A 65-year-old male with a significant 20-pack-year smoking history presented to our tertiary care center with a 15-month history of progressive, painless jaundice accompanied by severe pruritus and significant weight loss in June 2023. The patient denied any constitutional symptoms such as fever or night sweats. However, careful history revealed the recent onset of postprandial bloating and mild steatorrhea suggestive of pancreatic exocrine insufficiency. He also denied any history of significant alcohol consumption. His past medical history was significant only for well-controlled hypertension, with no history of diabetes mellitus or chronic pancreatitis. Germline testing was not accessible, and there was no family history of pancreatic or other cancers. Table 1 shows the baseline investigations at his initial clinical presentation.

As seen in Figure 1, the diagnostic workup started with an abdominal ultrasound that revealed modest intrahepatic biliary ductal dilatation with gallbladder distension.

Subsequent MRCP (July 2023) revealed a 1.8 cm narrowing (stricture) in the distal common bile duct (CBD) with upstream biliary dilation (standard hepatic duct diameter 12 mm) and a markedly distended gallbladder (transverse diameter 5.2 cm). ERCP with stent placement (August 2023) confirmed a tight, irregular distal CBD stricture suspicious for malignancy, prompting placement of dual plastic stents that relieved jaundice from 8.2 to 5.6. Figure 2 shows the CT imaging obtained in October 2023; progressive biliary dilation was noted despite stenting, and new soft tissue thickening was seen in the pancreatic head (2.1 cm), enhancing the arterial phase and suspicious peripancreatic lymphadenopathy.

Despite prior ERCP with stent placement, the patient continued to exhibit features of obstructive jaundice. In April 2024, recurrent biliary obstruction necessitated the implantation of a metallic stent. Although there was a partial decline in serum bilirubin levels following the metallic stent placement, purulent drainage from the ampulla was observed, raising concerns for superinfection or tumor necrosis complicating the clinical course. Figure 3 depicts the cholangiogram showing the placement of the metallic stent in the biliary tracts.

By May 2024, CT imaging demonstrated disease progression with a 3.5 cm heterogeneous mass in the pancreatic head and uncinate process, demonstrating 180° encasement of the superior mesenteric artery (SMA) and abutment of the aorta, as shown in Figure 4, radiographic features consistent with locally advanced, borderline resectable pancreatic adenocarcinoma.

While CEA stayed normal at 2.1 ng/mL, the serum carcinoembryonic antigen 19-9 (CA 19-9) levels had sharply increased to 12,000 U/mL. Well-differentiated adenocarcinoma was confirmed by EUS-FNA, and molecular profiling was not done due to affordability and accessibility issues. Figure 5 shows the histopathology of a pancreatic mass biopsy obtained via EUS-FNA, revealing features consistent with PDAC, stained with hematoxylin and eosin. Immunohistochemical staining was positive for cytokeratin 7 (CK7) and negative for CK20, supporting the pancreatic origin.

Following a multidisciplinary tumor board review, the patient was started on neoadjuvant-modified folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy (oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², and 5-FU 2400 mg/m² over 46 hours) with prophylactic growth factor support. After six cycles, restaging showed a partial response with a decreased tumor size to 2.4 cm and a CA 19-9 decline to 800 U/mL. He subsequently underwent SBRT (35 Gy in five fractions) targeting the SMA margin.

In October 2024, the patient underwent a successful pylorus-preserving pancreaticoduodenectomy (PPPD). Intraoperative findings included a firm 2.5 cm pancreatic head mass without peritoneal or liver metastases. Frozen section analysis confirmed R0 margins. A grade B pancreatic fistula complicated the surgical course, which was managed with percutaneous drainage, but the patient was ultimately discharged on postoperative day nine. Final pathology revealed ypT2N1 (2/28 lymph nodes) adenocarcinoma with a 60% treatment effect and negative margins. Adjuvant therapy with gemcitabine and capecitabine was initiated, with surveillance CA 19-9 normalizing to 35 U/mL by November 2024. Table 2 shows the progressive clinical events from start to end in this patient.