Prognostic implication of extra-pancreatic organ invasion in resectable pancreas ductal adenocarcinoma in the pancreas tail.

OBJECTIVES: To assess the prognostic significance of extra-pancreatic organ invasion in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreas tail. MATERIALS & METHODS: This retrospective study included patients with resectable PDAC in the pancreas tail who received upfront surgery between 2014 and 2020 at a tertiary institution. Preoperative pancreas protocol computed tomography (CT) scans evaluated tumor size, peripancreatic tumor infiltration, suspicious metastatic lymph nodes, and extra-pancreatic organ invasion. The influence of extra-pancreatic organ invasion, detected by CT or postoperative pathology, on pathologic resection margin status was evaluated using logistic regression. The impact on recurrence-free survival (RFS) was analyzed using multivariable Cox proportional hazard models (clinical-CT and clinical-pathologic). RESULTS: The study included 158 patients (mean age, 65 years ± 8.8 standard deviation; 93 men). Extra-pancreatic organ invasion identified by either CT (p = 0.92) or pathology (p = 0.99) was not associated with a positive resection margin. Neither CT (p = 0.42) nor pathological (p = 0.64) extra-pancreatic organ invasion independently correlated with RFS. Independent predictors for RFS included suspicious metastatic lymph node (hazard ratio [HR], 2.05; 95 % confidence interval [CI], 1.08-3.9; p = 0.03) on CT in the clinical-CT model, pathological T stage (HR, 2.97; 95 % confidence interval [CI], 1.39-6.35; p = 0.005 for T2 and HR, 3.78; 95 % CI, 1.64-8.76; p = 0.002 for T3) and adjuvant therapy (HR, 0.62; 95 % confidence interval [CI], 0.42-0.92; p = 0.02) in the clinical-pathologic model. CONCLUSION: Extra-pancreatic organ invasion does not independently influence pathologic resection margin status and RFS in patients with resectable PDAC in the pancreas tail after curative-intent resection; therefore, it should not be considered a high-risk factor.

Longitudinal multiomic profiling and corticosteroid modulation of the immediate innate immune response to an adenovirus-vector vaccine.

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.

Learning curve for single-port robot-assisted colectomy

Purpose@#Since the introduction of robotic surgery, robots for colorectal cancer have replaced laparoscopic surgery, and a single-port robot (SPR) platform has been launched and is being used to treat patients. We analyzed the learning curve and initial complications of using an SPR platform in colorectal cancer surgery. @*Methods@#We reviewed 39 patients who underwent SPR colectomy from April to October 2019. All surgeries were performed by the same surgeon using an SPR device. A learning curve was generated using the cumulative sum methodology to assess changes in total operation time, docking time, and surgeon console time. We grouped the patients into 3 groups according to the time period: the first 11 were phase 1, the next 11 were phase 2, and the last 17 were phase 3. @*Results@#The mean age of the patients was 61.28±13.03 years, and they had a mean body mass index of 23.79±2.86 kg/m2. Among the patients, 23 (59.0%) were male, and 16 (41.0%) were female. The average operation time was 186.59±51.30 minutes, the average surgeon console time was 95.49±35.33 minutes, and the average docking time (time from skin incision to robot docking) was 14.87±10.38 minutes. The surgeon console time differed significantly among the different phases (P<0.001). Complications occurred in 8 patients: 2 ileus, 2 postoperation hemoglobin changes, 3 urinary retentions, and 1 complicated fluid collection. @*Conclusion@#In our experience, the learning curve for SPR colectomy was achieved after the 18th case.

