[Early diagnosis and early treatment for liver cancer in Qidong: survival of patients and effectiveness of screening].

Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B, respectively, with significant differences between two groups (P<0.05). Conclusion: The findings show that screening of individuals at high-risk of development of liver cancer, with semiannual AFP and B ultrasound, according to the Expert Scheme, is effective not only in increasing detection rate but also in detecting liver cancer at early stage, and in improving patients' survival as well.

Cytomegalovirus immediate-early promoter efficiently drives heterogeneous gene expression in Spodoptera frugiperda (Sf9) insect cells.

Recently, wide attention has been given to the potential of recombinant baculovirus as a gene transfer vehicle for mammalian gene therapy. In this study, we packaged the recombinant baculoviruses with cytomegalovirus immediate-early (CMV-IE) promoter in Spodoptera frugiperda (Sf9) insect cells, and found that the CMV-IE promoter could efficiently drive the exogenic gene expression in the cells 12 h post-infection (h.p.i.). The expression level at 72 h.p.i. was only around half of that driven by polyhedrin promoter (Ppolh). However, the biological activity of the reporter proteins at 72 h.p.i. were similar with that driven by Ppolh. In addition, the Sf9 cells transfected with CMV-IE-containing plasmids also expressed foreign genes, suggesting that the CMV-IE-directed heterogeneous gene expression in the Sf9 cells was baculovirus-independent. These results demonstrate that the CMV-IE promoter might be used as a regular promoter in Sf9 cells.

Results of carbon ion radiotherapy for skin carcinomas in 45 patients.

UNLABELLED: BACKGROUND; Heavy ions represent the best tool for external radiotherapy (RT) of inoperable tumours. Heavy ion RT has been used in the treatment of various tumours, especially for radioresistant tumours mediated by hypoxia, localized near organs at risk. Most of these treatments are concentrated in deep-seated tumours such as those of the brain, head, lung, liver, rectum and urogenital organs, and treatment of skin carcinomas is limited. OBJECTIVES: To evaluate the outcome and toxicity after carbon ion RT for skin carcinomas at the Heavy Ion Research Facility in Lanzhou, China. METHODS: Between November 2006 and March 2009, 45 patients with skin carcinoma [squamous cell carcinoma (SCC) (n = 16), basal cell carcinoma (BCC) (n = 12), malignant melanoma (MM) (n = 7), Bowen disease (n = 8) and Paget disease (n = 2)] were treated with carbon ion RT within a clinical Phase I trial. Patients received total doses of 60-70 GyE for SCC and BCC, 61-75 GyE for MM, 60 GyE for Bowen disease and 42·5 GyE for Paget disease, administered in 6-11 fractions over 6-11 days, with a fraction dose of 7-10 GyE. RESULTS: The mean follow-up was 24 months, range 12-36 months. The actuarial local control rates at 1 and 3 years were 90·9% and 65·5% for SCC, 91·7% and 80·2% for BCC, 85·7% and 42·9% for MM, 90% and 90% for Bowen and Paget diseases, respectively. The actuarial 1- and 3-year overall survival rates for 45 patients were 88·9% and 86%, respectively. No severe side-effects greater than Common Toxicity Criteria grade 3 have been observed. CONCLUSIONS: The results demonstrated that heavy ion RT offers high local tumour control and progression-free survival rates without significant radiation-induced toxicity for patients with skin carcinomas.

[The establishment of Ting Hsien Experimental Project of Rural Health Service and its influence].

Founded by the Chinese Mass Education Movement (MEM) led by Dr.James Yen and Peking Union Medical College(PUMC), the Ting Hsien Experimental Project was a demonstration program for health service in a rural county. Through a 8-year endeavor (1929-1937) and using a bottom-up approach, Dr. Chen Chih-chien and Dr.YaoHsun-yuan took the leadership of a group of dedicated PUMC graduates and students, and created a three-level(village-district-county) system to deliver both curative as well as preventive medical service for rural population. This project, under the full support of MEM and Dr. John Black Grant, Director of the Department of Public Health of PUMC, offered an important example for rural community health care in contemporary China. Moreover, it demonstrated and inspired the concepts of the primary health care advocated by World Health Organization 40 years later.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: study design and clinical outcomes.

