Pancreatico-gastric fistula arising from IPMN associated with ductal adenocarcinoma of the pancreas: a case report and a literature review

Introduction

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are characterized by cystic tumors with papillary epithelial cells that produce excessive amounts of mucus (1, 2). Usually, IPMN exhibits different degrees of dysplasia (1, 3). There are three types of IPMNs, i.e., main duct, branch duct, and mixed (1). Histologically, IPMNs are subdivided into four groups, i.e., IPMN with low-grade dysplasia (LGD), IPMN with intermediate-grade dysplasia, IPMN with high-grade dysplasia (HGD), and IPMN with an associated invasive carcinoma (4). Fistulation of IPMN of the pancreas into adjacent organs has been previously reported with incidence rates ranging from 1.9% to 6.6% (3). It may involve several adjacent organs, most frequently the duodenum, but sometimes, it may even involve several organs at the same (5). Here, we report a case of a pancreatico-gastric fistula as a complication of IPMN associated with ductal adenocarcinoma of the pancreas.

Case presentation

A 69-year-old female suffering from chronic pancreatitis of unknown etiology since the year 2018 experienced sudden weight loss, diarrhea, and abdominal pain. Her medical history includes diabetes mellitus, hypertension, and pancreatic insufficiency. She is also a heavy smoker. She underwent medical testing to evaluate her sudden onset of symptoms. Blood tests revealed no signs of inflammation, with normal liver functions, a normal rheumatological panel, and a normal IGG4 level. A gastroscopy showed an ulcerative lesion covered with mucus (Figure 1). CT scans revealed signs of chronic pancreatitis with calcifications. The main pancreatic duct (MPD) was dilated to 1.3 cm, with the presence of a fistula between the main pancreatic duct and the stomach (Figure 2). Magnetic resonance cholangiopancreatography (MRCP) images showed no additional findings when compared with the CT scan (Figure 3). Endoscopic ultrasound (EUS) showed a non-homogenous pancreas with diffused calcifications and the MPD with a diameter of approximately 1.3 cm (Figure 3). Multiple biopsies from the edges of the fistula via a gastroscopy yielded main-branch IPMN.

Figure 1. Gastroscopy showing a pancreatico-gastric fistula covered with mucus.

Figure 2. (A) CT scan showing the MPD dilated to 1.3 cm with the presence of a fistula between the main pancreatic duct and the stomach. (B) Endoscopic ultrasound showing a non-homogenous pancreas with diffused calcifications with a dilated MPD of 1.3 cm. MPD, main pancreatic duct.

Figure 3. MRI images showing different views and sequences of the fistulation between the MPD and the stomach. Upper row, axial T1 + gadolinium; middle row, axial T2-weighted images; lower row, coronal T2-weighted images. MPD, main pancreatic duct.

Since both chronic pancreatitis and IPMN are considered risk factors for pancreatic malignancy, and also considering the high rate of malignancy due to main duct IPMN (MD-IPMN), a total pancreatectomy was proposed after a multidisciplinary discussion. An en bloc total pancreatectomy with wedge resection of the stomach including the fistula, splenectomy, and Roux-en-Y choledochojejunostomy and gastrojejunostomy were performed (Figure 4A). During the operation, there were no signs of peritoneal metastasis, and the surgery was uneventful. The postoperative course was complicated with bleeding from the stapler line of the gastric wedge resection that was treated with adrenaline injections via a gastroscopy. The neoplasm involved the head, body, and tail of the pancreas with a fistulation between the stomach and the MPD (Figure 4B). Pathological results revealed (1) a ductal adenocarcinoma of the pancreas that is G2 moderately differentiated and (2) IPMN with an associated invasive carcinoma. All margins were tumor-free, with no lymphovascular invasion (0/30) (pT3 pN0) (Figures 4C,D). The patient was discharged 2 weeks after the procedure. During a follow-up visit 10 days later, the physical examination was normal. The patient was referred to our oncology department and was scheduled for chemotherapy (the FOLFIRINOX regimen). No further complications were noted.

Figure 4. (A) An en bloc total pancreatectomy with wedge resection from the stomach including the fistula and splenectomy. (B) Gross sectional specimen showing a neoplasm involving the head, body, and tail of the pancreas and also showing the fistulation between the stomach and the main pancreatic duct (MPD). (C,D) Microscopic pathological pictures showing (1) ductal adenocarcinoma of the pancreas and intestinal-type morphology and (2) intraductal papillary mucinous neoplasm with an associated invasive carcinoma.

Discussion

IPMN accounts for approximately 5% of the majority of cystic pancreatic lesions and is predominant in older male patients (3). In 1982, Ohashi was the first one to report on IPMN (6). Of the patients, 33% are symptomatic and present with non-specific symptoms including recurrent pancreatitis, diabetes, weight loss, and steatorrhea (7). Although IPMN and invasive ductal adenocarcinoma originate from the ductal cells of the pancreas, they possess different features. IPMN is characterized by excessive secretion of mucin and slow and expansive growth associated with a low malignancy potential for metastasis (8).

