Chemoprevention of breast cancer with retinoids.

Fenretinide [N-(4-hydroxyphenyl)retinamide, 4-HPR] is an effective agent for the inhibition of N-nitroso-N-methylurea-induced breast cancer in rats. This compound has been studied extensively and proved to be safer and less teratogenic than many other retinoids. A major characteristic of 4-HPR is its ability to concentrate in the granular and fat tissue of the breast instead of in the liver. Between January and June 1986, we carried out a phase I study on 101 patients divided into four randomized groups receiving placebo and 100, 200, and 300 mg/day of 4-HPR. Patients received the drug for 6 months without any major toxic effect. This finding was confirmed by another 6-month study in which patients received a common dose of 200 mg/day. In March 1987, a phase III study was started to evaluate the effectiveness of 4-HPR in preventing contralateral primary tumors in women who had already been treated for breast cancer. If 4-HPR succeeds in preventing second primaries in breast cancer patients, it may be useful for a wider group of subjects at high risk for breast cancer. This randomized study was designed with two arms: an intervention group versus a group receiving no treatment. Patients in the intervention group will be treated with 200 mg/day 4-HPR for 5 years. Patients in the control group will not be treated. A further 2 years of follow-up is planned for both groups. Currently, 2450 patients have been recruited. We expect a total accrual of 3500 patients by the end of 1992.     

Epidemiological study of French uranium miners.

An epidemiological cohort study has been carried out to demonstrate any excess cancer mortality in a group of French uranium miners who worked underground for at least 2 years. The latency period of cancer associated with this type of professional exposure was long (10 to 20 years). The first study includes miners who began underground mining between 1946-1972. The individual monthly exposure to radon and its decay products has been recorded since 1956. The exposure of the first 10 years had to be estimated retrospectively for each miner regarding the working conditions. Problems associated with these two different exposure recordings are discussed. The results revealed an excess of lung cancer mortality for miners who had begun underground mining during the years 1946-1956.     

Breast cancer: a study into the value of a historical group as comparative material for new methods of treatment.

A large group of consecutive patients were studied who had been treated for a primary breast carcinoma by a radical mastectomy at the Netherlands Cancer Institute, during the period of 1960-1974. One of the objectives of that retrospective study was to record the results of treatment of a historical group of patients in such a way that they could presumably serve as a reference for new methods of treatment of breast cancer. To verify the validity of this presumption, the present study compares the treatment results of patients from the EORTC trial 10801, which addresses the value of breast conserving procedures, with that of matched controls from the historical group mentioned above. Matching was carried out with respect to the following prognostic factors: age, tumor size, localization, (number of) positive axillary nodes and grade of malignancy. Analysis of the results strongly suggests that the prognosis for the patients from the historical group is worse than for both groups of patients from the trial 10801. Therefore, this study again confirms that a historical group is not suitable as comparative material for new ways of treatment of breast cancer, and that prospective randomized studies are required to test new treatment schedules.     

Randomized controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum

To evaluate of adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer, randomized controlled study by 35 institutions in Kanagawa prefecture was conducted. From March 1985 till February 1987, 462 patients were assigned one of two different regimens. 448 patients (97.0%) of them satisfied the eligibility criteria. Control group received mitomycin C intravenously on the day and the day after the operations respectively followed by 5-FU orally over for 6 months. PSK group received in addition to mitomycin C and 5-FU as in control group, PSK orally for over 3 years. By February 1989, follow up studies of the patients after their operations had been carried out for two years to four years. The disease free curve and the survival curve of PSK group were higher than those of control group, differences between the two groups were statistically significant (Disease free curve: P = 0.0096, survival curve: p = 0.0391). From these results, adjuvant immunochemotherapy with PSK was considered beneficial for curatively resected colorectal cancer.     

Occupational lung cancer among copper smelters

Because a remarkably high lung cancer mortality rate was noted among males in a certain town, a case control study was carried out on the basis of mortality cards. The case group consisted of 19 males who died from lung cancer and the control group included 19 males who had died from diseases other than cancer of the lung, urinary bladder, and skin. The only significant difference between the groups was that 11 of the 19 who had died from lung cancer had been employed as smelters in a local copper refinery. Prolonged exposure to arsenic, and possibly also other compounds, seemed to be associated with cancer of the lung. The validity of the diagnosis of these lung cancer cases was also checked by blind examination of chest X-ray films of the patients with occupational cancer, a group of other lung cancer patients, and the controls. The occupational cancer was diagnosed at a higher rate than the tumors of other lung cancer cases. In all the 11 cases, the disease had become manifest after the men had stopped working at the refinery. None of them had been considered as having occupational cancer by the physicians who treated them, their previous employer, the authorities concerned, their family and friends, or indeed themselves, until this study was conducted. The necessity of a lifelong health care system for ex-smelters from copper refineries was emphasized.     

