Innovative method of alopecia treatment by autologous adipose-derived SVF.

BACKGROUND: Alopecia refers to a condition developed by gradual reduction of hair loss by various abnormal causes such as endocrine system, genetic factors, and stress. Stromal vascular fraction (SVF) isolated from the fat is one of the latest innovative solutions in the field of regeneration therapy. We focused on presenting effectiveness of clinical cases to improve AGA through transplantation of autologous SVF into the scalp. OBJECTIVE: To confirm the efficacy of the autologous SVF usage to the patients with AGA. METHODS: Nine patients (age range 43-64 years; 4 men, grade IV to V and 5 women, grade I to III), who are suffering from androgenic alopecia (AGA), were treated with single transplantation of autologous SVF in the upper scalp. Autologous SVF was isolated and characterized prior to the injection of live 7-9 × 106 cells into the patients' treatment site. The hair loss improvement effect was assessed by three test criteria: hair skin quality, hair thickness and hair density 3 and 6 months after post-injection compared to pre-injection status. RESULTS: Hair density of SVF-treated side was significantly increased after 3 and 6 months of transplantation compared to non-treated side (P = 0.01 and P = 0.009 per each). And significant improvement in the score of the keratin on the scalp was seen in the injected area as compared to the non-injected area 6 months after transplantation (P = 0.032). Although thickness increase was observed at 3 and 6 months after transplantation, there was no statistical significance (P = 0.142 and 0.155, respectively). CONCLUSIONS: One transplantation of autologous SVF for the AGA patients, hair density and score for the keratin were significantly increased within 6 months. This study shows that SVF is a very effective way to treat hair loss and most of subjects are satisfied with the result after treatment.

Endoscopic enucleation for gastric subepithelial tumors originating in the muscularis propria layer.

BACKGROUND: Subepithelial tumors (SETs) of the stomach are considered benign. However, they have the potential for malignant transformation, especially if they originate in the muscularis propria layer. This study aimed to determine the feasibility of endoscopic enucleation (EEN) for SETs in the muscularis propria layer and to evaluate the diagnostic efficacy and safety of EEN for SETs. METHODS: A total of 65 lesions in 64 patients were eligible for inclusion in the study during the period between June 2006 and September 2009. En bloc enucleation using an insulated-tip knife and snare was attempted for removal of gastric SETs from the muscularis propria. RESULTS: A total of 60 tumors were successfully resected by EEN (success rate, 92.3%). The mean tumor size, determined by endoscopic ultrasound, was 13.8 mm (range, 5-30 mm). A histologic diagnosis was obtained for 63 tumors (diagnostic yield, 96.9%), which was leiomyoma for 32 lesions, gastrointestinal stromal tumor for 26 tumors, and other for 5 tumors. The rate for complete resection in relation to the location of the lesion in the stomach was higher for the cardia, the mid/lower body (100%), and the high body (96%) than for the fundus (75%) or the antrum (50%, p=0.006). The rate of perforation was significantly higher for the fundus (50%) than for other locations (0% for the cardia and 4% for the high body) (p<0.001). CONCLUSIONS: Endoscopic enucleation of gastric SETs originating in the muscularis propria layer was a safe and effective method for the histologic diagnosis and removal of small gastric SETs, especially those located in the cardia and the high body of the stomach.

Successful outcomes of endoscopic resection for gastric adenomas and early cancers located on the pyloric ring (with video).

BACKGROUND: Endoscopic resection is difficult to perform in patients who have gastric neoplasms located on the pyloric ring, especially for lesions that extend from the pyloric area to the duodenal bulb, where it is difficult to retroflex the endoscope, and the risk of perforation is increased. OBJECTIVE: To assess the results of endoscopic resection of early gastric neoplasms located on the pyloric ring. DESIGN: Case series. SETTING: Tertiary-care referral center. PATIENTS: This study involved 16 patients with 5 gastric adenomas and 11 early cancers that were located on the pyloric ring. INTERVENTIONS: After a retroflexion trial within the duodenum for evaluation of tumor extension from the pyloric area to the duodenal bulb, en bloc resection was attempted. Endoscopic submucosal dissection was attempted at the duodenal bulb with an endoscope retroflexed for cases of duodenal invasion. MAIN OUTCOME MEASUREMENTS: The curative resection rate, en bloc resection rate, and complications were determined. RESULTS: The success rate of retroflexion within the duodenum was 88% (14 of 16). The curative resection rate was 81.3% (13 of 16), and the en bloc resection rate was 75% (12 of 16). En bloc resection was possible for 3 of 4 (75%) cases of duodenal bulb extension. Major procedure-related complications were not encountered. LIMITATIONS: Small number of patients. CONCLUSION: Endoscopic resection appears to be a feasible and effective treatment for early gastric neoplasms located on the pyloric ring, including lesions that extend from the pyloric area to the duodenal bulb.

