The longitudinal biomonitoring of residents living near the waste incinerator of Turin: Polycyclic Aromatic Hydrocarbon metabolites after three years from the plant start-up.

The waste-to-energy (WTE) incinerator plant located in the Turin area (Italy) started to recover energy from the combustion of municipal solid waste in 2013. A health surveillance program was implemented to evaluate the potential health effects on the population living near the plant. This program included a longitudinal biomonitoring to evaluate temporal changes of some environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs), in residents living in areas near the Turin incinerator (exposed group, E) compared to those observed in subjects living far from the plant (not exposed group, NE). Ten monohydroxy-PAHs (OH-PAHs), consisting in the principal metabolites of naphthalene, fluorine, phenanthrene, and pyrene, were analyzed in urines collected from the E and NE subjects after one (T1) and three years (T2) of plant activity and compared with those determined in the same cohort established before the plant start-up (T0). Spearman correlation analysis was undertaken to explore possible associations between OH-PAHs and personal characteristics, lifestyle variables, and dietary habits. A linear mixed model (LMM) approach was applied to determine temporal trends of OH-PAHs observed in the E and NE subjects and to evaluate possible differences in trend between the two groups. Temporal trends of OH-PAHs determined by LMM analysis demonstrated that, at all times, the E group had concentrations lower than those assessed in the NE group, all other conditions being equal. Moreover, no increase in OH-PAH concentrations was observed at T1 and T2 either in E or in NE group. Significant positive correlations were found between all OH-PAHs and smoking habits. Regarding variables associated to outdoor PAH exposure, residence near high traffic roads and daily time in traffic road was positively correlated with 1-hydroxynaphthalene and 1-hydroxypyrene, respectively. In conclusion, no impact of the WTE plant on exposure to PAHs was observed on the population living near the plant.

Percutaneous puncture during PCNL: new perspective for the future with virtual imaging guidance.

CONTEXT: Large and complex renal stones are usually treated with percutaneous nephrolithotomy (PCNL). One of the crucial steps in this procedure is the access to the collecting system with the percutaneous puncture and this maneuver leads to a risk of vascular and neighboring organs' injury. In the last years, the application of virtual image-guided surgery has gained wide diffusion even in this specific field. OBJECTIVES: To provide a short overview of the most recent evidence on current applications of virtual imaging guidance for PCNL. EVIDENCE ACQUISITION: A non-systematic review of the literature was performed. Medline, PubMed, the Cochrane Database and Embase were screened for studies regarding the use virtual imaging guidance for PCNL. EVIDENCE SYNTHESIS: 3D virtual navigation technology for PCNL was first used in urology with the purpose of surgical training and surgical planning; subsequently, the field of surgical navigation with different modalities (from cognitive to augmented reality or mixed reality) had been explored. Finally, anecdotal preliminary experiences explored the potential application of artificial intelligence guidance for percutaneous puncture. CONCLUSION: Nowadays, many experiences proved the potential benefit of virtual guidance for surgical simulation and training. Focusing on surgery, this tool revealed to be useful both for surgical planning, allowed to achieve a better surgical performance, and for surgical navigation by using augmented reality and mixed reality systems aimed to assist the surgeon in real time during the intervention.

Neonatal overfeeding by small-litter rearing sensitises hippocampal microglial responses to immune challenge: Reversal with neonatal repeated injections of saline or minocycline.

