Fundic gland differentiation of oncocytic/pancreatobiliary subtypes of pancreatic intraductal papillary mucinous neoplasm.

AIMS: Intraductal papillary mucinous neoplasms (IPMNs) differentiate in several histological directions, which are related to their clinical behaviour. Differentiation of IPMNs to the gastric foveolar epithelium/pyloric gland (PG) is well known. However, no study has been conducted regarding fundic gland (FG) differentiation. The aim of this study was to determine the frequency of FG differentiation and its relationship with the clinicopathological features of IPMNs, by studying 48 surgically resected IPMN cases consisting of 17 gastric IPMNs, 15 intestinal IPMNs, 10 pancreatobiliary IPMNs, and six oncocytic IPMNs. METHODS AND RESULTS: Clinicopathological data, including histological tumour grade, immunohistochemical data for mucins (MUCs), pepsinogen I, pepsinogen II, and H,K-ATPase, and GNAS/KRAS status, were analysed. Pepsinogen I and H,K-ATPase were used to assess FG differentiation, and pepsinogen II and MUC6 were used to identify the equivalent cell type of the normal FG. Reverse transcription polymerase chain reaction (RT-PCR) for PGA5/PGC (pepsinogen I and pepsinogen II mRNA, respectively) and quantitative real-time RT-PCR (qRT-PCR) for PGA5 were performed to confirm the immunohistochemistry results. Pepsinogen I expression was detected in 12.5% (6/48) of total IPMNs, of which 66.7% (4/6) of oncocytic IPMNs and 20.0% (2/10) of pancreatobiliary IPMNs were pepsinogen I-positive. No H,K-ATPase-positive cases were detected. Three oncocytic IPMNs with pepsinogen I expression showed similar histology to normal FG. RT-PCR and qRT-PCR confirmed the immunohistochemical results. All IPMNs with FG differentiation were of the oncocytic or pancreatobiliary subtype, were of histologically high grade, and were without GNAS mutation. CONCLUSIONS: The differentiation of IPMNs to gastric FG is related to oncocytic and pancreatobiliary subtypes, and to high grade. This is the first report to describe differentiation of IPMNs to the FG, and to reveal its relationship with the clinicopathological features of IPMNs.

Pancreatic duct lavage cytology with the cell block method for discriminating benign and malignant branch-duct type intraductal papillary mucinous neoplasms.

BACKGROUND: Differentiation between benign and malignant branch-duct type intraductal papillary mucinous neoplasms (IPMNs) remains challenging. OBJECTIVE: To examine the usefulness of pancreatic duct lavage cytology with cell block method for discriminating benign and malignant branch-duct type IPMNs. PATIENTS AND METHODS: Between December 2007 and April 2011, patients with branch-duct type IPMNs having mural nodules on EUS were examined by pancreatic duct lavage cytology by using the cell block method. Cell block sections underwent hematoxylin and eosin staining and mucin immunostainings (MUCs 1, 2, 5AC, and 6). DESIGN: Single-center, prospective study. SETTING: Academic medical center. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of cytology were assessed. The agreement between cytological and histological results for MUC was also examined. RESULTS: Cytology with this method was investigated in 44 patients. Cell block diagnosis was cancer positive (class V or IV) in 11 patients and negative (classes I, II, III, and noninformative) in 33. The sensitivity, specificity, and positive and negative predictive values of this method were 92%, 100%, 100%, and 97%, respectively. The cytological and histological results of MUCs 1, 2, 5AC, and 6 agreed in 88% (15/17), 94% (16/17), 88% (15/17), and 100% (17/17), respectively. LIMITATIONS: Single center and small number of patients. CONCLUSIONS: Pancreatic duct lavage cytology with the cell block method may be useful to differentiate between benign and malignant IPMNs preoperatively and as well as to determine their mucin type.

Reactive lymphoid hyperplasia of the liver associated with primary biliary cirrhosis.

