Suk Young Park

Germline mutations of E-cadherin gene in Korean familial gastric cancer patients.

AbstractGastric cancer is the most common cancer in Korea. Germline mutations of the E-cadherin gene have recently been identified in familial gastric cancer patients. We screened five Korean familial gastric cancer patients to investigate germline mutations of the E-cadherin gene. These patients fulfilled the following criteria: presence of at least two gastric cancer patients within first-degree relatives and one patient diagnosed before the age of 50 years. Abnormal band patterns were found in exons 6 and 10 in two familial gastric cancer patients by polymerase chain reaction-single strand conformation polymorphism analysis (probands from the SNU-G2 and SNU-G1001 families, respectively). DNA sequencing analysis of the E-cadherin gene of these two patients revealed missense mutations in each exon. The SNU-G2 proband harbored a missense mutation from aspartic acid (GAT) to glycine (GGT) at codon 244 in exon 6 of the E-cadherin gene, and the SNU-G1001 proband had a missense mutation from valine (GTG) to alanine (GCG) at codon 487 in exon 10. The SNU-G2 proband was diagnosed with gastric cancer at the age of 38; three brothers and two sisters had died of gastric cancer under the age of 50, and their mother had died of gastric cancer at the age of 63. The SNU-G1001 proband was diagnosed with gastric cancer at the age of 42 and one brother had died of gastric cancer at the age of 49. In summary, we found germline mutations of the E-cadherin gene in two of five Korean familial gastric cancer patients screened.

Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer.

The cytotoxic effects of gemcitabine (G) and cisplatin (C) seem to occur through induction of apoptosis. To examine whether the efficacy of GC chemotherapy might be influenced by the expression of death receptor 5 (DR5) and Bcl-2 of the tumor, we investigated the correlation between the tumor response rate and DR5 and Bcl-2 expression in a series of patients prospectively treated with GC. Thirty-four chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) received intravenously 1000 mg/m2 gemcitabine on d 1 and 8 along with 80 mg/m2 cisplatin on d 2, every 21 d. Tumor specimens were analyzed for DR5 and Bcl-2 expression by immunohistochemistry. The objective response rate was 56% (19 of 34 patients). With median follow-up of 10 mo, the predicted median survival time was 12 mo (95% confidence interval [CI], 9–15 mo). Eleven (32%) and 14 (41%) NSCLC cases were found positive for DR5 and Bcl-2, respectively. The response rate was significantly higher in patients with DR5 expression than those without DR5 expression (91% vs 39%; p=0.008). Patients with Bcl-2 expression were apparently less responsive than those without Bcl-2 expression (21% vs 80%; p=0.001). DR5 and Bcl-2 expression was significantly associated with response to GC chemotherapy. Therefore, DR5 and Bcl-2 status are useful factors for predicting the efficacy of GC.

Mucosa-associated lymphoid tissue (MALT) lymphoma combined with tuberculous enteritis at the same site in the jejunum

Mucosa-associated lymphoid tissue(MALT) lymphoma is derived from the marginal zone B-cell compartment and can be found at a wide variety of extranodal sites, most frequently at the gastrointestinal site. Recent clinicopathologic studies suggest a relationship between MALT lymphoma and chronic inflammatory disorders, such as Helicobacter pylori infection in the stomach or autoimmune disorders, such as Sjögrens syndrome in the salivary glands. Primary gastrointestinal MALT lymphomas most commonly arise in the stomach and less often in the small and large intestine. Recently we experienced a case who had MALT lymphoma combined with tuberculous enteritis at the same site (jejunum) confirmed by exploratory laparotomy. We suspect that there may be some relationship between MALT lymphoma and chronic inflammatory process of mycobacterial tuberculous enteritis.

Prognostic value of early response assessment using 18F-FDG PET/CT in chemotherapy-treated patients with non-small-cell lung cancer.

ObjectiveWe aimed to evaluate the prognostic value of early response assessment using a volumetric fluorine-18-fluorodeoxyglucose (18F-FDG) PET analysis in chemotherapy-treated patients with non-small-cell lung cancer (NSCLC). Materials and methodsWe retrospectively reviewed 33 patients with NSCLC who received first-line chemotherapy and performed 18F-FDG PET/computed tomography before (baseline PET) and after two cycles of chemotherapy (interim PET). The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of the total malignant lesion were measured in baseline (SUV1 and MTV1) and interim (SUV2 and MTV2) PET images, and percentage changes in SUVmax (&Dgr;SUV) and MTV (&Dgr;MTV) were calculated between the two images. We compared PET parameters and clinicopathologic variables in terms of the 2-year overall survival (OS). ResultsThe median follow-up period was 14.3 months and the 2-year OS was 31%. In PET images, the mean SUV1, MTV1, SUV2, MTV2, &Dgr;SUV, and &Dgr;MTV were 13.1±4.5, 307.9±340.0 cm3, 9.5±5.1, 180.4±29.6 cm3, 27±28%, and 42±65%, respectively. In univariable analysis, M stage, TNM stage, and all six PET parameters associated significantly with OS. Both the MTV1 and the &Dgr;MTV were tested against OS controlling for M stage, one at time, and the effect remained significant in multivariable analyses. ConclusionA smaller baseline MTV and greater decrease in MTV between baseline and interim PET images are associated with a significantly prolonged OS. A volume-based 18F-FDG PET analysis would facilitate prediction of clinical outcome and identification of treatment-resistant patients early during chemotherapy and could thus be used in personalized treatment approaches for patients with NSCLC.

