A 49-year-old man complained of left abdominal pain. He had a past medical history of duodenal ulcer and appendicitis, no smoking history, and no alcoholic history. Abdominal ultrasonography revealed a 33-mm tumor located in the pancreatic body, and he was referred to our hospital for further evaluation and treatment.
Laboratory data showed elevated tumor markers including CEA (6.0 ng/ml) and CA19-9 (72.9 U/ml). Computed tomography (CT) revealed a 54-mm hypovascular tumor in the body to tail of the pancreas (Fig. 1a). Direct tumor invasion was seen around the CeA, CHA, LGA, splenic artery (SpA), and GDA (Fig. 1b). There was no encasement around the superior mesenteric artery (SMA). No liver metastasis was found by gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). Positron emission tomography (PET)–CT showed increased metabolic activity in the pancreas (maximum standardized uptake value for the tumor was 5.7), but there were no suspicions of metastases in other organs. Endoscopic ultrasonography-guided fine-needle aspiration from the pancreas body tumor was performed, and the pathological findings revealed pancreatic adenocarcinoma.
According to the National Comprehensive Cancer Network (NCCN) guidelines version 2.2018, resectability was determined as UR-LA. We planned conversion surgery (CS) after multidisciplinary treatment, including chemotherapy and chemoradiotherapy.
First, three courses of chemotherapy were proposed. The regimen was standard (days 1, 8, and 15: injection of GEM (1000 mg/m2) and nab-PTX (125 mg/m2) every 4 weeks). Adverse events were general fatigue and Grade 3 neutropenia, so chemotherapy was omitted twice (thus, 7 cycles were given). After chemotherapy, CT imaging showed tumor size reduction to 40 mm, indicating stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Next, we performed radiotherapy together with S-1 administration. Radiotherapy consisted of 2 Gy per fraction given 5 days per week for a total of 50 Gy. S-1 was administrated orally at 80 mg/m2/day for 28 consecutive days. This treatment was not accompanied by any significant adverse events.
After chemoradiotherapy, tumor markers decreased to within the normal range (CEA: 2.6 ng/ml and CA19-9: 15.1 U/ml). CT imaging showed tumor size reduction to 31 mm, indicating partial response (PR) according to RECIST, but soft tissue density around CeA, CHA, LGA, SpA and GDA was still detected (Fig. 2). PET–CT imaging showed no suspicious distant metastases, and the maximum standardized uptake value for the pancreas body tumor was 2.2.
By angiography, we found that the left hepatic artery (LHA) branched off from the LGA, and the right hepatic artery (RHA) from the PHA. Proximal balloon occlusion of the CeA showed that RHA blood flow from the SMA was maintained. However, LHA blood flow could not be detected since the balloon blocked blood flow to the LGA, and a definite arterial connection between the right and left liver could not be observed.
In the preoperative evaluation, we considered that R0 status could be achieved by DP-CAR with arterial reconstruction, even if tumor invasion to the GDA or PHA had occurred. Surgery was then carried out 8 months after the initial start of treatment.
Intraoperative findings revealed that the tumor was located mainly in the pancreas body, but had also invaded into the arteries around the pancreas, including the CeA, CHA, LGA, SpA, and GDA (Fig. 3a). The GDA, CHA, and LGA could not be preserved on surgery. Firstly, the GDA was resected proximal to the branch of the right gastroepiploic artery (RGEA). Pancreatic transection was performed using a scalpel, and the pancreatic stump was closed by suturing. The root of the right gastric artery (RGA) was also involved in the tumor, and the PHA was divided on the hepatic side from the RGA. This meant that the PHA was practically the same as RHA since the replaced LHA arose from the LGA. After RHA resection, the backflow from the RHA stump appeared weak with only a small amount of blood flow, though we expected RHA blood flow from intrahepatic communicating arcades. Ultrasonography after RHA resection showed little change in the right hepatic blood flow before and after the LGA was clamped, and the decreased communication between the left and right hepatic arteries was a concern. We decided that it was necessary to reconstruct both the LGA and RHA to ensure hepatic and gastric blood flow because gastric blood flow would be supplied by the RGEA alone, and intraarterial communication between the left and right hepatic arteries was a concern. Thus, we performed a bypass procedure between the abdominal aorta below the renal artery with the PHA using the right great saphenous vein grafting (SVG). After anastomosis between the aorta and PHA, a Y-shaped bypass was constructed and anastomosed with the LGA (Fig. 3b–e).
Intraoperative frozen section pathology findings confirmed tumor-free margins of the CeA, GDA and pancreas stump. Based on these findings, we performed DP-CAR with arterial reconstruction using SVG to achieve R0 resection. The total duration of surgery was 754 min, and blood loss was 660 ml.
Postoperative complications included decreased appetite, although no clinically significant pancreatic fistula was identified. Postoperative gastrointestinal endoscopy showed erythematous mucosal surface and stenosis from the pyloric region to the duodenal bulb. These complications were treated with drug therapy (Clavien–Dindo classification IIIa). Postoperative CT imaging clearly showed blood flow through the aorta–LGA bypass, but the aorta–PHA bypass did not (Fig. 4). The increase in liver enzymes was mild (max AST: 250 IU/l, ALT: 203 IU/l), and liver function was preserved. Thus, no antiplatelet medication or heparin was administrated. The patient was discharged 73 days after surgery.
Histopathological findings showed a 52-mm moderately differentiated tubular adenocarcinoma in the body to tail of the pancreas (Fig. 5a–c). Although cancer cells invaded the pancreatic nerve plexus, 60% of tumor cells were destroyed by chemoradiotherapy, defined as grade IIb in the Evans classification (Fig. 5d, e). Severe fibrosis most likely caused by degeneration of cancer cells after chemoradiation and fragmentation of the external elastic membrane around the CeA wall were observed, but there were no arterial cancer invasion (Fig. 5f). According to the Union for International Cancer Control (UICC) TNM classification (8th edition), the tumor was T3 N0 M0, Stage IIA. No residual cancer cells were detected at the surgical margin, including the CeA, GDA, and pancreas stump (i.e., R0 resection was achieved) (Fig. 4d, e).
The patient completed 6 months of S-1 adjuvant chemotherapy (80 mg/day) and has been doing well without recurrence for more than 2 years after the initial treatment (> 16 months after surgery).