Reappraisal of Portal Vein Tumor Thrombosis as a Prognostic Factor for Patients with Hepatocellular Carcinoma

Background/Aims@#This study aimed to assess whether hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) could have favorable prognoses with proper treatment under selective conditions. @*Methods@#This retrospective, single-center study involved 1,168 patients diagnosed with HCC between January 2005 and December 2006, before the introduction of sorafenib. Overall survival (OS) was estimated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify and adjust the variables associated with OS. @*Results@#In nodular-type HCC, the OS differed significantly according to the presence of PVTT (log-rank p<0.001), and the level of PVTT, not only its presence, was a major independent factor affecting OS. PVTT at the Vp1-3 branch was associated with significantly longer OS than was PVTT at the Vp4 level (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.04 to 3.21). In multivariate analysis, the OS was further stratified according to the PVTT level and tumor type, representing that nodular HCC without PVTT exhibited the best OS, whereas nodular HCC with Vp4 PVTT (adjusted HR, 2.59; 95% CI, 1.57 to 4.28) showed a poor prognosis similar to that of infiltrative HCC. The PVTT level was consistently correlated with OS in patients treated with transarterial chemoembolization. Nodular HCC without PVTT showed the best prognosis, while nodular HCC with Vp1-3 PVTT also exhibited a favorable OS, although inferior to that without PVTT (adjusted HR, 1.47, 95% CI, 0.92 to 2.36). @*Conclusions@#Active treatment such as transarterial chemoembolization can be considered for selected PVTT cases. The level of PVTT and type of HCC were independent prognostic factors.

Risk Factors for the Mortality of Patients With Coronavirus Disease 2019Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study

Background@#Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. @*Methods@#We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan–Meier (KM) method. @*Results@#Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010–1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312–7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). @*Conclusion@#Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea

Background@#The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. @*Methods@#From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. @*Results@#Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6–73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. @*Conclusion@#This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Effectiveness and Tolerability of Combination Pharmacotherapy With Stimulant and Non-Stimulant in Children With Attention Deficit Hyperactivity Disorder

Objectives@#This study aimed to investigate the effectiveness and safety of combining psychostimulants and nonstimulants for patients under treatment for attention deficit hyperactivity disorder (ADHD). @*Methods@#The study included 96 patients aged 6–12 years who were diagnosed with ADHD, among whom 34 received combination pharmacotherapy, 32 received methylphenidate monotherapy, and 30 received atomoxetine monotherapy. Statistical analysis was conducted to compare treatment and adverse effects among groups and to analyze changes before and after combination pharmacotherapy.The difference between combination pharmacotherapy and monotherapy was investigated. Logistic regression analysis was used to identify the predictors of combination pharmacotherapy. @*Results@#No significant differences were observed between the groups in terms of age or pretreatment scores. The most common adverse effect experienced by 32% of patients in the combination pharmacotherapy group was decreased appetite. Clinical global impression-severity score decreased significantly after combination pharmacotherapy. All three groups showed significant clinical global impression-severity score improvements over time, with no significant differences among them. The predictive factors for combination pharmacotherapy included the Child Behavior Checklist total score internalizing subscale. @*Conclusion@#Combination pharmacotherapy with methylphenidate and atomoxetine is a relatively effective and safe option for patients with ADHD who do not respond to monotherapy.

Comparison between Proton Pump Inhibitor and H2 Receptor Antagonist in Relieving Cyclosporine-Associated Adverse Gastrointestinal Events: A Single Center, Randomized Controlled Trial / 대한피부과학회지

Background@#Cyclosporine (CS) has been effectively used in various skin diseases, but gastrointestinal (GI) adverse events are so common. However, there is no standardized treatment for managing CS-induced GI adverse events. @*Objective@#To analyze the effectiveness of two empirical GI medications, an H2 receptor antagonist (H2RA) and proton pump inhibitor (PPI), in relieving CS-induced GI adverse events. @*Methods@#This is a prospective, randomized clinical trial conducted at Ajou University Hospital. The patients completed a gastrointestinal symptom rating scale (GSRS) questionnaire to assess GI symptoms before and after taking the drugs. @*Results@#A total of 60 patients, divided into a PPI group (n=30) and an H2RA group (n=30), were analyzed. The onset of GI events occurred in 6.04 days on average. GSRS scores improved significantly in both groups (p＜0.01). While abdominal pain, reflux syndrome, and indigestion syndrome consistently improved, changes in diarrhea syndrome and constipation syndrome were not statistically significant. The overall change in GSRS scores was higher in the PPI group, but the difference was not significant (p=0.76). @*Conclusion@#Both PPI and H2RA significantly improved CS-induced GI side effects, with PPI showing a slight advantage over H2RA, but the cost of PPIs should be considered when deciding on first-line therapy. GI side effects typically appeared within 6.04 days of starting CS therapy, highlighting the importance of close monitoring and personalized intervention for improving patient compliance.

