Effect of a Proton Pump Inhibitor on Tumor Bleeding Prevention in Unresectable Gastric Cancer Patients: a Double-Blind, Randomized, Placebo-Controlled Trial

PURPOSE: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. MATERIALS AND METHODS: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). RESULTS: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. CONCLUSIONS: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

Preclinical Efficacy Testing for Stomach and Liver Cancers / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Hollow fiber assays offer an early in vivo method of anticancer drug screening. The assays have been optimized for human cancers originating from the lung, breast, colon, ovary, and brain, but not from the stomach and liver. The current study focused on optimization of hollow fiber assays for gastric and hepatocellular carcinoma cell lines. MATERIALS AND METHODS: Gastric (SNU-16, SNU-484, SNU-668) and hepatocellular (HepG2, SK-Hep-1, Hep3B) carcinoma cell lines in hollow fibers were transplanted subcutaneously and intraperitoneally into mice, which were subsequently treated with a standard anticancer agent, paclitaxel. The hollow fiber activity of paclitaxel in each cell line was compared with the xenograft activity. RESULTS: Using optimized inoculation densities and schedules, treatment with paclitaxel was effective in gastric carcinoma cell lines, SNU-16 and SNU-484, but not in SNU-668. In the hollow fiber assays, paclitaxel was effective in hepatocellular carcinoma cell lines, HepG2 and SK-Hep-1, but not in Hep3B. Consistent with the results of the hollow fiber assay, SNU-16 and SNU-484, but not SNU-668, showed tumor regression, and HepG2 and SK-Hep-1, but not Hep3B, showed effective tumor responses following treatment with paclitaxel in xenograft models. When EW7197, a novel compound, and flavopiridol were tested in SNU-16 cells under optimized conditions, the hollow fiber activity showed good correlation with the xenograft activity of each compound. CONCLUSION: Our protocols may be useful for screening candidate small molecules that may exhibit activity against stomach and liver cancers, both of which are common in Korea.

Chylothorax in Gorham's Disease

A 25-yr-old woman presented with a right pleural effusion. Destruction of 9th through 12th ribs, adjacent vertebral bodies, and transverse processes was noted on plain radiograph and a large low-attenuated, irregular shaped mass lesion with peripheral rim enhancement, destroying vertebral body and transverse process, was revealed on the computed tomographic scan. Magnetic resonance imaging showed high signal on T1- weighted image and iso- and low signal on T2-weighted image for the mass lesion replacing the vertebral bony cortex and marrow space. An open rib biopsy revealed the histopathological changes of Gorham's disease (essential osteolysis), even though only bloody fluid filling the empty space and rib and vertebral transverse process destruction were grossly observed on operation. Even though there was no definite response to radiotherapy and pleurodesis, the patient showed stable condition up to 20 months after diagnosis.

A Phase II Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in 5- Fluorouracil-Pretreated Metastatic Colorectal Cancer / 대한암학회지

PURPOSE: To evaluate antitumor response, time to progression, and toxicities of oxaliplatin, 5- fluorouracil (5-FU), and leucovorin (LV) continuous infusion in patients with metastatic colorectal cancer who progressed during or after treatment with a 5-FU-containing regimen. MATERIALS AND METHODS: Forty-eight patients with metastatic colorectal cancer, who progressed while receiving or after discontinuing palliative chemotherapy with 5- FU-based regimen, were enrolled in this study. Treatment consisted of oxaliplatin (85 mg/m2 on day 1) as a 2-hour infusion followed by bolus 5-FU (400 mg/m2 on day 1), and 5-FU 48-hour infusion 2.4~3 g/m2 concurrently with LV 48-hour infusion 150 mg/m2, without mixing. Cycles were repeated at 2-week intervals. The dose of 5-FU was modified, depending on the hematologic toxicity profile. RESULTS: The objective response rate was 28% for 43 assessable patients (95% confidence interval, 14% to 42%), including one complete remission (2%). Seventeen additional patients (39%) had stable disease, and fourteen (33%) progressed. The median time to progression was 5.9 months and the median overall survival was 13.2 months from the start of the chemotherapy. From the 297 cycles analyzed, hematologic toxicities per course were: leukopenia; grade I 26.6%, grade II 3.4%, and grade III 0.3%, thrombocytopenia; grade I 10.8%, grade II 3.0%, grade III 1.0%, and grade IV 0.3%. The most frequent nonhematologic adverse reactions were nausea/vomiting and peripheral neuropathy, which were rated as WHO grade II in 13 patients (49%) and 11 patients (22%), respectively. CONCLUSION: This phase II study of oxaliplatin, 5-FU, and LV continuous infusion showed enhanced antitumor activity in patients with 5-FU-pretreated metastatic colorectal cancer. Overall toxicity was acceptable; neurotoxicity and bone marrow suppression constituted the dose-limiting side effects.

