For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study ...were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy.
Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared.
In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different.
Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.
Introduction
Cerebral small vessel disease (SVD) is an important cause of dementia that lacks effective treatment. We evaluated the efficacy and safety of cilostazol, an antiplatelet agent with ...potential neurovascular protective effects, in slowing the progression of white matter hyperintensities (WMHs) in stroke‐ and dementia‐free subjects harboring confluent WMH on magnetic resonance imaging (MRI).
Methods
In this single‐center, randomized, double‐blind, placebo‐controlled study, we randomized stroke‐ and dementia‐free subjects with confluent WMHs to receive cilostazol or placebo for 2 years in a 1:1 ratio. The primary outcome was change in WMH volume over 2 years. Secondary outcomes were changes in brain volumes, lacunes, cerebral microbleeds, perivascular space, and alterations in white matter microstructural integrity, cognition, motor function, and mood.
Results
We recruited 120 subjects from October 27, 2014, to January 21, 2019. A total of 55 subjects in the cilostazol group and 54 subjects in the control group were included for intention‐to‐treat analysis. At 2‐year follow‐up, the changes in WMH volume were not statistically different between cilostazol treatment and placebo (0.3±1.0 mL vs −0.1±0.8 mL, p = 0.167). Secondary outcomes, bleeding and vascular events, were also not statistically different between the two groups.
Discussion
In this trial with stroke‐ and dementia‐free subjects with confluent WMHs, cilostazol did not impact WMH progression but demonstrated an acceptable safety profile. Future studies should address the treatment effects of cilostazol on subjects at different clinical stages of SVD.
Background
To study the epidemiology of chronic hepatitis C virus infection in Hong Kong and to estimate the service gap for achieving the WHO hepatitis elimination targets of attaining a diagnosis ...rate of 90%, treatment rate of 80% and 65% reduction in mortality rate by 2030.
Methods
From January 2005 to March 2017, patients who were tested positive for anti‐HCV were retrospectively retrieved from all public hospitals in Hong Kong. The epidemiological data of 15 participating hospitals were analysed.
Results
A total of 11 309 anti‐HCV+ patients were identified and the estimated diagnosis rate was 50.9%. Our HCV‐infected patients were ageing (median age 59). The all‐cause mortality rate increased from 26.2 to 54.8 per 1000 person‐years over the last decade. Our estimated treatment rate was 12.4%. Among the treated patients, 93.6% had received pegylated interferon/ribavirin (Peg‐IFN/RBV) but only 10.8% had received interferon‐free direct‐acting antivirals (DAAs). In a cohort of 1533 patients, 39% already had advanced liver fibrosis or cirrhosis. The sustained virological response rate for Peg‐IFN/RBV and DAAs were 74.8% and 97.2% respectively. However, more than 70% of patients were not subjected to interferon treatment for various reasons. Patients who achieved SVR were associated with a significantly lower risk of HCC (4.7% vs 9.6%, P = 0.005) and death (1.7% vs 23.8%, P < 0.001).
Conclusion
Our diagnosis rate, treatment rate and mortality rate reduction were still low, particularly the Peg‐IFN outcomes, making it difficult to meet the WHO hepatitis elimination targets. A more generalized use of DAAs is urgently needed to improve the situation.
See Editorial on Page 1902
Breast density notification laws, passed in 19 states as of October 2014, mandate that patients be informed of their breast density. The purpose of this study is to assess the impact of this ...legislation on radiology practices, including performance of breast cancer risk assessment and supplemental screening studies. A 20‐question anonymous web‐based survey was emailed to radiologists in the Society of Breast Imaging between August 2013 and March 2014. Statistical analysis was performed using Fisher's exact test. Around 121 radiologists from 110 facilities in 34 USA states and 1 Canadian site responded. About 50% (55/110) of facilities had breast density legislation, 36% of facilities (39/109) performed breast cancer risk assessment (one facility did not respond). Risk assessment was performed as a new task in response to density legislation in 40% (6/15) of facilities in states with notification laws. However, there was no significant difference in performing risk assessment between facilities in states with a law and those without (p < 0.831). In anticipation of breast density legislation, 33% (16/48), 6% (3/48), and 6% (3/48) of facilities in states with laws implemented handheld whole breast ultrasound (WBUS), automated WBUS, and tomosynthesis, respectively. The ratio of facilities offering handheld WBUS was significantly higher in states with a law than in states without (p < 0.001). In response to breast density legislation, more than 33% of facilities are offering supplemental screening with WBUS and tomosynthesis, and many are performing formal risk assessment for determining patient management.