Thoracic Duct Embolization for Treatment of Chyle Leakage After Thyroidectomy and Neck Dissection

Objective@#This study aimed to evaluate the safety and efficacy of intranodal lymphangiography and thoracic duct embolization (TDE) for chyle leakage (CL) after thyroid surgery. @*Materials and Methods@#Fourteen patients who underwent intranodal lymphangiography and TDE for CL after thyroid surgery were included in this retrospective study. Among the 14 patients, 13 underwent bilateral total thyroidectomy with neck dissection (central compartment neck dissection [CCND], n = 13; left modified radical neck dissection (MRND), n = 11;bilateral MRND, n = 2), and one patient underwent left hemithyroidectomy with CCND. Ten patients (76.9%) had high-output CL (> 500 mL/d). Before the procedure, surgical intervention was attempted in three patients (thoracic duct ligation, n = 1;lymphatic leakage site ligation, n = 2). Lymphangiographic findings, technical and clinical successes, and complications were analyzed. Technical success was defined as the successful embolization of the thoracic duct after access to the lymphatic duct via the transabdominal route. Clinical success was defined as the resolution of CL or surgical drain removal. @*Results@#On lymphangiography, ethiodized oil leakage near the surgical bed was identified in 12 of 14 patients (85.7%). The technical success rate of TDE was 78.6% (11/14). Transabdominal antegrade access was not feasible due to the inability to visualize the identifiable cisterna chyli or a prominent lumbar lymphatic duct. Among patients who underwent a technically successful TDE, the clinical success rate was 90.1% (10/11). The median time from the procedure to drain removal was 3 days (with a range of 1–13 days) for the 13 patients who underwent surgical drainage. No CL recurrence was observed during the follow-up period (ranging from 2–44 months; median, 8 months). There were no complications, except for one case of chylothorax that developed after TDE. @*Conclusion@#TDE appears to be a safe and effective minimally invasive treatment option for CL after thyroid surgery, with acceptable technical and clinical success rates.

Predicting Recurrence-Free Survival After Upfront Surgery in Resectable Pancreatic Ductal Adenocarcinoma: A Preoperative Risk Score Based on CA 19-9, CT, and 18F-FDG PET/CT

Objective@#To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose ( 18F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC). @*Materials and Methods@#Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage. @*Results@#A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; P < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; P = 0.06), suspicious regional lymph nodes (HR, 1.43; P = 0.02), possible distant metastasis on 18F-FDG PET/CT (HR, 2.32; P = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; P = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; P = 0.17). @*Conclusion@#The proposed risk score based on preoperative CA 19-9, CT, and 18F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC.

Association between Work-related Communication Devices Use during Work Outside of Regular Working Hours and Depressive Symptoms in Wage Workers

Background@#This study aimed to investigate the relationship between work-related communication devices use during work outside of regular working hours and depressive symptoms in wage workers. @*Methods@#Data from 50,538 workers aged 15 years or older who had participated in the 6th Korean Working Condition Survey (KWCS) were used. The final sample was 32,994 wage workers. The questionnaire asked the respondents how often they used communication devices for work during work outside of regular working hours. Depressive symptoms were assessed using WHO-5 Well-Being Index. Multiple logistic regression analysis was used to analyze the association between work-related communication devices use during work outside of regular working hours and depressive symptoms. @*Results@#The rate of depressive symptoms was highest among workers who did not use work-related communication devices during work outside of regular working hours. After adjusting for socio-demographic and work-related factors, the odds ratio of depressive symptoms among workers who used communication devices when working outside of regular working hours was 1.20 (95% CI: 1.09–1.32); the odds ratio of depressive symptoms in the group not using communication devices for free-time work was 1.66 (95% CI: 1.37–2.00), which was higher than that of the reference group, that is, workers who did not work outside of regular working hours, and was statistically significant. @*Conclusion@#Regardless of whether work-related communication devices are used, working outside of regular working hours increases depressive symptoms. The use of work-related communication devices during work outside of regular working hours can reduce the rate of depressive symptoms.

