Pyeloduodenal fistula complicating neoadjuvant chemotherapy in a patient diagnosed with muscle invasive bladder cancer

Abstract

A 72-year old male presented with muscle invasive bladder cancer was counseled on the standard of care neoadjuvant chemotherapy and he started treatment. He then presented with anemia, blood in the stool and gas in the right renal pelvis and was diagnosed with Pyeloduodenal fistula. The fistula was treated with clipping by gastroenterology and the bladder tumor treated with robotic partial cystectomy.

Introduction

Fistulae between the gastrointestinal tract and the urinary system most commonly occur between the sigmoid colon and the urinary bladder after an episode of diverticulitis, but very few cases of Pyeloduodenal fistula (PDF) are reported in the literature. PDF account are rare and generally associated with chronic kidney disease or trauma.¹ The retrograde pyelogram is positive in 60% of the patients and in upper gastrointestinal barium study is less than 20%, which is attributable to unidirectional flow from the kidney supported by lack of amylase in the urine of patients affected by PDF.¹ New modalities are available to treated PDF.

Case presentation

This is a 72 y.o. male with multiple comorbidities including Atrial fibrillation, chronic kidney disease with an atrophic right kidney due to childhood ureteropelvic junction obstruction, coronary artery disease (stent x 5), diabetes, hypothyroidism, obstructive sleep apnea, morbid obesity, and high grade papillary urothelial carcinoma with muscularis propria invasion and lymphovascular invasion diagnosed in an outside hospital. He was referred to Henry Ford Urology late 2018 and discussion was done with the patient about neoadjuvant chemotherapy with partial cystectomy. He underwent repeat transurethral resection of the bladder which showed high grade urothelial carcinoma with focal micropapillary/plasmacytoid features and muscle invasion. He then received 3 cycles of gemcitabine/cisplatin neoadjuvant chemotherapy, which was then discontinued due to severe fatigue and anemia. Shortly after the family called because he was dizzy and were asked to take him to the nearest hospital. There the patient was found to be severely anemic, having blood in his stool and computerized tomography imaging of the abdomen showed air in the collecting system of the right kidney (Fig. 1). It was suspected that he is suffering from pyelonephritis and sepsis caused by gas forming organisms and empiric antibiotics treatment started. However, repeat imaging during placement of nephrostomy tubes showed flow of contrast from the duodenum to the pelvis of the right kidney (Fig. 2) and a diagnosis of PDF was made. Such flow of contrast from the duodenum to the kidney is not usual with PDF, but the fact that his right kidney was atrophic may have reversed the commonly seen unidirectional from the kidney to the duodenum.

Fig. 1.

CT showing air in the collecting system of an atrophic right kidney (Arrow) in a patient who developed pyeloduodenal fistula after receiving neoadjuvant chemotherapy for bladder cancer.

Fig. 2.

Antegrade pyelogram showing contrast leaking from the right kidney into the duodenum (Arrow) in a patient who developed pyeloduodenal fistula after receiving neoadjuvant chemotherapy for bladder cancer.

To better treat the patients PDF, he was transferred to our main hospital and gastroenterology were consulted. Their team then proceeded with upper gastrointestinal tract endoscopy which showed patchy moderately erythematous gastropathy in the stomach and biopsies were taken with cold forceps for Helicobacter pylori testing. Moving into the duodenum, the team found 2–3 mm fistula in the second portion of in the bed of a crescent-shaped cratered ulcer roughly 15 mm × 6 mm. Contrast fluid (from recent pyelogram) was visualized exiting the opening. To repair the PDF defect, argon plasma at 25 W on 0.8L/min setting was used to coagulate the mucosa in and around the fistula and assist in eventual fistula closure. Attempts at tissue approximation with endoclips failed due to the central fibrosis and the marginal congestion. The tissue edges were therefore clipped circumferentially using 4 Duraclips. An endoloop was then placed around the clips to successfully close the tissue around the fistula using the “Tulip Bundle" method of closure (Fig. 3). On repeat inspection no further contrast fluid was noted to be exiting the region of the fistula. The patient recovered from the procedure and proceeded to be treated with robotic assisted partial cystectomy for his bladder cancer.

Fig. 3.

Endoscopic view of the fistula before (figure 3a) and after (figure 3b) clipping (arrow) in a patient who developed pyeloduodenal fistula after receiving neoadjuvant chemotherapy for bladder cancer.

Discussion

Chemotherapy-induced gastrointestinal side effects include a wide array of discomforting symptoms among 50%–80% of patients with cancer.² Direct or indirect reactive oxygen species generation is one of the mechanisms of action behind many chemotherapeutic drugs and used in cancer treatment to induce neoplastic cell death. Increased cellular oxidative stress, characterized by a higher concentration of reactive oxygen species, favors the formation of toxic compounds leading to cell necrosis and death in both the tumor and normal health tissue like the lining of the gastrointestinal tract, which in turn cause epithelial ulcers.³ These toxic side effects of cancer treatment are not limited to chemotherapeutic agents, and gastrointestinal side effects are commonly reported with immune check point inhibitors, the leading agents in treating many patients with bladder cancer. In fact, a recent study from a group at MD Anderson cancer center reported that, in patients treated with immune check point inhibitors, histological signs of inflammation of the stomach were evident in 83% of patients, and inflammation of the duodenum in 38%. The authors also reported that the rates of ulceration were similar in the cohorts with and without other risk factors for gastritis.⁴ Our case report highlights an extreme case of gastrointestinal ulceration due to chemotherapy that, with the presence of atrophic kidney tissue with limited healing capacity and reduced thickness, lead to the development of a PDF. Fortunately, the availability of advanced endoscopic techniques for managing diseases of the gastrointestinal tract has enabled us to treat this patient's PFD in a timely manner to allow him to proceed with the definitive treatment of his bladder cancer.