p53 status in radiation-induced soft-tissue sarcomas

BACKGROUND: Following therapeutic irradiation after a latency period of many years radiation-induced tumors, often sarcomas, can arise. Results of radiation-induced DNA damage can be 1. p53 over-expression, inducing growth arrest or apoptosis, and 2. occurrence of mutations, frequently including the p53 gene, as one molecular promotor for carcinogenesis. We were interested whether radiation-induced sarcomas are associated with alterations of the p53 status. MATERIAL AND METHODS: Samples from 11 radiation-induced soft-tissue sarcomas (STS) were studied by a non-radioactive PCR-SSCP sequencing analysis and by immunohistochemistry with five antibodies for their p53 status. RESULTS: A tumor of one patient possessed a G->A transition in codon 280 (exon 8). Of 11 tumors, 9 showed nuclear p53 positivity, detected by monoclonal antibody DO-1. Of these 9 patients, 7 died during the observation period, whereas the 2 patients with DO-1 negative tumor samples are still alive. CONCLUSIONS: p53 over-expression and p53 mutation occur in radiation-induced STS. p53 status is expected to have prognostic impact for radiation-induced STS.     

The use of hyperfractionated radiotherapy in soft-tissue sarcomas

In classical irradiation, the local control can be negatively influenced by the accelerated clonogenic tumoral repopulation. A modality of control of this phenomenon can be accelerated hyperfractionated irradiation. The aim of this paper is the study of the effect of this type of irradiation in soft tissue sarcomas on patients of the Radiological-Oncological Clinic Ia?i. Accelerated hyperfractionated irradiation causes a favorable response in the primary tumor with good local tolerance, but the "free of disease" period depends on the aim of irradiation (preoperative, postoperative or single therapeutical procedure).     

Growth rate of lung metastases and S-phase fraction as determined by flow cytometry from the primary tumour in 25 patients with bone or soft-tissue sarcomas

A significant correlation (r = -0.48) was found between the logarithm of the S-phase fraction of the primary tumour (SPF) and the logarithm of the doubling time of lung metastases (T2). The estimated median cell loss factor was 88% (range 35-99%).     

Prognostic value of immunohistochemistry for p53 in primary soft-tissue sarcomas: a multivariate analysis of five antibodies

Most changes of tumor suppressor p53 and its pathway involve a protein with prolonged half-life that permits immunohistochemical detection. The goal of this study was to compare the prognostic relevance of five different p53 antibodies in primary soft-tissue sarcomas (STS) with known p53 mutation status, using a multivariate Cox regression model (adjusted to tumor grading, staging, localization, tumor type, and therapy). A group of 198 primary STS of six types were investigated for p53 overexpression, using p53 antibodies DO-1, DO-7, Pab1801, Pab240, and CM-1. A positive marker frequency between 36.2% and 62.6% was detected. Out of 65 patients whose primary tumor reacted positively to all five antibodies, 52 (80%) died within the study period. Only the N-terminal-binding monoclonal antibodies DO-1, DO-7 and Pab1801 showed a multivariate correlation with survival (P = 0.0014, 0.0048 and 0.02). CM-1 and Pab240 had a univariate, but not a multivariate correlation, with a confounding effect of grading. The prognostic relevance for the five p53 antibodies was: DO-1 > Pab1801 > DO-7 > CM-1 > Pab240. This is the first study that investigates multivariately the prognostic relevance of p53 immunostaining in STS. If monoclonal antibodies with an epitope in the N-terminal region of the p53 protein (DO-1, Pab1801, DO-7) are applied, p53 immunohistochemistry provides an independent prognostic marker in STS.     

Survival of patients with advanced urothelial cancer treated with cisplatin-based chemotherapy

The aim of the present retrospective study was to assess long-term survival after cisplatin-based chemotherapy in 398 patients with advanced urothelial transitional cell carcinoma (TCC) treated at seven international oncological units. Various combinations of cisplatin, methotrexate, vinblastine (or vincristine) and doxorubicin were used. The complete response rate according to the WHO criteria was 17%. Partial responses were obtained in 42% of the patients. The overall cancer-related 2 year and 5 year survival rates were 21% and 11% respectively. Based on multivariate analyses, a good prognosis group could be identified comprising patients with a good performance status with disease confined to lymph nodes (14%) or patients with T4b disease only. These patients had a 28% 5 year survival rate, which, in part, has to be related to post-chemotherapy consolidation treatment in patients with pelvis-confined disease (radiotherapy, 26%; total cystectomy, 11%). Fifteen patients died of chemotherapy-related complications and in 16% of the patients toxicity led to discontinuation of treatment. Modern cisplatin-based chemotherapy leads to long-term survival and cure of selected patients with advanced urothelial transitional cancer. In routine clinical practice, chemotherapy should be offered to good prognosis patients; those presenting with a good performance status and a non-metastasising T4b tumour or with metastases confined to lymph nodes. Post-chemotherapy consolidation treatment by surgery or radiotherapy should always be considered. Such chemotherapy requires oncological expertise in order to avoid unnecessary toxicity.     

