Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions.

Numerous research works have emphasized the critical role that circadian rhythm plays in the tumor microenvironment (TME). The goal of clarifying chrono-pharmacological strategies for improving cancer treatment in clinical settings is a continuous endeavor. Consequently, to enhance the use of time-based pharmaceutical therapies in oncology, combining existing knowledge on circadian rhythms' roles within the TME is essential. This perspective elucidates the functions of circadian rhythms in the TME across various stages of cancer development, progression, and metastasis. Specifically, aging, angiogenesis, and inflammation are implicated in modulating circadian rhythm within the TME. Furthermore, circadian rhythm exerts a profound influence on current cancer treatments and thereby generates chronotheray to manage tumors. From a TME perspective, circadian rhythm offers promising opportunities for cancer prevention and treatment; nevertheless, further study is needed to address unanswered scientific problems.

A pan-cancer analysis of the oncogenic and immunological roles of transglutaminase 1 (TGM1) in human cancer.

BACKGROUND: There is currently a limited number of studies on transglutaminase type 1 (TGM1) in tumors. The objective of this study is to perform a comprehensive analysis across various types of cancer to determine the prognostic significance of TGM1 in tumors and investigate its role in the immune environment. METHOD: Pan-cancer and mutational data were retrieved from the TCGA database and analyzed using R (version 3.6.4) and its associated software package. The expression difference and prognosis of TGM1 were examined, along with its correlation with tumor heterogeneity, stemness, mutation landscape, and RNA modification. Additionally, the relationship between TGM1 expression and tumor immunity was investigated using the TIMER method. RESULTS: TGM1 is expressed differently in various tumors and normal samples and is associated with the overall survival and progression-free time of KIRC, ACC, SKCM, LIHC, and STES. In LICH, we found a negative correlation between TGM1 expression and 6 indicators of tumor stemness. The mutation frequencies of BLCA, LIHC, and KIRC were 1.7%, 0.3%, and 0.3% respectively. In BLCA and BRCA, there was a significant correlation between TGM1 expression and the infiltration of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells. CONCLUSION: TGM1 has the potential to serve as both a prognostic marker and a drug target.

Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential.

BACKGROUND: Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE: This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN: systematic review METHODS: PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION: These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF).

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pan-cancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications - review article.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.

Targeting Prolyl 4-Hydroxylase Subunit Beta (P4HB) in Cancer: New Roads to Travel.

Prolyl 4-hydroxylase subunit beta (P4HB) can catalyze the formation, breakage and rearrangement of disulfide bonds through two thioredoxin domains, which is important for the maintenance of oxidizing environment in endoplasmic reticulum. Recently, P4HB has been demonstrated its oncogenic role of tumorigenesis and development in cancers. Therefore, we comprehensively deciphered P4HB in human cancer from various aspects, including pan-cancer analysis and narrative summary. We also provided some possible interacted molecules and the top 10 predicted drugs targeting P4HB to contribute to future research. We proposed that P4HB was a potential target and brought new therapeutic opportunities for cancer patients.

Regulating POLR3G by MicroRNA-26a-5p as a promising therapeutic target of lung cancer stemness and chemosensitivity.

Cancer stem cells (CSCs) identified in lung cancer exhibit resistance to chemotherapy, radiotherapy, and targeted therapy. Therefore, a technology for controlling CSCs is needed to overcome such resistance to cancer therapy. Various evidences about the association between epithelial-mesenchymal transition related transcriptomic alteration and acquisition of CSC phenotype have been proposed recently. Down-regulated miR-26a-5p is closely related to mesenchymal-like lung cancer cell lines. These findings suggest that miR-26a-5p might be involved in lung cancer stemness. RNA polymerase III subunit G (POLR3G) was selected as a candidate target of miR-26a-5p related to cancer stemness. It was found that miR-26a-5p directly regulates the expression of POLR3G.Overexpression of miR-26a-5p induced a marked reduction of colony formation and sphere formation. Co-treatment of miR-26a-5p and paclitaxel decreased cell growth, suggesting that miR-26a-5p might play a role as a chemotherapy sensitizer. In the cancer genome atlas data, high miR-26a-5p and low POLR3G expression were also related to higher survival rate of patients with lung adenocarcinoma. These results suggest that miR-26a-5p can suppress lung cancer stemness and make cancer cell become sensitive to chemotherapy. This finding provides a novel insight into a potential lung cancer treatment by regulating stemness.

