Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Expression of prostate-specific membrane antigen in lung cancer cells and tumor neovasculature endothelial cells and its clinical significance.

BACKGROUND: Prostate-specific membrane antigen (PSMA) has been found in tumor neovasculature endothelial cells (NECs) of non-prostate cancers and may become the most promising target for anti-tumor therapy. To study the value of PSMA as a potential new target for lung cancer treatment, PSMA expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) tissues and its relationship with clinicopathology were investigated in the current study. METHODS: Immunohistochemistry was used to detect PSMA expression in a total of 150 lung specimens of patients with lung cancer. The data were analyzed using univariate and multivariate statistical analyses. RESULTS: The percentages of NSCLC patients who had PSMA (+) tumor cells and PSMA (+) NECs were 54.02% and 85.06%, respectively. The percentage of patients younger than 60 years old who had PSMA (+) tumor cells was 69.05%, which was significantly greater than the percentage of patients aged 60 years or older (40.00%, p<0.05). A significant difference was observed in the percentage of NSCLC patients with PMSA (+) NECs and stage I or II cancer (92.98%) and those patients with stage III or IV cancer (76.77%). In the SCLC tissues, NEC PSMA expression (70.00%) did not differ significantly from NSCLC. SCLC tumor cells and normal lung tissues cells were all negative. There was no significant correlation between the presence of PSMA (+) NECs in SCLC patients and the observed clinicopathological parameters. CONCLUSIONS: PSMA is expressed not only in NECs of NSCLC and SCLC but also in tumor cells of most NSCLC patients. The presence of PSMA (+) tumor cells and PSMA (+) NECs in NSCLC was negatively correlated with age and the clinicopathological stage of the patients, respectively.

Analysis of circulating regulatory T cells (CD4+CD25+CD127-) after cryosurgery in prostate cancer.

This study was performed to assess the response of regulatory T cells (Tregs) following cryosurgery in prostate cancer (PCa) patients by measuring their frequency and immune function. Blood was collected prior to and at 4 and 8 weeks after treatment in 30 patients with high-risk PCa who underwent cryosurgery and from 15 healthy volunteers. Circulating CD4(+)CD25(+)CD127(-) Tregs were isolated. Their frequency was detected by flow cytometry, and immune suppressive function was evaluated by measuring the proliferation of CD4(+)CD25(-) T cells cocultured with Tregs. The results showed that the percentage of circulating CD4(+)CD25(+)CD127(-) Tregs was increased in PCa patients compared to healthy volunteers (7.6% ± 0.73% vs. 5.8% ± 0.54%, P<0.001). The frequency of circulating CD4(+)CD25(+)CD127(-) Tregs was reduced 4 weeks after cryosurgery compared to before surgery (6.3% ± 0.58% vs. 7.6% ± 0.73%, P<0.001), and the decrease persisted for 8 weeks. However, the suppressive function of Tregs was increased in eight of 12 patients, which might contribute to cancer recurrence. Then the response of circulating Tregs is complicated after cryosurgery for PCa, and further studies are warranted.

[Clinical features and prognostic analysis in prostate cancer patients under 59 years of age: a report of 72 cases].

OBJECTIVE: To explore the clinicopathological characteristics and prognostic factors in prostate cancer patients under 59 years of age. METHODS: From January 2000 to October 2011, 566 prostate cancer patients underwent treatments. Among them, 72 (12.7%) patients under 59 years of age with the integrated clinical data were reviewed. The median follow-up period was 25 months (range: 1 - 108) and the median age 55 years (range: 16 - 59). Four (5.5%) cases had the clinical stage of II, 12 (16.7%) cases of stage III and 56 (77.8%) cases of stage IV. Progression-free survival (PFS), overall survival (OS) and prognostic factors were analyzed. RESULTS: The rate of adenocarcinoma was 86.1% (62/72) and the Gleason score of 8-10 69.1% (29/42). Special type carcinoma accounted for 13.9% (10/72). The median time to androgen-independent prostate cancer (AIPC) was 12 months after endocrine therapy. The 1-, 3- and 5-year PFS were 53.8%, 12.1% and 6.1% and those for OS 85.2%, 58.8% and 15.6% respectively. The prognostic factors were age, baseline prostate special antigen (PSA), types of pathology, tumor stage and local treatment by univariate analysis. The type of pathology was an independent prognostic factor of affecting significantly the prognosis by multivariate analysis. CONCLUSION: Prostate cancer patients under 59 years of age are characterized by misdiagnosis, complexity of pathology and high malignancy. Comprehensive regiment with predominant local therapy is an effective approach.