Clinical usefulness of sequential hepatitis B virus DNA measurement (the roadmap concept) during adefovir treatment in lamivudine-resistant patients.

BACKGROUND: Sequential on-treatment monitoring of hepatitis B virus (HBV) DNA levels, known as the roadmap concept, might predict the efficacy of oral therapy with nucleoside/nucleotide analogues among patients naive to this treatment. The goal of this study was to verify the usefulness of the roadmap concept to predict clinical outcomes of adefovir dipivoxil monotherapy in hepatitis B e antigen (HBeAg)-positive patients with lamivudine resistance. METHODS: In 231 patients, serum HBeAg, antibody against HBeAg and HBV DNA levels were measured at weeks 12, 24 and 48 of treatment and every 3 months thereafter. RESULTS: Complete (HBV DNA<60 IU/ml by PCR), partial (HBV DNA 60-<2,000 IU/ml) and inadequate (HBV DNA> or =2,000 IU/ml) virological responses at week 24 were observed in 49 (21.2%), 66 (28.6%) and 116 (50.2%) lamivudine-resistant patients, respectively, who were treated with adefovir dipivoxil monotherapy. At final assessment, rates of complete virological response in these groups were 100%, 71.2%, and 22.4%. Of the total 42 virological breakthroughs, 33 (78.6%) and 8 (19.1%) developed in the inadequate and partial response groups, respectively. Among the 91 patients who had HBV DNA<200 IU/ml at week 48, complete virological response and HBeAg seroconversion were finally achieved in 87 (95.6%) and 39 (42.9%) patients, respectively. Of these 91 patients, virological breakthrough and genotype mutations developed in only 4 (4.4%) and 3 (3.3%) patients. The roadmap concept predicted virological response, HBeAg seroconversion and breakthrough (odds ratios 3.68, 9.67 and 0.15, respectively). CONCLUSIONS: The roadmap concept is useful for choosing between continuation of adefovir dipivoxil monotherapy or early switching to another therapy, or to suggest additional therapy in patients showing lamivudine resistance.

Is pancreatic core biopsy sufficient to diagnose autoimmune chronic pancreatitis?

OBJECTIVES: This study aimed to evaluate the adequacy of pancreatic core biopsy in histological diagnosis of autoimmune chronic pancreatitis (AIP). METHODS: Histopathologic study as well as immunohistochemical staining using anti-IgG4 antibody was done with pancreatic tissue specimens of 26 AIP patients (19 transabdominal ultrasound (US)-guided core biopsies, 3 intraoperative wedge biopsies, and 4 surgical resections). Eight patients with alcoholic chronic pancreatitis and 10 patients with pancreatic cancer served as controls. RESULTS: Lymphoplasmacytic sclerosing pancreatitis (LPSP) histology was observed in 26% (5/19) of US-guided core biopsy specimens, 33% (1/3) of open biopsy specimens, and all 4 resection specimens in AIP patients. None of the patients in the control group showed the full spectrum of changes of LPSP. Abundant IgG4-positive cells (>10 cells/high-power field) in the pancreas were observed in 21% (4/19) of AIP patients with US-guided core biopsy specimen. Abundant IgG4-positive cells in the pancreas were also observed in 2 of 8 patients with chronic alcoholic pancreatitis and 1 of 10 patients with pancreatic cancer. CONCLUSIONS: Transabdominal US-guided pancreatic core biopsy may not provide enough tissue to evaluate characteristic histopathologic features of AIP that include LPSP or abundant IgG4-positive cell infiltration. The LPSP histology may be specific to AIP, but abundant IgG4-positive cells in the pancreas may not.