Characteristics of recurrent acute urinary retention in BPH patients in the United States: Retrospective analysis of US-based insurance claims database.

PURPOSE: The objective of this study is to analyze characteristics of recurrent acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH), utilizing a population based data set. Also, we sought to report on how AUR was treated, specifically regarding the need and length of catheterization and types of procedures utilized for mitigation. MATERIALS & METHODS: A retrospective observational cohort study was performed using Optum's deidentified Clinformatics® Data Mart Database. We compared two groups, BPH patients with AUR (n = 180,737) and BPH patients without AUR (n = 1,139,760) from January 1, 2003 to December 31, 2017. Also, we analyzed the factors affecting the development of multiple episodes of AUR through age-adjusted multivariate analysis. RESULTS: In contrast to the 47.7% of patients who had a single AUR episode, 33.5% of AUR patients developed 3 or more subsequent episodes of retention. For age matched patients, the risks of additional episodes of retention increase significantly with older age, Caucasian race, diabetes, neurologic conditions, or low income. Overall, the rate of BPH surgery in AUR patients over the study period decreased and the most common procedure was transurethral resection of the prostate. CONCLUSIONS: Risk factors for multiple episodes of AUR included age (60 and older), Caucasian race, lower income socioeconomic status, diabetes, and neurological disorders. Patients with a high probability of developing recurrent episodes of AUR are recommended to receive preemptive BPH medication before such AUR occurrences. Also, more expeditious surgical treatment should be considered rather than temporary catheterization when AUR occurs.

Expression of AKT1 Related with Clinicopathological Parameters in Clear Cell Renal Cell Carcinoma.

Pathways such as VEGF, EGF and mTOR are known to be one of the major mechanisms of tumorigenesis including kidney cancer. To identify potential signaling pathway proteins, we performed differential/correlation analyses of mTOR-associated genes from three public datasets. AKT1 protein, one of the PI3K/AKT/mTOR pathways, turned out to be the potential by showing a consistent discrepancy between ccRCC-associated conditions as well as strong correlation with other mTOR-associated genes across the datasets. Then, we analyzed how AKT1 alteration affects clear cell renal cell carcinoma. The pathology of 58 kidney cancer patients was constructed to analyze the relationship between the expression level of AKT1 through immunohistochemical staining and their clinicopathological data. Gender, age and TNM stage did not show significant results. AKT1 is a known oncogene. However, in this study, high expression of AKT1 showed a slight correlation with lower WHO/ISUP grade, longer recurrence-free and progression-free survival rates.

LPIN1 Induces Gefitinib Resistance in EGFR Inhibitor-Resistant Non-Small Cell Lung Cancer Cells.

Drug resistance limits the efficacy of targeted therapies, including tyrosine kinase inhibitors (TKIs); however, a substantial portion of the drug resistance mechanisms remains unexplained. In this study, we identified LPIN1 as a key factor that regulates gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cells. Unlike TKI-sensitive HCC827 cells, gefitinib treatment induced LPIN1 expression and increased diacylglycerol concentration in TKI-resistant H1650 cells, followed by the activation of protein kinase C delta and nuclear factor kappa B (NF-κB) in an LPIN1-dependent manner, resulting in cancer cell survival. Additionally, LPIN1 increased the production of lipid droplets, which play an important role in TKI drug resistance. All results were recapitulated in a patient-derived EGFR-mutant NSCLC cell line. In in vivo tumorigenesis assay, we identified that both shRNA-mediated depletion and pharmaceutical inhibition of LPIN1 clearly reduced tumor growth and confirmed that gefitinib treatment induced LPIN1 expression and LPIN1-dependent NF-κB activation (an increase in p-IκBα level) in tumor tissues. These results suggest an effective strategy of co-treating TKIs and LPIN1 inhibitors to prevent TKI resistance in NSCLC patients.

