Modified FOLFOX-4 as first-line and salvage treatment in advanced gastric cancer.

BACKGROUND/AIMS: Oxaliplatin, leucovorin and fluorouracil combination therapy (FOLFOX) was effective and safe treatment in AGC. The aim of this study was to evaluate the efficacy and safety of the modified FOLFOX-4 using low dose leucovorin for patients with advanced gastric cancer and analyze the efficacy of this regimen as first-line and salvage treatment. METHODOLOGY: Forty-two patients with recurrent or metastatic gastric cancer received oxaliplatin 85 mg/m2 and leucovorin 20 mg/m2 followed by 5-FU bolus 400 mg/m2 and then 5-FU 600 mg/m2 every 2 weeks. RESULTS: 1 (2.4%) complete response and 10 (23.8%) partial responses were observed. Stable disease and progressive disease were observed in 18 (42.9%) and 13 (30.9%). Median overall survival and progression free survival were 9.3 and 4.9 months. Among them, 26 (61.9%) and 16 (38.1%) of patients were treated as first-line and salvage treatment. Median overall survivals in the first-line and salvage treatment were 11.1 and 8.2 months respectively. And progression free survivals in first-line and salvage treatment were 6.0 and 4.7 month. Performance status was the only independent prognostic factor in overall survival in advanced gastric cancer. CONCLUSIONS: Our study showed modified FOLFOX-4 regimen had significant effects and favorable toxicities as first-line and salvage treatment for patients with advanced gastric cancer.

Expression of VEGF, EGFR, and IL-6 in gastric adenomas and adenocarcinomas by endoscopic submucosal dissection.

BACKGROUND: The degree of intratumoral microvascular density is thought to affect tumor metastasis and prognosis in various human cancers, including gastric cancer. Despite recent medical advancements, gastric adenoma or adenocarcinoma remains a considerable therapeutic challenge. Endoscopic submucosal dissection (ESD) is a more recent approach that is now commonly used for radical resection of gastric adenoma and adenocarcinoma. AIM AND METHODS: The expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and interleukin-6 (IL-6) are related to the prognosis of gastric adenocarcinoma. However, the expression of these factors in gastric adenoma/adenocarcinoma following ESD has not been clearly evaluated. Here, we report on our study of the expression of VEGF, EGFR, and IL-6 by immunohistochemical staining in extracted tissue from adenoma or adenocarcinoma of the stomach by ESD and subsequent evaluation of the correlation of VEGF, EGFR, and IL-6 with other clinicopathological parameters. The patient cohort consisted of 102 patients with adenoma or adenocarcinoma of the stomach. RESULTS: Immunohistochemical staining for VEGF and IL-6 was significantly higher in both high grade dysplasia and adenocarcinoma than in low grade dysplasia (P < 0.05). There was significant correlation between histological grade and intensity of immunohistochemical staining of VEGF (P = 0.039). Histological differentiation of adenocarcinoma was related to IL-6 expression (P = 0.028). The immunoreactivity of VEGF and IL-6 increased significantly in lesions >2 cm compared to lesions <2 cm (P < 0.05). CONCLUSION: The immunohistochemical expression of IL-6 and VEGF can be considered to be useful for clinical diagnosis and follow-up of adenoma or adenocarcinoma of the stomach.

[Clinical features of gas-forming liver abscesses: comparison between diabetic and nondiabetic patients].

BACKGROUND/AIMS: Patients with diabetes mellitus (DM) are more likely to have a pyogenic liver abscess with gas formation, which is associated with higher morbidity and mortality. The morbidity and mortality in pyogenic liver abscess are also higher in DM patients than in non-DM patients. This study evaluated the morbidity, mortality, and clinical features in patients with gas-forming liver abscesses associated with DM. METHODS: Among 379 cases of pyogenic liver abscess excluding malignancy from January 2001 through December 2009, 25 patients treated for pyogenic-gas-forming liver abscesses were reviewed retrospectively. We compared the morbidity, mortality, and clinical findings in patients with pyogenic-gas-forming liver abscesses between DM and non-DM patients. RESULTS: Gas formation was present in 25 (6.6%) of 379 cases with pyogenic liver abscess. DM was combined with gas-forming liver abscesses in 19 cases (76%). The most common organism responsible for the gas formation was Klebsiella pneumoniae (82%). Complications were present in 23 cases (92%) of gas-forming liver abscesses, with pulmonary complications (especially pleural effusion) being the most common (n=14, 61%). Four patients (16%) died of sepsis. CONCLUSIONS: Gas-forming liver abscesses are not uncommon in cases of pyogenic liver abscesses and are associated with high morbidity and mortality rates. The clinical manifestations and complications do not differ significantly between DM and non-DM patients.