The early-life period is extremely vulnerable to programming effects from the environment, many of which persist into adulthood. We have previously demonstrated that adult rats overfed as neonates have hypothalamic microglia that are hyper-responsive to an immune challenge, as well as hippocampal microglia that respond less efficiently to learning. We therefore hypothesised that neonatal overfeeding would alter the ability of hippocampal microglia to respond to an immune challenge with lipopolysaccharide (LPS) and that concomitant minocycline, a tetracycline antibiotic that suppresses microglial activity, could restore these responses. We induced neonatal overfeeding by manipulating the litter sizes in which Wistar rat pups were raised, so the pups were suckled in litters of four (neonatally overfed) or 12 (control-fed). We then examined the hippocampal microglial profiles 24 hour after an immune challenge with LPS and found that the neonatally overfed rats had dramatically increased microglial numbers in the hippocampus after immune challenge compared to control-fed rats. Attempts to reverse these effects with minocycline revealed repeated that neonatal injections, whether with minocycline or with saline, markedly suppressed microglial number and density throughout the hippocampus and abolished the difference between the groups in their responses to LPS. These data suggest that neonatal overfeeding not only can have lasting effects on hippocampal immune responses, but also that neonatal exposure to a protocol of repeated injections, irrespective of treatment, has a pronounced long-term impact, highlighting the importance of considering these effects when interpreting experimental data.

Gene Expression of Matrix Metalloproteinases and their Inhibitors (TIMPs) in Meningiomas of Dogs.

BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are considered to be key mediators of tumor invasion and metastasis. MMP-2 and MMP-9 are expressed in meningiomas of dogs, but TIMP expression, and variations of specific MMP/TIMP ratios still are unknown in this tumor. HYPOTHESIS/OBJECTIVES: Expression of MMP/TIMP might increase progressively from grade I to grade III meningioma. Therefore, genetic expression of MMP-2 and MMP-9, and specific TIMP-2 and TIMP-1, respectively, has been investigated in meningiomas of different grades. ANIMALS: Selected formalin-fixed paraffin-embedded tissue from 43 meningiomas of dogs was evaluated. METHODS: Genetic material was obtained from pathologic samples and used for quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR). RESULTS: MMP-9 was not expressed in all of the tumors, but MMP-2 was significantly more expressed in papillary meningioma. Likewise, the MMP-2/TIMP-2 ratio was numerically higher in papillary meningiomas compared to all grades (>3.5 times) showing a strong bias in favor of metalloproteinase. In the papillary meningioma, TIMP-1 gene expression was significantly higher than in grades I and III. CONCLUSIONS AND CLINICAL IMPORTANCE: MMP-2/TIMP-2 imbalance might contribute to the aggressive biologic behavior of papillary meningiomas in dogs. TIMP-1 expression may play a role independent of MMP-9 expression in neoplastic progression. These results further support that therapeutic and prognostic evaluations of dogs with meningioma need to be addressed according to different histologic patterns as is performed in humans.

Comparison Between Rapid Intraoperative and Central Laboratory Parathormone Dosage in 12 Kidney Transplant Candidates.

BACKGROUND: The rapid intraoperative parathormone (PTH) and at central laboratory PTH dosage gives similar results. The central laboratory provides results in longer times and higher costs. Intraoperative measurement can reduce time and costs during parathyroidectomy. METHODS: Twelve patients undergoing parathyroidectomy for hyperparathyroidism renal transplant candidates were included. Diagnosis was made by laboratory tests (serum calcium, PTH) and imaging techniques (ultrasonography and scintigraphy). All patients presented PTH levels of >400 pg/mL (the limit value to be maintained in list for kidney transplantation) and resistant to medical therapy. For each patient, 2 blood samples were collected before surgery at anesthesia induction for PTH testing intraoperative (rapid assay) and central laboratory, and 10 minutes after the removal of each gland. The times from collection-processing to communication to the surgeon of the results were compared for both the methods. It was considered successful the abatement of PTH of ≥70% at rapid intraoperative testing and consequently surgical intervention stopped before communication of central laboratory PTH testing. RESULTS: The average time of reporting the test results of the central laboratory was 41.5 minutes (SD ± 9), whereas with the rapid intraoperative PTH (ioPTH) testing the average time was 9.9 minutes (SD ± 2.02). An average of 33.6 minutes of the duration per intervention (SD ± 10.27) were virtually saved with the use of ioPTH testing. The 2 values of the Pearson correlation (ρ) of 0.99 obtained (for baseline) and 0.975 (for the 10-minute) lead us to conclude that there is an excellent correlation between the series of data. CONCLUSIONS: Rapid ioPTH testing, owing to its accuracy, permits a dramatic reduction of operating time for patients with secondary hyperparathyroidism that need to be treated before inclusion on the waiting list.

