Single-Drug Approach with Edoxaban is Effective for Resolving Non-Acute Cancer-Associated Venous Thrombosis: A Single-Arm Retrospective Analysis.

Recently, cancer-related venous thromboembolism (VTE) has been termed "cancer-associated thrombosis (CAT)" and is the focus of current research. We retrospectively investigated the efficacy of a single-drug approach with edoxaban for the treatment of non-acute CAT. Thirty-two non-acute CAT patients who received edoxaban were analyzed. The primary endpoint of this analysis was the thrombus disappearance rate at the first evaluation. Secondary endpoints included progression/recurrence of VTE, major bleeding, and D-dimer levels. The thrombus disappearance rate was 62.5%. Therefore, the null hypothesis for the primary endpoint (thrombus disappearance rate of ≤32.0%) was rejected (p = 0.00038) based on the rate of the previous study as the historical control. Recurrent VTE and major bleeding occurred in two patients each. After the start of treatment with edoxaban, a significant difference in D-dimer levels was observed (p = 0.00655). We demonstrated that a single-drug approach with edoxaban is a potential treatment option for non-acute CAT.

Variants of carboxylesterase 1 have no impact on capecitabine pharmacokinetics and toxicity in capecitabine plus oxaliplatin treated-colorectal cancer patients.

PURPOSE: Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of capecitabine. METHODS: We enrolled postoperative colorectal cancer (CRC) patients administered with adjuvant capecitabine plus oxaliplatin (CapeOX) and metastatic CRC patients receiving CapeOX. The pharmacokinetic analysis of the first capecitabine dose (1000 mg/m2) was done on day 1, and oxaliplatin administration was shifted to day 2. Plasma concentrations of capecitabine, 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine (5'-DFUR), and 5-FU were analyzed by high-performance liquid chromatography. CES1 polymorphisms (rs3217164, rs2244614, rs2244613, rs7187684, and rs11861118) and the functional CES1 genes (1A1, var1A1, 1A2, and pseudo 1A3) in their diplotype configurations were analyzed by direct sequencing. RESULTS: Thirty-seven patients were enrolled from September 2017 to February 2020. Patients with a higher area under the plasma concentration-time curve to capecitabine dose ratio (AUC/dose) of 5'-DFUR than its mean showed a higher frequency of overall ≥ grade 3 toxicity and lower relative dose intensity (RDI) of capecitabine than those with a lower ratio. Higher CES1 activity expressed as a metabolic ratio (AUC of capecitabine/sum of three AUCs of each metabolite) lower than its mean was associated with higher 5'-DFUR AUC/dose and lower RDI, indicating essential roles of CES1 in capecitabine activation to produce 5'-DFUR. However, the association between CES1 variants and capecitabine pharmacokinetics and toxicity was not significant. CONCLUSION: CES1 variants are not associated with capecitabine pharmacokinetics and toxicity.

VEGF Inhibitors Do Not Increase D-dimer Levels in Colorectal Cancer Patients Without Venous Thromboembolism: A Retrospective Non-inferiority Analysis

BACKGROUND/AIM: If VEGF inhibitors contribute to an increase in D-dimer levels, they may adversely affect the diagnosis of venous thromboembolism (VTE). Consequently, this retrospective study examined the effects of VEGF inhibitors on D-dimer levels in colorectal cancer patients. PATIENTS AND METHODS: A total of 104 colorectal cancer patients who received chemotherapy, were included in this study. To perform D-dimer analysis, patients were divided into two analysis targets: patients with VTE and without VTE. Statistical analysis included a natural logarithmic transformation of D-dimer data. RESULTS: In the D-dimer analysis of non-VTE patients, the natural logarithm D-dimer mean difference was -0.186, with a 95% CI of -0.525 to 0.154. The upper limit of the 95%CI (0.154) did not exceed the non-inferiority margin (Δ) of 0.199, and therefore met the non-inferiority criteria. CONCLUSION: VEGF inhibitors don't contribute to increased D-dimer levels in colorectal cancer patients without VTE.

Two cases of lymphangitic carcinomatosis as the primary symptom of colorectal carcinoma that achieved complete remission using combination anti-EGFR antibody therapy.

Clinicians often encounter cases of pulmonary lymphangitic carcinomatosis when treating patients with cancer. When such a condition develops before the diagnosis of cancer, its diagnosis is often challenging. Herein, we report about two patients with colorectal carcinoma diagnosed after the identification of lymphangitic carcinomatosis, which achieved complete remission with combination anti-epidermal growth factor receptor (anti-EGFR) antibody therapy. In case 1, a 74-year-old woman presented with cough and dyspnea that had persisted for 1 month. She had unresectable advanced carcinoma of the sigmoid colon with lymphangitic carcinomatosis. Her respiratory status gradually deteriorated due to the disease. Thus, FOLFIRI plus cetuximab therapy was initiated. Her dyspnea rapidly resolved with the treatment, and complete remission of lymphangitic carcinomatosis was achieved. In case 2, a 46-year-old man presented with fever and dyspnea that had persisted for 1 month. He had unresectable advanced carcinoma of the transverse colon with lymphangitic carcinomatosis. FOLFOXIRI therapy was then initiated. However, his respiratory status did not improve. Therefore, his treatment was immediately switched to FOLFIRI plus panitumumab. His dyspnea rapidly resolved with the treatment, and complete remission of lymphangitic carcinomatosis was achieved. In oncologic emergencies, such as lymphangitic carcinomatosis, requiring an early response to treatment, the administration of anti-EGFR antibodies may be a highly effective treatment option.

