Background/Aims: Rectal hyposensitivity (RH), as defined by the London Classification, has been linked to sensory dysfunction caused by diabetes mellitus and Parkinson’s disease (PD); however, its clinical interpretation has not been sufficiently validated. In this study, we aim to explore the correlations between rectal sensory thresholds and the clinical characteristics of patients with functional defecatory disorders. Methods: We reviewed data from patients who underwent high-resolution anorectal manometry and acquired their clinical characteristics using a standardized questionnaire. The associations between RH based on either 1 (borderline RH) or 2 (RH) abnormal rectal sensory thresholds and patients’ clinical and demographic characteristics were analyzed using linear and logistic regression models in the overall sex-stratified populations. Results: We enrolled 2540 patients, of whom 1046 (41.2%) were men. Overall, 150 (5.9%) patients were diagnosed with RH, whereas 422 (16.6%) had borderline RH. Multivariate linear regression analysis revealed that the Cleveland Clinic Constipation Score (CCCS) increased linearly with the increase in the number of abnormal rectal sensory thresholds (effect per threshold: 0.900 [standard deviation: 0.188]). Upon stratification by sex, borderline RH was positively associated with diabetes mellitus, PD, and CCCS (adjusted odds ratio [aOR] = 2.11, 95% confidence interval [1.08, 4.15]; aOR = 1.49 [1.03, 2.14]; aOR = 1.03 [1.01, 1.05], respectively) in women. However, RH was positively associated with only the CCCS. Conclusions Defining RH based on 1 or more abnormal sensory thresholds showed better clinical correlation with patient characteristics. However, further prospective studies are needed to validate these findings before proposing revisions to the current London classification criteria.

Background/Aims: Rectal hyposensitivity (RH), as defined by the London Classification, has been linked to sensory dysfunction caused by diabetes mellitus and Parkinson’s disease (PD); however, its clinical interpretation has not been sufficiently validated. In this study, we aim to explore the correlations between rectal sensory thresholds and the clinical characteristics of patients with functional defecatory disorders. Methods: We reviewed data from patients who underwent high-resolution anorectal manometry and acquired their clinical characteristics using a standardized questionnaire. The associations between RH based on either 1 (borderline RH) or 2 (RH) abnormal rectal sensory thresholds and patients’ clinical and demographic characteristics were analyzed using linear and logistic regression models in the overall sex-stratified populations. Results: We enrolled 2540 patients, of whom 1046 (41.2%) were men. Overall, 150 (5.9%) patients were diagnosed with RH, whereas 422 (16.6%) had borderline RH. Multivariate linear regression analysis revealed that the Cleveland Clinic Constipation Score (CCCS) increased linearly with the increase in the number of abnormal rectal sensory thresholds (effect per threshold: 0.900 [standard deviation: 0.188]). Upon stratification by sex, borderline RH was positively associated with diabetes mellitus, PD, and CCCS (adjusted odds ratio [aOR] = 2.11, 95% confidence interval [1.08, 4.15]; aOR = 1.49 [1.03, 2.14]; aOR = 1.03 [1.01, 1.05], respectively) in women. However, RH was positively associated with only the CCCS. Conclusions Defining RH based on 1 or more abnormal sensory thresholds showed better clinical correlation with patient characteristics. However, further prospective studies are needed to validate these findings before proposing revisions to the current London classification criteria.

Background/Aims: Rectal hyposensitivity (RH), as defined by the London Classification, has been linked to sensory dysfunction caused by diabetes mellitus and Parkinson’s disease (PD); however, its clinical interpretation has not been sufficiently validated. In this study, we aim to explore the correlations between rectal sensory thresholds and the clinical characteristics of patients with functional defecatory disorders. Methods: We reviewed data from patients who underwent high-resolution anorectal manometry and acquired their clinical characteristics using a standardized questionnaire. The associations between RH based on either 1 (borderline RH) or 2 (RH) abnormal rectal sensory thresholds and patients’ clinical and demographic characteristics were analyzed using linear and logistic regression models in the overall sex-stratified populations. Results: We enrolled 2540 patients, of whom 1046 (41.2%) were men. Overall, 150 (5.9%) patients were diagnosed with RH, whereas 422 (16.6%) had borderline RH. Multivariate linear regression analysis revealed that the Cleveland Clinic Constipation Score (CCCS) increased linearly with the increase in the number of abnormal rectal sensory thresholds (effect per threshold: 0.900 [standard deviation: 0.188]). Upon stratification by sex, borderline RH was positively associated with diabetes mellitus, PD, and CCCS (adjusted odds ratio [aOR] = 2.11, 95% confidence interval [1.08, 4.15]; aOR = 1.49 [1.03, 2.14]; aOR = 1.03 [1.01, 1.05], respectively) in women. However, RH was positively associated with only the CCCS. Conclusions Defining RH based on 1 or more abnormal sensory thresholds showed better clinical correlation with patient characteristics. However, further prospective studies are needed to validate these findings before proposing revisions to the current London classification criteria.

Purpose: We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype. Materials and Methods: Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort. Results: Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838). Conclusion Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.

As the aging population increases, the number of patients with osteoporosis is gradually rising. Osteoporosis is a metabolic bone disease characterized by low bone mass and the microarchitectural deterioration of bone tissue, resulting in reduced bone strength and an increased risk of low-energy or fragility fractures. Thus, the use of anti-resorptive agents, such as bisphosphonates (BPs), to prevent osteoporotic fractures is growing annually. BPs are effective in reducing hip and other fractures. However, the longer a patient takes BPs, the higher the risk of an atypical femoral fracture (AFF). The exact mechanism by which long-term BP use affects the development of AFFs has not yet been clarified. However, several theories have been suggested to explain the pathogenesis of AFFs, such as suppressed bone remodeling, impaired bone healing, altered bone quality, and femoral morphology. The management of AFFs requires both medical and surgical approaches. BPs therapy should be discontinued immediately, and calcium and vitamin D levels should be evaluated and supplemented if insufficient. Teriparatide can be used for AFFs. Intramedullary nailing is the primary treatment for complete AFFs, and prophylactic femoral nailing is recommended if signs of an impending fracture are detected.

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Background/Aims: Biofeedback therapy is widely used to treat patients with chronic constipation, especially those with dyssynergic defecation. Yet, the utility of high-resolution manometry with novel parameters in the prediction of biofeedback response has not been reported. Thus, we constructed a model for predicting biofeedback therapy responders by applying the concept of integrated pressurized volume in patients undergoing high-resolution anorectal manometry. Methods: Seventy-one female patients (age: 48-68 years) with dyssynergic defecation who underwent initial high-resolution anorectal manometry and subsequent biofeedback therapy were enrolled. The manometry profiles were used to calculate the 3-dimensional integrated pressurized volumes by multiplying the distance, time, and amplitude during simulated evacuation. Partial least squares regression was performed to generate a predictive model for responders to biofeedback therapy by using the integrated pressurized volume parameters. Results: Fifty-five (77.5%) patients responded to biofeedback therapy. The responders and non-responders did not show significant differences in the conventional manometric parameters. The partial least squares regression model used a linear combination of eight integrated pressurized volume parameters and generated an area under the curve of 0.84 (95% confidence interval: 0.76-0.95, P < 0.01), with 85.5% sensitivity and 62.1% specificity. Conclusions Integrated pressurized volume parameters were better than conventional parameters in predicting the responsiveness to biofeedback therapy, and the combination of these parameters and partial least squares regression was particularly promising. Integrated pressurized volume parameters can more effectively explain the physiology of the anorectal canal compared with conventional parameters.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.