- Case Report
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Conversion surgery for initially unresectable carcinoma of the ampulla of Vater following pathological complete response to chemotherapy: a case report
Surgical Case Reportsvolume 5, Article number: 122 (2019)
Carcinoma of the ampulla of Vater with distant metastases is regarded as unresectable. Systemic chemotherapy is basically the treatment of choice for such tumors.
A 68-year-old woman was referred to our hospital and diagnosed with carcinoma of the ampulla of Vater with lymph node and multiple liver metastases. She underwent systemic chemotherapy with a combination of gemcitabine and cisplatin. After 19 months of treatment, the primary tumor and liver metastases were difficult to detect on follow-up images. Shrinkage of the enlarged lymph nodes was also confirmed. Surgical resection was performed with curative intent after a multidisciplinary meeting. Pathological examination of the resected specimen showed no residual tumors. Systemic chemotherapy achieved a pathological complete response. The postoperative course was uneventful, and the patient remained free of recurrent disease at 10 months of follow-up.
This case shows the possibility of conversion surgery after systemic chemotherapy for carcinoma of the ampulla of Vater.
Complete surgical resection is the only potential curative treatment for carcinoma of the ampulla of Vater (AC) . Previous reports have indicated that the possibility of curative resection was 50%  and that the 5-year survival rate ranged from 33 to 66% [3,4,5,6,7]. However, tumors with distant metastasis such as liver metastasis, para-aortic lymph node metastasis, or peritoneal carcinomatosis are regarded as unresectable. Palliative chemotherapy is often administered to these patients. We herein report a case of AC with synchronous liver metastasis in which a pathological complete response (CR) was obtained by chemotherapy.
A 68-year-old woman was admitted to the hospital because of melena and epigastric pain. She had a medical history of hypertension, dyslipidemia, and psoriasis vulgaris for which she was undergoing treatment with prednisolone (1 mg/day). The patient’s serum amylase and lipase levels were elevated at 2238 IU/L and 3900 U/L, respectively. Her white blood cell count was 9700/μL, and her C-reactive protein level was 0.61 mg/dL. Tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9 were within normal limits. Upper gastrointestinal endoscopy showed an irregular ulcerative tumor located at the ampulla of Vater. Pathological examination of the tumor showed severely atypical epithelial cells arranged in sheets and vague glands. The feature suggested moderately to poorly differentiated adenocarcinoma (Fig. 1a, b). Computed tomography (CT) revealed a hypovascular tumor of 32 mm in size at the head of the pancreas. The common bile duct and pancreatic duct were dilated. In addition, two hypovascular masses were found in the liver: a 1-cm mass at segment 7 and a 2-cm mass at segment 6. The regional lymph nodes along the superior mesenteric artery (SMA) (#14d) and the right side of the common bile duct (#12b2) had swollen to 3 cm and 2 cm in size, respectively (Fig. 2a–c).
Given these findings, the patient was diagnosed with AC with lymph node and synchronous liver metastases. Because the disease was so advanced, surgical treatment was not feasible. First, she was treated for acute pancreatitis by stent placement into bile duct and pancreatic duct. Chemotherapy with gemcitabine (GEM) and cisplatin (CDDP) was then performed at dosages of 1000 mg/m2 and 25 mg/m2 weekly for 2 weeks, followed by a 1-week rest. Four months later, grade 2 bone marrow suppression occurred and was successfully managed by reducing the administered doses to 80%. After 6 months, the chemotherapy frequency was changed to biweekly administration. Because follow-up CT revealed shrinkage of the liver metastases and enlarged lymph nodes, we decided to continue the treatment. The liver metastases became difficult to identify at the 14-month CT scan. Because of grade 3 thrombocytopenia, the CDDP was reduced to 60% of the original dose and then stopped. GEM was reduced to 50% of the original dose and continued as monotherapy. Upper gastrointestinal endoscopy at 19 months from treatment initiation showed only a 0-IIa–like bulge in the papillary area, and the biopsy result was high-grade adenoma (Fig. 3a, b). Abdominal CT showed significant shrinkage of the main tumor. The liver metastases had almost vanished and were difficult to identify. The enlarged lymph nodes (#14d) had shrunk but remained present (Fig. 4a–c). However, fluorodeoxyglucose positron emission tomography/CT showed no accumulation in the primary tumor, liver metastases, or lymph nodes.