Associations of Step Volume and Intensity with Metabolic Syndrome among Korean Adults: A Cross-sectional Observational Study / 대한스포츠의학회지

Purpose@#This study was performed to investigate the association between step volume and intensity with the prevalence of metabolic syndrome (MS) in Korean adults. @*Methods@#The study analyzed 2,038 adults from the 2014 to 2017 Korea National Health and Nutrition Examination Survey, defining MS based on waist circumference, blood pressure, triglycerides, glucose, and high-density lipoprotein cholesterols. Step volume and intensity were calculated using average number of steps per day and peak 30-minute cadence, respectively. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of MS by tertiles of step volume and intensity. A joint analysis was conducted to examine the combined association between step volume and intensity with the prevalence of MS. We divided the participants into nine groups according to their step volume (tertiles) and intensity (tertiles). @*Results@#There were 478 MS cases. Compared to the lowest tertile of volume, the ORs of MS were 1.06 (95% CI, 0.79–1.42) and 0.64 (95% CI, 0.47–0.88) in the middle and highest tertile of volume. Compared to the lowest tertile of intensity, the ORs were 1.02 (95% CI, 0.76–1.36) and 0.74 (95% CI, 0.55–1.01) in the middle and highest tertile of intensity. In the joint analysis, compared to the group with both lowest volume and intensity, the ORs were significantly lower in all groups with the highest volume, except the group with the lowest intensity. @*Conclusion@#Although only greater step volume, not intensity, was independently related to MS, both step volume and intensity appear to be important for preventing MS.

Factors associated with the Discrepancy between Exercise Capacity and Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

Background@#Exercise capacity is associated with lung function decline in chronicobstructive pulmonary disease (COPD) patients, but a discrepancy between exercisecapacity and airflow limitation exists. This study aimed to explore factors contributingto this discrepancy in COPD patients. @*Methods@#Data for this prospective study were obtained from the Korean COPD SubgroupStudy. The exercise capacity and airflow limitation were assessed using the6-minute walk distance (6-MWD; m) and forced expiratory volume in 1 second (FEV1).Participants were divided into four groups: FEV1 >50%+6-MWD >350, FEV1 >50%+6-MWD ≤350, FEV1 ≤50%+6-MWD >350, and FEV1 ≤50%+6-MWD ≤350 and their clinicalcharacteristics were compared. @*Results@#A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) wereenrolled. Among 591 patients with FEV1 >50%, 242 were in the 6-MWD ≤350 group, andamong 292 patients with FEV1 ≤50%, 185 were in the 6-MWD >350 group. The multipleregression analyses revealed that male sex (odds ratio [OR], 8.779; 95% confidence interval[CI], 1.539 to 50.087; p=0.014), current smoking status (OR, 0.355; 95% CI, 0.178to 0.709; p=0.003), and hemoglobin levels (OR, 1.332; 95% CI, 1.077 to 1.648; p=0.008)were significantly associated with discrepancies in exercise capacity and airflow limitationin patients with FEV1 >50%. Meanwhile, in patients with FEV1 ≤50%, diffusioncapacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantlyassociated with discrepancies between exercise capacity and airflow limitation. @*Conclusion@#The exercise capacity of COPD patients may be influenced by factors otherthan airflow limitation, so these aspects should be considered when assessing andtreating patients.

Dexamethasone Effect on Sudden Hearing Loss is Validated in Stress-induced Animal Models: Hypothetical Study.