Prognostic factors of breast cancer in Koreans / 대한내과학회지

BACKGROUND: The aim of this study is to determine prognostic factors of breast cancer in Korean patients who underwent curative mastectomy. METHODS: Medical records of 181 patients who underwent curative mastectomy were reviewed. Relapse-free survival and overall survival were documented for each patient. Factors influencing survival were analyzed using Cox proportional hazard model. RESULTS: Overall 5-year survival rate was 82.0%, and 8-year survival rate was 74.7%. Multivariate analysis indicated that multiple axillary lymph node involvement (> or =4), postmenopausal status, and negative estrogen receptor were independent adverse prognostic factors. The adjusted relative risks of multiple axillary lymph node involvement (> or =4), postmenopausal status, and negative estrogen receptor were estimated 2.60 (95% Confidence Interval (CI): 1.28-5.30), 2.64 (95% CI: 1.46-4.79), and 2.27 (95% CI: 1.19-4.35), respectively. CONCLUSION: Multiple axillary lymph node involvement (> or =4), postmenopausal status, and negative estrogen receptor were independent adverse prognostic factors in Korean breast cancer patients after curative mastectomy.

Prognostic Factors of Gastrointestinal Leiomyosarcoma in Korea / 대한암학회지

PURPOSE: The clinicopathologic features and prognostic factors of gastrointestinal leiomyosarcoma have been a source of controversy. MATERIALS AND METHODS: A retrospective study was made of 91 incident cases of gastrointestinal leiomyosarcoma from 1979 to 1998 to identify clinicopathologic features and prognostic factors. RESULTS: The median age of study subjects was 56 years and 58.2% was male. Tumors consisted of 2 esophagus, 39 stomach, 38 small bowel, 12 large bowel leiomyosarcoma. Mean size of the tumors was 10.9 cm and 52.9% of them was larger than 10 cm. The tumors were classified as localized stage (42 cases), advanced stage (21 cases), and metastatic stage (28 cases). Again, the tumors were classified as low grade (48 cases) and high grade (18 cases). Median overall survival was 37.4 months and median disease-free survival was 28.2 months. In univariate analysis, the significant factors affecting the overall survival of patients with leiomyosarcoma were stage, size greater than 10 cm, performance status, and histologic grade. In multivariate analysis, stage, performance status, and histologic grade were independent factors affecting the overall survival. In univariate analysis, the significant factors affecting the disease-free survival were stage, performance status, and histologic grade. In multivariate analysis, histologic grade was the only independent factor affecting the disease-free survival. CONCLUSION: Stage, performance status, and histologic grade were independent factors affecting the overall survival. Histologic grade was independent factor affecting the disease-free survival.

The Long-term Effect of Induction Chemotherapy with All-trans-retinoic Acid(ATRA) Follwed by Consolidation Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia / 대한혈액학회지

No abstract available.

Patterns of the Recurrence of Breast Cancer in Korean Female Patients / 대한암학회지

PURPOSE: The major aim of this study is to evaluate the pattems of recurrence of breast cancer and to determine risk factom influencing the pattem. MATERIALS AND METHODS: Medical records of 322 female patients who underwent mastectomy from 1989 till 1992 were reviewed. Recurrence pattem and the length of survival after the first relapse of each relapsed patient were identified. Factors influencing the pattem of recurrence and the length of survival after relapse were analyzed using Cox proportional hazards model. RESULTS: Locoregional relapse was identified in the first failure sites of sixteen patients (5-year relapse rate, 5.7%). Risk of locoregional relapse was associated with the number of positive axillary lymph nodes [adjusted Relative Risk (aRR), 31.28 (95% Confidence Interval (CI), 6.81-143.77)]. The 5-year estimates of the first relapse at bone, lung, pleura, liver, and brain were 15.4%, 6.9%, 1.9%, 3.1%, and 0.8%, respectively. The multivariate analysis indicated that distant metastasis was associated with the number of positive axillary lymph nodes [aRR, 3.14 (95% CI, 1.56-6.32)] and with the age of 35 years and younger [aRR, 1.95 (95% CI, 1.01-3.75)]. The statistical association of negative estrogen receptor (ER) with distant relapse was borderline [aRR, 1.89 (95% CI, 0.99-3.61)]. Factors independently affecting the survival of relapsed patients were the pattem of metastasis and the disease-free interval. CONCLUSION: Bone metastasis was the most frequent pattem of first relapse in Korean breast cancer patients. The number of positive axillary lymph nodes, younger age, and negative ER were independent risk factors for distant relapse in Korean female breast cancer patients.

