Comparison of irinotecan and oxaliplatin as the first-line therapies for metastatic colorectal cancer: a meta-analysis.

BACKGROUND: Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC. METHODS: This meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: Nineteen trials involving 4571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82-0.98, P = 0.02), but not with OS (pooled HR = 0.91, 95% CI = 0.80-1.03, P = 0.15). CONCLUSION: Although the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. The combination of anti-VEGF antibody and IRI was associated with better PFS compared with anti-VEGF antibody and Ox. Both regimens could be used as the first-line treatments for mCRC with consideration of the patients' condition or toxicity profiles.

Oxidative Annulation of Arenecarboxylic and Acrylic Acids with Alkynes under Ambient Conditions Catalyzed by an Electron-Deficient Rhodium(III) Complex.

It has been established that an electron-deficient Cp(E) rhodium(III) complex catalyzes the oxidative [4+2] annulation of substituted arenecarboxylic and acrylic acids with alkynes under ambient conditions (at RT-40 °C, under air) without using excess amounts of substrates to produce the corresponding substituted isocoumarins and α-pyrones in high yields. Minor modification of reaction conditions depending on the coordination ability of alkynes realized the high efficiency.

Diagnostic accuracy of cerebrospinal fluid liquid biopsy and MRI for leptomeningeal metastases in solid cancers: A systematic review and meta-analysis.

Background: Cerebrospinal fluid (CSF) cytology remains the gold standard approach for diagnosing of leptomeningeal metastases (LM), but has clinical problems due to its low sensitivity. This systemic review and meta-analysis evaluated the diagnostic accuracy of the novel CSF biomarkers of liquid biopsy and magnetic resonance imaging (MRI) for detecting LM in patients with solid cancers. Methods: A systematic search of electronic databases was conducted to identify all published diagnostic accuracy studies on CSF liquid biopsies and MRI since January 2000 with registration for PROSPERO (#CRD42022301988). Articles were selected based on pre-defined inclusion and exclusion criteria following the PRISMA 2020 statement. Results: The search yielded 3790 citations, and 10 studies with 668 patients were included in the final analysis. The pooled prevalence of LM was 50.9% (340/668). The respective sensitivity and specificity for index tests were as follows: circulating tumor cells (CTC), 87.0% (95% confidence interval [CI] 77.9-92.6%) and 93.8% (86.9-97.2%); cell-free tumor DNA, 97.9% (19.3-100%) and 89.0% (25.3-99.5%); MRI 59.4% (60.7-76.9%) and 97.6% (77.3-99.8%); cytology, 71.9% (54.7-82.9%) and 100%. The diagnostic odds ratio was 100.6 (29.38-344.09) for CTC and 93.3 (88.42-1034.05) for MRI. Conclusion: Novel CSF liquid biopsies and MRI may offer improved diagnostic accuracy for LM from solid cancers; however, further research is required to specify the threshold values and to construct standards for individual primary cancers.

Gastric carcinoma in a South American sea lion (Otaria flavescens).

A 22-year-old captive male South American sea lion (Otaria flavescens) developed an undifferentiated carcinoma originating in the cardiac region of the stomach. Clinical symptoms included vomiting, anorexia and weight loss. Ultrasonography and endoscopy showed gastric wall thickness. At necropsy, the gastric wall had significant thickening around the cardiac region, and metastases were found in some organs. Histologically, samples from the stomach wall and metastases showed the same tumor tissue. Immunohistochemistry was positive for epithelium markers. Ductal growth, keratinocytes or signet ring cells were absent. The tumor was classified as an undifferentiated carcinoma using the World Health Organization's (WHO) guide to international classification of tumors in domestic animals. This is the first report of a primary gastric carcinoma in a pinniped.

Porencephaly in a fennec fox (Vulpes zerda).

A postmortem examination revealed a large brain cavity in the right cerebral hemisphere of a 9-year-old male fennec (Vulpes zerda). The cavity was filled with cerebrospinal fluid and extended to the right lateral ventricle. Swelling and displacement of the right hippocampal area were also observed. Histologic examination revealed no evidence of previous infarct lesions, hemorrhage, inflammation or invasive tumor cells. Observation of the defective part suggested a local circulatory disorder during the fetal stage, although the cause was not detected. No neurological symptoms that could enable a provisional diagnosis were observed during the course of his life. This is the first report of asymptomatic porencephaly in a fennec fox.

Prevalence of low-penetrant germline TP53 D49H mutation in Japanese cancer patients.

Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline TP53 and found 10 types of non-synonymous single nucleotide variants. In the present study, we focused on 6 patients with germline D49H mutation located in the transactivation domain 2 of p53 protein, since the mutation seemed to be prevalent in cancer patients and to be pathogenic. According to the initial survey for family history of the proband with the germline TP53 D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline TP53 mutation screening. Since this patient possesses double germline mutations of TP53 D49H and A159D, further studies are required to evaluate contribution of the D49H mutation in this morbidity. The remaining 5 patients had family histories of cancer, but none fulfills the criteria either for the Li-Fraumeni/Li-Fraumeni-like syndromes or the 2009 Chompret criteria for germline TP53 mutation screening. It is possible to postulate that the germline TP53 D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline TP53 mutation plays an important role in clinical practice as it will prevent mistaking cancer patients with unusual heredities for sporadic cases.

Tetra-n-butylammonium Iodide Catalyzed C-H Azidation of Aldehydes with Thermally Stable Azidobenziodoxolone.

Tetra-n-butylammonium iodide can efficiently catalyze direct azidation of aldehyde C-H bonds with thermally stable azidobenziodoxolone at room temperature. Compared to conventional methods, which require excessive amounts of highly explosive azide sources, this is a safe and convenient procedure.

The first report of peritoneal tetrathyridiosis in squirrel monkey (Saimiri sciureus).

This report describes a case of peritoneal larval cestodiasis caused by tetrathyridia of Mesocestoides sp. in an adult female squirrel monkey. The monkey had lived in a zoological garden in Japan and had a clinical history of wasting. At necropsy, numerous whitish oval masses were found in the liver and peritoneal cavity. These masses contained larval cestodes. Morphological observation and molecular analyses of the mitochondrial 12S ribosomal RNA gene and cytochrome c oxidase subunit 1 gene sequences allowed us to identify the larva as the tetrathyridium of Mesocestoides sp. This is the first report of Mesocestoides larvae in a squirrel monkey in Japan.