Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission.

BACKGROUND: In 2011, IARC classified radiofrequency radiation (RFR) as possible human carcinogen (Group 2B). According to IARC, animals studies, as well as epidemiological ones, showed limited evidence of carcinogenicity. In 2016, the NTP published the first results of its long-term bioassays on near field RFR, reporting increased incidence of malignant glial tumors of the brain and heart Schwannoma in rats exposed to GSM - and CDMA - modulated cell phone RFR. The tumors observed in the NTP study are of the type similar to the ones observed in some epidemiological studies of cell phone users. OBJECTIVES: The Ramazzini Institute (RI) performed a life-span carcinogenic study on Sprague-Dawley rats to evaluate the carcinogenic effects of RFR in the situation of far field, reproducing the environmental exposure to RFR generated by 1.8 GHz GSM antenna of the radio base stations of mobile phone. This is the largest long-term study ever performed in rats on the health effects of RFR, including 2448 animals. In this article, we reported the final results regarding brain and heart tumors. METHODS: Male and female Sprague-Dawley rats were exposed from prenatal life until natural death to a 1.8 GHz GSM far field of 0, 5, 25, 50 V/m with a whole-body exposure for 19 h/day. RESULTS: A statistically significant increase in the incidence of heart Schwannomas was observed in treated male rats at the highest dose (50 V/m). Furthermore, an increase in the incidence of heart Schwann cells hyperplasia was observed in treated male and female rats at the highest dose (50 V/m), although this was not statistically significant. An increase in the incidence of malignant glial tumors was observed in treated female rats at the highest dose (50 V/m), although not statistically significant. CONCLUSIONS: The RI findings on far field exposure to RFR are consistent with and reinforce the results of the NTP study on near field exposure, as both reported an increase in the incidence of tumors of the brain and heart in RFR-exposed Sprague-Dawley rats. These tumors are of the same histotype of those observed in some epidemiological studies on cell phone users. These experimental studies provide sufficient evidence to call for the re-evaluation of IARC conclusions regarding the carcinogenic potential of RFR in humans.

Results of lifespan exposure to continuous and intermittent extremely low frequency electromagnetic fields (ELFEMF) administered alone to Sprague Dawley rats.

BACKGROUND: Up to now, experimental studies on rodents have failed to provide definitive confirmation of the carcinogenicity of extremely low frequency electromagnetic fields (ELFEMF). Two recent studies performed in our laboratory on Sprague-Dawley rats reported a statistically significant increase in malignant tumors of different sites (mammary gland, C-cells carcinoma, hemolymphoreticular neoplasia, and malignant heart Schwannoma) when ELFEMF exposure was associated with exposure to formaldehyde (50 mg/l) or acute low dose of γ-radiation (0.1 Gy) (Soffritti et al., 2016a) (Soffritti et al., 2016b). The same doses of known carcinogenic agents (50 mg/l formaldehyde, or acute 0.1 Gy γ-radiation), when administered alone, previously failed to induce any statistically significant increase in the incidence of total and specific malignant tumors in rats of the same colony. OBJECTIVES: A lifespan whole-body exposure study was conducted to evaluate the possible carcinogenic effects of ELFEMF exposure administered alone to Sprague-Dawley rats, as part of the integrated project of the Ramazzini Institute (RI) for studying the effects on health of ELFEMF alone or in combination with other known carcinogens. METHODS: Male and female Sprague-Dawley rats were exposed 19 h/day to continuous sinusoidal-50 Hz magnetic fields (S-50 Hz MF) at flux densities of 0 (control group), 2, 20, 100 or 1000µT, and to intermittent (30 min on/30 min off) S-50 Hz MF at 1000 µT, from prenatal life until natural death. RESULTS: Survival and body weight trends in all groups of rats exposed to ELFEMF were comparable to those found in sex-matched controls. The incidence and number of malignant and benign tumors was similar in all groups. Magnetic field exposure did not significantly increase the incidence of neoplasias in any organ, including those sites that have been identified as possible targets in epidemiological studies (leukemia, breast cancer, and brain cancer). CONCLUSIONS: Life-span exposures to continuous and intermittent sinusoidal-50 Hz ELFEMFs, when administered alone, did not represent a significant risk factor for neoplastic development in our experimental rat model. In light of our previous results on the carcinogenic effects of ELFEMF in combination with formaldehyde and γ-radiation, further experiments are necessary to elucidate the possible role of ELFEMF as cancer enhancer in presence of other chemical and physical carcinogens.

Potential carcinogenic effects of world trade center dust after intratracheal instillation to Sprague-Dawley rats: first observation.

