Post-ERCP pancreatogastric fistula associated with an intraductal papillary-mucinous neoplasm of the pancreas – a case report and literature review

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have unique clinico-pathological characteristics and show a wide spectrum of histological types, ranging from adenomatous hyperplasia to invasive cancer. While non-invasive IPMNs show slow growth and good prognosis after resection, the outcome can become poor if they transform into invasive ductal cancers. There are three types of IPMN: main duct,, branch, and combined. The main duct and combined types are associated with higher rates of invasive cancer than the branch type [1].

A feature of IPMNs is occasional fistula formation with surrounding organs such as the duodenum, bile ducts, stomach and even the peritoneal or pleural cavity [2–10]. While such fistula formation is generally thought to be associated with invasive IPMNs, some non-invasive IPMNs also form fistulas. Thus, IPMN fistula formation raises intriguing issues concerning pathogenesis, diagnosis and patient prognosis.

We report here a rare non-invasive "borderline-malignant" IPMN that formed a pancreatogastric fistula. Fistula formation was triggered by acute pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP).

To our knowledge, the present report is only the second describing a case of IPMN associated with pancreatogastric fistulae without invasive cancer. Yago et al reported a rare case of non-invasive intraductal papillary adenocarcinoma of the pancreas that was associated with development of a pancreatogastric fistula in the absence of cancer invasion [5]. In that case, neoplastic epithelia were observed only on the surface of the fistula and gastric mucosa, while the structure of the gastric wall beside the fistula was maintained without invasive cancer. Those authors speculated that the pancreatogastric fistula developed due to high pressure in the MPD. Baek et al and Watanabe et al reported the same phenomenon in mucinous cystic tumors (MCTs) [11, 12]. The mechanism of such fistula formation without cancer spread could be explained by a combination of high pressure in the MPD and inflammatory stimulation [3, 4, 13].

In the present case, ERCP played a key role in fistula formation. To our knowledge, this is the first report to show an absence of a pancreatogastric fistula immediately prior to ERCP, and then the presence of a fistula following post-ERCP pancreatitis. Post-ERCP pancreatitis, which is reported to occur in approximately 1.8–10% of patients, should be carefully investigated in IPMN cases [14, 15].

We emphasize here that development of an IPMN-associated fistula does not necessarily represent underlying invasive cancer. Fistula formation can result in an incorrect preoperative diagnosis of invasive cancer and lead to the undertaking of unnecessary surgical procedures. Although the lesion in the present case was a non-invasive tumor, surgery was appropriate given the indications of invasive cancer. While non-invasive IPMNs have a good prognosis, there remains the possibility of dissemination by tumor penetration. When treating IPMNs associated with fistula, the extent of resection should depend on the extent of cancer invasion. To avoid dissemination, the fistula should be removed independent to cancer invasion. The extent of resection of affected organs should be individually determined based on the results of preoperative images and precise intraoperative histological examinations.

The present case highlights that a pancreatogastric fistula can develop in the absence of invasive cancer. Further data regarding IPMN-associated fistulae are necessary in order to clarify the pathogenesis, diagnosis, appropriate surgical intervention and prognosis for this disorder.