Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Sclerosis in bisphosphonate-related osteonecrosis of the jaws and its correlation with the clinical stages: study of 43 cases.

We analysed the degree of sclerosis in the different stages of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and studied the relation between the grade of sclerosis, the clinical symptoms, and the depth of lucency. We compared 43 patients with mandibular BRONJ with a control group of 40 cases with no bony lesions. The presence of sclerotic bone, cortical irregularities, radiolucency, fragmentation or sequestration, periostitis, and narrowing of the mandibular canal were studied from computed tomographic (CT) scans using the program ImageJ 1.47v (National Institute of Health, Bethesda, USA) to measure the radiolucency, width of the cortices, and degree of sclerosis. Patients with BRONJ had more severe sclerosis than controls (p<0.01). There was also a significant difference among the different stages of BRONJ, with the highest values found in stage III (p=0.02). The degree of sclerosis differed according to sex, type of bisphosphonate, and the clinical characteristics such as pain, or suppuration, but not significantly so (p>0.05). We conclude that the degree of sclerosis increases with the clinical stage of BRONJ, and is correlated with the depth of lucency.

Factors Affecting Pseudomonas savastanoi pv. savastanoi Plant Inoculations and Their Use for Evaluation of Olive Cultivar Susceptibility.

ABSTRACT Pseudomonas savastanoi pv. savastanoi causes olive knot disease, which is present in most countries where olive trees are grown. Although the use of cultivars with low susceptibility may be one of the most appropriate methods of disease control, little information is available from inoculation assays, and cultivar susceptibility assessments have been limited to few cultivars. We have evaluated the effects of pathogen virulence, plant age, the dose/response relationship, and the induction of secondary tumors in olive inoculation assays. Most P. savastanoi pv. savastanoi strains evaluated were highly virulent to olive plants, but interactions between cultivars and strains were found. The severity of the disease in a given cultivar was strongly dependent of the pathogen dose applied at the wound sites. Secondary tumors developed in noninoculated wounds following inoculation at another position on the stem, suggesting the migration of the pathogen within olive plants. Proportion and weight of primary knots and the presence of secondary knots were evaluated in 29 olive cultivars inoculated with two pathogen strains at two inoculum doses, allowing us to rate most of the cultivars as having either high, medium, or low susceptibility to olive knot disease. None of the cultivars were immune to the disease.

Importance of blood pressure control in hemodialysis patient survival.

BACKGROUND: In the general population, hypertension is the leading cause of cardiovascular mortality. In dialysis patients, however, the relationship between blood pressure (BP) and mortality is controversial. We analyzed this relationship in hemodialysis (HD) patients. METHODS: The study population included 405 patients who had survived at least two years on HD. The observation period was initiated at the beginning of the third year. Predialysis BP measurements of all the dialysis treatments performed during the second year of HD was collected as the baseline data. Mean systolic BP (SBP) and mean diastolic BP (DBP) were calculated. Demographic and comorbidity data were collected at the start of the observation period (beginning of third year of HD). Mortality was analyzed at the end of the follow-up (death or December 31, 1998; total mortality), during the first two years of follow-up (years 3 and 4 of HD; early mortality) and after the second year of follow-up (> or = 5 years of HD; late mortality). RESULTS: In the multivariate analysis, SBP and DBP were significantly associated with death. The adjusted total mortalities were U shaped. When early mortality was analyzed, only low BP (DBP <74.5 mm Hg) was significantly associated with mortality. When late mortality was analyzed, only high BP (SBP> 160 mm Hg) was significantly associated with mortality. In the early deaths, a cardiac cause was significantly less frequent, while withdrawal and malignancy were more frequent than in late deaths. CONCLUSIONS: This study confirms that hypertension is a risk factor for mortality in HD patients, and shows the importance of the length of the follow-up time to demonstrate this relationship. The low frequency of a cardiac cause in the early death group suggests that the association between hypotension and mortality in HD patients is not related to cardiovascular causes, and only reflects the association between hypotension and other severe medical conditions.

