A Randomized Controlled Trial for Chemoprevention of Gastric Cancer in High-risk Japanese Population; Study Design, Feasibility and Protocol Modification

We have initiated a population-based, double-blind, randomized controlled trial to examine the effects of supplementation of beta-carotene and vitamin C on the incidence of gastric cancer. The subjects were participants in an annual health screening program conducted by four municipalities in Akita prefecture, one of the regions with the highest mortality from gastric cancer in Japan. We measured their serum levels of pepsinogens (PGs) I and II, and asked persons diagnosed with chronic atrophic gastritis (defined as PGI < 70 ng/ml and PGI/PGII ratio <3.0) to take diet supplements containing 0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C for 5 years. During the first year of recruitment conducted in one village from June through September, 1995, 52% (635/1214) of screening participants had chronic atrophic gastritis and 73% (439/602) of eligible persons responded. However, in response to a National Cancer Institute press report released on January 18, 1996, indicating that two beta-carotene trials had shown no benefit and potential harm from the supplement, we discontinued the beta-carotene and continued with the trial using only vitamin C. Of 397 participants remaining at this point, 77% (305) consented to stay in the study. The results indicate that a randomized controlled trial for cancer prevention is feasible in the Japanese asymptomatic population.     

Effects of Three-month Oral Supplementation of β-Carotene and Vitamin C on Serum Concentrations of Carotenoids and Vitamins in Middle-aged Subjects: A Pilot Study for a Randomized Controlled Trial to Prevent Gastric Cancer in High-risk Japanese Population

Prior to a randomized controlled trial to prevent gastric cancer by oral supplementation of β-carotene and vitamin C in a high-risk Japanese population, we examined the serum response to threemonth oral supplementation of β-carotene (0, 3, 30 mg/day) and vitamin C (0, 50, 1000 mg/day) by a three-by-three factorial design using 54 subjects (age range=40–69 years). Serum concentrations of carotenoids, α-tocopherol, and ascorbic acid were examined at baseline, and one, two, and threemonth points. Both serum β-carotene and ascorbic acid were significantly higher in high-dose groups than in each placebo group during the supplementation. The serum β-carotene increased gradually (597–830% increase) during the study, whereas the serum ascorbic acid reached nearly a steady-state at the one-month point and remained stable thereafter (88–95% increase). No statistically significant interaction between β-carotene and vitamin C supplementations was observed either for serum β-carotene or for serum ascorbic acid. Among carotenoids and α-tocopherol examined, serum lycopene in the high-dose β-carotene group was significantly higher than in the placebo group at all points. No unfavorable change in carotenoids and α-tocopherol was observed in any group.     

Interventional Trial for Colorectal Cancer Prevention in Osaka: An Introduction to the Protocol

We established a protocol for an interventional randomized controlled trial for prevention of colorectal cancer by attaching special importance to feasibility. The subjects were patients with multiple colorectal tumors. Two regimens were formulated for prevention of colorectal cancer. One was dietary guidance alone (Regimen I), and the other was dietary guidance plus eating wheat bran biscuits (Regimen II). The main end points of the trial were examinations for recurrence of colorectal tumors after 2 and 4 years. The target number of patients was 200 in total, i.e. 100 for each group. During the 18 months from the beginning of recruiting of subjects (up to November 1994), 28 (97%) of the 29 patients recruited for Regimen I and 32 (97%) of the 33 patients recruited for Regimen II agreed to participate in the trial. The trial is progressing well.     

Survival after Laparoscopic versus Abdominal Radical Hysterectomy in Early Cervical Cancer: A Randomized Controlled Trial

Background: Previous studies have reported the safety of laparoscopic radical hysterectomy for treatment of early cervical cancer, as option to laparotomy. This study aims to compare overall survival between laparoscopic versus abdominal radical hysterectomy for early cervical cancer. Methods: A single-center randomized controlled trial enrolled 30 patients with clinically staged IA2 cervical cancer and lymphovascular invasion, IB and IIA, who underwent laparoscopic radical hysterectomy (16) or abdominal radical hysterectomy (14). Result: The mean overall survival time was 74.74 months (CI 95%: 54.15-95.33) for LRH 91.67 months (CI 95%: 74.97-108.37) for ARH (log-rank test = 0.30). The mean disease-free survival time was 81.07 months (CI 95%: 60.95-101.19) for LRH and 95.82 months (CI 95%: 80.18-111.47) for ARH (log-rank test = 0.371). The overall survival hazard ratio was 2.05 (CI 95%: 0.51-8.24), and the disease-free hazard ratio was 2.13 (CI 95%: 0.39-11.7). Conclusion: Our study suggests a non-significant trend of worse outcomes for LRH. In light of recent controversy and need for prospective studies, further studies in different populations are required for definite conclusions and until then, patients should be aware of risks and benefits, survival data and quality of life outcomes related to both surgical techniques.     

