A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial)

PurposeIntraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate.MethodsThis study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.DiscussionThis is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy. We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03975179","term_id":"NCT03975179"}}NCT03975179; Clinical Research Information Service Identifier: KCT0004606     

Efficacy and durability of hyaluronic acid fillers for malar enhancement: A prospective,randomized, split-face clinical controlled trial

Various hyaluronic acid fillers can be used for facial attenuation and rejuvenation. The efficacy and durability of hyaluronic acid fillers are of major concern to dermatologists and patients. This study aimed to evaluate three-dimensional morphology, tissue distribution, and changes in volume after injection of two different hyaluronic acid fillers. Ten Korean women were enrolled in this study. Each subject was injected with monophasic hyaluronic acid filler in one malar area and biphasic filler in the other. Clinical outcome was measured before and after injection, and after 2, 4, 6, 8, 12, and 24 weeks, using the Global Aesthetic Improvement Scale, photographs and Moire’s topography. Facial magnetic resonance imaging (MRI) was performed twice over six months. Both products showed good results after injection and demonstrated good durability over time. MRI was a useful modality for assessing tissue distribution and volume changes. The effects and durability after injection of monophasic hyaluronic acid filler and biphasic hyaluronic acid filler are generally comparable.     

A retrospective analysis of re‐exploration after living donor right lobe liver transplantation: incidence,causes, outcomes,and risk factors

Despite technical difficulties, right lobe liver grafting is preferred in living donor liver transplantation because of the graft size. Re‐exploration after living donor right lobe liver transplantation (LRLT) has never been separately analyzed. We aimed to analyze the incidence, causes, outcomes, and risk factors of re‐exploration after LRLT. We reviewed medical records of 1016 LRLT recipients from October 2003 to July 2017 and identified recipients who underwent re‐exploration within hospital stay. Separate analyses were also performed according to cause of re‐exploration. The overall incidence of re‐exploration was 17.0% (173/1016). The most common cause of re‐exploration was bleeding (50%). Overall re‐exploration was associated with clinical outcome, but different results were shown on analyses according to cause of re‐exploration. Risk factors of re‐exploration were underlying hepatocellular carcinoma and operative duration [Odds ratio (OR), 1.49; 95% confidence interval (CI), 1.05–2.12; P = 0.03, and OR, 1.002; 95% CI, 1.001–1.004; P = 0.0023, respectively]. Re‐exploration after LRLT is relatively common, and is strongly associated with mortality and graft failure.     

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy

Background:

With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy.

Methods:

The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed.

Results:

From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14% P=0.04), and less severe hepatitis (0 vs 17% P=0.002).

Conclusion:

Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.     

Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in Asian patients

Background and Aims: A single nucleotide polymorphism near the interleukin‐28B (IL28B) gene has been shown to predict hepatitis C virus (HCV) treatment response. We aim to determine the role of the IL28B genotype in Asian patients. Methods: A total of 118 patients (all Korean, 55 patients with genotype 1 infection and 63 patients with genotype 2 infection) were consecutively enrolled and analyzed. Results: The sustained virological response (SVR) rate was 74% (87/118), while 26 patients (22%) relapsed and five patients were non‐responders (4%). For rs8099917, the frequencies of major homozygotes (TT), heterozygotes (GT), and minor homozygotes (GG) were 0.85, 0.14 and 0.01, respectively. Of the 55 patients with HCV genotype 1 infection, the SVR rate was 67% and 44% (P = 0.19) and the non‐response rate was 2% and 22% (P = 0.015) for the major allele and minor or hetero allele, respectively. Of the 63 patients with HCV genotype 2 infection, the SVR rate was 80% and 100% (P = 0.13) and the non‐response rate was 4% and 0% (P = 0.55) for major allele and hetero allele, respectively. Conclusions: The IL28B genotype may help identify non‐responding patients in HCV genotype 1, but not in HCV genotype 2. Because of the high frequency of favorable alleles and the low frequency of non‐response, the IL28B polymorphism may play a smaller role in Asian patients.     

Efficacy of peg-interferon-α-2a plus ribavirin for patients aged 60 years and older with chronic hepatitis C in Korea

Background and Aim: In the present study, we evaluated the safety and efficacy of combination therapy with pegylated interferon and ribavirin for treating chronic hepatitis C (CHC) patients aged 60 years and older. Methods: A total of 314 CHC patients, who were treated with combination therapy, were classified into three groups according to age: (i) younger than 50 years (n = 137); (ii) 50–59 years (n = 109); and (iii) 60 years or older (n = 68). The sustained virological response (SVR) and discontinuation rates were compared between the three groups. Results: Discontinuation of therapy due to adverse event was more frequent in the older patient groups: 1%, 5%, and 10% for the < 50‐year, the 50–59‐year, and the ≥ 60‐year patient groups, respectively (P = 0.018). However, the older patient groups showed a SVR rate that was comparable to the SVR rates of the other age groups: 80%, 73%, and 75% for the < 50‐year, 50–59‐year, and ≥ 60‐year‐ patient groups, respectively (P = 0.420). A multivariate analysis showed that the aspartate aminotransferase : platelet ratio index (APRI) was an independent predictor of an SVR. An SVR was achieved in 95% (19/20) of the elderly patients with an APRI < 0.80. Conclusions: Although physicians must pay more attention to adverse events in the older patients, combination therapy can be considered for older patients, especially for patients with a low APRI.     

Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4

Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.     

Survey of the application of the korean clinical practice recommendations on breast cancer treatment: the utility of the korean breast cancer society guidelines

This survey was performed to analyze the usability of the third edition of the Korean breast cancer clinical practice guidelines (KBCCPG) in clinical practice. We made a questionnaire composed of 18 general and 82 specific questions regarding benign breast disease (B; 1 question); non-invasive disease (N; 12 questions); early-stage disease (E; 26 questions); advanced disease (A; 24 questions); and metastatic (M) breast cancer-related problems (19 questions). A total of 100 questionnaires, with a link to an online survey, were delivered via e-mail to over 700 members of the Korean Breast Cancer Society (KBCS), and associated academy members, over 20 days between 26th February and 16th May 2010. Out of 270 respondents who read the e-mail, 96 answered the questionnaire. Participants included 87 surgical oncologists, 5 radiation oncologists, 2 oncoplastic surgeons, 1 pathologist, and 1 medical oncologist. The third KBCCPG were perceived as differing from the second guidelines in terms of the level of clinical evidence required before choosing a recommendation. For the progress of the KBCCPG, the guideline committee should try to reinforce all courses of guideline development with several elements including data from clinical trials of Korean breast cancer patients, securing a multidisciplinary approach, developing consistent and reasonable processes for each step of the revision of the guidelines, induction of liberal scientific and ethical discussion about all issues with all KBCS members. The cost-effectiveness of healthcare and the logical development of the KBCCPG would also be ensured. Timely updates of the clinical guidelines for breast cancer treatment are essential to facilitate optimal decision-making in daily practice, and to ensure adequate patient feedback.