BACKGROUND: Although reactive lymphoid hyperplasia (RLH) can be found in various organs, including the gastrointestinal tract, orbit, lung, and skin, its occurrence in the liver is rare. CASE REPORT: We report the case of a 47-year-old RLH woman who was identified with RLH of the liver during clinical follow- up of primary biliary cirrhosis. The mass, found incidentally during a medical examination, appeared on ultrasonogram as a hypoechoic mass in the 7th segment of the liver. Further analyses using composed tomography, magnetic resonance imaging, and angiography suggested malignancy, and we performed lateral segmentectomy of the liver. Histologically, the tumor was composed of lymphoid follicles with germinal centers that expressed kappa and lambda light-chain B-cell markers at equal frequency, and no IgH gene rearrangements were detected in Southern blots. Based on these results, we identified the lesion as RLH. CONCLUSIONS: We suggest that this diagnosis be taken into consideration in other cases involving a space-occupying liver mass associated with autoimmune disease.

Early detection of extrahepatic bile-duct carcinomas in the nonicteric stage by using MRCP followed by EUS.

BACKGROUND: Most extrahepatic bile-duct carcinomas are usually diagnosed when they are already in an advanced stage, which is the main reason for the poor prognosis of this tumor. OBJECTIVE: To examine the usefulness of MRCP followed by EUS in the early diagnosis of extrahepatic bile-duct carcinoma in the nonicteric stage. PATIENTS: This study included patients who were nonicteric, who had abnormal serum concentrations of alkaline phosphatase and gamma glutamyl transpeptidase, and whose common hepatic duct was more than 8 mm in diameter on abdominal US because of unknown reasons. DESIGN: A single-center, prospective study. SETTING: An academic medical center. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of MRCP followed by EUS for the early diagnosis of extrahepatic bile duct carcinoma in the nonicteric stage. RESULTS: A total of 142 patients who were nonicteric underwent prospective MRCP, and 26 of them underwent EUS. Ten patients (5 with stricture, 4 with filling defect, and 1 with no stricture or filling defect) had extrahepatic bile-duct carcinoma, including 5 patients with an incidentally diagnosed T1 stage tumor. The sensitivity and specificity of MRCP followed by EUS were 90% and 98%, respectively. LIMITATIONS: A single center and small number of patients. CONCLUSIONS: MRCP followed by EUS was highly sensitive and specific for the early diagnosis of extrahepatic bile-duct carcinoma in the nonicteric stage, including T1 stage tumors. Filling defects, as well as stenosis in the bile duct, are important MRCP findings of T1 stage carcinoma.

Pancreatic-duct-lavage cytology in candidates for surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas: should the International Consensus Guidelines be revised?

BACKGROUND: The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. OBJECTIVE: To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. PATIENTS: Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. DESIGN: Single-center retrospective study. SETTING: Academic medical center. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. RESULTS: More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. LIMITATIONS: Single-center and small number of patients. CONCLUSIONS: Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.

Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography.

AIM: To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. METHODS: Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. RESULTS: The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (kappa statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. CONCLUSION: Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

Double-balloon endoscopy for treatment of long-term abdominal discomfort due to small bowel penetration by an eel bone.

BACKGROUND: Penetration of the GI tract by a fish bone was treated by laparotomy. DBE is a useful procedure for removal of a foreign body from the small bowel. CASE REPORT: A 33-year-old male presented with bothersome postprandial fullness. He was diagnosed previously with functional dyspepsia, and had been treated with medication for 8 months with no success. During antegrade DBE, which was performed to rule out of small intestinal abnormalities, an eel bone found stuck in the jejunum was grasped with forceps and pulled out. Following removal of the bone, the patient's postprandial fullness ameliorated dramatically. CONCLUSIONS: This is the first report of DBE-based diagnosis and treatment of a small bowel penetration by a fish bone.