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study

BACKGROUND In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. METHODS Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. RESULTS Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). CONCLUSION This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate.

A Prospective Multicentre Study to Evaluate the Efficacy and Tolerability of Osmotic Release Oral System (Oros®) Hydromorphone in Opioid-Naive Cancer Patients: Results of the Korean South West Oncology Group Study

Early and active management of cancer pain is important for improving patients’ satisfaction with treatment and quality of life. The efficacy and tolerability of osmotic release oral system (OROS®) hydromorphone was evaluated in opioid-naive cancer patients experiencing moderate to severe cancer pain. The authors believe the results of this study will provide meaningful information regarding the clinical benefit of OROS hydromorphone as front-line therapy in opioid-naive cancer patients.

Usefulness of target delineation based on the two extreme phases of a four-dimensional computed tomography scan in stereotactic body radiation therapy for lung cancer.

An evaluation of the usefulness of target delineation based only on the two extreme phases of a four‐dimensional computed tomography (4D CT) scan in lung stereotactic body radiation therapy (SBRT).

Fasciitis after allogeneic peripheral blood stem cell transplantation in a patient with chronic myelogenous leukemia.

Fasciitis, one of the presentations of chronic skin graft-versus-host disease (GVHD), is characterized by symmetrical inflammatory swelling of extremities with or without eosinophilia, but it is rarely reported. This article describes a patient with the clinical and histologic features of fasciitis, as the only form of chronic GVHD that developed 20 months after HLA-matched allogeneic peripheral hematopoietic stem cell transplantation (HSCT) for chronic myelogenous leukemia (CML). She reported tightness of the skin and pain in both wrists and elbows on motion, with edema of the limbs. A deep cutaneous biopsy showed thickening of the subcutaneous fascia with inflammatory infiltrates. The patient was treated with cyclosporine and prednisone, which resulted in much improvement of her symptoms and signs related to the fasciitis. The authors recommend that clinicians maintain a high index of suspicion for fasciitis because fasciitis is a distinct entity among the chronic GVHD that may lead to a functional disability.

Three-dimensional conformal reirradiation for locoregionally recurrent lung cancer previously treated with radiation therapy.

To evaluate the efficacy and toxicity of reirradiation using three‐dimensional conformal radiotherapy (3D‐CRT) in symptomatic patients with locoregionally recurrent lung cancer.

Intrapleural Chemotherapy with Cisplatin and Cytarabine in the Management of Malignant Pleural Effusion

PURPOSE The purpose of this study was to evaluate the efficacy of intrapleural chemotherapy (IPC) with cisplatin and cytarabine in the management of malignant pleural effusion (MPE) from non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS A prospective analysis was carried out on 40 patients with pathologically proven MPE from NSCLC who had received IPC. A single dose of cisplatin 100 mg/m(2) plus cytarabine 1200 mg/m(2) in 250 ml normal saline was instilled into the pleural space via a chest tube and drained 4 hours later. Patients were evaluated for toxicities and responses at 1, 2, & 3 weeks and then at monthly intervals if possible. Systemic chemotherapy was administered, if the patient agreed to receive it, after achieving complete control (CC) of MPE. RESULTS The median duration of chest tube insertion for drainage was 7 (3 approximately 32) days. Among the assessable 37 patients, CC and partial control (PC) were 32 (86.5%) and 4 (10.8%) patients, respectively (overall response rate 97.3%). The median duration of response was 12 months (2 approximately 23) and there were only two relapses of IPC after achieving CC. Among the 35 patients who were assessable until they died, 28 patients (80.0%) maintained CC until the last follow-up. There was only one toxic death and the toxicities of IPC, versus the results obtained, were deemed acceptable. CONCLUSION The procedures were tolerable to the patients and chemotherapy-induced complications were at an acceptable level. The outcome of this trial indicates that IPC has a superior and long lasting treatment response in the management of patients with MPE from NSCLC.