Cellular immunotherapy with chimeric antigen receptor (CAR) T-cells has revolutionized the treatment of lymphoid malignancies. This review addresses the need for CAR expression in our endogenous T-cells to kill tumor cells with a focus on the basic principles of T-cell receptor recognition of major histocompatibility complex-peptide complexes.We review the factors associated with CAR T-cell outcomes and recent efforts to employ CAR T-cells in earlier lines of therapy. We also discuss the value of bispecific T-cell engagers as off-the-shelf products with better toxicity profiles. Finally, natural killer cells are discussed as an important cellular immunotherapy platform with the potential to broaden immunotherapeutic applications beyond lymphoid malignancies.

Tracheopathia osteoplastica(TO) is a rare, clinical and pathologic benign condition of unknown cause and characterized by submucosal cartilaginous or bony projections into tracheobroncheal lumen, usually not involved posterior membranous portion of tracheobroncheal tree. We report two cases of tracheopathia osteoplastica that involved trachea and both main bronchus, diagnosed by chest CT, fiberoptic bronchoscopic biopsy.
Biopsy ; Bronchi ; Tomography, X-Ray Computed ; Trachea

Pacemaker lead endocarditis is treated with total removal of the infected device and proper antibiotics. The outcomes of patients undergoing percutaneous lead extraction for large vegetations (>2 cm) have not yet been shown. In this case report, we present two patients with pacemaker lead endocarditis with large vegetations of maximum diameter 2.4 cm and 3.2 cm. The first patient had multiple vegetations attached to the tricuspid and mitral valves and developed septic emboli to the brain, lung, and liver. The second patient had a large, persistent vegetation on the tricuspid valve, even two weeks after complete removal of the leads. Both patients were successfully treated with transvenous pacemaker lead removal and antibiotics.
Anti-Bacterial Agents ; Brain ; Endocarditis* ; Humans ; Liver ; Lung ; Mitral Valve ; Pacemaker, Artificial ; Tricuspid Valve

OBJECTIVE: The purpose of the present study was to evaluate treatment outcomes and prognostic factors in cervical cancer patients with isolated para-aortic lymph node (PALN) metastases. We especially tried to evaluate PALN factors such as size, site and number. METHODS: From August 1994 to December 2009, 40 cervical cancer patients with isolated PALN node metastases at initial diagnosis were selected for analysis. Patients underwent both extended field external beam and intracavitary brachytherapy. Fourteen patients received 5-fluorouracil and cisplatin (FP) and 16 patients received weekly concurrent cisplatin. Information of PALN, such as size, site, and number, was founded before PALN radiotherapy. RESULTS: The median follow-up time after primary treatment was 28.5 months (range, 2 to 213 months). The 3-year overall and progression-free survival rate after primary treatment was 44.3% and 31.3%, respectively. In multivariate analysis including tumor stage, performance status, and chemotherapy, FP regimen concurrent chemoradiotherapy was more effective than radiotherapy alone (p=0.030). The 3-year progression-free survival rate was 41.9% and 11.1% in patients with PALN numbers of < or =1 and > or =2, respectively (p=0.008). The 3-year progression-free survival rate was 42.1% and 19.2% in patients with PALN size of <1.5 cm and > or =1.5 cm, respectively (p=0.031). CONCLUSION: The radiologic features of PALN, such as number or size, can be used to determine prognosis in PALN metastatic cervical cancer patients. Furthermore, FP regimen concurrent chemoradiotherapy was associated with better patient survival than radiotherapy alone. However, more studies are required to confirm possible different treatment outcomes between FP and weekly cisplatin regimens.
Brachytherapy ; Chemoradiotherapy ; Cisplatin ; Disease-Free Survival ; Fluorouracil ; Follow-Up Studies ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Treatment Outcome ; Uterine Cervical Neoplasms

