Exercise training mode effects on myokine expression in healthy adults: A systematic review with meta-analysis.

BACKGROUND: The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle-organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment. METHODS: A systematic search was undertaken in PubMed, Medline, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on IL-15, irisin, SPARC, OSM, and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change. RESULTS: Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn. CONCLUSION: Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and 3 patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6, 12.4, and 18.1 months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Serious Complications of the Percutaneous A1 Pulley Release: Case Reports and Literature Review.

Percutaneous first annular pulley (A1 pulley) release, which has been increasingly used to treat trigger fingers, has been widely established as a safe and simple procedure. Multiple studies have reported positive results of percutaneous A1 pulley release. In this study, however, we report cases of patients who developed complications after undergoing percutaneous A1 pulley release at local clinics. A total of six patients visited our hospital for infectious complications after percutaneous A1 pulley release. Various sequelae such as damage to normal structures, insufficient procedure, and tissue necrosis were observed during the exploration. A retrospective study was conducted to identify the cause and trend of the observed complications by instruments (HAKI knife or needle). In the HAKI knife group, there was a tendency for damage to normal structures, while in the needle group, an insufficient release or serious soft tissue necrosis was observed. Based on these cases, our findings confirm the existence and characteristics of infectious complications following the percutaneous A1 pulley release. We further identify that the type of instrument used predicts the nature of complications. Thus, reliable and skilled performance of the procedure by experts is essential for safe treatment.

Hand Reconstruction Using Anterolateral Thigh Free Flap by Terminal Perforator-to-Digital Artery Anastomosis: Retrospective Analysis.

This study aimed to analyze cases of anterolateral thigh (ALT) free flap used for hand reconstruction with terminal perforator-to-digital artery anastomosis. Patients who underwent ALT free flap placement with terminal perforator-to-digital artery anastomosis for hand reconstruction between January 2011 and August 2021 were included. The number, length, and diameter of the perforators and veins, flap size, and operative time were investigated through a retrospective review of charts and photographs. The occurrences of arterial thrombosis, venous thrombosis, arterial spasm, and flap necrosis were analyzed. In total, 50 patients were included in this study. The mean diameter and length of the perforators were 0.68 mm and 3.25 cm, respectively, and the mean number of veins anastomosed was 1.88, with a mean diameter of 0.54 mm. Complications included four cases of arterial thrombosis, one case of venous thrombosis, seven cases of partial necrosis, and one case of total flap failure. Regression analysis showed that a longer perforator was associated with arterial thrombosis whereas larger flap size and number of anastomosed veins were associated with partial necrosis ( p < 0.05). The terminal perforator-to-digital artery anastomosis offers advantages in using compact free flaps with short pedicle lengths to cover small hand defects.

The "Swing-Door" Regrafting of Donor Site: An Alternative Method for Split-Thickness Skin Graft in the Hand.

Background Skin defects in the hands are common injuries, and autologous skin grafting is the ideal treatment. However, complications can occur at the donor and recipient sites. This study compares the "Swing-door" technique with conventional skin grafting. Methods From August 2019 to February 2023, 19 patients with skin defects of hand underwent the "Swing-door" split-thickness skin graft (STSG) technique. The thin epithelial layer was elevated with proximal part attached. Skin graft was harvested beneath. Donor site was then closed with epithelial flap like a "Swing-door". The outcomes were evaluated in terms of healing time, scar formation, and pain at the donor and recipient sites. The data were compared with the conventional STSG. Results The "Swing-door" group had lower graft take percentages, but complications did not significantly differ between the two groups. The "Swing-door" technique resulted in better cosmetic outcomes, as evidenced by lower Vancouver Scar Scale scores, faster donor site epithelialization, and reduced pain and discomfort during the early postoperative period, as measured by Visual Analog Scale. Conclusion The "Swing-door" STSG is a useful alternative for treating hand skin defects.

Trends in Childhood Glaucoma Prevalence and Incidence in South Korea, 2002-2019: A Nationwide Population-Based Study.