A Randomized Controlled Study of Integrated Smoking Cessation in a Lung Cancer Screening Program

IntroductionSmoking cessation activities incorporated into lung cancer screening programs have been broadly recommended, but studies to date have not shown increased quit rates associated with cessation programs in this setting. We aimed to determine the effectiveness of smoking cessation counseling in smokers presenting for lung cancer screening.MethodsThis study is a randomized control trial of an intensive telephone-based smoking cessation counseling intervention incorporating lung cancer screening results versus usual care (information pamphlet). All active smokers enrolled in the Alberta Lung Cancer Screening Study cohort were randomized on a 1:1 ratio with a primary endpoint of self-reported 30-day abstinence at 12 months.ResultsA total of 345 active smokers participating in the screening study were randomized to active smoking cessation counseling (n = 171) or control arm (n = 174). Thirty-day smoking abstinence at 12 months post-randomization was noted in 22 of 174 (12.6%) and 24 of 171 (14.0%) of participants in the control and intervention arms, respectively, a 1.4% difference (95% confidence interval: -5.9 to 8.7, p = 0.7). No statistically significant differences in 7-day or point abstinence were noted, nor were differences at 6 months or 24 months.ConclusionsA telephone-based smoking cessation counseling intervention incorporating lung cancer screening results did not result in increased 12-month cessation rates versus written information alone in unselected smokers undergoing lung cancer screening. Routine referral of all current smokers to counseling-based cessation programs may not improve long-term cessation in this patient cohort. Future studies should specifically focus on this subgroup of older long-term smokers to determine the optimal method of integrating smoking cessation with lung cancer screening (clinicaltrials.gov NCT02431962).     

Helicobacter pylori Screening to Prevent Gastric Cancer: anEconomical Analysis for a Tropical Developing Country

Gastric cancer is an important gastrointestinal carcinoma. Presently, it is accepted that the strongest etiologicalrelationship is with Helicobacter pylori infection. Screening for the bacterium thus becomes an issue for discussionin gastric cancer prevention. Here, the author covers the use of H. pylori screening as a strategy based on aneconomical analysis in the scenario of a tropical developing country.     

A Prospective Study of Atrophic Gastritis and Stomach Cancer Risk

The relation of atrophic gastritis, other gastric lesions and lifestyle factors to stomach cancer risk was prospectively studied among 3,914 subjects who underwent gastroscopic examination and responded to a questionnaire survey at the Aichi Cancer Center Hospital. During 4.4 years of follow-up on average, 45 incident cases of stomach cancer were identified at least three months after the initial examination. If the baseline endoscopic findings indicated the presence of atrophic gastritis, the risk of developing stomach cancer was increased 5.73-fold, compared with no indication at the baseline. The risk further increased with advancing degree of atrophy and increasing extension of atrophy on the lesser curvature. These trends in the relative risks were statistically significant ( P = 0.027 and P = 0.041, respectively). The risk of developing stomach cancer was statistically significantly increased among subjects with gastric polyps, but not among those with gastric ulcer. Stomach cancer cases tended to consume more cigarettes, alcohol, rice, pickles and salted fish gut/cod roe and less fruits and vegetables and to have more family histories of stomach cancer than noncases, although these differences were not statistically significant. The results of the present study provide additional evidence on the relation between atrophic gastritis and stomach cancer and suggest a need for intensive follow-up of patients with atrophic gastritis and gastric polyps.     

