Safety and feasibility comparison between three different CT-guided localization techniques under systemic approach algorithm.

INTRODUCTION: In the era of lung cancer screening, more and more sub-centimeter indeterminate lung lesions are being identified. It is difficult to approach these lesions and obtain tissue to confirm diagnosis. CT-guided navigation followed by surgical resection is the best way to overcome this difficulty. The aim of this study is to compare the safety and feasibility of wire and dye-tattoo CT-guided localization techniques. MATERIALS AND METHODS: From September 2019 to August 2021, 418 patients who presented with single lung lesion and received single CT-guided localization were included in this study. Procedure details, navigation results, and related complications were compared. RESULTS: For patients who received wire localization, majority (98.3 %) had perihilar lesions. In addition, 68 (57.1 %) patients received tangential approach because of lesions were blocked by bony or vital structure, abutting major fissure, or previous approach failure. The characteristics of lesion location was quite different than dye-tattooing technique (p = 0.033). As regards persistence of the target lesion localization, the interval between localization and surgery using ICG tattooing was 829.0 ± 552.9 min; much longer than the other two navigation techniques (p < 0.0001). As regards safety, patients who received wire localization had a higher rate of pneumothorax (p = 0.042) and pulmonary hemorrhage (p < 0.001) than the dye-tattooing techniques. DISCUSSION: CT-guided navigation techniques are safe and feasible. Wire localization is suitable for centrally located lesions but the wire needs to be fixed properly and symptomatic pneumothorax monitored for. Dye-tattooing is more suitable for peripheral lesions, while ICG localization persists longer than other techniques.

Ultrasound tissue scatterer distribution imaging: An adjunctive diagnostic tool for shear wave elastography in characterizing focal liver lesions.

OBJECTIVES: Focal liver lesion (FLL) is a prevalent finding in cross-sectional imaging, and distinguishing between benign and malignant FLLs is crucial for liver health management. While shear wave elastography (SWE) serves as a conventional quantitative ultrasound tool for evaluating FLLs, ultrasound tissue scatterer distribution imaging (TSI) emerges as a novel technique, employing the Nakagami statistical distribution parameter to estimate backscattered statistics for tissue characterization. In this prospective study, we explored the potential of TSI in characterizing FLLs and evaluated its diagnostic efficacy with that of SWE. METHODS: A total of 235 participants (265 FLLs; the study group) were enrolled to undergo abdominal examinations, which included data acquisition from B-mode, SWE, and raw radiofrequency data for TSI construction. The area under the receiver operating characteristic curve (AUROC) was used to evaluate performance. A dataset of 20 patients (20 FLLs; the validation group) was additionally acquired to further evaluate the efficacy of the TSI cutoff value in FLL characterization. RESULTS: In the study group, our findings revealed that while SWE achieved a success rate of 49.43 % in FLL measurements, TSI boasted a success rate of 100 %. In cases where SWE was effectively implemented, the AUROCs for characterizing FLLs using SWE and TSI stood at 0.84 and 0.83, respectively. For instances where SWE imaging failed, TSI achieved an AUROC of 0.78. Considering all cases, TSI presented an overall AUROC of 0.81. There was no statistically significant difference in AUROC values between TSI and SWE (p > 0.05). In the validation group, using a TSI cutoff value of 0.67, the AUROC for characterizing FLLs was 0.80. CONCLUSIONS: In conclusion, ultrasound TSI holds promise as a supplementary diagnostic tool to SWE for characterizing FLLs.

Bioinformatic analysis and verification of a lipid metabolism-related long noncoding RNA prognostic signature for head and neck squamous cell carcinoma.