Allelic alterations in well-differentiated neuroendocrine tumors (carcinoid tumors) identified by genome-wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors.

Well-differentiated neuroendocrine tumors (WDNT, carcinoid tumors) are uncommon indolent neoplasms. The genetic alterations of these tumors are not well characterized. We used genome-wide high-density single nucleotide polymorphism (SNP) array analysis to detect copy number alterations in 29 WDNTs, including seven lung, seven nonileal gastrointestinal, and 15 ileal tumors, and compared with allelic imbalances in 15 pancreatic endocrine tumors (PETs). Most frequent allelic imbalances in WDNTs were losses of chromosome 18 in 10 tumors (34%), chromosome 21 or 21q in six (21%), chromosome 13 or 13q in five (17%) and chromosome 16 or 16q in four (14%) tumors, and amplification of chromosome 20 or 20p in seven (24%) tumors. We also found one tumor with loss of heterozygosity of chromosomes 10 and 15 without copy number loss. These allelic imbalances were associated with primary site of tumor: loss of chromosome 18 was present exclusively in ileal WDNTs (P = 0.001), and loss of chromosome 21 or 21q was more frequent in nonileal gastrointestinal WDNTs (P = 0.02). The tumors with loss of chromosome 21 were larger compared to tumors without loss (P = 0.03). Chromosomal aberrations were less common in WDNTs from lung and gastrointestinal tract compared to PETs (P = 0.001). Our study shows that genome-wide allelotyping using SNP array is a powerful new tool for the analysis of allelic imbalances in WDNTs, and some of these alterations are tumor site-dependent and are different than in PETs.

Reactive oxygen species-dependent EndoG release mediates cisplatin-induced caspase-independent apoptosis in human head and neck squamous carcinoma cells.

Cisplatin is a chemotherapeutic agent that is widely used to treat cancers such as head and neck squamous cell carcinoma (HNSCC). Previously, we have reported that cisplatin induced an early caspase-dependent apoptosis (8 hr) in a HNSCC cell, HN4. In this study, we examined a late caspase-independent apoptosis as well as an early caspase-dependent apoptosis in cisplatin-treated HN4 cells. While z-VAD-fmk, a pan-caspase inhibitor, blocked the caspase activities and protected cells from the early apoptosis, it did not provide protection against delayed apoptosis occurring after extended exposure (16 hr) to cisplatin, suggesting that the delayed apoptotic response in the presence of z-VAD-fmk was caspase-independent. Cisplatin treatment induced reactive oxygen species (ROS) generation, loss of the mitochondrial membrane potential (MMP) and nuclear translocation of endonuclease G (EndoG). Small interfering RNA mediated-knockdown of EndoG significantly protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Overexpression of Bcl-2 in HN4 cells prevented loss of MMP, nuclear translocation of EndoG and protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, prevented both ROS generation, loss of the MMP and nuclear translocation of EndoG. Together, our data indicate that cisplatin treatment induced ROS-mediated loss of the MMP, and, then, the nuclear translocation of EndoG, which played a crucial role in caspase-independent apoptosis of HN4 cells in the presence of z-VAD-fmk. This is the first report about the involvement of EndoG in cisplatin-induced caspase-independent apoptosis of cells.

[Hemobilia from pancreatic arteriovenous malformation: successful treatment with transportal coil embolization of draining veins].

Pancreatic arteriovenous malformations (AVM) are extremely rare diseases frequently complicated by gastrointestinal hemorrhage. While surgical resection of affected lesion is preferred for the treatment of pancreatic AVM, angiographic intervention can be used as an alternative treatment, especially in surgically high-risk patients. We experienced a patient with pancreatic AVM manifested by hemobilia and biliary sepsis. Superior mesenteric and common hepatic arteriography showed pancreaticoduodenal AVM composed of nidus supplied by numerous fine feeding arteries and of draining veins encircling the common bile duct (CBD). Hemobilia was controlled by transportal coil embolization of draining veins of AVM around the CBD. Herein, we report this case with the review of literatures.