Background/Aims: Altered DNA methylation is a key mechanism of epigenetic modification in gastric cancer (GC). This study aimed to evaluate the changes in epigenetic and genetic expression of multiple Rho GTPases in Helicobacter pylori-related gastric carcinogenesis by comparing H. pylori-positive GCs and negative controls. Methods: The messenger RNA expression and methylation of Rho GTPases (RhoA, Rac1, DOCK180, ELMO1, and CDC42) were evaluated in H. pylori-negative (control) human gastric tissues and H. pylori-positive GCs by using real-time reverse transcription-polymerase chain reaction and the quantitative MethyLight assay, respectively. Changes in expression and methylation levels of the genes were also compared between H. pylori-eradicated and -persistent GCs at 1-year follow-up. Results: In GCs, the methylation and expression levels of DOCK180 and ELMO1 were higher than in controls, while RhoA and Rac1 had lower levels than controls. CDC42 had the same expression pattern as DOCK180 and ELMO1 without DNA methylation. Although methylation levels of DOCK180 and ELMO1 had no difference betweenH. pylori-eradicated and -persistent GCs at the index endoscopic resection, those of H. pylori-persistent GCs increased and H. pylorieradicated GCs decreased for 1 year. The expression levels of DOCK180, ELMO1, and CDC42 in H. pylori-persistent GCs were higher than those in H. pylori-eradicated GCs over 1 year, unlike those of RhoA and Rac1. The methylation levels at index and the degrees of change over time of RhoA and Rac1 had no difference between H. pylori-persistent and -eradicated GCs. Conclusions Epigenetic alterations of DOCK180 and ELMO1 are involved in H. pylori-related gastric carcinogenesis. This epigenetic field could be improved by H. pylori eradication.

Pegylated-interferon plus ribavirin is the standard treatment for chronic hepatitis C. Sustained virological response (SVR) rates of up to 80% are reported in genotype 2 and 3 chronic hepatitis C cases. Obesity, a modifiable risk factor, may have a deleterious effect on antiviral treatment. We performed this study to examine the efficacy and safety of pegylated-interferon and ribavirin therapy in Korean patients with genotype 2 and 3 chronic hepatitis C and to investigate the risk factors for nonresponse to antiviral treatment. A total of 121 patients were treated with peginterferon alpha-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks. The end-of-treatment virologic response (ETVR), the SVR, the end-of-treatment biochemical response (ETBR), the sustained biochemical response (SBR), and the adverse events were analyzed. The ETVR and SVR were 94.1% and 89.1%, respectively. The ETBR was 80.2% and the SBR was 96%. Multivariate analysis showed that a body mass index of 25 and over was the only independent factor that affected the SVR (odds ratio=10.5, 95% confidence interval: 2.006-54.948, p=0.005). Twenty patients (16.5%) dropped out at the end of treatment, and 7 (5.8%) patients discontinued treatment because of treatment-related adverse events. Our study showed that combination therapy with pegylated-interferon and ribavirin as an initial treatment for genotype 2 and 3 chronic hepatitis C is very effective and safe, and that body mass index is an independent risk factor for nonresponse to antiviral treatment in patients with genotype 2 and 3 chronic hepatitis C.
Body Mass Index ; Genotype ; Hepatitis C, Chronic ; Hepatitis, Chronic ; Humans ; Interferon-alpha ; Multivariate Analysis ; Obesity ; Polyethylene Glycols ; Recombinant Proteins ; Ribavirin ; Risk Factors

BACKGROUND: Isolated myeloid sarcoma (MS) is a rare extramedullary tumor mass composed of malignant myeloid precursor cells without any evidence of leukemia in the peripheral blood and bone marrow. We describe the clinical characteristics and outcomes of patients diagnosed with isolated MS at our institution. METHODS: We retrospectively reviewed 9 of 497 acute myeloid leukemia (AML) patients (1.8%) with isolated MS. Isolated MS patients were divided into 2 groups according to the first-line treatment strategy: systemic treatment only (S) or local treatment with or without systemic treatment (LS). RESULTS: The most common site of MS occurrence was the head and neck area (N=4, 44.4%), followed by the anterior mediastinum (N=2, 22.2%) and the gastrointestinal tract (N=2, 22.2%). The tumors of 4 patients (44.4%) eventually evolved to AML, in a median time of 13.4 months (range, 2.4–20.1 mo). The number of patients achieving complete remission after first-line treatment was higher in the LS group (N=5, 83.3%) than in the S group (N=1, 33.3%) (P =0.226). All patients in the LS group survived, but those in the S group died (P=0.012). CONCLUSION: Accurate and rapid diagnosis using various modalities and the early initiation of intensive combined treatment may be the optimal strategies to reduce the risk of isolated MS subsequently evolving to AML. To fully understand the characteristics of isolated MS, a larger number of patients from a multinational study is necessary.
Bone Marrow* ; Diagnosis ; Gastrointestinal Tract ; Head ; Humans ; Leukemia ; Leukemia, Myeloid, Acute ; Mediastinum ; Neck ; Retrospective Studies ; Sarcoma, Myeloid*

