Differential diagnosis, investigation and treatment
As a result of the examination, the patient was diagnosed with primary
GB cancer and metastasis of right lower lobe (S6) lung cancer
(adenocarcinoma, cT1N2 M0, cStage ⅢA). Endoscopic ultrasound-guided fine
needle aspiration (EUS-FNA) of lymph nodes in the hepatoduodenal
ligament revealed small-cell-type neuroendocrine carcinomas (SCNEC)
which indicated primary GB cancer with lymph node metastasis, rather
than metastases of the lung adenocarcinoma.
Prognosis of GB carcinoma with lymph node metastasis and SCNEC is quite
poor [5, 6]. The patient, an octogenarian, had performance status of
0 (CTC Version 2.0) , but he had various critical comorbid diseases such
as recurrence of lung cancer. Therefore, we first recommended
chemotherapy instead of definitive surgery. However, the standard
platinum-based regimen of SCNEC proved intolerable because of his
general status. Although there are few studies suggesting that nivolumab
is effective against neuroendocrine carcinoma and GB cancers [4, 7],
Nivolumab monotherapy (240 mg, every two weeks) was initiated. At that
time, neuron-specific enolase (NSE) was significant (35.7 ng/mL).
Outcome and follow-up
After 10 courses of nivolumab, a CT scan showed that the
GB tumor had shrunk without
remarkable lymphadenopathy in the hepatoduodenal ligament, but with
limited lymphadenopathy adjacent to the abdominal aorta (Figure 2). A
tumor marker, NSE, turned negative (12.9 ng/mL) (Figure 3). Even though
prognosis of GB carcinoma with lymph node metastases is quite poor
(median OS: 13.5 months) [8], radical resection of the tumor can
prolong survival in cases in which metastases disappear after
chemotherapy. Therefore, we decided to operate for the following
reasons: 1. We could remove the tumor completely with lymphadenectomy
next to the abdominal aorta. 2. If the tumor increased during further
nivolumab monotherapy, we would have been unable to achieve complete
resection by surgery.
Furthermore, surgery seemed likely to be tolerated by the patient
because he was almost healthy and because the surgery did not require
major hepatectomy or bile duct resection. We meticulously explained the
foregoing to the patient and his family and obtained consent for
surgery. Then, an extended cholecystectomy and lymphadenectomy around
hepatoduodenal ligament and sampling of lymph nodes proximal to the
abdominal aorta were performed. After surgery, no major adverse events
were observed, except delayed gastric emptying, Clavien dindo grade Ⅱ,
and acute gastric mucosal lesions, Clavien dindo grade IIIa.
Histopathologically, the atrophied gallbladder had a tumor in its fundus
(15x8x10 mm). (Figure 4). Upon microscopic
examination, NEC and
adenocarcinoma (in situ) components were mixed (Figure 5). Most
components of the tumor were NEC, and adenocarcinoma in situ (AIS) was
present at both ends of the NEC. Histologically, there was no metastasis
in the hepatoduodenal ligament, but there was metastasis beside the
abdominal aorta. PD-L1 28-8 IHC showed that the PD-L1 expression rate
was less than 10% (Figure 5). Histological evaluation of the
chemotherapeutic effect was Grade 0, no change (6th Ed. of General Rules
for Clinical and Pathological Studies of Cancer of the Biliary Tract).
One month after the surgery, adjuvant nivolumab monotherapy was
initiated. Three months have elapsed since the surgery, and no recurrent
lesion has been observed.