Genotoxicity and radioresistance in electroplating workers exposed to chromium.

A biomonitoring study was carried out to investigate the genetic risk associated to occupational exposure to chromium. The induction of genetic damage was measured by analysing the frequency of micronuclei (MN) in peripheral blood lymphocytes. In addition to the 40 electroplater exposed workers who participated in the study, a group constituted by 18 volunteer donors, without exposure to chromium, was analysed as a control group. Measures of chromium levels at working place and in erythrocytes and urine were obtained, as indicators of exposure. The results from this study indicate that the blood from exposed workers contained higher levels of chromium, when compared with those obtained in the control group, and that a significant increase in the frequency of both the total number of MN and the number of binucleated cells carrying MN (BNMN) was detected. Furthermore, a good direct relationship was obtained between the amount of chromium present in air, erythrocytes or urine and the frequency of MN. To determine the existence of radioresistance as consequence of chromium exposure, the response of lymphocytes to the in vitro gamma-radiation was studied. The results of this experiment show a lower induction in the increase of the frequency of MN after challenge irradiation in the lymphocytes of chromium exposed workers, which should be indicative of an adaptive response.

Comparison of survival for haemodialysis patients vs renal transplant recipients treated in Uruguay.

BACKGROUND: Our aim was to compare survival among renal transplant recipients and haemodialysis patients treated in Uruguay. METHODS: All the patients transplanted in Uruguay (n=460) and all the patients who started haemodialysis (HD) in three centres in Uruguay (n=695) from 01 January 1981 to 31 December 1998 were included. Overall survival, adjusted survival and survival of the patients in the low-risk group were compared for HD patients and renal transplant recipients. Diabetic and non-diabetic patients were considered independently. The low-risk group was defined by the absence of any significant risk factor related to mortality on the Cox proportional hazard regression model (age more than 55 years at start of HD, previous history of diabetes, heart disease, cancer, and smoking habit). The significant variables were also used to adjust the survival curve. RESULTS: Overall survival was significantly greater in renal transplant recipients (P<0.0001). One-, five- and ten-year survival rates were 95.2, 88.0 and 78.8% for renal transplant recipients and 90.6, 62.7 and 39.8% for HD patients. In non-diabetic patients, adjusted survival rates (for age, heart disease, cancer, and smoking habit) were similar in renal transplant recipients and HD patients (P=0.8713). In the low-risk group as well, significant differences in survival between renal transplant recipients (n=289) and HD patients (n=134) were not observed (P=0.2312). Ten-year survival rates were 82.6 and 87.9% respectively. In diabetic patients 5-year survival rates adjusted for heart disease, smoking habit, and chronic pulmonary disease were 89.2% for renal transplant recipients and 40.9% for HD patients (P=0. 0168) The relative risk of haemodialysis patients related to renal graft recipients was 2.85 (1.21-6.75). CONCLUSIONS: We conclude that when the outcome is adjusted to co-morbid factors there is no difference between renal transplant recipients and haemodialysis patients survival in non-diabetic patients, while renal transplantation gives better survival rates than haemodialysis in diabetic patients.

Low sensitivity of the sister chromatid exchange assay to detect the genotoxic effects of radioiodine therapy.

