Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

BACKGROUND: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. PATIENTS AND METHODS: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). RESULTS: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. CONCLUSIONS: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.

GERD questionnaire for diagnosis of gastroesophageal reflux disease in systemic sclerosis.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is clinically-identified in patients with systemic sclerosis (SSc). The GERD-questionnaire (GERD-Q) score is a sensitive, non-invasive, diagnostic screening tool for diagnosis of GERD in general patients, but it has been not investigated for use in SSc. Our aim was to evaluate the proper cut-off GERD-Q score, sensitivity and specificity for a diagnosis of GERD in SSc patients. METHODS: A cross-sectional study using the GERD-Q was performed during May 2012-January 2013 on patients over 18 with the diffuse SSc subset. Both esophago-gastro-duodenoscopy (EGD) and 24-hr pH-monitoring (24hr-pH) were performed as the gold standard tests for both symptomatic and asymptomatic GERD. RESULTS: A total of 75 SSc patients completed the GERD-Q, EGD and 24hr-pH. We identified 22 males (29.3%), 53 females (70.7%) with a mean age of 54.2 years. The respective number of symptomatic and asymptomatic GERD was 69 and 6 cases. For a GERD diagnosis, a cut-off GERD-Q score of 4 provided the best balance between sensitivity and specificity (96.9% and 50%, respectively). Of 48 participants (69.6%) with symptomatic GERD (i.e. positive for both EGD and 24hr-pH), 65 (94.2%) were positive for either EGD or 24hr-pH, and 4 (5.8%) were negative for both EGD and 24hr-pH. A respective majority (83%) vs. one-third of the asymptomatic group had reflux as detected by 24hr-pH vs. EGD CONCLUSIONS: A GERD-Q score of 4 or higher indicates a high sensitivity for a diagnosis of GERD in SSc. It can thus be used as a non-invasive screening tool for diagnosing GERD in cases where EGD and 24hr-pH are unavailable.

Clinico-epidemiology of hepatitis C viral infection in northeastern Thailand.

Hepatitis C virus (HCV) is responsible for a large number of cases of chronic liver disease worldwide. A study of clinico-epidemiology of HCV infection was conducted in 214 patients who were seropositive for antibody to HCV (anti-HCV) in Srinagarind Hospital, Khon Kaen University, northeastern Thailand, during August 1997 to December 1998. There were 199 males, 15 females and their mean age was 34.96 +/- 9.75 years with a range from 16 to 72 years. The clinical features of acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC) and asymptomatic HCV infection were 2, 115, 15, 2 and 80 cases. Risk factors for HCV acquisition were intravenous drug use (IVDU), tattooing and blood transfusion in 46.7, 32.2 and 18.8% of cases, respectively. 23.36% had a history of multiple risk factors while 28.9% had no history of risk factor exposure.

Clinico-epidemiology of hepatitis B viral infection in Northeastern Thailand.

Hepatitis B viral (HBV) infection is a common disease world wide. A study of clinico-epidemiology of HBV infection was conducted in 381 patients who seropositive for hepatitis B surface antigen (HBsAg) in Srinagarind Hospital, Khon Kaen University, Northeastern Thailand, during August 1997 to December 1998. 293 males, 88 females and their mean age was 30.96 +/- 12.78 years with a range from 15 to 77 years. The clinical features of acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC) and asymptomatic carrier were 2.36, 34.12, 4.99, 1.05 and 57.48% of cases. Possible routes for HBV transmission were family history of hepatitis, tattooing, intravenous drug addict and blood transfusion in 20.3, 11.3, 8.2 and 6.9% of cases, respectively. Signs of chronic liver disease were common in liver cirrhosis and HCC. Acute fulminating hepatitis was not found in this study.

Comparison of adult somatic and excretory-secretory antigens in enzyme-linked immunosorbent assay for serodiagnosis of human infection with Fasciola gigantica.

Adult somatic antigen extract of Fasciola gigantica was compared with excretory-secretory (ES) antigen in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of human fascioliasis gigantica. The absorbance values in ELISA using the adult somatic antigen were not significantly different from the values obtaining using ES antigen (p > 0.05). The diagnostic sensitivity, specificity and positive and negative predictive values of the test using adult somatic extract as antigen were 100%, 98%, 70% and 100%, respectively. On the other hand, these values of the test using adult ES antigen were 100%, 99.3%, 87.5% and 100%, respectively. It appears that both somatic and ES antigens are effective antigens for use in the serodiagnosis of human fascioliasis gigantica.

Intestinal capillariasis: a cause of chronic diarrhea and hypoalbuminemia.

Seventeen cases of intestinal capillariasis in Srinagarind Hospital, Khon Kaen University, Thailand were reviewed. The mean age was 40.41 years with a range from 21 to 69 years. Most cases had intermittent or continuous voluminous watery diarrhea for one month to three years with hypoalbuminemia. Borborygmi, vague abdominal pain, weight loss and pedal edema were significant associated symptoms. Fecal examination was the most useful for diagnosis by finding the Capillaria philippinensis ova in all cases. Mebendazole 400 mg per day for 20 to 28 days is the treatment of choice. Usually, relapse and death are unusual, inadequate treatment is a major factor.

The study of discriminant values of dyspeptic symptoms for identifying the etiology of dyspepsia.

This prospective study aims to determine whether specific symptoms or group of symptoms could positively discriminate the etiology of patients who present with dyspepsia. Two hundred and eight patients were studied and 111, 55, 35 patients were classified as non-ulcer dyspepsia, peptic ulcer disease and hepatobiliary disease, respectively. All patients completed a structured history questionnaire by personal interview and completed investigation with complete blood count, stool examination, liver function test, HBsAg, HBsAb, ultrasonography of the abdomen and endoscopy. Variable of interest and variables of statistical significance by univariate analysis were put into discriminant function of logistic model for discrimination. The results suggest that anorexia and no periodicity of epigastric pain significantly discriminated non-ulcer dyspepsia from peptic ulcer disease and hepatobiliary disease, pain occurring before a meal or when the patient was hungry and nocturnal epigastric pain significantly discriminated peptic ulcer disease from hepatobiliary disease.