Definitive Chemoradiotherapy with Capecitabine and Cisplatin in Patients with Esophageal Cancer: A Pilot Study

We aimed to evaluate the feasibility of concurrent chemoradiotherapy (CRT) with capecitabine and cisplatin in patients with squamous cell carcinoma of the esophagus. Eighteen patients with esophageal cancer were enrolled on the study. The chemotherapy during CRT consisted of two cycles of intravenous cisplatin of 60 mg/ m2 on day 1 and oral capecitabine 825 mg/m2 twice daily from day 1 to 14 at 3-week intervals. The radiotherapy (2.0 Gy fraction/day to a total dose of 60 Gy) was delivered to the primary tumor site and regional lymph node. After concurrent CRT, 2 cycles of capecitabine (1,000 mg/m2 b.i.d from days 1 to 14) plus cisplatin (60 mg/m2 on day 1) were added every 3 weeks. All patients completed the planned treatment. After the chemoradiotherapy, 12 complete responses (CR, 66.7%) and 6 partial responses (PR, 33.3%) were confirmed. Grade 3 or 4 neutropenia only occurred in 2 patients, plus no treatment-related death was observed. At a median follow-up duration of 14.9 months, the estimated overall survival and progression-free survival rate at 2-yr was 70.7% and 54.4%, respectively. Concurrent CRT with capecitabine and cisplatin was found to be well-tolerated and effective in patients with esophageal cancer.

Salvage treatments with all-trans retinoic acid and arsenic trioxide-based regimens in acute promyelocytic leukemia / 대한내과학회지

BACKGROUND/AIMS: Acute promyelocytic leukemia is a distinct subtype of acute myeloid leukemia with a specific clinical and molecular presentation. Treatment of acute promyelocytic leukemia with all-trans retinoic acid or arsenic trioxide in association with anthracyclin has improved outcomes in this disease. We report the results of all-trans retinoic acid and arsenic trioxide-based treatment regimens in acute promyelocytic leukemia patients diagnosed in a single center. METHODS: Thirty-seven treatment events in 26 patients with acute promyelocytic leukemia were retrospectively reviewed. RESULTS: Complete remission was achieved in 29 (78.4%) of 37 treatment events. One-year overall survival rate and 1-year event-free survival rate were 74.3% and 66.3%, respectively. Among 16 patients treated with an arsenic trioxide-based regimen, 14 patients (87.5%) achieved complete remission. The 1-year overall survival rate and 1-year event-free survival rate were 78.4% and 69.6%, respectively. CONCLUSIONS: The short-term use of arsenic trioxide for salvage treatment of acute promyelocytic leukemia seems to be efficacious and could be a bridge to intensive chemotherapy or stem cell transplantation in terms of minimizing the risk of severe disseminated intravascular coagulation.

Association of Vascular Endothelial Growth Factor Gene Polymorphisms with Susceptibility and Clinicopathologic Characteristics of Colorectal Cancer

Since vascular endothelial growth factor (VEGF) is known to be a potent pro-angiogenic factor, we evaluated the potential association of two VEGF gene polymorphisms (-634G>C and 936C>T) with the susceptibility and the clinicopathologic characteristics of colorectal cancer (CRC). The VEGF genotypes were determined using fresh colorectal tissue from 465 patients who had undergone a surgical resection and peripheral blood lymphocytes from 413 healthy controls by PCR/DHPLC assay. For the -634G>C polymorphism, the -634 GC or CC genotype was associated with a decreased risk of CRC (odds ratio [OR], 0.62; p=0.001) as a dominant model of C allele, whereas the 936 TT genotype correlated with advanced stage/ metastasis, a high serum level of CA19-9, and an higher grade in patients with CRC. In the haplotype analyses, haplotype -634C/936C and -634G/936T were associated with a decreased susceptibility of CRC (OR, 0.53 and 0.56; p<0.001, respectively). These observations imply that the VEGF gene polymorphisms may be associated with the susceptibility or clinicopathologic features of CRC. However, further studies of other VEGF sequence variants and their biological functions are needed to understand the role of the VEGF gene polymorphisms in the development and progression of CRC.

