Invasion Rate Research Articles

Biohybrid hydrogel inhibiting β-klotho/HDAC3 axis for hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC), ranking as the fourth most prevalent cancer globally, has garnered significant attention due to its high invasiveness and mortality rates. However, drug therapies face challenges of inadequate efficacy and unclear mechanisms. Here, we propose a novel biohybrid hydrogel that targets β-klotho (KLB) for HCC treatment. As a dual-network hydrogel, this gel combines gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA) to ensure biocompatibility while enhancing controlled drug release. Notably, it exhibits good storage stability, high drug load capacity, and efficient water absorption. By introducing the HDAC3 inhibitor RGFP966, we can selectively inhibit the activation of KLB. This deactivation effectively blocks the FGF21-KLB signaling pathway and inhibits the progression of HCC. Importantly, we have successfully validated this unique phenomenon both in vivo and in vitro, providing substantial evidence for the efficacy of this hydrogel-based anti-tumor drug delivery system as a promising strategy for HCC treatment. This innovative research outcome brings new hope to the field of tumor therapy, providing a reliable theoretical foundation for future clinical applications.

Extended procedure has no oncological benefits over segmental resection in the treatment of non-metastatic splenic flexure colon cancer, a population-based cohort study and a single center's decade-long experience.

To compare the oncological survival outcome between extended resections (ER) and segmental resection (SR) for non-metastatic splenic flexure tumors. A total of 10,063 splenic flexure colon cancers patients who underwent ER (n = 5546) or SR (n = 4517) from 2010 to 2018 were included from the Surveillance, Epidemiology, and End Results (SEER)-registered database. Additionally, we included 135 patients from our center who underwent ER (n = 54) or SR (n = 81) between 2011 and 2021. Survival rates were compared between groups. To reduce the inherent bias of retrospective studies, propensity score matching (PSM) analysis was performed. In the SEER database, patients in the ER group exhibited higher pT stage, pN stage, larger tumor size, and elevated rates of CEA level, perineural invasion, and tumor deposits compared to those in the SR group (each P < 0.05). The 5-year cancer-specific survival (CSS) rate was slightly lower in the ER group than in the SR group (79.2% vs. 81.6%, P = 0.002), while the 5-year overall survival (OS) rates were comparable between the two groups (66.2% vs. 66.9%, P = 0.513). After performing PSM, both the 5-year CSS and 5-year OS rates were comparable between the ER and SR groups (5-year CSS: 84.9% vs. 83.0%, P = 0.577; 5-year OS: 70.6% vs. 66.0%, P = 0.415). These findings were consistent in the subgroup analysis that included only patients with stage III disease or tumor size ≥ 7cm. Furthermore, although the number of harvested lymph nodes was higher in the ER group compared to the SR group (14.4 vs. 12.7, P < 0.001), the number of invaded lymph nodes remained similar between the two groups (0.5 vs. 0.5, P = 0.90). Similarly, our center's data revealed comparable 3-year OS and 3-year disease-free survival (DFS) rates between the two groups. ER have no significant oncological benefits over SR in the treatment of non-metastatic splenic flexure colon cancer, even for locally advanced cases.

AB092. Imaging the histopathology subtypes of the growth hormone-secreting pituitary neuroendocrine tumor.

Sparsely granulated (SG) growth hormone-secreting pituitary neuroendocrine tumors (GH-PitNETs) often present with a more aggressive clinical course compared to densely granulated (DG) tumors. These subtypes exhibit distinct biological and imaging characteristics. Thus, this study aims to differentiate between the histopathological subtypes of GH-PitNETs using pre-operative magnetic resonance imaging (MRI). A retrospective analysis was conducted on 83 acromegalic patients treated at our institution between 2000 and 2010. Tumor volumes were segmented from preoperative MRIs, including T1-weighted, T2-weighted, T1 with contrast, and T2 fluid attenuated inversion recovery (FLAIR) sequences. Reference regions of interest (ROIs) were delineated using gray and white matter from the same sequences. Two pathologists reviewed pathology specimens for anti-cytokeratin (CAM 5.2) and Pit-1 expression. Clinical and radiological biomarkers were compared between SG and DG patients. A total of 83 patients with complete histopathology and 51 patients with complete MRIs were included in the analysis. SG PitNETs exhibited higher rates of supra-sellar invasion (61.5%, P<0.001), larger tumor sizes, lower pre-operative GH levels, and increased post-operative residual tumor (65.4%, P<0.001) compared to DG PitNETs. Additionally, SG PitNETs showed greater hyperintensity on T2-weighted images and enhanced contrast, whereas DG PitNETs exhibited less contrast enhancement. Utilization of these imaging biomarkers demonstrated an 94.1% accuracy in T2 FLAIR and overall of 78.7% predicting the histopathological subtypes of GH-PitNETs. Distinct histopathological subtypes of GH-PitNETs represent crucial prognostic factors. Utilizing multimodal pre-operative MRIs, clinicians can accurately identify sparsely granulated GH-PitNETs, facilitating improved treatment planning strategies.

