Accurately Locating Metastatic Foci in Lymph Nodes With Lugol's Iodine-Enhanced Micro-CT Imaging.

BACKGROUND: Accurate evaluation of lymph node (LN) status is the key factor to determine the treatment and evaluate prognosis for patients with cancer. However, traditional pathological examination resulted in a 30% false-negative rate of detection of metastases in LNs. This study aimed to utilize Lugol's iodine (I2-IK)-enhanced micro-CT imaging to reveal the 3-dimensional structure of regional LNs and decrease the false-negative rate in pathological examination. METHODS: To explore the feasibility of I2-IK-enhanced micro-CT imaging in locating metastatic lesion in LNs, nonmetastatic and metastatic LNs from mice were used to mimic the imaging process. Then, the LNs from oral squamous cell carcinoma (OSCC) patients were applied to verify the value of I2-IK-enhanced micro-CT imaging in revealing LN structure and locating metastatic lesions in LNs. The glycogen content in nonmetastatic and metastatic LNs was further detected by the use of a glycogen assay kit and periodic acid-Schiff (PAS) staining to explain the imaging differences between them. RESULTS: In nude mice, 0.5% I2-IK staining for 4 h was the best parameter for normal LN. The metastatic foci in metastatic LNs were also clearly outlined in this condition. For nonmetastatic LNs from patients with OSCC, 1% I2-IK staining for 12 h was the best parameter. However, due to the increased volume of metastatic LNs, the image effect of 3% I2-IK staining for 12 h was superior to 1% I2-IK staining [tumor background ratio (TBR), 3% vs. 1%, 1.89 ± 0.10 vs. 1.27 ± 0.07, p < 0.001]. Compared with subsequent pathological sections, we found the CT intensity of metastatic foci in LNs and muscle tissues was significantly higher than in nonmetastatic regions. Meanwhile, the glycogen content of metastatic foci in LNs detected was also significantly higher than in nonmetastatic region. CONCLUSIONS: I2-IK-enhanced micro-CT imaging could identify the spatial location of metastatic foci in LNs. This will be an effective method to assist in decreasing the LN false-negative rate for cancer pathology.

Comparative study on the diagnostic value of intravenous/peritumoral injection of indocyanine green for metastatic lymph node location in patients with head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: Accurate assessment of regional lymph node (LN) status is essential for the treatment of head and neck squamous cell carcinoma (HNSCC) patients. In this study, we aimed to compare the difference between intravenous injection of indocyanine green (ICG) and peritumoral injection of ICG in the location of metastatic LNs. METHODS: Twenty-nine patients were enrolled in this study with 13 patients receiving intravenous injection of ICG and 16 patients receiving peritumoral injection of ICG. During the surgery, the fluorescence-positive LNs in vivo were sent to undergo frozen section after fluorescence intensity was recorded. After the cervical LN dissection, all LNs were sorted by region, and the fluorescence intensity was recorded before the LNs were sent for paraffin section. RESULTS: During the surgery, both intravenous or peritumoral injections with near-infrared (NIR) fluorescence imaging of ICG had their respective pros and cons in vivo, with the sensitivity and specificity being 62.5%/75% and 98.1%/89.1% respectively. After the surgery, both methods could reduce the pathological workload by preselecting the LNs at-risk in the premise of accurate assessing the cervical LN stage. However, intravenous ICG administration was more valuable in determining all types of LN status according to the fluorescence intensity [area under the curve (AUC): 0.91 vs. 0.78, P<0.001]. CONCLUSIONS: With the assistance of NIR fluorescence imaging using ICG, both administration methods could reduce the postoperative complication and the pathological workload, whereas the intravenous mode of ICG administration is superior in application value.

The Diagnostic Accuracy of Liquid Exosomal miRNAs for Cancer Detection: a Meta-Analysis.