Several radiological imaging methods have been reported in diagnosing intraductal papillary mucinous neoplasm. Those methods include CT (a pancreatic protocol), MRI/MRCP, EUS, contrast-enhanced EUS (CE-EUS), and needle-based confocal laser endomicroscopy. To increase the diagnostic yield of IPMN, a biopsy via an endoscopic ultrasound–guided through-the-needle biopsy has been helpful in certain cases (9). Studies proved that CE-EUS, when conducted with a dedicated harmonic mode, presented an optimal sensitivity, high specificity, and positive predictive value through its ability to provide information on tissue micro vascularization by differentiating between enhanced mural nodules and other non-enhanced solid components (10).

The Fukuoka and Sendai consensus guidelines demonstrate the risk factors for high-grade dysplasia or malignancy transformation of IPMN. The Fukuoka consensus guidelines provided higher positive and negative values to predict high-risk IPMN than those provided by the Sendai consensus guidelines, i.e., 88% vs. 67% and 92.5% vs. 88%, respectively (11). According to the modified Fukuoka consensus guidelines, enhanced mural nodules, MPD ≥10 mm, and jaundice were classified as high-risk stigmata features (12). On the other hand, MPD dilation between 5 and 9.9 mm, cystic growth rate ≥5 mm/year, increased level of serum CA 19-9 (>37 U/mL), symptoms, enhanced mural nodules (<5 mm), cyst diameter ≥40 mm, and finally, adjacent lymphadenopathy were classified as worrisome features (12).

Whether benign or malignant, IPMN has complication potentials. Fistulation to adjacent organs occurred in 6.6% of IPMN cases (3). The duodenum (most common), common bile duct, stomach, and spleen (rarest) are the organs commonly involved in IPMN fistulation (3). Given the MRI, CT, and EUS findings, our case had MD-IPMN with a pancreatico-gastric fistula.

In the last three decades, several reports of pancreatic IPMN fistulation to adjacent organs have been reported in the literature (Table 1). Of the 27 cases reviewed (Table 1), the majority had adenomas (30%) and adenocarcinomas (30%). Only 10% of the patients had IPMN, of which 4% had borderline carcinoma. In 30% of the cases, the pathology was not mentioned. With regard to surgical management, 18% of the patients underwent pancreatoduodenectomy. While 15% had total pancreatectomy together with resection of the fistulated adjacent organs, only 4% underwent distal pancreatectomy together with resection of the fistulated adjacent organs. Only one patient had conservative treatment, and one died before surgical intervention. It is noteworthy to mention that in 44% of the cases reported, surgical management was not described.

Table 1. Previously reported pancreatic intraductal papillary mucinous neoplasms with penetration to adjacent organs.

Pathologically, MD-IPMN has a substantial potential for progression into an aggressive invasive carcinoma (7). Two factors have been considered for the pathogenesis of fistula formation in IPMN, i.e., invasive penetration of cancer cells and mechanical penetration caused by elevated pressure in the mucus-filled pancreatic duct (8, 32). The first mechanism is seen in malignant tumors, while the second one is mostly seen in benign tumors; nevertheless, a large malignant IPMN would mechanically fistulate into adjacent organs by the effect of direct contact and high pressure on the surrounding organs. In our case, we point out that invasive penetration of the cancerous tumor contributed to the fistula formation.

Conclusion

In this paper, we reported a main duct IPMN that has differentiated into adenocarcinoma and, in the process, fistulated the stomach. In the treatment of IPMN with fistulation to adjacent organs, en bloc resection of the IPMN together with the fistula should be done to avoid possible malignant dissemination. Typically, the extent of resection depends on the extent of cancer invasion. In addition, the main duct IPMN should be considered for surgical resection because of its high risk for malignant transformation.

Data availability statement

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.

Ethics statement

Written informed consent was obtained from the patient for the publication of this case report and accompanying images.

Author contributions

MA wrote the paper. YM and GO revised the manuscript critically and provided academic guidance. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

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References

1. Jabłońska B, Szmigiel P, Mrowiec S. Pancreatic intraductal papillary mucinous neoplasms: current diagnosis and management. World J Gastrointest Oncol. (2021) 13(12):1880. doi: 10.4251/wjgo.v13.i12.1880

CrossRef Full Text | Google Scholar

2. Jabłońska B. Pancreatic cysts: etiology, diagnosis and management. Cent Eur J Med. (2014) 9(1):92–107. doi: 10.2478/s11536-013-0244-8

CrossRef Full Text | Google Scholar

3. Aliyev KV, Amr B. Pancreatico-gastric fistula: a rare complication of intraductal papillary mucinous neoplasm. J Pancreas. (2017) 18(4):362–4.

Google Scholar

4. Komo T, Oishi K, Kohashi T, Hihara J, Kanou M, Nakashima A, et al. Pancreatobiliary fistula associated with intraductal papillary mucinous carcinoma accompanying obstructive jaundice: a case report. Int J Surg Case Rep. (2018) 48:126–30. doi: 10.1016/j.ijscr.2018.05.019

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Maubert A, Vanbiervliet G, Benizri EI. Pancreatico-gastric fistula complicating an intraductal papillary mucinous neoplasm. J Visc Surg. (2017) 154(2):137–8. doi: 10.1016/j.jviscsurg.2016.11.006

PubMed Abstract | CrossRef Full Text | Google Scholar

6. Ohashi K. Four cases of “mucin-producing” cancer of the pancreas on specific findings of the papilla of Vater. Prog Dig Endosc. (1982) 20:348–52.