Clinical feasibility of deep learning-based synthetic CT images from T2-weighted MR images for cervical cancer patients compared to MRCAT.

This work aims to investigate the clinical feasibility of deep learning-based synthetic CT images for cervix cancer, comparing them to MR for calculating attenuation (MRCAT). Patient cohort with 50 pairs of T2-weighted MR and CT images from cervical cancer patients was split into 40 for training and 10 for testing phases. We conducted deformable image registration and Nyul intensity normalization for MR images to maximize the similarity between MR and CT images as a preprocessing step. The processed images were plugged into a deep learning model, generative adversarial network. To prove clinical feasibility, we assessed the accuracy of synthetic CT images in image similarity using structural similarity (SSIM) and mean-absolute-error (MAE) and dosimetry similarity using gamma passing rate (GPR). Dose calculation was performed on the true and synthetic CT images with a commercial Monte Carlo algorithm. Synthetic CT images generated by deep learning outperformed MRCAT images in image similarity by 1.5% in SSIM, and 18.5 HU in MAE. In dosimetry, the DL-based synthetic CT images achieved 98.71% and 96.39% in the GPR at 1% and 1 mm criterion with 10% and 60% cut-off values of the prescription dose, which were 0.9% and 5.1% greater GPRs over MRCAT images.

Diagnostic Performance of Endoscopic Ultrasound Elastography for Differential Diagnosis of Gallbladder Polyp.

BACKGROUND AND AIMS: It is difficult to differentiate between neoplastic and non-neoplastic gallbladder (GB) polyps before surgery. Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method. The utility of EUS-EG in the differential diagnosis of GB polyps has not been investigated. We aimed to investigate the diagnostic performance of EUS-EG for the differential diagnosis of GB polyps. METHODS: Patients with GB polyps were prospectively enrolled from June 2020 until November 2022. EUS-EG and semi-quantitative evaluation of the strain ratio (SR) were performed for differential diagnosis of GB polyps. Fifty-three eligible patients were divided into two groups based on the final diagnosis after surgery. Patient demographics, EUS characteristics, and SR values were compared. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff SR value that discriminates between neoplastic and non-neoplastic GB polyps. RESULTS: The median SR value for neoplastic polyps (32.93 [interquartile range: 22.37-69.02]) was significantly higher than for non-neoplastic polyps (5.40 [2.36-14.44]; p<0.001). There were significant differences in SR values between non-neoplastic, benign neoplastic (23.38 [13.62-39.04]), and malignant polyps (49.25 [27.90-82.00]). The optimal cut-off SR value to differentiate between neoplastic and non-neoplastic polyps was 18.4. In multivariable logistic regression, SR value >18.4 (odds ratio 33.604, 95% confidence interval 2.588-436.292) was an independent predictor of neoplastic polyps. CONCLUSIONS: EUS-EG and SR values can be used as a supplementary method for evaluating GB polyps.

Pancreatic Cancer Treatment Targeting the HGF/c-MET Pathway: The MEK Inhibitor Trametinib.

Pancreatic cancer is characterized by fibrosis/desmoplasia in the tumor microenvironment, which is primarily mediated by pancreatic stellate cells and cancer-associated fibroblasts. HGF/c-MET signaling, which is instrumental in embryonic development and wound healing, is also implicated for its mitogenic and motogenic properties. In pancreatic cancer, this pathway, along with its downstream signaling pathways, is associated with disease progression, prognosis, metastasis, chemoresistance, and other tumor-related factors. Other features of the microenvironment in pancreatic cancer with the HGF/c-MET pathway include hypoxia, angiogenesis, metastasis, and the urokinase plasminogen activator positive feed-forward loop. All these attributes critically influence the initiation, progression, and metastasis of pancreatic cancer. Therefore, targeting the HGF/c-MET signaling pathway appears promising for the development of innovative drugs for pancreatic cancer treatment. One of the primary downstream effects of c-MET activation is the MAPK/ERK (Ras, Ras/Raf/MEK/ERK) signaling cascade, and MEK (Mitogen-activated protein kinase kinase) inhibitors have demonstrated therapeutic value in RAS-mutant melanoma and lung cancer. Trametinib is a selective MEK1 and MEK2 inhibitor, and it has evolved as a pivotal therapeutic agent targeting the MAPK/ERK pathway in various malignancies, including BRAF-mutated melanoma, non-small cell lung cancer and thyroid cancer. The drug's effectiveness increases when combined with agents like BRAF inhibitors. However, resistance remains a challenge, necessitating ongoing research to counteract the resistance mechanisms. This review offers an in-depth exploration of the HGF/c-MET signaling pathway, trametinib's mechanism, clinical applications, combination strategies, and future directions in the context of pancreatic cancer.

