We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.

Objectives: It is important that inflammatory bowel disease (IBD) patients adhere to their prescribed medication regimens to avoid the repeat exacerbations, complications, or surgeries associated with this disorder. However, there are few studies on medication adherence in patients with IBD, especially in Asian populations. So, we analyzed the factors associated with medication adherence in Korean IBD patients. Methods: Patients who had been diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) more than 6 months previously and receiving oral medications for IBD were enrolled. Medication adherence was measured using the Medical Adherence Reporting Scale (MARS-5), a self-reported medication adherence measurement tool. Results: Among 207 patients in the final study population, 125 (60.4%) had CD and 134 (64.7%) were men. The mean age was 39.63 years (SD, 13.16 years) and the mean disease duration was 10.09 years (SD, 6.33 years). The mean medication adherence score was 22.46 (SD, 2.86) out of 25, and 181 (87.4%) patients had score of 20 or higher.In multiple linear regression analysis, self-efficacy (β=0.341, P<0.001) and ≥3 dosing per day (β=–0.192 P=0.016) were revealed to be significant factors associated with medication adherence. Additionally, there was a positive correlation between self-efficacy and medication adherence (r=0.312, P<0.001). However, disease related knowledge, depression, and anxiety were not significantly associated with medication adherence. Conclusion To improve medication adherence among patients with IBD, a reduction in the number of doses per day and an improved self-efficacy will be helpful.

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal 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.

Purpose: Carcinoma arising from Crohn disease (CD) is rare, and there is no clear guidance on how to properly screen for at-risk patients and choose appropriate care. This study aimed to evaluate the clinicopathological characteristics, treatment, and oncologic outcomes of CD patients diagnosed with colorectal cancer (CRC). Methods: Using medical records, we retrospectively enrolled a single-center cohort of 823 patients who underwent abdominal surgery for CD between January 2006 and December 2015. CD-associated CRC patients included those with adenocarcinoma, lymphoma, or neuroendocrine tumors of the colon and rectum. Results: Nineteen patients (2.3%) underwent abdominal surgery to treat CD-associated CRC. The mean duration of CD in the CD-associated CRC group was significantly longer than that in the benign CD group (124.7 ± 77.7 months vs. 68.9 ± 60.2 months, P = 0.006). The CD-associated CRC group included a higher proportion of patients with a history of perianal disease (73.7% vs. 50.2%, P = 0.035) and colonic location (47.4% vs. 6.5%, P = 0.001). Among 19 CD-associated CRC patients, 17 (89.5%) were diagnosed with adenocarcinoma, and of the 17 cases, 15 (88.2%) were rectal adenocarcinoma. On multivariable analyses for developing CRC, only colonic location was a risk factor (relative risk, 7.735; 95% confidence interval, 2.862–20.903; P = 0.001). Conclusion Colorectal malignancy is rare among CD patients, even among patients who undergo abdominal surgery. Rectal adenocarcinoma accounted for most of the CRC, and colonic location was a risk factor for developing CRC.

Purpose: Upper gastrointestinal (GI) tract involvement in Crohn disease (CD) is rare and effectiveness of surgical treatment is limited. The aim of this study was to evaluate characteristics and surgical outcomes of upper GI CD. Methods: Medical records of 811 patients who underwent intestinal surgery for CD between January 2006 and December 2015 at a single institution were reviewed. Upper GI CD was defined by involvement of the stomach to the fourth portion of duodenum, with or without concomitant small/large bowel CD involvement according to a modification of the Montreal classification. Results: We identified 24 patients (21 males, 3 females) who underwent surgery for upper GI CD. The mean age at diagnosis was 27 ± 12 years, the mean age at surgery was 33 ± 11 years, and the mean duration of CD was 73.6 ± 56.6 months.Fifteen patients (62.5%) had history of previous perianal surgery. Ten patients (41.7%) had duodenal or gastric stricture and 14 patients (58.3%) had penetrating fistula; patients with fistula were significantly more likely to develop complications (57.1% vs. 20.0%, P = 0.035). One patient with stricture had surgical recurrence. In seven patients with fistula, fistula was related to previous anastomosis. Patients with fistula had significantly longer hospital stays than those with stricture (16 days vs. 11 days, P = 0.01). Conclusion Upper GI CD is rare among CD types (2.96%). In patients with upper GI CD, penetrating fistula was associated with longer hospital stay and more complications.