Impact of MUC1 Expression on the Progression of Intraductal Papillary Mucinous Neoplasm With Worrisome Features During Follow-up.

OBJECTIVES: The aim of this study was to investigate whether MUC1 expression is associated with progression of intraductal papillary mucinous neoplasms with worrisome features during follow-up. METHODS: Fifteen patients positive for MUC1 and negative for MUC2 (MUC1 group) and 16 patients negative for MUC1 and MUC2 (control group) were followed up and examined for changes in diameters of the main and ectatic branches of pancreatic ducts, enlargement of mural nodules, and appearance of a solid mass, by imaging studies. All of them presented worrisome features, and none had "high-risk stigmata." RESULTS: The sizes of the main and ectatic branches of pancreatic ducts increased in 8 (53.3%) and 8 (53.3%) patients, respectively, of the MUC1 group and in 1 (6.3%) and 1 (6.3%) patients, respectively, of the control group (P = 0.0059 and 0.0059, respectively). A solid mass developed in 6 patients (33.3%) of the MUC1 group but in none of the control group patients (P = 0.0373). CONCLUSIONS: Positive MUC1 expression in cell block cytology specimens may be associated with progressive dilation of the main and ectatic branches of pancreatic ducts and appearance of a solid mass in patients with intraductal papillary mucinous neoplasm with worrisome features during follow-up.

A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction: A hint for early diagnosis of gallbladder carcinoma.

A 62-year-old man with progressive thickening of the gallbladder wall visited our outpatient clinic. The biliary amylase level in the common bile duct was 19,900 IU/L and that of the gallbladder was 127,000 IU/L, although endoscopic retrograde cholangiopancreatography revealed no pancreaticobiliary maljunction. Histology demonstrated a moderately differentiated adenocarcinoma of the gallbladder. Pancreatobiliary reflux and associated gallbladder carcinoma were confirmed in the present case, in the absence of a pancreaticobiliary maljunction. Earlier detection of the pancreatobiliary reflux and progressive thickening of the gallbladder wall might have led to an earlier resection of the gallbladder and improved this patient's poor prognosis.

Gallbladder carcinoma associated with pancreatobiliary reflux.

AIM: To detect the patients with and without pancreaticobiliary maljunction who had pancreatobiliary reflux with extremely high biliary amylase levels. METHODS: Ninety-six patients, who had diffuse thickness (>3 mm) of the gallbladder wall and were suspected of having a pancreaticobiliary maljunction on ultrasonography, were prospectively subjected to endoscopic retrograde cholangiopancreatography, and bile in the common bile duct was sampled. Among them, patients, who had extremely high biliary amylase levels (>10000 IU/L), underwent cholecystectomy, and the clinicopathological findings of those patients with and without pancreaticobiliary maljunction were examined. RESULTS: Seventeen patients had biliary amylase levels in the common bile duct above 10000 IU/L, including 11 with pancreaticobiliary maljunction and 6 without pancreaticobiliary maljunction. The occurrence of gallbladder carcinoma was 45.5% (5/11) in patients with pancreaticobiliary maljunction, and 50% (3/6) in those without pancreaticobiliary maljunction. CONCLUSION: Pancreatobiliary reflux with extremely high biliary amylase levels and associated gallbladder carcinoma could be identified in patients with and without pancreaticobiliary maljunction, and those patients might be detected by ultrasonography and bile sampling.

Safety of immediate endoscopic sphincterotomy in acute suppurative cholangitis caused by choledocholithiasis.