[A case of autoimmune pancreatitis combined with extensive involvement of biliary tract].

Autoimmune pancreatitis is a distinct disease characterized by the presence of autoantibodies and hypergammaglobulinemia, inflammation of the pancreatic parenchyma, and irregular stricture of the pancreatic duct. The involvement of distal common bile duct is frequently observed, but intrahepatic bile duct involvement is very rare, which seem to have similar feature to primary sclerosing cholangitis. We report a case of the patient with autoimmune pancreatitis combined with extensive involvement of extrahepatic and intrahepatic bile duct, which had a favorable response to steroid therapy.

[Predictive significance of serum IL-6, VEGF, and CRP in gastric adenoma and mucosal carcinoma before endoscopic submucosal dissection].

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is commonly used for radical resection of gastric adenoma and mucosal cancer, but there is about 30% of discrepancy rate between the histology of the endoscopic biopsy and that of the resected specimen obtained from the same lesion by ESD. The aim of this study was to clarify the clinical significance of IL-6, VEGF, CRP before ESD. METHODS: We investigated the correlation between serum IL-6, VEGF, CRP level and discrepancy rate of gastric neoplastic lesions (10 low-grade dysplasias, 18 high-grade dysplasias, and 25 early gastic cancers). RESULTS: Serum levels of IL-6 in gastric adenoma and mucosal cancer patients were significantly higher than in healthy controls (p<0.05). Especially, serum IL-6 level of high-grade dysplasia patient was significantly higher than low-grade dysplasia and mucosal cancer patients, and the positive rate, sensitivity, and negative predictive value of serum IL-6 levels were higher in high-grade dysplasia patient compared to low-grade dysplasia patient and mucosal cancer patient. Serum levels of VEGF in patients with gastric adenoma and mucosal cancer were significantly higher than healthy controls (p<0.01). Serum levels of CRP in patients with mucosal cancer were significantly higher than in the controls (p<0.05), and the positive rate, sensitivity, and positive predictive value of serum CRP levels were higher in high-grade dysplasia and mucosal cancer patients compared to low-grade dysplasia patient. CONCLUSIONS: Serum levels of IL-6, VEGF, and CRP in patients with gastric neoplastic lesions were significantly higher than healthy controls, especially, serum IL-6 level of high grade dysplasia patient was significantly higher than low-grade dysplasia and mucosal cancer patients.

[Obstructive jaundice due to compression of the common bile duct by right hepatic artery originated from gastroduodenal artery].

Obstructive jaundice by vascular compression is rare. The causative arteries were identified as the right hepatic artery, gastroduodenal artery, cystic artery, proper hepatic artery, and an unspecified branch of the common hepatic artery. Also the venous system, such as enlarging collateral veins in cases of portal hypertension was a causative vessel. Herein, we describe a case of a proximal choledocholithiasis due to compression of the common bile duct by right hepatic artery originated from gastroduodenal artery. Final diagnosis and treatment were achieved through an operation.

[Clinical outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C].