BACKGROUND: Stress could be a contributing cause of sudden hearing loss. This study intended to develop an animal model of stress-induced sudden hearing loss and to evaluate the effects of dexamethasone. METHODS: Two stress models (I and II) for rats were designed using various stressors and modified by adjusting the stress protocol to increase the threshold significantly. For the stress model with a significant increase in threshold after stress exposure, changes in cortisol levels according to stress exposure were measured. The threshold shift and the change in the cellular structure associated with stress exposure and dexamethasone administration were analyzed. RESULTS: While hearing thresholds increased only at 16 kHz in rats of stress model I (n=10), the thresholds increased at 16 and 32 kHz in rats of stress model II (n=16). Cortisol level increased after stress exposure (P = .015) in stress model II. Among stress model II rats (stress only and stress+dexamethasone groups), the threshold shift at 16 kHz significantly decreased 1 day after dexamethasone injection in the stress+dexamethasone group (n=8). Histologically, the cochlear cellularity of the stress+dexamethasone group was more compact than that of the stressonly group (n=8). CONCLUSION: Our preliminary study presented the development of an animal model of stress-induced sudden hearing loss and the positive results of steroids in terms of hearing recovery.

Is High-Grade Tumor Budding an Independent Prognostic Factor in Stage II Colon Cancer?

BACKGROUND: Risk factors, including lymphatic, vascular, and perineural invasion, are considered indications for adjuvant treatment in stage II colon cancer. However, tumor budding is not included in the above risk factors. OBJECTIVE: This study aimed to assess the value of tumor budding as a prognostic factor in stage II colon cancer. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted in a tertiary referral center. PATIENTS: This study examined 1390 patients with stage II colon cancer who received curative resection from 2007 to 2013 at an institution. INTERVENTIONS: These patients were classified according to tumor budding status: low-grade tumor budding (less than 10 buds) and high-grade tumor budding (10 buds or more). Differences between the 2 groups were corrected by propensity score matching. MAIN OUTCOME MEASURES: Disease-free survival and overall survival were the primary end points. RESULTS: Among 1390 patients, 146 (10.5%) had high-grade tumor budding. The high-grade tumor budding group showed adverse histological characteristics such as advanced T stage, histological grade of differentiation, and presence of lymphatic/perineural invasion. After matching, the 5-year disease-free survival rate for the high-grade tumor budding group was significantly lower than for the low-grade group. We also compared survival outcomes according to tumor budding grade for patients who did not have risk factors and did not receive adjuvant treatment. The 5-year overall survival was similar between the 2 groups. However, the 5-year disease-free survival decreased significantly in the high-grade tumor budding group than in the low-grade tumor budding group. LIMITATIONS: This was a retrospective study with a single-center design. CONCLUSIONS: High-grade tumor budding is a poor prognostic factor in stage II colon cancer and is considered one of the risk factors for adjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B962 . ES LA GEMACIN TUMORAL UN FACTOR PRONSTICO INDEPENDIENTE EN EL CNCER DE COLON EN ESTADIO II: ANTECEDENTES:Los factores de riesgo, incluida la invasión linfática/vascular/perineural, se consideran indicaciones para el tratamiento adyuvante en el cáncer de colon en estadio II. Sin embargo, la gemación tumoral (desdiferenciación tumoral aislada), no está incluida en los factores de riesgo anteriores.OBJETIVO:El objeto de este estudio fue evaluar el valor de la gemación tumoral como factor pronóstico en el cáncer de colon en estadio II.DISEÑO:Este es un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un centro de referencia terciario.PACIENTES:Este estudio analizó 1390 pacientes con cáncer de colon en estadio II que recibieron una resección curativa entre 2007 y 2013 en una institución.INTERVENCIONES:Estos pacientes se clasificaron según el estado de gemación tumoral: gemación tumoral de bajo grado (<10 yemas) y gemación tumoral de alto grado (≥10 yemas). Las diferencias entre los dos grupos se corrigieron mediante el emparejamiento por puntaje de propensión.PRINCIPALES MEDIDAS DE VALORACIÓN:La supervivencia libre de enfermedad y la supervivencia global fueron los puntos finales primarios.RESULTADOS:Entre 1.390 pacientes, 146 (10,5%) tenían brotes tumorales de alto grado. El grupo de gemación tumoral de alto grado mostró características histológicas adversas como estadio T avanzado, grado histológico de diferenciación y presencia de invasión linfática/perineural. Después del emparejamiento, la tasa de supervivencia libre de enfermedad a cinco años para el grupo de brotes de tumores de alto grado fue significativamente menor que para el grupo de bajo grado. También comparamos los resultados de supervivencia según el grado de gemación del tumor para pacientes que no tenían factores de riesgo y que no recibieron tratamiento adyuvante. La supervivencia global a cinco años fue similar entre los dos grupos. Sin embargo, la supervivencia libre de enfermedad a cinco años disminuyó significativamente en el grupo de brotes de tumores de alto grado que en el grupo de brotes de tumores de bajo grado.LIMITACIONES:Este fue un estudio retrospectivo con un diseño de centro único.CONCLUSIÓNES:La gemación tumoral de alto grado es un factor de mal pronóstico en el cáncer de colon estadio II y se considera uno de los factores de riesgo para el tratamiento adyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B962 . (Traducción-Dr. Ingrid Melo ).