AIM: To examine the safety of immediate endoscopic sphincterotomy (EST) in patients with acute suppurative cholangitis (ASC) caused by choledocholithiasis, as compared with elective EST. METHODS: Patients with ASC due to choledocholithiasis were allocated to two groups: Those who underwent EST immediately and those who underwent EBD followed by EST 1 wk later because they were under anticoagulant therapy, had a coagulopathy (international normalized ratio > 1.3, partial thromboplastin time greater than twice that of control), or had a platelet count < 50000 × 10(3)/µL. One of four trainees [200-400 cases of endoscopic retrograde cholangiopancreatography (ERCP)] supervised by a specialist (> 10000 cases of ERCP) performed the procedures. The success and complication rates associated with EST in each group were examined. RESULTS: Of the 87 patients with ASC, 59 were in the immediate EST group and 28 in the elective EST group. EST was successful in all patients in both groups. There were no complications associated with EST in either group of patients, although white blood cell count, C-reactive protein, total bilirubin, and serum concentrations of liver enzymes just before EST were significantly higher in the immediate EST group than in the elective EST group. CONCLUSION: Immediate EST can be as safe as elective EST for patients with ASC associated with choledocholithiasis provided they are not under anticoagulant therapy, or do not have a coagulopathy or a platelet count < 50000 × 10(3)/µL. Moreover, the procedure was safely performed by a trainee under the supervision of an experienced specialist.

Prior minimal endoscopic sphincterotomy to prevent pancreatitis related to endoscopic balloon sphincteroplasty.

AIM: To investigate the efficacy of prior minimal endoscopic sphincterotomy (EST) to prevent pancreatitis related to endoscopic balloon sphincteroplasty (EBS). METHODS: After bile duct access was gained and cholangiogram confirmed the presence of stones < 8 mm in the common bile duct at endoscopic retrograde cholangiography, patients were subjected to minimal EST (up to one-third of the size the papilla) plus 8 mm EBS (EST-EBS group). The incidence of pancreatitis and the difference in serum amylase level after the procedure were examined and compared with those associated with 8-mm EBS alone in 32 patients of historical control (control group). RESULTS: One hundred and five patients were included in the EST-EBS group, and complete stone removal was accomplished in all of them. The difference in serum amylase level after the procedure was - 25.0 (217.9) IU/L in the EST-EBS group and this value was significantly lower than the 365.5 (576.3) IU/L observed in the control group (P < 0.001). The incidence of post-procedure pancreatitis was 0% (0/105) in the EST-EBS group and 15.6% (5/32) in the control group (P < 0.001). CONCLUSION: Prior minimal EST might be useful to prevent the elevation of serum amylase level and the occurrence of pancreatitis related to EBS.

Severe dysplasia of the gallbladder associated with occult pancreatobiliary reflux.

Pancreatobiliary reflux usually occurs in patients with pancreaticobiliary maljunction and can be associated with the occurrence of gallbladder carcinoma. We present the case of a patient with pancreatobiliary reflux despite having a normal pancreatobiliary junction (occult pancreatobiliary reflux; OPBR), in whom the resected gallbladder presented severe dysplasia. The patient, a 61-year-old woman, showed thickness of the gallbladder wall, detected by ultrasonography and computed temography (CT). Her biliary amylase level in the common bile duct was 103,000 IU/l, and in the gallbladder it was 153,500 IU/l, although endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction. Immunohistochemical staining showed many p53-positive nuclei in the dysplastic lesion, and about 50% of the dysplastic cells exhibited diffuse nuclear staining for Ki-67. In the present patient, early diagnosis of occult pancreatobiliary reflux led to early detection of a precancerous lesion of the gallbladder mucosa.

[Occult pancreatobiliary reflux and gallbladder carcinoma].

A total of 108 patients with a normal pancreaticobiliary junction who had gallbladder wall thickness as shown by ultrasonography or computed tomography underwent secretin injection magnetic resonance cholangiopancreatography. Based on the changes in the diameter of the biliary system after secretin injection, patients were categorized into the intensified group (n = 19) or the non-intensified group (n = 89). The mean (+/- SD) biliary amylase level in the bile duct was 41674 (+/- 59779) IU/L in the intensified group, which was significantly higher than that in the non-intensified group (210 (+/- 418)) IU/L (p < 0.0001). There were four patients with carcinoma of the gallbladder in the intensified group and their biliary amylase level in the bile duct was 90783 (+/- 82528) IU/L. Pancreatobiliary reflux similar to that seen in patients with pancreaticobiliary maljunction can occur in persons with a normal pancreaticobiliary junction and this may be associated with carcinoma of the gallbladder. Secretin injection magnetic resonance cholangiopancreatography proved useful to identify such persons.