Clinicopathological features of hepatoid adenocarcinoma and non-hepatoid adenocarcinoma of the stomach: A systematic review and meta-analysis.

Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique malignant gastric tumor with a significantly worse prognosis than non-hepatoid adenocarcinoma of the stomach (non-HAS). The present study explored the clinicopathological features of HAS and non-HAS patients to provide insights into HAS treatment strategies. From December 26, 2023, we performed a comprehensive search of the PubMed, Web of Science, Cochrane Library, and Embase.com databases for relevant studies. Two authors independently screened the studies, evaluated their quality, extracted data, and performed the analyses. This study was registered with PROSPERO on January 2, 2024. Nine retrospective studies were included for analysis after screening 833 articles. A total of 350 and 924 patients were enrolled in the HAS and non-HAS groups, respectively. While no significant differences were observed in age, sex, tumor size, T3 or T4 stage, and N2 or N3 stage between the two groups, the HAS group exhibited higher rates of lymph node metastasis (OR = 1.93, 95% CI: 1.19-3.13, p = 0.007), liver metastasis (OR = 3.45, 95% CI: 2.26-5.28, p < 0.001), and vascular invasion (OR = 2.76, 95% CI: 2.05-3.71, p < 0.001). Additionally, the HAS group had lower 3-year survival rates (HR = 2.35, 95% CI: 1.70-3.25, p < 0.001) and 5-year survival rates (HR = 3.63, 95% CI: 1.49-8.88, p = 0.005), but lower rates of lymphatic permeation (OR = 0.68, 95% CI: 0.47-0.99, p = 0.040). Based on the current clinical evidence, patients with HAS present distinct clinicopathological features, greater invasiveness, and poorer prognosis than non-HAS patients. Further research is warranted to develop optimal treatment strategies for HAS.

Minimally invasive distal pancreatectomy for pancreatic adenocarcinoma: A propensity-matched national analysis on surgical outcomes and healthcare disparities

BackgroundPancreatic adenocarcinoma of distal pancreas is hard to treat due to late presentation. While open distal pancreatectomy with splenectomy has had favourable outcomes, it has also had many complications which were low among Minimally invasive procedures. This retrospective cohort analysis compares minimally invasive and open distal pancreatectomy (MIDP) outcomes using a national inpatient database. MethodsThe study used 2016–2020 NIS data. The study included 1577 distal pancreatic malignant tumor surgery patients. There were 530 Minimally Invasive and 1047 Open groups. Propensity matched analysis was performed on surgical groups to reduce confounding variables. ResultsIn comparison to open procedures, minimally invasive techniques reduced hospital stays by 10 ​% (OR ​= ​0.90, 95 ​% CI 0.86–0.93). While not statistically significant, the unmatched analysis linked MIDP to lower in-hospital mortality. African Americans were 37 ​% less likely to undergo MIDP than Caucasians (OR ​= ​0.63, 95 ​% CI ​= ​0.40–0.96). ConclusionNationwide analysis suggests MIDP may be a safe and effective surgical treatment for distal pancreatic adenocarcinoma. It may reduce hospital stays and mortality over open surgery. The study also suggests race may affect minimally invasive procedure rates.