Controlled study of MQF-OK therapy with FT and with UFT on various advanced gastrointestinal cancers. Hirosaki Cooperative Study Group of Cancer Chemotherapy

Our cooperative study group carried out a controlled study of MQF-OK therapy with tegafur (FT) (group A) and with UFT (group B), a compound of FT and uracil in the molar ratio of 1:4, on various advanced gastrointestinal cancers. From January 1985 to May 1987, 91 patients were entered into this study, and 11 cases were ineligible for the protocol (11%). Fifty of 80 cases had advanced gastric cancer, 30 had pancreatic cancer or other cancers, such as colon cancer, and biliary tract cancer. They were divided into group A or B at random. There was no difference in the patient characteristics between group A and B. In gastric cancer, 23 of 50 cases were randomized into group A and 27 cases into group B. Two cases in group A (8.7%) and 7 cases in group B (25.9%) showed PR. The response rate of group B was better than that of group A, but the value of P by Kruskal-Wallis test was 0.27. Thirteen of the 30 other cancers were randomized into group A and 17 cases into group B. Three cases in group A and B, respectively, showed PR. There was no significant difference between the two groups in terms of antitumor effect, prolongation of life or side effects. In conclusion, it was suggested that the MQF-OK therapy with UFT was beneficial for the Remission Induction Therapy in advanced gastric cancer.     

Adjuvant therapy of breast cancer with tamoxifen and endometrial carcinoma]

Twenty cases of endometrial carcinoma are reported, observed in women who had received long term tamoxifen treatment as adjuvant therapy for breast cancer. Furthermore, a specific study was carried out on an homogeneous group of 790 women with an operable breast cancer, 318 receiving tamoxifen as adjuvant treatment. Five endometrium carcinoma were observed in the group under tamoxifen versus none in the other group. From an analysis of these cases, authors will carry out a case control study to evaluate the relative risk of endometrial carcinoma for patients under tamoxifen. They underline the importance of gynecologic follow up procedures for all women receiving this endocrine therapy.     

Breast cancer bone metastasis in femur: surgical considerations and reconstruction with Long Gamma Nail.

AIM: The femur is the most common long bone involved in metastatic breast cancer. Several studies have been published on the surgical management of metastatic disease of the femur. However, only few studies have been published specifically on the outcomes following reconstruction of femoral metastasis from breast cancer using a third generation intramedullary nail. The aim of this study is to review the outcomes after intramedullary surgical stabilization of femoral metastases from breast cancer. This is often associated with significant bone destruction. METHODS: A retrospective study of 18 femoral metastatic lesions in 15 patients treated with a Long Gamma Nail over a 6-year period was carried out. Pain relief, mobilization status and implant related complications were the main outcome measures analyzed. RESULTS: Thirteen out of 15 patients had complete pain relief and all patients regained their preoperative mobilization status with or without walking aids. There were no implant failures or perioperative deaths. Four (26%) patients developed minor complications. Ten patients died with an average survival of 9 months and five patients are alive with an average survival of 32 months. CONCLUSION: Stabilization of femoral metastases due to breast cancer with Long Gamma Nail is a safe and effective method with acceptable risks.     