BACKGROUND: Early diagnosis of cancer is related to a good prognosis. Noninvasive methods of body fluid diagnosis are receiving more and more attention. Many studies have shown that exosomal miRNAs in body fluids may be potential biomarkers. Therefore, we conducted a meta-analysis to assess the overall diagnostic value of liquid exosomal miRNAs for cancer. METHODS: Relevant research was retrieved from multiple electronic databases. The research quality was evaluated based on the QUADAS-2 scale in Review Manager 5.3. Diagnostic value was evaluated by data analysis using Stata 16.0, and Meta-DiSc 1.4. RESULTS: The meta-analysis included 23 articles and 79 research units. The pooled sensitivity was 0.74, specificity was 0.78, the diagnostic likelihood ratio positive was 3.55, the diagnostic likelihood ratio negative was 0.29, diagnostic OR was 14.26, and area under the curve was 0.8621. These results provide evidence for liquid exosomal miRNAs as potential biomarkers. CONCLUSIONS: Liquid exosomal miRNAs are potential biomarkers for cancer diagnosis. In particular, diagnosis based on multiple miRNAs is more valuable than a single miRNA.

Lugol's Iodine-Enhanced Micro-CT: A Potential 3-D Imaging Method for Detecting Tongue Squamous Cell Carcinoma Specimens in Surgery.

BACKGROUND: A positive surgical margin (PSM) following oral cancer resection results in local recurrence and poor prognosis. Mono-block tumor specimens, especially from the tumor base, are difficult to evaluate. This inaccurate sampling ultimately leads to a false pathological diagnosis. Lugol's iodine (I2-IK)-enhanced micro-CT is an emerging method to image tumor specimens. This study explores the feasibility of I2-IK-enhanced micro-CT to evaluate the surgical margin for tongue squamous cell carcinoma (TSCC) specimens and to further seek optimal staining parameters. METHODS: Rabbit tongue tissues and human TSCC samples were imaged via I2-IK-enhanced micro-CT. The optimal I2-IK concentration and staining time were determined before clinical application using tissue shrinkage, micro-CT image quality, and effect on pathological diagnosis as assessment criteria. Next, 6 TSCC specimens were used to verify the process feasibility of surgical margin imaging with the optimal parameters. Finally, the possible reason by which I2-IK could enhance micro-CT imaging was validated in vitro. RESULTS: I2-IK staining influenced specimen shrinkage, micro-CT image quality, and pathological image quality in a concentration- and time-dependent manner. After comprehensively considering these indicators, 3% I2-IK staining for 48 and 12 h were found to be optimal for rabbit tongue tissues and TSCC samples, respectively. This method could provide a detailed 3-D structure of TSCC samples compared with H&E sections. Moreover, tumor and normal tissues could be differentiated by their glycogen content, which has high affinity with I2-IK. CONCLUSIONS: I2-IK-enhanced micro-CT could, thus, indicate the tumor margin and assist pathological sampling in patients with TSCC postoperation.

Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206+ M2-like macrophage polarization.

Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix deposition with limited treatment options. Based on our previous observation, we hypothesized microcystin-leucine arginine (LR), an environmental cyanobacterial toxin, could potentially suppress pulmonary fibrosis. In this study, we first demonstrated that chronic exposure of microcystin-LR by oral for weeks indeed attenuated the pulmonary fibrosis both on bleomycin-induced rat and fluorescein isothiocyanate-induced mouse models. Our data further indicated that treatment with microcystin-LR substantially reduced TGF-ß1/Smad signaling in rat pulmonary tissues. The experiments in vitro found that microcystin-LR was capable of blocking epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT) through suppressing the differentiation of CD206+ macrophages. Mechanically, microcystin-LR was found to bind to glucose-regulated protein 78 kDa (GRP78) and suppress endoplasmic reticulum unfolded protein response (UPRER) signaling pathways. These events led to the modulation of M2 polarization of macrophages, which eventually contributed to the alleviation of pulmonary fibrosis. Our results revealed a novel mechanism that may account for therapeutic effect of microcystin-LR on IPF.