Conversion surgery after gemcitabine and cisplatin plus durvalumab for advanced intrahepatic cholangiocarcinoma:A case report

BACKGROUND The combination of immune checkpoint inhibitors and chemotherapy has shown promising results for the treatment of advanced biliary tract cancer(BTC).Based on the results of the TOPAZ-1 trial,a gemcitabine and cisplatin plus durvalumab(GCD)regimen was recently approved as first-line therapy for patients with advanced BTC.However,post-GCD conversion surgery has not been previously studied.Herein,we describe a case of advanced intrahepatic cholangiocarcinoma(ICC)successfully treated with radical surgery after GCD.CASE SUMMARY A 65-year-old female diagnosed with advanced ICC with periductal infiltration into the hepatic hilum underwent eight cycles of GCD,followed by durvalumab maintenance treatment,with mild adverse events.Partial response was obtained.Subsequently,a conversion surgery with extended left hepatectomy and bile duct resection was performed.The resection margins were negative,and the pathological diagnosis was compatible with small duct type ICC.The patient remained disease-free for 8 months without adjuvant chemotherapy.CONCLUSION We describe the case of a patient who received successful conversion surgery after GCD treatment for advanced ICC.

Current state and future of co-inhibitory immune checkpoints for the treatment of glioblastoma

In the interaction between a tumor and the immune system,immune checkpoints play an important role,and in tumor immune escape,co-inhibitory immune checkpoints are important.Immune checkpoint inhibitors(ICIs)can enhance the immune system's killing effect on tumors.To date,impressive progress has been made in a variety of tumor treatments;PD1/PDL1 and CTLA4 inhibitors have been approved for clinical use in some tumors.However,glioblastoma(GBM)still lacks an effective treatment.Recently,a phase III clinical trial using nivolumab to treat recurrent GBM showed no significant improvement in overall survival compared to bevacizumab.Therefore,the use of immune checkpoints in the treatment of GBM still faces many challenges.First,to clarify the mechanism of action,how different immune checkpoints play roles in tumor escape needs to be determined;which biomarkers predict a benefit from ICIs treatment and the therapeutic implications for GBM based on experiences in other tumors also need to be determined.Second,to optimize combination therapies,how different types of immune checkpoints are selected for combined application and whether combinations with targeted agents or other immunotherapies exhibit increased efficacy need to be addressed.All of these concerns require extensive basic research and clinical trials.In this study,we reviewed existing knowledge with respect to the issues mentioned above and the progress made in treatments,summarized the state of ICIs in preclinical studies and clinical trials involving GBM,and speculated on the therapeutic prospects of ICIs in the treatment of GBM.

Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

Biomarkers for the early diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.

Potentiality of immunotherapy against hepatocellular carcinoma

Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence,treatment options remain limited for advanced HCC,and as a result prognosis continues to be poor. Current therapeutic options,surgery,chemotherapy and radiotherapy,have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising,novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here,we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies,such as tumor-associated antigen therapy,immune checkpoint inhibitors and cell transfer immunotherapy,have demonstrated safety and feasibility in HCC patients. Unfortunately,immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this chal lenge will place immunotherapy at the forefront of HCC treatment,possibly in the near future.

Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.

Prospects for immunotherapy as a novel therapeutic strategy against hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is a highly aggressive malignant disease,with a poor clinical prognosis.Many standard therapies are often considered for HCC treatment today; however,these conventional therapies often fail to achieve sufficiently effective clinical results.Today,HCC therapy is set to undergo a major revolution,owing to rapid developments in cancer immunotherapy,particularly immune checkpoint inhibitor therapy.Cancer immunotherapy is a novel and promising treatment strategy that differs significantly from conventional therapies in its approach to achieve antitumor effects.In fact,many cancer immunotherapies have been tested worldwide and shown to be effective against various types of cancer; HCC is no exception to this trend.For example,we identified a specific cancer antigen called glypican-3(GPC3) and performed clinical trials of GPC3-targeted peptide vaccine immunotherapy in patients with HCC.Here,we present an overview of the immune mechanisms for development and progression of HCC,our GPC3-based immunotherapy,and immune checkpoint inhibitor therapy against HCC.Finally,we discuss the future prospects of cancer immunotherapy against HCC.We believe that this review and discussion of cancer immunotherapy against HCC could stimulate more interest in this promising strategy for cancer therapy and help in its further development.

Erratum: Author’s Affiliation Correction. Type Ⅱ human epidermal growth factor receptor heterogeneity is a poor prognosticator for type Ⅱ human epidermal growth factor receptor positive gastric cancer (World J Clin Cases 2019;Aug 6;7 (15): 1964-1977)

Correction to"Type II human epidermal growth factor receptor heterogeneity is a poor prognosticator for type II human epidermal growth factor receptor-positive gastric cancer"World J Clin Cases 2019;7(15):1964-1977.In this article,one of the affiliation of the first author was lacked.Akio Kaito,the first author,belonged to Course of Advanced Clinical Research of Cancer,Juntendo University Graduate School of Medicine,Tokyo 163-8001,Japan.