Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Objectives: . This study aimed to elucidate the patterns of upper airway collapse in obstructive sleep apnea (OSA) patients with a low body mass index (BMI). Methods: . We designed and conducted a retrospective cohort study. Consecutive patients diagnosed with OSA who underwent drug-induced sleep endoscopy (DISE) were included. Patients were classified into four groups according to their BMI. Age, sex, and polysomnography data were investigated. The patterns of upper airway collapse were characterized by the structures involved (soft palate, tongue base, lateral pharyngeal wall, and epiglottis). We compared the patterns of upper airway collapse in the supine and lateral decubitus position among the four BMI groups using the chi-square test and multivariate binary logistic regression analysis. Results: . A total of 627 patients (male, 517; mean age, 47.6±12.8 years) were included, consisting of 45, 79, 151, and 352 patients who were underweight or lower normal-weight (defined as the low BMI group), upper normal-weight, overweight, and obese, respectively. Severity indicators of OSA, such as the overall apnea-hypopnea index and duration of SaO2 below 90%, were significantly lower in patients with a low BMI than in obese patients, while their average oxygen saturation was significantly higher. The most common obstruction site in the supine position was the tongue base in patients with a low BMI (100%), whereas this obstruction site was significantly less common in obese patients (54.8%). Tongue base obstruction was mostly relieved in the lateral position, with no discernible obstruction in 86.7% of the low BMI patients. Conclusion . Airway obstruction in OSA patients with a low BMI is mostly due to tongue base obstruction, which improves in the lateral position. These characteristics should be kept in mind when considering treatment options for this subgroup of OSA patients.

PURPOSE: Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification. MATERIALS AND METHODS: From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox’s proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis. RESULTS: The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell’s C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients. CONCLUSION: These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.
Biliary Tract Neoplasms* ; Biliary Tract* ; Carcinoembryonic Antigen ; Dataset ; Drug Therapy ; Humans ; Hypoalbuminemia ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Reference Values ; Social Identification

PURPOSE: This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients. MATERIALS AND METHODS: Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O’Quigley method, and then analyzed in association with prognosis—overall survival (OS), using Cox's proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis. RESULTS: Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively). CONCLUSION: We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection.
Adenocarcinoma* ; Carcinoembryonic Antigen ; Drug Therapy ; Humans ; Methods ; Multivariate Analysis ; Pancreatic Neoplasms ; Prognosis ; Proportional Hazards Models ; Reference Values ; Research Design ; Retrospective Studies

Solitary fibrous tumor of the pleura (SFTP) is a rare primary intrathoracic tumor that arises from mesenchymal tissue underlying the mesothelial layer of the pleura. It usually has an indolent clinical course. The hypoglycemia that accompanies SFTP was first described by Doege and Potter independently in 1930, hence the eponym Doege-Potter syndrome (DPS). The incidence of DPS is reported to be ~4%. In this report, we present a typical case of DPS that was cured through complete surgical resection.
Eponyms ; Hypoglycemia* ; Incidence ; Pleura* ; Solitary Fibrous Tumor, Pleural ; Solitary Fibrous Tumors

Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by its dual differentiation into luminal cells and myoepithelial cells. In most cases these tumors have a benign clinical course, but distant metastases have been reported. We present the case of a 51-year-old woman diagnosed with malignant AME. The patient underwent a right modified radical mastectomy, and pathological examination confirmed the diagnosis of malignant AME. Ten months after the operation, multiple hepatic, pleural, and abdominal wall metastases were detected. A number of palliative chemotherapeutic agents were tried, including anthracycline and taxanes. However, the disease continued to progress, and superior vena cava syndrome developed as a result of direct tumor invasion. The patient received salvage eribulin monotherapy. After two cycles of this treatment, her clinical symptoms were ameliorated, and a computed tomography scan showed a partial response. Eribulin chemotherapy was thus effective in treating malignant AME in this case.
Abdominal Wall ; Adenomyoepithelioma* ; Breast* ; Diagnosis ; Drug Therapy ; Female ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Metastasis ; Phenobarbital ; Superior Vena Cava Syndrome ; Taxoids

BACKGROUND AND OBJECTIVES: The purposes of this study are 1) to investigate the relationship between resting baseline Pd/Pa, determined by the ratio of the pressures proximal (Pa) and distal (Pd) to the target lesion before, inducing hyperemia and fractional flow reserve (FFR) and 2) to identify a resting baseline Pd/Pa range that might reliably preclude the need for hyperemic induction. SUBJECTS AND METHODS: A total of 622 pressure wire data sets obtained from intermediate stenotic lesions were analyzed. RESULTS: There was a good linear relationship between resting baseline Pd/Pa and FFR (r=0.746, p<0.001). Receiver-operating characteristic curves of the resting baseline Pd/Pa with FFR < or =0.80 as the reference variable showed an area under the curve of 0.89 (95% confidence intervals 0.863-0.914, p<0.001) with a diagnostic accuracy of 82.3% when the resting baseline Pd/Pa was < or =0.92. These results showed that certain cutoff values can reliably predict FFR, whether positive or negative. The resting baseline Pd/Pa >0.95 (n=257, 41.3%) had a negative predictive value (NPV) of 98.1% and a sensitivity of 97.3%. the resting baseline Pd/Pa < or =0.88 (n=65, 10.5%) had a positive predictive value (PPV) of 96.2% and a specificity of 99.8%. These were consistent regardless of coronary vessel, lesion location, lesion length, or degree of stenosis. CONCLUSION: In intermediate lesions, the resting baseline Pd/Pa was linearly related to FFR. A certain range of the resting baseline Pd/Pa values had an excellent NPV with high sensitivity or excellent PPV with high specificity for determining the lesion significance.
Coronary Vessels ; Fractional Flow Reserve, Myocardial ; Glycosaminoglycans ; Hyperemia ; Sensitivity and Specificity

