Background/Aims: Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods: This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results: This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. Conclusions In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

Antigen delivery systems play critical roles in determining the quality and quantity of Ab responses in vivo. Induction of protective antibodies by B cells is essential in the development of vaccines against infectious pathogens, whereas production of IgE antibodies is prerequisite for investigation of allergic responses, or type 1 hypersensitivity reactions. Viruslike particles (VLPs) are efficient platforms for expression of proteins of interest in highly repetitive manners, which grants strong Ab responses to target antigens. Here, we report that delivery of hen egg lysozyme (HEL), a model allergen, through VLP could provoke strong HEL specific IgE Ab responses in mice. Moreover, acute allergic responses were robustly induced in the mice sensitized with VLPs that express HEL, when challenged with recombinant HEL protein. Our data show that antigen delivery in the context of VLPs could function as a platform for sensitization of mice and for subsequent examination of allergic reactions to molecules of interest.

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.
Biphasic Insulins ; Body Weight ; Diabetes Mellitus, Type 2 ; Drug Toxicity ; Fasting ; Glucose ; Hemoglobins ; Humans ; Incidence ; Insulin ; Insulin Aspart ; Insulin, Isophane ; Insulin, Long-Acting ; Patient Selection ; Plasma ; Quality of Life ; Republic of Korea ; Treatment Outcome ; Insulin Detemir

A 46-year-old diabetic woman visited our hospital with generalized edema and high blood pressure. An appropriately sized noninvasive blood pressure cuff was placed on her right arm above the elbow to measure blood pressure. While we were checking her blood pressure, we noticed small red petechial spots distal to the cuff involving her entire right forearm. Her blood pressure was 170/96 mmHg. The laboratory findings showed no abnormality of anticoagulation. The rest of the patient's extremities were not affected. The petechiae on the right arm resolved spontaneously after ten days. The most likely explanation for these petechiae is acute dermal capillaryrupture, which is called the Rumpel- Leede phenomenon. Acute dermal capillary rupture appears as petechiae in an area following application of vascular constriction such as application of tourniquet to draw blood specimen or use of blood pressure cuff due to capillary fragility or abnormal platelets in numbers or in function. This situation has been reported previously in the literature as the Rumpel-Leede phenomenon in association with prolonged noninvasive BP monitoring. In the patient described herein, increased venous pressure from blood pressure measurement and capillary fragility associated with diabetes mellitus may have increased the risk of acute dermal capillary rupture.
Arm ; Blood Platelets ; Blood Pressure ; Capillaries ; Capillary Fragility ; Constriction ; Diabetes Mellitus ; Diabetic Nephropathies ; Edema ; Elbow ; Extremities ; Female ; Forearm ; Humans ; Hypertension ; Middle Aged ; Purpura ; Rupture ; Tourniquets ; Venous Pressure

PURPOSE: Although surgical resection is the most effective treatment for hepatocellular carcinoma (HCC), high recurrence after resection is a major challenging problem. We attempted to determine the optimal strategies for improving the long-term surgical outcome through the review of our 10 years' experience with surgically treating HCC. METHODS: We retrospectively reviewed 497 patients who received curative resection at the Yonsei University Health System from January 1996 to August 2006. RESULTS: The 5 year disease-free rate and the overall survival rate after curative resection were 45.0% and 63.9%, respectively. Of the 497 patients, 491 (98.8%) were Child-Pugh A and 107 (56.3%) were diagnosed with liver cirrhosis. The postoperative complication and mortality rates were 28.6% and 1.8%, respectively. Of the 243 recurrent patients, 184 (75.7%) were diagnosed with intrahepatic recurrence alone. Of these intrahepatic recurrent patients, 169 (91.9%) received active treatment, including transplantation (n=7), re-resection (n=12), local ablation therapy (n=18) and transarterial chemoembolization (n=132). Multivariate analysis revealed that perioperative transfusion, a satellite nodule, the pathologic TNM stage, the Edmondsons-Steiner grade, the serum alkaline phosphatase (ALP) and aspartate aminotransferase levels and cirrhosis were associated with disease free survival, and perioperative transfusion, a satellite nodule, macroscopic vascular invasion, the Edmondsons-Steiner grade, the ALP and serum albumin levels and the platelet count were related with overall survival after resection. CONCLUSIONS: The long-term surgical outcome of HCC can be further improved by proper patient selection, delicately performed surgery and administering postoperative adjuvant therapy for patients with a high risk of recurrence. Early diagnosis and aggressive treatment are needed to treat the recurrence
Alkaline Phosphatase ; Aspartate Aminotransferases ; Carcinoma, Hepatocellular ; Disease-Free Survival ; Early Diagnosis ; Fibrosis ; Humans ; Liver Cirrhosis ; Multivariate Analysis ; Patient Selection ; Platelet Count ; Postoperative Complications ; Recurrence ; Retrospective Studies ; Serum Albumin ; Survival Rate ; Transplants