BACKGROUND: More than 10 years have passed since the terrorist attack on the New York City World Trade Center on September 11, 2001. It is well known that long-term carcinogenic bioassays on rodents can predict the potential carcinogenic effects of chemical and physical agents for humans. OBJECTIVE: A life-span carcinogenicity bioassay was conducted on Sprague-Dawley rats at the CMCRC of the Ramazzini Institute to test the potential carcinogenic effects of settled dust collected at the WTC immediately after the terrorist attack. METHODS: The WTC material tested is a complex mixture of coarse particles (95%) contain pulverized cement, glass fibres, asbestos, lead, polycyclic aromatic hydrocarbons (PAH(S) ), polychlorinated biphenyls (PCB(S) ) and polychlorinated furans, and dioxin. The test matter was suspended in sterile saline and administered by intratracheal instillation (IT) to 8-week-old Sprague-Dawley rats (100 animals/sex), 3-4 days/week for 4 weeks. A group of 200 male and female rats served as controls. The animals were kept under observation until natural death. RESULTS: Histopathological evaluation of the lungs (target organ) of instilled control and treated male and female rats, did not show any significant increased incidence of lung tumors. Two hemangiomas (one with endothelial atypia) and one hemangiosarcoma were found in the lungs of treated males. Moreover a modest increased incidence of terminal bronchiolar hyperplasia (TBH) and squamous metaplasia occurred in the lung of treated males and females compared to the controls. CONCLUSION: Hemangioma and hemangiosarcoma are extremely rare tumors in the lung of our colony and we believe they are caused by WTC dust.

Prevalence of musculoskeletal symptoms among aluminium workers.

The aim of this study was to determine the prevalence of musculoskeletal symptoms (MSS) in workers in the aluminium industry, and to test the relationship with work by using the duration of employment as a measure of exposure. A total of 5654 workers (92%) answered a questionnaire. Operators, who were more exposed to physically demanding work, showed a greater incidence of MSS than did office workers. Among operators, the duration of employment was significantly correlated with MSS in nine out of ten areas of the body, when adjusted by multiple regression analyses for age, gender, height, weight, smoking and physical activity. Among office workers this relationship was weaker and was significant only for neck and lower back areas. The higher prevalence of MSS among operators and the association between their duration of employment and MSS suggests that a higher risk of MSS is related to the working environment.

Evidence based assessment of long-term results of plaque incision and vein grafting for Peyronie's disease.

PURPOSE: We assessed the long-term outcome of plaque incision and vein grafting in select patients with Peyronie's disease by extensive preoperative and postoperative subjective and objective analysis. MATERIALS AND METHODS: From January 1995 to June 1998, 50 men 28 to 62 years old (mean age 44) underwent surgery. Patients were evaluated preoperatively, 3 months after surgery and at a mean long-term followup of 32 months by sexual history, physical examination, determination of penile length and degree of curvature, dynamic color power Doppler sonography of the penile vessels and nocturnal RigiScan* evaluation for 3 nights. Study inclusion criteria were penile curvature 45 degrees or greater that made vaginal intromission impossible, stable disease for at least 6 months, patient reported normal penile rigidity, normal penile hemodynamics on color power Doppler ultrasound, normal nocturnal penile rigidity with at least 1 erection nightly (including base and tip rigidity greater than 60%, and a duration of 10 minutes) and absent base-tip discrepancies. Plaque was usually approached via a combined subcoronal and midline sagittal scrotal incision. Maximal rigidity was created intraoperatively and 1 to 3 plaque incisions were made. Saphenous vein patches were then grafted at the incision sites. Postoperatively patients were systemically treated with neurotrophic factors and low molecular weight heparin. Local vacuum supported corporeal stretching was done and weekly alprostadil injections were given to optimize corporeal oxygenation. RESULTS: At long-term followup complete penile straightening was achieved in 40 cases (80%), minor residual curvature of 30 degrees or less persisted in 7 (14%) and significant disease recurred in 3 (6%). Penile rigidity was equal to that preoperatively in 47 patients (94%), while 3 (6%) reported clinically significant decreased potency. Penile length was equal to that preoperatively in 30 patients (60%), while 20 (40%) noticed slight penile shortening. Postoperatively penile color power Doppler sonography showed vascular impairment in 5 men (10%) and nocturnal RigiScan testing revealed a significant decrease in nightly erections in 5 (10%). Surgical complications included penile hypoesthesia in 1 case (2%), penile hematoma in 2 (4%), wound infection in 1 (2%) and glandular ischemia in 1 (2%). CONCLUSIONS: Plaque incision and vein grafting achieved satisfactory clinical results in the majority of patients with severe and stable Peyronie's disease, intact penile rigidity preoperatively, normal penile color power Doppler ultrasound and normal nocturnal RigiScan testing.

Mega-experiments to identify and assess diffuse carcinogenic risks.

Diffuse carcinogenic risks, that is, those of low potency involving large areas of population and sometimes all mankind, pose a serious public health problem. Controlling these risks might help to reduce the incidence of, and mortality from, cancer. Because of their low expected carcinogenic potential, these risks are difficult to expose or assess. Epidemiologic investigation is of limited use in this field and yields its data too late to be useful. Experimental studies offer the only possible approach for assessing such risks. To increase experimental sensitivity and consistency of results, mega-experiments must be designed. That is, experiments that use a large number of animals with a well-known basic tumorigram, that extend the exposure and the biophase for as long as possible, that carefully observe the effects, and that are performed with suitable standardized methods. In the last 15 years the Ramazzini Foundation, in its Cancer Research Center at Bentivoglio, has conducted or planned five mega-experiments. Initial results indicate the great potential of these methods for identifying and assessing diffuse risks.