Effect of HY7602 Fermented Deer Antler on Physical Fatigue and Antioxidant Activity in Mice.

Lactobacillus curvatus HY7602 fermented antler (FA) ameliorates sarcopenia and improves exercise performance by increasing muscle mass, muscle fiber regeneration, and mitochondrial biogenesis; however, its anti-fatigue and antioxidant effects have not been studied. Therefore, this study aimed to investigate the anti-fatigue and antioxidant effects and mechanisms of FA. C2C12 and HepG2 cells were stimulated with 1 mM of hydrogen peroxide (H2O2) to induce oxidative stress, followed by treatment with FA. Additionally, 44-week-old C57BL/6J mice were orally administered FA for 4 weeks. FA treatment (5-100 µg/mL) significantly attenuated H2O2-induced cytotoxicity and reactive oxygen species (ROS) production in both cell lines in a dose-dependent manner. In vivo experiments showed that FA treatment significantly increased the mobility time of mice in the forced swimming test and significantly downregulated the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), and lactate. Notably, FA treatment significantly upregulated the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione ratio (GSH/GSSG) and increased the mRNA expression of antioxidant genes (SOD1, SOD2, CAT, GPx1, GPx2, and GSR) in the liver. Conclusively, FA is a potentially useful functional food ingredient for improving fatigue through its antioxidant effects.

Enhanced Anti-tumor Effect of Flavopiridol in Combination With Gemcitabine in Pancreatic Cancer.

BACKGROUND/AIM: The efficacy of current chemotherapies for pancreatic ductal adenocarcinoma (PDAC) is still unsatisfactory. Flavopiridol inhibits multiple cyclin-dependent kinases, causing cell cycle arrest and inducing cancer cell apoptosis. This study aimed to evaluate the anti-tumor effect of flavopiridol and gemcitabine in PDAC in vitro and in vivo. MATERIALS AND METHODS: PANC-1 and MIA PaCa-2 cell lines were treated with gemcitabine and flavopiridol alone, in combination, and sequentially, and cell proliferation, apoptosis, and the cell cycle were evaluated. Proteins related to cell cycle progression (cyclin A, CDK2, E2F-1, and p53) were quantified using western blotting. A xenograft mouse model was generated, and the effects of gemcitabine and flavopiridol, administered alone or in combination, were evaluated by measuring tumor volume and apoptosis degree using the TUNEL assay. RESULTS: Sequential administration of gemcitabine and flavopiridol suppressed PDAC cell proliferation and induced apoptosis. Flavopiridol treatment led to an increase in the number of cells in the S and a decrease in those in the G0/G1 phases. Gemcitabine increased and decreased the number of S- and G2/M-phase cells, respectively. Furthermore, flavopiridol treatment decreased cyclin A and CDK2 expression and increased E2F-1 expression. In a xenograft mouse model, the combined administration of gemcitabine and flavopiridol demonstrated the most significant reduction in tumor volume and induction of apoptosis. CONCLUSION: Flavopiridol potentiates the anti-tumor activity of gemcitabine by inducing cell cycle arrest and apoptosis. Its synergistic inhibition of PDAC cell proliferation, when combined with gemcitabine, positions flavopiridol as a promising candidate for cancer treatment.