PURPOSE: Both lipid metabolism reprogramming and lncRNAs exert effects on tumor development. We aimed to predict the prognosis of head and neck squamous cell carcinoma (HNSCC) based on lipid metabolism-related (LR)-lncRNAs. METHODS: LR-lncRNAs were determined from the RNA-ref profiles of HNSCC samples in The Cancer Genome Atlas (TCGA). The prognostic model was established by univariate Cox and Lasso regression analysis. Clinical relevance and predictive accuracy were investigated, and external validation was also performed in the Gene Expression Omnibus (GEO) cohort. Tumor immune infiltration and relevant functional analysis, including the association of autophagy with prognostic signatures, were conducted through single-sample gene set enrichment analysis (ssGSEA). The regulatory network of candidate LR-lncRNAs was investigated via coexpression, ceRNA and cis/trans acting interactions. Potential genes were selected through qRT-PCR analysis, and their effects on tumor biological activities and autophagic activity were explored after gene knockdown. RESULTS: A total of 222 LR-lncRNAs were identified. Among the 41 genes with prognostic significance, 17 lncRNAs were eligible for the risk model. Patients in the high-risk group had a poorer prognosis than those in the low-risk group, and the risk score was found to be positively associated with tumor microenvironment infiltration via multiple algorithms. Furthermore, improved prognosis was found in patients with high autophagic scores and low risk scores, and autophagy-related genes such as PINK1 and CCL2 showed significantly lower expression in the low-risk group. The expression of immune checkpoint genes such as CD28, CTLA4 and PDCD1 decreased dramatically in the high-risk group. The target genes of candidate lncRNAs were confirmed, such as ENO2 and PPAR-gamma. Furthermore, MIR4435-2HG was the most significantly overexpressed lncRNA in HNSCC cell lines and tumor samples, which could promote proliferation and migration and inhibit apoptosis. Additionally, MIR4435-2HG silencing activated autophagy by increasing LC3B expression. CONCLUSION: This study constructed an LR-lncRNA prognostic signature for HNSCC and indicated its relationships with tumor immunity and autophagy, which provides a promising future for LR-lncRNA-oriented prognostic tools and therapeutic targets.

Temporal patterns and distribution of pyroptosis-related molecules and effects of human mesenchymal stem cells on pyroptosis following cerebral ischemia/reperfusion in rats.

OBJECTIVES: Pyroptosis is a new type of programmed cell death that has a strong proinflammatory effect. The present study investigated the dynamic changes of pyroptosis-related molecules and the effect of mesenchymal stem cells (MSCs) on pyroptosis following cerebral ischemia/reperfusion (I/R). MATERIALS AND METHODS: The temporal pattern and cellular distribution of caspase-1, Gasdermin D and E (GSDMD and GSDME) in the peri-infarct area, and the effect of human MSCs on GSDMD, IL-1ß, IL-18, Lactate dehydrogenase (LDH) and neurological function were studied in a rat model of transient focal cerebral ischemia. RESULTS: The expression of caspase-1 mRNA increased with time, with a protein level of pro-caspase-1 comparable to its mRNA level, while the level of cleaved-caspase-1 protein peaked at 48 h following I/R. Increased levels of GSDMD mRNA and protein were also observed, with a peak level at 24 h. There were no significant changes in GSDME mRNA or protein expression after I/R. In regards to changes in the number of cells expressing GSDMD after I/R, that for neurons was more significant than those for microglia and astrocytes. The modified neurological severity score discrepancy and the expression of GSDMD showed no significant differences within 24 h following I/R between the MSC- and NS-treated groups, but MSCs treatment promoted the secretion of IL-1ß, IL-18 and LDH. CONCLUSIONS: In the early stage of cerebral infarction in rats, there were dynamic changes in pyroptosis-related molecules (caspase-1 and GSDMD), but MSCs showed no effect on the levels of GSDMD or neurological function.

Microglial and Neuronal Cell Pyroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation Aggravates Cell Injury via Activation of the Caspase-1/GSDMD Signaling Pathway.

Pyroptosis is a new type of programmed cell death, which induces a strong pro-inflammatory reaction. However, the mechanism of pyroptosis after brain ischemia/reperfusion (I/R) and the interaction between different neural cell types are still unclear. This study comprehensively explored the mechanisms and interactions of microglial and neuronal pyroptosisin the simulated I/R environment in vitro. The BV2 (as microglial) and HT22(as neuronal) cells were treated by oxygen-glucose deprivation/reoxygenation (OGD/R). Both BV2 and HT22 cells underwent pyroptosis after OGD/R, and the pyroptosis occurred at earlier time point in HT22than that of BV2. Caspase-11 and Gasdermin E expression in BV2 and HT22 cells did not change significantly after OGD/R. Inhibition of caspase-1 or GSDMD activity, or down-regulation of GSDMD expression, alleviated pyroptosis in both BV2 and HT22 cells after OGD/R. Transwell studies further showed that OGD/R-treated HT22 or BV2 cells aggravated pyroptosis of adjacent non-OGD/R-treated cells, which could be relieved by inhibition of caspase-1 or GSDMD. These results suggested that OGD/R induces pyroptosis of microglia and neuronal cells and aggravates cell injury via activation of caspase-1/GSDMD signaling pathway. Our findings indicated that caspase-1 and GSDMD may be therapeutic targets after cerebral I/R.