Survival of patients with carcinoma of the esophagus treated with combined-modality therapy

Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years.     

Evaluation of fluorodeoxyglucose positron emission tomography in the management of soft-tissue sarcomas

OBJECTIVE: This study aimed to determine whether clinical tests of ocular function and macular appearance independently can help to predict which patients with unilateral neovascular age-related macular degeneration (AMD) will have a choroidal neovascular membrane (CNVM) develop in their fellow eye. DESIGN: The study design was a prospective cohort study. PARTICIPANTS: One hundred twenty-seven patients with unilateral neovascular AMD observed for up to 4.5 years participated. INTERVENTION: Functional measurements included visual acuity, macular visual field, glare recovery time, and foveal electroretinogram amplitude and implicit time. MAIN OUTCOME MEASURE: The age-adjusted proportion of patients having a CNVM develop over follow-up assessed by the Cox proportional hazards model with stepwise selection was measured. RESULTS: On average, 8.8% of patients had a CNVM develop each year. Independent risk factors for the fellow eye were its glare recovery time in minutes (relative risk = 1.30, confidence interval = 1.10-1.54, P = 0.003) and its extent of visible macular abnormalities on a four-point scale (relative risk = 1.62, confidence interval = 1.06-2.59, P = 0.03). Of the fellow eyes that converted, the interval to have a CNVM develop was inversely related to the foveal electroretinogram implicit time. CONCLUSIONS: A slower recovery from glare and more extensive funduscopic changes appear to be independent risk factors for the development of a CNVM in the fellow eyes of patients with unilateral neovascular AMD. A slower foveal electroretinogram implicit time may be a sign of early stage CNVM development, perhaps because of outer retinal ischemia. These results have clinical management implications, particularly for those patients at high risk of having a potentially treatable form of AMD develop.     

阻塞性睡眠呼吸暂停低通气综合征患者戴用口腔矫治器6年以上牙(牙合)改变

目的:观察长期口腔矫治器治疗后阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)患者牙(牙合)变化情况.方法:对7例接受口腔矫治器治疗OSAHS的患者,通过治疗前、后牙(牙合)模型资料的三维测量分析,观察患者牙弓宽度及各牙位的三维变化.结果:7例长期使用口腔矫治器的患者,经平均使用8.5年后,上第二磨牙远中颊尖处增宽(2.11±2.14)mm,P=0.040;上第一磨牙远中颊尖处增宽(0.56±0.61)mm,P=0.049;下第一磨牙远中颊尖处增宽(1.25±0.93)mm,P=0.040.在三维方向上,除上、下磨牙个别牙尖点出现(牙合)向压低外,其余测量结果差异无统计学意义.结论:患者使用口腔矫治器后,牙(牙合)有微小的改变趋势,医生应予以关注.     

Enhanced spasticity in primary progressive MS patients treated with interferon beta-1b

Spasticity is a disabling symptom of MS that is enhanced during interferon beta-lb (IFNbeta-1b) treatment. Nineteen patients with primary progressive MS were treated with IFNbeta-1b; an additional 19 patients did not receive this treatment. Thirteen of the 19 patients treated with IFNbeta-1b had increased spasticity requiring increased antispasticity drug administration. This observation suggests that further studies are needed before interferons can be so widely used in primary progressive MS patients.     

Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study

BACKGROUND: Endoscopic retrograde cholangiopancreatography was introduced in the early 1970s, making a more reliable diagnosis of primary sclerosing cholangitis (PSC) possible. Since then decreased survival and increased risk of cholangiocarcinoma have been reported. However, no population-based studies have quantified these outcomes. METHODS: A population-based cohort of 125 patients with a verified PSC diagnosis was followed up through linkage to the Swedish Death Registry and the Swedish Cancer Registry for occurrence of death and cholangiocarcinoma. RESULTS: The diagnosis of PSC was associated with a substantially decreased survival, with an overall 10-year survival of 68.8%. Patients with a diagnosis of inflammatory bowel disease (IBD) had a somewhat better prognosis, 71.8%, compared with 60% for patients without. Fourteen subsequent cholangiocarcinomas yielded a cumulative risk of 11.2% 10 years after diagnosis. Sex, duration of IBD, and colectomy influenced neither the survival nor the cholangiocarcinoma risk. CONCLUSION: Patients with PSC have a substantially decreased survival, which is most pronounced among patients without IBD.     