BACKGROUND: There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM. METHODS: This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement. RESULTS: Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001). CONCLUSION Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of minimal deviation adenocarcinoma (MDA) and to analyze its prognostic factors. METHODS: We retrospectively analyzed the medical records of 17 patients who were diagnosed with MDA at a single institution between January 2005 and December 2015. RESULTS: The median age of the patients was 47.7 years (33–75 years). MDA was diagnosed in 7 patients (41.2%) before performing definitive surgery. Stage IB disease was diagnosed in 12 patients (70.6%) and advanced stage disease (stage II: 3, stage III: 2) in 5. MDA was incidentally diagnosed following hysterectomy for benign conditions in 6 patients. Adjuvant therapy was administered to 13 patients (76.5%). During median follow-up over 33.6 months (7–99 months), 11 patients (64.7%) showed no evidence of disease, 6 (35.3%) showed persistent or recurrent disease and 5 died of the disease. Peutz-Jeghers syndrome was not suspected in any patient, and no mutation was detected in the 3 patients who underwent genetic testing. Univariate analysis showed that advanced stage disease (P=0.016) and lymphovascular space invasion (P=0.002) demonstrated a statistically significant association with poor overall survival (OS) rates. Advanced stage disease continued to show a significant association with poor OS rates (hazard ratio, 2.92; 95% confidence interval, 1.097–7.746; P=0.032) even after multivariate analysis. CONCLUSION: Early diagnosis is important to manage MDA. Clinicians should consider MDA among the differential diagnoses in patients with a suspicious clinical presentation even with negative cervical screening tests.
Adenocarcinoma* ; Cervix Uteri* ; Diagnosis, Differential ; Early Diagnosis ; Female ; Follow-Up Studies ; Genetic Testing ; Humans ; Hysterectomy ; Mass Screening ; Medical Records ; Multivariate Analysis ; Peutz-Jeghers Syndrome ; Retrospective Studies ; Uterine Cervical Neoplasms

BACKGROUND/AIMS: Fructose malabsorption (FM) mimics symptoms of irritable bowel syndrome (IBS), and its prevalence has increased. Diagnosing FM in IBS is challenging because of its overlap with small intestinal bacterial overgrowth (SIBO). We assessed the prevalence of FM by comparing patients with IBS with asymptomatic control individuals after excluding SIBO using the glucose hydrogen breath test (HBT). METHODS: Patients diagnosed with IBS and asymptomatic control individuals were enrolled prospectively. Dietary habits were assessed with the Food Frequency Questionnaire. After excluding SIBO, participants underwent HBTs with both 15 g and 25 g of fructose. RESULTS: Thirty-five patients with IBS and 35 age- and sex-matched asymptomatic control individuals were enrolled. The 15-g fructose HBT yielded positive results in 7 of the 35 (20.0%) patients with IBS and in 2 of 35 (5.7%) controls (P = 0.070). The 25-g fructose HBT was positive in 16 of the 35 (45.7%) patients with IBS and in 8 of the 35 (22.9%) controls (P = 0.040). Analysis of the Food Frequency Questionnaire responses showed no significant differences between the 2 groups in dietary intake, although patients with IBS showed a significantly higher mean fiber intake than controls (21.24 ± 11.35 g vs 15.87 ± 7.07 g, respectively, P = 0.040). CONCLUSIONS: The 25-g fructose HBT identified FM in a significantly higher percentage of SIBO-negative patients with IBS than in asymptomatic control individuals, suggesting that FM may correlate with IBS. Education regarding dietary control of foods containing fructose may be useful for the management of patients with IBS.
Breath Tests ; Education ; Food Habits ; Fructose ; Glucose ; Humans ; Hydrogen ; Irritable Bowel Syndrome ; Prevalence ; Prospective Studies

We present a case of an endometrial cancer patient with germline mutation in MutS homolog 6 (MSH6), associated with Lynch syndrome. A 60-year-old Korean woman had a personal history of colon cancer 23 years ago. She also had a family history of endometrial cancer and colon cancer of her sisters and brothers. Immunohistochemistry was negative for MutL homolog 1 (MLH1) and positive for MutS homolog 2 (MSH2). Based on these findings, she underwent genetic counseling and testing that revealed a frameshift germline mutation at MSH6 (c. 3261dupC).
Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Endometrial Neoplasms* ; Female ; Genetic Counseling ; Germ-Line Mutation* ; Humans ; Immunohistochemistry ; Korea* ; Middle Aged ; Siblings