Patterns of the First Failure after Curative Resection of Gastric Cancer in Korean Female Patients / 대한암학회지

PURPOSE: The major aim of this study is to evaluate the patterns of recurrence of the stomach cancer after curative resection. MATERIALS AND METHODS: Patterns of the fimt failure and survival after relapse of 136 female gastric cancer patients who had received curative resection were evaluated. Factors influencing survival after relapse were analyzed using Cox proportional hazard model. RESULTS: Peritoneal relapse was the most common pattern of the first failure, with 3-year estimate of overall peritoneal relapse being 13.0%. The 3-year estimates of overall local- regional relapse, liver metastasis, and extraabdominal relapse were 11.2%, 4.8%, and 3.8%, respectively. Patients younger than 45 years developed peritoneal relapse at a significantly higher rate than patients aged 45-65 years (p 0.037). The most significant factor affecting the survival of relapsed patients was whether resection was performed for recurrent disease without remaining gross residual disease. Patterns of relapse did not significantly affect survival, but patients whose recurrences were limited to local-regional area tended to survive longer than those with extraaMominal component (p=0.067). CONCLUSION: Peritoneal relapse was the most common pattem and significantly associated with younger age after curative resection af gastric cancer of Korean female patients.

An Autopsied Case of Primary Pulmonary Hypertension

A twenty four-year-old female patient had suffered progressive dyspnea for 6 years until death. She denied any symptoms suggestive of connective tissue disease, or deep vein thrombosis. She suffered an episode of pontine infarct in 1995. Four years after diagnosis of primary pulmonary hypertension, she died of sudden death during hospitalization. Gross features of pulmonary arteries at autopsy were as follows: left main pulmonary artery showed dilation of the lumen and thickening of the wall, and right main pulmonary artery was markedly dilated and contained fresh thrombus. Hematoxylin and eosin-stained sections of lung tissue showed plexiform lesions of pulmonary arteries, complete luminal obliteration of pulmonary arterioles and dilated lesion of pulmonary arterioles, and capillaries. This patient represents a typical case with a primary pulmonary arteriopathy with plexiform lesions with thrombotic lesion, demonstrating the importance of thrombosis in situ in the pathogenesis of primary pulmonary hypertension. To our knowledge, this is the first autopsy report on the primary pulmonary hypertension in Korea.

Prognostic Factor Analysis of Aggressive Non - Hodgkin's Lymphoma Based on International Prognostic Index Model / 대한암학회지

PURPOSE: International Prognostic Index Model (IPIM) in aggressive non-Hodgkin's lymphoma was published and accepted generally as a better predictive model for prognosis. This study was undertaken to identify prognostic factors of aggressive non- Hodgkin's lymphoma and usefulness of IPIM in Korea. MATERIALS AND METHODS: Previously untreated, pathologically proven 226 aggressive non-Hodgkin's lymphoma patients who were treated with CHOP or COP-BLAM V between 1986 and 1995 in Seoul National University Hospital were evaluated for clinical features predictive of overall survival. RESULTS: Complete response (CR) was reached in 76% of all patients. With a median follow-up of 62 months, 5-year disease free survival of complete reponders was 67% and 5-year overall survival of all patients was 54%. In a univriate analysis, age, ECOG performance status, Ann Arbor stage, histologic subtype, bone marrow involvement, bulkiness, serum LDH level and number of extranodal involvement were significant prognostic factors for CR and survival (p<0.05). Of these, by multivariate analysis, age(RR 0.4, 95% CI 0.2~0.9) alone was a independent prognostic factor for CR. For disease free survival, no independent prognostic factor was found. For overall survival, Ann Arbor stage (RR 1.7, 95% CI 1.1~2.8), age (RR 1.7, 95% CI 1.1~2.6), Histologic subtype (RR 1.7, 95% CI 1.1~2.8), serum LDH level (RR 1.7, 95% CI 1.1~2.6) and bone marrow involvement (RR 1.8, 95% CI 1.0~3.1) were independent prognostic factors. According to risk group of IPIM, 5-year overall survival rate was 72% in low risk group, 46% in low intermediate risk group, 32% in high intermediate risk group, respectively, and median survival of high risk group was 12 months (RR 1, 2.3, 4.3, 6.4 respectively). CONCLUSION: IPIM is a useful model for identifying poor prognostic groups in aggressive non-Hodgkin's lymphoma.