Development of a novel nomogram for predicting delayed methotrexate excretion following high-dose methotrexate in adult patients with hematologic malignancies.

PURPOSE: High-dose methotrexate (HDMTX) is integral in treating hematologic malignancies but carries risks of severe toxicities due to prolonged MTX exposure. However, knowledge of delayed MTX excretion is primarily derived from pediatric and adolescent cohorts, with the reported predictors being presented as rough dichotomous values. This study aimed to identify risk factors for delayed MTX excretion exclusively in adult patients with hematologic malignancies and develop a more applicable predictive nomogram based on continuous clinical and laboratory variables. METHODS: 517 HDMTX cycles in 194 patients were retrospectively analyzed. Delayed MTX excretion was defined as either MTX concentration ≥ 1.0 µmol/L at 48 h or ≥ 0.1 µmol/L at 72 h after HDMTX initiation. Multivariate logistic regression analysis was used to construct the nomogram internally validated with the bootstrap method. RESULTS: Delayed MTX excretion was observed in 24.0% of cycles. Six significant predictors were identified: relapsed/refractory disease (Odds ratio [OR] 2.03), fewer HDMTX cycles (OR 0.771), treatment intent (OR 2.13), lower albumin (OR 0.563) and creatinine clearance levels (OR 0.993), and increased γ-glutamyl transpeptidase levels (OR 1.004, all P < 0.05). These were incorporated into a web-based nomogram as continuous variables with good prediction accuracy (area under the curve, 0.73) and without significant overfitting. Delayed MTX excretion increased risks of developing acute kidney injury, even solely at the 72 h timepoint (OR 2.57, P = 0.025), without providing any benefit of clinical outcomes. CONCLUSION: This study comprehensively characterized MTX elimination failure following HDMTX in adult patients and could pave the way for individualized risk prediction.

Prognostic relevance of tumor-infiltrating CD4+ cells and total metabolic tumor volume-based risk stratification in diffuse large B-cell lymphoma.

In order to elucidate the relationship between pretreatment radiomic parameters and the proportions of various tumor-infiltrating (TI) cells, we retrospectively analyzed the association of total metabolic tumor volume (TMTV) and TI cells on biopsied tumor lesions in 171 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The surface markers of TI cells were analyzed by multicolor flow cytometry using a dissected single-cell suspension. In examining the correlation between TI cells and positron-emission tomography-derived parameters (maximum standardized uptake value [SUVmax], total metabolic tumor volume [TMTV], and total lesion glycolysis), intratumoral cell types minimally influenced the results, except for a weak negative correlation between CD4+ cells and SUVmax (R=-0.16, P=0.045). Even for the lesion fluorodeoxyglucose uptake at the biopsied site, CD19+ cells (indicative of malignant burden) showed only a weak correlation with the highest SUV (R=0.21, P=0.009), whereas CD3+ (R=-0.25, P=0.002) and CD4+ cells (R=-0.29, P<0.001) demonstrated a similarly weak inverse correlation. High TMTV and low TI CD4+ cells were independently associated with poor prognosis and their combination identified the most adverse population (3-year progression-free survival: 32.3%, 95% confidence interval [CI]: 19.4-53.7; 3-year overall survival: 48.4%, 95% CI: 33.6-69.6). Moreover, radiomic parameters incorporating the international prognostic index significantly improved the 3-year survival prediction (area under the curve: 0.76, P<0.05) compared to their standalone use. This study underscores the prognostic impact of TI CD4+ cells on DLBCL and suggests that integration of TMTV and TI cell analysis enhances the accuracy of prognostic prediction.

Analysis of baseline circulating tumor cells integrated with PET/CT findings in transplant-ineligible multiple myeloma.

ABSTRACT: We aimed to improve prognostic predictors in patients with transplant-ineligible multiple myeloma (TIE-MM) by combining baseline circulating clonal tumor cells (CTCs) and positron emission tomography/computed tomography (PET/CT) findings. The factors associated with prognosis were retrospectively investigated in 126 patients with TIE-MM who underwent CTC quantification by multiparameter flow cytometry and PET/CT at the initial presentation. The total lesion glycolysis (TLG) level was calculated using the Metavol software. The median percentage of CTC was 0.06% (range, 0%-4.82%), and 54 patients (42.9%) demonstrated high CTC levels. High CTC levels were associated with significantly poorer progression-free survival (PFS, 2-year 43.4% vs 68.1%; P < .001) and overall survival (OS, 5-year 39.0% vs 68.3%; P < .001). Similarly, high TLG levels significantly worsened the PFS (2-year, 41.2% vs 67.6%; P = .038) and OS (5-year, 37.7% vs 63.1%; P = .019). The multivariate analyses showed that Revised International Staging System (R-ISS) III, high CTC and TLG levels, and complete response were significant prognostic factors for PFS and OS. A novel predictive model was constructed using CTCs, TLG, and R-ISS III. The patients were stratified into 3 groups according to the number of risk factors, revealing an extremely high-risk group with a 2-year PFS of 0% and a 5-year OS of 20%. Patients without any high-risk features had better prognosis, with a 2-year PFS of 78.6% and a 5-year OS of 79.5%. The combination of CTCs and volumetric assessment of PET/CT at diagnosis augments the existing stratification systems and may pave the way for a risk-adapted treatment approach.