The effectiveness of intraoperative ultrasound control in removing foreign bodies of soft tissues in military personnel with fragmentation wounds at the stage of specialized surgical care

BACKGROUND: The involvement of civilian medical institutions in medical care in military conflicts and counter-terrorism operations has become an important area of the medical support system. Modern methods of surgical navigation make possible minimal invasive, effective and safe removing foreign bodies from soft tissues. Clear understanding of injuries’ character allows better planning of procedures. AIM: Improving the results of treatment of military personnel with fragment wounds by taking into account the character of injury and the use of ultrasound control during removing soft tissue foreign bodies at the stage of specialized surgical care. MATERIAL AND METHODS: Data from 253 case histories who were treated at the State Budgetary Institution RO “Central City Hospital named Semashko”. Indications for the removal of fragments included the size of the fragment over 7 mm, localization near to large vessels and nerve trunks, and an acute purulent process. The patients were been randomized to two groups. Group I (control) included 118 patients in whom surgery was been performed in the traditional way. Group II (main) included 135 patients in whom procedures were performed with ultrasound navigation. The research methods are ultrasound, X-ray, clinical, and statistical. RESULTS: In 164 patients (64.8%), the wounds were of an isolated nature, where fragments were localized in various anatomical areas. 89 patients (35.2%) had combined shrapnel wounds. Of the 118 patients in group I, in whom surgery was performed in the traditional way, 65 patients (55.1%) underwent surgery under local anesthesia, 53 (44.9%) — under general anesthesia (anesthesia is always general). In 135 patients of group II, operations were performed by only one surgeon under local anesthesia. The duration of surgery, surgery invasion and wound infections rate were significantly lower in group II. CONCLUSION: The part of isolated fragment wounds is 64.8%, combined — 35.2%. The use of ultrasound navigation during surgery can significantly improve the effectiveness of surgical treatment of patients with fragmentation wounds: reduce the invasiveness and duration of surgery, blood loss, and the rate of wound infectious complications.

The evaluation of melatonin and EGF interaction on breast cancer metastasis.

Metastasis in breast cancer is the first cause of death in patients. The epidermal growth factor (EGF) increases cancer cells' invasion, and migration. Melatonin's inhibitory effects on various types of cancer were confirmed. This study aimed to investigate whether melatonin could apply its impact through the EGF-related pathways or not. First, MDA-MB-231 and MCF7 cells were cultured, and then melatonin effects on cell viability were determined by MTT assay. Transwell invasion assay was applied to identify the invasiveness of these breast cancer cell lines under treatment of EGF and melatonin. Real-time RT-PCR then investigated the expression of MMP9 and MMP2 in determined groups. Cell proliferation was also assayed under EGF and melatonin treatment using Ki67 assessment by flow cytometry. The rate of invasion and migration of EGF-treated cells increased in both groups, in which melatonin caused increased invasion by EGF just in MCF7 cells. MMP9 and MMP2 expression increased significantly in both cell lines under EGF treatment, and melatonin increased these genes' expression in both cell lines (p<0.05). EGF increased the MMP9 and MMP2 gene expression, and melatonin increased EGF-induced expression (p<0.05). The EGF reduced the expression of the Ki67 protein in the MCF7 cell line, which was negatively affected by melatonin and EGF. In contrast, along with melatonin, EGF did not affect the proliferation of the MDA-MB-231 cell line. The results of this study show that melatonin in the presence of EGF does not show the anti-cancer properties previously described for this substance.

Radiation exposure and screening yield by digital breast tomosynthesis compared to mammography: results of the TOSYMA Trialbreast density related.

