Chronicles of EGFR Tyrosine Kinase Inhibitors: Targeting EGFR C797S Containing Triple Mutations

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wildtype EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and thirdgeneration EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/ T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

Common ABCB1 SNP, C3435T could affect systemic exposure of dapagliflozin in healthy subject

P-glycoprotein (P-gp) is a transporter that plays an excretory role in epithelial cells. It is encoded by ABCB1, and single nucleotide polymorphisms (SNPs) in this gene can affect systemic drug exposure. Dapagliflozin and sitagliptin, used in type 2 diabetes treatment, are P-gp substrates. Here, we aimed to investigate whether ABCB1 polymorphisms affect dapagliflozin and sitagliptin pharmacokinetics (PK) in healthy Korean subjects.The study population consisted of 100 healthy Korean subjects (94 men and 6 women) who participated in four different clinical trials and received dapagliflozin and sitagliptin doses of 10 and 100 mg, respectively. We determined ABCB1 genotypes for the C3435T, C1236T, and G2677T/A SNPs. The relationship between the genotypes and dapagliflozin PKs was examined.Dapagliflozin and sitagliptin PK parameters were not statistically significantly affected by ABCB1 SNP genotypes. However, homozygous 3435TT subjects showed higher dapagliflozin PK parameters than CT and CC subjects. In subjects with the 3435TT and those with 3435CC and 3435CT genotypes, mean Cmax, AUCinf, and AUC0-1 values of dapagliflozin were 223.06 ng/mL and 194.81 ng /mL (p = 0.2767), 673.58 ng*h/mL and 573.96 ng*h/mL (p = 0.0492), and 128.53 ng*h/mL and 104.61 ng*h/mL (p = 0.2678), respectively.In summary, dapagliflozin and sitagliptin PK parameters were not significantly different between individuals with C1236T and C2677T/A ABCB1 genetic polymorphisms. Dapagliflozin exhibited higher systemic exposure in 3435TT subjects than in CC/CT subjects.

Effect of Dexamethasone Combination With Gentamicin in Chemical Labyrinthectomy on Hearing Preservation in Patients With Meniere’s Disease / 대한이비인후과학회지

Chemical labyrinthectomy may be performed in patients with Meniere’s disease who have intractable vertigo that does not respond to drug. By using aminoglycosides, the surgical procedure ablates vestibular type 1 hair cells. However, the risk of hearing loss remains a main concern for clinicians because gentamicin ablates cochlear hair cells as well as vestibular hair cells. To deal with the concern for hearing loss, dexamethasone can be combined with gentamicin during chemical labyrinthectomy. Herein, we show that chemical labyrinthectomy using gentamicin combined with dexamethasone preserve hearing at high-frequency compared to the conventional method.

Clinicopatholgic Characteristics to the Relapse on Ductal Carcinoma In Situ: Ki-67 Index as the Most Influential Prognostic Factor

Purpose@#The biggest concern related to ductal carcinoma in situ (DCIS) is local recurrence and recurrence patterns. The purpose of this study was to investigate the relationship between clinicopathological factors and relapse in patients treated with DCIS. @*Methods@#We reviewed medical records of 104 patients who were diagnosed as DCIS between January 1999 and December 2015 at a single institute. We compared and analyzed clinicopathological factors such as age at diagnosis, preoperative lesions on ultrasonography, preoperative tumor markers, operation methods in the breast, histological grade, nuclear grade, resection margin, comedonecrosis, estrogen receptor/ progesterone receptor expression, human epidermal factor receptor 2eu expression, Ki-67, postoperative implementation of adjuvant hormonal therapy, and radiotherapy by dividing them into recurrent and non-recurrent groups. @*Results@#Seventeen patients (16.3%) of 104 patients relapsed in the ipsilateral or contralateral breast. The median follow-up period of non-relapsed group was 4.9 years (range, 0.5–19.15) and the median follow-up period of relapsed group was 3.5 years (range, 1.4–14.13). Clinicopathological factors that were significantly related to relapse were nuclear grade (p=0.022) and Ki-67 (p=0.025) based on the results of chi-square or Fisher’s exact analysis. In multivariate analysis using logistic regression, Ki-67 (p=0.021) was significantly associated with DCIS relapse. @*Conclusion@#This study suggested that the higher Ki-67 over 14% was strongly associated with DCIS relapse.