The role of intracellular calcium-store-mediated calcium signals in in vivo sensor and effector functions of microglia.

Under physiological conditions microglia, the immune sentinels of the brain, constantly monitor their microenvironment. In the case of danger, damage or cell/tissue dyshomeostasis, they react with changes in process motility, polarization, directed process movement, morphology and gene expression profile; release pro- and anti-inflammatory mediators; proliferate; and clean brain parenchyma by means of phagocytosis. Based on recent transcriptomic and in vivo Ca2+ imaging data, we argue that the local cell/tissue dyshomeostasis is sensed by microglia via intracellular Ca2+ signals, many of which are mediated by Ca2+ release from the intracellular Ca2+ stores. These signals encode the strength, duration and spatiotemporal pattern of the stimulus and, at the same time, relay this information further to trigger the respective Ca2+ -dependent effector pathways. We also point to the fact that microglial Ca2+ signalling is sexually dimorphic and undergoes profound changes across the organism's lifespan. Interestingly, the first changes in microglial Ca2+ signalling are visible already in 9- to 11-month-old mice, roughly corresponding to 40-year-old humans.

The combination of sarcopenia and biochemical factors can predict the survival of hepatocellular carcinoma patients receiving transarterial chemoembolization.

Background: Transarterial chemoembolization(TACE) is the suggested treatment for hepatocellular carcinoma (HCC) not amenable to curative treatments. We investigated the role of sarcopenia on overall survival in HCC patients receiving TACE and proposed a new prognostic scoring system incorporating sarcopenia. Materials and methods: We retrospectively analyzed 260 HCC patients who received TACE between 2010 and 2015. Total psoas muscle was measured on a cross-sectional CT image before the first TACE session. Sarcopenia was defined by the pre-determined sex-specific cutoff value. We assessed the impact of sarcopenia and other biochemical factors on the overall survival and compared the new scoring system with other prognostic scoring systems. Results: One hundred and thirty patients (50%) were classified as sarcopenia before the first TACE. They were older with a higher male tendency and a significantly lower body mass index (BMI). Cox regression multivariate analysis demonstrated that sarcopenia, multiple tumors, maximal tumor diameter≥ 5cm, major venous thrombosis, sarcopenia, AFP ≥ 200 ng/ml, and albumin<3.5mg/dL were independent poor prognostic factors for overall survival in HCC patients receiving TACE. Our scoring system comprising these factors outperformed other major scoring systems in terms of predicting survival after TACE. Conclusion: The current study demonstrated that sarcopenia was an independent prognostic factor for HCC undergoing TACE therapy. Our newly developed scoring system could effectively predict patient survival after TACE. Physicians could, based on the current score model, carefully select candidate patients for TACE treatment in order to optimize their survival. Further studies are warranted to validate our findings.

Endoscopic salvage therapy after failed biliary cannulation using advanced techniques: A concise review.

Therapeutic endoscopic retrograde cholangiopancreatography (ERCP) begins with successful biliary cannulation. However, it is not always be successful. The failure of the initial ERCP is attributed to two main aspects: the papilla/biliary orifice is endoscopically accessible, or it is inaccessible. When the papilla/biliary orifice is accessible, bile duct cannulation failure can occur even with advanced cannulation techniques, including double guidewire techniques, transpancreatic sphincterotomy, needle-knife precut papillotomy, or fistulotomy. There is currently no consensus on the next steps of treatment in this setting. Therefore, this review aims to propose and discuss potential endoscopic options for patients who have failed ERCP due to difficult bile duct cannulation. These options include interval ERCP, percutaneous-transhepatic-endoscopic rendezvous procedures (PTE-RV), and endoscopic ultrasound-assisted rendezvous procedures (EUS-RV). The overall success rate for interval ERCP was 76.3% (68%-79% between studies), and the overall adverse event rate was 7.5% (0-15.9% between studies). The overall success rate for PTE-RV was 88.7% (80.4%-100% between studies), and the overall adverse event rate was 13.2% (4.9%-19.2% between studies). For EUS-RV, the overall success rate was 82%-86.1%, and the overall adverse event rate was 13%-15.6%. Because interval ERCP has an acceptably high success rate and lower adverse event rate and does not require additional expertise, facilities, or other specialists, it can be considered the first choice for salvage therapy. EUS-RV can also be considered if local experts are available. For patients in urgent need of biliary drainage, PTE-RV should be considered.

