Imaging features of localized IDH wild-type histologically diffuse astrocytomas: a single-institution case series

Abstract Isocitrate dehydrogenase wild-type (IDHwt) diffuse astrocytomas feature highly infiltrative patterns, such as a gliomatosis cerebri growth pattern with widespread involvement. Among these tumors, localized IDHwt histologically diffuse astrocytomas are rarer than the infiltrative type. The aim of this study was to assess and describe the clinical, radiographic, histopathological, and molecular characteristics of this rare type of IDHwt histologically diffuse astrocytomas and thereby provide more information on how its features affect clinical prognoses and outcomes. We retrospectively analyzed the records of five patients with localized IDHwt histologically diffuse astrocytomas between July 2017 and January 2020. All patients were female, and their mean age at the time of the initial treatment was 55.0 years. All patients had focal disease that did not include gliomatosis cerebri or multifocal disease. All patients received a histopathological diagnosis of diffuse astrocytomas at the time of the initial treatment. For recurrent tumors, second surgeries were performed at a mean of 12.4 months after the initial surgery. A histopathological diagnosis of glioblastoma was made in four patients and one of gliosarcoma in one patient. The initial status of IDH1, IDH2, H3F3A, HIST1H3B, and BRAF was “wild-type” in all patients. TERT promoter mutations (C250T or C228T) were detected in four patients. No tumors harbored a 1p/19q codeletion, EGFR amplification, or chromosome 7 gain/10 loss (+ 7/ − 10). We assessed clinical cases of localized IDHwt histologically diffuse astrocytomas that resulted in malignant recurrence and a poor clinical prognosis similar to that of glioblastomas. Our case series suggests that even in patients with histologically diffuse astrocytomas and those who present with radiographic imaging findings suggestive of a localized tumor mass, physicians should consider the possibility of IDHwt histologically diffuse astrocytomas

Colonic Absorption of Low-Molecular-Weight Metabolites Influenced by the Intestinal Microbiome: A Pilot Study

<div><p>Low-molecular-weight metabolites produced by the intestinal microbiome play a direct role in health and disease. However, little is known about the ability of the colon to absorb these metabolites. It is also unclear whether these metabolites are bioavailable. Here, metabolomics techniques (capillary electrophoresis with time-of-flight mass spectrometry, CE-TOFMS), germ-free (GF) mice, and colonized (Ex-GF) mice were used to identify the colonic luminal metabolites transported to colonic tissue and/or blood. We focused on the differences in each metabolite between GF and Ex-GF mice to determine the identities of metabolites that are transported to the colon and/or blood. CE-TOFMS identified 170, 246, 166, and 193 metabolites in the colonic feces, colonic tissue, portal plasma, and cardiac plasma, respectively. We classified the metabolites according to the following influencing factors: (i) the membrane transport system of the colonocytes, (ii) metabolism during transcellular transport, and (iii) hepatic metabolism based on the similarity in the ratio of each metabolite between GF and Ex-GF mice and found 62 and 22 metabolites that appeared to be absorbed from the colonic lumen to colonocytes and blood, respectively. For example, 11 basic amino acids were transported to the systemic circulation from the colonic lumen. Furthermore, many low-molecular-weight metabolites influenced by the intestinal microbiome are bioavailable. The present study is the first to report the transportation of metabolites from the colonic lumen to colonocytes and somatic blood <i>in vivo</i>, and the present findings are critical for clarifying host-intestinal bacterial interactions.</p></div

Metabolomic snapshots of the known phenomenon of intestinal microbiome-dependent production of pro-atherogenic trimethylamine <i>N</i>-oxide by degradation of carnitine/choline in the intestinal tract.

<p>FMO: flavin-containing monooxygenase.</p

Estimation of metabolites to transport to body from colonic lumen using the difference of concentration between GF and Ex-GF mice (Ex-GF/GF ratio).

<p>(A) Metabolites with similar Ex-GF/GF ratios in colonic feces, colonic tissue, portal plasma, and cardiac plasma were considered to be transported from the colonic lumen to cardiac blood. (B) Metabolites with different Ex-GF/GF ratios between colonic feces and colonic tissue are controlled by (i) membrane transport system (C) Metabolites with different Ex-GF/GF ratios between colonic tissue and portal plasma are controlled by (ii) metabolism during transcellular transport. (D) Metabolites with different Ex-GF/GF ratios between portal plasma and portal.</p

Metabolites detected in colonic feces but not in colonic tissue.

<p>Metabolites detected in colonic feces but not in colonic tissue.</p

Differences in the metabolomes of GF and Ex-GF mice.

<p>(A) Number of metabolites that were significantly (<i>p</i> < 0.05) or not significantly different between GF and Ex-GF mice.(B) PCA of metabolome profiles. Fec-Ex, colonic feces of Ex-GF mice; Fec-GF, colonic feces of GF mice; Col-Ex, colon of Ex-GF mice; Col-GF, colon of GF mice; PP-Ex, portal plasma of Ex-GF mice; PP-GF, portal plasma of GF mice; CP-Ex, cardiac plasma of Ex-GF mice; CP-GF, cardiac plasma of GF mice.(C) PCA of metabolome profiles in each specimen.</p

The ExGF/GF ratio and the influence of 3 gateways on each metabolite detected in the colonic feces, colon, portal plasma, and cardiac plasma.

<p>The ExGF/GF ratio and the influence of 3 gateways on each metabolite detected in the colonic feces, colon, portal plasma, and cardiac plasma.</p