Association Between Eustachian Tube Dysfunction Questionnaire-7 Scores and Eustachian Tube Function Test Results in Symptomatic Patients With a Normal Drum

Background and Objectives@#We investigated the clinical validity of and correlation between the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores and the eustachian tube function test (ETFT) results in patients with a normal drum. @*Subjects and Methods@#The study included 49 patients (93 ears) with unilateral or bilateral ear fullness over >3 months. All patients were administered the ETDQ-7 survey and underwent the ETFT on the same day. The receiver operating characteristic (ROC) curve and the association between the results were statistically analyzed. @*Results@#ETDQ-7 scores were not significantly correlated with the ETFT results or with middle ear pressure. ETDQ-7 scores in patients with eustachian tube dysfunction (ETD) were significantly higher than those in patients with normal ETFT results (p=0.039) when ETD was defined as a pressure change <10 daPa on the ETFT. The area under the ROC curve was 0.631, with a sensitivity of 37.0% and specificity of 89.4%. @*Conclusions@#The ETDQ-7 has limited clinical significance in patients with ETD but a normal drum. Therefore, concomitant objective tests should be performed to diagnose patients with ETD.

A Case of Recurrent Ischemic Stroke Associated with Immunoglobulin G4-Related Disease

Immunoglobulin G4-related disease (IgG4 RD) is a systemic immune-mediated inflammatory disease that presents as multiple organ dysfunction or mass lesions with lympho-plasmacytic infiltration. However, there are few case reports presenting central nervous system involvements. Herein, we report a case of a 70-year-old man with recurrent ischemic stroke which induced by IgG4 RD. IgG4 RD should be considered and treated as one of etiologies manifesting small vessel disease infarctions, especially when it occurs multiply and recurrently.

Acute Liver Failure Secondary to Hepatic Infiltration of Malignant Melanoma

Acute liver failure due to malignant melanoma is uncommon. We presents a case of acute liver failure secondary to hepatic infiltration of a malignant melanoma. An 86-year-old man was admitted with elevated liver enzymes and an increased lactate dehydrogenase level. His condition progressed to acute liver failure, but the etiology of liver failure was unclear. Esophagogastroduodenoscopy was performed to evaluate dyspepsia, which showed signs indicative of malignant melanoma. Based on the endoscopy findings and elevated liver enzyme levels, liver biopsy was performed to confirm the presence of malignant melanoma. Hepatic infiltration of malignant melanoma was observed histologically. However, massive and diffuse liver metastasis is very rare and difficult to identify on imaging studies. If the etiology of liver failure is unclear, diffuse metastatic melanoma infiltration should be considered as differential diagnosis. Early liver biopsy can help to clarify the diagnosis.

A comparison on health-related lifestyle, dietary habits, and depression by exercise frequency of college students

BACKGROUND/OBJECTIVES@#The study was performed to investigate health-related lifestyle, dietary habits, and depression according to exercise frequency to understand complex factors that affect effective health management. Thus, exercise frequency, health-related lifestyle, dietary habits, and depression were evaluated in college students in Seoul and Gyeonggi-do areas. @*SUBJECTS/METHODS@#A survey was conducted on college students, aged 19–29, in Seoul and Gyeonggi-do areas from May 13 to May 31, 2020. A total of 594 questionnaires were collected and 566 (269 from males, 297 from females) were statistically analyzed, except 28 with incomplete responses. Collected data were analyzed using SPSS WIN 21.0 program. @*RESULTS@#The sex distribution of the 3 groups according to exercise frequency was significantly different; the ratio of males in over 3 times/week group was significantly higher than those in 1–2 times/week group and no-exercise group (P < 0.001). The height (P < 0.001), weight (P < 0.001), and body mass index (P < 0.05) were significantly higher in over 3 times/week group compared to no-exercise group. The ratio of subjects who answered ‘good’ or ‘very good’ for subjective health condition was significantly high in the order of ‘over 3 times/week’ group (59.1%), ‘1–2 times/week’ group (34.5%), and ‘no-exercise’ group (25.0%) (P < 0.001). The ratio for meal regularity was high as 56.6% in ‘over 3 times/week’ group and the ratio for irregular meals was significantly higher in ‘no-exercise’ group (67.2%) and ‘1–2 times/week’ group (54.9%) (P < 0.001). Among questions on dietary habits, ‘Eat meat, fish, egg or beans’ (P < 0.01) and ‘Eat fruit’ (P < 0.01) were significantly higher in ‘over 3 times/ week’ group compared to ‘no-exercise’ group. ‘Drink more than 2 liters of water’ (P < 0.001) was 0.70 in ‘over 3 times/week’ group, which was significantly higher than 0.54 in ‘1–2 times/ week’ group and 0.38 in ‘no-exercise’ group. Moderate depression and severe depression that need treatments were significantly lower in ‘over 3 times/week’ group (18.7%) compared to ‘1–2 times/week’ group (26.0%) and ‘no-exercise’ group (29.7%) (P < 0.05). @*CONCLUSIONS@#It is considered that combined intervention for exercise habits, proper dietary habits, and depression management is needed for effective health management.