Comparison of S urvival between P atients with H ereditary N on - polyposis C olorectal C ancer (HNPCC) and S poradic C olorectal C ance

Background: Hereditary non polyposis colorectal cancer (HNPCC) appears to have a better prognosis thansporadic cancer. In the present study we evaluated the clinical outcomes of HNPCC patients in comparison withtheir sporadic colorectal cancer counterparts arising from the general population recorded in a populationbasedcancer registry in Iran. Patients and methods: The population studied consisted of 121 individuals including61 patients with sporadic colorectal cancer and 60 patients with HNPCC who were followed-up between 2003and 2008 in Taleghani hospital Tehran. The subjects with HNPCC were screened according to Amsterdamcriteria II and Bethesda Guidelines. All those with sporadic cancer had no familial history of colorectal cancer.Observed survival was estimated using the Kaplan-Meier method and compared with log rank test. Multivariateanalysis was performed using the Cox regression analysis. Results: In the HNPCC group, 85.0% showed tumorsin the colon, vs. 68.9% in the sporadic cancer group. The 5-year survival was 82.5% in the HNPCC study groupcompared with only 56.4% in the sporadc cancer group (P=0.044). The age distribution at diagnosis of sporadicpatients was significantly higher than HNPCC patients (mean 50.1 years vs 44.3 years P=0.008). The hazardratio for sporadic cases was 2.93 (95% CI 1.06-8.11) compared with the HNPCC group (P=0.038). Conclusion:Our findings corroborate the results of previous studies which showed overall survival of colorectal cancer inpatients with HNPCC is better than for sporadic CRC patients.     

An evaluation of screening for lung cancer in Niigata Prefecture, Japan: a population-based case-control study.

Although an annual screening programme for lung cancer has been carried out widely in Japan since 1987, there is insufficient evidence to confirm its efficacy in terms of reducing mortality. In order to evaluate the efficacy of the lung cancer screening which has been widely carried out in Japan since 1987, a case-control study was conducted in Niigata Prefecture, Japan. In the study area, chest X-ray examinations for all participants and sputum cytology for high-risk participants were offered annually. Case subjects, who had died from lung cancer (174), and control subjects matched by sex, year of birth, residence and smoking status (801), who had been alive at the time of diagnosis of the corresponding case, were selected from the National Health Insurance holders. Screening histories of the subjects were compared between cases and matched controls for the identical calendar period before the time of diagnosis of the cases. The odds ratio of death from lung cancer for those screened within 12 months vs those not screened was 0.401 (95% CI: 0.272-0.591) with adjustment by smoking index. Our results suggest that annual lung cancer screening might reduce mortality from lung cancer by approximately 60%.     

Lung cancer following Hodgkin's disease: a case-control study.

It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer. A collaborative group of population-based cancer registries and major treatment centers carried out a case-control study, in which 98 cases of lung cancer were identified in patients who had survived at least 1 year following a diagnosis of Hodgkin's disease. A total of 259 matched controls were selected from patients with Hodgkin's disease who did not develop subsequent lung cancer, and for both cases and controls detailed information was abstracted from medical records concerning stage and treatment of Hodgkin's disease. Patients treated with chemotherapy alone had about twice the risk of developing lung cancer than those treated by radiotherapy alone or both modalities. There was no increase in risk with cumulative number of cycles of chemotherapy. Among patients treated with radiotherapy alone, there was an increase in risk related to estimated radiation dose to the lung. There was also a strong association between cigarette smoking and the risk of lung cancer. The finding of a higher risk following chemotherapy than following radiotherapy was unexpected, but could not be explained by any identified methodological flaws. A plausible inference from the study is that all forms of Hodgkin's disease therapy are carcinogenic to the lung and that, in particular, chemotherapy is associated with an increase in risk which is at least comparable to and perhaps higher than the risk produced by radiotherapy.     

CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性与肺癌遗传易感性

目的：探讨辽宁地区CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性对肺癌发生的影响。方法：采用病例-对照研究方法,选取肺癌患者和健康对照者各200例。应用KI法快速抽提人外周血基因组DNA,PCR-RFLP的方法检测CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性。结果：G4268/G、G4268/C和C4268/C这3种基因型在病例和对照组的分布频率分别为1.50%、58.00%、40.50%和2.50%、44.00%、53.50%,非C4268/C基因型的个体发生肺癌的风险是C4268/C基因型个体的1.73倍（95%CI=1.02-2.95）,在腺癌中OR=2.75（95%CI=1.27-5.94）;按吸烟情况进行分层分析后发现不吸烟者及轻度吸烟者中携带非C4268/C基因型的个体患肺癌的风险显著增高,OR值为2.09（95%CI=1.09-4.25）和3.41（95%CI=1.24-9.93）;非A8092/A基因型的个体发生肺癌的风险是A8092/A基因型个体的0.98倍（95%CI=0.52-2.17）。结论：C4268/C基因型在不吸烟者和轻度吸烟者中可能作为保护因素而降低肺癌的易感性,ERCC1 C8092A多态性与肺癌易感性无相关性。     