[A Case of Gastrointestinal Stromal Tumor(GIST)of the Sigmoid Colon with Early Colon Cancer].

A 67-year-old male patient was referred to our department for fecal occult blood in March 2019. In April, lower intestinal endoscopic examination revealed a 25-mm pedunculated polyp in the sigmoid colon. Endoscopic mucosal resection was then performed. The pathological diagnosis was tub1-tub2 with an invasion depth of pT1b 3,000 µm, and ly0 and v1 vascular invasion. The tumor marker levels were normal, with CEA of 1.1 ng/mL and CA19-9 of 13.9 U/mL. An additional laparoscopic low anterior resection and D2 dissection were performed in June. After the endoscopic mucosal resection, pathologic examination revealed densely hyperplastic spindle cells arranged in bundles at the proper muscular layer of the scar site. There was no lymph node metastasis. On immunostaining, the lesion tested positive for c-kit, CD34, and DOG1, but negative for desmin, SMA, and S-100, with a MIB-1 index of 2%. The patient was diagnosed with very low risk gastrointestinal stromal tumor(GIST). We encountered a rare case of early sigmoid colon cancer, complicated by sigmoid colon GIST.

Detection of cellular damage by hydrogen peroxide using SV40-T2 cells on shear horizontal surface acoustic wave (SH-SAW) sensor.

The rat lung epithelial cell line SV40-T2 was used to develop a cellular biosensing system to assay for environmental toxicants. The novel approach on which this system is based involves direct attachment of cultured rat or human cells onto a cell-adhesive matrix on the device through which shear horizontal surface acoustic waves (SH-SAW) are transmitted using 50 MHz SAW resonator. This novel design enables sensitive monitoring of changes of the electrophysical characteristics of cells, such as their conductivity and relative permittivity. A time-dependent change of phase of SAW and change of insertion loss (change of amplitude) were observed when the cells were treated with 0.5 or 1.0 mM H2O2. The change of insertion loss was biphasic, with an early phase (1-3 h) and a late phase (3-6 h). The late phase coincided with the destruction of cell-cell tight junctions detected by measurement of the transepithelial electrical resistance and paracellular permeability; in contrast, the early phase coincided with the destruction of intracellular actin filaments by H2O2. The early-phase effect of H2O2 on phase shift may be attributable to the change of intracellular permittivity by a change of cellular polarity. Immunofluorescence microscopy showed the disappearance of zonula occludens protein 1 from the region of cell-cell contact. These results suggest the correlation between the change of insertion loss as an SAW parameter and the destruction of tight junctions of the cells on the SH-SAW device in the late phase.

Visual colorimetry for trace antimony(V) by ion-pair solid-phase extraction with bis[2-(5-chloro-2-pyridylazo)-5-diethylaminophenolato]cobalt(III) on a PTFE type membrane filter.

A new visual colorimetry for trace antimony(V) based on ion-pair solid-phase extraction to a PTFE-type membrane filter with bis[2-(5-chloro-2-pyridylazo)-5-diethylaminophenolato]cobalt(III) ion ([Co(5-Cl-PADAP)(2)](+)) has been developed. Experiments showed that hexachloroantimonate(V) ion (SbCl(6)(-)) was adsorbed with [Co(5-Cl-PADAP)(2)](+) to the front surface of the PTFE filter. The adsorption of antimony(V) ion was promoted by the addition of lithium chloride as a source of chloride ion. The excess reagent of [Co(5-Cl-PADAP)(2)](+) was eluted by rinsing with a 10 wt% methanol aqueous solution. In this case, the slow rate of the hydrolysis reaction of SbCl(6)(-) and the difference of the hydrophobicity of the ion pairs were important for adsorption and separation with a PTFE-type membrane filter. The antimony(V) concentration was determined through a visual comparison with a standard series. The visual detection limit was 0.10 microg. The calibration curve assessed with the reflection spectrometric responses at 580 nm was linear in the concentration range of 0.10 - 1.2 microg (r = 0.996). The proposed method has been applied to the determination of sub-microgram levels of antimony(V) ion in water samples.