A 63-year-old woman was referred to a breast surgeon with a breast mass discovered incidentally during follow-up study after colon cancer surgery. Invasive adenocarcinoma was revealed on core needle biopsy. Wide excision of the breast including the tumor was performed. On standard histological examination the tumor showed features of moderately differentiated adenocarcinoma. The immunohistochemistry study revealed positive results for cytokeratin (CK)20 and CDX2, but negative for CK7. These are typical characteristics for colon cancer. Considering her history of subtotal colectomy for sigmoid colon cancer, it is presumable that the mass in the breast was of colonic origin, and it was an extremely rare case of metastasis to the breast from primary colorectal neoplasm. Although the instance is rare, clinicians should keep the possibility of breast metastasis from colorectal cancer in mind for early and correct diagnosis.
Adenocarcinoma ; Biopsy, Large-Core Needle ; Breast ; Colectomy ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Keratins ; Middle Aged ; Neoplasm Metastasis ; Sigmoid Neoplasms

In recent years, as the aging population grows, aging-induced cognitive impairments including dementia and Alzheimer's disease (AD) have become the biggest challenges for global public health and social care. Therefore, the development of potential therapeutic drugs for aging-associated cognitive impairment is essential. Metabolic dysregulation has been considered to be a key factor that affects aging and dementia. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a primary sensor of cellular energy states and regulates cellular energy metabolism. Metformin (1,1-dimethylbiguanide hydrochloride) is a well-known AMPK activator and has been widely prescribed for type 2 diabetes mellitus (T2DM). Since the incidence of T2DM and dementia increases with aging, metformin has been considered to be one of the most promising drugs to target dementia and its related disorders. To that end, here, we tested the efficacy of metformin and HL271, a novel metformin derivative, in aging-induced cognitive decline. Water (control), metformin (100 mg/kg) or HL271 (50 mg/kg) were orally administered to aged mice for two months; then, the mice were subjected to behavioral tests to measure their cognitive function, particularly their contextual, spatial and working memory. AMPK phosphorylation was also measured in the drug-treated mouse brains. Our results show that oral treatment with HL271 (50 mg/kg) but not metformin (100 mg/kg) improved cognitive decline in aged mice. AMPK activation was correlated with behavior recovery after aging-induced cognitive decline. Taken together, these results suggest that the newly synthesized AMPK activator, HL271, could be a potential therapeutic agent to treat age-related cognitive decline.
Adenosine Monophosphate ; Aging ; Alzheimer Disease ; AMP-Activated Protein Kinases ; Animals ; Behavior Rating Scale ; Brain ; Cognition ; Cognition Disorders ; Dementia ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Energy Metabolism ; Incidence ; Memory, Short-Term ; Metformin ; Mice ; Phosphorylation ; Protein Kinases ; Public Health ; Water