Trastuzumab With S-1 Plus Cisplatin in HER2-positive Advanced Gastric Cancer Without Measurable Lesions: OGSG 1202.

BACKGROUND/AIM: Trastuzumab with S-1 plus cisplatin was proved to be effective for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer with measurable lesions. However, the efficacy and safety of this regimen in the absence of measurable lesions are unknown. PATIENTS AND METHODS: Patients with HER2-positive gastric cancer without measurable lesions received cisplatin plus trastuzumab intravenously on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The primary end-point was overall survival, and 40 patients were planned to be enrolled. RESULTS: Fifteen patients were enrolled. The median overall survival was 14.4 months. The 1- and 3-year overall survival rates were 66.7 % and 26.7 %, respectively. Major grade 3-4 adverse events included neutropenia (47%), anemia (40%), diarrhea (20%), nausea (20%), and anorexia (20%). CONCLUSION: Trastuzumab with S-1 plus cisplatin might be effective and tolerable for HER2-positive advanced gastric cancer without measurable lesions.

Improved Visualization of Middle Ear Cholesteatoma with Computed Diffusion-weighted Imaging.

Computed DWI (cDWI) is a mathematical technique that calculates arbitrary higher b value images from at least two different lower b values. In addition, the removal of high intensity noise with image processing on cDWI could improve cholesteatoma-background contrast-to-noise ratio (CNR). In the present study, noise reduction was performed by the cut-off values of apparent diffusion coefficient (ADC) less than 0 and 0.4 × 10-3 s/mm2. The cholesteatoma to non-cholesteatoma CNR was increased using a noise reduction algorithm for clinical setting.

Early tumor shrinkage as a predictor of favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX.

There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in pancreatic cancer. We therefore investigated whether the ETS will predict outcomes in 59 patients with advanced pancreatic cancer treated with FOLFIRINOX therapy. The association of ETS with progression-free survival (PFS) and overall survival (OS) was evaluated but also we addressed to the correlation between outcomes and DpR. ETS was defined as a reduction ≥ 20% of target lesions' diameters measured at 6 to 8 weeks from treatment start. DpR was percentage of maximal tumor shrinkage observed at the nadir diameter compared with baseline. Among 47 evaluable patients for the ETS, 12 (25.5%) patients experienced ETS. The ETS was significantly associated with better PFS (9.0 vs. 4.2 months) as well as OS (24.0 vs. 9.1 months); moreover, the association had a statistically significance for PFS but a strong trend for OS in multivariate analysis. The DpR was statistically significantly but weakly associated with OS. In conclusion, this is the first report that the early response to chemotherapy may predict favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX therapy.

The application of dynamic contrast-enhanced MRI and diffusion-weighted MRI in patients with maxillofacial tumors.

RATIONALE AND OBJECTIVES: To elucidate the characteristics of four types of tumors, including squamous cell carcinoma (SCC), malignant lymphoma (ML), malignant salivary gland tumors (MSGTs), and pleomorphic adenoma (Pleo), in the maxillofacial region using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted MRI (DW-MRI）data. MATERIALS AND METHODS: A total of 59 tumors were included in this research. DCE-MRI and DW-MRI were performed. We applied the Tofts and Kermode model (TK model) for the DCE-MRI data and obtained three dependent parameters: the influx forward volume transfer constant into the extravascular extracellular space from the plasma (K(trans)), the fractional volume of extravascular extracellular space per unit volume of tissue (ve), and the fractional volume of plasma (vp). RESULTS: Among the K(trans) values, there were no significant differences between the three types of malignant tumors; however, there was a significant difference between the SCC and Pleo (P = .0099). The ve values of the Pleo were highest, with significant differences compared to the other categories (SCC, P = .0012; ML, P = .0017; and MSGT, P = .041). The ML had the lowest ve values, and there were significant differences between ML and the other two types of malignant tumors (SCC, P = .0278 and MSGT, P = .0062). In 14 (24%) cases, apparent diffusion coefficient (ADC) could not be measured because of poor image quality. The ADC values of the ML were lowest, whereas those of Pleo were highest, similar to that observed for ve. CONCLUSIONS: The Pleo tumors had lower K(trans) values and higher ve values, which are useful for differentiating them from the malignant tumors. Moreover, the ve was also useful for establishing a diagnosis of ML.

Factors influencing EPA+DHA levels in red blood cells in Japan.

The blood eicosapentaenoic and docosahexaenoic acid (EPA+DHA) concentration is an important inverse risk factor for sudden cardiac death. However, it is not known what kinds of factors influence the EPA+DHA levels in the total phospholipid fraction in red blood cells (RBC EPA+DHA) in Japan, who regularly eat more fish with increasing age. Four hundred and fifty-six healthy individuals (320 men and 136 women, 18 to 70 years old) were recruited between 2002 and 2005. RBC EPA+DHA were measured by gas chromatography and questionnaires were administered. Multivariate analysis indicated that there were significant correlations between RBC EPA+DHA and (i) dietary EPA+DHA (beta=0.31), (ii) age (beta=0.33), (iii) gender (beta=-0.15) and (iv) physical activity (beta=-0.11) but not with body mass index or smoking.