The randomized TOmosynthesis plus SYnthesized MAmmography (TOSYMA) screening trial has shown that digital breast tomosynthesis plus synthesized mammography (DBT + SM) is superior to digital mammography (DM) in invasive breast cancer detection varying with breast density. On the other hand, the overall average glandular dose (AGD) of DBT is higher than that of DM. Comparing the DBT + SM and DM trial arm, we analyzed here the mean AGD and their determinants per breast density category and related them to the respective invasive cancer detection rates (iCDR). TOSYMA screened 99,689 women aged 50 to 69 years. Compression force, resulting breast thickness, the calculated AGD obtained from each mammography device, and previously published iCDR were used for comparisons across breast density categories in the two trial arms. There were 196,622 exposures of 49,227 women (DBT + SM) and 197,037 exposures of 49,132 women (DM) available for analyses. Mean breast thicknesses declined from breast density category A (fatty) to D (extremely dense) in both trial arms. However, while the mean AGD in the DBT + SM arm declined concomitantly from category A (2.41 mGy) to D (1.89 mGy), it remained almost unchanged in the DM arm (1.46 and 1.51 mGy, respectively). In relative terms, the AGD elevation in the DBT + SM arm (64.4% (A), by 44.5% (B), 27.8% (C), and 26.0% (D)) was lowest in dense breasts where, however, the highest iCDR were observed. Women with dense breasts may specifically benefit from DBT + SM screening as high cancer detection is achieved with only moderate AGD elevations. TOSYMA suggests a favorable constellation for screening with digital breast tomosynthesis plus synthesized mammography (DBT + SM) in dense breasts when weighing average glandular dose elevation against raised invasive breast cancer detection rates. There is potential for density-, i.e., risk-adapted population-wide breast cancer screening with DBT + SM. Breast thickness declines with visually increasing density in digital mammography (DM) and digital breast tomosynthesis (DBT). Average glandular doses of DBT decrease with increasing density; digital mammography shows lower andmore constant values. With the smallest average glandular dose differencein dense breasts, DBT plus SM had thehighest difference in invasive breast cancer detection rates.

Clinicopathological spectrum, management, and outcome of ectopic parathyroid carcinoma: Experience with 24 cases.

Ectopic parathyroid carcinoma (EPC) is a rare clinical entity with multiple diagnostic pitfalls, making surgical cures challenging. We assessed the clinicopathological spectrum and outcome of EPCs. In this retrospective cohort study, 24 EPCs were identified from 133 PC patients treated at a tertiary referral center. The relationship between clinicopathological findings and locations was analyzed. The locations of EPCs were predominantly intrathyroidal (62.5%), followed by 16.7% in the mediastinum, 8.3% in the retropharyngeal space, 8.3% in the carotid sheath, and 4.2% in the upper neck. Intrathyroidal EPC patients experienced higher serum calcium (p = 0.020), a higher rate of vascular invasion (p = 0.040), and a slightly higher incidence of non-R0 initial resection (p = 0.092) than those in other ectopic locations. Intrathyroidal EPC patients also suffered a trend of higher upper aerodigestive tract (UAT) invasion rate (p = 0.070) and higher risks of distant metastasis (p = 0.037) than the other PC patients. The 5-year disease-free survival rate after surgery was slightly compromised at 41.5% in intrathyroidal EPC patients compared with 77.8% among those in other ectopic locations (p = 0.143) and 59.7% among the other PC patients (log-rank = 3.194; p = 0.074), though without statistical significance. Intrathyroidal EPC might cause a more biochemically and invasively distinct PC picture compared with other PCs. Special caution should be exercised in the preoperative diagnosis and management of such cases.

S. aureus Surveillance and Decolonization Associated with Decreased MRSA, but not MSSA, Infections in the Neonatal ICU

Background: Invasive Staphylococcus aureus infections cause significant morbidity and mortality in neonatal intensive care unit (NICU) infants.1 Colonization (asymptomatic carriage in the nose, skin, or gut) is a risk factor for subsequent invasive infection (e.g., pneumonia, bone infections, bloodstream infections, etc.). Active surveillance and decolonization measures for S. aureus-colonized infants have been associated with decreased invasive infection rates. 2-4 Methods: A methicillin-resistant S. aureus (MRSA) surveillance and decolonization program, consisting of admission and weekly MRSA nasal cultures followed by intranasal mupirocin plus chlorhexidine baths for colonized infants, was implemented in our level IV NICU with 150 beds in 2006.5 Due to poor compliance with decolonization protocols5, existing practices were reviewed and multiple interventions to increase compliance were implemented in 2018. These renewed efforts included revision of the existing MRSA decolonization protocol, updating the associated electronic medical record order set, re-education of unit staff, and weekly review by the Infection Prevention (IP) and NICU leadership teams to ensure the decolonization protocol was followed for newly colonized infants. Mean MRSA bloodstream infection (BSI) rates were calculated quarterly pre- (January 2014-December 2017) and post- (January 2018-December 2023) implementation of renewed efforts and compared via unpaired t-test. In July 2020 a similar methicillin-susceptible S. aureus (MSSA) surveillance and decolonization program was implemented with an associated revision of existing documents, education campaign, and weekly review of infants with new MSSA colonization. Mean MSSA BSI rates pre- (July 2018-June 2020) and post- (July 2020-December 2023) implementation were compared via unpaired t-test. Results: Renewed implementation of MRSA surveillance and decolonization was associated with a sustained decrease in the mean MRSA BSI rate (Figure 1): 0.10 per 1000 patient-days pre-implementation, 0.03 post-implementation (p=0.02). Following implementation of MSSA surveillance and decolonization, there was no statistically significant change in the mean MSSA BSI rate (Figure 2): 0.20 per 1000 patient-days pre-implementation, 0.15 post-implementation (p=0.32). Conclusions: Implementation of a robust MRSA surveillance and decolonization program in the NICU was associated with a sustained decrease in invasive MRSA infections. No change in invasive MSSA infection rates was observed following implementation of a similar protocol for MSSA. Additional research is needed to better understand the role of MSSA surveillance and decolonization in the NICU.

