Sorafenib Monotherapy in a Patient with Unresectable Hepatic Epithelioid Hemangioendothelioma

A 49-year-old Japanese man had multiple huge masses (max. size 60 mm diameter) in his liver. These tumors were pathologically diagnosed by tumor biopsy as epithelioid hemangioendotheliomas of the liver. In this case, multiple liver tumors existed in both lobes. Also this patient did not agree to receive surgical resection including liver transplantation. Chemotherapy with sorafenib at a dose of 400 mg/body twice a day was started. About 6 months later, CT findings revealed that these tumors were shrinking slightly; 33 months later, the tumors obviously showed a partial response in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST). Also 60 months later, the partial response continued with sorafenib monotherapy

Clinical Outcomes of Everolimus Rechallenge in Patients with Pancreatic Neuroendocrine Neoplasms with No Other Treatment Options

Background: The clinical outcomes of everolimus rechallenge in patients with pancreatic neuroendocrine neoplasms (PNENs) are unknown. This study aimed to investigate the treatment outcomes and safety of everolimus rechallenge treatment with PNENs. Methods: Clinical data of everolimus-treated patients with PNENs at two institutions were collected. Patients who underwent everolimus rechallenge were included in the study. We analyzed the progression-free survival (PFS) and treatment response associated with everolimus rechallenge and the adverse events. Results: Between 2008 and 2020, 117 patients received initial treatment with everolimus, of which 14 patients received everolimus rechallenge. With regard to the grade of PNENs, there were 2 cases of G1, 11 cases of G2, and 1 case of G3. The median rechallenge PFS was 5.7 months. The objective response rate was 21.4%. the disease control rate was 71.4%. The only major grade 3 or 4 adverse event was neutropenia (n = 1, 7.1%). No other severe adverse event was observed. Conclusion: The outcomes and safety of everolimus rechallenge were verified, and it was deemed an acceptable treatment. Everolimus rechallenge may provide a new drug therapy for patients with advanced PNENs for whom no other drug treatment option is available

Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer.

Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture supernatants (CM) of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC

Exosomal miRNA expression in malignant ascites (MA), peritoneal lavage fluid (PLF), and cell culture media (CM).

<p>Variation and commonality between the samples were examined. Evaluation of total exosomal RNA used a Bioanalyzer 2100. The electropherograms show the size distribution (nucleotides, nt) and fluorescence intensity (FU) of total exosomal RNA isolated from CM, MA, and PLF. The lowest spike (around 25 nt) in each sample is the marker of the Agilent RNA 6000 Pico kit.</p

Signal intensity distribution among MA (A), PLF (B), and CM (C) samples and among the groups (D).

<p>Signal intensity distribution among MA (A), PLF (B), and CM (C) samples and among the groups (D).</p

Coefficient of correlation between samples. MA, Malignant ascites; PLF, Peritoneal lavage fluid; CM, Cell culture medium

<p>Coefficient of correlation between samples. MA, Malignant ascites; PLF, Peritoneal lavage fluid; CM, Cell culture medium</p

Relative expression levels of exosomal miRNAs in intraoperative peritoneal lavage fluid of T4 and T1–T3 gastric cancer patients.

<p>An asterisk indicates P < 0.05.</p