Plasma insulin-like growth factor in primary breast cancer patients treated with adjuvant chemotherapy

Insulin-like growth factor 1 (IGF-1) plasma level was assayed in 60 breast cancer patients undergoing six courses of adjuvant chemotherapy. The only observed variation was a slight decrease (10%) in IGF-1 concentrations, assayed before treatment, between the first and the second courses of chemotherapy. During chemotherapy courses, there were no statistically significant variations in IGF-1. These results suggest that chemotherapy, unlike the specific hormonal treatments tamoxifen and somatostatin, certainly does not act via a decrease in plasma IGF-1.     

Long-term survival (10 years or more) in 30 patients with primary amyloidosis

The median survival in primary systemic (AL) amyloidosis is less than 18 months. No published series of patients with AL amyloidosis have reported survival of more than 10 years. The records of all Mayo Clinic patients with a diagnosis of AL amyloidosis between January 1, 1966 and March 1, 1987 were reviewed. Patients with secondary amyloidosis, familial amyloidosis, senile systemic amyloidosis, and localized amyloidosis were excluded. During the 21 years of the study, 841 patients with AL amyloidosis were seen. Of these, 29 were excluded because the diagnosis was made at autopsy, and 2 others were excluded because no follow-up data were available. Actuarial survival for the 810 patients was 51% at 1 year, 16% at 5 years, and 4.7% at 10 years. Thirty patients survived for 10 years or more after the histologic diagnosis of AL amyloidosis; all received alkylating-agent therapy. In 14 patients, the monoclonal protein disappeared from the serum or urine. Of 10 patients with nephrotic syndrome, 4 had an objective response. Congestive heart failure, older age, creatinine value of 2 mg/dL or more, bone marrow plasma cell value of 20% or more, platelet count of 500 x 10(9)/L or less, and the presence of peripheral neuropathy were underrepresented in the 10-year survivors and are unfavorable prognostic features. Five percent of patients with AL amyloidosis survived for 10 years or more.     

Survival and daily physical activity in patients treated for advanced midgut carcinoid tumors

BACKGROUND: Prospects for survival and quality of life ought to influence treatment strategies in patients with midgut carcinoids. METHODS: A total of 121 patients with midgut carcinoid received a combined medical and surgical treatment from 1980 to 1993. In all, 158 operations were undertaken for removal of mesentericointestinal lesions and occasional liver metastases or as repeat intervention for abdominal complications. Survival was analyzed together with estimates of daily physical activity during follow-up. RESULTS: Cause of death (63 patients) included carcinoid heart disease (41%) and cachexia (mesentericointestinal entrapment, 35%). Median survival was 11 years in patients with irresectable mesenteric metastases, 7 years with liver metastases, and 1 year with extraabdominal spread. Extensive liver metastases or substantial weight loss (9 kg or greater) reduced survival to a median of 4 to 5.5 years, and surgically treated intestinal ischemia reduced survival to a median of 8 years. Patients with carcinoid syndrome survived a median 7 years, those with 5-hydroxyindoleacetic acid values greater than 500 mumol/24 hr or a valvular heart disease survived a median of 5 years, those with heart failure a median of 2.5 years. Most patients retained an acceptable daily physical activity; impairment occurred in cases of malnutrition, high 5-hydroxyindoleacetic acid values, or heart valve fibrosis, and activity was markedly reduced in the presence of extraabdominal metastases or overt heart disease. CONCLUSIONS: Favorable survival statistics and the maintenance of daily physical activity support active medical and surgical management in patients with advanced midgut carcinoids.     

Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine

BACKGROUND: Crohn's ulcerative gastrointestinal disease is presently managed through a variety of medical interventions, including-according to severity of illness-anti-inflammatory, immunosuppressive, and corticosteroid agents; and with remedial surgery to correct anatomical abnormalities caused by disease processes. The immunosuppressant azathioprine (or its metabolite, 6-mercaptopurine) is considered an efficient maintenance therapy for Crohn's, but there is always concern about bone-marrow suppression, liver damage, and other adverse effects. For how long persons with this disease should be given these drugs has not been determined. METHODS: Patients who were treated with azathioprine or 6-mercaptopurine for more than 6 months, and who were in prolonged clinical remission (> 6 months without steroids) were followed. The time-to-relapse was analysed in those on treatment, in those who stopped treatment for reasons other than a relapse, and in the whole sample, taking into account that they could be treated with the drugs or not, as a function of time. The influence of concomitant variables on time-to-relapse rate was examined using the Cox proportional hazard model. FINDINGS: In the 157 patients who continued to take the therapy, cumulative probabilities of relapse at 1 and 5 years were 11% and 32% respectively. Female gender, younger age, and a time for achieving remission more than 6 months were associated with a higher risk of relapse. In 42 patients who stopped therapy, probabilities of relapse at 1 and 5 years were 38% and 75%, respectively. Male gender, younger age and duration of remission less than 4 years were associated with a higher risk of relapse. After 4 years of remission on these drugs, the risk of relapse appeared to be similar, whether the therapy was maintained or stopped. INTERPRETATION: Taking into account the potential risks of long-term immunosuppressive therapy, the usefulness of maintaining azathioprine or 6-mercaptopurine in patients who have been in remission for more than 4 years is questionable.     

Experiences of 23 patients > or = 90 years of age treated with radiation therapy

Previous studies showed that the 5-HT2 receptor antagonist, amperozide, is somewhat more potent than the opiate antagonist, naltrexone, in reducing alcohol drinking in high alcohol-preferring (P) rats. The purpose of this study was to determine in the P rat whether the effect of either drug could be due, in part, to an alteration in gustatory function. In an unlimited, 24-h free choice paradigm, P rats were offered water simultaneously with either a highly palatable 0.1% saccharin solution or a 1:4 dilution of Nestlé Sweet Success chocolate drink. Throughout all phases of the study, the P rats always consumed significantly greater volumes of the chocolate drink than of the saccharin solution, i.e., 526 ml/kg vs. 181 ml/kg, respectively. Successive 12-day experimental periods consisted of three phases: a 4-day predrug control interval; 4 days of administration of saline control vehicle or either drug; and a final 4 day postdrug interval. In a counterbalance design, saline, amperozide (1.0 or 5.0 mg/kg) or naltrexone (2.5 or 5.0 mg/kg) was administered subcutaneously twice daily at 1600 and 2200 h for 4 days. Amperozide and naltrexone significantly reduced the drinking of chocolate in a dose-dependent manner. Conversely, only the two higher doses of amperozide and naltrexone decreased the intake of saccharin significantly. Thus, these findings suggest that different populations of central serotonin and opioid receptors concurrently underpin, in part, the preferences for both palatable and/or nutrient fluids. Finally, because both the opiate and 5-HT2A antagonists reduce the ingestion of saccharin and chocolate solutions differentially, it is apparent that preferences for alternative palatable fluids should be examined when candidate drugs are screened for suppressing alcohol drinking and ultimately the treatment of alcohol abuse.     

Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996)

OBJECTIVE: To determine results of surgery for treatment of soft-tissue sarcomas in dogs and to identify prognostic variables that can be used to predict outcome. DESIGN: Retrospective case series. ANIMALS: Dogs with soft-tissue sarcomas that had surgical treatment only. PROCEDURE: Records were examined for clinically relevant data. Histologic samples were reviewed. Follow-up information was obtained by physical examination or telephone conversations with referring veterinarians or owners. RESULTS: 75 dogs with soft-tissue sarcomas of the trunk and extremities were identified. Median age was 10.6 years. Malignant peripheral nerve sheath tumors were of a significantly lower grade than other tumors. Tumors recurred locally in 11 of 75 (15%) dogs. Evaluation for lack of tumor cells at surgical margins was prognostic for local recurrence. Metastatic disease developed in 13 of 75 (17%) dogs. Tumor mitotic rate was prognostic for development of metastasis. Twenty-five of 75 (33%) dogs died of tumor-related causes. Percentage of tumor necrosis and tumor mitotic rate were prognostic for survival time. Median survival time was 1,416 days. CLINICAL IMPLICATIONS: On the basis of a low local recurrence rate and high median survival time, wide excision of tumor margins or radical surgery appeared to be an effective means for managing soft-tissue sarcomas of the trunk and extremities. Analysis of histologic characteristics for prognosis supported use of preoperative biopsy. Surgical margins should be evaluated, and early use of aggressive surgery is indicated in the management of soft-tissue sarcomas in dogs.     

