Trends of Clinical Outcomes of Patients with Advanced Hepatocellular Carcinoma Treated with First-line Sorafenib in Randomized Controlled Trials

Background: Sorafenib has consistently served as the control arm in multiple RCTs evaluating novel therapies for advanced HCC for more than a decade. Analyzing trends in clinical outcomes of patients treated with sorafenib for the same indication over time offers the opportunity for unique insight into the evolution of clinical trial conduct and potential non-drug factors impacting outcomes. Methods: We identified RCTs in patients with treatment-naïve advanced HCC where sorafenib was compared to another systemic therapy or placebo. We extracted trial-level demographic, clinicopathologic, and outcome data (OS, progression-free survival (PFS), objective response rate (ORR) and duration of therapy). Sample-weighted linear regression was used to identify temporal trends with significance set at p0.05. Results: Sixteen RCTs (9 phase III and 7 phase II) enrolling 4086 patients treated with sorafenib were included in the analysis. Included trials enrolled patients from 2005-2019. OS has significantly improved by 4.5 months from 2005-2019 (p=0.048) over time. Thirteen studies provided data on PFS using RECIST 1.1, with no significant change over time (p=0.69). ORR assessed by RECIST 1.1 has significantly improved by 6.0% over time (p=0.003). Median duration of therapy with sorafenib has decreased by 53% since the enrollment of the first clinical trial in 2005, from 23.1 weeks to 12.2 weeks (p=0.0037). There was no significant change in patient demographics were identified over time to explain the OS findings. Conclusion: The median OS of patients with advanced HCC treated with sorafenib has improved significantly over 15 years. At the same time, the median duration of therapy with sorafenib has decreased. The reason for these findings was not explained by changing demographics of patients enrolled in these trials and has implications for ongoing clinical trials.

Gallbladder Neuroendocrine Tumors (NETs): Is there a need for a specific approach?

Neuroendocrine tumors (NETS) of the Gallbladder or the biliary tree are rare. Most of the current guidelines and protocols are derived from the experience of managing Lung small cell neuroendocrine carcinoma (SCNEC) or gastrointestinal (GI) NETS. But the overall outcome of Gallbladder NETS (GB NETS) seems worse than similarly staged lung NETS and adenocarcinoma of the gallbladder. This may be due to its rarity and lack of literature for a focused approach towards its treatment. Hence the need for a specifically designed approach might help improve the results of treatment for these rare tumours. We share our experience of two patients with GB NETS and their 5-year outcome.

Lower Extremity Varicose Veins: An Unusual Presentation of Small Bowel Leiomyosarcoma

Leiomyosarcomas are extremely rare and comprise only 1.2% of small bowel malignancies. Advancements in immunohistochemical techniques have allowed for the differentiation between leiomyosarcomas and gastrointestinal stromal tumors (GISTs). Leiomyosarcomas remain difficult to detect via endoscopy and require a more intricate diagnostic approach. The staging and sizing of these tumors are important prognostic indicators. We report a case of a 67-year-old male who presented with bulging lower extremity veins, abdominal bloating, and weight loss. A CT of the abdomen and pelvis revealed a pelvic mass arising from the small bowel and a metastatic hepatic lesion, which was found to be compressing the inferior vena cava. A biopsy of the hepatic lesion confirmed the diagnosis of metastatic leiomyosarcoma.

Thyroid disease and hepatocellular carcinoma survival. A Danish nationwide cohort study

Introduction Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide. Recent animal studies suggest that thyroid hormone treatment improves HCC prognosis. The aim of this study was to describe the association between thyroid disease and HCC prognosis in humans. Methods We performed a nationwide cohort study including all persons with an HCC diagnosis from 2000-2018. Patients’ age, sex, HCC treatment, and diagnoses of thyrotoxicosis, nontoxic goitre, and myxoedema, were obtained from Danish national healthcare registries. We used regression models to examine the association between thyroid disease and mortality hazard and restricted mean survival time after HCC diagnosis, adjusting for confounding by sex and age. Results We included 4,812 patients with HCC and 107 patients with thyroid disease. Median follow-up time was 5 months (total 5,985 person-years). The adjusted mortality hazard ratio was 0.68 (95% CI 0.47-0.96) for thyrotoxicosis and 0.60 (95% CI 0.41-0.88) for nontoxic goitre. The restricted mean survival time during the five years following HCC diagnosis was 6.8 months (95% CI 1.1–12.6) longer for HCC patients with thyrotoxicosis than for patients without thyroid disease, and it was 6.9 months (95% CI 0.9–12.9) longer for HCC patients with nontoxic goitre than for patients without thyroid disease. Conclusions In this large nationwide cohort study, thyrotoxicosis and nontoxic goitre were associated with prolonged HCC survival.

Abdominal Viscera Migration Performing Hemodynamic Instability after Esophagectomy: A Case Report

Hiatal hernia is a rare postoperative complication of esophagectomy in the treatment of esophageal cancer. Although rare, its incidence increased after the establishment of minimally invasive surgical techniques. The patient is usually oligosymptomatic, and the diagnosis is made in the late postoperative period, during outpatient follow-up. The initial presentation of hiatus hernia with hemodynamic instability is a rare condition that has never been described in the literature before. In the following report, we address the clinical picture, diagnosis, and treatment for this condition, discussing the main nuances of the literature.