Outpatient-basis Chemotherapy of Oxaliplatin, 5-fluorouracil, and Leucovorin as First-line Treatment for Patients with Metastatic or Recurrent Colorectal Cancer

The objectives of the present study were to evaluate the efficacy and safety of an outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as the first-line treatment for patients with advanced colorectal cancer. Forty-three histologically confirmed patients with metastatic or recurrent colorectal cancer were enrolled. The chemotherapy consisted of oxaliplatin 85 mg/m2 as a 2-hr infusion on day 1, plus leucovorin 30 mg/m2 over 10 min, followed by bolus 5-fluorouracil 400 mg/m2 and an 8-hr infusion of 5-fluorouracil 600 mg/m2 on days 1 and 2 (modified FOLFOX4), all of which were administered on an outpatient basis every 2 weeks. The median age was 58 yr (range 33-72 yr), and 25 (58.1%) patients had metastatic diseases. Eventually, 39 patients were assessable for efficacy and all assessable for toxicity. Four (9.3%) complete responses and 11 (25.6%) partial responses were confirmed, giving an overall response rate of 34.9% (95% CI; 20.0-49.7%). The median time to progression and median overall survival for all patients was 6.1 months and 17.4 months, respectively. Grade 3/4 neutropenia occurred in 2 patients (4.7%) and febrile neutropenia was observed in 1 patient (2.3%). Modified FOLFOX4, an outpatient-basis regimen, was found to be well-tolerated and effective as the firstline chemotherapy in patients with advanced colorectal cancer.

Impact of Day +11 Methotrexate on the Incidence of Graft-versus-host Disease after HLA-identical Allogeneic Peripheral Blood Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Cyclosporine (CSA) plus 4 doses of methotrexate (MTX) is the commonly used regimen for GVHD prophylaxis. It has been previously found that the omission of the day +11 dose of MTX was associated with an increased risk of acute GVHD in the allogeneic BMT setting. However, little is known about its impact in the PBSCT setting. METHODS: Of the 68 patients, 30 patients (44%) received 4 doses of MTX (the MTX4 group), while 38 patients (56%) received less than 4 doses (the MTX3 group) because of their severe mucositis, hepatic dysfunction or renal failure. RESULTS: The cumulative incidence of acute GVHD was 60% in the MTX4 and 86% in the MTX3 group (P=0.038), while that of grade III and IV acute GVHD was 7% in the MTX4 group and 39% in the MTX3 group (P=0.017). Of the 61 patients evaluated for chronic GVHD, the cumulative incidence of chronic GVHD was 54% in the MTX4 group and 97% in the MTX3 group (P=0.001), while that of extensive chronic GVHD was 26% in the MTX4 group and 63% in the MTX3 group (P=0.004). There were no differences in the overall survival and the incidence of relapse between the two groups. On multivariate analyses, MTX3 was a poor prognostic factor in terms of acute GVHD and extensive chronic GVHD. CONCLUSION: This study suggested that omitting day +11 MTX and the clinical situation of the MTX3 group seemed to be associated with an increased incidence of acute and chronic GVHD. Accordingly, administration of day +11 MTX accompanied by active treatment of mucositis may prevent GVHD in the allogeneic PBSCT setting, but we need to conduct a large scale prospective study.

Toxic Hepatitis Associated with Carp Juice Ingestion / 대한간학회지

The potential hepatotoxicity of herbal remedies and/or health foods is usually ignored in daily life. There have been cases showing the toxic hepatitis and renal failure associated with the ingestion of raw carp bile. We experienced a case of toxic hepatitis without any evidence of renal failure that was associated with carp juice ingestion. The clinical manifestations were characterized by nausea and vomiting after the ingestion of carp juice for 3 months. The diagnosis of toxic hepatitis was made on the basis of the patient's history, laboratory data, RUCAM (Russel Uclaf Causality Assessment) and the results of ultrasonography guided liver biopsy. The patient showed rapid improvement after instituting supportive therapy.

Acetaminophen-Induced Acute Liver Failure

Acetaminophen (AAP) is an antipyretic and analgesic agent, which is sold under many brand names including Tylenol. Although AAP rarely induces hepatotoxicity by an idiosyncratic mechanism, it is one of intrinsic hepatotoxins with a narrow therapeutic window. The overdose of AAP is the single most common cause of acute liver failure in the United States. In Korea, recent increase of working parents adds to the cause of overlooking children's AAP intoxication. Therapeutic dose of AAP is mostly converted to an inactive compound in the liver by conjugation with sulfate and glucuronide, with a small fraction (less than 5%) metabolized via the cytochrome P-450(CYP) system. The CYP enzymes oxidize AAP to produce a highly reactive metabolite: N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified in the liver by conjugation with hepatic glutathione (GSH). In case of AAP overdose a large amount of NAPQI depletes hepatic glutathione. Then the excess NAPQI binds to hepatocellular proteins, initiating cell death. The toxicity of AAP may be enhanced by agents that either increase the production of NAPQI or reduce the supply of GSH. N-acetylcysteine(NAC) replenishes hepatic GSH, thereby detoxifying NAPQI. Early administration of NAC minimizes the hepatotoxicity. In general the survival rate from AAP-induced acute liver failure has been increased with the use of NAC and liver transplantation.