PRCIS: This nationwide analysis identified the prevalence and incidence of childhood glaucoma for an 18-year period. The prevalence and incidence of primary congenital glaucoma showed increasing trends. Juvenile open angle glaucoma, meanwhile, showed a decreasing tendency. PURPOSE: We aimed to determine the trends in the prevalence and incidence of childhood glaucoma in the entire population of South Korea. PATIENTS AND METHODS: A nationwide retrospective cohort study was performed with an age-specific and sex-specific population of South Korea. The Korean National Health Insurance Service claims database for 2002 to 2019 was accessed to identify cases of ophthalmologist-confirmed primary childhood glaucoma [ie, primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG)]. Incidence for PCG was estimated for a same-birth-year population, while that for JOAG was estimated using age-specific and sex-specific population figures. To verify the glaucoma cases, we also analyzed the diagnostic codes as well as any information on medication prescriptions and/or ocular-surgery history. RESULTS: During the 18-year observational period, totals of 505 and 7538 patients were diagnosed with PCG and JOAG, respectively. The mean prevalences of PCG and JOAG were 3.96±0.72 and 14.17±5.18, respectively. The prevalence of PCG showed an overall increasing trend during the study period, but the pattern was not significant ( ß =0.049, P =0.143); that of JOAG, meanwhile, showed a significant decreasing tendency ( ß =-0.713, P =0.001). PCG prevalence showed no difference between urban and rural areas, but JOAG showed a higher prevalence in rural areas ( P <0.001). As for mean incidence, the rates for PCG and JOAG were 1.54±0.49 and 5.02±1.95 (per 100,000 person-years), respectively, and were higher in males ( P <0.001 and P =0.013). CONCLUSION: This study identified childhood glaucoma prevalence and incidence in a general population of East Asian ethnicity. This data could help to promote a better understanding of the typical epidemiological features and clinical courses of childhood glaucoma patients.

Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset.

PURPOSE: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment-related AEs occurred with lazertinib than gefitinib. CONCLUSION: Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial. MATERIALS AND METHODS: The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)-based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis. RESULTS: Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable. CONCLUSION: Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

Improvement of weanling pigs immune status and metabolic condition using ultraweak light.

Weaning stress is the most common issue in swine farms, which increases mortality and morbidity. The use of artificial light is an option for modifying the immune system and metabolic pathways. This study aimed to evaluate the influence of ultraweak light (Photonia) on growth performance, immune system and metabolism of weanling pigs, and the carry-over effect on the growth performance in postweanling growing stages. A total of 30 weaned pigs with an average initial body weight of 7.06 ± 0.11 kg (age: 21 days) were allotted two treatments (Control and Photonia) with 15 replicates. The pelleted form diets were prepared for pigs in three phases including phase 1 (Days 0-14), phase 2 (Days 15-28) and phase 3 (Days 29-48). The gain-to-feed ratio (G:F) of pigs was significantly greater in the Photonia treatment. On Day 28, a higher concentration of immunoglobin A (IgA) (p < 0.01) and IgG (p < 0.01) was observed in the Photonia pigs. On Day 48, the Photonia treatment showed a greater serum IgA (p < 0.01) and IgG (p < 0.05). The concentration of interleukin (IL)-6 was decreased (p < 0.05) in the Photonia treatment. At Day 48, the concentrations of tumour necrotic factor-α, IL-1ß and IL-6 in serum were decreased (p < 0.05) in pigs in the Photonia treatment. Metabolic pathways analysis showed that the Photonia treatment increased the d-glutamine, d-glutamate, alanine, aspartate, glutamate and phenylalanine compared with the control treatment. In conclusion, the use of Photonia for weanling pigs is recommended due to improved G:F, immune status and activation of amino acids metabolic pathways including d-glutamine, d-glutamate, alanine, aspartate, glutamate and phenylalanine.

Base editing of organellar DNA with programmable deaminases.

Mitochondria and chloroplasts are organelles that include their own genomes, which encode key genes for ATP production and carbon dioxide fixation, respectively. Mutations in mitochondrial DNA can cause diverse genetic disorders and are also linked to ageing and age-related diseases, including cancer. Targeted editing of organellar DNA should be useful for studying organellar genes and developing novel therapeutics, but it has been hindered by lack of efficient tools in living cells. Recently, CRISPR-free, protein-only base editors, such as double-stranded DNA deaminase toxin A-derived cytosine base editors (DdCBEs) and adenine base editors (ABEs), have been developed, which enable targeted organellar DNA editing in human cell lines, animals and plants. In this Review, we present programmable deaminases developed for base editing of organellar DNA in vitro and discuss mitochondrial DNA editing in animals, and plastid genome (plastome) editing in plants. We also discuss precision and efficiency limitations of these tools and propose improvements for therapeutic, agricultural and environmental applications.

Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy.

PURPOSE: This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment. MATERIALS AND METHODS: We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group. RESULTS: The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively). CONCLUSION: In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

A risk-adjusted cumulative sum analysis of the progression from a novice to an expert surgeon at a single institution.

BACKGROUND/OBJECTIVE: Laparoscopic surgery for rectal cancer is challenging for novice surgeons because it requires a sharp dissection in a narrow pelvis with visual limitations. Therefore, this study aimed to analyze the learning curve and clinical outcomes of laparoscopic surgery for rectal cancer performed by a novice surgeon en route to becoming an expert. METHODS: In total, 119 patients who underwent laparoscopic surgery for rectal cancer performed by a single surgeon between June 2010 and December 2019 were analyzed. A single hybrid model based on the operative time, open conversion, complications, and resection margin involvement was generated to assess the success of laparoscopic surgery. Furthermore, the learning curve was evaluated using the risk-adjusted cumulative sum (RA-CUSUM) method. RESULTS: The learning period was categorized into three phases according to the RA-CUSUM method (phase 1, 1st-33rd cases; phase 2, 34th-84th cases; and phase 3, 85th-119th cases). Tumor size (p = 0.004), distal resection margin (p = 0.003), and the number of harvested lymph nodes (p < 0.001) significantly increased with the learning period. The time to tolerable soft diet became shorter according to the learning period (p = 0.017). Advanced T stage (p = 0.024) and adjuvant chemotherapy (p = 0.012) were more common in phase 3. CONCLUSIONS: This study suggested that the initial technical competence of laparoscopic surgery for rectal cancer was acquired in the 33rd case. Technical mastery was achieved in the 84th case. After mastering the technique, the surgeon tended to challenge more advanced cases, however, the complication rates did not increase.

Suppressive effects of exercise-conditioned serum on cancer cells: A narrative review of the influence of exercise mode, volume, and intensity.

Cancer is a major cause of morbidity and mortality worldwide, and the incidence is increasing, highlighting the need for effective strategies to treat this disease. Exercise has emerged as fundamental therapeutic medicine in the management of cancer, associated with a lower risk of recurrence and increased survival. Several avenues of research demonstrate reduction in growth, proliferation, and increased apoptosis of cancer cells, including breast, prostate, colorectal, and lung cancer, when cultured by serum collected after exercise in vitro (i.e., the cultivation of cancer cell lines in an experimental setting, which simplifies the biological system and provides mechanistic insight into cell responses). The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors, such as skeletal muscle-induced cytokines (i.e., myokines) and hormones. However, exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated, constraining more precise application of exercise medicine within clinical oncology. To date, it remains unclear what role different training modes (i.e., resistance and aerobic training) as well as volume and intensity have on exercise-conditioned serum and its effects on cancer cells. Nevertheless, the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects, while for chronic training interventions, exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode. Insights for future research investigating training modes, volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.

Computed tomography-assessed presarcopenia and clinical outcomes after laparoscopic surgery for rectal cancer.

PURPOSE: Previous studies have reported that presarcopenia negatively affects rectal cancer treatment. However, most studies have analyzed patients including majority of open surgery, and the association between presarcopenia and clinical outcomes after laparoscopic rectal cancer surgery remains unclear. This study aimed to evaluate the impact of presarcopenia on the clinical and oncological outcomes after laparoscopic rectal cancer surgery. METHODS: Three hundred and one patients undergoing laparoscopic rectal cancer surgery between December 2009 and May 2016 were enrolled. Body composition was assessed using computed tomography by measuring the muscle and fat areas at the third lumbar (L3) vertebra. The L3 skeletal muscle area was used to calculate the skeletal muscle index and evaluate presarcopenia. RESULTS: Presarcopenia was more common in older ( ≥ 70 years, P = 0.008) or female patients (P = 0.045). Patients with presarcopenia had decreased skeletal muscle area (P < 0.001), lower hemoglobin level (P = 0.034), longer time to first flatus (P < 0.001), and more frequent surgical site infection (P = 0.001). However, survival rates were not significantly different between those with and without presarcopenia. CONCLUSION: Computed tomography-assessed presarcopenia was associated with delayed functional recovery and increased surgical site infection, although it was not revealed as a prognostic factor for oncological outcomes.

Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentation facilitates multi-cancer early detection.