Glycogen Storage Disease Phenotypes Accompanying the Perturbation of the Methionine Cycle in NDRG3-Deficient Mouse Livers.

N-Myc downstream regulated gene 3 (NDRG3) is a unique pro-tumorigenic member among NDRG family genes, mediating growth signals. Here, we investigated the pathophysiological roles of NDRG3 in relation to cell metabolism by disrupting its functions in liver. Mice with liver-specific KO of NDRG3 (Ndrg3 LKO) exhibited glycogen storage disease (GSD) phenotypes including excessive hepatic glycogen accumulation, hypoglycemia, elevated liver triglyceride content, and several signs of liver injury. They suffered from impaired hepatic glucose homeostasis, due to the suppression of fasting-associated glycogenolysis and gluconeogenesis. Consistently, the expression of glycogen phosphorylase (PYGL) and glucose-6-phosphate transporter (G6PT) was significantly down-regulated in an Ndrg3 LKO-dependent manner. Transcriptomic and metabolomic analyses revealed that NDRG3 depletion significantly perturbed the methionine cycle, redirecting its flux towards branch pathways to upregulate several metabolites known to have hepatoprotective functions. Mechanistically, Ndrg3 LKO-dependent downregulation of glycine N-methyltransferase in the methionine cycle and the resultant elevation of the S-adenosylmethionine level appears to play a critical role in the restructuring of the methionine metabolism, eventually leading to the manifestation of GSD phenotypes in Ndrg3 LKO mice. Our results indicate that NDRG3 is required for the homeostasis of liver cell metabolism upstream of the glucose-glycogen flux and methionine cycle and suggest therapeutic values for regulating NDRG3 in disorders with malfunctions in these pathways.

Early response evaluation of doxorubicin-nanoparticle-microbubble therapy in orthotopic hepatocellular carcinoma rat model using contrast-enhanced ultrasound and intravoxel incoherent motion-diffusion MRI

Purpose@#This study aimed to apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) for response evaluation. @*Methods@#Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (group [G] 1, n=8), doxorubicin (Dox) alone (G2, n=7), nanoparticle microbubbles alone (G3, n=7), or saline (G4, control, n=6) on days 0 and 7, and were sacrificed on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia. Efficacy was estimated by the percentage of tumor volume growth inhibition compared with control. Toxicity was assessed by body weight changes and blood tests. Post-treatment changes in IVIM-DWI and CEUS parameters were analyzed. @*Results@#Tumor volume growth was inhibited by 48.4% and 90.2% in G1 and G2 compared to G4, respectively. Compared to G2, G1 had a significantly lower degree of body weight change (median, 91.0% [interquartile range, 88.5%-97.0%] vs. 88.0% [82.5%-88.8%], P<0.05) and leukopenia (1.75×103 cells/μL [1.53-2.77] vs. 1.20×103 cells/μL [0.89-1.51], P<0.05). After the first treatment, an increase in peak enhancement, wash-in rate, and wash-in perfusion index on CEUS was observed in G3 and G4 but suppressed in G1 and G2; the apparent diffusion coefficients, true diffusion coefficients, and perfusion fractions significantly increased in G1 and G2 compared to baseline (P<0.05). @*Conclusion@#Dox-NP-MB showed reduced Dox toxicity. Early changes in some CEUS and IVIM-DWI parameters correlated with the therapeutic response.

Diagnostic criteria of perfluorobutane-enhanced ultrasonography for diagnosing hepatocellular carcinoma in high-risk individuals: how is late washout determined?