Treatment outcomes of primary central nervous system lymphoma: Multi-center retrospective study / 대한내과학회지

BACKGROUND: A primary central nervous system lymphoma (PCNSL) is a rare neoplasm with a poor prognosis. The treatment of PCNSL involves a combination of chemotherapy, intrathecal chemotherapy and radiotherapy. This study retrospectively evaluated the treatment outcomes and prognostic factors of Korean patients with PCNSL. METHODS: Between 1995 and 2003, 58 patients diagnosed with PCNSL from the multi-center hospitals were enrolled in this study. Among 56 patients who had received treatment, 16 patients were treated with radiotherapy alone, while 40 patients were treated with combined chemotherapy (CHOP; 9 cases, high-dose methotrexate; 31 cases) and radiotherapy. RESULTS: The median age of the patients was 58 years (range, 19-76). A diffuse large B-cell lymphoma was diagnosed in 56 cases (96.6%), while a peripheral T-cell lymphoma was diagnosed in 2 cases. Of the 47 patients who could be assessed for their response after treatment, a CR and PR was observed in 32 (68%) and 11 patients (23%), respectively, giving an overall response rate of 91% (95% CI, 82~100%). The estimated 3-year overall survival rate for all the patients was 67+/-7.9% and the 3-year disease free survival rate was 53+/-8.3%. The overall survival of the high-dose methotrexate group was superior to that of the CHOP group (77+/-10% versus 47+/-19%, p=0.05). Leukoencephalopathy was observed as a late complication in 9 patients (21%). No significant prognostic factors affecting survival were found by univariate analysis. CONCLUSIONS: Approximately half of the patients could have long-term survival after treatment in this study. High-dose methotrexate containing chemotherapy followed by radiotherapy was found to be an effective treatment.

Acute Toxic Hepatitis: RUCAM Application to Drug-induced Liver Injury and Its Limitations / 대한간학회지

No abstract available.

Clinical and Biochemical Parameters of Nutrition to Predict Hepatic Encephalopathy in Cirrhotic Patients / 대한소화기학회지

BACKGROUND/AIMS: Protein-calorie malnutrition is a common complication in cirrhosis. Protein restriction for the treatment of hepatic encephalopathy (HE) may cause disease progression and poor prognosis. Therefore, we evaluated important clinical parameters for nutritional state in cirrhotic patients with or without HE to predict the development of HE. METHODS: Twenty-two cirrhotic patients were divided into two groups; group A-13 patients without HE and group B-9 patients with HE. Clinical and biochemical parameters, serum proteins {serum albumin, insulin-like growth factor-1 (IGF-1), transferrin, leptin, etc}, immunologic parameters and anthropometry were measured. RESULTS: Child-Pugh score and Model for End-stage Liver Disease (MELD) scale were higher in group B (p<0.01). After correction of various factors affecting nutritional assessment, especially of Child-Pugh score and MELD scale, leptin was higher in group B (p<0.05). There was no difference in anthropometric measurements. Transferrin correlated inversely with MELD scale in group A (p<0.01). IGF-1 correlated inversely with total lymphocyte count in group B (p<0.05). Leptin correlated with Child-Pugh scores, total lymphocyte count and mid-arm muscle cirumference in group A (p<0.05, p<0.05 and p<0.05, respectively), and correlated inversely with CD8 in group B (p<0.05). CONCLUSIONS: Leptin level is higher in patients with HE, and further studies for parameters of nutrition to predict HE in many cirrhotic patients will be needed.