Association between stress and dietary habits, emotional eating behavior and insomnia of middle-aged men and women in Seoul and Gyeonggi

BACKGROUND/OBJECTIVES@#The study was performed to investigate the degree of perceived stress by sex in middle-aged people, and to provide basic data for appropriate nutrition education and interventional measures for middle-aged subjects through comparative analysis of association between stress and dietary habits, emotional eating behavior, and insomnia. @*SUBJECTS/METHODS@#A survey was conducted in 670 middle-aged subjects (320 men and 350 women) aged 40–64 years, resided in Seoul and Gyeonggi area. Collected data were analyzed using SPSS WIN 25.0 program. @*RESULTS@#Perceived stress in middle-aged subjects was not different by sex. Stress was higher in men with low dietary habits level compared to other groups (P < 0.001), and was higher in women with low and moderate dietary habits level compared to women with high dietary habits level (P < 0.05). Stress in men was higher in the group with emotional eaters (P < 0.05), and the same result was shown in women (P < 0.001). Stress was higher in both men and women with poor sleep quality (P < 0.001). Stress score was positively correlated with emotional dietary behavior and insomnia (P < 0.001) and negatively correlated with dietary habits (P < 0.001). @*CONCLUSIONS@#It is considered that proper nutrition education and interventional measures according to sex are needed for stress control and proper dietary behavior and lifestyle in middle-aged people population, along with projects and policies at the national level.

Evaluation of Diet Quality Determined by Dietary Patterns of Elderly Koreans Living Alone: Data Retrieved from the 2016∼2018 Korea National Health and Nutrition Examination Survey

This study was undertaken to identify dietary patterns of Korean elderly people living alone, and to compare the quality of diet consumed. Data of 821 elderly people aged 65 years or older who were living alone, was obtained from the 2016∼2018 National Health and Nutrition Survey. The percentage energy intake from 24 food groups was calculated, and a cluster analysis was applied to identify dietary patterns. General characteristics, energy and nutrient intake, nutrient adequacy ratio (NAR), mean adequacy ratio (MAR), and index of nutritional quality (INQ) were analyzed. Dietary variety score (DVS) and dietary diversity score (DDS) were subsequently calculated. The rice-centered diet group and mixed diet group were characterized as consuming higher intake of rice and a wider variety of food groups, respectively. The mean age and percentage of participants living in rural areas were higher, whereas education level and monthly income were lower, in the rice-centered diet group (P＜0.001 for all). Intakes of energy and all other nutrients (except carbohydrate and thiamine) were lower in the rice-centered diet group (P＜0.001 for all). The NAR for all nutrients (except thiamine), MAR, and INQs (except thiamine and iron) were significantly lower in the rice-centered diet group (P＜0.001 for all). The rice-centered diet group had significantly lower DVS (P＜0.001) and DDS (P＜0.001), as compared with the mixed diet group (P＜0.001). Due to the insufficient energy and nutrient intake in the rice-centered diet group, it is necessary to develop nutritional monitoring and customized nutrition policies for these individuals.