Nanotopology-Enabled On-Site Pathogen Detection for Managing Atopic Dermatitis.

Atopic dermatitis (AD), a prevalent skin condition often complicated by microbial infection, poses a significant challenge in identifying the responsible pathogen for its effective management. However, a reliable, safe tool for pinpointing the source of these infections remains elusive. In this study, a novel on-site pathogen detection that combines chemically functionalized nanotopology with genetic analysis is proposed to capture and analyze pathogens closely associated with severe atopic dermatitis. The chemically functionalized nanotopology features a 3D hierarchical nanopillar array (HNA) with a functional polymer coating, tailored to isolate target pathogens from infected skin. This innovative nanotopology demonstrates superior pathogenic capture efficiency, favorable entrapment patterns, and non-cytotoxicity. An HNA-assembled stick is utilized to directly retrieve bacteria from infected skin samples, followed by extraction-free quantitative loop-mediated isothermal amplification (direct qLAMP) for validation. To mimic human skin conditions, porcine skin is employed to successfully capture Staphylococcus aureus, a common bacterium exacerbating AD cases. The on-site detection method exhibits an impressive detection limit of 103 cells mL-1 . The HNA-assembled stick represents a promising tool for on-site detection of bacteria associated with atopic dermatitis. This innovative approach enables to deepen the understanding of AD pathogenesis and open avenues for more effective management strategies for chronic skin conditions.

Liver-Directed Combined Radiation Therapy for Downstaging Beyond-Milan Hepatocellular Carcinoma to Liver Transplantation.

PURPOSE: Curative surgery involving either resection or liver transplantation (LT) is indicated only for early-stage hepatocellular carcinoma (HCC). Over the years, numerous efforts have been made to downstage advanced HCC to curative surgery using various locoregional therapies. In this study, we investigated the role of liver-directed combined radiation therapy (LD-CRT) as a downstaging strategy for converting beyond-Milan advanced HCC to LT. METHODS AND MATERIALS: From January 2009 to February 2022, 53 patients with HCC who were initially beyond-Milan criteria were treated with LD-CRT and subsequent LT. These patients were compared with those who underwent upfront LT for within-Milan HCCs. The primary endpoint was overall survival (OS) and the secondary endpoint recurrence-free survival (RFS). RESULTS: After LD-CRT, substantial downstaging was achieved in 35 patients (66%) who were initially beyond-Milan to within-Milan. At a median follow-up period of 47.6 months (range, 6.9-151.7 months), 5-year OS and 2-year RFS of the patients who received downstaging LD-CRT followed by LT were 66.9% and 63.2%, respectively. Patients who were successfully downstaged to within-Milan after LD-CRT had improved 5-year OS compared with their counterparts (81.9% vs 74.3%, P = .219). Recurrence after transplantation was observed in 18 patients (4 intrahepatic recurrences and 14 extrahepatic metastases). CONCLUSIONS: LD-CRT achieved favorable oncological outcomes as a downstaging strategy for LT in patients with beyond-Milan HCC. The findings of this study suggest that the active adoption of LD-CRT needs full consideration for patients with beyond-Milan HCC, presenting the possibility of curing patients with advanced HCC.

Biceps Rerouting Regardless of a Biceps-Labral Lesion During Rotator Cuff Repair Results in Lower Retear Rates and Comparable Clinical Outcomes to Subpectoral Biceps Tenodesis.

