A long-term survival case after resection of the pancreatic metastasis from lung cancer

Highlights • Significance of resection in patients with pancreatic metastasis from lung cancer.• A long-term survivor of pancreatic metastasis from lung cancer after pancreatectomy.• Consider resection if the disease is localized and the patient’s condition is good.


Introduction
The impact of surgical resection of limited metastatic tumor, such as liver or lung metastasis, has been clearly defined. However, the benefits of surgical resection in patients with pancreatic metastasis remains unclear because pancreatic metastasis is rarely resected given that most patients present with additional organ metastases [1,2]. This study reports the case of a cancer survivor who lived for more than 5 years after the resection of pancreatic metastatic tumors from lung cancer and present a literature review to discuss the significance of surgical resection in such patients. This work has been reported in line with the SCARE criteria [3].

Case presentation
A 67-year-old woman presented with a mass located in the pancreatic tail. The patient's past medical history included pneumonia and lung cancer. Six years prior to presentation, she had undergone left lower lobectomy with systematic lymphadenectomy for stage IIIA adenocarcinoma. After resection, she received adjuvant gefitinib for 7 months; however, this treatment was discontinued due to side effects. Two years after resection, the patient received radiation therapy for mediastinal lymph node metastasis and she eventually became cancer-free. Two years after radiation therapy, the patient's carcinoembryonic antigen (CEA) level was elevated at 13.5 U/mL, and computed tomography (CT) revealed a low-density mass, which measured 20 mm in diameter, in the pancreatic tail (Fig. 1A). Positron emission tomography (PET)/CT revealed a hypermetabolic mass in the pancreatic tail, with no other distant metastases (Fig. 1B). Primary pancreatic cancer or metastasis from lung cancer was suspected. The tumor was localized in the pancreas and the patient's general status was good; therefore, distal pancreatectomy and splenectomy with lymph node   dissection were performed for curative intent. The resected specimen from the pancreatic tail was a 25 × 25-mm tumor ( Fig. 2A,  B). The pathological diagnosis was metastatic lung adenocarcinoma (Fig. 2C, D), with immunohistochemical profiles (cytokeratin 7-and thyroid transcription factor 1-positive) similar to those of the resected primary lung cancer (Fig. 2E). The postoperative course was uneventful. The patient survived for 5 years and 3 months after pancreatectomy, and no evidence of recurrence was noted. However, she died of acute renal failure after acquiring pneumonia.

Discussion
The pancreas is an unusual site for metastasis. Pancreatic metastasis accounts for approximately 1%-5% of all pancreatic malignant diseases [2,[4][5][6][7]. Conversely, the most common primary tumors of pancreatic metastasis include renal cell carcinoma, followed by lung and colorectal tumors [8]. Moreover, pancreatic metastasis has been reported in up to 18% of patients with lung cancer [9,10], thus suggesting that pancreatic metastasis from lung cancer is not extremely rare. However, only few patients are qualified for resection because most patients with lung cancer present with widespread diseases in multiple organs [10]. Therefore, the importance of surgical resection in patients with pancreatic metastasis from lung cancer is inadequately evaluated in the literature.
The most common diagnostic examination for pancreatic metastasis is annual examination, which includes radiological imaging or serum tumor marker level assessment s during the treatment of lung cancer. Other patients present with obstructive jaundice and acute pancreatitis [11]. In our study, PET/CT was immediately performed when the patient presented with an elevated CEA level, which was useful for detecting metastatic lesion and evaluating surgical indication.
The differential diagnosis between primary and metastatic pancreatic tumors on the basis of CT, endoscopic retrograde cholangiopancreatography, or ultrasonography is challenging [12,13]. In our study, we could not distinguish the primary pancreatic tumor from the metastatic pancreatic tumor preoperatively. Therefore, we decided to perform curative resection at least for the primary tumor. We believe that even if patients present with pancreatic metastasis, resection can also be performed for curative intent; however, the significance of survival benefit remains uncertain.
We conducted a review of the literature, which includes Japanese studies, by searching PubMed, and identified 22 reports on aggressive surgical resection for both primary lung cancer and pancreatic metastasis. We assessed 23 cases, including the case in the present study. The following cases were observed: n = 10, histopathologically confirmed adenocarcinoma; n = 6, squamous cell carcinoma; n = 3, large-cell carcinoma; n = 2 adenosquamous carcinoma; and n = 2, small-cell carcinoma. Only 2 cases involved synchronous metastases, whereas the remaining 21 cases were metachronous. Moreover, the median interval time from pulmonary resection to pancreatic recurrence was 22 months. Patient survival for more than 5 years after metastatic pancreatic tumor resection was only reported in the study by Ida [14] and in our study. Ida reported that pancreatic metastasis was diagnosed in the patient 3 years after pneumonectomy for lung squamous cell carcinoma. This patient underwent total pancreatectomy and survived for more than 8 years without recurrence. Conversely, the patient in our study received combined therapy, which includes chemotherapy after the resection of primary tumor, radiation for lymph node metastasis, and resection of metastatic pancreatic tumor. In our literature review, no specific clinicopathological features were observed in long-term survivors.
Iida et al. [15] have reported that the mean survival time in patients with pancreatic metastasis from lung cancer without pancreatectomy is 6.3 months. Although the indication for pancreatectomy for pancreatic metastasis from lung cancer cannot be defined based on only two long-term survivors, we believe that radical treatment, including pancreatectomy, results in the marked improvement of prognosis in some cases. Further studies discussing treatment options, including surgical resection, for pancreatic metastasis from lung cancer are warranted.

Conclusion
If the disease is localized and the patient's condition is good, aggressive resection for pancreatic metastasis from lung cancer should be considered. In the present case, combined therapy, including surgical resection, resulted in long-term survival, and the patient was declared cancer-free despite repeated cancer recurrence.

Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Ethical approval
The ethical approval has been exempted by our institution because this is a case report.

Consent
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.

Author contribution
YK prepared the draft of the report and collected data. RY supervised the treatment of the patient and edited the manuscript. SW and KA assisted in preparing the manuscript. FS, HF, MY, YT and TI contributed to drafting the manuscript. All authors have read and approved the final manuscript.

Registration of research studies
Not applicable.

Provenance and peer review
Not commissioned, externally peer-reviewed

Declaration of Competing Interest
No conflict of interest.