Necessity of adjuvant therapy after radical mastectomy based on a study of patients with negative nodes, who have recurrent breast cancer

The status of the regional lymph nodes influences the prognosis of women with breast cancer who have received a radical mastectomy. To investigate the characteristics of patients with negative nodes who have had a recurrent breast cancer, a statistical study has been carried out involving 279 women who had received a radical mastectomy in our hospital from July 1970 to October 1986. From this study we conclude that systemic adjuvant therapy after radical mastectomy is necessary for patients with negative nodes who have had a breast cancer greater than 2.1 cm (T2) in diameter or a solid-tubular carcinoma.     

Clinico-pathological study of autopsy cases of nonresected gastric cancer in the young and old

To elucidate the difference between the natural history of gastric cancer in young and old patients, this study was carried out. Fifty-four cases were studied, representing the autopsy findings of gastric cancer patients who did not undergo operation. The characteristics of the gastric cancer in the young patients were as follows: had infiltrative macroscopical types, had histologically diffuse types, had deeper and wider infiltration, showed a severer invasion into the vessels, and, showed marked lymphatic disseminated, and distant metastasis. The elderly, in comparison, showed various types of gastric cancers. The extension of the cancer in the old group was significantly, less than in the young, even in the same diffuse type. The period from the onset to death was almost same in both groups. The age of the host seems one of the important factors influencing the natural history of gastric cancer.     

Lung cancer in patients under 50 years old.

A long-term retrospective study was carried out on 790 cases of lung cancer to determine if the clinicopathologic characteristics and survival rates of lung cancer patients under the age of 50 differ from those of patients 50 years of age or older at diagnosis by analyzing data on patients registered at Tochigi Cancer Center Hospital. Of the 790 patients, 77 (9.7%) were under the age of 50 at diagnosis. The percentage of women in the younger patient group was significantly higher than that in the older patient group (39.0% vs. 27.5%; P = 0.034). Tumor histology revealed a significant preponderance of adenocarcinomas (60 patients, 77.9%) and a paucity of squamous cell carcinomas (8 patients, 10.4%) in the younger age group (P<0.001). The preponderance of adenocarcinoma was significant in both males and females (male: P = 0.004, female: P = 0.004). Smoking rates and rate of detection by cancer screening did not differ between the two age groups. Because of the paucity of smokers among the younger female patients, causes of lung cancer other than smoking should be sought in younger patients. No difference was found in the stage of the disease at presentation, treatment methods and survival rates between the two age groups. It is suggested that the prognosis for patients with lung cancer under the age of 50 is not significantly worse than for those aged 50 years or older, as has been shown by several investigators.     

Mixed adherence to clinical practice guidelines for colorectal cancer in the Southern Netherlands in 2002.

AIMS: Population-based cancer registries can provide excellent data for insight in disease management practice. This study examines the extent to which the consensus-based national clinical guidelines (version 2000-2001) for colorectal cancer (CRC) had been implemented in the diagnostic and treatment approach in the Southern Netherlands in 2002. METHODS: Data were gathered from the medical records for a random sample from the Eindhoven Cancer Registry of 308 patients with colorectal cancer. Adherence to clinical guidelines was determined for diagnostic assessment, pathology, and treatment during the first year after diagnosis. RESULTS: Surgical procedures and referral for pre-operative radiotherapy were carried out largely conform the recommendations. The number of performed colonoscopies among colon cancer patients amounted to 60%; contrast enemas after incomplete colonoscopy were performed in only 27% of patients. The median number of examined lymph nodes was only six for patients with colon and five for patients with rectal cancer; the administration of adjuvant chemotherapy for patients with stage III colon cancer decreased from 95% of patients younger than 70 years to 48% of patients over 70. CONCLUSIONS: Adherence to clinical guidelines was not optimal. Feedback to surgeons and pathologists should improve adherence, especially with respect to nodal retrieval and assessment.     

Improved care of patients with small cell lung cancer. Nutritional and quality of life aspects.