PURPOSE: To evaluate the radiographic and clinical outcomes when rerouting a pathologic biceps during arthroscopic rotator cuff repair by comparing it with concomitant subpectoral biceps tenodesis (SPBT). METHODS: This retrospective, historical cohort study was conducted with patients who underwent an arthroscopic repair of a full-thickness rotator cuff tear, with intraoperative confirmation of biceps pathology including partial tears, subluxation, pulley lesions, or type II SLAP lesions. Until May 2018, such patients were treated with concomitant subpectoral tenodesis (group SPBT). Afterward, biceps rerouting (BR) was done regardless of biceps pathology (group BR) without biceps or SLAP repair. Radiographic parameters, including fatty degeneration, acromiohumeral distance, Sugaya classification, and retears, were evaluated using preoperative and 1-year postoperative magnetic resonance imaging results. Clinical evaluation with a minimum 2-year follow-up included pain visual analog scale, American Shoulder and Elbow Surgeons, Simple Shoulder Test, and Constant-Murley scores. Whether individual patients exceeded these scores' minimal clinically important difference also was determined. RESULTS: A total of 64 patients (group SPBT = 32; group BR = 32) were included in the final analysis. The duration of clinical follow-up was 36.2 ± 9.3 months in group SPBT and 29.4 ± 6.9 months in the BR group (P = .002). Compared with group SPBT, group BR demonstrated a significantly lower retear rate (SPBT vs BR: 34.4% vs 12.5%, P = .039). In the BR group, 8 of 32 (25%) patients demonstrated a postoperative LHBT tear. The 4 cuff retears in group BR only took place within these patients. Other postoperative radiographic and clinical outcomes were comparable between the groups. Within each group, significant postoperative improvements were demonstrated (P < .05 for all clinical scores). CONCLUSIONS: Even in the presence of a pathologic LHBT and/or a type II SLAP lesion, augmenting the rotator cuff repair with BR significantly reduced retear rates while achieving clinical scores comparable with SPBT in a minimum 2-year follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Re-evaluation of battery-grade lithium purity toward sustainable batteries.

Recently, the cost of lithium-ion batteries has risen as the price of lithium raw materials has soared and fluctuated. Notably, the highest cost of lithium production comes from the impurity elimination process to satisfy the battery-grade purity of over 99.5%. Consequently, re-evaluating the impact of purity becomes imperative for affordable lithium-ion batteries. In this study, we unveil that a 1% Mg impurity in the lithium precursor proves beneficial for both the lithium production process and the electrochemical performance of resulting cathodes. This is attributed to the increased nucleation seeds and unexpected site-selective doping effects. Moreover, when extended to an industrial scale, low-grade lithium is found to reduce production costs and CO2 emissions by up to 19.4% and 9.0%, respectively. This work offers valuable insights into the genuine sustainability of lithium-ion batteries.

Safety and Efficacy of Neoadjuvant SABR in Pancreatic Cancer: Effect of Magnetic Resonance Imaging-Guided Respiratory-Gated Adaptive Radiation Therapy.

Purpose: We aimed to evaluate the safety and efficacy of neoadjuvant SABR using magnetic resonance imaging-guided respiratory-gated adaptive radiation therapy (MRgRg-ART) in pancreatic cancer. Methods and Materials: We performed a single-institution retrospective review in patients with pancreatic cancer who underwent neoadjuvant SABR followed by surgical resection. After neoadjuvant chemotherapy, those considered resectable by the multidisciplinary team received SABR over 5 consecutive days using MRgRg-ART. Factors associated with severe postoperative complications (Clavien-Dindo grade ≥III) and prognostic factors for overall survival were analyzed. Results: Sixty-two patients were included in the analysis, with a median follow-up of 10.3 months. The median prescribed dose to the planning target volume was 50 Gy. Fifty-two (85.3%) patients underwent R0 resection, and 11 (18.0%) experienced severe postoperative complications. No factors were associated with the incidence of severe postoperative complications. There were 3 cases of locoregional recurrence, resulting in a 12-month local control rate of 93.1%. Elevated postoperative carbohydrate antigen 19-9 was significantly associated with poor overall survival in the multivariate analysis (P = .037). Conclusions: Neoadjuvant SABR with 50 Gy using MRgRg-ART delivered to pancreatic cancer resulted in a notable survival outcome with acceptable toxicities. Further studies are warranted to investigate the long-term effects of this method.

Clinical Significance of Venous Thromboembolism in Patients with Advanced Cholangiocarcinoma.

Background/Aims: Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA. Methods: We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA. Results: During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02; p<0.001) was associated with poor overall survival. Conclusions: Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Early Detection of Botrytis cinerea Infection in Cut Roses Using Thermal Imaging.