[-2]proPSA versus ultrasensitive PSA fluctuations over time in the first year from radical prostatectomy, in an high-risk prostate cancer population: A first report.

BACKGROUND: [-2]proPSA and its derivatives have an higher diagnostic accuracy than PSA in predicting prostate cancer (PCa). In alternative to PSA, ultrasensitive PSA (uPSA) and [-2]proPSA could be potentially useful in recurrent disease detection. This research focused on [-2]proPSA and uPSA fluctuations over time and their possible clinical and pathological determinants, in the first year after RP. METHODS: A cohort of 106 consecutive patients, undergoing RP for high-risk prostate cancer (pT3/pT4 and/or positive margins), was enrolled. No patient received either preoperative/postoperative androgen deprivation therapy or immediate adjuvant RT, this latter for patient choice. [-2]proPSA and uPSA were measured at 1, 3, 6, 9, 12 months after RP; their trends over time were estimated by the mixed-effects linear model. The uPSA relapse was defined either as 3 rising uPSA values after nadir or 2 consecutive uPSA >0.2 ng/ml after RP. RESULTS: The biochemical recurrence (BCR) rate at 1 year after RP was either 38.6 % (in case of 3 rising uPSA values) or 34.9 % (in case of PSA >0.2 ng/ml after nadir), respectively. The main risk factors for uPSA fluctuations over time were PSA at diagnosis >8 ng/ml (p = 0.014), pT (p = 0.038) and pN staging (p = 0.001). In turn, PSA at diagnosis >8 ng/ml (p = 0.012) and pN (p < 0.001) were the main determinants for [-2]proPSA trend over time. In a 39 patients subgroup, uPSA decreased from month 1 to 3, while [-2]proPSA increased in 90 % of them; subsequently, both uPSA and [-2]proPSA increased in almost all cases. The [-2]proPSA trend over time was independent from BCR status either in the whole cohort as well in the 39 men subgroup. CONCLUSIONS: Both uPSA and [-2]proPSA had independent significant fluctuations over time. PSA at diagnosis >8 ng/ml and pathological staging significantly modified both these trends over time. Since BCR was not confirmed as determinant of [-2]proPSA fluctuations, its use as marker of early biochemical relapse may not be actually recommended, in an high-risk prostate cancer patients population.

Early surgery after coronary revascularization: a fine line between bleeding and thrombosis.

Management of PCI patients undergoing early surgery is still a matter of debate. Noteworthy, PCI patients require a dual antiplatelet therapy (DAPT), with aspirine and a thienopiridine (clopidogrel, prasugrel, ticagrelor), because of the high risk of stent thrombosis (ST), myocardial infarction (MI) and death, especially within the first month. Indeed, the number of surgical interventions after PCI is actually increasing, and physicians are looking for the best antiplatelet therapy management, in order to reduce both, bleeding and thrombosis risk. In this paper, current guidelines therapy management and new optional strategies to reduce the cardiovascular risk, related to early surgery, are discussed.

Actualización de la estadificación del cáncer de próstata

En nuestro país el cáncer de próstata es la neoplasia más frecuente en hombres de edad avanzada. Por ello, resulta indispensable una adecuada estadificación al momento de establecer la estrategia terapéutica. En este artículo se presenta la 7.a edición del sistema TNM de estadifi cación para el cáncer de próstata, vigente desde el 1.º de enero de 2010. El mismo ha tenido modifi caciones mayores con respecto a la 6.a edición.

In our country prostate cancer is the most common malignancy in older men. An accurate staging is very important to establish treatment strategies.This article presents the 7th edition TNM staging system for prostate cancer, effective January 1, 2010. This has undergone major changes over the 6th edition.

A simple technique to improve residual skin plasticity for scrotal reconstruction in Fournier's Gangrene.