GAME-SCORE predicts pathological and radiological response to chemotherapy in patients with colorectal liver metastases

BackgroundGenetic And Morphological Evaluation (GAME) score is the newest prognostic model for patient with colorectal liver metastases (CRLMs). Pathological and radiological responses to neoadjuvant chemotherapy (NAC) are key factors for prognostic stratification of these patients. The present study aims to evaluate the GAME-score's ability to predict pathological and radiologic responses to NAC. MethodsCRLM patients who underwent liver resection after NAC from January 2010 to December 2021 were categorized by GAME scores: low risk (LR, 0–1), moderate risk (MR, 2–3), and high risk (HR, ≥4). Correlations between groups and radiological/pathological features were analyzed. Poor pathological response was defined as Tumor Regression Grade 4–5. ResultsOf 1054 liver resections for CRLMs, 448 were included. GAME scores were LR: 80 (18 %), MR: 228 (51 %), and HR: 140 (31 %). In this cohort, HR-GAME scores were associated with lower pathological response (LR: 67.1 %, MR: 74.9 %, HR: 82.6 %; p = 0.010). Radiologic progression occurred in 10 % of HR patients, significantly more than in LR (3.8 %) and MR (3.5 %) groups (p = 0.011). Multivariable analysis for independent predictors of pathological response confirmed HR-GAME (RR 1.843, p=0.025) along with age higher than 70 years (RR 2.111, p=0.022) and irinotecan-based NAC (RR 3.066, p < 0.001). For radiological progression disease after NAC, the HR-GAME score (RR 2.77, p=0.016) was the only independent predictor. HR-GAME scores were also associated with higher rates of mucinous differentiation (p = 0.021), satellitosis (p = 0.001), vascular invasion (p = 0.011), and perineural invasion (p = 0.010). ConclusionsGAME score category should be considered into planning of therapeutic strategy of patients with CRLMs.

VEGFA locus amplification potentially predicts a favorable prognosis in gastric adenocarcinoma

Gastric adenocarcinoma harbors a range of genetic and epigenetic alterations, including alterations in DNA copy number. However, the key genes that promote the development and progression of gastric adenocarcinoma remain unknown.To identify the key genes amplified in gastric adenocarcinoma, we performed array comparative genomic hybridization on formalin-fixed paraffin-embedded samples of surgically resected gastric adenocarcinoma. We detected a relatively wide genomic region of gain containing the vascular endothelial growth factor A (VEGFA) gene locus on chromosome 6p. VEGFA locus amplification in gastric adenocarcinoma was validated by fluorescence in situ hybridization. To assess the frequency of VEGFA locus amplification in gastric adenocarcinoma, we conducted multiplex ligation-dependent probe amplification (MLPA) assays using homemade probes designed to target the VEGFA gene locus. Eleven of 54 (20 %) gastric adenocarcinomas with MLPA values above 1.3 were defined as having VEGFA locus amplification. Next, we investigated the effect of VEGFA locus amplification on the clinicopathological characteristics of gastric adenocarcinomas and patient survival. VEGFA locus amplification demonstrated a significantly close relationship with pathological intestinal type and lower rates of venous invasion Furthermore, a Kaplan-Meier analysis showed that patients with VEGFA locus amplification had significantly better overall survival than those without amplification (p = 0.038), particularly in the long-term follow-up period. In conclusion, VEGFA locus amplification can predict modest aggressiveness and good outcomes, suggesting the possibility that it may predict a favorable prognosis in patients with gastric adenocarcinoma.