Purpose@#The aim of this study was to investigate the optimal washout criteria of perfluorobutane-enhanced ultrasonography (PFB-US) for the diagnosis of hepatocellular carcinoma (HCC) in high-risk individuals. @*Methods@#Participants at risk of HCC with treatment-naïve solid hepatic observations (≥1 cm) who underwent PFB-US from March 2019 to September 2020 were prospectively recruited. Arterial phase hyperenhancement (APHE), washout time, and washout degree were evaluated. The diagnosis of HCC was made by non-rim APHE with late and mild washout. The per-lesion diagnostic performance for diagnosing HCC using different cutoffs for late washout (50, 55, 60, 65, and 70 seconds postcontrast) and the different time windows for determining washout (until 2, 3, 4, 5, 6, 7, 8, 9, and 10 minutes postcontrast) were compared using the McNemar test. @*Results@#In total, 101 participants with 113 observations (mean size, 33.5±2.8 mm; HCCs [n=82], non-HCC malignancies [n=16], benign [n=15]) were evaluated. Non-rim APHE was observed in 86.6% (71/82) of HCCs. As the cutoff time for late washout increased, the specificity increased to 100% (95% confidence interval [CI], 88.8% to 100%) at the 60-second cutoff with 62.2% sensitivity (95% CI, 50.8% to 72.7%). When the time window for determining washout became wider, the sensitivity and accuracy increased until 6 minutes, with 100% specificity at all times. @*Conclusion@#Determining washout within 6 minutes after contrast injection with a 60-second cutoff for late washout showed the highest sensitivity without losing specificity for diagnosing HCC using PFB-US in individuals at high risk.

Prevalence and impact of airway diseases on clinical outcomes in idiopathic pulmonary fibrosis

Background/Aims@#The prevalence and effects of airway diseases, including asthma, eosinophilic bronchitis (EB), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have not been thoroughly studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the prevalence of airway diseases in patients with IPF and to identify the differences in symptoms based on the presence of airway diseases. @*Methods@#This single-institution prospective cohort study was conducted from June 2017 to September 2018, at the Seoul National University Hospital. Spirometry with bronchodilator, methacholine bronchial provocation test, induced sputum with eosinophil stain, and exhaled nitric oxide were performed to confirm the presence of airway disease. The modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), EuroQol-5 dimension (EQ-5D) index, and cough-specific quality of life questionnaire (CQLQ) data were collected to assess symptom severity. @*Results@#Total 147 patients with IPF were screened, and 70 patients were analyzed. The prevalence of airway diseases in the participants was as follows: 5.0% had COPD, 1.7% had asthma, 3.3% had ACO, and 1.7% had EB. The mMRC, CAT, SGRQ, EQ-5D, and CQLQ scores did not differ regardless of combined airway disease. After 3 months, the SGRQ (p = 0.028) and CQLQ (p = 0.030) scores were significantly higher in patients with airway disease than in those without. @*Conclusions@#The prevalence of airway diseases in patients with IPF is low, but when airway diseases are accompanied by IPF, symptom severity and quality of life may worsen rapidly.

Prevalence of Bladder Pain Syndrome-like Symptoms: a Population-based Study in Korea.