Cell-free DNA (cfDNA) sequencing has demonstrated great potential for early cancer detection. However, most large-scale studies have focused only on either targeted methylation sites or whole-genome sequencing, limiting comprehensive analysis that integrates both epigenetic and genetic signatures. In this study, we present a platform that enables simultaneous analysis of whole-genome methylation, copy number, and fragmentomic patterns of cfDNA in a single assay. Using a total of 950 plasma (361 healthy and 589 cancer) and 240 tissue samples, we demonstrate that a multifeature cancer signature ensemble (CSE) classifier integrating all features outperforms single-feature classifiers. At 95.2% specificity, the cancer detection sensitivity with methylation, copy number, and fragmentomic models was 77.2%, 61.4%, and 60.5%, respectively, but sensitivity was significantly increased to 88.9% with the CSE classifier (p value < 0.0001). For tissue of origin, the CSE classifier enhanced the accuracy beyond the methylation classifier, from 74.3% to 76.4%. Overall, this work proves the utility of a signature ensemble integrating epigenetic and genetic information for accurate cancer detection.

Mucocutaneous ulcer positive for Epstein-Barr virus, misdiagnosed as a small bowel adenocarcinoma: A case report.

BACKGROUND: Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (MCUs) are an uncommon disorder characterized by ulcerative lesions in the skin, oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression. The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas. We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU. Through this case, we aim to emphasize the importance of accurately distinguishing between the two conditions. CASE SUMMARY: The patient presented with an incidental finding of a small bowel tumor during computed tomography (CT) examination performed for hematuria. The CT scan showed irregular thickening of the distal ileum, which was suggestive of a malignant small bowel tumor. An exploratory laparotomy revealed an 8-cm mass in the distal ileum; thus, a segment of the small intestine, including the mass, was resected. Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing, marked inflammatory cell infiltration, and large atypical lymphoid cells (positive for EBV-encoded small RNA). A final diagnosis of an EBV-MCU was established. The postoperative course was uneventful, and the patient was discharged on postoperative day 7. The patient remained recurrence-free until 12 mo after surgery. CONCLUSION: This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.

Comparative detection of syndecan-2 methylation in preoperative and postoperative stool DNA in patients with colorectal cancer.

BACKGROUND: Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morbidity and mortality. Stool DNA (sDNA) testing is an emerging method for early CRC detection. Syndecan-2 (SDC2) methylation is a potential biomarker for the sDNA testing. Aberrant DNA methylation is an early epigenetic event during tumorigenesis and can occur in the normal colonic mucosa during aging, which can compromise the sDNA test results. AIM: To determine whether methylated SDC2 in sDNA normalizes after surgical resection of CRC. METHODS: In this prospective study, we enrolled 151 patients with CRC who underwent curative surgical resection between September 2016 and May 2020. Preoperative stool samples were collected from 123 patients and postoperative samples were collected from 122 patients. A total of 104 samples were collected from both preoperative and postoperative patients. Aberrant promoter methylation of SDC2 in sDNA was assessed using linear target enrichment quantitative methylation-specific real-time polymerase chain reaction. Clinicopathological parameters were analyzed using the results of SDC2 methylation. RESULTS: Detection rates of SDC2 methylation in the preoperative and postoperative stool samples were 88.6% and 19.7%, respectively. Large tumor size (3 cm, P = 0.019) and advanced T stage (T3-T4, P = 0.033) were positively associated with the detection rate of SDC2 methylation before surgery. Female sex was associated with false positives after surgery (P = 0.030). Cycle threshold (CT) values were significantly decreased postoperatively compared with preoperative values (P < 0.001). The postoperative negative conversion rate for preoperatively methylated SDC2 was 79.3% (73/92). CONCLUSION: Our results suggested that the SDC2 methylation test for sDNA has acceptable sensitivity and specificity. However, small size and early T stage tumors are associated with a low detection rate of SDC2 methylation. As the cycle threshold values significantly decreased after surgery, SDC2 methylation test for sDNA might have a diagnostic value for CRC.

Synergistic Effects of Metformin and Trastuzumab on HER2 Positive Gastroesophageal Adenocarcinoma Cells In Vitro and In Vivo.

