Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer.

Adhesion-regulating molecule 1 (ADRM1) has been implicated in tumor development, yet its specific role in bladder cancer (BC) remains undefined. This study aimed to elucidate the function of ADRM1 in BC through a combination of bioinformatics analysis and immunohistochemical analysis (IHC). Utilizing R version 3.6.3 and relevant packages, we analyzed online database data. Validation was conducted through IHC data, approved by the Institutional Ethics Committee (Approval No. K20220830). In both paired and unpaired comparisons, ADRM1 expression was significantly elevated in BC tissues compared to adjacent tissues, as evidenced by the results of TCGA dataset and IHC data. Patients with high ADRM1 expression had statistically worse overall survival than those with low ADRM1 expression in TCGA dataset, GSE32548 dataset, GSE32894 dataset, and IHC data. Functional analysis unveiled enrichment in immune-related pathways, and a robust positive correlation emerged between ADRM1 expression and pivotal immune checkpoints, including CD274, PDCD1, and PDCD1LG2. In tumor microenvironment, samples with the high ADRM1 expression contained statistical higher proportion of CD8 + T cells and Macrophage infiltration. Meanwhile, these high ADRM1-expressing samples displayed elevated tumor mutation burden scores and stemness indices, implying potential benefits from immunotherapy. Patients with low ADRM1 expression were sensitive to cisplatin, docetaxel, vinblastine, mitomycin C, and methotrexate. According to the findings from bioinformatics and IHC analyses, ADRM1 demonstrates prognostic significance for BC patients and holds predictive potential for both immunotherapy and chemotherapy responses. This underscores its role as a biomarker and therapeutic target in BC.

A novel endothelial-related prognostic index by integrating single-cell and bulk RNA sequencing data for patients with kidney renal clear cell carcinoma.

Background: Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data. Methods: Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages. Results: The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the "pRRophetic" algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC. Conclusion: By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.

Development of a novel nomogram for predicting clinically significant prostate cancer with the prostate health index and multiparametric MRI.

Introduction: On prostate biopsy, multiparametric magnetic resonance imaging (mpMRI) and the Prostate Health Index (PHI) have allowed prediction of clinically significant prostate cancer (csPCa). Methods: To predict the likelihood of csPCa, we created a nomogram based on a multivariate model that included PHI and mpMRI. We assessed 315 males who were scheduled for prostate biopsies. Results: We used the Prostate Imaging Reporting and Data System version 2 (PI-RADS V2) to assess mpMRI and optimize PHI testing prior to biopsy. Univariate analysis showed that csPCa may be identified by PHI with a cut-off value of 77.77, PHID with 2.36, and PI-RADS with 3 as the best threshold. Multivariable logistic models for predicting csPCa were developed using PI-RADS, free PSA (fPSA), PHI, and prostate volume. A multivariate model that included PI-RADS, fPSA, PHI, and prostate volume had the best accuracy (AUC: 0.882). Decision curve analysis (DCA), which was carried out to verify the nomogram's clinical applicability, showed an ideal advantage (13.35% higher than the model that include PI-RADS only). Discussion: In conclusion, the nomogram based on PHI and mpMRI is a valuable tool for predicting csPCa while avoiding unnecessary biopsy as much as possible.

Clinical outcomes of endoscopic versus laparoscopic resection for senile patients with gastric gastrointestinal stromal tumours (2 to 4 cm) originating from the muscularis propria layer.