To assess the genotoxic risk associated with 131I therapy, sister chromatid exchanges (SCEs) and cells with unusually high SCE counts (HFC) were determined in a follow-up study performed with 46 hyperthyroidism and 39 thyroid cancer patients treated with 131I. In addition, a cross-sectional study was also carried out with 78 control persons and 51 thyroid cancer patients that had completed radioiodine therapy from 1 to 6 years prior to the current investigation. In the follow-up analysis, the study was conducted over time and four blood samples were drawn from each patient: the first one prior to the radioiodine treatment, with the remaining three taken sequentially over the year after therapy. Concerning the results obtained for the whole population in the follow-up study, the SCE and HFC values found after radioiodine therapy did not show any significant increase, neither in the hyperthyroidism nor thyroid cancer groups. Unlike the results mentioned above, when the effect of smoking habit was considered, there was a slight but significant increase in SCE in the samples taken 3 months and 1 week after 131I therapy in the hyperthyroidism and thyroid cancer non-smokers, respectively. The data obtained in the cross-sectional study did not show differences in SCE and HFC between the control group and the cancer group treated with 131I. It is noteworthy that among the different parameters analysed, smoking habit is the only factor that showed a direct relationship with SCE and HFC and, as a consequence, smokers had significantly more SCE and HFC than non-smokers. Taking into account our previous investigations showing a highly significant increase in the frequency of micronuclei for the same patients and sampling times, the outcomes obtained would suggest that the eventual genotoxic effect of 131I therapy could not be clearly detected by the SCE assay. This would reinforce the view that ionizing radiation appears to be a poor inducer of SCEs.

ESRD patients without co-morbid risk factors at the start of haemodialysis are ideal as survival comparison population.

BACKGROUND: Our aim was to identify co-morbid risk factors in ESRD patients at the start of the treatment, to select patients in the low-risk group (LRG) and to compare overall survival, adjusted overall survival and LRG survival in three centres (A, B and C). METHODS: Population includes 531 patients entering haemodialysis from 1 January 1981 to 31 December 1996 (mean age 59.6 +/- 16.7 years). Demographics and co-morbidity data collected at the start of HD were independent variables for the analysis. Univariate and multivariate analysis of survival were used to identify significant prognostic factors (Kaplan-Meier and Cox hazard regression model respectively). According to this analysis the LRG was defined by the absence of the identified significant mortality risk factors except age. RESULTS: The overall median survival was 7.92 years, with 92.0% survival at 1 year, 65.2% at 5 years and 40.4% at 10 years. The median survival in centre C (10.83 years) was significantly higher than median survival in centre A (7.0 years) and in centre B (7.83 years). Centres A and B were afterwards analysed together (A-B). In the multivariate analysis, five variables (starting age, diabetes, cancer, smoking habit, and arteriosclerotic heart disease) were associated with survival. The variable centre (A-B or C) was not significant. The adjusted survival curve for centres A-B and C were not different. The LRG included patients of any age, without diabetes, cancer, smoking habit, and arteriosclerotic heart disease. The frequency of the patients in the LRG was 66.3% in centre C and 45.7% in centre A-B (P = 0.0004). Taking into account only the LRG, the survival comparison between centres A-B and C, did not show significant differences (P = 0.196). CONCLUSIONS: We conclude that for purposes of comparison of mortality in ESRD, low-risk population is better than overall ESRD population.

Cytogenetic damage after 131-iodine treatment for hyperthyroidism and thyroid cancer. A study using the micronucleus test.

To detect the incidence and persistence of potential chromosome damage induced by iodine-131 therapy, we applied the cytokinesis-block micronucleus assay to peripheral blood lymphocytes from hyperthyroidism and thyroid cancer patients treated with 131I. Two groups of patients were evaluated in a longitudinal study; one group was composed of 47 hyperthyroid patients and the other of 39 thyroid cancer patients. In the hyperthyroidism group, the micronuclei frequency was determined before 131I therapy and 1 week, 1 month and 3 months after it. Furthermore, an additional sample was taken from a subgroup of 17 hyperthyroidism patients 6 months after treatment. In the thyroid cancer group, the analysis was also conducted over time, and four samples were studied: before treatment and 1 week, 6 months and 1 year later. Simultaneously, a cross-sectional study was performed with 70 control subjects and 54 thyroid cancer patients who had received the last therapeutic dose 1-6 years before the present study. In the hyperthyroidism group a significant increase in the micronuclei average was found over time. In the sample obtained 6 months after therapy, the micronuclei mean frequency was practically the same as in the sample taken 3 months before. In the thyroid cancer group a twofold increase in the frequency of micronuclei was seen 1 week after therapy. Although this value decreased across time, the micronuclei frequency obtained 1 year after 131I therapy remained higher than the value found before it. Concerning the data from the cross-sectional study, a significant increase in the frequency of micronuclei was detected in the subgroup of thyroid cancer patients treated between 1 and 3 years before the current study. These results indicate that exposure to 131I therapy induces chromosome damage in peripheral lymphocytes and that the cytokinesis-block micronucleus assay is sensitive enough to detect the genetic damage by exposure to sufficiently high levels of radiation from internal radioactive sources.