Correlation of S100A4 and S100A14 Expression With Clinico-Pathological Features and Tumor Location in Colorectal Cancer Patients.

Background Colorectal cancer (CRC) remains a major cause of morbidity and mortality worldwide. Understanding the clinical and pathological characteristics of CRCpatients is essential for improving diagnosis, treatment, and prognostication. S100 proteins play a crucial role in CRC by promoting tumor growth, metastasis, and inflammation through their involvement in various cellular processes such as proliferation, migration, and immune response modulation. Elevated levels of specific S100 proteins have been associated with poor prognosis and serve as potential biomarkers for early detection and therapeutic targets in CRC. This study aims to analyze the general and medical characteristics of CRC patients, with a particular focus on the expression patterns of S100A4 and S100A14 proteins and their correlation with tumor location and various clinical parameters. Methods This cross-sectional study included 98 CRC patients aged 21 to 92 years. Clinical data were collected from Vajeen Hospital (Duhok/ Iraq), including age, gender, and presenting symptoms. Pathological data such as tumor site, tumor size, tumor, node, and metastasis (TNM) stage, tumor grade angio-lymphatic invasion, perineural invasion, and metastasis were analyzed. The expression of S100A4 and S100A14 proteins was assessed using immunohistochemistry, and their correlation with clinico-pathological features and tumor location was evaluated using statistical analysis. Results The 98 patients with a mean age of 57.27 years. The majority were over 50 years old (68, 69.39%) with a nearly equal gender distribution. The most common symptom was bleeding per rectum (36, 36.74%). TNM staging revealed 25.51% (n=25) of patients at stage I, 32.65% (n=32) at stage II, 24.49% (n=24) at stage III, and 17.35% (n=17) at stage IV. Angio-lymphatic invasion was present in 65.31% (n=64) of patients, and lymph node invasion in 38.78% (n=38). All tumors were adenocarcinomas, with 82.65% (n=81) being intermediate grade. S100A4 expression was low in early-stage tumors but significantly higher in advanced stages (P < 0.0001). High S100A4 expression was associated with vascular invasion (P = 0.0006), perineural invasion (P = 0.0002), lymph node invasion (P < 0.0001), and metastasis (P = 0.0010). S100A14 expression was inversely correlated with disease severity. Low S100A14 expression was more common in advanced stages (P < 0.0001) and was associated with higher rates of vascular invasion (P = 0.0018), lymph node invasion (P < 0.0001), and metastasis (P = 0.0001). Conclusion This study highlights significant correlations between S100A4 and S100A14 expression with various clinico-pathological features in CRC patients. High S100A4 expression is linked with tumor aggressiveness, whereas low S100A14 expression is associated with advanced disease stages and increased metastasis. However, there is no observed correlation between the expression of these proteins and the tumor site.

PSME3 promotes lung adenocarcinoma development by regulating the TGF-β/SMAD signaling pathway.

Lung adenocarcinoma (LUAD) is one of the most common types of cancer worldwide. Proteasome activator subunit 3 (PSME3) is a subunit of a proteasome activator, and changes in PSME3 can lead to the development of many diseases in organisms. However, the specific mechanism of PSME3 in LUAD has not yet been elucidated. This study initially revealed the mechanism of PSME3 promoting the progression of lung adenocarcinoma, which provided a potential molecular target for clinical treatment. PSME3 expression in LUAD cells and tissues was assessed by bioinformatics analysis, immunohistochemistry (IHC), Western blotting (WB), and quantitative real time polymerase chain reaction (qRT-PCR). A series of functional experiments were used to evaluate the effects of PSME3 knockdown and overexpression on LUAD cell proliferation, migration, and apoptosis. The potential mechanism of PSME3 was explored by transcriptome sequencing and WB experiments. In this study, our initial findings indicated that PSME3 expression was abnormally high in LUAD and was associated with poor patient prognosis. Further, we found that the downregulation of PSME3 significantly inhibited LUAD cell proliferation, an effect that was verified by subcutaneous tumor formation experiments in nude mice. Similarly, the rate of invasion and migration of LUAD cells significantly decreased after the downregulation of PSME3. Using flow cytometry, we found that the knockdown of PSME3 caused cell cycle arrest at the G1/S phase. Through transcriptome sequencing, we found that the transforming growth factor-beta (TGF-β)/SMAD signaling pathway was closely related to LUAD, and we then validated the pathway using WB assays. We demonstrated that PSME3 was abnormally highly expressed in LUAD and related to poor patient prognosis; therefore, targeting PSME3 in the treatment of LUAD may represent a novel therapeutic approach.