Prognostic and Clinicopathologic Significance of Discoidin Domain Receptors in Different Human Malignancies: A Meta-Analysis

<b><i>Background:</i></b> Discoidin domain receptors (DDRs) belong to the receptor tyrosine kinases family and are activated by different types of collagens, which play roles in various physiological processes. An abnormal expression of DDRs is reported in different types of cancers. Despite many reports about the association and roles of high DDR expression levels in cancers, the prognostic values of DDRs are still unclear. This meta-analysis was performed to evaluate the prognostic effect of DDRs in different tissue cancers. <b><i>Method:</i></b> A literature search was performed in several related databases to find eligible English articles. Based on our research, 20 appropriate studies with 2,602 patients were selected till October 5, 2020. The pooled hazard ratio (HR) with a corresponding 95% confidence interval (CI) was computed to evaluate the strength of correlation between DDRs and survival of cancer patients. <b><i>Result:</i></b> Pooling results showed that a high DDR expression was significantly associated with poorer overall survival (OS) (HR = 1.304, 95% CI 1.007–1.69, <i>p</i> = 0.04). Subgroup analysis based on cancer type revealed a significant link between a high DDR expression level and poor OS both in gastrointestinal (pooled HR = 1.78, 95% CI 1.214–2.624, <i>p</i> = 0.003) and urological cancers (pooled HR = 1.42, 95% CI 1.062–1.82, <i>p</i> = 0.018). <b><i>Conclusion:</i></b> Our meta-analysis results suggest that high DDRs expression has the potential to be used as a biomarker of poor prognosis in cancers.

The Potential Role of Changes in the Glucose and Lipid Metabolic Pathways in Gastrointestinal Cancer Progression: Strategy in Cancer Therapy

<b><i>Background:</i></b> Changes in cell metabolism are a well-known feature of some cancers, and this may be involved in the etiology of tumor formation and progression, as well as tumor heterogeneity. These changes may affect fatty acid metabolism and glycolysis and are required to provide the increase in energy necessary for the high rate of proliferation of cancer cells. Gastrointestinal cancers remain a difficult-to-treat cancer, particularly as they are usually diagnosed at a late stage of disease and are associated with poor outcomes. <b><i>Summary:</i></b> Recently, the changes in the metabolic pathways, including the expression of the rate-limiting enzymes involved, have been considered to be a potential target for therapy for gastrointestinal tumors. <b><i>Key Message:</i></b> A combination of routine chemotherapy drugs with metabolic inhibitors may improve the effectiveness of treatment.

Cholangiocarcinoma: An Emerging Target for Molecular Therapy

<b><i>Background:</i></b> Cholangiocarcinoma has been traditionally considered a tumor with poor prognosis. Until now, surgical treatment has been the only more or less effective approach. <b><i>Summary:</i></b> Over 10 years, chemotherapy with a combination of gemcitabine and cisplatin remains the standard first-line therapy for patients with locally advanced or metastatic cholangiocarcinoma, which leads to a median overall survival of 11.7 months. Several inhibitors of HER (ERBB), HGF/c-MET, Hedgehog, KRAS-BRAF-MEK-ERK, and PI3K/AKT/mTOR signaling pathways did not show their superiority to standard chemotherapy. The rise of hope is associated with the emergence of novel fibroblast growth factor receptors and isocitrate dehydrogenase inhibitors as well as immune checkpoint inhibitors.

CircRNAs: Insights into Gastric Cancer

<b><i>Background:</i></b> Gastric cancer (GC) is recorded as the fifth most common cancer globally. The classic resemblance of early symptoms of chronic gastritis including nausea, dysphagia, and dyspepsia with GC is the current challenge limiting the early diagnosis of GC. The current diagnostic procedures of GC are limited due to their invasive nature. This directs the research question toward alternative approaches, specifically at the molecular level. Recent advances in molecular regulation of cancer suggest the prominence of circular RNAs (circRNAs) in the multistep process of tumourigenesis. <b><i>Summary:</i></b> CircRNAs are a class of non-coding RNAs, abundant in eukaryotes, with key roles in regulating genes and miRNAs as well as the alteration of processes involved in pathological conditions. Research studies have demonstrated the participation of circRNAs in the initiation and progression of tumours. This review provides a comprehensive insight into the potential of circRNAs as disease biomarkers for the early detection and treatment of GC. <b><i>Key Messages:</i></b> This study is an amalgamation of the implications and future prospects of circRNAs for the detection and potential treatment of GC.

Hepatic Arterial Infusion Chemotherapy Is a Feasible Treatment Option for Hepatocellular Carcinoma: A New Update

<b><i>Background:</i></b> Hepatic arterial infusion chemotherapy (HAIC) is one option for treating massive tumors and unresectable hepatocellular carcinoma (HCC). However, there is a lack of remedial treatment after these treatments are ineffective or failed. <b><i>Summary:</i></b> Some studies have discovered that HAIC has greater survival in patients with advanced HCC. A previous study has shown that HAIC is effective in the treatment of advanced HCC, and the data on randomized clinical trials are limited and unclear. <b><i>Key Message:</i></b> More clinical trials and research are needed in order to make HAIC a standard and recommended therapy for advanced HCC. Our review focuses on the clinical applications of hepatic artery infusion treatment.