PMC8523915_01
Imaging scans, pathological findings, and timeline with relevant data from the episode of care. HE staining of the postoperative pathological specimen indicated adenocarcinoma (scale bars represent 100 microm). Before first-line treatment, representative PET-CT images were shown. Regular revision computed tomography (CT) was used to assess treatment efficacy during first-line treatment. After five cycles of gemcitabine and cisplatin chemotherapy followed by three cycles of nab-paclitaxel in combination with gemcitabine and cisplatin chemotherapy, representative PET-CT images were shown. No lesions were detected by PET-CT, when an elevated CA199 was tested. When the patient began to experience progressively worsening abdominal pain and an abnormal increase in CA199, PET-CT was performed and representative images were shown. CT scan was performed after two cycles of nab-paclitaxel plus gemcitabine and cisplatin chemotherapy, and showed a PR of all tumor lesions. Rx, treatment; PET-CT, positron emission tomography-computed tomography; CT computed tomography; CA199, cancer antigen 199; PR partial response; CR, complete response; G, gemcitabine; A, nab-paclitaxel; P, cisplatin.
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His postoperative pathology confirmed the diagnosis of GBC, and suggested a stage of pT3N1M0, stage IIIB according to the National Comprehensive Cancer Network staging criteria ( Figure 1 ). December 2018, a fluorodeoxyglucose (FDG)-positron emission tomography computed tomography (PET-CT) at our hospital revealed multiple masses in the liver, extensive lymph nodes enlargement involving the anterior abdominal aorta, lesser omentum, and anterior supra-diaphragmatic, all with high FDG accumulation; and multiple nodules in the lung were considered inflammatory nodules ( Figure 1 ). Detection of tumor markers showed that CA199 was >1,000.00 U/ml and carcinoembryonic antigen (CEA) was 21.63 ng/ml ( Figure 2 ). After three cycles of the triple-drug chemotherapy, a CT scan showed disappearance of the tumor lesions, and PET-CT demonstrated no lesions in the liver and upper abdominal lymph nodes; the anterior group of lymph nodes in the diaphragm was smaller than before, and no increase in glucose metabolism was observed ( Figure 1 ). In June 2020, his CA199 was abnormally elevated to 115 U/ml, while no other hematological abnormalities were observed, and no lesions were detected by PET-CT ( Figure 1 ). S-1 in July 2020, and he began to experience progressively worse epigastric pain and signs of epigastric tenderness after 4 months, with an increase in CA199 and CEA to 733.40 U/ml and 7.52 ng/ml, respectively. Subsequently, PET-CT, conducted in December 2020, showed multi-metastatic lesions in both lungs and liver, along with tumor metastases in the right parasternal, parietal trunk, and para-aortic lymph nodes ( Figure 1 ). After two cycles of chemotherapy, an enhanced CT revealed significant downsizing of the tumor lesion with an evaluation of a PR efficacy ( Figure 1 ).
Changes in CA199 levels during the treatment and follow-up. The CA199 tumor marker was measured in patients' blood at periodic intervals throughout the clinical course and annotated with date, therapeutic approach, and treatment efficacy. CA199, cancer antigen 199; CR complete response; PR partial response.
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After surgery, the serum CA199 level decreased to 80 U/ml ( Figure 2 ). December 2018, a fluorodeoxyglucose (FDG)-positron emission tomography computed tomography (PET-CT) at our hospital revealed multiple masses in the liver, extensive lymph nodes enlargement involving the anterior abdominal aorta, lesser omentum, and anterior supra-diaphragmatic, all with high FDG accumulation; and multiple nodules in the lung were considered inflammatory nodules ( Figure 1 ). Detection of tumor markers showed that CA199 was >1,000.00 U/ml and carcinoembryonic antigen (CEA) was 21.63 ng/ml ( Figure 2 ). Moreover, CA199 dropped to the normal range of 8.65 U/ml and CEA was 2.74 ng/ml ( Figure 2 ). CA199 and CEA levels also gradually decreased ( Figure 2 ). Currently, the patient is still receiving regular triple-drug chemotherapy and his disease is well controlled.
Immunohistochemical results from post-operative pathological tissues of the patient. The results showed higher number of CD4+ and CD8+ T cells and the lower number of FOXP3+ Tregs and PD-(L)1 expression in tumor microenvironment. Scale bars represent 100 microm (20 microm in the inset images). FOXP3, Forkhead box P3; PD-L1, programmed cell death-ligand 1.
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In addition, compared to Forkhead box P3 (FoxP3)+ regulatory T cells (Tregs), the number of CD8+ cytotoxic T lymphocytes and CD4+ T helper lymphocytes was higher in the tumor microenvironment ( Figure 3 ).