A 60-year-old man visited the hospital after experiencing dyspnea after exertion for 2 weeks. An electrocardiogram showed sinus arrest with junctional escape rhythm at 40 beats/min. Transthoracic echocardiography showed that the right ventricular systolic pressure (RVSP) was approximately 71 mmHg and that the left ventricular ejection fraction was preserved. The ratio of peak early diastolic transmitral inflow velocity to early diastolic peak mitral annular velocity (E/E') was 29. Cardiac catheterization revealed a systolic pulmonary artery pressure (SPAP) of 63 mmHg, a mean pulmonary artery pressure of 27 mmHg, and a pulmonary capillary wedge pressure of 22 mmHg with a rhythm of 40 beats/min. The patient was diagnosed with pulmonary hypertension (group 2) due to sick sinus syndrome. SPAP decreased to 48 mmHg during atrial pacing at 60 beats/min. After permanent pacemaker insertion, RVSP decreased from 71 mmHg to 44 mmHg. In this case, passive group 2 pulmonary hypertension occurred due to sick sinus syndrome.
Blood Pressure ; Cardiac Catheterization ; Cardiac Catheters ; Dyspnea ; Echocardiography ; Electrocardiography ; Humans ; Hypertension, Pulmonary* ; Middle Aged ; Pulmonary Artery ; Pulmonary Wedge Pressure ; Sick Sinus Syndrome* ; Stroke Volume ; United Nations

Purpose: As the rate of endoscopic resection for early gastric cancer (EGC) has increased in patients with comorbid diseases, it is necessary to elucidate the efficacy of endoscopic submucosal dissection (ESD) for EGC in patients with comorbidities. This study aimed to analyze the clinical outcomes of ESD for EGC in patients with comorbidities. Materials and Methods: A total of 969 patients with 1,015 lesions who underwent ESD for EGC at Seoul National University Hospital between 2010 and 2014 were analyzed. The shortand long-term clinical outcomes were evaluated according to the comorbidity status. Results: Comorbidities were observed in 558 patients (57.6%). The comorbidity group had a higher proportion of patients using antithrombotic agents (29.5% vs. 0.9%; P<0.0001).Although procedure-related complications (bleeding and perforation) were not significantly different between the two groups, the length of hospital stay was significantly longer (1.8 vs.1.4 days, P=0.023), while survival was significantly shorter in the comorbidity group (5-year overall survival rate: 90.5% vs. 97.2%, P<0.0001; 5-year disease-specific survival rate: 97.9% vs. 100%, P=0.018; 5-year disease-free survival rate: 83.4% vs. 89.2%, P=0.007). Conclusions Gastric ESD can be performed in patients with comorbidities without increasing the risk of complications.

Objectives: The A2142G and A2143G mutations in the 23S ribosomal ribonucleic acid (rRNA) of Helicobacter pylori are the most common mutations associated with clarithromycin resistance. This study aimed to determine the differences in H. pylori eradication rates in patients infected with bacteria carrying the A2142G and A2143G mutations who were treated with clarithromycin-based triple therapy. Methods: Data from a previous randomized controlled trial were analyzed retrospectively. Eradication rates were compared based on the presence of H. pylori carrying the A2142G and A2143G mutations. A meta-analysis was also conducted of relevant studies containing data regarding patients who received clarithromycin-based therapy due to infections with H. pylori harboring 23S rRNA mutations. Results: No significant difference was observed in H. pylori eradication rates between patients infected with wild-type bacteria (95.7% [44/46]) compared with those infected with bacteria carrying the A2142G mutation (100.0% [3/3]; p>0.9). However, the eradication rate was significantly lower for patients infected with bacteria carrying the A2143G mutation (16.7% [1/6]; p<0.001) than for those infected with wild-type bacteria or bacteria with the A2142G mutation (100.0% [3/3]; p=0.048). In the meta-analysis, the between-group comparisons yielded similar results. Although patients infected with bacteria having the A2142G mutation exhibited no significant risk difference (RD) for eradication compared with those infected with wild-type bacteria (RD=-0.05 [-0.18 to 0.08]; I2=0%; p=0.42), those infected with bacteria having the A2143G mutation demonstrated a lower H. pylori eradication rate compared with patients infected with either wild-type (RD=0.72 [0.64–0.80]; I2=0%; p<0.001) or A2143G mutant bacteria (RD=0.76 [0.61–0.91]; I2=0%; p< 0.001). Conclusions The A2143G mutation may play a more significant role in clarithromycin triple therapy H. pylori eradication failure than does the A2142G mutation. Additionally, H. pylori strains with the A2142G mutation can be treated effectively with clarithromycin-based triple therapy.