BACKGROUND/AIMS: The purpose of this study is to elucidate the efficacy and safety of combined peginterferon and ribavirin therapy in Korean patients with chronic HCV infection. METHODS: We retrospectively analyzed the clinical records of 84 patients. Thirty five patients with genotype 1 HCV infection were treated with peginterferon alpha-2a 180 microg/week and ribavirin 1,000-1,200 mg/day for 48 weeks, and 49 patients with genotype non-1 were treated with peginterferon alpha-2a 180 microg/week and ribavirin 800 mg/day for 24 weeks. RESULTS: An early virologic response was seen in 87.0% of patients with genotype 1 HCV. An end of treatment response (ETR) was seen in 82.6% and 97.6% of patients with genotype 1 and genotype non-1, respectively. An overall sustained virologic response (SVR) was seen in 53 patients (82.8%) of the 64 patients: in 16 (69.6%) of 23 patients with genotype 1 and in 37 (90.2%) of 41 patients with genotype non-1. An end of treatment biochemical response was seen in 58 patients (90.6%) [genotype 1, 20 patients (87.0%); genotype non-1, 38 patients (92.7%)], and a sustained biochemical response was achieved in 49 patients (76.6%) [genotype 1, 14 patients (60.9%); genotype non-1, 35 patients (85.4%)]. Independent factors affecting an SVR were HCV genotype and the baseline HCV RNA level. CONCLUSIONS: This study shows that a combination therapy of peginterferon and ribavirin is highly effective for chronic HCV infection, producing a high SVR and ETR.

[Endoscopic submucosal dissection for early gastric cancer and gastric adenoma].

BACKGROUND/AIMS: Endoscopic Submucosal Dissection (ESD) is a new endoscopic mucosal resection (EMR) technique which enables en bloc resection even in large and depressed lesions. The aims of this study were to assess the therapeutic efficacy and the safety of ESD in gastric adenoma and in early gastric cancer (EGC). METHODS: We analyzed 101 lesions in 101 patients. ESD with insulated-tipped (IT) knife were performed in 52 adenomas and 49 EGCs from January 2003 to December 2005 in Dong-A University Hospital. RESULTS: The mean size of the lesion was 2.58 cm (0.7-4.5 cm). En bloc resection rate was 90.1% which was influenced by size (p0.05). Complete resection rate was 83.2% even in large or in malignant tumors (p0.05). Bleeding after ESD occurred in 41.6%. Tumor recurrence rate was 2.0%. CONCLUSIONS: ESD with IT knife is effective for the treatment of EGC and gastric adenoma even in large or in malignant lesions without definite increased risk of complications.

[Prognostic factors for survival in patients with hepatocellular carcinoma after radiofrequency ablation].

BACKGROUND/AIMS: Currently there is no consensus on which staging system is the best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify independent factors to predict survival and to compare 4 available prognostic staging systems in patients with early HCC after radiofrequency ablation. METHODS: We retrospectively studied 100 Korean patients with early HCC. Prognostic factors for survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, Cancer of the Liver Italian Program (CLIP), TNM and Japanese integrated staging score (JIS score) were evaluated before the treatments. RESULTS: Overall survival rates of 12, 24 and 36 months were 89%, 76%, and 64% respectively and the mean survival duration was 45 months. Multivariable analysis showed that albumin, total bilirubin and size of tumor were independent prognostic factors. Multivariate analysis showed that TNM and JIS score staging systems were significant staging systems for the prediction of prognosis. CONCLUSIONS: Both TNM and JIS score are more effective than the Okuda and CLIP staging systems in stratifying patients into different risk groups with early HCC. However, JIS score gives better prediction of prognosis in patients with HCC after radiofrequency ablation.

[A case of the treatment in an adult with hepatic undifferentiated (embryonal) sarcoma].

Undifferentiated embryonal sarcoma is a rare primary malignant neoplasm of the liver. Undifferentiated sarcoma of the liver in adult is an uncommon hepatic tumor of mesenchymal origin, generally considered an aggressive neoplasm with an unfavorable prognosis. We present a case of undifferentiated sarcoma in a 61-year-old woman. CT scan demonstrated a large heterogenous, exophytic growing hepatic mass in the right lobe with pulmonary metastatic nodules. US guided liver biopsy was done and pathological findings of the liver specimen revealed that isolated or grouped round pleomorphic cells and spindle to stellate cells were present. Immunohistochemical stain showed that tumor cells expressed positivity for vimentin and partially positivity or negativity for cytokeratin. She was diagnosed as having undifferentiated sarcoma of the liver. She received seven courses of VAIA chemotherapy by CWS protocols. Chemotherapy was efficacious and the size of the tumor decreased considerably after the treatment. No tumor recurrence for 12 months is noted.