OBJECTIVES: To investigate the prevalence of bladder pain syndrome (BPS)-like symptoms in the general population of South Korea. METHODS: Between April 16, 2016 and April 29, 2016, we conducted an online survey and computer-assisted personal interviews with adults aged 40-79 years in Korea using structured questionnaires. The sample size was 3,000 (95% confidence level standard error ± 1.79%), and the sampling method was simple randomization according to sex, age, and residential area in proportion to the resident registration demographics of the Korean Ministry of Interior and Safety as of March 2016. All participants were surveyed using the Korean version of the Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale and Geriatric Depression Scale (GDS). The primary outcome was the prevalence of BPS-like symptoms, defined as a total PUF score of ≥ 12. RESULTS: Overall, the prevalence of BPS-like symptoms was 16.4% (483 of 3,000 participants). Women (21.4%) had a significantly higher prevalence of BPS-like symptoms than men (10.7%) (P < 0.01). The prevalence by age was significantly higher in the 70s group than in the other age groups (P < 0.01), and increased significantly with the increasing severity of depression on the GDS (P < 0.01). The prevalence of BPS-like symptoms according to the marital status was significantly different, that is, the prevalence among divorced/bereaved individuals was higher than those of married or unmarried individuals (P < 0.01). CONCLUSION: Our large, representative population-based study showed that BPS-like symptoms are widespread among the general population of South Korea. BPS is considered a disease that deserves greater attention as it is far more common than previously thought and can negatively affect many people's quality of life.

Rapid Recurrence of Giant Multilocular Prostatic Cystadenoma after Laparoscopic Excision for Primary Case: A Case Report.

Giant multilocular prostatic cystadenoma is a rare benign tumor of the prostate gland that presents as a large retroperitoneal pelvic mass. The mass is usually located between the urinary bladder and rectum, and results in obstructive voiding symptoms and a change in bowel habits. Complete surgical excision is the treatment of choice. We present a case of rapid recurrent giant multilocular prostatic cystadenoma after laparoscopic excision for primary case. A previously healthy 54-year-old man presented with acute urinary retention. Prostate MRI showed a large cystic mass approximately 13 cm in size, multiple septa and lobulation in the prostate, and no visible solid lesions. Laparoscopic marsupialization of giant multilocular prostatic cystadenoma cysts was performed. One year later, the patient presented with local recurrence. Repeated laparoscopic complete resection was performed without any complications and further recurrence. Giant multilocular prostatic cystadenoma has the risk of recurrence in case of incomplete resection. Surgical treatment should be performed with the goal of complete removal following the same principles as cancer surgery.

A Case of Incidental Schwannoma Mimicking Necrotic Metastatic Lymph Node from Bladder Cancer.

Background and Objectives: Retroperitoneal schwannoma is a very rare case of schwannoma which commonly occurs in the other part of the body. However, it is difficult to distinguish schwannoma from other tumors before pathological examination because they do not show specific characteristics on imaging study such as ultrasound, computed tomography (CT), and magnetic resonance image (MRI). Case summary: A 60-year-old male showed a retroperitoneal cystic tumor which is found incidentally during evaluation of coexisted bladder tumor. Neurogenic tumor was suspicious for the retroperitoneal tumor through pre-operative imaging study. Finally, a schwannoma was diagnosed by immunohistochemical examination after complete surgical excision laparoscopically. Conclusion: As imaging technology is developed, there may be more chances to differentiate schwannoma from other neoplasm. However, still surgical resection and histopathological examination is feasible for diagnosis of schwannoma.

PKM2 Regulates HSP90-Mediated Stability of the IGF-1R Precursor Protein and Promotes Cancer Cell Survival during Hypoxia.

Insulin-like growth factor-1 receptor (IGF-1R), an important factor in promoting cancer cell growth and survival, is commonly upregulated in cancer cells. However, amplification of the IGF1R gene is extremely rare in tumors. Here, we have provided insights into the mechanisms underlying the regulation of IGF-1R protein expression. We found that PKM2 serves as a non-metabolic protein that binds to and increases IGF-1R protein expression by promoting the interaction between IGF-1R and heat-shock protein 90 (HSP90). PKM2 depletion decreases HSP90 binding to IGF-1R precursor, thereby reducing IGF-1R precursor stability and the basal level of mature IGF-1R. Consequently, PKM2 knockdown inhibits the activation of AKT, the key downstream effector of IGF-1R signaling, and increases apoptotic cancer cell death during hypoxia. Notably, we clinically verified the PKM2-regulated expression of IGF-1R through immunohistochemical staining in a tissue microarray of 112 lung cancer patients, demonstrating a significant positive correlation (r = 0.5208, p < 0.0001) between PKM2 and IGF-1R expression. Together, the results of a previous report demonstrated that AKT mediates PKM2 phosphorylation at serine-202; these results suggest that IGF-1R signaling and PKM2 mutually regulate each other to facilitate cell growth and survival, particularly under hypoxic conditions, in solid tumors with dysregulated IGF-1R expression.