Allelic alterations in pancreatic endocrine tumors identified by genome-wide single nucleotide polymorphism analysis.

Pancreatic endocrine tumors (PETs) are uncommon and the genetic alterations in these indolent tumors are not well characterized. Chromosomal imbalances are frequent in tumors but PETs have not been studied by high-density single nucleotide polymorphism (SNP) array. We used genome-wide high-density SNP array analysis to detect copy number alterations using matched tumor and non-neoplastic tissue samples from 15 patients with PETs. In our study, whole or partial loss of chromosomes 1, 3, 11, 22 was present in 40, 47, 53, 40% of tumors respectively, and gain of chromosomes 5, 7, 12, 14, 17, and 20 was present in 47, 60, 47, 53, 53, and 47% of tumors respectively. One tumor had loss of heterozygosity of chromosome 3 and another of chromosome 22 without copy number alterations, suggesting uniparental disomy due to non-disjunction and deletion or to chromosomal recombination. Chromosomal aberrations of the autosomal chromosomes were correlated with chromosomal loss or gain of other chromosomes (r>0.5, P<0.5). About 60% of PETs had high allelic imbalances (AI) defined by more than four chromosomal aberrations, and 40% of tumors had low AI. The PETs with high AI were larger: the mean tumor size with high AI was 5.4 +/- 3.1 cm compared with 2.3 +/- 1.3 cm for low AI (P = 0.03). Our study shows that genome-wide allelotyping is a powerful new tool for the analysis of AI in PETs.

A gastrointestinal stromal tumor of the duodenum masquerading as a pancreatic head tumor.

Gastrointestinal stromal tumor (GIST) represents the most common kind of mesenchymal tumor that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor showing CD117 (c-kit protein) positivity at immunohistochemistry. Throughout the whole length of the gastrointestinal tract, GIST arises most commonly from the stomach followed by the small intestine, the colorectum, and the esophagus. Only 3%-5% of GISTs occur in the duodenum, and especially, if GIST arises from the C loop of the duodenum, it can be difficult to differentiate from the pancreas head mass because of its anatomical proximity. Here, we report a case of duodenal GIST, which was assessed as a pancreatic head tumor preoperatively.

[Clinical outcomes of lamivudine therapy in HBeAg positive chronic hepatitis B with minimally elevated ALT].

BACKGROUND/AIMS: The aim of this study was to compare the efficacy of lamivudine therapy between chronic hepatitis B (CHB) patients, whose ALT levels less than 2 times the upper limit of normal (ULN) and patients whose ALT levels are more than 2 times ULN. METHODS: We retrospectively analyzed 508 consecutive patients with HBeAg-positive CHB who were treated with lamivudine for 1 year or more. Forty-six patients (Group A) with pretreatment ALT levels less than 2 times ULN were retrospectively compared with 462 patients (Group B) whose ALT levels are more than 2 times ULN. RESULTS: HBeAg seroconversion was achieved in 15 (32.6%) of group A and 162 (35.1%) of group B. The cumulative rates of HBeAg seroconversion in group A and B were 19% and 21% at 12 months; 35% and 31% at 24 months; and 38% and 39% at 36 months, respectively. HBV breakthrough was observed in 20 (43.5%) of group A and 192 (41.6%) of group B. The cumulative breakthrough rates of group A and B were 18% and 12% at 12 months; 33% and 29 % at 18 months; 45% and 42% at 24 months, respectively. Post-treatment relapse in group A and B occurred in 56% (5/9) and 41% (44/108), respectively. Therefore, the rates of the HBeAg seroconversion, breakthrough, and post-treatment relapse were not significantly different between these two groups. CONCLUSIONS: Lamivudine therapy in HBeAg-positive CHB patients whose ALT levels are minimally elevated is as effective as in treatment of the patients whose pretreated ALT levels are twice more than ULN.

Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors).