A 50 years-old man developed 24 hours after hemorrhoidectomy a severe Fournier's gangrene of the scrotum necessitating surgical exeresis of more than 2/3 of scrotal skin followed by hyperbaric oxygen therapy. After the resolution of the septic phase, scrotum reconstruction was obtained by tissue expansion to avoid more invasive advanced reconstructive techniques. The procedure consisted of an enzymatic and mechanical debridement and progressive skin expansion by package of gauzes of increasing volume covered with a collagenasecloramphenicol ointment (Iruxol®- Smith and Nephew, Italy), then closing the wound edges by temporary stitches to put under tension the skin. The reestablishment of the natural elasticity of the scrotal skin was obtained in ten days and at the final closure of the wound edges an acceptable optimal aesthetic result was achieved.

[Gastric leiomyosarcoma: case report and review of literature]. / Il leiomiosarcoma dello stomaco: caso clinico e revisione della letteratura.

True smooth muscle neoplasms of the wall of digestive tract are rare, in particular in the stomach, and the benign ones are prevalent. We report a case of gastric leiomyosarcoma (LMS) that we observed, diagnosed to a 71 years-old man, with important comorbidities, who had already underwent the amputation of the right lower limb. In consequence of the discovery of anaemia and melaena he underwent an endoscopy of the upper GI tract and CT scan, which showed the presence of a neoformation of the gastric wall, but because of the thrombosis of the common iliac artery and the occurrence of the clinical picture of critical ischaemia, at first the patient underwent the amputation of the left lower limb e only then an intervention of atypical gastroresection. Despite the neoplastic infiltration of the resection margins and the impossibility to undertake an adjuvant chemotherapy, the follow-up at 6, 12 and 28 months did not show a recurrence of the disease that remained in phase of clinical remission.

[Role of the vesico-urethral anastomosis biopsy in the diagnosis of local recurrence following radical prostatectomy.Our experience].

In the long-term there is biochemical evidence of recurrent prostate carcinoma in approximately 40% of patients after radical prostatectomy (RP). Detecting the site of recurrence (local vs distant) is critical for defining the optimum treatment. Pathological and clinical variables (Gleason score, involvement of seminal vesicles or lymph nodes, margin status at surgery, and especially the timing and pattern of PSA recurrence) may help to predict the site of relapse. Transrectal ultrasonography (TRUS) of the prostatic fossa in association with TRUS-guided needle biopsy is considered more sensitive than a digital rectal examination for detecting local recurrence, especially if PSA levels are low. Although it cannot detect minimal tumor mass at very low PSA levels (<1 ng/mL), TRUS biopsy is presently the most sensitive method for detecting local recurrence. Nevertheless, the conclusive role of biopsy of the vesico-urethral anastomosis remains unclear. However, [11C]-choline tomography (which is better than conventional imaging for detecting metastatic tumor) has low detection rates for local disease and is considered complementary to TRUS in this setting. Patients with a high PSA after RP may be managed with external beam salvage radiotherapy. An initial PSA of <1 ng/mL, Gleason score < 8 and radiation dose of 66-70 Gy seem to be key factors in determining success. Although a positive TRUS anastomotic biopsy may predict a better outcome after radiation therapy, the need of taking a biopsy in the event of PSA failure remains under investigation. The value of salvage radiation to the prostatic bed for PSA-only progression after RP remains in question.

Changing trends in surgery for acute appendicitis.