[Evaluation of predictive value of Okuda, TNM, CLIP and JIS staging systems for hepatocellular carcinoma patients].

BACKGROUND/AIMS: The aims of this study were to validate the prognostic value of the JIS score for HCC and to compare discriminatory ability and predictive power with other staging systems such as Okuda, TNM and CLIP. METHODS: We analyzed the clinical records of 210 patients who were diagnosed as HCC from 2000 to 2002. Univariate and multivariate survival analyses were done to find out factors to affect survival. To validate prognostic value of those staging systems, survival curve was obtained and analyzed by the Kaplan-Meier's method, and to compare discriminatory ability and predictive power, Homogeneity LR X(2) test and AIC score were used. RESULTS: The median survival was 19.5 months (19.1+/-14.9). The number of patients and 3-year survival rate for those staging systems were Okuda 1(126, 57.7%), 2(63, 9.0%) and 3(21, 0.0%) (p<0.001); TNM I (34, 63.1%), II (71, 59.4%), III (50, 22.4%), IV-A (6, 14.3%) and IV-B (1, 6.5%) (p<0.001); CLIP 0 (79, 68.5%), 1 (39, 34.2%), 2 (36, 16.7%), 3 (25, 20.0%), 4 (18, 5.1%), 5 (9, 11.1%) and 6 (4, 0.0%) (p<0.001) and JIS 0 (26, 78.9%), 1 (65, 65.3%), 2 (43, 21.9%), 3 (40, 25, 8.0%) and 5 (11, 2.0%)(p<0.001) in univariate analysis using Kaplan-Meier analysis. Homogeneity LR X(2) test showed more stratification power in JIS (Okuda, 102.8; TNM, 128.2; CLIP, 148.4 and JIS, 185.6) and AIC score showed superior predictive power in JIS system (Okuda, 1228.5; TNM, 1130.3; CLIP, 1117.1 and JIS, 1093.6). CONCLUSIONS: The proposed JIS system is useful system to predict survival of HCC patients. The discriminate ability of the JIS score is much better than other staging systems and has better prognostic predictive power compared to other staging systems.

[A case of cavernoma of portal vein associated with polycythemia vera].

Cavernoma of the portal vein is defined as a formation of venous channels within or around a previously thrombosed portal vein. We experienced a 50-year-old woman who presented a huge hepatic mass with right upper quadrant dull pain. Abdominal computed tomography showed a huge sponge-like hepatic mass with cavernous transformation of portal vein along the common bile duct and common hepatic duct. She had increased hemoglobin/hematocrit (15.7 g/dL/49.1%) and red blood cell mass (35 mL/kg). Platelet count was 450,000/microL and white blood cell count was 13,500/microL. Erythropoietin level was low normal range (10.2 mU/mL). Bone marrow biopsy showed a moderately hypercellular marrow and overall cellularity was about 80-90%. Megakaryocytes were slightly increased in number with abnormal clusterings Myelopoiesis and erythropoiesis were also slightly increased with moderate to severe fibrosis. She was diagnosed as polycythemia vera with cavernous transformation of portal vein. Repeated thrombosis occurred in the leg and the toe and was treated with angioplasty and thrombolytic therapy with phlebotomy.

[Modified CLIP score as a new prognostic index for patients with hepatocellular carcinoma].

BACKGROUNDS/AIMS: The prognosis of cirrhotic patients with hepatocellular carcinoma (HCC) depends on both residual liver function and tumor characteristics. The aims of this study was to construct a new prognostic index for HCC patients: the modified CLIP score, and to compare its discriminatory ability and predictive power with those of the CLIP score that is currently the most commonly used integrated staging score in patients of HCC. METHODS: A retrospective analysis of 237 cases of HCC diagnosed at Dong-A university hospital was performed. Prognostic analysis was performed for single variables by estimating survival distributions with the Kaplan-Meier's method, and statistically compared by the log-rank test. RESULTS: Patients had a mean age of 57.5 years and were predominantly males (79.7%). The overall median survival period was 25.7 months. It was correlated to ascites, portal vein thrombosis, AFP, tumor size, and Child-Pugh classification. The median survival period was 41.0, 25.2, 13.8, 13.4, and 6.5 months for CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001), and 42.1, 34.0, 25.7, 14.0, and 6.8 months for modified CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001). The Kaplan-Meier's curve showed that the modified CLIP score had additional explanatory power above that of the CLIP score. CONCLUSIONS: The modified CLIP score, compared with the CLIP score, particularly in the score 2- to 3- patient groups of HCC, had greater discriminant ability and survival predictive power, but was not able to discriminate 4- to 6- patient group.