Introduction: Currently, there still are no selection criteria for endoscopic resection (ER) versus laparoscopic resection (LR) of gastric gastrointestinal stromal tumours (GIST) (2 to 4 cm) originating from the muscularis propria layer (MP-GISTs). Aim: To investigate and compare the long-term prognosis of ER and LR for resecting gastric MP-GISTs, with at least 5 years of follow-up. Material and methods: Between January 2010 and December 2015, 134 patients with gastric MP-GISTs were consecutively enrolled in this study. The main comparison measurements included the short-term and long-term outcomes between the ER group (n = 89) and the LR group (n = 45). Results: In this study, there were no significant differences in the rates of complete resection (p = 0.220) and short-term complications (p = 0.663) between the ER group and the LR group. The ER group had a shorter operation time (50.1 ±18.2 min vs. 120.6 ±32.5 min, p < 0.001), shorter hospital stays (5.1 ±1.9 days vs. 6.4 ±3.7 days, p = 0.026), and lower hospitalization costs (16639.5 ±5091.3 CNY vs. 24030.4 ±6803.1 CNY, p < 0.001) than the LR group. The ER group had a lower rate of long-term complications than the LR group (p = 0.001) during the follow-up period (84.2 ±17.9 months vs. 89.0 ±16.8 months, p = 0.207). Conclusions: Our results showed that ER was a more feasible treatment approach than LR when the gastric MP-GIST was located in or near the cardia/pylorus. ER also had several other advantages over LR, such as a shorter procedure time, shorter hospital stay, and lower hospitalization costs.

Esophageal Mucosal Autograft for Preventing Stricture After Widespread Endoscopic Submucosal Dissection of Superficial Esophageal Lesions.

BACKGROUND: Although esophageal mucosal autograft prevents esophageal stricture after widespread endoscopic submucosal dissec- tion and has been reported as a new technique, it is relatively unproven in clinical practice. This prospective study was conducted to evaluate our experience using esophageal mucosal autograft to prevent strictures after widespread endoscopic submucosal dissection in patients with widespread superficial esophageal lesions. METHODS: Between October 2017 and June 2018, 15 patients with widespread superficial esophageal lesions were consecutively treated with widespread endoscopic submucosal dissection and then underwent esophageal mucosal autograft. The main outcomes measured included esophageal epithelialization and esophageal stricture. RESULTS: The median longitudinal diameter of the widespread superficial esophageal lesions was 5.2 cm. All 15 patients were success- fully treated with widespread endoscopic submucosal dissection and esophageal mucosal autograft, and the median procedural time was 182 minutes. During follow-up (median, 23 months), esophageal epithelialization was found in 13 patients (86.7%), and 7 patients experienced esophageal stricture (46.7%). In those 7 patients, the esophageal strictures were successfully relieved after endoscopic bal- loon dilation or endoscopic radial incision. No complications related to endoscopic balloon dilation/endoscopic radial incision occurred. Additionally, local recurrence was found in 1 patient with poorly differentiated squamous cell carcinoma, and further surgical resection was performed. CONCLUSIONS: Esophageal mucosal autograft appears to be an efficient approach to reconstructing local esophageal epithelium and might have a potential role in preventing esophageal stricture after widespread endoscopic submucosal dissection. However, as a new technique, it needs more improvement to enhance its role in preventing esophageal stricture after widespread endoscopic submucosal dissection.

Pelvic lipomatosis with cystitis glandularis managed with cyclooxygenase-2 inhibitor: A case report.

BACKGROUND: Pelvic lipomatosis (PL) is a rare benign condition with characteristic overgrowth of histologically benign fat and invasion and compression of pelvic organs, often leading to non-specific lower urinary tract symptoms (LUTS). Approximately 40% of patients with PL have cystitis glandularis (CG). The cause of PL combined with CG is poorly understood, and there is currently no effective treatment. Refractory CG with upper urinary tract obstruction even requires partial or radical bladder resection. CASE SUMMARY: In this case, a patient suffering from PL with CG was treated by transurethral resection of bladder tumour (TUR-BT) and oral administration of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. The LUTS were alleviated, and the cystoscopy results improved significantly. Immunohistochemistry showed up-regulated COX-2 expression in the epithelium of TUR-BT samples, suggesting that COX-2 may participate in the pathophysiological process of PL combined with CG. CONCLUSION: We report for the first time that celecoxib may be an effective treatment strategy for PL combined with refractory CG.