In 1995, 234 adults from Qidong, Jiangsu Province, People's Republic of China, where hepatocellular carcinoma is the leading cause of cancer deaths and exposure to dietary aflatoxins is widespread, were enrolled and followed in a Phase II chemoprevention trial. The goals of the study were to define a dose and schedule of oltipraz for reducing levels of validated aflatoxin biomarkers and to characterize dose-limiting toxicities. Healthy eligible individuals, including those infected with hepatitis B virus, were randomized to receive either 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor toxicities and evaluate biomarkers over the 8-week intervention period and subsequent 8-week follow-up period. Unique trial aspects included a synchronous follow-up schedule, daily observed administration of all medications, timely international data transference, and use of biomarkers as outcomes. One hundred thirty-two participants took their medications without interruptions, approximately 77% contributed all nine urine samples, and 78% contributed all seven blood samples. Fifty-one participants (21.8%) reported clinical adverse events. An extremity syndrome, developing soon after the start of treatment, was the only event that occurred more frequently (P = 0.002) among the active groups (18.4 and 14.1% of the daily 125 and weekly 500 mg arms, respectively) compared with placebo (2.5%). The oltipraz arms did not differ in symptom type or severity, and there were no indications of exacerbated drug intolerance among the few participants infected with hepatitis B virus. The good compliance with an intense follow-up schedule shows that chemoprevention trials with biomarker end points may be conducted in such populations.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers.

In 1995, 234 adults from Qidong, People's Republic of China, were enrolled and followed in a Phase IIa 4-methyl-5-(N-2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz) chemoprevention trial. Residents of this area are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods. The intervention was a randomized, placebo-controlled, double-blind study. Elements of the study design and clinical outcomes have been recently published (Jacobson et al, Cancer Epidemiol. Biomark. Prev., 6: 257-265, 1997). The primary objective was to conduct a preliminary assessment of the ability of oltipraz to modulate levels of a validated biomarker of aflatoxin exposure and of the risk of hepatocellular carcinoma by determining levels of aflatoxin-albumin adducts in sera. Healthy eligible individuals were randomized into three arms to receive p.o. 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo for 8 weeks. There were no consistent changes in biomarker levels in the placebo arm over the 16-week observation period, nor was any apparent effect observed in the arm receiving 125 mg of oltipraz each day. However, individuals receiving 500 mg of oltipraz once a week for 8 weeks showed a triphasic response to oltipraz. No effect was observed during the 1st month of the intervention, whereas a significant (P = 0.001) diminution in adduct levels was observed during the 2nd month of active intervention and during the lst month of follow-up. A partial rebound in adduct levels toward baseline values was observed during the 2nd month postintervention. Linear regression models up to week 13 confirmed a significant (P = 0.008) weekly decline of biomarker levels in the group receiving 500 mg of oltipraz once a week. However, despite these effects relative to baseline values within the 500-mg weekly arm, there were no statistically significant differences in biomarker trajectories between treatment arms. The genotype for glutathione S-transferase M1, an oltipraz-inducible isoform involved in the detoxification of aflatoxin B1, did not appear to affect either baseline levels or rates of decline in the biomarker. A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term.

A clinical study on diabetic retinopathy.

A clinical research on the diabetic retinopathy(DR) is reported. In the 662 cases of diabetes mellitus examined, the prevalence of DR was 51.3%, of which 7.6% were preproliferative and 7% proliferative. The study showed that when the disease progressed to the preproliferative and proliferative DR, laser photocoagulation could be the best treatment of choice, and panretinal photocoagulation was also quite effective in the treatment of pregnant patients with proliferative diabetic retinopathy.

A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China.

The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.

[Establishment of a primary eye care network and creation of a cataract-free zone in Shunyi County of Beijing].

Based on the epidemiological survey of eye diseases in 1985, a primary eye care network was established in Shunyi County of Beijing in 1987. Cataract surgery was the primary measure for the prevention of blindness, with the aim of creating a cataract-free zone in the county. The activities included (1) establishment of a County Guiding Committee for the prevention of blindness; (2) establishment of a 3-levelled primary eye care network and a referral and monitor system; (3) training of 7 ophthalmologists, 449 eye care workers and 6 optometrists; (4) extensive publicity of knowledge for the prevention of blindness; (5) screening of low vision and blindness in which 815 cataract blind patients were identified; and (6) conducting benefit ophthalmic counselling services. Up to December, 1991, 667 cataract operations were performed, representing 81.84% of the total cataract blind, to meet the qualifications of a cataract-free zone. 90.64% of the blind were restored sight and 59.16% of the blind were able to resume work. Operative infection occurred in none and 97.42% of the operations had no complication.

Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China.

Oltipraz has been used clinically in many regions of the world as an antischistosomal agent and is an effective inhibitor of aflatoxin hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-blind intervention was conducted in residents of Qidong, People's Republic of China, who are at high risk for exposure to aflatoxin and development of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the participants, and to further characterize dose-limiting side effects. Two hundred thirty-four healthy eligible individuals, including those infected with HBV, were randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potential toxicities and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow-up periods. Overall, compliance in the intervention was excellent; approximately 85% of the participants completed the study. Objective evaluation of adverse events was greatly facilitated by inclusion of a placebo arm in the study design. A syndrome involving numbness, tingling, and pain in the fingertips was the only event that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved with non-steroidal antiinflammatory agents. A more complete understanding of the chemopreventive utility of oltipraz awaits completion of an assessment of the efficacy of oltipraz in modulating levels of aflatoxin biomarkers.