Differential Response to Sorafenib Administration for Advanced Hepatocellular Carcinoma.

Sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). However, there is no evidence for a response of different target lesions to sorafenib administration. Therefore, we aimed to evaluate the effect of sorafenib on various aHCC target lesions. The outcomes of sorafenib treatment on aHCC, i.e., treatment response for all Child A status patients receiving the drug, were analyzed. Of 377 aHCC patients, 73 (19.3%) had complete/partial response to sorafenib, while 134 (35.4%) and 171 (45.2) had a stable or progressive disease, respectively, in the first six months. Of the evaluated metastatic lesions, 149 (39.4%), 48 (12.7%), 123 (32.5%), 98 (25.9%), 83 (22.0%), and 45 (11.9%) were present in liver, bone, lung, portal/hepatic vein thrombus, lymph nodes, and peritoneum, respectively. The overall survival and duration of treatment were 16.9 ± 18.3 and 8.1 ± 10.5 months (with median times of 11.4 and 4.6, respectively). Our analysis showed poor outcomes in macroscopic venous thrombus and bone, higher AFP, and multiple target lesions. ALBI grade A had a better outcome. Sorafenib administration showed good treatment outcomes in selected situations. PD patients with thrombus or multiple metastases should be considered for sorafenib second-line treatment. The ALBI liver function test should be selected as a treatment criterion.

Reappraisal of the Role of Alkaline Phosphatase in Hepatocellular Carcinoma.

Background: Alkaline phosphatase (ALP) is a marker of liver function and is associated with biliary tract disease. It was reported as a prognostic factor for hepatocellular carcinoma (HCC). The genetic expression in tumor-tissue microarrays and the perioperative serologic changes in ALP have never been studied for their correlation with HCC prognosis. Methods: The genetic expression of ALP isoforms (placental (ALPP), intestinal (ALPI) and bone/kidney/liver (ALPL)) was analyzed in tumor and non-cancerous areas in 38 patients with HCC after partial hepatectomy. The perioperative change in ALP was further analyzed in a cohort containing 525 patients with HCC to correlate it with oncologic outcomes. A total of 43 HCC patients were enrolled for a volumetry study after major and minor hepatectomy. Results: The genetic expression of the bone/kidney/liver isoform was specifically and significantly higher in non-cancerous areas than in tumors. Patients with HCC with a higher ALP (>81 U/dL) had significantly more major hepatectomies, vascular invasion, and recurrence. Cox regression analysis showed that gender, major hepatectomies, the presence of satellite lesions, higher grades (III or IV) and perioperative changes in liver function tests were independent prognostic factors for recurrence-free survival, and a postoperative increase in the ALP ratio at postoperative day (POD) 7 vs. POD 0 > 1.46 should be emphasized. A liver regeneration rate more than 1.8 and correlation analysis revealed that the ALP level at POD 7 and 30 was significantly higher and correlated with remnant liver growth. Conclusions: This study demonstrated that the perioperative ALP change was an independent prognostic factor for HCC after partial hepatectomies, and the elevation of ALP represented a functional biomarker for the liver but not an HCC biomarker. The higher regeneration capacity was possibly associated with the elevation of ALP after operation.

Reconstruction of Separated Intrahepatic Ducts Using the Cystic and Common Hepatic Ducts in Right-Lobe Living-Donor Liver Transplantation: Experiences of Surgical Techniques, Biliary Complications, and Outcomes in a Single Institution.