The purpose of this Phase II study was to determine the response rate, the toxicity, and the effect on survival of the combination of cisplatin, doxorubicin, 5-fluorouracil, and alpha-IFN (PIAF) in ...advanced unresectable hepatocellular carcinoma. Fifty patients with either unresectable or metastatic disease were treated with PIAF: cisplatin (20 mg/m2 i.v., days 1-4), doxorubicin (40 mg/m2 i.v., day 1), 5-fluorouracil (400 mg/m2 i.v., days 1-4), and alpha-IFN (5 MU/m2 s.c., days 1-4). Treatment was repeated every 3 weeks to a maximum of six cycles. All patients were evaluable for response, toxicity, and survival. As assessed by conventional imaging criteria, there were no complete responses, but 13 patients (26%) had a partial response. Among the 36 patients who had an initially high alpha-fetoprotein level (>500 ng/ml), 15 (42%) had a >50% fall after therapy. Nine patients underwent surgical resection after achieving partial response and, in 4 of these patients, histological examination of the resected specimens revealed no viable tumor cells. All these nine patients are alive, and eight patients remain in complete remission at between 7.6 and 25.8 months at the time of analysis. The overall median survival was 8.9 months. Toxicity was mainly myelosuppression and mucositis. There were two treatment-related deaths due to neutropenic sepsis. PIAF is active in hepatocellular carcinoma despite considerable hematological toxicity. Complete pathological remission is possible with this systemic combination. Apparently, persistent radiological lesions may still represent complete pathological resolution of active disease.
Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) ...with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia.
A systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine.
The experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus.
These recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations.
•Management of hepatocellular carcinoma differs between Asia and Western regions.•Comprehensive Asian guidelines on selective internal radiation therapy are needed.•Consensus statements were developed using a 3-step modified Delphi method.•Statements are based on systematic literature review and expert consensus of ≥80%.•Statements are presented for use in treatment of hepatocellular carcinoma in Asia.
We reported here a series of 49 patients with unresectable hepatocellular carcinoma (HCC) who underwent nonsurgical treatment to downstage the disease followed by salvage surgery, their long-term ...outcome, and pattern of recurrence.
Most HCC patients present with unresectable disease and are treated with chemotherapy or intra-arterial therapy with a palliative intent. Occasionally, there are good responses to treatment so that salvage surgery becomes feasible afterward. However, long-term outcomes of these patients are seldom reported.
Patients with unresectable hepatocellular carcinoma, from September 1993 to June 2002, who received salvage surgery after downstaging by systemic chemotherapy, intra-arterial yttrium-90 microspheres, or sequential treatment were included in this study. Systemic chemotherapy consisted of combination doxorubicin, cisplatin, interferon-alpha and 5-fluorouracil (5-FU), or single-agent doxorubicin. The choice of treatment was according to stage of disease and contemporary clinical trial protocol. Survival, recurrence pattern, and surgical outcome were studied.
There were 49 patients in this study with 40 males and 9 females, age ranged from 12 to 69 years. Forty patients (81.6%) were hepatitis B positive. Thirty-two patients had combination chemotherapy alone (65.3%), 8 patients had single agent chemotherapy alone (16.3%), 4 patients received intra-arterial yttrium-90 microspheres alone (8.2%), and 5 patients received sequential therapy (10.2%). Twenty-eight (57.1%) patients received major hepatic resection. Thirteen patients (26.5%) had complete necrosis of the tumor after treatment. Twenty-one patients (42.9%) had recurrence after surgery, and 14 of them were intrahepatic recurrence. The median survival was 85.9 months. The 1-year, 3-year, and 5-year survival rates were 98%, 64%, and 57%, respectively.
Salvage surgery after successful downstaging can provide long-term control of disease in a small proportion of patients with unresectable hepatocellular carcinoma.
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