PURPOSE: Recent studies have reported improved perioperative and long-term outcomes for the initial postoperative results for patients with a huge HCC. The purpose of this study was to investigate the surgical outcomes of patients with a huge HCC and we wanted to identify any subgroup that would likely benefit from hepatic resection. METHODS: From January 1996 to August 2006, 55 patients were diagnosed with a huge HCC (> or = 10cm in diameter). All the tumors were classified as either the expanding nodular type or the non- expanding nodular type. RESULTS: The mean age of the patients was 50.6 years and 39 patients were male. The most common cause of liver disease was hepatitis B virus. The mean size of tumor was 11.9 cm. Microscopic liver cirrhosis was present in 17 patients. Twenty-three patients had tumors of the expanding nodular type. Curative resection was performed in 50 patients. The 5-year diseasefree and overall survival rates after resection were 35.8% and 41.0%, respectively. Univariate analysis revealed that surgical margins of < or = 1.0, a non-curative resection, the non-expanding nodular type and microscopic vascular invasion were adverse prognostic factors for survival. Multivariate analysis indicated that the gross tumor classification (expanding nodular vs. nonexpanding nodular) was the only independent prognostic factor. CONCLUSIONS: Huge HCC is not a homogenous group and the gross tumor pattern may represent the biologic behavior of huge HCC. Because the outcome of surgical treatment is far better than that of non-surgical treatment, resection should be actively considered for patients with a huge HCC. An expanding nodular type tumor is the best candidate for surgical resection.
Carcinoma, Hepatocellular ; Hepatitis B virus ; Humans ; Liver Cirrhosis ; Liver Diseases ; Male ; Multivariate Analysis ; Prognosis ; Survival Rate

BACKGROUND: Protease-activated receptor 2 (PAR2) belongs to a family of G protein- coupled receptors activated by proteolytic cleavage. Trypsin-like serine proteases interact with PAR2 expressed by a variety of tissues and immune cells. The aim of our study was to investigate whether PAR2 stimulation can lead to the activation of human macrophages. METHODS: PAR2-mediated proliferation of human macrophage cell line THP-1 was measured with MTT assay. We also examined the extracellular regulated kinase (ERK) phosphorylation and cytokine production induced by trypsin and PAR2-agonist using western blot and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Treatment of trypsin or PAR2-activating peptide increased cell proliferation in a dose-dependent manner, and induced the activation of ERK1/2 in THP-1 cells. In addition, trypsin-induced cell proliferation was inhibited by pretreatment of an ERK inhibitor (PD98059) or trypsin inhibitor (SBTI). Moreover, PAR2 activation by trypsin increased the secretion of TNF-alpha in THP-1 cells. CONCLUSION: There results suggest that PAR2 activation by trypsin-like serine proteases can induce cell proliferation through the activation of ERK in human macrophage and that PAR2 may play a crucial role in the cell proliferation and cytokine secretion induced by trypsin-like serine proteases.
Blotting, Western ; Cell Line* ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Humans* ; Macrophages* ; Phosphorylation ; Phosphotransferases ; Receptor, PAR-2* ; Serine Proteases ; Trypsin ; Tumor Necrosis Factor-alpha

