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.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.
Acute Disease ; Alanine Transaminase/blood ; Antibodies, Viral/blood ; Aspartate Aminotransferases/blood ; Bilirubin/analysis ; Cholestasis/*drug therapy ; Guillain-Barre Syndrome/complications/*diagnosis ; Hepatitis E/*diagnosis/etiology ; Hepatitis E virus/immunology ; Humans ; Immunoglobulin M/blood ; Liver/pathology ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Republic of Korea ; Steroids/*therapeutic use

Hyperthermia can cause severe complications such as rhabdomyolysis, which can induce acute kidney injury. Normal thermoregulation can be disturbed by high fever, and maintenance of a normal body temperature by external cooling can reduce oxygen consumption, and increase vascular tone. Several studies have been conducted to determine the effectiveness of external cooling in treat rhabdomyolysis or renal failure. We report a case of rhabdomyolysis leading to multiple organ dysfunction, including renal failure. The use of an external cooling device achieved fever control and successfully treated rhabdomyolysis and renal failure.
Acute Kidney Injury* ; Body Temperature ; Body Temperature Regulation ; Fever ; Oxygen Consumption ; Renal Insufficiency ; Rhabdomyolysis*

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

PURPOSE: High voltage electrical injury mainly occurs in the industrial field. It can cause serious complications and sequelae that lead to high social and economic costs. We investigated the causes of this to try to help prevent these injuries. METHODS: We reviewed 128 patients who incurred high voltage electrical injury during a 3-years period from Jan. 1, 2006 to Dec. 31, 2008. We performed a retrospective analysis of the medical records to review the epidemiology. We also performed a survey by telephone. The survey questions addressed the following: the duration of work, wearing safety equipment, the reason for working without safety equipment, did they receive safety education, was the safety education adequate, recognition of a high tension wire before working and did they understand the effect of high voltage on the human body. RESULTS: The safety education was relatively carried out well. But most patients did not wear safety equipment even though they knew they had to wear it (92%). The major reason was discomfort of wear it (72%). The hand was the most common injury site (80%). Most injuries occurred with 22,900 volt or less (92%). In spite of safety education, many patients were unaware of the effects of electrical injury on their body. CONCLUSION: Strengthened safety education can play a significant role in preventing high voltage electrical injury. At this point, the doctors who are experienced in treating high voltage electrical injury must actively participate in this safety education. We suggest that handy safety equipment can lessen the incidence of high voltage electrical injury. It is essential to develop a handy safety glove for 22,900V with considering that the hand was the most common injury site and the most frequent voltage for injury was 22,900 volt or less.
Electric Injuries ; Hand ; Human Body ; Humans ; Incidence ; Medical Records ; Protective Devices ; Retrospective Studies ; Safety Management ; Telephone

PURPOSE: High voltage electrical injuries can cause many complications of central nervous system. We tried to define the indication range of brain CT (computerized tomography) in high voltage electrical injuries. METHODS: We performed a retrospective analysis of 51 high voltage electrical injured patients who were confirmed by brain CT, they had visited our emergency department from January 2005 to December 2007. All patients were classified by brain CT findings, presences of combined injuries and neurologic symptoms. RESULTS: 48 patients were confirmed normal in brain CT findings. 3 patients had brain lesions that were associated with secondary trauma. There was no abnormal CT finding in the 23 patients who did not have loss of consciousness, falling and combined injuries. CONCLUSION: If patient with electrical injury did not have neurologic symptoms or sufficient mechanical force, brain CT is not recommended. The results of this study may help emergency physicians to avoid unnecessary brain CT examination in the emergency triage to a high voltage electrical injury patients.
Brain ; Burns ; Central Nervous System ; Emergencies ; Humans ; Neurologic Manifestations ; Retrospective Studies ; Triage ; Unconsciousness

The Rastelli operation has been a standard procedure for repairing complete transposition of the great arteries combined with a ventricular septal defect and pulmonary stenosis. Yet this procedure has several shortcomings, including the risk of incurring left ventricular outflow tract obstruction on long-term follow-up. In this regard, aortic translocation has recently been regarded as a potent alternative to Rastelli's operation. We report here on a case of complete transposition of the great arteries that was combined with an inlet-extended perimembranous ventricular septal defect and pulmonary stenosis in a 2-year-old boy. All the problems were successfully repaired using the aortic translocation technique. Postoperative echocardiography showed a straight and wide left ventricular outflow tract.
Arteries ; Echocardiography ; Follow-Up Studies ; Heart Septal Defects, Ventricular ; Preschool Child ; Pulmonary Valve Stenosis ; Transposition of Great Vessels

Subcellular localizaton of HBcAg have been found to be related to the activity of liver disease and HBV replication. The aim of this study was to determine whether the degree of expression of HBcAg in the hepatocyte nucleus and cytoplasm reflects the level of viral replication and histological activity in chronic HBV infection. A total of 102 patients with biopsy proven chronic hepatitis B were included. There was a highly significant correlation between the levels of HBV DNA in serum and the degree of expression of HBcAg in the nucleus for HBeAg-positive(p=0.000) and negative patients(p=0.04). There was a highly significant, correlation between the degrees of expression of HBcAg in hepatocyte cytoplasm and histologic activities (p<0.01) for HBeAg-positive patients. The degrees of expression of HBcAg in the hepatocyte cytoplasm correlated positively with the lobular activities (p<0.01), but not correlated with the portal activity and fibrosis for HBeAg-negative patients. In conclusion, in the young patients with chronic B viral hepatitis, the degree of expression of HBcAg in the hepatocyte nucleus may affect viral load, and the degree of expression of HBcAg in the hepatocyte cytoplasm may affect histologic activities of liver disease.
Male ; Liver/pathology/virology ; Humans ; Hepatocytes/pathology/*virology ; Hepatitis B, Chronic/*pathology/*virology ; Hepatitis B e Antigens/metabolism ; Hepatitis B Core Antigens/*metabolism ; DNA, Viral/blood ; Cytoplasm/virology ; Cell Nucleus/virology ; Adult ; Adolescent

BACKGROUND: It is known that the hepatic nitric oxide (NO) production is induced by various pathologic inflammatory response such as viral hepatitis and mediated by various cytokines from hepatic immune or non-immune cells. We have investigated nitric oxide metabolites (NOx) concentration to know the effect of lamivudine treatment on NOx in chronic hepatitis B patients, and the association between NO metabolic concentration and other clinical factors. METHODS: The study subjects comprised 70 candidates for antiviral treatment for chronic viral hepatitis B. We observed the concentration of NOx in patients group before and after antiviral treatment with lamivudine 100 mg for 24 weeks and compared them with controls. We also examined clinical factors which can affect the concentration of NOx. RESULTS: The mean concentration of NOx in chronic viral hepatitis B patients was significantly higher than that of control group. (patient group: 78.2+/-12.7 micrometer and healthy control group: 31.8+/-11.3 micrometer, p=0.014). The mean concentration of NOx significantly decreased after lamivudine treatment (after treatment: 44.2+/-17.9 micrometer and before treatment: 78.2+/-12.7 micrometer, p=0.027). HBV DNA titer and ALT level were significantly correlated with the concentration of NOx (HBV DNA titer: r=0.697, p=0.038 and ALT level: r=0.402, p=0.012). CONCLUSIONS: The fact that serum NO concentration increased proportionally to the amount of ALT and HBV DNA and decreased after the treatment with lamivudine suggests that serum concentration of NO have correlation with course of HBV infection.
Cytokines ; DNA ; Hepatitis ; Hepatitis B ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Lamivudine* ; Nitric Oxide*