Progression of Pre-Existing Vitiligo during Secukinumab Treatment for Psoriasis

Vitiligo has been considered an unexplained paradoxical phenomenon during biologics use.Herein, we report an adult case of progression of pre-existing vitiligo during secukinumab treatment for psoriasis, and we also examined the immunohistochemical changes in relation to biologics use. He was being administered monthly secukinumab of 300 mg dose for 2 years, and all psoriatic lesions were cleared, but pre-existing hypopigmented lesions became more distinct and larger than before unlike when using adalimumab. A skin biopsy of the hypopigmented lesion showed loss of epidermal melanocytes and absence of gp100 immune activities, and he was finally diagnosed with progression of pre-existing vitiligo.Immunohistochemical staining of vitiligo lesion showed decrease in interleukin-17 and tumor necrosis factor-α and increase in CD8+ T cells, interferon-γ, and CXCL10 after the use of secukinumab. In this study, we suggest that biologics-induced cytokine imbalance play a critical role in vitiligo progression in patients with chronic inflammatory diseases, including psoriasis.

Novel Genome-Wide Interactions Mediated via BOLL and EDNRA Polymorphisms in Intracranial Aneurysm

Objective@#: The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. @*Methods@#: Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. @*Results@#: Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. @*Conclusion@#: BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

Redo pull-through for postoperative complications following pull-through in Hirschsprung disease: a single center experience

Purpose@#Although surgical management of Hirschsprung disease (HD) is effective in most patients, some patients experience long-term postoperative complications, and require redo pull-through (PT). The present study evaluated clinical outcomes of redo PT in HD patients at a single center. @*Methods@#Patients with HD who underwent redo PT procedures between 2003 and 2019 were retrospectively reviewed. @*Results@#Thirteen patients were included. Five (38.5%) had undergone initial PT surgery at our center and 8 (61.5%) at other centers. Redo PT procedures were transanal endorectal PT in 12 patients (92.3%) and the posterior sagittal approach in 1 patient (7.7%). Indications for redo PT included pathologic misdiagnosis in 8 patients (61.5%); stricture in 2 (15.4%); and rectal stenosis, obstructing Duhamel pouch and remnant septum in 1 each (7.7%). At a median follow-up of 68 months (range, 3–227 months) after redo PT, 8 patients (61.5%) had normal bowel function, 2 (15.4%) had incontinence, and 1 (7.7%) had constipation. @*Conclusion@#Redo PT procedures could be an effective approach for improving obstructive symptoms in HD patients with anatomic or pathologic reasons following primary PT. Careful selection of patients and discreet indications for redo PT are crucial.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. @*Materials and Methods@#This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. @*Results@#Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). @*Conclusion@#Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). @*Materials and Methods@#Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. @*Results@#Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. @*Conclusion@#Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.