Characteristics of HER2-Positive Breast Cancer according to HER2 2+/ Low or 3+/High Classification by Immunohistochemistry Assay: Study of 205 Cases Treated in a Single Center

Purpose@#To investigate the characteristics of HER2-positive breast cancer according to HER2 low (2+) or high (3+) classification using immunohistochemistry (IHC). @*Methods@#Data were collected from 205 HER2-positive breast cancer patients in the final assay, regardless of IHC or in situ hybridization (ISH). We thus classified patients into two groups: HER2 2+/low and HER2 3+/high based on the IHC assay. We subsequently compared the clinical and pathological characteristics between groups. @*Results@#The median patient age was 49 years in the HER2 2+/low group and 53 years in the HER2 3+/high group. We observed a significantly lower Allred score for estrogen receptor (ER) and progesterone receptor (PR) (0-6) (p<0.001), less lymphatic invasion (LI), (p=0.010), neural invasion (p=0.041), higher Ki-67 (p=0.001), and lower Bcl-2 (p<0.001) in the HER2 3+/high group than in the HER2 2+/low group. Lymph node recurrence was more frequently observed in the HER2 2+/low group than in HER2 3+/high group (p=0.005). Disease-free survival (DFS) was better in the HER2 3+/high group than in the HER2 2+/low group (p=0.028), but there were no significant differences in overall survival between the groups (p=0.233). @*Conclusion@#The HER2 3+/high group was associated with lower ER and PR expression, less LI, higher Ki-67, and lower Bcl-2 than that in HER2 2+/low group in HER2-positive breast cancer. Furthermore, compared to the HER2 2+/low group, the HER2 3+/high group had an improved DFS.

Transmural Mesh Migration From the Abdominal Wall to the Rectum After Hernia Repair Using a Prolene Mesh: A Case Report

Mesh erosion or migration is a rare and late complication after hernia repair. Its incidence is increasing as the utilization of prosthetic mesh gains popularity for abdominal hernia repair. However, mesh migration is exceedingly rare and its clinical presentation is atypical and diverse. Therefore, the management of mesh migration should be individualized to each patient. This research reports the case of a 94-year-old man with transmural migration of Prolene mesh (Ethicon) from the abdominal wall to the rectum 14 years after incisional hernia repair. He presented with only chronic abdominal pain and constipation. Migration of the mesh and a fistula between the right abdominal wall and transverse colon was observed on computed tomography. The mesh was evacuated manually from the anus without any sequelae. These findings made this case atypical, since complete transluminal migration of mesh is exceedingly rare and mesh erosion or migration requires surgical treatment in many cases.

Prognostic Factors Affecting Disease-Free Survival and Overall Survival in T4 Colon Cancer

Purpose@#It is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer. @*Methods@#Patients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS. @*Results@#Eighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS. @*Conclusion@#Tumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.

A comparison on health-related lifestyle, dietary habits, and depression by exercise frequency of college students

BACKGROUND/OBJECTIVES@#The study was performed to investigate health-related lifestyle, dietary habits, and depression according to exercise frequency to understand complex factors that affect effective health management. Thus, exercise frequency, health-related lifestyle, dietary habits, and depression were evaluated in college students in Seoul and Gyeonggi-do areas. @*SUBJECTS/METHODS@#A survey was conducted on college students, aged 19–29, in Seoul and Gyeonggi-do areas from May 13 to May 31, 2020. A total of 594 questionnaires were collected and 566 (269 from males, 297 from females) were statistically analyzed, except 28 with incomplete responses. Collected data were analyzed using SPSS WIN 21.0 program. @*RESULTS@#The sex distribution of the 3 groups according to exercise frequency was significantly different; the ratio of males in over 3 times/week group was significantly higher than those in 1–2 times/week group and no-exercise group (P < 0.001). The height (P < 0.001), weight (P < 0.001), and body mass index (P < 0.05) were significantly higher in over 3 times/week group compared to no-exercise group. The ratio of subjects who answered ‘good’ or ‘very good’ for subjective health condition was significantly high in the order of ‘over 3 times/week’ group (59.1%), ‘1–2 times/week’ group (34.5%), and ‘no-exercise’ group (25.0%) (P < 0.001). The ratio for meal regularity was high as 56.6% in ‘over 3 times/week’ group and the ratio for irregular meals was significantly higher in ‘no-exercise’ group (67.2%) and ‘1–2 times/week’ group (54.9%) (P < 0.001). Among questions on dietary habits, ‘Eat meat, fish, egg or beans’ (P < 0.01) and ‘Eat fruit’ (P < 0.01) were significantly higher in ‘over 3 times/ week’ group compared to ‘no-exercise’ group. ‘Drink more than 2 liters of water’ (P < 0.001) was 0.70 in ‘over 3 times/week’ group, which was significantly higher than 0.54 in ‘1–2 times/ week’ group and 0.38 in ‘no-exercise’ group. Moderate depression and severe depression that need treatments were significantly lower in ‘over 3 times/week’ group (18.7%) compared to ‘1–2 times/week’ group (26.0%) and ‘no-exercise’ group (29.7%) (P < 0.05). @*CONCLUSIONS@#It is considered that combined intervention for exercise habits, proper dietary habits, and depression management is needed for effective health management.