PURPOSE: To overcome the limitations of cancer gene therapy using replication-incom- petent adenovirus, we generated E1B 55 kD-deleted adenovirus (YKL-1) by polymerase chain reaction (PCR) and homologous recombination. We then investigated tumor-specific virus replication and cytotoxicity of YKL-1 in vitro and in vivo. MATERIALS AND METHODS: YKL-1 was constructed by reintroducting E1A and E1B 19 kD into pTG-CMV El/E3-deficient adenoviral vector and inducing homologous recombination in E. coli. The recombinant vector pYKL-1 was transfected into 293 cells to generate YKL-1. The properties of newly constructed YKL-1 was defined by PCR and immuno- blotting analysis. Virus replication was examined by infecting human normal and cancer cells on 6-wells at multiplicity of infection (MOI) of 10 for 3 days. Virus was then recovered and titered. Cytopathic effect was analyzed by infecting human normal and cancer cells on 24-wells at MOIs of 10, 1 or 0.1 for 7 to 10 days and staining them with crystal violet solution. Inhibition of tumor growth was examined in human cancer cell xenografts in nu/nu mice by intratumoral injection of YKL-l. RESULTS: PCR and immunoblotting analysis confirmed that YKL-1 contained E1A and E1B 19 kD but not E1B 55 kD. In human normal cells, virus replication and subsequent cytopathic effect of E1B 55 kD-deleted adenovirus YKL-1 was markedly attenuated by larger than 2 to 3 log in magnitude, compared to that of wild-type ad-XJ. In contrast, YKL-1 was capable of replicating and inducing cytotoxicity i.n most human cancer cells. C33A and Hep3B containing p53 mutation were much more sensitive, whereas HeLa and H460 with wild type p53 were relatively resistant to YKL-1. Finally, the tumor growth was dramatically retarded by intratumoral injection of YKL-1 in C33A cervical cancer xenograft and the histology showed significant necrosis by intratumoral injection of YKL-1. CONCLUSION: The results here demonstrated the ability of preferential virus replication and cytotoxicity of ElB 55 kD-deleted adenovirus YKL-1 in human cancer cells. Therefore, these indicated a promising potential of YKL-1 as an antitumoral virus agent and a selective replication-competent virus vector.
Adenoviridae* ; Animals ; Genes, Neoplasm ; Genetic Therapy ; Gentian Violet ; Heterografts ; Homologous Recombination ; Humans ; Immunoblotting ; Mice ; Necrosis ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms ; Virus Replication*

OBJECTIVES: Hand-assisted laparoscopic surgery had both technical advantages of open surgery and better postoperative short-term follow-up results of laparoscopic surgery. We compared open colectomy, laparoscopic colectomy and hand-assisted laparoscopic colectomy, and tried to find the most effective operative modality. METHODS: 90 patients, who were diagnosed with colorectal cancer and underwent colectomy in our institution, were categorized as 3 groups of open colectomy (OC) group, laparoscopic colectomy (LC) group and hand-assisted laparoscopic colectomy (HALC) group by the surgical modality. RESULTS: In this study, ratio of male and female was 57 : 37, and mean age was 64.1 years old. LC group and HALC group showed longer operation time, shorter hospital stay after operation, lesser pain and earlier removal of closed drainage catheter than OC group. Amount of bleeding during operation, frequency of transfusion and incidence of complication showed no significant difference. In permanent pathologic results, the number of harvested lymph nodes had significant difference between OC group and other groups (P=0.030), but it was probably caused by the bias of the different distribution of the stages in each group. Overall 14 of the cases resulted in complications while there was no mortality. CONCLUSION: Laparoscopic colectomy and hand-assisted laparoscopic colectomy showed better short-term follow-up results rather than open colectomy. And hand-assisted laparoscopic surgery could provide tactile sensation to operator, which lacked in laparoscopic surgery. Hand-assisted laparoscopic colectomy could be an alternative surgical option for colorectal cancer with these advantages.
Bias (Epidemiology) ; Catheters ; Colectomy ; Colorectal Neoplasms ; Drainage ; Female ; Follow-Up Studies ; Hand-Assisted Laparoscopy ; Hemorrhage ; Humans ; Incidence ; Laparoscopy ; Length of Stay ; Lymph Nodes ; Male ; Sensation

Lead insertion for cardiac implantable electronic devices requires venous access into the right side of the heart. The access route commonly used is from the axillary vein, through the subclavian vein and the superior vena cava. However, in patients with congenital heart malformations or those with vascular stenosis, and/or those who have undergone previous cardiac surgery, the passage of leads might be difficult, and the implantation procedure would show restricted scope. In such cases, insertion of leads through the hepatic vein is known to be a safe procedure. We report 2 cases of patients with limited vascular access who underwent lead implantation using the transhepatic approach—1 patient who underwent placement of an implantable cardioverter defibrillator and the other who underwent placement of a permanent pacemaker.
Axillary Vein ; Constriction, Pathologic ; Defibrillators ; Defibrillators, Implantable ; Heart ; Hepatic Veins ; Humans ; Subclavian Vein ; Thoracic Surgery ; Vena Cava, Superior

