time to peak (13)CO(2) excretion. Plasma desacyl-ghrelin levels were measured in blood samples collected at three time points: immediately pre-test and 1 and 2 hours after ingestion of the test meal. RESULTS: Rabeprazole significantly delayed gastric emptying of the liquid meal. However, plasma desacyl-ghrelin levels after ingestion of the liquid meal showed little difference before or after rabeprazole administration. CONCLUSION: The results indicate that desacyl-ghrelin was not associated with changes in gastric emptying caused by rabeprazole.

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.

Effect of cigarette smoking on gastric emptying of solids in Japanese smokers: a crossover study using the 13C-octanoic acid breath test.

BACKGROUND: Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease. Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases. Thus, studies examining a link between smoking and gastric emptying disorders have clinical relevance. This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers. METHODS: The (13)C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions (either sham smoking or actively smoking). The time vs (13)CO(2) excretion rate curve was mathematically fitted to a conventional formula of y (t) = m*k*beta*e(-k*t)*(1 - e(-k*t))(beta-1), and the parameters of k and beta were determined: under the crossover protocol, a larger (smaller) beta indicates slower (faster) emptying in the early phase, and a larger (smaller) k indicates faster (slower) emptying in the later phase. The half (13)CO(2) excretion time (t(1/2b) = -[ln(1 - 2(-1/beta))]/k) and the time of maximal (13)CO(2) excretion rate (t(max) = [lnbeta]/k) were also calculated. Between the two occasions, k, beta, t(1/2b), and t(max) were compared by the Wilcoxon signed-rank test. RESULTS: After smoking, k was significantly increased. No significant differences were found in beta, t(1/2), and t(max) between the two occasions. CONCLUSIONS: The increase in k suggests the acceleration of gastric emptying in the later phase. For the first time, this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers.

[The validity of serum acetaminophen concentration at 45 min as an index of gastric emptying rate: a study based on pharmacokinetic theories].

The reliability of the serum acetaminophen (APAP) concentration at 45 min (C45) as a measure of gastric emptying (GE) has been evaluated using a pharmacokinetic simulation work. The present results have revealed that C45 is a useful index to conveniently detect delayed GE, but it is unreliable to measure rapid GE. In addition, the following simple criteria for diagnosis of delayed GE has been proposed based on the pharmacokinetic theories: after ingestion of 20 mg/kg APAP dissolved in a 200 kcal-containing liquid meal, 1) the delayed GE is excluded when C45 > 5.0 micrograms/ml, 2) whether GE is delayed or not is inconclusive when 2.0 < C45 < 5.0 micrograms/ml, and 3) the delayed GE is confirmed when C45 < 2.0 micrograms/ml.

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.