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INTRODUCTION Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas –Intraductal proliferation of mucin-producing epithelial cells –Cystic dilation of the pancreatic ducts –Pathological changes : from hyperplasia to adenocarcinoma Main-duct type vs Branch-duct type The cell block method : hematoxylin and eosin (H&E) stain and mucin immunostaining (MUC) (MUC1, 2, 5AC, and 6) Mucins are high molecular weight glycoproteins, and the malignant potential of IPMNs is reported to differ depending on their mucin type characterized by the MUC.

METHODS Patients December 2007 and April 2011, outpatient clinic Branch duct type IPMNs by CT or MRI EUS Endoscopic retrograde pancreatography (ERP) Pancreatic duct lavage cytology

The type of IPMN the World Health Organization classification Surgical intervention indication –Cytology were positive –When mural nodules ≥5 mm or a pancreatic mass was detected by EUS –Progressive enlargement of the main and the ectatic branch pancreatic ducts, mural nodules, or a pancreatic mass during follow-up on CT or MRI underwent EUS

Pancreatic duct lavage cytology with the cell block method Duodenoscope (JF 240 and JF 260V; Olympus, Tokyo, Japan) Coaxial double-lumen catheter (5F; Cathex, Tokyo, Japan) H&E as well as with MUCs 1, 2, 5AC, and 6. The monoclonal antibodies –Ma695 (Novocastra, Newcastle, UK) against MUC1 –Ccp58 (Novocastra) against MUC2 –CLH2 (Novocastra) against MUC5AC –CLH5 (Novocastra, Newcastle, UK) against MUC6

Class I : completely benign and non-neoplastic epithelium showing no or slight dysplasia Class II : regenerative or neoplastic epithelium showing slight dysplasia Class III : neoplastic epithelium showing mild dysplasia corresponding to adenoma Class IV : neoplastic epithelium showing moderate dysplasia highly suggestive of adenocarcinoma Class V : unequivocally malignant epithelium corresponding to adenocarcinoma

MUC1MUC2MUC5AC Intestinal type IPMN++-Invasive mucinous carcinoma Pancreatobiliary and oncocytic IPMN +-+Invasive tubular adenocarcinoma Gastric foveolar type IPMN --+Noninvasive

Procedure induced pancreatitis –New or worsened abdominal pain –Amylase serum concentration ≥3 times the upper limit of normal at 24 hours Severity of pancreatitis (length of hospitalization) –Mild : 2 to 3 days –Moderate : 4 to 10 days –Severe pancreatitis ≥ 10 days

Statistical analysis paired t test

RESULTS Branch-duct type IPMN : 58 patients by CT, 31 patients by MRI Mural nodules on EUS : 44  ERP followed by pancreatic duct lavage cytology The patients consisted of 30 men and 14 women age 66 years, range years Clinical manifestations of those patients –Abdominal pain (n=4) –Anorexia (n=2) –Weight loss (n=3) –Diarrhea (n=1) –Deterioration caused by diabetes mellitus (n=9) –No clinical symptoms or signs(n=29)

The ectatic branch duct location –31 patients in the head and/or uncinate process –13 patients in the body and/or tail Main pancreatic duct was 3.5 ± 1.8 mm (range mm) Ectatic branch duct was 28.9 ± 7.1 mm ( mm) Size of the mural nodules was 3.9 ± 2.7 mm ( mm) on EUS.

Complication Upper abdominal pain or discomfort : 4 patients(10%) The mean maximum serum amylase level after lavage cytology was ± IU/L(range IU/L) –Before the procedure (73.3 ± 33.0 IU/L, range 31 to 238 IU/L) Serum amylase levels ≥375 IU/L : 5 patients (11.4%)

The sensitivity(92%) / specificity(100%) / positive (100% )/ negative (97% )

88% (15/17) 94% (16/17) 88% (15/17) 100% (17/17)

CONCLUSION Pancreatic duct lavage cytology with the cell block method For differentiating between benign and malignant branch-duct type IPMNs For identifying its mucin type For deciding whether surgical intervention Further studies in a larger series of patients are required to confirm the reliability of this diagnostic procedure.