Association between stress and dietary habits, emotional eating behavior and insomnia of middle-aged men and women in Seoul and Gyeonggi

BACKGROUND/OBJECTIVES@#The study was performed to investigate the degree of perceived stress by sex in middle-aged people, and to provide basic data for appropriate nutrition education and interventional measures for middle-aged subjects through comparative analysis of association between stress and dietary habits, emotional eating behavior, and insomnia. @*SUBJECTS/METHODS@#A survey was conducted in 670 middle-aged subjects (320 men and 350 women) aged 40–64 years, resided in Seoul and Gyeonggi area. Collected data were analyzed using SPSS WIN 25.0 program. @*RESULTS@#Perceived stress in middle-aged subjects was not different by sex. Stress was higher in men with low dietary habits level compared to other groups (P < 0.001), and was higher in women with low and moderate dietary habits level compared to women with high dietary habits level (P < 0.05). Stress in men was higher in the group with emotional eaters (P < 0.05), and the same result was shown in women (P < 0.001). Stress was higher in both men and women with poor sleep quality (P < 0.001). Stress score was positively correlated with emotional dietary behavior and insomnia (P < 0.001) and negatively correlated with dietary habits (P < 0.001). @*CONCLUSIONS@#It is considered that proper nutrition education and interventional measures according to sex are needed for stress control and proper dietary behavior and lifestyle in middle-aged people population, along with projects and policies at the national level.

Evaluation of Diet Quality Determined by Dietary Patterns of Elderly Koreans Living Alone: Data Retrieved from the 2016∼2018 Korea National Health and Nutrition Examination Survey

This study was undertaken to identify dietary patterns of Korean elderly people living alone, and to compare the quality of diet consumed. Data of 821 elderly people aged 65 years or older who were living alone, was obtained from the 2016∼2018 National Health and Nutrition Survey. The percentage energy intake from 24 food groups was calculated, and a cluster analysis was applied to identify dietary patterns. General characteristics, energy and nutrient intake, nutrient adequacy ratio (NAR), mean adequacy ratio (MAR), and index of nutritional quality (INQ) were analyzed. Dietary variety score (DVS) and dietary diversity score (DDS) were subsequently calculated. The rice-centered diet group and mixed diet group were characterized as consuming higher intake of rice and a wider variety of food groups, respectively. The mean age and percentage of participants living in rural areas were higher, whereas education level and monthly income were lower, in the rice-centered diet group (P＜0.001 for all). Intakes of energy and all other nutrients (except carbohydrate and thiamine) were lower in the rice-centered diet group (P＜0.001 for all). The NAR for all nutrients (except thiamine), MAR, and INQs (except thiamine and iron) were significantly lower in the rice-centered diet group (P＜0.001 for all). The rice-centered diet group had significantly lower DVS (P＜0.001) and DDS (P＜0.001), as compared with the mixed diet group (P＜0.001). Due to the insufficient energy and nutrient intake in the rice-centered diet group, it is necessary to develop nutritional monitoring and customized nutrition policies for these individuals.