Variable Number of Tandem Repeats (VNTR) Disparity between Donor and Recipient has a Potential to Predict the Outcomes of HLA-identical Allogeneic Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Detection of variable number of tandem repeats (VNTR) between recipient and donor has been adopted to monitor the degree of chimerism after allogeneic stem cell transplantation (SCT). In allogeneic SCT, besides MHC-disparity, the disparity of various polymorphous proteins encoded by several genes may play a critical role in the pathogenesis of graft-versus-host disease (GVHD). However, the biologic effect of VNTR disparity has been scarcely studied. METHODS: We analyzed 84 patients receiving SCT from HLA-identical sibling (n=68) or unrelated donors (n=16). Enrolled diseases included AML 48, ALL 8, CML 15, NHL 10, and high-risk MDS 3. The PCR was performed to amplify 3 VNTR regions (D1S80, D1S111, and D17S5). RESULTS: We observed strong correlation between the D1S80 disparity and transplant outcomes in terms of OS (P=0.0179) or non-relapse mortality (NRM) (P=0.0305), but not for D1S111 or D17S5 disparity. The D1S80-fully matched pair showed a better OS (72% vs 38%) and lower NRM (17% vs 50%) compared to partially matched or mismatched pairs. In multivariate analyses, D1S80-fully matched pair was found to be independent favorable prognostic factor for OS (P=0.03) or NRM (P=0.05). In addition, the D1S80 disparity was significantly associated with the myeloid engraftment speed (P=0.01) or the occurrence of gut chronic GVHD (P=0.05). CONCLUSION: Our data suggest that disparities in D1S80-located on chromosome1-seemed to be associated with increased incidence of gut chronic GVHD and NRMs, thus suggesting the existence of unknown genes of minor histocompatibility antigens targeting gut or cytokine/cytokine receptor on chromosome 1.

Docetaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer / 대한내과학회지

BACKGROUND: We evaluated the efficacy and toxicity of docetaxel plus cisplatin combination as first-line chemotherapy for advanced gastric cancer. METHODS: Patients with metastatic or recurrent gastric adenocarcinoma, performance score

Immunohistochemical Expression of Bcl-2, Bcl-xL, Bax, p53 Proteins in Gastric Adenoma and Adenocarcinoma / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to investigate the immunohistochemical expression of bcl-2, bcl-xL, bax, and p53 proteins according to the pathological parameters such as grade of dysplasia, histological type, depth of invasion, lymph node metastasis, and TNM stage in the gastric adenoma and gastric adenocarcinoma. METHODS: Immunohistochemical staining using monoclonal bcl-2, bcl-xL, bax, p53 antibodies were performed on paraffin embedded specimens from forty-one gastric adenomas and 100 gastric adenocarcinomas. RESULTS: The expression rate of bcl-2 was higher in adenomas (34.2%), especially in high grade dysplasia (52.4%), than adenocarcinomas (2.0%). The expression rate of bcl-xL was higher in adenocarcinomas (55.0%) than adenomas (22%). The expression rate of the bax was higher in adenocarcinomas (58.0%) than adenomas (14.6%). In the adenocarcinoma, the bax expression was significantly related with the depth of invasion, lymph node metastasis, and TNM stage. The expression rate of p53 was higher in adenocarcinomas (64.0%) than adenomas (14.6%). CONCLUSIONS: Bcl-2 protein would be related with the development of gastric adenoma, especially with high grade dysplasia. Bcl-xL and p53 proteins would be involved in the development of relatively early stage of gastric adenocarcinoma but not in tumor progression. Bax protein would be involved in the development of gastric adenocarcinoma and related with depth of invasion, lymph node metastasis, and TNM stage.

Do Natural Health Products Cause Toxic Hepatitis?

Medicinal herb-induced liver injury reported on the literature ranges from mild elevation of liver enzymes to fulminant liver failure and liver cirrhosis. Medicinal herbs are common ingredients of traditional Chinese herbs. The mechanisms of medicinal herb-induced liver injury are mainly intrinsic hepatotoxicity. In addition to the potential for hepatotoxicity, medicinal herbs frequently induce herb-drug interaction and herb-herb interaction and may affect its own efficacy and safety. Sometimes hepatotoxicity of medicinal herbs originates from the substances of illegal adulterations and contaminations rather than its own indigenous components. Moreover, individual susceptibility to toxic liver injury should be considered in every instance. Two big problems exist in the management of medicinal herbs-induced liver injury. Because the release of prescriptions is not obligatory in Korea, it is impossible to identify ingredients in case of medicinal herbsinduced liver injury. Misconception on the safety of medicinal herbs prevails throughout the country.

Medicinal Herbs and Toxic Hepatitis

Medicinal herb-induced liver injury reported on the literature ranges from mild elevation of liver enzymes to fulminant liver failure and liver cirrhosis. Medicinal herbs are common ingredients of traditional Chinese herbs. The mechanisms of medicinal herb-induced liver injury are mainly intrinsic hepatotoxicity. In addition to the potential for hepatotoxicity, medicinal herbs frequently induce herb-drug interaction and herb-herb interaction and may affect its own efficacy and safety. Sometimes hepatotoxicity of medicinal herbs originates from the substances of illegal adulterations and contaminations rather than its own indigenous components. Moreover, individual susceptibility to toxic liver injury should be considered in every instance. Two fundamental problems exist in the management of medicinal herbs-induced liver injury. One is a problem on the verification of herbal medicinal prescriptions, because the details of the herbal prescriptions are not usually disclosed to the public in Korea. Another one is a nation-wide prevailed misconception asserting natural products such as medicinal herbs are not harmful.