Endoscopic resection of large (≥ 4 cm) upper gastrointestinal subepithelial tumors originating from the muscularis propria layer: a single-center study of 101 cases (with video).

BACKGROUND AND AIMS: Although endoscopic resection (ER) is already established as a minimally invasive technique for small (< 4.0 cm) upper gastrointestinal subepithelial tumors originating from the muscularis propria layer (MP-SETs), published data of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs are extremely rare and limited to case reports. This retrospective study aimed to evaluate the feasibility and safety of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs in a large case series. METHODS: Between June 2012 and December 2018, 101 patients with large (≥ 4 cm) upper gastrointestinal MP-SETs were enrolled in this study. The main outcome measures included complete resection, total complications, and local residual or recurrent tumor. RESULTS: The rate of complete resection was 86.1%. Thirteen patients (12.9%) experienced complications including gas-related complications (6/101, 5.9%), localized peritonitis (4/101, 4.0%), esophageal/cardiac mucosal laceration (2/101, 2.0%), and delayed bleeding (1/101, 1.0%). These 13 patients recovered after endoscopic and conservative treatment. The independent risk factor for incomplete resection was tumor size (P = 0.005), and the independent risk factors for total complications were tumor size (P = 0.011) and tumor extraluminal growth (P = 0.037). During the median follow-up of 36 months, local residual tumor was detected in 1 patient. No local recurrence occurred in any patient. CONCLUSIONS: Despite being associated with a relatively low complete resection rate, ER is an alternative therapeutic method for large (≥ 4.0 cm) upper gastrointestinal MP-SETs when performed by an experienced endoscopist. This method is especially valuable for patients who are unwilling to undergo surgery.

Association of HLA-G 3' UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections.

BACKGROUND: Human leukocyte antigen (HLA)-G is an immune checkpoint molecule, which expression in cervical cancer cells enables them to escape immunosurveillance. To date, limited information has been published on the association of HLA-G genetic background in malignant cells with levels of HLA-G expression and the clinical outcome of patients. METHODS: We investigated the influence of the HLA-G 14 bp In/Del (rs66554220) and + 3142C/G (rs1063320) polymorphisms in 130 cases of HPV16 infection, 130 cases of HPV18 infection and 185 age-matched, unrelated, HPV-negative, and cytologically normal Chinese Han women. Case-matched cervical biopsy tissues were evaluated by immunohistochemistry. RESULTS: Our findings show that the frequency of alleles, 14 bp In (38.5% vs 29.2%, OR = 1.52, P < 0.05) and + 3142G (72.7% vs 57.0%, OR = 2.01, P < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The HLA-G polymorphisms (alleles 14 bp In and + 3142G) are also associated with the progression of HPV18-related cervical lesions. Moreover, HLA-G expression increased from CIN1 to CIN2/3 lesions and was highest in patients with adenocarcinoma; however, a significant association between these characteristics and the HLA-G polymorphisms was not observed. CONCLUSION: Our results support that the HLA-G 14 bp In and + 3142G alleles are risk factors for HPV18 infections and influence the progression of HPV18-related cervical lesions. This suggests that HLA-G-driven immune mechanisms play an important role in cervical carcinogenesis.

Safety of endoscopic resection for duodenal subepithelial lesions with wound closure using clips and an endoloop: an analysis of 68 cases.