Diabetes Mellitus Promotes Smooth Muscle Cell Proliferation in Mouse Ureteral Tissue through the P-ERK/P-JNK/VEGF/PKC Signaling Pathway.

Background and objectives: The aim of our study was to evaluate the role of diabetes mellitus (DM) as a significant factor affecting spontaneous stone expulsion, as suggested by previous research. Materials and methods: We investigated the influence of DM on the ureter using a murine model. The mouse-model arm of this study used 20 15 -week-old mice, including 10 normal (control) mice and 10 DM mice. We measured the proximal, middle and distal ureteral smooth muscle thickness in each mouse and the differences among ureteral sections were analyzed. Mouse ureteral specimens were also analyzed via western blotting to detect relative protein expression of phosphor-extracellular signal regulated kinases (P-ERK), phosphor-C-Jun N-terminal kinase (P-JNK), vascular endothelial growth factor (VEGF), and protein kinase C (PKC), which are representative factors involved in cell regulation. Results: We observed significant hyperproliferation of ureteral smooth muscle in DM mice compared to normal mice, which may provoke reduced peristalsis. The ureteral smooth muscle of DM mice was significantly thicker than that of normal mice in all ureteral tissues: proximal (p = 0.040), mid (p = 0.010), and distal (p = 0.028). The relative protein expression of P-ERK (p = 0.005) and P-JNK (p = 0.001) was higher in the diabetic group compared to the normal group. Additionally, protein expression of VEGF (p = 0.002) and PKC (p = 0.001) were remarkably up-regulated in DM mice. Conclusions: Hyperproliferation of ureteral smooth muscle was observed in DM mice, but not in normal mice. The pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role in pathological ureteral conditions.

Clinical Outcomes and Risk Factor Analysis of Patients Presenting with Emphysematous Cystitis: A 15-Year Retrospective Multicenter Study.

Background and objectives: To investigate the risk factors for emphysematous cystitis (EC) compared to those of acute cystitis (AC) to increase clinicians awareness of the possibility for the aggravation of patient status. Materials and methods: We retrospectively reviewed a total of 54 patients who were hospitalized with a diagnosis of EC by abdominal computed tomography (CT) scan from 2006 to 2020. The control group included 92 patients who were hospitalized for the treatment of AC in the same period. We sought to identify the clinical features and predisposing diseases, such as age, sex, diabetes mellitus (DM), hypertension (HTN), cerebrovascular accident (CVA), chronic kidney disease (CKD), neurogenic bladder (NB), history of urinary tract infection (UTI), and emphysematous pyelonephritis (EPN), that were associated with the development of EC. Results: The median (interquartile range (IQR)) age of the patients with EC was older than that of the patients with AC (78.5 (15.3) years (range: 52-100) vs. 70.0 (26.5) years (range: 28-97 years)). Sepsis and mortality occurred only in the EC group (48.1% and 11.1%, respectively). The univariate analysis of predisposing factors revealed that age, DM, HTN, CVA, CKD, and NB were significantly associated with EC. In the multivariate analysis, DM (OR, 6.251; 95% CI, 2.254-17.250; p < 0.001), CKD (OR, 18.439; 95% CI, 3.421-99.404; p = 0.001), NB (OR, 7.374; 95% CI, 1.993-27.285; p = 0.003) were associated with EC. Conclusions: The results of this study revealed that DM, CKD, and NB were significant risk factors for EC. The tendency toward sepsis and high mortality underscore the need for careful observation while treating patients with EC with the risk noted above.