BACKGROUND Duct-to-duct biliary reconstruction has been increasingly used in living-donor liver transplantation. Information regarding dual duct-to-duct biliary anastomoses is limited. We present the largest case series to date on the use of the cystic and common hepatic ducts as dual-ductal anastomosis, along with long-term follow-up results. MATERIAL AND METHODS In this study, 740 patients underwent right-lobe living-donor liver transplantation; 56 of them were documented as dual-ductal anastomoses. We analyzed recipient and donor characteristics, surgical procedures, appearance of biliary complications, corresponding interventions, and long-term biliary outcomes. RESULTS Cystic and common hepatic ducts were utilized in 56 cases of dual-ductal biliary reconstruction, which we categorized into 2 types: A (78.6%), in which the right anterior intrahepatic duct was anastomosed to the common hepatic duct and the right posterior intrahepatic duct to the cystic duct; and B (21.4%), which was the reverse of A. After a median follow-up period of 46.4 months, 23 patients (41.1%) experienced complications, including biliary leakage and biliary stricture. However, after aggressive intervention (patent biliary anastomosis in most of them), 50 of 56 patients (89.3%) had patent biliary anastomosis and restored normal liver function at the end of follow-up. A small graft (graft-to-recipient weight ratio <0.9%) was the only predictor of biliary complications after multivariate analysis. CONCLUSIONS Dual-ductal biliary reconstruction in adult right-lobe living-donor liver transplantation is challenging but feasible. Our findings support the use of the cystic duct for reconstruction in selected patients. Good long-term results can be achieved with adequate management of patients with biliary complications.

Risk Factors of Duodenobiliary Reflux-Related Dysfunction of Covered Biliary Metal Stents after Treatment of Duodenal Stricture in Patients with Malignant Biliary and Duodenal Obstruction.

Duodenal obstruction is often accompanied with unresectable malignant distal biliary obstruction in patients who have undergone biliary self-expandable metal stent (SEMS) placement. Duodenobiliary reflux (DBR) is a major cause of recurrent biliary obstruction (RBO) after covered biliary SEMS placement. We analyzed the risk factors for DBR-related SEMS dysfunction following treatment for malignant duodenal obstruction. Sixty-one patients with covered SEMS who underwent treatment for duodenal obstruction were included. We excluded patients with tumor-related stent dysfunction (n = 6) or metal stent migration (n = 1). Fifty-four patients who underwent covered biliary SEMS placement followed by duodenal metal stenting or surgical gastrojejunostomy were included. Eleven patients had DBR-related biliary SEMS dysfunction after treatment of duodenal obstruction. There was no difference between the duodenal metal stenting group and the surgical gastrojejunostomy group. Duodenal obstruction below the papilla of Vater and a score of ≤2 on the Gastric Outlet Obstruction Scoring System after treatment for duodenal obstruction were associated with DBR-related covered biliary SEMS dysfunction. Thus, creating a reliable route for ensuring good oral intake and avoiding DBR in patients with duodenal obstruction below the papilla of Vater are both important factors in preventing DBR-related covered biliary SEMS dysfunction.

Predictors of Invasive Adenocarcinomas among Pure Ground-Glass Nodules Less Than 2 cm in Diameter.

Benign lesions, atypical adenomatous hyperplasia (AAH), and malignancies such as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) may feature a pure ground-glass nodule (pGGN) on a thin-slide computed tomography (CT) image. According to the World Health Organization (WHO) classification for lung cancer, the prognosis of patients with IA is worse than those with AIS and MIA. It is relatively risky to perform a core needle biopsy of a pGGN less than 2 cm to obtain a reliable pathological diagnosis. The early and adequate management of patients with IA may provide a favorable prognosis. This study aimed to disclose suggestive signs of CT to accurately predict IA among the pGGNs. A total of 181 pGGNs of less than 2 cm, in 171 patients who had preoperative CT-guided localization for surgical excision of a lung nodule between December 2013 and August 2019, were enrolled. All had CT images of 0.625 mm slice thickness during CT-guided intervention to confirm that the nodules were purely ground glass. The clinical data, CT images, and pathological reports of those 171 patients were reviewed. The CT findings of pGGNs including the location, the maximal diameter in the long axis (size-L), the maximal short axis diameter perpendicular to the size-L (size-S), and the mean value of long and short axis diameters (size-M), internal content, shape, interface, margin, lobulation, spiculation, air cavity, vessel relationship, and pleural retraction were recorded and analyzed. The final pathological diagnoses of the 181 pGGNs comprised 29 benign nodules, 14 AAHs, 25 AISs, 55 MIAs, and 58 IAs. Statistical analysis showed that there were significant differences among the aforementioned five groups with respect to size-L, size-S, and size-M (p = 0.029, 0.043, 0.025, respectively). In the univariate analysis, there were significant differences between the invasive adenocarcinomas and the non-invasive adenocarcinomas with respect to the size-L, size-S, size-M, lobulation, and air cavity (p = 0.009, 0.016, 0.008, 0.031, 0.004, respectively) between the invasive adenocarcinomas and the non-invasive adenocarcinomas. The receiver operating characteristic (ROC) curve of size for discriminating invasive adenocarcinoma also revealed similar area under curve (AUC) values among size-L (0.620), size-S (0.614), and size-M (0.623). The cut-off value of 7 mm in size-M had a sensitivity of 50.0% and a specificity of 76.4% for detecting IAs. In the multivariate analysis, the presence of air cavity was a significant predictor of IA (p = 0.042). In conclusion, the possibility of IA is higher in a pGGN when it is associated with a larger size, lobulation, and air cavity. The air cavity is the significant predictor of IA.

