Keywords
acetylcysteine - cholangitis - IPMN - chronic pancreatitis
Introduction
Intraductal papillary mucinous neoplasms (IPMNs) are papillary neoplasms within the
main pancreatic duct showing mucin hypersecretion, leading to dilatation of the pancreatic
duct. They are uncommon pancreatic neoplasms with malignant potential. We report a
case of chronic pancreatitis in a patient in whom main duct IPMN was detected on pancreatoscopy
and he was successfully managed by incorporating preoperative intrabiliary acetylcysteine
infusion.
Case Report
A 50-year-old male, who had been diagnosed with chronic pancreatitis since 5 years
and was on pancreatic enzymes replacement therapy, presented to us with abdominal
pain, decreased appetite, and jaundice. Laboratory investigations showed a neutrophilic
predominant leukocytosis and cholestatic jaundice (total bilirubin of 23.5 mg/dL)
with a direct fraction of 16 mg/dL, AST (aspartate aminotransferase) of 351 IU/mL,
ALT (alanine aminotransferase) of 276.2 IU/mL, and ALP (alkaline phosphatase) of 340
IU/ mL. MDCT (multi detector computed tomography) abdomen showed a multicystic mass
involving the head and uncinate process and communicating with pancreatic duct and
measuring 4.6 cm × 5.3 cm × 6 cm. It showed 180° encasement of portal vein. Atrophy
of pancreatic body and tail with dilated pancreatic duct and multiple pancreatic ductal
calculi in the distal body and tail region were noted. Marked biliary dilatation was
also noted. Duodenoscopy ([Fig. 1]) showed a patulous ampulla with mucus plug and mucous extruding from orifice (“fish
mouth” appearance). Pancreatogram showed a dilated pancreatic duct and pancreatoscopy
([Fig. 2]) performed using Spy glass system (Boston Scientific, Spencer, IN, USA), showed
a dilated duct with calculi and large quantities of mucinous material and papillary
projections, suggestive of IPMN (“fish egg” appearance). As his cholangiogram showed
a markedly dilated CBD (common bile duct), and possibility of stent migration was
high, we placed a 7 Fr 7 cm double pigtail plastic stent (Cook) in the CBD. As he
continued to have worsening jaundice and fever spikes, a second ERCP (endoscopic retrograde
cholangiopancreatography) was done after 2 days. Blocked stent in situ was noted which
was removed using snare. Balloon sweeps after a 5 to 7 mm sphincterotomy revealed
copious amounts of mucinous material. A 10 Fr 7 cm double pigtail stent (COOK) was
deployed into the CBD in the hope that this would ensure adequate biliary drainage.
As he continued to have cholangitis, a third ERCP was done after 5 days from the second
ERCP. Mucus plug was noted at ampulla and previous stent appeared to be plugged with
mucus. A 10 Fr nasobiliary drain (COOK) placed in the CBD and N-acetylcysteine (NAC)
was instilled (4,000 mg NAC in 500 mL NS); 100 mL of NAC was flushed every 3 hours.
He was also continued on broad-spectrum IV (intra venous) antibiotics. With these
measures we noticed a steady decline in the hyperbilirubinemia and our patient reported
clinical improvement of symptoms. However, his symptoms were not completely resolved.
He underwent open cholecystectomy with placement of a T-tube through which infusion
of acetylcysteine was continued while he was in the hospital for an earlier resolution
before definitive surgery. Subsequently, he was discharged and continued on nutritional
rehabilitation. On follow-up after 1 week, his liver function tests had normalized.
He was subsequently taken up for Whipple’s resection. The resected specimen showed
intraductal papillary mucinous neoplasm of pancreas (intestinal type) with low- and
high-grade dysplasia and microinvasion, against a background of severe chronic pancreatitis.
He was asymptomatic at follow-up of over 1 year.
Fig. 1 “Fish mouth” appearance of ampulla on duodenoscopy.
Fig. 2 “Fish egg” appearance on pancreatoscopy using Spyglass system.
Discussion
World Health Organization (WHO) defines IPMNs as intraductal mucin-producing neoplasms
with tall, columnar, mucin-containing epithelium with or without papillary projections.
What differentiates IPMNs from other mucinous cystic neoplasms is the lack of the
ovarian stroma. Based on histology, IPMNs are classified into benign (adenoma), borderline,
or malignant (carcinoma in situ or invasive). Clinically, patients may present with
history of abdominal pain, nausea, steatorrhea, and weight loss, and may mimic chronic
pancreatitis. Rarely may they coexist together in same patient as in our case. Surgical
resection is the preferred treatment in IPMN with high-grade dysplasia or invasive
malignancy. Prognosis after resection is good with 5-year disease-specific survival
of at least 75%. A consensus guideline for the management of IPMN was established
in 2006.[1]
Radiological cross-sectional imaging (magnetic 3 imaging [MRI] with magnetic resonance
cholangiopancreatography [MRCP] or computed tomography [CT]) are useful for diagnosis
and preoperative staging. Additional evaluation with endoscopic ultrasound (EUS) with
fine-needle aspiration (FNA) may be needed to confirm a diagnosis or to assess for
malignant features. Pancreatoscopy and direct visualization of the pancreatic duct
is very sensitive for making a diagnosis, especially in the main duct type. The patulous
pancreatic orifice can be cannulated easily with a pancreatoscope during ERCP, permitting
direct visualization of the pancreatic duct. Pancreatoscopy can help determine the
extent of IPMN, especially if skip lesions are present, which may aid preoperative
staging. Features suggesting malignancy include spotty or linear red markings, “fish
egg”–like lesions, villous proliferations, and vegetative-type lesions.
The uses of acetylcysteine (NAC) in health care are manifold. Its mucolytic action
is utilized in the management of chronic obstructive pulmonary disease and idiopathic
pulmonary fibrosis.[2]
[3] It also has antioxidant and anti-inflammatory properties and is a very safe agent.
Intrabiliary use of acetylcysteine for advanced biliary IPMN has been reported in
recent case reports.[4] Acetylcysteine can be used in palliative setting as well as preoperatively (as in
our case) to decrease the tenacious mucinous secretion in IPMN where biliary drainage
alone by stenting alone proves inadequate.
Our case shows the rare occurrence of the radiological features of chronic pancreatitis
and endoscopic evidence of intraductal papillary mucinous neoplasm. Our case also
demonstrates successful use of a novel approach to reduce cholestatic jaundice in
IPMN patients by the intrabiliary instillation of NAC prior to definitive surgical
resection.