Botrytis cinerea (B. cinerea) causes gray mold disease (GMD), which results in physiological disorders in plants that decrease the longevity and economic value of horticultural crops. To prevent the spread of GMD during distribution, a rapid, early detection technique is necessary. Thermal imaging has been used for GMD detection in various plants, including potted roses; however, its application to cut roses, which have a high global demand, has not been established. In this study, we investigated the utility of thermal imaging for the early detection of B. cinerea infection in cut roses by monitoring changes in petal temperature after fungal inoculation. We examined the effects of GMD on the postharvest quality and petal temperature of cut roses treated with different concentrations of fungal conidial suspensions and chemicals. B. cinerea infection decreased the flower opening, disrupted the water balance, and decreased the vase life of cut roses. Additionally, the average temperature of rose petals was higher for infected flowers than for non-inoculated flowers. One day before the appearance of necrotic symptoms (day 1 of the vase period), the petal temperature in infected flowers was significantly higher, by 1.1 °C, than that of non-inoculated flowers. The GMD-induced increase in petal temperature was associated with the mRNA levels of genes related to ethylene, reactive oxygen species, and water transport. Furthermore, the increase in temperature caused by GMD was strongly correlated with symptom severity and fungal biomass. A multiple regression analysis revealed that the disease incidence in the petals was positively related to the petal temperature one day before the appearance of necrotic symptoms. These results show that thermography is an effective technique for evaluating changes in petal temperature and a possible method for early GMD detection in the cut flower industry.

Transcriptome analysis of Haemaphysalis flava female using Illumina HiSeq 4000 sequencing: de novo assembly, functional annotation and discovery of SSR markers.

BACKGROUND: Ticks are ectoparasites capable of directly damaging their hosts and transmitting vector-borne diseases. The ixodid tick Haemaphysalis flava has a broad distribution that extends from East to South Asia. This tick is a reservoir of severe fever with thrombocytopenia syndrome virus (SFTSV) that causes severe hemorrhagic disease, with cases reported from China, Japan and South Korea. Recently, the distribution of H. flava in South Korea was found to overlap with the occurrence of SFTSV. METHODS: This study was undertaken to discover the molecular resources of H. flava female ticks using the Illumina HiSeq 4000 system, the Trinity de novo sequence assembler and annotation against public databases. The locally curated Protostome database (PANM-DB) was used to screen the putative adaptation-related transcripts classified to gene families, such as angiotensin-converting enzyme, aquaporin, adenylate cyclase, AMP-activated protein kinase, glutamate receptors, heat shock proteins, molecular chaperones, insulin receptor, mitogen-activated protein kinase and solute carrier family proteins. Also, the repeats and simple sequence repeats (SSRs) were screened from the unigenes using RepeatMasker (v4.0.6) and MISA (v1.0) software tools, followed by the designing of SSRs flanking primers using BatchPrimer 3 (v1.0) software. RESULTS: The transcriptome produced a total of 69,822 unigenes, of which 46,175 annotated to the homologous proteins in the PANM-DB. The unigenes were also mapped to the EuKaryotic Orthologous Groups (KOG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) specializations. Promiscuous presence of protein kinase, zinc finger (C2H2-type), reverse transcriptase, and RNA recognition motif domains was observed in the unigenes. A total of 3480 SSRs were screened, of which 1907 and 1274 were found as tri- and dinucleotide repeats, respectively. A list of primer sequences flanking the SSR motifs was detailed for validation of polymorphism in H. flava and the related tick species. CONCLUSIONS: The reference transcriptome information on H. flava female ticks will be useful for an enriched understanding of tick biology, its competency to act as a vector and the study of species diversity related to disease transmission.

Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: Clinical Outcome after Long-term Follow-up.