BACKGROUND: Endoscopic removal of a duodenal lesion is still considered to be a challenging procedure that can be fraught with potentially serious complications, specifically perforation or delayed bleeding. This study was to assess the safety of endoscopic resection for duodenal subepithelial lesions (SELs) with wound closure using clips and an endoloop. METHODS: From October 2010 to July 2015, a total of 68 consecutive patients with duodenal SELs were treated with endoscopic resection with wound closure using clips and an endoloop. The main outcome measures considered were the incidence of complete resection, perioperative perforation, delayed perforation, delayed bleeding, residual lesions, and lesion recurrence. RESULTS: Complete resection was successfully achieved for all 68 patients. The median lesion size was 1.7 cm. The median procedure time was 62 min. The mean hospital stay was 5.5 days. During the procedure, five patients developed perioperative perforations (7.4 %) and no patients developed delayed bleeding, delayed perforation, or other serious complications. The five patients with perioperative perforations recovered after conservative treatment. The perioperative perforation rate was significantly higher for lesions originating in the muscularis propria layer (18.2 %) than in the submucosal layer (2.2 %; p < 0.05). No residual or recurrent lesions were detected during the follow-up period (median: 27 months). CONCLUSIONS: Endoscopic resection with wound closure using clips and an endoloop is an effective and reasonably safe therapeutic method for treating/removing duodenal SELs when managed by an experienced endoscopic team, and it can provide an alternative treatment option for patients with duodenal SELs.

Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer.

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study was to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia.

Safety of Endoscopic Resection for Upper Gastrointestinal Subepithelial Tumors Originating from the Muscularis Propria Layer: An Analysis of 733 Tumors.

OBJECTIVES: Although endoscopic resection is an accepted technique for upper gastrointestinal subepithelial tumors (SETs) originating from the muscularis propria (MP) layer, published data regarding its complications are highly variable and limited to small data series. This study aimed to analyze the safety of endoscopic resection in a large case series. METHODS: A total of 726 consecutive patients with 733 upper gastrointestinal SETs originating from the MP layer underwent endoscopic resection from June 2005 to December 2014. The complete resection rate, perioperative perforation rate, and perioperative bleeding rate were the main outcome measurements. RESULTS: The complete resection rate was 97.1%. Ninety-four patients had complications (12.9%), including 88 with perioperative perforations (12.1%), 13 with perioperative bleeding (1.8%), 5 with localized peritonitis (0.7%), and one with delayed bleeding (0.1%). Eleven patients required surgery; the others were treated endoscopically. Risk factors for incomplete resection were extensive connection of the tumor to the MP layer (P=0.007) and extraluminal growth (P=0.048). Risk factors for perioperative perforation were larger tumor size (≤2.0 cm vs. 2.1-3.0 cm vs. >3.0 cm, P=0.021), extraluminal growth (P=0.046), and extensive connection (P<0.001). A risk factor for perioperative bleeding was larger tumor size (P=0.045). No residual or recurrent lesions were detected during the follow-up period (median: 28 months). CONCLUSIONS: Endoscopic resection is an effective and reasonably safe therapeutic method for treating/removing upper gastrointestinal SETs originating from the MP layer when managed by an experienced endoscopic team.

Complete circular endoscopic resection using submucosal tunnel technique combined with esophageal stent placement for circumferential superficial esophageal lesions.

BACKGROUND AND AIMS: At present, removing a circumferential superficial esophageal lesion (SEL) via en bloc resection is still a great challenge. Based on the previous success of submucosal tunneling endoscopic resection, this study aimed to evaluate the safety and effectiveness of complete circular endoscopic resection (CER) using a submucosal tunnel technique combined with esophageal stent placement for patients with circumferential SELs. METHODS: From August 2012 to June 2014, 23 patients with circumferential SELs were treated by CER using a submucosal tunnel technique combined with esophageal stent placement. The following steps were performed: (1) circular mucosa incisions were made at the anal and oral side of the lesion after marking the margin, (2) two submucosal tunnels were created from the oral to anal side using a hybrid knife, which was followed by submucosal dissection, and (3) following the completion of CER, a retrievable esophageal stent was placed to prevent postoperative stricture. RESULTS: CER using the submucosal tunnel technique combined with esophageal stent placement was successfully performed for all 23 cases. The complete resection and success rate were 100%, while the mean longitudinal diameter of the lesions was 65 mm. Mediastinal emphysema, pneumothorax, and postoperative stenosis were detected in 8.7% (2/23), 4.3% (1/23), and 17.4% (4/23) of the cases, respectively. Pathological diagnoses of the lesions included carcinomas (13/23) and high-grade intraepithelial neoplasias (10/23). No residual or recurrent tumors were detected in any patient during the follow-up period. CONCLUSIONS: CER using the submucosal tunnel technique combined with esophageal stent placement seems to be a safe and effective procedure for treating patients with SELs that result in a higher en bloc resection rate with fewer or minor complications.