PURPOSE: Recent evidence suggests that early repolarization (ER) is related with myocardial ischemia. Compression of coronary artery by a myocardial bridging (MB) can be associated with clinical manifestations of myocardial ischemia. This study aimed to evaluate the associations of MB in patients with ER. MATERIALS AND METHODS: In consecutive patients (n=1303, age, 61±12 years) who had undergone coronary angiography, we assessed the prevalence and prognostic implication of MB in those with ER (n=142) and those without ER (n=1161). RESULTS: MB was observed in 54 (38%) and 196 (17%) patients in ER and no-ER groups (p<0.001). In multivariate analysis, MB was independently associated with ER (odd ratio: 2.9, 95% confidence interval: 1.98–4.24, p<0.001). Notched type ER was more frequently observed in MB involving the mid portion of left anterior descending coronary artery (LAD) (69.8% vs. 30.2%, p=0.03). Cardiac event was observed in nine (6.3%) and 22 (1.9%) subjects with and without ER, respectively. MB was more frequently observed in sudden death patients with ER (2 out of 9, 22%) than in those without ER (0 out of 22). CONCLUSION: MB was independently associated with ER in patients without out structural heart disease who underwent coronary angiography. Notched type ER was closely related with MB involving the mid portion of the LAD. Among patients who had experienced cardiac events, a higher prevalence of MB was observed in patients with ER than those without ER. Further prospective studies on the prognosis of MB in ER patients are required.
Aged ; Coronary Angiography ; Electrocardiography ; Electrophysiological Phenomena ; Female ; Humans ; Male ; Middle Aged ; Myocardial Bridging/*complications/*diagnostic imaging/epidemiology/physiopathology ; Myocardial Ischemia/*etiology/physiopathology ; Odds Ratio ; Prevalence ; Prognosis ; Prospective Studies

Weight-control drugs (known as anorexigens) such as fenfluramine have been linked with pulmonary hypertension in previous reports. In our case, a 29 year old woman was admitted for shortness of breath and was diagnosed with pulmonary hypertension. Three months ago, she had been taking phentermine for five weeks. Other factors that might have contributed to the development of pulmonary hypertension were excluded. With treatment, her symptoms improved. This is the first case that can suggest a possible connection between phenermine single medication with pulmonary hypertension. Phentermine has been considered a relatively safe drug to treat obesity, and further investigation is needed to decide the safety and dosage of phentermine.
Adult ; Antihypertensive Agents/therapeutic use ; Electrocardiography/methods ; Female ; Humans ; Hypertension, Pulmonary/*drug therapy/*etiology ; Models, Chemical ; Obesity/drug therapy ; Phentermine/*adverse effects/*therapeutic use ; Radiography, Thoracic/methods ; Safety ; Sulfonamides/therapeutic use

Background: Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation. Methods: Three-dimensional heart geometry was constructed from computed tomography images. The finite ele‑ ment method was used to elucidate the electric wave propagation in the heart. The electric excitation and mechani‑ cal contraction were coupled with vascular hemodynamics by the lumped parameter model. The model parameters for three-dimensional (3D) heart and vascular mechanics were estimated by matching computed variables with measured physiological parameters. CRT effects were simulated in a patient with HF and left bundle branch block (LBBB). LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV ejection fraction (LVEF), and CRT responsiveness measured from the in silico simulation model were compared with those from clinical observation. A CRT responder was defined as absolute increase in LVEF ≥ 5% or relative increase in LVEF ≥ 15%. Results: A 68-year-old female with nonischemic HF and LBBB was retrospectively included. The in silico CRT simu‑ lation modeling revealed that changes in LVEDV, LVESV, and LVEF by CRT were from 174 to 173 mL, 116 to 104 mL, and 33 to 40%, respectively. Absolute and relative ΔLVEF were 7% and 18%, respectively, signifying a CRT responder.In clinical observation, echocardiography showed that changes in LVEDV, LVESV, and LVEF by CRT were from 162 to 119 mL, 114 to 69 mL, and 29 to 42%, respectively. Absolute and relative ΔLVESV were 13% and 31%, respectively, also signifying a CRT responder. CRT responsiveness from the in silico CRT simulation model was concordant with that in the clinical observation. Conclusion This in silico CRT simulation method is a feasible technique to screen for CRT non-responders in patients with HF and LBBB.