Background/Aims: : The optimal duration and interval of follow-up for cystic lesions of the pancreas (CLPs) is not well established. This study was performed to investigate the optimal duration and interval of follow-up for CLPs in clinical practice. Methods: : Patients with CLPs without worrisome features or high-risk stigmata underwent follow-up with computed tomography at 6, 12, 18, and 24 months and then every 12 months thereafter. A retrospective analysis of prospectively collected data was performed. Results: : A total of 227 patients with CLPs detected from 2000 to 2008 (mean initial diameter, 1.3±0.6 cm) underwent follow-up for a median of 120 months. Twenty-two patients (9.7%) underwent surgery after a median of 47.5 months. Malignancies developed in four patients (1.8%), one within 5 years and three within 10 years. One hundred and fourteen patients (50.2%) were followed up for more than 10 years. No malignancy developed after 10 years of follow-up. During surveillance, 37 patients (16.3%) experienced progression to surgical indication. In patients with CLPs less than 2 cm in diameter, development of surgical indications did not occur within 24 months of follow-up. Conclusions: : CLPs should be continuously monitored after 5 years because of the persistent potential for malignant transformation of CLPs. An interval of 24 months for initial follow-up might be enough for CLPs with initial size of less than 2 cm in clinical practice.

Genetic susceptibility to post-endoscopic retrograde cholangiopancreatography pancreatitis identified in propensity score-matched analysis.

BACKGROUND/AIMS: A previous history of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a risk factor for PEP, suggesting that there may be a genetic predisposition to PEP. However, nothing is known about this yet. The aim of this study was to identify genetic variations associated with PEP. METHODS: A cohort of high-risk PEP patients was queried from December 2016 to January 2019. For each PEP case, two propensity score-matched controls were selected. Whole exome sequencing was performed using blood samples. Genetic variants reported to be related to pancreatitis were identified. To discover genetic variants that predispose to PEP, a logistic regression analysis with clinical adjustment was performed. Gene-wise analyses were also conducted. RESULTS: Totals of 25 PEP patients and 50 matched controls were enrolled. Among the genetic variants reported to be associated with pancreatitis, only CASR rs1042636 was identified, and it showed no significant difference between the case and control groups. A total of 54,269 non-synonymous variants from 14,313 genes was identified. Logistic regression analysis of these variants showed that the IRF2BP1 rs60158447 GC genotype was significantly associated with the occurrence of PEP (odds ratio 2.248, FDR q value = 0.005). Gene-wise analyses did not show any significant results. CONCLUSION: This study found that the IRF2BP1 gene variant was significantly associated with PEP. This genetic variant is a highly targeted PEP risk factor candidate and can be used for screening high-risk PEP groups before ERCP through future validation. (ClinicalTrials.gov no. NCT02928718).

Glenohumeral versus subacromial steroid injections for impingement syndrome with mild stiffness: a randomized controlled trial.

BACKGROUND: The subacromial (SA) space is a commonly used injection site for treatment of impingement syndrome. For shoulder stiffness, glenohumeral (GH) injections are commonly performed. However, in cases of impingement syndrome with mild shoulder stiffness, the optimal site of steroid injection has yet to be identified. METHODS: This prospective, randomized study compared the short-term outcomes of ultrasound-guided GH and SA steroid injections in patients who were diagnosed with impingement syndrome and mild stiffness. Each group comprised 24 patients who received either a GH or SA injection of 40 mg of triamcinolone. Range of motion and clinical scores were assessed before and 3, 7, and 13 weeks after the injection. RESULTS: GH and SA injections significantly improved the range of motion and clinical scores after 13 weeks of follow-up. Notably, targeting the GH joint resulted in an earlier gain of forward elevation, external rotation, and internal rotation in 3 weeks (P<0.001, P=0.012, and P=0.002, respectively) and of internal rotation and a Constant-Murley score in 7 weeks (P<0.001 and P=0.046). Subsequent measurements were similar between the groups and showed a steady improvement in all ranges of motion and clinical scores. CONCLUSIONS: GH injections may be more favorable than SA injections for treatment of impingement syndrome with mild stiffness, especially in improving the range of motion in the early period. However, the procedures showed similar outcomes after 3 months. Level of evidence: I.