Neuroendocrine tumors including carcinoid tumors and pancreatic endocrine tumors are uncommon, and the genetic alterations in these indolent tumors are not well characterized. We studied global hypomethylation by analyzing long interspersed nucleotide elements (LINE)-1 and Alu methylation using pyrosequencing in 35 neuroendocrine tumors and corresponding normal tissue. The tumor samples were less methylated than normal tissue at LINE-1 (P=0.04) and Alu (P=0.001). The mean relative tumor hypomethylation (difference in methylation between normal tissue and in tumor) was 11.5+/-10.0 for LINE-1 and 5.8+/-6.4 for Alu, and were correlated with each other (correlation coefficient 0.6, P=0.001). Relative tumor hypomethylation of LINE-1 was higher in ileal carcinoid tumors than in non-ileal carcinoid tumors and pancreatic endocrine tumors (P=0.047), and tumors with lymph node metastasis (P=0.02), chromosome 18 loss (P=0.001) and RAS-association domain family 1, isoform A gene methylation (P=0.02). Alu methylation in tumors was inversely correlated with methylation of O(6)-methyl-guanine methyltransferase gene (P=0.02). Our study shows that hypomethylation is more common in carcinoid tumors than in pancreatic endocrine tumors and is associated with clinicopathologic features, and genetic and epigenetic alterations in these tumors, including lymph node metastasis.

Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive.

AIM: To determine the changes of quantitative hepatitis B e antigen (HBeAg) that predicts early detection of non-response or breakthrough to long-term lamivudine (LAM) therapy. METHODS: Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 mo, we retrospectively analyzed 220 patients who had received LAM more than 24 mo. RESULTS: The mean duration of LAM therapy was 36 (range, 24-72) mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 (24.1%) patients. Viral breakthrough was observed in 105 (47.7%) patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy, we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively. Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg: decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict non-response or breakthrough was the first 9 mo of therapy. At 9 mo of therapy, 49 (92.5%) of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four (7.5%) had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 mo, 95.2% (negative predictive value) failed to achieve HBeAg seroconversion. CONCLUSION: Almost all patients who failed to show a continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore, monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.

Metastasis of hepatocellular carcinoma to the small bowel manifested by intussusception.

Hepatocellular carcinoma (HCC) is a highly invasive tumor that metastasizes hematogenously and lymphogenously to distant site. Frequent sites are lung, regional lymph node, bone, and adrenal gland. But metastasis to the gastrointestinal (GI) tract is rare, and most common site is stomach. Metastasis to the small intestine is extremely rare. Moreover, metastatic HCC of the small bowel causing intussusception has not been reported until now. Here, we report a case of metastasis of HCC to the small bowel manifested by intussusception.

A phase II study of docetaxel and cisplatin in patients with gastric cancer recurring after or progressing during 5-FU/platinum treatment.

BACKGROUND: Docetaxel plus cisplatin (DP) is a combination chemotherapy regimen that is active against untreated advanced gastric cancer. We evaluated the feasibility of DP treatment in patients with recurring or metastatic gastric cancer who had been previously treated with other chemotherapy regimens. PATIENTS AND METHODS: The DP regimen consisted of docetaxel (75 mg/m(2) i.v.) and cisplatin (60 mg/m(2) i.v.) over 1 h on Day 1 every 4 weeks for a maximum of nine cycles. RESULTS: Thirty-seven patients (28 men, 9 women; median age, 53 years; range 28-71 years) received a total of 128 cycles of therapy (median, 3; range 1-9). Twenty-six patients had recurrent disease and 11 had metastatic tumors. The objective response rate was 32.4% (95% confidence interval = 16.6-48.3%), including 1 complete response and 11 partial responses. Eleven had stable disease, whereas 12 had progressive disease. The median duration of response was 70.5 days (range 30-392 days). Grade 3/4 toxicities included anemia (10.8%), leukopenia (27.0%), neutropenia (51.4%), thrombocytopenia (2.7%), nausea/vomiting (5.4%) and oral mucositis (13.5%). Median time to progression was 136 days and median overall survival was 235 days. CONCLUSION: The DP combination was well tolerated and effective for patients with metastatic gastric cancer treated previously with 5-fluorouracil/platinum chemotherapy.

[A randomized, comparative study of rabeprazole vs. ranitidine maintenance therapies for reflux esophagitis--multicenter study].