Barriers to Participation in a Randomized Controlled Trial of Qigong ExercisesAmongst Cancer Survivors: Lessons Learnt

Background: Clinical trials on cancer subjects have one of the highest dropout rates. Barriers to recruitmentrange from patient-related, through institutional-related to staff-related factors. This paper highlights the lowresponse rate and the recruitment barriers faced in our Qigong exercises trial. Materials and Method: The Qigongtrial is a three-arm trial with a priori power size of 114 patients for 80% power. The University Malaya MedicalCentre database showed a total of 1,933 patients from 2006-2010 and 751 patients met our inclusion criteria.These patients were approached via telephone interview. 131 out of 197 patients attended the trial and the finalresponse rate was 48% (n=95/197). Results: Multiple barriers were identified, and were regrouped as patientrelated,clinician-related and/or institutional related. A major consistent barrier was logistic difficulty relatedto transportation and car parking at the Medical Centre. Conclusions: All clinical trials must pay considerableattention to the recruitment process and it should even be piloted to identify potential barriers and facilitatorsto reduce attrition rate in trials.     

Antiemetic Efficacy of High-Dose Intravenous Metoclopramide and Dexamethasone in Patients Receiving Cisplatin-Based Chemotherapy: A Randomized Controlled Trial

High-dose intravenous (IV) metoclopramide has shown efficacywith few side effects for the treatment of nausea and vomitingon the day of cisplatin administration. From November 1984 toJanuary 1986, two randomized trials in an antiemetic study wereconducted. In trial I, the antiemetic effect of a short courseof high-dose dexamethasone was compared with that of high-dosemetoclopramide in 29 patients with lung cancer receiving chemotherapycon taining cisplatin (80 mg/m² IV) in a randomized controlledtrial. Dexamethasone was given IV at a dose of 16 mg 1/2 hrbefore and 8 mg, 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin.Metoclopramide was given IV at a dose of 2 mg/kg, 1/2 hr beforeand 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Major emeticcontrol (0–2 episodes of vomiting) during the 24 hr aftercisplatin administration was achieved in 55% (6/11) and 67%(12/18) of the patients receiving dexa methasone and metoclopramide,respectively, without serious toxicity. The dura tion of nauseaor anorexia was similar for the two treatment groups. In trial11, the combination of metoclopramide and dexamethasone wascompared with metoclopramide alone to assess the additive antiemeticeffect of the two drugs in 23 patients with lung cancer receivingcisplatin at a dose of 120 mg/m IV in a randomized cross-overstudy. A major antiemetic response was observed in 27% (3/11)and 92% (11/12) of the patients receiving metoclopramide aloneand metoclopramide plus dexamethasone, respectively (p <0.005). The duration of nausea and anorexia was similar forthe two treatment groups. Pa tients tended to prefer the combinationof metoclopramide and dexamethasone; however, the differencewas not statistically significant (p = 0.14) in the small numberof patients entered in this study. Despite excellent controlof acute chemotherapy-induced emesis, 45% of 52 patients experienceddelayed nausea and vomiting more than 24 hr after cisplatinadministration even among those who had had an excellent short-termresponse to the antiemetic agents.     

Feasibility of a Pilot Randomized Controlled Trial Examining a Multidimensional Intervention in Women with Gynecological Cancer at Risk of Lymphedema

There is limited knowledge on non-invasive lymphedema risk-reduction strategies for women with gynecological cancer. Understanding factors influencing the feasibility of randomized controlled trials (RCTs) can guide future research. Our objectives are to report on the design and feasibility of a pilot RCT examining a tailored multidimensional intervention in women treated for gynecological cancer at risk of lymphedema and to explore the preliminary effectiveness of the intervention on lymphedema incidence at 12 months. In this pilot single-blinded, parallel-group, multi-centre RCT, women with newly diagnosed gynecological cancer were randomized to receive post-operative compression stockings and individualized exercise education (intervention group: IG) or education on lymphedema risk-reduction alone (control group: CG). Rates of recruitment, retention and assessment completion were recorded. Intervention safety and feasibility were tracked by monitoring adverse events and adherence. Clinical outcomes were evaluated over 12 months: presence of lymphedema, circumferential and volume measures, body composition and quality of life. Fifty-one women were recruited and 36 received the assigned intervention. Rates of recruitment and 12-month retention were 47% and 78%, respectively. Two participants experienced post-operative cellulitis, prior to intervention delivery. At three and six months post-operatively, 67% and 63% of the IG used compression ≥42 h/week, while 56% engaged in ≥150 weekly minutes of moderate-vigorous exercise. The cumulative incidence of lymphedema at 12 months was 31% in the CG and 31.9% in the IG (p = 0.88). In affected participants, lymphedema developed after a median time of 3.2 months (range, 2.7–5.9) in the CG vs. 8.8 months (range, 2.9–11.8) in the IG. Conducting research trials exploring lymphedema risk-reduction strategies in gynecological cancer is feasible but challenging. A tailored intervention of compression and exercise is safe and feasible in this population and may delay the onset of lymphedema. Further research is warranted to establish the role of these strategies in reducing the risk of lymphedema for the gynecological cancer population.     

