Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.

Pancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting. Video Abstract.

Early changes in apparent diffusion coefficient as an indicator of response to sorafenib in hepatocellular carcinoma.

OBJECTIVE: The relationship between apparent diffusion coefficient (ADC) and chemotherapy has been established. However, whether ADC could be considered as a measure for monitoring response to sorafenib in hepatocellular carcinoma (HCC) has not been demonstrated. This study was to investigate the ADC changes of advanced HCC under sorafenib treatment. METHODS: Athymic mice with HepG2 xenografts were allocated to two groups: control and sorafenib (40 mg/kg, bid). T2 and diffusion images were acquired at each time point (0, 10, 14, and 18 d post-therapy). Tumor volume and changes in ADC were calculated. RESULTS: Tumor volumes on Days 10, 14, and 18 after treatment showed significant decreases in the sorafenib-treated group compared with the control. Pretreatment ADC values were not significantly different between the control and treated groups. A slow increase in ADC in the peripheral zone of tumors appeared in the treated group, which was significantly higher compared with the control group on Days 10, 14, and 18. In the central part of tumors on Day 10 after treatment, an increase in ADC appeared in the treated and control groups, the ADC of the control group being significantly lower compared with the treated tumors. From Day 10 to Day 14, the ADC map showed a progressive decrease in the central region of tumors in the treated and control groups. However, this change is more significant in the treated groups. CONCLUSIONS: Early changes in mean ADC correlated with sorafenib treatment in HCC, which are promising indicators for predicting sorafenib response in this carcinoma.

Inhibition of SIRT1 combined with gemcitabine therapy for pancreatic carcinoma.

BACKGROUND: Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods. METHODS: Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells) received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo. RESULTS: The cleaved poly ADP ribose polymerase (PARP)-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05) and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05). CONCLUSION: Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single gemcitabine therapy. The combination therapy method is a potential treatment method for pancreatic carcinoma.

Analysis of pancreatic fistula according to the International Study Group on Pancreatic Fistula classification scheme for 294 patients who underwent pancreaticoduodenectomy in a single center.

OBJECTIVES: The purposes of this study were to validate the value of the International Study Group on Pancreatic Fistula (ISGPF) classification scheme for pancreatic fistula (PF) and to identify predictive factors for clinically significant PF. METHODS: From January 2000 to December 2007, 294 consecutive patients underwent pancreaticoduodenectomy in a single medical center. Pancreatic fistula was evaluated by the ISGPF criteria and Johns Hopkins Hospital's definition (JHH). Then, logistic regression analysis was performed to identify predictive factors for PF development. Our own management strategies with PF were also discussed. RESULTS: The overall incidence of PF was 19.4% (57/294) according to the ISGPF criteria, and 8.8% (26/294) using the JHH definition. Thirty-one patients with PF classified by the ISGPF were missed by the JHH definition. By logistic regression analysis, we found that besides the lack of cardiovascular disease and malignant diseases, our single-layer continuous circular invaginated pancreaticojejunostomy was another independent factor for the lowered incidence of PF. CONCLUSIONS: The ISGPF classification scheme was accurate for evaluating PF. Single-layer continuous circular invaginated pancreaticojejunostomy may be a promising method that may have been responsible for the lower incidence of PF in this study.