Biomonitoring of workers exposed to lead. Genotoxic effects, its modulation by polyvitamin treatment and evaluation of the induced radioresistance.

A population monitoring study was performed, by using the micronucleus (MN) assay in human peripheral lymphocytes, to investigate whether occupational exposure to lead is genotoxic to workers. In addition to the exposed workers group, two more groups were studied, an external group from a factory without exposure to lead and an internal control group, from the same factory as the exposed workers, but that were not directly exposed to lead. Measures of lead levels at working place and in blood were calculated, and blood samples were collected to carry out a MN study. The results from these studies indicate that the blood from workers directly exposed contained high levels of lead, compared with the other groups, and a significant increase in the frequency of both the total number of MN and the number of binucleated cells carrying MN appeared. In addition, a study on the antimutagenic effects of a polyvitamin rich diet was conducted by measuring the frequency of MN after the workers had a four month daily intake of a polyvitamin-polymineral complex. These results clearly show a significant reduction of the MN frequency evaluated after this treatment, obtaining values that were even lower than those obtained in the internal control group. Finally, a challenge assay was carried out to determine response to gamma-radiation as indication of any kind of radiosensitivity or radioresistance. The results of this experiment did not show any significant variation in the increase of the frequency of MN after challenge irradiation in the lead exposed workers; nevertheless this increase was significantly reduced in the sample obtained after the polyvitamin treatment indicating a radioresistance response.

Floriceps saccatus plerocerci (Trypanorhyncha, Lacistorhynchidae) as parasites of dolphin fish (Coryphaena hippurus L.) and pompano dolphin (Coryphaena equiselis L.) in western Mediterranean and eastern Atlantic waters. Ecological and biological aspects.

A study of the plerocerci of Floriceps saccatus from the abdominal cavity of dolphin fish (Coryphaena hippurus) and pompano dolphin (Coryphaena equiselis) was conducted. In all, 565 dolphin fishes were collected from Majorcan waters (Balearic Islands, western Mediterranean) during 3 summer and autumn seasons (1990, 1991, and 1995). From the Canary Islands (eastern Atlantic), 41 specimens of dolphin fish were caught during 1994 and 49 specimens of pompano dolphin during 1995. Cysts of different shapes and sizes appeared in the conjunctive tissues of the abdomen and viscera, mainly in the liver, gonads, and pancreas. A larva was found inside every cyst examined. Small, medium size, and large larvae were found. The largest larvae correspond to Floriceps saccatus plerocercoids. Stomach contents indicated that crustaceans and fish larvae were the main prey items of juvenile C. hippurus, whereas teleosts and cephalopods were the only food found in adult dolphin fishes. Infection of F. saccatus plerocercoids takes place in preadult dolphin fishes. Prevalence increases as fishes grow and change to a diet of teleosts. Coryphaena equiselis was not infected.

Micronuclei analysis in lymphocytes of pesticide sprayers from Concepción, Chile.

To estimate the genetic risk associated with pesticide exposure in a defined population, the frequency of micronuclei (MN) in peripheral blood lymphocytes from a group of 22 pesticide sprayers from Concepción, Chile, occupationally exposed to pesticide mixtures was evaluated. After scoring 1,000 binucleated cells for each donor, no significant increases were observed either for the total number of MN or for binucleated cells with MN, when compared with a concurrent control population. In addition, when the effects of different confounding factors such as age, smoking, and drinking habits were considered, no significant effect was observed. Our conclusion is that, in this specific group of workers and under the particular conditions of exposure to pesticides, when evaluated by the micronucleus assay, no genetic risk was detected.