The incidence of HER2 amplification in advanced gastroesophageal adenocarcinoma (GC) reportedly ranges between 10% and 20%, depending on the population studied and the geographical region. Trastuzumab (Tmab) is the standard treatment for GCs with HER2 amplification. Metformin, a widely used antidiabetic drug, is an activator of AMP kinase that can affect the mTOR signaling pathway. The following GC cells were evaluated: HER2+ NCI-N87, YCC-19, YCC-38, OE19, OE33, and HER2- AGS. The effects of Tmab and metformin on these cell lines were assessed as single agents and in combination using cell viability assays, Western blotting, and xenograft models. Metformin induced phosphorylation of AMP kinase in all tested GC cells and dephosphorylation of mTOR in Tmab-sensitive GC cells. We observed that treatment with Tmab in combination with metformin induced a significant decrease in the number of colonies formed on soft agar by N87, YCC-19, YCC-38, and OE19 cells (88%, 95%, 73%, and 98%, respectively), in comparison to the number formed by control cells or cells in the single-treatment groups. No growth inhibition was detected in OE33 cells treated with Tmab alone. Combination with metformin resulted in decreased phosphorylation of HER2 and its downstream targets, AKT and ERK, in Tmab-sensitive HER2+ cells. Phospho-receptor tyrosine kinase (RTK) arrays were used to profile the phospho-proteome, which demonstrated a synergistic decrease in phosphorylation of EGFR, HER2, and HER3. Furthermore, the combination of Tmab and metformin exhibited enhanced antitumor effects in a xenograft model. Collectively, these data suggest that Tmab and metformin act synergistically in HER2+ GC cells. Since metformin is widely used and relatively non-toxic, its addition to the therapeutic regimen along with Tmab could enhance the clinical efficacy in patients with HER2+ GC.

Single or double Kirschner wire fixation: which provides better outcomes for pediatric proximal phalanx base fractures?

PURPOSE: The most common hand fracture in children is seen at the base of the proximal phalanx. This study aims to compare clinical outcomes of single versus double Kirschner wire pinning for pediatric proximal phalanx base fractures. PATIENTS AND METHODS: The retrospective study enrolled patients who underwent closed K-wire pinning for proximal phalanx base fractures from January 2016 to February 2022. We divided patients into two groups based on the number of K-wire inserted (single versus double). Demographics, removal of implant, complication rate were analyzed. Patients were asked to answer the Michigan Hand Outcomes Questionnaire (MHQ) by telephone. Data including fracture type, diaphyseal axis-metacarpal head angle (DHA) and Total Active Flexion Scale (TAFS) were analyzed. RESULTS: This study included 37 pediatric patients with proximal phalanx base fractures, treated with either single (n = 10) or double K-wire (n = 27) fixation. The mean operation time was significantly shorter for the single K-wire group. No significant differences were observed in complication rates, TAFS, implant removal times, MHQ, or pre- and post-operative DHA between the two groups. CONCLUSION: The single K-wire technique demonstrates similar effectiveness to the double K-wire technique in treating pediatric proximal phalanx base fractures, with the added benefit of shorter operation time. Therefore, the choice between using one or two K-wires should be determined based on the surgeon's proficiency and preference.

Establishment and characterization of BMC-PDC-019: a novel patient-derived cell line of EGFR-mutant pulmonary adenocarcinoma transformed into small-cell lung cancer.

Transformed small-cell lung cancer (tSCLC) from EGFR-mutant adenocarcinoma is a rare and aggressive form of lung cancer that can occur when the tumor develops resistance to EGFR targeted therapy and the cancer cells acquire additional genomic alterations that cause them to transform into SCLC. Treatment for tSCLC has not been established yet, and chemotherapy regimens for de novo SCLC are mostly recommended. However, these treatments showed disappointing outcome, and novel anti-cancer agents and immunological approaches are currently being developed. The patient-derived cell line is a critical tool for pre-clinical and translational research, but cell line models for tSCLC are not publicly available from cell banks. The aim of this study was to establish and characterize a novel cell line for tSCLC. Using a lymph-node biopsy tissue from a 58-year-old female patient, whose tumor was EGFR-mutant lung adenocarcinoma progressed on afatinib, we successfully established a cell line, named BMC-PDC-019. The tumor sample and cell line showed a typical expression of SCLC markers, such as CD56 and synaptophysin. The population doubling-time of BMC-PDC-019 cells was 48 h. We examined a range of proliferation-inhibiting effects of anti-cancer drugs currently used for de novo SCLC, using BMC-PDC-019 cells. We concluded that BMC-PDC-019 would be a useful tool for pre-clinical and translational research.