Redundant mechanisms for vascular growth factors in retinopathy of prematurity in vitro.

BACKGROUND: Current treatments for retinopathy of prematurity (ROP) targeting single vascular growth factors are ineffective in preventing neoangiogenesis. METHODS: We investigated the redundant/compensatory mechanisms between vascular growth factors in ROP. Cultured retinal vascular endothelial cells under CoCl2-induced hypoxia were transfected with recombinant adeno-associated virus type 2-vascular endothelial growth factor (VEGF) or pGIPZ-VEGF RNA interference to up- and downregulate VEGF expression, respectively. At 48 h after transfection, basic fibroblast growth factor (bFGF) and angiopoietin 1 (ANG1) gene expression as well as mitotic cycle changes were analyzed in the cells and correlated with the change in VEGF expression. RESULTS: Compared with the normal control group 1, at 30 min, 12 h and 24 h, the expressions of VEGF, bFGF and ANG1 in the hypoxia control group 2 were significantly higher. In the highly expressing VEGF group (group 3), the expressions of bFGF and ANG1 were downregulated, while in the low-expressing VEGF group 4, the expressions of bFGF and ANG1 were significantly upregulated. In the bevacizumab treatment group 5, the expressions of VEGF, bFGF and ANG1 were similar to those in group 2, and the difference was not significant. CONCLUSIONS: A compensatory mechanism (redundancy) exists between vascular growth factors in ROP. Such a phenomenon could partially explain why the inhibition of a single growth factor cannot effectively prevent the recurrence of neovascularization in ROP. A more effective strategy for treating ROP may be to inhibit VEGF and its redundant pathways.

Expression and location of Smad2, 4 mRNAs during and after liver fibrogenesis of rats.

AIM: To investigate the location alteration of Smad2 and Smad4 mRNAs in the liver during and after fibrogenesis in rats. METHODS: Eighty male Wistar rats weighing approximately 200 g each were used. The rat models of experimental hepatic fibrosis were established by injection with carbon tetrachloride (CCl4), normal rats and rats were injected with olive oil and served as control groups. In situ hybridization(ISH) was used to detect the Smad2 and Smad4 mRNA in liver. RESULTS: In situ hybridization showed Smad2 and Smad4 mRNA expressions in the cytoplasm of hepatic stellate cells (HSC), fibroblasts and myofibroblasts around the central vein and hepatic sinus during and after fibrogenesis. Expression of Smad2, 4 mRNA was higher than that in normal and control rats. CONCLUSION: In the process of and after hepatic fibrosis formation, HSC, fibroblasts and myofibroblasts are the major cells that express Smad2 and Smad4. The more serious the hepatic fibrosis is in the injured liver, the higher the level of Smad2 and Smad4 gene expression is during and after fibrogenesis respectively.

[Extranodal Rosai-Dorfman disease].

OBJECTIVE: To investigate the diagnosis and differential diagnosis of extranodal Rosai-Dorfman disease. METHODS: Two cases of extranodal Rosai-Dorfman disease were studied using hematoxylin-eosin, and immunohistochemical staining, along with a literature review. RESULTS: The lesions of RDD were characterized by the presence of large histiocytes with emperipolesis, accompanied by infiltration of lymphocytes, plasma cells and other inflammatory cells. The large histiocytes had an abundant cytoplasm, pale to eosinophilic in appearance, positive for S-100 protein staining, with a vesicular nucleus and a small basophilic nucleolus in each cell. CONCLUSIONS: Extranodal Rosai-Dorfman disease is known as an idiopathic proliferative disease of histiocytes with a distinct morphologic feature and is very rare. Differential diagnosis from other types of fibrohistiocytic proliferation lesions is recommended.