The alkaline single-cell gel electrophoresis (SCGE) assay applied to the analysis of radiation-induced DNA damage in thyroid cancer patients treated with 131I.

The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be a promising tool for measuring DNA damage at the individual cell level in both in vitro and in vivo studies. To provide further data on the possible applicability of this assay in human biomonitoring studies, we have evaluated the eventual genetic damage induced by therapeutic exposure to 131I, by measuring the Comet length and the amount of DNA damage in peripheral blood leukocytes from a group of 28 thyroid cancer patients who received 131I sodium iodide via oral administration. Blood samples were taken just before the treatment and 1 week after it. From the results obtained after radioiodine therapy, a small increase in the Comet length and in the grade of DNA damage is observed; however, this increase is not statistically significant because of inter-individual variability and the variable responses before and after 131I treatment. Considering our previous studies showing significant increases in the frequency of cytogenetic damage (when measured as micronuclei) in patients treated with relatively low doses of 131I, the results obtained in the present work by using the Comet assay could indicate that 1 week after the exposure most of the radioiodine-induced DNA lesions, that can be detected with this assay, have already been repaired.

Application of the single cell gel electrophoresis (SCGE) assay to the detection of DNA damage induced by 131I treatment in hyperthyroidism patients.

To provide further data on the possible applications of the single cell gel electrophoresis (SCGE) or Comet assay in human biomonitoring studies, we have evaluated the eventual genetic damage induced by therapeutic exposure to 131I, by measuring the tail length of the comet and the amount of DNA damage in peripheral blood cells from 16 hyperthyroidism patients treated with [131I]sodium iodide by oral administration. Blood samples were taken just before the treatment and 1 week and 1 month after. The results show a slight but significant increase in the mean tail length in the sample obtained 1 month after treatment. When the cells were classified according to the grade of damage the two post-treatment samples showed a clear increase in the proportion of damaged cells. The results of this study indicate that the DNA damage caused by 131I can be detected with the Comet assay, but when comparing the data reported here with our previous results obtained from the same patients and sampling times with the sensitive and well-established micronucleus test, the response in the Comet assay was less clear.

SCE analysis in peripheral blood lymphocytes of a group of filling station attendants.

Petroleum derivatives constitute a complex mixture of chemicals which contain known genotoxicants. Thus, chronic occupational exposure to such derivatives may be considered to possess genotoxic risk. Service station attendants are workers exposed to petroleum derivatives and, as consequence, biomonitoring studies designed to evaluate the genetic risk are required. Here we present the data on sister chromatid exchange (SCE) frequencies, proliferation rate index (PRI) and cells with high frequency of SCE (HFC) from a group of 42 attendant workers. In addition, data from a group of 45 unexposed (controls) are presented. The results obtained indicate that there are no significant differences in SCE values between the exposed workers when compared to the non-exposed individuals. The only difference is found when smoking habit is considered, the smokers having significant increases in the SCE frequency. There is a slight increase in the HFC frequency of the occupationally exposed group but the difference did not attain statistical significance.

Genotoxic evaluation of the herbicide paraquat in cultured human lymphocytes.

The widely used herbicide paraquat was evaluated for genotoxicity in peripheral blood human lymphocyte cultures. Sister-chromatid exchanges (SCE), chromosome aberrations (CA), and micronuclei (MN) were scored as genetic endpoints. Paraquat was administered either alone or in combination with an external source of metabolic activation. Our data indicate that paraquat induced slight but significant increases in the frequency of SCE. This genotoxic effect was not modified by cotreatments with S9 fraction from rat liver. However, paraquat did not increase the frequency of CA and MN, indicating that this bipyridylium compound is not effective in these assays, which would mean a general lack of effectiveness of the herbicide to induce clastogenic damage. In addition, cotreatments with the S9 fraction, did not modify the genotoxic ability detected in the SCE assay.