The short-term safety and efficacy of TANDEM microspheres of various sizes and doxorubicin loading concentrations for hepatocellular carcinoma treatment.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) is the most common treatment for unresectable hepatocellular carcinoma (HCC). However, the effect of drug loading concentration and microsphere size on treatment outcomes remains unclear. This retrospective study compares the outcomes of 87 HCC patients who underwent DEB-TACE with half-loaded or full-loaded doxorubicin (maximum capacity 50 mg/mL) in 75-µm or 100-µm microspheres. Treatment with 100-µm microspheres resulted in significantly lower rates of procedure-related complications (6.6% vs. 26.9%; P < 0.05), post-embolization syndrome (32.8% vs. 61.5%, P < 0.05), SIR complications (32.8% vs. 61.5%; P < 0.01) and adverse events involving abdominal pain (19.7% vs. 42.3%; P < 0.05). Half-load doxorubicin microspheres resulted in greater treatment response (OR, 4.00; 95% CI 1.06-15.13; P, 0.041) and shorter hospital stays (OR, - 1.72; 95% CI - 2.77-0.68; P, 0.001) than did microspheres loaded to full capacity. Stratified analysis further showed that patients treated with 100-µm half-load doxorubicin microspheres had a higher CR (63.6% vs 18.0%) and ORR (90.9 vs 54.0%) and a shorter hospital stay (1.6 ± 1.3 vs 4.2 ± 2.3 days) than did those treated with full-load microspheres (P < 0.05). Thus, the drug-loading concentration of microspheres in DEB-TACE should be carefully considered.

A preliminary study of hepatocellular carcinoma post proton beam therapy using MRI as an early prediction of treatment effectiveness.

PURPOSE: To demonstrate the feasibility of magnetic resonance imaging (MRI) for early prediction of proton beam therapy (PBT) effectiveness in hepatocellular carcinoma (HCC). METHODS: Clinical data of the HCC patients without regional lymph node involvement or distant metastasis who received PBT at this institution between 2014 and 2017 were reviewed. A total of 43 patients were included. Tumor regression pattern after PBT were examined on the basis of follow-up duration. The variables were compared between patients with and without early tumor regression (ETR). RESULTS: The median follow-up duration was 40 months (range, 9-62 months). The cumulative overall survival rate at 6 months, 1 years and 5 years was 100%, 88.4%, 63.4%, respectively. Child-Pugh class A, local tumor control (LTC), complete response (CR), and ETR were significantly associated with overall survival (p < 0.05 each). Of 43 patients, 25 patients (58.1%) reached CR in the PBT-irradiated region. Twelve patients (27.9%) had a partial response and 3 patients (7.0%) had a stationary disease. Three patients (7.0%) developed in-field progression. The LTC rate at 5 years was 93.0%. Of the 25 patients who achieved a CR in the PBT-irradiated region, the median time to CR was 5 months (range, 1-19 months). Twenty-two patients (51.2%) showed ETR of the HCC, while 21 patients (48.8%) showed non-ETR. A significant association was observed between ETR and CR of the HCC after PBT (p < 0.001). CONCLUSION: The post-PBT MRI follow-up at 3 months is helpful for monitoring therapeutic response. ETR of the HCC predicted a higher rate of CR and was associated with overall survival, which provides more accurate clinical management.