[Endoscopic injection treatment for gastric dieulafoy lesion in two newborn infants].

Dieulafoy lesion is an abnormally large calibered submucosal artery associated with a minute mucosal defect in the gastrointestinal mucosa. It is a rare cause of profuse, but intermittent gastrointestinal bleeding. The lesion is usually located in the stomach, although it may occur anywhere in the gastrointestinal tract. Dieulafoy lesion is extremely rare in the neonates. We report two newborn infants with a gastric Dieulafoy lesion which was treated by endoscopic epinephrine injection therapy without complication and recurrence.

[A case of giant gastric villous tumor with carcinomatous change].

Villous tumors of the stomach are somewhat rare with approximately 100 cases only reported in the literatures and have tendency to undergo malignant transformation as high as 72%. They are frequently multiple and associated with other gastrointestinal neoplasm. Thirty percent of them are associated with an independent gastric carcinoma. Gastric villous tumor has certain radiologic characteristics that may permit a preoperative diagnosis and also some distinctive clinicopathologic features which make early diagnosis and proper treatment possible. We experienced a 64-year-old man who complained of prolonged general weakness, weight loss for several months and left upper quadrant pain for four days. Esophagogastroduodenoscopy and barium study of upper gastrointestinal tract demonstrated typical, irregular, frond-like surfaced villous tumor occupying nearly whole gastric lumen and located eccentrically along the lesser curvature side. Endoscopic biopsy of the tumor revealed a gastric villous tumor with carcinomatous change.

[Prognostic factors and survival according to the Okuda stage in patients with hepatocellular carcinoma].

BACKGROUND/AIMS: There are several staging systems to decide the stage of hepatocellular carcinoma (HCC), but yet incomplete. Okuda stage which includes both tumor characteristics and liver function is widely used. The aims of this study were to assess the usefulness of known prognostic factors and Okuda staging system in 237 cases of HCC. METHODS: A retrospective analysis of 237 cases of HCC diagnosed from 2000 to 2002 was performed. We analyzed prognostic factors such as age, sex, liver cirrhosis, Child-Pugh classification, tumor size, albumin, bilirubin, alpha-FP, ascites, encephalopathy and Okuda stage. Prognostic analysis was performed for single variables and estimating survival distributions were analyzed by the Kaplan-Meier method, statistically compared by the log-rank test. RESULTS: Patients had a mean age of 57.5 years and were predominantly men (79.7%). Liver cirrhosis were noticed in 214 cases (90.3%). The overall median survival period was 25.7 months. The median survival period was correlated to bilirubin, ascites, alpha-FP, tumor size, and Child-Pugh classification, but not to age, sex, and pattern of viral infection. The median survival period of the Okuda stage I, II and III cases was 35.8, 11.9 and 8.5 months (p<0.001). CONCLUSIONS: The median survival period of patients with HCC is significantly correlated to Okuda staging system, and survival period has improved than the initial data when the Okuda staging system was published in 1985. However, in order to discriminate early staged HCC more accurately, other prognostic factors such as alpha-FP and tumor morphology should be included in future staging system for HCC.

[A case of Heyde's syndrome with abnormal von Willebrand factor].

A 68-year-old woman with known severe aortic stenosis was admitted to the hospital because of hematochezia and dizziness. She had received several blood transfusions over the preceding 3 years and undergone right hemicolectomy 2 years ago for severe lower gastrointestinal bleeding. Postoperative histology revealed angiodysplasia involving the ascending colon. After the hemicolectomy, she continued to have hematochezia and anemia and required additional blood transfusions for anemia. During this admission, platelet count, activated partial-thromboplastin time, von Willebrand factor antigen, and von Willebrand factor ristocetin cofactor were normal. She had a severe deficiency of high-molecular-weight multimers of von Willebrand factor. Colonoscopy showed angiodysplasia in the transverse colon at this time. Successful coagulation of the bleeding angiodysplasia was achieved by argon plasma coagulator. No additional bleeding was observed thereafter. We report a case of Heyde's syndrome with abnormal von Willebrand factor in a patient who presented with intestinal angiodysplasia and aortic stenosis.