Characteristics of HER2-Positive Breast Cancer according to HER2 2+/ Low or 3+/High Classification by Immunohistochemistry Assay: Study of 205 Cases Treated in a Single Center

Purpose@#To investigate the characteristics of HER2-positive breast cancer according to HER2 low (2+) or high (3+) classification using immunohistochemistry (IHC). @*Methods@#Data were collected from 205 HER2-positive breast cancer patients in the final assay, regardless of IHC or in situ hybridization (ISH). We thus classified patients into two groups: HER2 2+/low and HER2 3+/high based on the IHC assay. We subsequently compared the clinical and pathological characteristics between groups. @*Results@#The median patient age was 49 years in the HER2 2+/low group and 53 years in the HER2 3+/high group. We observed a significantly lower Allred score for estrogen receptor (ER) and progesterone receptor (PR) (0-6) (p<0.001), less lymphatic invasion (LI), (p=0.010), neural invasion (p=0.041), higher Ki-67 (p=0.001), and lower Bcl-2 (p<0.001) in the HER2 3+/high group than in the HER2 2+/low group. Lymph node recurrence was more frequently observed in the HER2 2+/low group than in HER2 3+/high group (p=0.005). Disease-free survival (DFS) was better in the HER2 3+/high group than in the HER2 2+/low group (p=0.028), but there were no significant differences in overall survival between the groups (p=0.233). @*Conclusion@#The HER2 3+/high group was associated with lower ER and PR expression, less LI, higher Ki-67, and lower Bcl-2 than that in HER2 2+/low group in HER2-positive breast cancer. Furthermore, compared to the HER2 2+/low group, the HER2 3+/high group had an improved DFS.

Transmural Mesh Migration From the Abdominal Wall to the Rectum After Hernia Repair Using a Prolene Mesh: A Case Report

Mesh erosion or migration is a rare and late complication after hernia repair. Its incidence is increasing as the utilization of prosthetic mesh gains popularity for abdominal hernia repair. However, mesh migration is exceedingly rare and its clinical presentation is atypical and diverse. Therefore, the management of mesh migration should be individualized to each patient. This research reports the case of a 94-year-old man with transmural migration of Prolene mesh (Ethicon) from the abdominal wall to the rectum 14 years after incisional hernia repair. He presented with only chronic abdominal pain and constipation. Migration of the mesh and a fistula between the right abdominal wall and transverse colon was observed on computed tomography. The mesh was evacuated manually from the anus without any sequelae. These findings made this case atypical, since complete transluminal migration of mesh is exceedingly rare and mesh erosion or migration requires surgical treatment in many cases.

Prognostic Factors Affecting Disease-Free Survival and Overall Survival in T4 Colon Cancer

Purpose@#It is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer. @*Methods@#Patients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS. @*Results@#Eighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS. @*Conclusion@#Tumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.

A validated simple LC-MS/MS method for quantifying trimethylamine N-oxide (TMAO) using a surrogate matrix and its clinical application

Trimethylamine N-oxide (TMAO) is a small molecular amine oxide generated from dietary choline and carnitine through intestinal microbial metabolism. Recently, TMAO has attracted much public attention as its role in disease progression has been proven in many clinical studies. The plasma concentration of TMAO in humans was found to be positively associated with the increased risk of many diseases including cardiovascular diseases and chronic kidney diseases. To achieve accurate and sensitive quantitation of TMAO for clinical applications, we established and validated a simple quantitative method using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. We constructed an eight-point calibration curve in an artificial surrogate matrix instead of the commonly used biological matrices to avoid interference from the endogenous TMAO. The calibration curve showed excellent linearity in the range of 1 to 5,000 ng/mL, with a correlation coefficient (R2 ) higher than 0.996 in each validation batch. Moreover, both the intra-day and inter-day assays achieved satisfactory precision and accuracy results ranging from 1.65–7.15% and 96.36–111.43%, respectively. Further, this method was cross-validated using a human plasma matrix and applied to a clinical pharmacology study. Overall, these results demonstrate that the developed quantitation method is applicable in clinical research for monitoring disease progression and evaluating drug effects.