Efficacy and Safety of Preoperative vs. Intraoperative Computed Tomography-Guided Lung Tumor Localization: A Randomized Controlled Trial.

Background: Thoracoscopic removal of small pulmonary nodules is traditionally accomplished through a two-step approach-with lesion localization in a CT suite as the first step followed by lesion removal in an operating room as the second step. While the advent of hybrid operating rooms (HORs) has fostered our ability to offer a more patient-tailored approach that allows simultaneous localization and removal of small pulmonary nodules within a single-step, randomized controlled trials (RCTs) that compared the two techniques (two- vs. single-step) are still lacking. Methods: This is a RCT conducted in an academic hospital in Taiwan between October 2018 and December 2019. To compare the outcomes of traditional two-step preoperative CT-guided small pulmonary nodule localization followed by lesion removal vs. single-step intraoperative CT-guided lesion localization with simultaneous removal performed by a dedicated team of thoracic surgeons. The analysis was conducted in an intention-to-treat fashion. The primary study endpoint was the time required for lesion localization. Secondary endpoints included radiation doses, other procedural time indices, and complication rates. Results: A total of 24 and 25 patients who received the single- and two-step approach, respectively, were included in the final analysis. The time required for lesion localization was significantly shorter for patients who underwent the single-step procedure (median: 13 min) compared with the two step-procedure (median: 32 min, p < 0.001). Similarly, the radiation dose was significantly lower for the former than the latter (median: 5.64 vs. 10.65 mSv, respectively, p = 0.001). Conclusions: The single-step procedure performed in a hybrid operating room resulted in a simultaneous reduction of both localization procedural time and radiation exposure.

The Use of Artificial Intelligence in the Differentiation of Malignant and Benign Lung Nodules on Computed Tomograms Proven by Surgical Pathology.

The purpose of this work was to evaluate the performance of an existing commercially available artificial intelligence (AI) software system in differentiating malignant and benign lung nodules. The AI tool consisted of a vessel-suppression function and a deep-learning-based computer-aided-detection (VS-CAD) analyzer. Fifty patients (32 females, mean age 52 years) with 75 lung nodules (47 malignant and 28 benign) underwent low-dose computed tomography (LDCT) followed by surgical excision and the pathological analysis of their 75 nodules within a 3 month time frame. All 50 cases were then processed by the AI software to generate corresponding VS images and CAD outcomes. All 75 pathologically proven lung nodules were well delineated by vessel-suppressed images. Three (6.4%) of the 47 lung cancer cases, and 11 (39.3%) of the 28 benign nodules were ignored and not detected by the AI without showing a CAD analysis summary. The AI system/radiologists produced a sensitivity and specificity (shown in %) of 93.6/89.4 and 39.3/82.1 in distinguishing malignant from benign nodules, respectively. AI sensitivity was higher than that of radiologists, though not statistically significant (p = 0.712). Specificity obtained by the radiologists was significantly higher than that of the VS-CAD AI (p = 0.003). There was no significant difference between the malignant and benign lesions with respect to age, gender, pure ground-glass pattern, the diameter and location of the nodules, or nodules <6 vs. ≥6 mm. However, more part-solid nodules were proven to be malignant than benign (90.9% vs. 9.1%), and more solid nodules were proven to be benign than malignant (86.7% vs. 13.3%) with statistical significance (p = 0.001 and <0.001, respectively). A larger cohort and prospective study are required to validate the AI performance.

Preoperative versus intraoperative image-guided localization of multiple ipsilateral lung nodules.