The combination of coronary arteriovenous fistula to the coronary sinus (CS), dilatation of the entire length of coronary artery, coronary aneurysm and persistent left superior vena cava (PLSVC) is very rare. We present the case of a 63-year-old female admitted for dyspnea on exertion, orthopnea, and facial edema. Echocardiography detected a giant coronary artery with shunt flow, dilated CS and PLSVC and a coronary angiography reaffirmed these findings. The calculated ratio of pulmonary blood flow to systemic blood flow by cardiac catheterization was 1.53. After multidisciplinary review considering old age, hypoactivity due to underlying Parkinsonism and relatively small amount of shunt flow, medical therapy was chosen. The patient remained asymptomatic for 10 months after discharge without intervention.
Aneurysm ; Arteriovenous Fistula ; Cardiac Catheterization ; Cardiac Catheters ; Coronary Aneurysm ; Coronary Angiography ; Coronary Sinus ; Coronary Vessels ; Dilatation ; Dyspnea ; Echocardiography ; Edema ; Female ; Fistula ; Humans ; Middle Aged ; Parkinsonian Disorders ; Vena Cava, Superior

BACKGROUND/AIMS: Intestinal involvement with bleeding and perforation is one of the main causes of morbidity and mortality in patients with Behcet's disease (BD); however, the clinical course of intestinal BD has not been defined. The aim of this study was to determine the clinical course of intestinal BD based on the characteristics of ulcers visualized during colonoscopy. METHODS: We retrospectively reviewed the medical records and colonoscopic findings of 41 patients with intestinal BD. All patients were classified into subgroups according to ulcer depth, size, and number, and we analyzed the clinical manifestations, subset type of BD, medications, surgical procedures, and relapse rate among the subgroups. RESULTS: The median age at the time of diagnosis was 38 years (range, 18-74 years); 25 patients were females (M:F=1:1.56). Abdominal pain (n=40), diarrhea (n=27), and RLQ tenderness (n=21) were common symptoms. The number of complete, incomplete, and suspected types was 3, 17, and 21, respectively. In an analysis according to ulcer depth, the rate of steroid use and intestinal surgeries was more frequent in the deep ulcer group compared with the aphthous and shallow ulcer groups (50.0% vs. 0% vs. 17.6%; P=0.012; 42.9% vs. 0% vs. 23.5%: P=0.013) The rate of steroid use and relapse tended to be higher as the size of the ulcer increased; however, there was no difference in the rates of steroid use, surgeries, and relapse based on the number of intestinal ulcers. CONCLUSIONS: The prognosis was worse in patients with intestinal BD who have deeper and larger ulcers. Therefore, we suggest that such patients need to be treated aggressively.
Abdominal Pain ; Colonoscopy ; Diarrhea ; Female ; Hemorrhage ; Humans ; Medical Records ; Prognosis ; Recurrence ; Retrospective Studies ; Ulcer

BACKGROUND/AIMS: Intestinal involvement with bleeding and perforation is one of the main causes of morbidity and mortality in patients with Behcet's disease (BD); however, the clinical course of intestinal BD has not been defined. The aim of this study was to determine the clinical course of intestinal BD based on the characteristics of ulcers visualized during colonoscopy. METHODS: We retrospectively reviewed the medical records and colonoscopic findings of 41 patients with intestinal BD. All patients were classified into subgroups according to ulcer depth, size, and number, and we analyzed the clinical manifestations, subset type of BD, medications, surgical procedures, and relapse rate among the subgroups. RESULTS: The median age at the time of diagnosis was 38 years (range, 18-74 years); 25 patients were females (M:F=1:1.56). Abdominal pain (n=40), diarrhea (n=27), and RLQ tenderness (n=21) were common symptoms. The number of complete, incomplete, and suspected types was 3, 17, and 21, respectively. In an analysis according to ulcer depth, the rate of steroid use and intestinal surgeries was more frequent in the deep ulcer group compared with the aphthous and shallow ulcer groups (50.0% vs. 0% vs. 17.6%; P=0.012; 42.9% vs. 0% vs. 23.5%: P=0.013) The rate of steroid use and relapse tended to be higher as the size of the ulcer increased; however, there was no difference in the rates of steroid use, surgeries, and relapse based on the number of intestinal ulcers. CONCLUSIONS: The prognosis was worse in patients with intestinal BD who have deeper and larger ulcers. Therefore, we suggest that such patients need to be treated aggressively.
Abdominal Pain ; Colonoscopy ; Diarrhea ; Female ; Hemorrhage ; Humans ; Medical Records ; Prognosis ; Recurrence ; Retrospective Studies ; Ulcer