Safety and short-term outcomes of esophagectomy after neoadjuvant immunotherapy combined with chemotherapy or chemoradiotherapy for locally advanced esophageal squamous cell cancer: analysis of two phase-II clinical trials.

Preoperative chemotherapy (CT) or chemoradiotherapy (CRT) show survival benefits in patients with locally advanced esophageal squamous cell carcinoma (ESCC); however, ESCC patients still have a dismal prognosis. We conducted two phase-II, single-armed clinical trials to assess the potential benefits, efficacy, feasibility, and safety of esophagectomy after combining preoperative CT or CRT and neoadjuvant programmed cell death protein 1 (PD-1) inhibitors in the treatment of ESCC. Patients were included with histologically confirmed ESCC (clinical stage II-IVA according to the American Joint Committee on Cancer 8th staging system) from two phase-II, single-arm trials (NCT04506138 and NCT03940001). Patients underwent two doses of intravenous PD-1 inhibitor (either camrelizumab or sintilimab) every 3 weeks, combined with two cycles of either CT or CRT. The primary endpoint of the study was the safety and short-term outcomes of esophagectomy as measured by the risk of developing complications within 30 days, after the combination of preoperative PD-1 inhibitor and CT or CRT Secondary endpoint was to evaluate the pCR rates (pT0N0), primary tumor pCR rates (pT0), operation time, postoperative stay, and 30-day mortality rate between both groups. Results between both groups were compared using a multivariable log-binomial regression model to obtain the adjusted relative risk ratios (RRs). Between May 2019 and June 2022, 55 patients were included. All patients completed neoadjuvant therapy. Age, sex, performance status, clinical stage, histologic subtype, procedure type, operative time, and blood loss volume were similar between the two groups. The primary tumor pCR rates were 52.9% in the nICRT group and 21.6% in the nICT group (P=0.03), while the postoperative pCR rates were 41.2% in the nICRT group and 21.6% in the nICT group (P=0.19). The minimally invasive surgery rates were 89.2% (33/37) in the nICT group and 94.1% (16/17) in the nICRT group. The risk of developing pulmonary, anastomotic, or other complications were similar between the two groups. Esophagectomy was safe after the addition of the PD-1 inhibitor to preoperative CT or CRT in ESCC neoadjuvant therapies. Follow-up and the exploratory endpoints, including biomarkers analyses, are ongoing.

The Trypanosoma cruzi pleiotropic protein P21 orchestrates the intracellular retention and in-vivo parasitism control of virulent Y strain parasites.

P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21-/-) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21-/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21-/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21-/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21-/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia.

Relationship between BRAF V600E and some aggressive features in papillary thyroid carcinoma ≤1.5 cm

Objectives: Determine the association between BRAF V600E mutation in papillary thyroid microcarcinoma (PTMC), small papillary thyroid carcinoma (PTC 1-1.5 cm), with tumour-aggressive characteristics. Subjects and methods: Retrospective descriptive study of 104 patients with PTMC diagnosed by histopathology and with BRAF V600E gene mutation testing results. Study subjects were divided into 2 groups: PTMC (tumour size ≤1.0 cm) and PTC 1-1.5 cm (tumour size 1-1.5 cm) and evaluated aggressive features (macroscopic extrathyroidal invasion, lymph node metastasis, high-risk variants). Results: BRAF V600E gene mutation was detected in 72.8% of PTMC and 76.5% of PTC 1-1.5 cm. The proportion of tumours with aggressive features in PTMC with and without mutations was 66.7 and 52.63%, respectively (p=0.28). The proportion of tumours with aggressive features in PTC 1-1.5 cm with and without mutations was 80.7 and 100%, respectively (p=0.309). In the PTMC group, the rate of extrathyroidal invasion was higher in tumours with BRAF V600E mutation (p&lt;0.05). No association was found between BRAF V600E gene mutation and lymph node metastasis, high cell variation, and more than one aggressive feature in both PTMC and PTC 1-1.5 cm patient groups. Conclusions: In the PTMC group, the rate of extrathyroidal invasion was higher in patients with the BRAFV600E mutation. No association was found between BRAFV600E gene mutation and other aggressive features in patients with PTMC and PTC 1-1.5 cm.

