A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

食管癌高、低发区食管鳞癌患者生存及其影响因素分析

目的 探讨食管癌高、低发区食管鳞癌患者的生存状况及其影响因素。方法 收集38 741例经病理学证实为食管鳞癌患者的资料，其中，高发区患者23 273例（60.1%），低发区15 468例（39.9%）。所有患者均行食管癌根治术。运用卡方检验分析不同临床病理特征患者的组间差异，Kaplan-Meier法绘制不同临床病理特征患者的生存曲线并用Log rank进行检验。多因素Cox比例风险回归模型法分析影响生存的主要因素。结果 低发区男性患者所占比例高于高发区（P<0.001），低发区诊断年龄≥50岁食管癌患者所占比例高于高发区（P<0.001）。高发区食管鳞癌患者的整体生存优于低发区患者（P<0.001）。Cox比例风险回归模型综合分析结果表明：高低发区、性别、确诊年龄、肿瘤部位、分化程度、TNM分期和肿瘤家族史均是影响食管鳞癌患者生存的独立因素。结论 高发区食管鳞癌患者整体生存优于低发区；低发区是食管鳞癌患者预后差的独立危险因素。     

Optimal combination of antiangiogenic therapy for hepatocellular carcinoma

The success of sorafenib in prolonging survival of patients with hepatocellular carcinoma (HCC) makes therapeutic inhibition of angiogenesis a component of treatment for HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination of antiangiogenic agents with chemotherapy, radiotherapy or other targeted agents were evaluated. Nevertheless, the use of antiangiogenic therapy remains suboptimal regarding dosage, schedule and duration of therapy. The issue is further complicated by combination antiangiogenesis to other cytotoxic or biologic agents. There is no way to determine which patients are most likely respond to a given form of antiangiogenic therapy. Activation of alternative pathways associated with disease progression in patients undergoing antiangiogenic therapy has also been recognized. There is increasing importance in identifying, validating and standardizing potential response biomarkers for antiangiogenesis therapy for HCC patients. In this review, biomarkers for antiangiogenesis therapy including systemic, circulating, tissue and imaging ones are summarized. The strength and deficit of circulating and imaging biomarkers were further demonstrated by a series of studies in HCC patients receiving radiotherapy with or without thalidomide.     

The Effect of Helicobacter pylori on Gastric Cancer Treated with Adjuvant Chemotherapy After Curative Resection

Helicobacter pylori has been associated with diverse pathologies of varying severity. We investigated the H. pylori infection status and its association with the pathologic features and clinical outcomes in stage III gastric cancer patients treated with adjuvant therapy after curative resection. Between 2004 and 2009, the records of 76 consecutive patients were retrospectively reviewed. H. pylori infection was confirmed by examination of pathological specimen. The relationship between H. pylori and the clinicopathological features was analyzed by Fisher exact test, Student’s t test, and Kaplan-Meier method. Of the 76 patients, 16 patients (21.1 %) were confirmed for H. pylori infection. The median age was 59 years. Twenty-three patients received chemotherapy and remainder received chemoradiotherapy. H. pylori status did not correlate with the clinicopathologic features. It was greater in non-neoplastic tissue than the tumor tissue (21.1 vs 7.9 %). Median follow-up was 21 months. During this period, 88.2 % patients had experienced tumor recurrence, and 85.5 % patients had died. Recurrence was observed in 87.5 % patients and in 88.3 % patients in H. pylori-positive and H. pylori-negative patients, respectively (P = 0.92). Disease-free survival was 28.4 ± 7.9 months and overall survival was 31.5 ± 7.4 months in H. pylori-positive patients compared with 28.3 ± 3.7 and 33.2 ± 3.4 months, respectively, in H. pylori-negative patients. H. pylori infection status did not have effect on the overall or disease-free survival (p = 0.85 and P = 0.86), respectively. H. pylori status might not be useful as a prognostic and predictive factor for clinical outcomes.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

The role of WNT signalling in urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies, causing considerable morbidity and mortality worldwide. It is unique among the epithelial carcinomas as two distinct pathways to tumourigenesis appear to exist: low grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS whereas high grade, muscle invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma. Over the last two decades, a number of transgenic mouse models of UCC, containing deletions or mutations of key tumour suppressor genes or oncogenes, have helped us understand the mechanisms behind tumour development. In this summary, I present my work investigating the role of the WNT signalling cascade in UCC.     

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

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