[Clinical efficacy of transcatheter renal arterial embolization plus cryoablation for medium and advanced renal carcinomas].

OBJECTIVE: To investigate the clinical efficacy of transcatheter renal arterial embolization (TRAE) plus cryoablation in the treatment of medium and advanced stage renal carcinomas. METHODS: The patients with medium and advanced stage renal carcinomas were randomized into 2 groups: TRAE group (A, n = 53) and TRAE plus cryoablation group (B, n = 51) undergoing cryoablation 2 - 3 weeks after TRAE. A total of 128 tumors (8.7 ± 3.2) (4.0 - 19.8) cm in diameter were detected. And the largest tumor in a specific patient with multiple lesions was selected for observation. At pre- and post-treatment, their clinical symptoms, kidney function and tumor diameters (computed tomography or magnetic resonance imaging) were observed. And their post-treatment profiles of tumor necrosis and survival were assessed. RESULTS: There was no difference in gender, age, size and Robson stage between two groups. The tumor necrosis of Group B was significantly higher than that of Group A (61% vs 35%, t = 6.784, P < 0.01). The median survival duration of Group B was significantly longer than that of Group A (24 vs 15 months, P < 0.05). There was no significant change of kidney function at pre- and post-treatment (P > 0.05). The quality-of-life scores improved at post-treatment (P < 0.01). CONCLUSION: As compared with TRAE therapy alone, the combination of TRAE and cryoablation may improve the tumor necrosis rate and prolong the patient survival duration.

[Experimental study on the immune functions of splenic dendritic cells after a combined therapy of cryoablation and granulocyte macrophage-colony stimulating factor for prostate cancer].

OBJECTIVE: To assess the changes about numbers and immune functions of splenic DC (dendritic cell) after a combined therapy of cryoablation and GM-CSF (granulocyte macrophage-colony stimulating factor) for prostate cancer. METHODS: Murine model of prostate cancer was established. And the tumor-bearing mice were divided into 4 groups: control group (Group A), GM-CSF treatment (Group B), cryoablation treatment (Group C) and a combined therapy of cryoablation and GM-CSF (Group D). Spleens were sampled before and 7, 14, 21 days after treatment. Immunohistochemistry of DC was performed. And splenic lymphocytes were isolated and their activated percents analyzed by flow cytometry. The tumor-specific cytolytic activity of cytotoxic T lymphocyte (CTL) was measured by LDH (lactate dehydrogenase) assay. And the lung metastasis rates were calculated. RESULTS: At Day 7 post-treatment, the number of DC per high-power field was 26.4 ± 1.1, 36.6 ± 2.1, 25.8 ± 1.3 and 58.2 ± 1.9 (P < 0.05); the activated percent of DC 13.60% ± 1.67%, 9.50% ± 0.21%, 14.40% ± 1.14% and 32.80% ± 2.39% (P < 0.05); cytolytic activity of CTL against prostate cancer cells 7.76% ± 0.11%, 8.10% ± 0.92%, 9.38% ± 0.45% and 41.68% ± 0.82% in Groups A, B and C respectively (P < 0.05). At Day 21 post-treatment, the rate of lung metastasis was 5/5, 4/5, 4/5 and 1/5 respectively. CONCLUSION: A combined therapy of cryoablation and GM-CSF may increase the number and activated percent of DC in spleen, enhance the tumor-specific immune responses and decrease lung metastasis rate.

[Effect of transcatheter renal arterial embolization combined with cryoablation on regulatory CD4+ CD25+ T lymphocytes in the peripheral blood of patients with advanced renal carcinoma].

OBJECTIVE: To analyze the effect of Argon-Helium cryosurgery (AHCS) combined with transcatheter renal arterial embolization (TRAE) on the differentiation of regulatory CD4+ CD25+ T cell (Treg) and its implication in patients with renal carcinoma. METHODS: 77 patients were called in the study, and were divided into two groups: TRAE group (n = 45, receiving TRAE only) and TRAE + cryoablation group (n = 32, receiving cryoablation 2-3 weeks after TRAE). The percentage of Treg cells and T lymphocyte subsets (CD3+T, CD4+T, CD8+T, and CD4+T/CD8+ T) in the peripheral blood was measured by flow cytometry before and 3 months after therapy. Meanwhile, the extent of tumor necrosis was measured by MRI or CT 1 month after therapy. RESULTS: The percentages of Treg cells of patients in TRAE + cryoablation group were decreased from 6.6% +/- 1.2% to 3.9% +/- 1.2%, (t = 42.768, P < 0.01), and the percentages of CD3+ T, CD4+ T, CD8+T, NK and CD4+T/CD8+T were significantly increased (P < 0.01). However, among the patients in TRAE group, the percentages of Treg, CD3+ T, CD4+ T, CD8+T, NK and CD4+T/CD8+T were increased (P > 0.05). The tumor necrosis rates of TRAE + cryoablation groups were 57.5%, significantly higher than those of TRAE group, which shows 31.6% (t = 6.784, P < 0.01). The median survival duration of the TRAE + cryoablation group was 20 months, significantly longer than that of the TRAE group (chi(2) = 7.368, P < 0.01). The decreasing extent of Treg cells is correlated with tumor necrosis rates (r = 0.90 P < 0.01) and life time (r = 0.67 P < 0.01). CONCLUSION: The therapy of TRAE combined with cryoablation contributed to reduce the percentage of Treg cells and improve the immune situation of patients with renal cell carcinoma, consequently increase tumor necrosis rate and prolongs the patients' survival duration.