Assessing risk of lymph node invasion in complete responders to neoadjuvant chemotherapy for muscle-invasive bladder cancer.

To investigate the lymph node invasion (LNI) rate in patients exhibiting complete pathological response (CR) to neoadjuvant chemotherapy (NAC) and to test the association of CR status with lower LNI and better survival outcomes. We included patients with bladder cancer (BCa; cT2-4a; cN0; cM0) treated with NAC and radical cystectomy (RC) + pelvic lymph node dissection (PLND) at our institution between 2012 and 2022 (N = 157). CR (ypT0) and LNI (ypN+) were defined at final pathology. Univariable and multivariable logistic regression analysis was performed to test the association between CR and LNI after adjusting for number of lymph nodes removed (NLR). Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS), metastasis-free survival (MFS) and disease free-survival (DFS) according to CR status. Overall CR and LNI rates were 40.1% and 19%, respectively. The median (interquartile range [IQR]) NLR was 26 (19-36). The LNI rate was lower in patients with CR vs those without CR (2 [3.2%] vs 61 [29.8%]; P < 0.001). After adjusting for NLR, CR reduced the LNI risk by 93% (odds ratio 0.07, 95% confidence interval [CI] 0.01-0.25; P < 0.001). Kaplan-Meier plots depicted better 5-year OS (69.7 vs 52.2%), MFS (68.3 vs 45.5%) and DFS (66.6 vs 43.5%) in patients with CR vs those without CR. After multivariable adjustments, CR independently reduced the risk of death (hazard ratio [HR] 0.44, 95% CI 0.24-0.81; P = 0.008), metastatic progression (HR 0.41, 95% CI 0.23-0.71; P = 0.002) and disease progression (HR 0.41, 95% CI 0.24-0.70; P = 0.001). Based on these findings, we postulate that PLND could potentially be omitted in patients exhibiting CR after NAC, due to negligible risk of LNI. Prospective Phase II trials are needed to explore this challenging hypothesis.

Risk Factors of Distant Metastatic Parathyroid Carcinoma and Insights into Therapeutic Perspectives.

Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC. In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM. The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM. Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care.

Prognosis and recurrence of spontaneously ruptured hepatocellular carcinoma treated after hepatectomy: A single institution experience.

Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study aimed to investigate the prognosis and recurrence after hepatectomy in patients with srHCC. From 2015 to 2020, a retrospective analysis of patients with srHCC who underwent hepatectomy was performed, and compared with patients with unruptured HCC. Among the 86 patients with HCC who underwent hepatectomy, 11 had srHCC. The median tumor size in the ruptured group was significantly larger than that in the unruptured group (P = .001). The incidence rate of vascular invasion and Glisson capsule invasion in the ruptured group was significantly higher than that in the unruptured group. (P = .012 and P < .001, respectively). The American Joint Committee on Cancer was significantly higher in the ruptured group than in the unruptured group (P < .001). In total, 8 (73%) patients in the ruptured group experienced recurrence, whereas the median recurrence-free survival (RFS) and overall survival (OS) periods in the ruptured group were 15 (11-32) and 23 (17-38) months, respectively. In the unruptured group, 34 (45%) patients experienced recurrence, and the median RFS and OS periods were 20 (8-37, P = .099) and 33 (12-51, P = .394) months, respectively. Patients who developed peritoneal metastases were included in the ruptured group (n = 3). Ruptured HCCs exhibit worse oncological outcomes have poorer survival and higher recurrence rates than unruptured HCCs.