A comprehensive cancer care project was carried out in Uppsala with the aim of improving the overall situation for patients treated with intensive chemotherapy with curative intent. This report gives the results in 58 patients with small cell lung cancer (SCLC), focusing on the nutritional aspects of the care and chemotherapy-related adverse effects. Responses, survival and simple nutritional parameters were compared with a historical control group (n = 81), and quality-of-life parameters with a pre-project group (n = 22). Groups were comparable with respect to pre-treatment characteristics. In contrast to the historical control group, weight, body mass index and S-albumin did not decrease during treatment in patients diagnosed during the project period. Yet, food intake in the study group was low, and for most patients below what is recommended. Survival, proportion of responses and response duration did not differ from those of the control group. Compared with the pre-project quality-of-life controls, a number of scores were more favourable for study patients (n = 36) interviewed in association with the 8th treatment course by a Swedish version of the Cancer Inventory of Problem Situations (CIPS). The global score was lower in the study group than in the pre-project group (0.80 vs 1.20, p < 0.001). Significant differences in a favourable direction were also seen in several higher order factors and miscellaneous subscales constituting the CIPS. On individual items, the study group expressed less problems with appetite/food taste in hospital, nervousness before chemotherapy and worry about adverse effects. The greatest differences in positive direction for the study group were seen within areas where the project focused on caring activities. We therefore conclude that a cancer care project with the present goals and means of intervention can improve the quality of life in patients with SCLC treated with intensive chemotherapy.     

Quality of life assessment through the EORTC questionnaires of colorectal cancer patients in advanced disease stages

Purpose The purpose of the present work is to evaluate Quality of Life in a group of colorectal cancer patients in advanced stages of their disease, along a standard chemotherapy treatment protocol, through the EORTC core questionnaire QLQ-C30 and the colorectal cancer module QLQ-CR38. These two questionnaires had previously been validated in our country. The present study has the novelty of its use during the chemotherapy treatment. Materials and methods A consecutive sample of 44 colon o rectal cancer patients in stage IV, from an initial group of 46 patients who were addressed, have filled in the questionnaires, in three moments during their treatment process. Clinical and demographic data have also been recorded. Quality of Life scores and changes in them among the three assessments have been calculated. Results The quality of life scores of patients who have followed the treatment have been >70 points (100) in most dimensions, and has shown similar to the clinical data. Changes of >20 points in the quality of life scores during the treatment process appear in areas related to toxicity, fatigue and insomnia. Quality of life has been stable or has had small changes (between 10 and 20 points) in most dimensions. Conclusions Quality of Life in the present sample has been good in general. The treatment has been administered to patients who could tolerate it adequately. This study has been carried out with the support of a grant from the Gobierno de Navarra Health Department.     

Local control after curative surgery for cancer of the extraperitoneal rectum. Twenty years of experience

A retrospective study was carried out in 264 patients with low rectal cancer surgically treated with curative intent from January 1975 to December 1995 to analyze the influence of stapling devices on surgical and disease outcome. Patients were classified as follows: group 1 underwent surgery from 1975 to 1980, when staplers were not employed, and group 2 from 1981 to 1995, when stapling devices were routinely used. The use of stapling devices determined a corresponding increase in low anterior resection (LAR) and a decrease in postoperative mortality. A statistically significant difference in local recurrence rate between abdominoperineal resection (APR) patients and LAR sutured cases of group 1 was observed. In T3, N+ cases local recurrence rate was comparable in APR patients and LAR cases with stapled anastomosis. Improved local control occurred in stapled group 2 patients which was independent of the distal clearance. Although APR still plays an important role in treatment of lower rectal cancer, results indicated that a similar outcome after stapled LAR can also be expected in locally advanced carcinoma of the distal rectum, if accurate excision of perirectal tissue is carried out.     

动态观测胃粘膜不典型增生MC5抗原表达与临床随访研究

应用本院制备的抗结肠癌单克隆抗体ＭＣ５及ＡＢＣ免疫组化染色检测了６４例具有随访结果的胃粘膜异型增生标本。其中癌变组３０例，未癌变组３４例，随访时间６￣７２个月。结果：癌变组中有２０例表达阳性，未癌变组中有８例表达阳性，两组相比相差显著。表明ＭＣ５－Ａｇ表达阳性的不典型增生与胃癌关系密切。在未癌变组ＭＣ５表达阴性的２６例标本中，随访后病变减轻或无变化者２３例，ＭＣ５仍呈阴性表达，而未癌变组ＭＣ５表达