Jae Ho Byun

Primary Adenocarcinoma of the Small Intestine: Presentation, Prognostic Factors and Clinical Outcome

BACKGROUND Malignant small intestine tumor accounts for 0.1-0.3% of all malignancies. Although primary adenocarcinoma is the most common histologic subtype, there is no report of the clinical characteristics and natural history in the Asian population. METHODS We conducted retrospective analysis for the patients with the small intestine adenocarcinoma to explore the clinical characteristics and prognosis. All patients with adenocarcinoma of small intestine diagnosed between March 1997 and March 2007 in the Catholic Medical Center in Korea were identified through the cancer registry. The medical records were reviewed for patient characteristics, treatment and outcome data. RESULTS Data on 53 patients were available. Twenty-six patients (49.0%) underwent curative resection and 13 patients receiving adjuvant chemotherapy. Fifteen patients received palliative chemotherapy. Median of overall survival of all patients was 12 months (95% confidence interval (CI): 8.5-15.1 months). Three-year survival and relapse-free survival rates after curative resection was 66.1 and 50.8%, respectively. Median survival of patients received palliative chemotherapy was 8.0 months (95% CI: 3.5-12.4). CONCLUSIONS The prognosis of primary adenocarcinoma of small intestine was poor, especially in cases where curative resection could not to be performed. Further study on the methods for early detection and effective systemic chemotherapy should be investigated.

Prognostic significance of CD44s expression in resected non-small cell lung cancer.

BackgroundCD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC).MethodsUsing immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82) and squamous cell carcinoma (SCC; n = 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically.ResultsHigh CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P < 0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P < 0.001), high-grade tumor differentiation (P = 0.046), and high CD44s expression (P = 0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015). No significant association was found between CD44s and clinical outcome (P = 0.311).ConclusionsHigh CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

Expression of placental growth factor gene in lung cancer.

Differences in the gene expression profiles in small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC) may explain their different clinical characteristics. The aims of this study were (1) to identify genes differentially expressed in SCLC and NSCLC using mRNA differential display, and (2) to determine the clinical relevance of such genes in lung cancer. RNA differential display using three SCLC and six non-SCLC cell lines was used to identify a differentially expressed gene. Differential expression of the gene was confirmed in additional lung cancer cell lines using RT-PCR. Immunohistochemical staining for the gene product was performed on paraffin-embedded tissue from lung cancer patients. We examined the relationship between the expression of the gene and clinical parameters, including disease stage, response to treatment and survival time. The placental growth factor (PGF) gene was identified as preferentially expressed in SCLC compared with NSCLC cell lines using mRNA differential display. Further analysis of 45 lung cancer cell lines using RT-PCR showed that the placental growth factor (PGF) gene was expressed in nine of 13 SCLC cell lines (69%) and five of 32 NSCLC cell lines (15.6%) (p < 0.001, Fisher’s exact test). Immunohistochemistry using anti-PGF antibody on the paraffin blocks from lung cancer patients showed that PGF expression was significantly higher in SCLC than NSCLC tissue sections (32 vs. 5.6%, p = 0.041, Fisher’s exact test). Expression of PGF protein did not correlate with disease stage, response to treatment or survival time in SCLC patients. The present study suggests there is higher expression of PGF in SCLC compared to NSCLC. It may be that higher expression of the angiogenic factor PGF contributes to differences between the progression of SCLC and NSCLC, especially in regard to the nature of SCLC metastasis.

Clinical characteristics and prognostic factors for primary appendiceal carcinoma.

Aim:  Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms.

Clinical Characteristics of Primary Peritoneal Carcinoma

PURPOSE The goal of this study was to determine the clinical and therapeutic characteristics of women with a primary peritoneal carcinoma (PPC). MATERIALS AND METHODS A retrospective clinical study was conducted to evaluate 22 women diagnosed with a PPC from 1993 to 2007 at the Hospitals of The Catholic University of Korea. Diagnoses were based on the Gynecologic Oncology Group criteria and clinical data. We collected patient clinicopathological data including age, presenting symptoms, pretreatment CA-125 values (U/ml), clinical stage (based on the FIGO stage), performance status (using the Eastern Cooperative Oncology Group scale), whether cytoreductive surgery was optimal or not, types of chemotherapy and response to treatment. We evaluated the clinical characteristics and response to treatment, time to treatment failure and overall survival. RESULTS The median overall survival of all patients was 23.1 months. The estimated 3-year survival rate was 29% (SE, 13%). The response rate to first-line platinum-based chemotherapy was 79% and the median time to treatment failure was 9.9 months (95% confidence interval, 1.38~18.4 months). By univariate and multivariate analysis, performance status was the only significant factor associated with overall survival (p<0.05). CONCLUSION We evaluated the clinical characteristics and treatment response of patients with a primary peritoneal carcinoma. Our results showed that it is possible to achieve long-term survival in patients with PPC. A further clinical study is to need to establish clinical characteristics and treatment outcomes.

Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma

Endostatin is the C‐terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor‐derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 ± 16.6 vs. 52.2 ± 6.2 ng/mL [p < 0.001]; VEGF, 55.1 ± 7.6 vs. 32.1 ± 2.4 ng/mL [p < 0.001]; mean ± SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow‐up at 42 months; median survival time, 9 vs. 20 months [log‐rank, p = 0.017]; median time to progression, 5 vs. 10 months [log‐rank, p = 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.

Clinical Significance of Vascular Endothelial Growth Factors (VEGF)-C and -D in Resected Non-Small Cell Lung Cancer

PURPOSE Lymphatic spread of tumor is an important prognostic factor for patients with non-small cell lung carcinoma (NSCLC). Vascular endothelial growth factor-C (VEGF-C) and VEGF-D play important roles in lymphangiogenesis via the VEGF receptor 3 (VEGFR-3). We sought to determine whether VEGF-C, VEGF-D and VEGFR-3 are involved in the clinical outcomes of patients with resected NSCLC. MATERIALS AND METHODS Using immunohistochemical staining, we investigated the protein expressions of VEGF-C, VEGF-D and VEGFR-3 in the tissue array specimens from patients who underwent resection for NSCLC. The immunoreactivity for p53 was also examined. The clinicopathological implications of these molecules were statistically analyzed. RESULTS Analysis of a total of 118 specimens showed that VEGF-C, VEGF-D and their co-expression were significantly associated with more advanced regional lymph node metastasis (p=0.019, p=0.044 and p=0.026, respectively, N2 versus N0 and N1). A VEGFR-3 expression had a strong correlation with peritumoral lymphatic invasion (p=0.047). On the multivariate analysis for survival and recurrence, pathologic N2 lymph node metastasis was the only independent prognostic factor, but none of the investigated molecules showed any statistical correlation with recurrence and survival. CONCLUSIONS The present study revealed that high expressions of VEGF-C and VEGF-D were strongly associated with more advanced regional lymph node metastasis in patients with resected NSCLC.

Circulating Stromal Cell Derived Factor-1α (SDF-1α) is Predictive of Distant Metastasis in Gastric Carcinoma

This study was conducted to investigate the value of the pretreatment circulating stromal cell derived factor-1α(SDF-1α) in patients with gastric carcinoma. We measured SDF-1α serum concentrations and evaluated the relationship between serum SDF-1α and serum vascular endothelial growth factor (VEGF) levels and clinical factors in 107 gastric cancer patients. Serum levels of SDF-1α and VEGF levels were higher in gastric cancer patients than in controls (p < 0.001). Serum SDF-1α levels were higher in metastatic patients than non-metastatic patients (p < 0.001). SDF-1α levels were correlated with the presence of distant metastases (r = 0.528; p < 0.001) and correlated with VEGF levels (r = 0.789; p < 0.001). SDF-1α might serve as a possible marker for predicting or monitoring distant metastasis in gastric carcinoma.

Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years.

Purpose Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. Materials and Methods Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. Results Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. Conclusion Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

Up-regulation of the DR5 Expression by Proteasome Inhibitor MG132 Augments TRAIL-Induced Apoptosis in Soft Tissue Sarcoma Cell Lines

Purpose Current chemotherapeutics for treating locally advanced or metastatic soft tissue sarcomas (STS) are limited. Accordingly, the present in vitro study was conducted to evaluate the effects of treatment of STS cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) applied as a single agent or in combination with a proteasome inhibitor, MG132. Materials and Methods Sensitivity to TRAIL and activity of TRAIL-induced apoptotic pathways were analyzed in four STS cell lines: HTB-82 (rhabdomyosarcoma), HT-1080 (fibrosarcoma), HTB-93 (synovial sarcoma), and HTB-94 (chondrosarcoma). Reduction of the dye dimethylthiazolyl 2,5 diphenyltetrazolium bromide (MTT) was used to evaluate cytotoxic activity; western blots were used to evaluate TRAIL-induced apoptosis. Results TRAIL induced apoptosis in HTB-93 cells, but had little effect in HTB-82, HT-1080, or HTB-94 cells. Expression of TRAIL receptor-1 and -2 did not correlate with sensitivity to TRAIL. Co-incubation of cells with TRAIL and a proteasome inhibitor, MG132, augmented the apoptotic effect of TRAIL in both TRAIL-sensitive and TRAIL-resistant cells. This effect was due to up-regulation of TRAIL receptors and members of the pro-apoptotic BCL-2 family by MG132. Conclusion These data show that combining TRAIL with MG132 enhances apoptosis and overcomes TRAIL resistance. This restoration of TRAIL sensitivity occurs through an increase in the expression of death receptor 5 and of pro-apoptotic BCL-2 family members such as BAX.