Survival of patients with the most frequent malignant neoplasms in the population of Krakow in the years 1985-1989

In 1985-1989 there was not significant improvement of survival rates for the most common cancer sites in Cracow population. Survival of Cracow patients with colorectal, breast and larynx cancer and chronic lymphatic leukaemia were significantly below European mean. This situation is probably typical for whole Polish population.     

Intracranial abscesses: a review of treated patients over 20 years

A series of 49 consecutive patients with an intracranial abscess treated over a 20 year period is analysed and reported. The overall mortality was 28 per cent. The authors regard this figure as quite unacceptable and stress that the combination of isotope scans and computerized axial tomography (CAT) should allow an immediate reduction in mortality to around 10 per cent. The plea is made that whenever a primary source of infection is present the possibility that an intracranial mass could be an abscess is constantly borne in mind. Under such circumstances the patient should be referred immediately to a neurosurgical department (where computerised axial tomography is usually available) without a preceding lumbar puncture.     

Survival analysis in patients with cutaneous malignant melanoma

INTRODUCTION: Cutaneous malignant melanoma (MM) takes only 3% of all malignant tumours of the skin, but for reason of its increased frequency and pronounced tendency to rapid growth and metastases, it causes 60% of total lethal outcomes due to malignant tumours of the skin [1]. Primary MM is a diagnostic problem because of the great variety of its clinical features. Asymmetric configuration, irregular border, speckled color(r)diameter of more than 6 mm, and elevation of the surface, suggest suspicion of malignant alteration, but even then misdiagnosis is possible. For the final diagnosis of MM histopathological confirmation is necessary. The method to use is the extensive excisional biopsy of the lesion and its borders [2]. Histopathological diagnosis is based on microscopic findings which include: histogenetic type of MM, tumour thickness according to Breslow, level of invasion according to Clark, presence of ulceration, grade of lymphocyte infiltration, mitote rate, type of cells, presence of melanin in cells [2, 3]. PATIENTS AND METHODS: A five-year survival of patients with cutaneous malignant melanoma (MM) was studied according to sex, age and distinct features of the tumour: site, type of initial therapy, stage of the disease, time from the first signs of the disease to diagnosis of MM, histological findings (histogenetic type, Breslow's tumour thickness, Clark's level of invasion, presence of ulceration, degree of lymphocyte infiltration, number of mitoses, type of cells, intensity of pigmentation) and presence of metastases. The retrospective study included 336 patients with cutaneous MM. There were 185 female (55.1%) and 151 male patients (44.9%), aged 14-83 years, mean age 48.8 years, who were treated at the institute of Oncology and Radiology in Belgrade from 1978 to 1990. The mean follow-up was 60 months (1-144 months). Melanoma in situ had 16 (4.1%) patients. Stage I had 45 patients (14.1%), stage II 163 (48.5%), stage III 83 (24.7%) and stage IV 29 (8.6%) patients. Acral location on hands and feet had 40 (11.9%) patients, on head and neck 36 (10.7%), on the trunk 146 (43.5%) and on the extremities (except hands and feet) 114 (33.9%) patients. Nodular melanoma (NM) was the most frequent histogenetic type revealed in 150 (44.6%) patients, superficial spreading melanoma (SSM) in 105 (31.1%) patients, acral melanoma (AM) in 39 (11.5%) and lentigo malignant melanoma (LMM) in 32 (9.4%) patients (Table 1). Five-year survival rate was calculated according to Kaplan-Meier's method and significance of the difference between some categories was tested by Long-Rank's test; the significance less than 0.05 was accepted. RESULTS: Statistically highly significant differences in a five-year survival (p < 0.01) were related to sex p = 0.0005, age p = 0.0017, tumour site p = 0.0025, initial therapy p = 0.0036, stage of MM p = 0.0000, histological features of the tumour p = 0.0000 and presence of metastases p = 0.0000. A better five-year survival prognosis was found in female patients (64.5%) compared to male patients 44.5%, aged 27-46 years (87.3%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (66.7%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (65.7%) compared to patients with melanoma on the trunk or acral melanoma (47.3%). Higher survival was recorded in the group of patients with the tumour 1.5-3 mm thick, in whom the tumours was excised and regional nodes dissected as the primary therapy (66.9%) compared to those who underwent excision of the tumor only (48.8%). A five-year survival of patients with MM in situ was 100% for those in stage I; 85% in stage II; 42% in stage III, 16% and 0% in stage IV. The patients in whom the diagnosis of MM was established within 10 months after the first signs of the disease had significa