Micronuclei induction by 131I exposure: study in hyperthyroidism patients.

To evaluate the eventual genetic damage induced by therapeutic exposure to 131I, we have studied the presence of micronuclei (MN) in binucleated peripheral blood lymphocytes from a group of 28 hyperthyroidism patients who received 131I sodium iodide, via oral administration. The study was conducted over time and blood samples were obtained before the treatment, and 1 week, 1 month and 3 months after it. The results obtained indicate a positive relationship between dose and BNMN frequency as calculated by the linear regression coefficient, showing significant increases in the frequency of MN and BNMN (binucleated cells with MN) in the subgroup of patients that received more than 500 MBq. Taking into account that the patients studied were treated with relatively low doses of 131I, our positive results support the view that the MN assay is sensitive enough to monitor the chromosome damage resulting from the exposure.

Cytogenetic analysis in peripheral lymphocytes of cancer patients treated with cytostatic drugs: results from an EC Collaborative Study.

Many of the cytostatic drugs commonly used in cancer chemotherapy treatments have been shown to be genotoxic in vivo and in vitro. We present a cytogenetic collaborative study on 13 cancer patients treated with different antitumor agents. For comparison we also carried out a cytogenetic analysis on 14 healthy untreated controls. The frequency of sister chromatid exchanges and structural chromosome aberrations in peripheral blood lymphocytes of the cancer patients was determined prior to the treatment, just after it and 3-7 weeks later. The results obtained show clear differences between the basal levels of cytogenetic alterations in cancer patients, even though the mean value is higher in this group than the basal levels of the group of healthy individuals. Treatment with cytostatics increases the frequency of both cytogenetic biomarkers analyzed, which declined to values similar to those initially observed several weeks after the treatment. Our data are in qualitative and quantitative agreement with other results previously found by other authors.

Temporary variations in chromosomal aberrations in a group of agricultural workers exposed to pesticides.

The induction of chromosomal aberrations (CA) was studied in the peripheral lymphocytes of 29 male agricultural workers occupationally exposed to several pesticides. To investigate possible exposure-related changes in the frequency of CA, a longitudinal study has been conducted. Two blood samples were taken from each individual: one in a period of high exposure (spring-summer) and the other in a period of lower exposure (autumn-winter). Simultaneously, two matched control groups constituted by 29 and 24 healthy men, without indication of exposure to pesticides, were analysed. During the period of major exposure, the group of agricultural workers showed a significant increase in the frequency of CA, mainly of chromatid-type, when compared to the unexposed control group; nevertheless, this increase in the expression of CA was not found in the period of minor exposure. This finding could indicate that the frequency of CA is related to the intensity of the pesticide exposure, and that CA have a relatively short-life, recovering the control value a few months later. In addition to the cytogenetic analysis, biochemical and haemotological blood parameters were also analysed and no significant variations were detected.

SCE analysis in human lymphocytes of a Spanish control population.

SCE (sister-chromatid exchanges), HFC (high frequency cells) and PRI (proliferative rate index) were studied in the peripheral blood lymphocytes of 154 healthy male volunteers, from Barcelona (Spain). SCE, HFC and PRI variability between and/or within individuals was estimated by means of a mixed linear model. This model allows a determination of the relationship between confounding factors (demographics, life style, work exposure and medical history) and the cytogenetic and cytokinetic parameters analyzed. The results obtained indicate the existence of an important intra-individual heterogeneity in SCE rates, as well as in HFC and PRI values. Although age did not seem to affect either the SCE frequency or the HFC percentage, it showed a significant positive association with the presence of cells with higher SCE frequencies. With respect to the confounding factors, only cigarette smoking increased the SCE rates and the HFC values. On the other hand, PRI mean showed significant differences dependent on age and was inversely correlated with alcohol consumption and X-ray exposure.