BACKGROUND/AIMS: Reflux esophagitis is a recurring condition for which many patients require maintenance therapy. This comparative, randomized multicenter study was designed to evaluate the effect of long-term maintenance treatment comparing proton pump inhibitor, rabeprazole and H2 receptor antagonist, ranitidine. METHODS: Eighty four patients with healed reflux esophagitis confirmed by endoscopy were randomly allocated to receive maintenance treatment with either rabeprazole 10 mg once daily or ranitidine 300 mg once daily for 32 weeks. Patients were seen every 8 weeks or at symptomatic relapse. RESULTS: Of 84 initially treated patients, 73 entered the maintenance study. The percentage of asymptomatic patients after 90-day and 210-day treatment were 97% and 81.5%, for rabeprazole and 74.3% and 62.3%, for ranitidine, respectively. After 32 weeks, the relapse rates of esophagitis were 21.3% in the rabeprazole group and 62.9% in the ranitidine group (RR: 0.405, 95% CI: 0.215-0.766). CONCLUSIONS: Maintenance treatment with rabeprazole (10 mg once daily) is superior to ranitidine (300 mg once daily) in keeping the patients with reflux esophagitis in remission over a 32 week period.

Santorinicele containing a pancreatic duct stone in a patient with incomplete pancreas divisum.

Santorinicele, a focal cystic dilatation of the distal duct of Santorini, has been suggested as a possible cause of the relative stenosis of the accessory papilla, is associated with complete pancreas divisum, which results in acute episodes of pancreatitis or pain. This report describes a case of a santorinicele, which was initially detected by upper gastrointestinal endoscopy as a polypoid mass, in a patient with recurrent abdominal pain. The mass was subsequently proved to be a santorinicele containing a pancreatic duct stone associated with incomplete pancreas divisum on endoscopic retrograde pancreatography. To the best of our knowledge this is believed to be the first description of a santorinicele associated with these characteristic findings.

Duodenal duplicated cyst manifested by acute pancreatitis and obstructive jaundice in an elderly man.

A duodenal duplication cyst is an uncommon congenital anomaly that is usually encountered during infancy or in early childhood. Duodenal duplication cysts generally appear on the first or second portion of the duodenum and may cause duodenal obstruction, hemorrhage or pancreatitis. Here, we report a case of a duodenal duplication cyst on the second and third portion of the duodenum in an old aged man with obstructive jaundice and acute pancreatitis, which was treated successfully by a surgical excision.

Combination chemotherapy with 5-fluorouracil and heptaplatin as first-line treatment in patients with advanced gastric cancer.

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.

[Predictive factors and clinical outcome of viral breakthrough during lamivudine treatment for chronic hepatitis B infection].

BACKGROUND/AIMS: Long-term treatment with lamivudine causes breakthrough, but the clinical course after lamivudine breakthrough is not well known. The aims of this study were to evaluate the clinical course in lamivudine after breakthrough, and to identify predictive factors of breakthrough. METHODS: 124 patients with chronic hepatitis B infection, who represented viral breakthrough during lamivudine therapy, were included. The mean duration of lamivudine therapy and additional lamivudine therapy after breakthrough was 30.5 months and 12.5 months, respectively. RESULTS: The cumulative breakthrough rates at 12, 18, 24 and 36 months were 8, 24, 36 and 52%, respectively. After viral breakthrough, only 4 patients maintained normal ALT levels. 120 patients showed ALT elevation. The number of patients with ALT levels greater than 5 times, and greater than 10 times, the upper normal limit were 67 (56%) and 29 (24%), respectively. While still on lamivudine therapy after breakthrough, 98 patients presented ALT elevation. Only 22 had normalized ALT levels. Hepatic decompensation developed in 2 patients. HBeAg seroconversion after breakthrough occurred in 10 patients. The changing pattern of quantitative HBeAg levels during lamivudine therapy was the only predictive factor associated with viral breakthrough. The mean time of turning points in decrescendo-crescendo patterns of HBeAg levels during lamivudine therapy was earlier than viral breakthrough (9 months vs. 17 months). CONCLUSIONS: These results suggested that deterioration of hepatic function can usually be observed after breakthrough. The serial monitoring of serum quantitative HBeAg levels may allow an early recognition of viral breakthrough.