The effect of chemotherapy almost achieved CR according to the radiological and pathological findings. After a multidisciplinary meeting, the patient was considered a surgical candidate. Twenty-one months after the initial diagnosis and induction of chemotherapy, she underwent subtotal stomach-preserving pancreaticoduodenectomy with D2 lymph node dissection. Lymph node along the SMA (#14d) detected preoperatively were harvested with preserving the SMA nerve plexus. This was the choice to reduce the possibilities of serious postoperative complications. No metastatic liver tumors were detected by intraoperative sonography; therefore, liver resection was not performed. Pathological examination of the resected specimen demonstrated no residual carcinoma in the ampulla of Vater, distal bile duct, or pancreatic head. The definitive diagnosis was intestinal-type adenoma. An enlarged lymph node located around the SMA was composed of necrotic tissue and showed no signs of residual tumor cells (Fig. 5a–d).
The postoperative course was uneventful, and the patient was discharged 20 days after surgery. Adjuvant chemotherapy was not performed because the patient had already received long-term preoperative chemotherapy and had no signs of residual tumors. The patient remained free of recurrent disease at the 10-month follow-up.
AC is relatively rare, and the reported incidence is around 7% of all periampullary tumors . The frequency of adenocarcinoma is the highest among all malignant tumors, and differentiation from bile duct cancer, pancreatic cancer, and duodenal cancer infiltration is required. According to the Japanese registry of biliary tract cancer, the resectability rate of AC is 89.4% and the curative resection rate is 93.0%. The 5-year survival rate after resection is 52.8%, which is higher than that of cholangiocarcinoma (32.7%) or gallbladder cancer (41.6%). Thus, AC has a relatively good prognosis. However, patients with distant metastasis have a poor prognosis, and the 5-year survival rate is 0.0% . Chemotherapy is the first choice for advanced AC with distant metastases. According to a recent randomized phase III study from the UK (ABC-02 trial), the combination of GEM and CDDP (GC) has become the current standard for unresectable biliary tract cancer . A Japanese multicenter phase III trial also demonstrated the advantage of GC over GEM alone . In the present case, we started the GC regimen with palliative intent, not as curative treatment. However, a dramatic effect was observed for both the primary and metastatic tumors. Disappearance of the liver metastasis and benign results of the biopsy from the ampulla of Vater offered hope of curative resection.
We searched previous reports and found four case reports describing curative resection of initially unresectable AC due to distant metastases [10,11,12,13]. All reports described favorable outcomes. However, to the best of our knowledge, this is the first report of successful conversion surgery for AC following the achievement of pathological CR in the primary tumor and metastatic lesions.
Recent advances in chemotherapy have led to several cases of successful conversion surgery in patients with advanced biliary tract cancer or pancreatic cancer, as for patients with colorectal cancer [14,15,16]. However, because no comprehensive reports are available, no consensus has been reached regarding the timing of resection, its impact on the prognosis, or the need for postoperative adjuvant therapy. Because of the rarity of the disease, performing well-powered clinical trials of conversion surgery after chemotherapy in patients with AC will be much more limited. We consider that surgical options should be discussed among a multidisciplinary team, at least when dramatic effects of chemotherapy are confirmed, as in our case. Further collection of additional cases is expected.
Because the liver metastasis could not be confirmed during surgery in the present case, there was a concern that pathological CR could not be demonstrated for the liver metastasis. Postoperative adjuvant therapy was not performed because of the long-term neoadjuvant chemotherapy and pathological CR of the primary tumor and metastatic lymph nodes. We will continue close follow-up with particular attention to relapse of liver metastasis.
We have herein reported a case of conversion surgery after chemotherapy for an initially unresectable AC with synchronous multiple liver metastases. The possibility of conversion surgery may increase with the development of chemotherapies. Collection of additional successful cases and further investigation are required to evaluate the safety, feasibility, and advantages of this approach.
Availability of data and materials
Data will be made available from the corresponding author upon request.
Carcinoma of the ampulla of Vater
Gemcitabine and cisplatin
Superior mesenteric artery
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We thank Angela Morben, DVM, ELS, from Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.
This work was not funded by any educational or commercial organization.
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All procedures performed involving human participants were in accordance with the ethical standards of the Institutional Review Board of National Hospital Organization Kyushu Medical Center.
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Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.
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