Acute pancreatitis in children and adolescents.

In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable.

Efficacy of low-fat diet against dyspepsia associated with nonalcoholic mild pancreatic disease diagnosed using the Rosemont criteria.

OBJECTIVES: The objective of this study was to examine the efficacy of low-fat diet against dyspepsia in patients who had endosonographic evidence of nonalcoholic mild pancreatic disease. METHODS: Patients with unknown cause of upper abdominal pain suggesting pancreatic disease without a history of alcohol consumption were prescribed a low-fat diet (<20 g of fat/d) for 4 weeks. Based on endoscopic ultrasonographic findings and the Rosemont criteria, the patients were distributed into those with 5 or more minor features of chronic pancreatitis (suggestive group), those with 3 or 4 (indeterminate group), and those with 2 or less (control group). Patients with major features were excluded. Symptom severity was recorded before and after the diet therapy using a 10-cm visual analog scale. Improvement of symptoms was compared among the 3 groups. RESULTS: Of 45 patients, 14 were in the suggestive group, 18 were in the indeterminate group, and 13 served as controls. Improvement of visual analog scale score was significantly greater in the suggestive group than in the indeterminate group (P < 0.001) and the control group (P < 0.001). CONCLUSIONS: A low-fat diet may be effective in patients with dyspepsia associated with endosonographic evidence of mild pancreatic disease, who do not habitually drink alcohol.

Identification of cerebral response to balloon distention of the bile duct.

AIM: To identify the brain loci that process human biliary sensation. METHODS: In 6 patients (age range: 42-74 years; 4 men), who underwent percutaneous transhepatic biliary drainage (PTBD), the distal biliary tract was stimulated by repeatedly inflating the balloon of the PTBD catheter so that it reached volumes that produced a definite painless sensation. The functional magnetic resonance imaging (fMRI) of the cortical response to biliary sensation was examined. RESULTS: Biliary balloon stimulation elicited activation of the insular cortex, prefrontal cortex, and somatosensory cortex (P < 0.001). CONCLUSION: Biliary balloon stimulation evoked a cerebral cortical response detectable by fMRI.

Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease.

BACKGROUND: The aim of the present study was to examine the potential efficacy of camostat mesilate, a protease inhibitor, against dyspepsia associated with non-alcoholic mild pancreatic disease. METHODS: Patients with upper abdominal pain suggesting pancreatic disease (persistent over hours, pain aggravated by ingestion of food, epigastric pain radiating to the back), without a history of alcohol consumption and who exhibited no abnormalities regarding serum amylase and lipase, ultrasonography, CT and upper gastrointestinal endoscopy, were prescribed 200 mg camostat mesilate three times daily for 2 weeks. The patients were subjected to endoscopic ultrasonography (EUS) while under treatment and were distributed into those who had 4 or more suggestive findings of chronic pancreatitis (suspected pancreatic disease group), 2 or 3 (equivalent group) and those with 1 or no findings (control group). Symptom severity was recorded before and after treatment using a 10-cm visual analog scale (VAS). RESULTS: Among 95 patients, 40 were in the suspected pancreatic disease group, 30 were in the equivalent group and 25 served as controls. A significant intra- and intergroup improvement of symptoms was observed not only in the suspected pancreatic disease group but also in the equivalent group. CONCLUSIONS: Camostat mesilate may serve as a therapeutic agent for patients with dyspepsia associated with mild pancreatic disease, who do not habitually drink alcohol.