BACKGROUND: Renal dysfunction occurs in up to 75% of patients with liver cirrhosis and is a major cause for mortality and morbidity. Hyperbilirubinemia, hepatic encephalopathy, spontaneous bacterial peritonitis and underlying renal insufficiency have been reported as risk factors for renal dysfunction in patients with liver cirrhosis, but further evaluations are still being required. METHODS: We retrospectively analized 91 liver cirrhosis patients hospitalized at Severance Hospital between Jan 1, 1996 and Dec 31, 2001 who had normal renal function at admission. RESULTS: Forty-four patients were enrolled in renal dysfunction group and forty-seven patients in control group. There were no significant differences between two groups in age, cause for liver cirrhosis, presence of diabetes mellitus, history of aminoglycoside treatment, serum albumin level, and prothrombin time. The incidence of ascites (95% vs. 47%), hepatic encephalopathy (66% vs. 17%), bacteremia (38% vs. 4%), urinary tract infection (16% vs. 2%), spontaneous bacterial peritonitis (30% vs. 6%), and upper gastrointestinal bleeding (25% vs. 9%) were significantly high in renal dysfunction group, compared to control group (p<0.05). In renal dysfunction group, the level of total bilirubin (9.1+/-8.3 mg/dL vs. 3.5+/-6.2 mg/dL) was also much higher than control group. Multiple logistic regression analysis showed ascites, hepatic encephalopathy, and bacteremia as independent risk factors for renal dysfunction. CONCLUSION: Ascites, hepatic encephalopathy, and bacteremia are postulated to be risk factors for renal dysfunction in liver cirrhosis patients. Renal function and urine output should be cautiously monitored in liver cirrhosis patients with these risk factors.
Ascites ; Bacteremia ; Bilirubin ; Diabetes Mellitus ; Hemorrhage ; Hepatic Encephalopathy ; Humans ; Hyperbilirubinemia ; Incidence ; Liver Cirrhosis* ; Liver* ; Logistic Models ; Mortality ; Peritonitis ; Prothrombin Time ; Renal Insufficiency ; Retrospective Studies ; Risk Factors* ; Serum Albumin ; Urinary Tract Infections

BACKGROUND: Local anesthetics combined with an opiate are frequently used as a postoperative epidural PCA regimen. Ropivacaine is known to have a selective blockade of the sensory nerve without motor blockade. This study is designed to show advantages of ropivacaine over bupivacaine. METHODS: Patients undergoing elective abdominal and orthopedic surgeries were randomly selected and divided into two groups, B and R. The patients in group B and R received 0.2% bupivacaine and 0.2% ropivacaine respectively through an epidural catheter using a PCA pump. Both local anesthetic solutions were mixed with 4 microgram/ml of fentanyl. The PCA pumps of both groups were set in the same manner. A basal rate of 2 ml/hr was infused from 1hour after the onset of surgery. This basal rate was continued postoperatively. A bolus dose and lock out time were set at 2 ml and 20 minutes respectively. The Visual analogue pain scale (VAS), demand dose, complication and additional intramuscular analgesic requirements were checked up to 24 hours after surgery in 6-hour interval. RESULTS: The VAS was significantly lower in group R than in group B at 6, 12, 18 and 24 hours after the surgery (P < 0.05). Total additional bolus doses of the PCA pump were not significantly different in either group at 6, 12, 18 and 24 hours after surgery. The patients in group R showed more satisfaction and less additional intramuscular injections. CONCLUSIONS: 0.2% Ropivacaine, mixed with 4microgram/ml of fentanyl, was more effective than bupivacaine, mixed with the same concentration of fentanyl, in controlling postoperative pain using an epidural PCA pump.
Analgesia ; Analgesia, Patient-Controlled* ; Anesthetics, Local ; Bupivacaine* ; Catheters ; Fentanyl ; Humans ; Injections, Intramuscular ; Orthopedics ; Pain Measurement ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis

Pachydermoperiostosis is a rare hereditary syndrome characterized by finger clubbing, periosteal new bone formation of tubular bones, and hypertrophic skin changes (pachydermia). This syndrome is known to be associated with a variety of diseases such as cranial suture defect, female escuchen, bone marrow failure and autonomic nervous system symptoms such as facial flushing and hyperhidrosis. There are just a few reports documenting gastric ulcer, hypertrophic gastropathy and Crohn's disease as associated diseases. A case is herein reported of pachydermoperiostosis accompanied by hypertrophic gastropathy and early gastric cancer.
Autonomic Nervous System ; Bone Marrow ; Cranial Sutures ; Crohn Disease ; Female ; Fingers ; Flushing ; Humans ; Hyperhidrosis ; Osteoarthropathy, Primary Hypertrophic* ; Osteogenesis ; Skin ; Stomach Neoplasms* ; Stomach Ulcer