Background and Objectives: Atrial high-rate episodes (AHREs) can be continuously detected by cardiovascular implantable electronic devices (CIEDs); however, the predictors of clinically relevant AHREs are unclear. Methods: This prospective multicenter study monitored 816 patients (median age 73 years, 40.4% male) without atrial fibrillation (AF) from September 2017 to July 2020. AHREs was defined as a programmed atrial detection rate >220 beats/min. The reference values of 6 minutes and 6 hours were set to analyze clinical implication of AHREs based on previously published data that the 6 minutes excluded most episodes of oversensing. Results: During a median follow-up of 18 months (interquartile interval 9–26 months), AHREs with the longest durations of >15 seconds, >6 minutes, and >6 hours and clinically documented AF by electrocardiography were noted in 246 (30.1%), 112 (13.7%), 49 (6.0%), and 24 (2.9%) patients, respectively. Among patients developing AHREs >6 minutes, 102 (91.1%) of 112 patients were identified at the 6-month visit. Patients with AHREs >6 minutes had higher proportions of sick sinus syndrome, subjects with atrial premature beat >1% on Holter monitoring, and larger left atrium (LA) size than patients with AHREs ≤6 minutes.Multivariable logistic regression analysis showed that LA diameter >41 mm (odds ratio [OR], 2.08; 95% confidence interval [95% CI], 1.25–3.45), and sick sinus syndrome (OR, 3.22; 95% CI, 1.91–5.43) were associated with AHREs >6 minutes. Conclusions In patients with LA diameter >41 mm, and sick sinus syndrome before CIEDs implantation is associated with risk of developing AHREs >6 minutes.

Background and Objectives: Atrial high-rate episodes (AHREs) can be continuously detected by cardiovascular implantable electronic devices (CIEDs); however, the predictors of clinically relevant AHREs are unclear. Methods: This prospective multicenter study monitored 816 patients (median age 73 years, 40.4% male) without atrial fibrillation (AF) from September 2017 to July 2020. AHREs was defined as a programmed atrial detection rate >220 beats/min. The reference values of 6 minutes and 6 hours were set to analyze clinical implication of AHREs based on previously published data that the 6 minutes excluded most episodes of oversensing. Results: During a median follow-up of 18 months (interquartile interval 9–26 months), AHREs with the longest durations of >15 seconds, >6 minutes, and >6 hours and clinically documented AF by electrocardiography were noted in 246 (30.1%), 112 (13.7%), 49 (6.0%), and 24 (2.9%) patients, respectively. Among patients developing AHREs >6 minutes, 102 (91.1%) of 112 patients were identified at the 6-month visit. Patients with AHREs >6 minutes had higher proportions of sick sinus syndrome, subjects with atrial premature beat >1% on Holter monitoring, and larger left atrium (LA) size than patients with AHREs ≤6 minutes.Multivariable logistic regression analysis showed that LA diameter >41 mm (odds ratio [OR], 2.08; 95% confidence interval [95% CI], 1.25–3.45), and sick sinus syndrome (OR, 3.22; 95% CI, 1.91–5.43) were associated with AHREs >6 minutes. Conclusions In patients with LA diameter >41 mm, and sick sinus syndrome before CIEDs implantation is associated with risk of developing AHREs >6 minutes.