生长抑素对胃癌VEGFs和VEGF受体影响的实验研究

目的探讨VEGFs/VEGFRs与胃癌的恶化及不良预后的关系。方法将60例患者随机分成生长抑素预处理组和安慰剂组,采用酶联免疫法、实时定量PCR法和免疫组化法检测VEGF水平。结果生长抑素预处理组血清VEGF水平明显下降,但mRNA水平并无明显变化,并且血清VEGF水平下降是由于蛋白降解而非mRNA转录下降引起的。同时,预处理组VEGF受体-3蛋白明显下降。结论生长抑素通过下调血清VEGF水平和VEGF受体-3的表达,从而达到抗血管生成作用,为应用生长抑素治疗胃癌提供实验依据。     

The Role of GPs in Increasing Compliance to Colorectal Cancer Screening: A Randomised Controlled Trial (Italy)

Aims To assess the effect of the provider (GPs versus hospital) on the compliance in returning the faecal occult blood test. To analyse the characteristics of the GP associated with high compliance among his beneficiaries. Methods A questionnaire about screening attitudes was mailed to the 1192 GPs working in 13 districts of the Lazio region. We asked the GPs to participate in a randomised trial, we sampled 130 GPs and about 1/10 of the GPs’ 50–75 year old beneficiaries (n = 3657) were invited to be screened at the GP office and 1/10 (3675) at the nearest gastroenterology centre. Results 58.5% of the GPs completed the questionnaire and 22.7% agreed to participate in the trial. The compliance in the GP arm was 50%, in the hospital arm 16% (RR 3.4; 95% CI: 3.13–3.70). There was a high variability in the compliance obtained by the GPs. GPs with more than 25 patients visited/day and those incorrectly recommended screening of colorectal cancer obtained a lower compliance (OR 0.74, 95% CI: 0.57–0.95 and OR 0.76, 95% CI: 0.59–0.97, respectively). Conclusions The involvement of GPs in colorectal cancer screening can be very effective to enhance the compliance, but the effectiveness is dependent on their willingness to be involved.     

Manual Lymphatic Drainage for Breast Cancer-related Lymphedema: A Systematic Review and Meta-analysis of Randomized Controlled Trials

BackgroundThe purpose of this systematic review was to meta-analyze the effectiveness of manual lymphatic drainage (MLD) in breast cancer-related lymphedema (BCRL) patients.MethodsThe following databases: the Cochrane Library, the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Web of Science, ClinicalTrials.gov were systematically searched. All English publications before April 2021 have been retrieved without any restrictions of countries, time, or article type. We included randomized controlled trials (RCTs) examining the effectiveness of MLD versus control group without MLD of women with BCRL. The outcomes were (1) the incidence of lymphedema, (2) volumetric changes of lymphedema, (3) pain, (4) quality of life. Review Manager 5.3 was used to perform statistical analysis.ResultsIn total, 11 RCTs involving 1564 patients were included, in which 10 trials were deemed viable for inclusion in the meta-analysis. Due to the effects of MLD for BCRL, statistically significant improvements were found on the incidence of lymphedema (RR = 0.58, 95% CI [0.37, 0.93], P =.02) and pain intensity (SMD = -0.72, 95% CI [-1.34, -0.09], P = .02). Besides, the meta-analysis carried out implied that the effects that MLD had on volumetric changes of lymphedema and quality of life, were not statistically significant.ConclusionThe current evidence based on the RCTs shows that pain of BCRL patients undergoing MLD is significantly improved, while our findings do not support the use of MLD in improving volumetric of lymphedema and quality of life. Note that the effect of MLD for preventing BCRL is worthy of discussion.