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CECT and Immunohistochemistry for Case 1. (A, B) Tumor condition at first CECT scan. (C) Immunohistochemistry of PD-L1 expression. (D, E) Tumor conditions after seven cycles of treatment of tislelizumab + S-1. (F) irP after treatment. (G, H) The tumor shrank after continued immunotherapy, but the patient developed irP. (I) New lymph node metastasis. (J) irP developed during postoperative tislelizumab administration. (K) Lung metastasis. (L) irP after administration of nivolumab. CECT, contrast-enhanced computed tomography; PD-L1, Programmed Cell Death-Ligand 1; irP, immune-related pneumonia.
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Further, there were multiple metastatic nodules in the omentum and multiple metastases in the hilar and retroperitoneal lymph nodes ( Figures 1A, B ). Immunohistochemistry demonstrated high expression of PD-L1 (Dako 22-C3, tumor proportion score (TPS) 90%, combined positive score (CPS) 90) in the tumor tissues ( Figure 1C ). CECT indicated that the patient's tumor shrank 89.37% (186.25 cm3 to 19.80 cm3, partial remission [PR]) and the abdominal metastases disappeared ( Figures 1D, E ). However, the patient developed immune-related pneumonia (irP) ( Figure 1F ) and had to discontinue immunotherapy but he continued S-1 treatment. Therefore, he restarted tislelizumab and S-1 ( Figures 1G, H ). After two cycles of treatment, CECT indicated that the primary tumor continued to shrink and the abdominal metastases had disappeared, but there were newly enlarged lymph nodes in the hilar area ( Figure 1I ). S-1 monotherapy ( Figure 1J ). Six months after monotherapy, the patient began to develop lung metastases ( Figure 1K ). However, the tumor continued to enlarge and irP recurred ( Figure 1L ).
PMC10067585_02
CECT, HE, and Immunohistochemistry for Case 2. (A) Intrahepatic mass at diagnosis. (B) A second intrahepatic mass at diagnosis. (C) Peri-gallbladder condition at diagnosis. (D) Hematoxylin and eosin staining of biopsy tissue (original magnification x200). (E) Hematoxylin and eosin staining of biopsy tissue (original magnification x400). (F) PD-L1 staining of biopsy tissue (original magnification x400). (G) The reduction of the intrahepatic mass after 5 months of treatment. (H) Significant reduction in a second intrahepatic mass after 5 months of treatment. (I) Significant reduction in the peri-gallbladder mass after 5 months of treatment. (J) Persistent reduction of the intrahepatic mass after 18 months of treatment. (K) Persistent reduction in a second intrahepatic mass after 18 months of treatment. (L) Persistent reduction in the peri-gallbladder mass after 18 months of treatment. CECT, contrast-enhanced computed tomography; HE, hematoxylin and eosin; PD-L1, Programmed Cell Death-Ligand 1.
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In addition, the tumor had invaded the hilar vessels, and the patient was unable to undergo surgery (T4NxM1, IVB) ( Figures 2A-C ). Ultrasonography-guided liver biopsy confirmed liver invasive or metastatic poorly differentiated carcinoma ( Figures 2D, E ). Immunohistochemistry indicated low expression of PD-L1 (Dako 22-C3, TPS 10%) in the tumor tissues ( Figure 2F ). As of November 2022, CECT indicated that the patient's tumors shrank 98.28% (from 66.33 cm3 to 1.14 cm3, PR) ( Figures 2G-L ).
PMC10067585_03
CECT and Macroscopy for Case 3-5. (A) Preoperative tumor conditions of case 3. (B) Postoperative 6 months reexamination of case 3. (C) Postoperative 18 months reexamination of case 3. (D) Preoperative tumor conditions of case 4. (E) Postoperative progression and bile duct dilatation of case 4. (F) Postoperative progression and hilar soft tissue effects of case 4. (G) Postoperative neck metastasis of case 4. (H) Hilar soft tissue shadow slightly reduced after immunotherapy in case 4. (I) Neck tumor disappeared after immunotherapy in case 4. (J) Preoperative tumor conditions of case 5. (K) Postoperative intrahepatic metastasis of case 5. (L) Intrahepatic metastases reduced after immunotherapy in case 5. CECT, contrast-enhanced computed tomography; HE, hematoxylin and eosin; PD-L1, Programmed Cell Death-Ligand 1.
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CECT revealed GBC with local intrahepatic invasion ( Figure 3J ). CT showed intrahepatic metastasis ( Figure 3K ). As of February 2023, he had received 10 cycles of treatment and CECT showed that the tumor shrank 97.55% (from 7.75 cm3 to 0.19 cm3, PR) ( Figure 3L ).
PMC10067585_04
CECT and Macroscopy for Case 3-5. (A) Preoperative tumor conditions of case 3. (B) Postoperative 6 months reexamination of case 3. (C) Postoperative 18 months reexamination of case 3. (D) Preoperative tumor conditions of case 4. (E) Postoperative progression and bile duct dilatation of case 4. (F) Postoperative progression and hilar soft tissue effects of case 4. (G) Postoperative neck metastasis of case 4. (H) Hilar soft tissue shadow slightly reduced after immunotherapy in case 4. (I) Neck tumor disappeared after immunotherapy in case 4. (J) Preoperative tumor conditions of case 5. (K) Postoperative intrahepatic metastasis of case 5. (L) Intrahepatic metastases reduced after immunotherapy in case 5. CECT, contrast-enhanced computed tomography; HE, hematoxylin and eosin; PD-L1, Programmed Cell Death-Ligand 1.
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CECT revealed GBC with local intrahepatic invasion ( Figure 3J ). CT showed intrahepatic metastasis ( Figure 3K ). As of February 2023, he had received 10 cycles of treatment and CECT showed that the tumor shrank 97.55% (from 7.75 cm3 to 0.19 cm3, PR) ( Figure 3L ).
PMC10067585_05
CECT and Macroscopy for Case 3-5. (A) Preoperative tumor conditions of case 3. (B) Postoperative 6 months reexamination of case 3. (C) Postoperative 18 months reexamination of case 3. (D) Preoperative tumor conditions of case 4. (E) Postoperative progression and bile duct dilatation of case 4. (F) Postoperative progression and hilar soft tissue effects of case 4. (G) Postoperative neck metastasis of case 4. (H) Hilar soft tissue shadow slightly reduced after immunotherapy in case 4. (I) Neck tumor disappeared after immunotherapy in case 4. (J) Preoperative tumor conditions of case 5. (K) Postoperative intrahepatic metastasis of case 5. (L) Intrahepatic metastases reduced after immunotherapy in case 5. CECT, contrast-enhanced computed tomography; HE, hematoxylin and eosin; PD-L1, Programmed Cell Death-Ligand 1.
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CECT revealed GBC with local intrahepatic invasion ( Figure 3J ). CT showed intrahepatic metastasis ( Figure 3K ). As of February 2023, he had received 10 cycles of treatment and CECT showed that the tumor shrank 97.55% (from 7.75 cm3 to 0.19 cm3, PR) ( Figure 3L ).
Timelines of Case 1-5. (A) The timeline of case 1. (B) The timeline of case 2. (C) The timeline of case 3. (D) The timeline of case 4. (E) The timeline of case 5.
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