Results of three life-span experimental carcinogenicity and anticarcinogenicity studies on tamoxifen in rats.

Tamoxifen was submitted to carcinogenicity bioassays on Sprague-Dawley rats (of the colony used at the Cancer Research Center in the Castle of Bentivoglio of the European Ramazzini Foundation of Oncology and Environmental Sciences) at the dose of 3.3 mg/kg b.w., by stomach tube, in three experiments. In the first experiment the drug was administered once daily, 6 days a week to male and female rats, 8 weeks old at start for their life span. In the second experiment, the drug was administered to female rats, 12 weeks old at start, once daily for 8 consecutive days every 8 weeks for their life span. In the third experiment the drug was administered to female rats, 56 weeks old at start, 6 times weekly for 40 weeks; and then the animals were kept alive for their life span. In the first experiment, a mild increase in hepatocarcinomas with low grading was detected. In the first and second experiments, a borderline increase in uterine malignancies was found. No carcinogenic effect was observed in the third experiment. In the three experiments, tamoxifen showed a strong, long-lasting chemopreventive effect on mammary benign tumors and cancers. The presented data also indicate that tamoxifen treatment reduces the incidence of other tumors: pituitary adenomas, adrenal pheochromocytomas, islet cell pancreatic tumors, Leydig cell testicular tumors, and polyps of the uterus.

[Radical transcoccygeal prostatectomy]. / Prostatectomia radicale per via transcoccigea.

OBJECTIVE: A non randomized prospective study aimed at verifying the clinical outcome and pathological features of a group of patients submitted to transcoccygeal radical prostatectomy. METHODS: Radical transcoccygeal prostatectomy was carried out at our institution in 26 patients after laparoscopic (24 cases) or open surgical (2 cases) pelvic lymphadenectomy. Eighteen patients were selected if considered at risk for nodal metastases on the basis of preoperative staging (PSA > or = 20 ng/ml and/or Gleason score > 5), while the remaining 8 were affected by incidental prostate carcinoma. RESULTS: Intraoperative complications included rectal injury and massive blood los in one case (3.8%). Transitory leakage at the site of the urethrovesical anastomosis and urethrorectal fistula occurred postoperatively in two patients. The rate of positive surgical margins was 26.9%. The mean follow-up time was 27 months (range 3-39 months). Total urinary continence was obtained in 21 cases (80.8%), while 5 patients (19.2%) still require urinary pads. Four patients (15.4%) have experienced tumour recurrence evidenced only by elevated serum PSA levels. Local tumour recurrence with positive biopsy of urethrovesical junction was diagnosed in 3 patients (11.5%), while systemic tumour recurrence occurred in one case (3.8%). CONCLUSIONS: Radical transcoccygeal prostatectomy is a safe procedure for the surgical treatment of prostate cancer both from a clinical and pathological point of view. Operative complications, as well as pathological features and clinical outcome reported in this series of patients, must be related to selection criteria use in the majority of cases. The exact role of radical transcoccygeal prostatectomy in the clinical setting has yet to be defined. According to these preliminary results, radical transcoccygeal prostatectomy should be further investigated in the treatment of incidental carcinoma following TURP or suprapubic prostatectomy.

[Current diagnostic-therapeutic trends in treatment of pediatric appendicitis]. / Attuali atteggiamenti diagnostici-terapeutici nel trattamento della appendicite in età infantile.

Acute appendicitis is the first cause of emergency surgery in children. Actually, emergency abdominal sonography has evolved in differential diagnosis of acute appendicitis in children to differentiate it from other causes of acute abdomen as mesenteric lymphoadenitis, acute right pyelonephritis, acute diverticulitis in Meckel's diverticulum, intestinal intussusception, regional enterits, primary peritonitis, anaphylactoid purpura of Henoch-Schonlein. The aim of this study is the evaluation of the usefulness of abdominal sonography in diagnosing acute appendicitis in our current series of pediatric patients. We have operated 102 patients afflicted by appendicitis admitted to the pediatric department of Ospedale San Raffaele, Milano in a period of 5 years and operated on for appendectomy. In the last 2 years 36 patients were evaluated with abdominal sonography. This diagnostic tool showed in 34 (94.4%) a liquid effusion, sometimes thick of the right iliac fossa. In 2 patients the appendix had thickened layers, was edematous and the lumen was clearly filled with debris. Abdominal sonography has given a clear cut picture of the acute inflammatory process of the appendix. None of these patients has suffered from septic or obstructive complications. Mean duration of hospital stay was 6.35 days (3-15 days). Differential diagnosis of acute appendicitis can be extremely variable, from simple, paradigmatic situations to the most intriguing ones. This concept is well emphasized by William Silen when he says that "differential diagnosis of acute appendicits is an encyclopedic compendium of every abdominal disease that causes pain" in the 11th edition of Harrison's Principles of Internal Medicine.(ABSTRACT TRUNCATED AT 250 WORDS)