Management of giant hepatic cysts in the laparoscopic era.

PURPOSE: We sought to evaluate the feasibility and outcomes of laparoscopic resection of giant hepatic cysts and surgical success, focusing on cyst recurrence. METHODS: From February 2004 to August 2011, 37 consecutive patients with symptomatic hepatic cysts were evaluated and treated at Dong-A University Hospital. Indications were simple cysts (n = 20), multiple cysts (n = 6), polycystic disease (n = 2), and cystadenoma (n = 9). RESULTS: The median patient age was 64 years, with a mean lesion diameter of 11.4 cm. The coincidence between preoperative imaging and final pathologic diagnosis was 54% and half (n = 19) of the cysts were located in segments VII and VIII. Twenty-two patients had American Society of Anesthesiologists (ASA) classification I and II, and nine had ASA classification III. Surgical treatment of hepatic cysts were open liver resection (n = 3), laparoscopic deroofing (n = 24), laparoscopic cyst excision (n = 4), laparoscopic left lateral sectionectomy (n = 2), hand assisted laparoscopic procedure (n = 2), and single port laparoscopic deroofing (n = 2). The mean fellow-up was 21 months, and six patients (16%) experienced radiographic-apparent recurrence. Reoperation due to recurrence was performed in two patients. Among the factors predicting recurrence, multivariate analysis revealed that interventional radiological procedures and pathologic diagnosis were statistically significant. CONCLUSION: Laparoscopic resection of giant hepatic cysts is a simple and effective method to relieve symptoms with minimal surgical trauma. Moreover, the recurrence is dependent on the type of pathology involved, and the sclerotherapy undertaken.

Prognostic significance of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in biliary tract cancer patients receiving adjuvant 5-fluorouracil-based chemotherapy.

Biliary tract cancer (BTC) is a relatively uncommon type of cancer, accounting for ∼4% of the malignant neoplasms of the gastrointestinal tract. The aim of this study was to determine whether the expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) predict clinical outcome in BTC patients treated with adjuvant 5-fluorouracil (5-FU)-based chemotherapy. TS and TP expression were found to be significantly correlated with cancer location (P=0.044 and 0.031, respectively). The multivariate analysis revealed that age [hazard ratio (HR)=2.157, P=0.008], stage (HR=2.234, P<0.001), resection margin status (HR=2.748, P=0.004) and TP expression (HR=2.014, P=0.039) were independently associated with overall survival (OS).

A case of synchronous esophagus and stomach cancer successfully treated by combined chemotherapy.

Although cases of simultaneous esophagus and stomach cancer have been reported sporadically, there are rare reports of successful treatment using chemotherapy. We report a case of synchronous esophageal and gastric cancer successfully treated using docetaxel and cis-diammineedichloro-platinum (CDDP) combination chemotherapy instead of surgery. A 82-years-old man with anorexia and progressive weight loss was diagnosed with synchronous esophageal and gastric cancer by endoscopy. Both cancers were diagnosed as resectable by the preoperative clinical staging. However, surgery was contraindicated because of severe lung dysfunction. Moreover, he actively refused radiotherapy and endoscopic management. Therefore, the patient was given combined chemotherapy with docetaxel (65 mg/m²) and CDDP (60 mg/m²). The esophageal and gastric lesion completely disappeared on endoscopy, and there were no residual tumor cells on endoscopic biopsy after three cycles of chemotherapy. Metastatic lymph nodes also completely disappeared on the CT scan. The patient received a total of ten cycles of chemotherapy, without severe adverse effects. The patient remained asymptomatic for 18 months after discontinuation of the chemotherapy, without evidence of local recurrence or distant metastasis. Surgery or endoscopic treatment of both esophageal and gastric cancers is desirable, but, if medically inoperable, chemotherapy can be alternative treatment option.