A Case of the Hepatocellular Carcinoma during the Pregnancy and Metastasis to the Left Atrium / 대한간학회지

A 28-year-old female with a pregnant state of 29th gestational week was admitted because of nausea and vomiting. MRI showed a huge hepatocellular carcinoma. At the 36th gestational week, a normal delivery was done. Surgery of hepatocellular carcinoma was done at 20 days after delivery. After 22 months from the operation, pulmonary metastasis was found and resection of lung mass was done. About 3 years after resection, a low attenuating nodule was detected in the left atrial chamber of heart. We report a case of hepatocellular carcinoma with metastatic lesions to lung and heart in a pregnant woman.

A Case of Lower GI Bleeding from Portal Hypertensive Colopathy Successfully Treated with Octreotide Administration and Endoscopic Hemoclipping / 대한소화기내시경학회지

Cirrhotic patients with portal hypertension are often found to have changes in their colonic mucosa. Such mucosal changes are termed portal hypertensive colopathy. Most patients with portal hypertension remained asymptomatic but some may show massive bleeding. The mainstay of treatment for portal hypertensive gastropathy include non-surgical methods such as octreotide injection, endoscopic hemostasis, and interventional methods such as TIPS. However, treatment for portal hypertensive colopathy remained unresolved. The authors here report a case of a 41 year old male with liver cirrhosis admitted for fever and abdominal pain, who reported an episode of hematochezia in the course of admisssion period. Subsequent colonoscopy revealed angiodysplasia-like lesions throughout the entire colon. We observed that such lesions were the source of hematochezia and that direct clipping with octreotide injection was successful in controlling the bleeding.

Herbal Preparation-induced Liver Injury / 대한소화기학회지

Recently the use of herbal preparations as remedies for various medical conditions, has been rapidly increasing in Korea. In our previous study, 38.9% of patients with chronic liver disease were found to use some sorts of herbal preparations. They believe herbal preparations are safe although the ingredients has never been rigorously substantiated. Toxicities of certain herbal preparations are caused by their contaminants and adulterated ingredients or concurrently used conventional drugs rather than specific components of the herbal preparations. Furthermore, in most instances, multiple herbal ingredients are used by the prescribers of oriental medicine. All of these conditions frequently impose diagnostic difficulties. There are myriads of plant-derived hepatotoxic substances which may or may not cause liver injury in individuals. The severity of liver injury depends largely on the toxicity of the substance, the amount of exposure and the individual's susceptibility. These toxic substances cause liver injury not only through the mechanism of intrinsic hepatotoxicity but also through the idiosyncrasy as in conventional drug-induced injury. Therefore, theoretically, it is possible to apply pre-existing CAMs (Causality Assessment Methods) to the assessment of causality in cases with diagnostic difficulties.

A Case of Gastric Lipoma with Early Gastric Cancer Removed by Subtotal Gastrectomy / 대한소화기내시경학회지

Gastric lipomas account for less than 3% of benign gastric tumor arising from the submucosal layer. Gastric lipomas are usually asymptomatic, but occasionally diagnosed from epigastric pain, obstruction and bleeding by their size and location. A 68-year-old female with melena was diagnosed as gastric lipoma, having a bleeding focus at endoscopy. Endoscopy with biopsy revealed a yellowish fat containing lipoma which was located prepyloric antrum and protruded to the duodenal lumen, and synchoronous adenocarcinoma which was located at the gastric angle and distal body. Adenocarcinoma was confined to the mucosa and seperated from lipoma by normal stomach tissue. The patient received Billroth-II subtotoal gastrectomy, and gastric lipoma and early gastric cancer were resected, completely.

A case of toxic hepatitis caused by the chinese diet food / 대한내과학회지

Recently over 500 victims with toxic hepatitis associated with some sort of Chinese diet food for weight reduction were developed in Japan, China, Singapore and Malaysia. These Chinese goods contain several kinds of Chinese herbs and fenfluramine, the well known anti-appetite drug. However, until today, it is not determined which component of the diet food is responsible for the hepatic injury. Nowadays, toxic hepatitis is frequently seen in daily practice, second only to viral origin in Korea. We present a 38-year-old woman who developed mixed cholestatic and hepatocellular injury after 5 week's ingestion of the Chinese diet food. The causality of this agent to the hepatotoxicity was assessed by RUCAM and M and V scale. Herein we described the clinical course and liver pathology of this patient.