OBJECTIVES: Computed tomography (CT)-guided localization of multiple ipsilateral pulmonary nodules remains challenging. Hybrid operating rooms equipped with cone-beam CT and laser navigation systems have the potential for improving clinical workflows and patient outcomes. METHODS: Patients with multiple ipsilateral pulmonary nodules requiring localization were divided according to the localization method [preoperative CT-guided (POCT group) localization versus intraoperative CT-guided (IOCT group) localization]. The 2 groups were compared in terms of procedural efficacy, safety and radiation exposure. RESULTS: Patients in the IOCT (n = 12) and POCT (n = 42) groups did not differ in terms of demographic and tumour characteristics. Moreover, the success and complication rates were similar. Notably, the IOCT approach allowed multiple nodules to be almost simultaneously localized-resulting in a shorter procedural time [mean difference (MD) -15.83 min, 95% confidence interval (CI) -7.97 to -23.69 min] and lower radiation exposure (MD -15.59 mSv, 95% CI -7.76 to -23.42 mSv) compared with the POCT approach. However, the total time under general anaesthesia was significantly longer in the IOCT group (MD 34.96 min, 95% CI 1.48-68.42 min), despite a similar operating time. The excess time under anaesthesia in the IOCT group can be attributed not only to the procedure per se but also to a longer surgical preparation time (MD 21.63 min, 95% CI 10.07-33.19 min). CONCLUSIONS: Compared with the POCT approach, IOCT-guided localization performed in a hybrid operating room is associated with a shorter procedural time and less radiation exposure, albeit at the expense of an increased time under general anaesthesia.

Safety and Feasibility of Repeated Intrathecal Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells in Patients with Neurological Diseases.

Mesenchymal stromal cells (MSCs) have become the most commonly used adult stem cells in regenerative medicine. Preclinical studies have shown that MSCs-based therapy is a potential new treatment approach for neurological diseases. Intrathecal injection has unique feature which allows stem cells to directly migrate to the lesion site in patients with central nervous system (CNS) diseases. In this study, we evaluate the safety and feasibility of intrathecal allogeneic bone marrow-derived MSCs (BM-MSCs) in patients with neurological diseases. This open-label clinical study included 37 patients (14 diseases). Eligible patients underwent a baseline assessment and were intrathecally injected with allogeneic BM-MSCs (1 × 106 cells/kg, 4 consecutive treatments at 1-week intervals). After four infusions, the patients were followed up for at least 6 months. Adverse events, cerebrospinal fluid (CSF) test results, clinical symptoms, physical examination, and haematological and imaging examinations were used to assess the safety and feasibility of the treatment. Also, we performed a systematic review of the safety of all types of intrathecal stem cells and compared our result to previous studies. In our study, the highest adverse event was a slight ache at the injection site (4.11%), followed by fever (3.42%) and mild headache (2.05%). No severe adverse events were reported. After the intrathecal injections, the white blood cell (WBC) counts in the CSF increased in 30 patients and the protein concentration in the CSF exceeded the normal range in 26 patients, while other CSF indicators remained normal. Moreover, these patients had no suspected manifestations of CNS infection. Haematological and imaging examinations showed no abnormal changes after BM-MSCs infusion. Compared with previous studies, the incidence of adverse events was nearly consistent or even lower for headache, fever, nausea, and neck pain. In conclusion, repeated intrathecal allogeneic BM-MSCs are safe, feasible, and promising for the treatment of patients with neurological diseases.

Preoperative CT versus intraoperative hybrid DynaCT imaging for localization of small pulmonary nodules: a randomized controlled trial.

BACKGROUND: Localization of small and/or deep pulmonary nodules before thoracoscopic exploration is paramount to minimize the likelihood of unplanned conversion to thoracotomy. As far as the percutaneous approach is concerned, the most common workflow consists of preoperative computed tomography (POCT) imaging-guided tumor marking (performed in an interventional CT suite) followed by their removal in an operating room (OR). However, the advent of hybrid ORs has allowed intraoperative computed tomography (IOCT)-guided lesion localization. This single center, open-label, randomized, controlled clinical trial aims to compare the efficacy and safety of IOCT versus POCT. METHODS/DESIGN: The study sample will consist of patients presenting with small and/or deep pulmonary nodules who will be randomly allocated to either POCT or IOCT. The time required to complete lesion localization will be the primary efficacy outcome. The following parameters will serve as secondary endpoints: rate of successful targeting during localization and in the operating field, time at risk, operating time, length of time under anesthesia, global OR utilization time, complication (pneumothorax and hemorrhage) rates, and radiation exposure. DISCUSSION: Owing to the increased availability of HORs, our data will be crucial to clarify the feasibility and safety of IOCT versus the traditional POCT approach. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03395964 . Registered on October 8, 2018.