[Experimental study of anti-tumor immunologic response induced by cryoablation for prostate cancer].

OBJECTIVE: To assess the anti-tumor immune response of cryoablation for prostate cancer. METHODS: Mouse model of prostate cancer was established. And the tumor-bearing mice were divided into three groups: control group (Group A), surgery group (Group B) and cryoablation group (Group C). Blood samples were withdrawn before and at Days 7, 14, 21 post-treatment. IFN-gamma and IL-4 were analyzed by enzyme-linked immunosorbent assay (ELISA). Th1/Th2 ratio was estimated from the IFN-gamma/IL-4 ratio. Lymphocytes of draining lymph node (DLN) and spleen were isolated. And the post-therapeutical number of tumor-specific IFN-gamma+CD4+ Th cells was measured by the method of enzyme link immunological spot (ELISPOT). And tumor-specific cytolytic activity of CD8+ cytotoxic T lymphocyte (CTL) was measured by LDH assay. The rate of metastasis was assessed. RESULTS: At Day 7 post-treatment in Groups A, B and C, Th1/Th2 ratio was 4.97+/-0.31, 10.07+/-0.62 and 13.71+/-0.57 respectively (P<0.05); the number of IFN-gamma+ cells every 10(6) CD4+ Th cells in DLN 22.3+/-1.0, 24.0+/-1.2 and 243.4+/-46.2 respectively; cytolytic activity of cytotoxic T lymphocyte against prostate cancer cells (14.6+/-1.1)%, (15.2+/-0.8)% and (62.6+/-2.3)% respectively (P<0.05). But for T cells derived from spleen, there were no difference in IFN-gamma+CD4+ Th cells or cytolytic activity of CTL among the groups. At Day 28 post-treatment, the rate of DLN metastasis was 100%, 80% and 40% respectively. And the rates of lung metastasis were all 100%. CONCLUSION: Cryoablation for prostate cancer can induce the Th1 advantage of anti-tumor immunity and generate the tumor-specific immune response in DLN. But the response remains limited. Further studies are warranted.

[Cryoablation for prostate cancer induces tumor-specific immune response].

OBJECTIVE: To assess the anti-tumor immune response to percutaneous cryoablation in patients with local prostate cancer. METHODS: We treated 10 patients with local prostate cancer by percutaneous cryoablation, collected the blood samples before and 2 weeks after the treatment and isolated peripheral blood mononuclear cells (PBMCs). Protein lysates were made by biopsy from autologous prostate cancer or non-cancer tissues. The levels of serum TNF-alpha, IFN-gamma, IL4 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA) and the Th1/Th2 ratio was calculated by the IFN-gamma/IL-4 ratio. The number of IFN-gamma + T cells under the stimulation of different protein lysates was counted by enzyme link immunol spot (ELISPOT). And the cytolytic activity of cytotoxic T lymphocytes (CTL) was detected by LDH assay. RESULTS: Compared with pre-treatment, the levels of TNF-alpha and IFN-gamma, the Th1/ Th2 ratio and the number of IFN-gamma + T cells induced by tumor protein lysates in PBMCs were increased significantly after cryosurgery (P < 0.01), while the levels of IL4 and IL-10 decreased slightly, and the non-tumor protein lysates induced no obvious changes in the number of IFN-gamma T cells. The cytolytic activity of cytotoxic T lymphocytes against human prostate cancer cells LNCaP was markedly increased, but not that against renal cancer cells GRC-1. One case of recurrence was found during the 3-6 months follow-up. CONCLUSION: Percutaneous cryoablation for prostate cancer could induce a tumor-specific immune response.