Discussion:
CDF is a rare clinical entity, typically associated with chronic
inflammatory pathologies, malignancies, and trauma. (5,6). It is
well-established that chemotherapy for gastrointestinal neoplasms can be
associated with complications such as haemorrhage and perforation, and,
in some instances, fistula formation (2,5,6,7). A comprehensive review
of the literature using the terms “choledochoduodenal fistula”,
“pneumobilia”, “lymphoma”, “neoplasms” and “Non-Hodgkin’s
Lymphoma” across the databases Ovid Medline, PubMed, Scopus and Google
Scholar identified two documented cases in which chemotherapy treatment
of duodenal lymphoma and methotrexate-induced lymphoproliferative
disease led to CDF formation. However, no documented cases of CDF
arising from chemotherapy for pancreatic lymphoma were identified (2,5).
The pathogenesis of fistula formation secondary to chemotherapy is
thought to stem from the rapid regression in tumour and lymph node size,
as well tumour tissue destruction (2,5). In cases of duodenal lymphoma,
fistula development is postulated to arise from transmural invasion by
the tumour, establishing a contiguous tissue bridge between the duodenum
and CBD. As transmural invasion progresses, normal tissue is
progressively replaced by the developing tumour. With chemotherapy, the
tumour in the common wall established between the two organs becomes
necrotic and is destroyed, resulting in fistula formation. (2)
Similarly, in a patient with methotrexate-associated lymphoproliferative
disorder, the development of their fistula was thought to be a
consequence of the chemotherapy regimen of rituximab, brentuximab and
nivolumab causing rapid regression of lymph nodes adjacent to both the
duodenal wall and common bile duct, leading to CDF formation (5). In our
case, the CDF likely developed from inflammation, necrosis, and the
formation of a distal biliary stricture, following chemotherapy for
pancreatic lymphoma.
The diagnosis of CDF can be challenging due to the non-specific nature
of symptoms. In some instances, patients may present asymptomatically,
further complicating early detection. In our case, the only symptoms
reported were chronic lethargy and weight loss, with chronic LFT
derangement on biochemical investigation. The suspicion of CDF
development in this patient from his initial presentation was
understandably low given the rarity of this condition and the
non-specific clinical presentation. Suspicion of CDF was raised when
pneumobilia was identified on CT, and a formal diagnosis of CDF was
confirmed following ERCP. In a review article of CDF cases in China,
most patients presented with epigastric pain (80.91%), cholangitis
(54.26%) and fever (50.69%). In the same review, ERCP was determined
to be the most reliable diagnostic modality, with 475 of 728 cases
confirmed using this method, while ultrasound and CT were of limited
utility for CDF diagnosis (6). As such, the non-specific nature and
scarcity in documented cases of CDF, combined with the necessity for
invasive procedures such as ERCP to establish a formal diagnosis, make
clinical recognition and diagnosis very challenging.