BACKGROUND: Laparoscopic appendicectomy (LA) offers faster recovery times and a reduced rate of wound infection compared with open appendicectomy (OA) but may be associated with more intra-abdominal abscesses. This study examines the changing trends in management of appendicitis in a regional setting during service reorganization and compares infective complication rates for each procedure. METHODS: Data were retrieved from the Lothian Surgical Audit database on 1824 patients treated for appendicitis by OA or LA during equal 31-month periods before and after service reorganization in August 2002. Outcome measures were duration of admission, recovery time from operation to discharge and reintervention for infective complications. Analysis was by intention to treat. RESULTS: The rate of LA in Lothian increased from 29.9 to 39.4 per cent (P < 0.001) after subspecialist service reorganization. Recovery time from operation to discharge was significantly shorter after LA than OA when results were stratified with respect to sex (mean 2.5 versus 4.4 days respectively in women, P < 0.001; 2.7 and 3.1 days in men, P = 0.023), timing of surgery (2.7 versus 3.3 days before subspecialization, P = 0.007; 2.5 versus 3.6 days after subspecialization, P < 0.001) and whether appendicitis was associated with peritoneal contamination (2.2 versus 3.0 days for uncontaminated surgery, P < 0.001; 4.3 versus 5.1 days for contaminated surgery, P = 0.060). Peritoneal contamination at primary operation was the only independent risk factor that predicted reintervention for infective complications. CONCLUSION: LA is associated with a shorter hospital stay from operation to discharge than OA, with no evidence of an increased rate of intra-abdominal infective complications.

Peritoneal leiomyosarcoma in a kidney transplant patient: a case report.

Sarcomas are rare neoplasms, accounting for a 1.7% incidence among all transplanted patients presenting with de novo malignancies. Our present report focused on a 46-year-old woman who received immunosuppressive therapy based on cyclosporine and steroids for renal transplantation. Eight years after transplantations, she suffered lower abdominal pain and a mass involving peritoneal soft tissues was located near the right iliac vessels. Upon radical tumor excision, the histological examination revealed a high-grade leiomyosarcoma. Immunosuppression was reduced and cyclosporine switched to rapamycin. After 30 days, a computed tomography scan revealed two small pulmonary metastases, so the patient received adriamycin. Six months after the diagnosis, there was no intra-abdominal relapse and the pulmonary metastasis remain stable. The function of the transplanted kidney was normal and the patient was listed for laparoscopic pulmonary resection. Sarcomas in solid organ transplant patients appear to have aggressive features with 62% being high grade and 40% metastatic at the time of primary diagnosis with a recurrence rate of 30% and a 5-year survival rate of 25%. Patients diagnosed with sarcoma should be treated with multimodality therapy. After aggressive surgery whenever possible, a combination of a traditional cytotoxic drug and a "signal" blocking agent like rapamycin may increase selectivity toward tumor cells.

In vitro and in vivo characterization of Indium-111 and Technetium-99m labeled CCK-8 derivatives for CCK-B receptor imaging.

Cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with 111In or 99mTc for CCK-B receptor imaging. Derivatives of CCK8 were obtained by addition at the N-terminus in solid phase of a DTPA derivative (DTPAGlu) linked through a glycine spacer (DTPAGlu-G-CCK8) or cysteine, glycine and a diphenylphosphinopropionyl moiety (PhosGC-CCK8) for labeling with 111In and 99mTc, respectively. CCK-BR overexpressing A431 cancer cell lines were utilized to characterize in vitro properties of the two compounds as well as for generating xenografts in nude mice for in vivo characterization. Both 111In-DTPAGlu-G-CCK8 and 99mTcPhosGC-CCK8 showed similar binding affinities for CCK-BR with dissociation constants of 20-40 nM, were internalized after interaction with the receptor and displayed prolonged cellular retention times. Specific in vivo interaction with the receptor of both CCK8 analogs was observed in our animal model. 111In-DTPAGlu-G-CCK8 showed better target to non-target ratios, although it appeared to be rapidly metabolized after injection and activity cleared through the kidneys. 99mTc-PhosGC-CCK8 was more stable in vivo but showed marked hepatobiliary clearance with resulting high background activity in the bowel. The rapid clearance and lower background obtained with 111In-DTPAGlu-G-CCK8 make this a better candidate for further development.

The number of lymph nodes examined and staging accuracy in renal cell carcinoma.

OBJECTIVE: To determine the number of lymph nodes that need to be examined to accurately stage the pN variable in patients undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC). PATIENTS AND METHODS: We reviewed the operative and pathology reports of 725 patients with RCC submitted for RN. All tumours were classified using the fifth edition of the Tumour-Nodes-Metastasis classification. For each patient the number of lymph nodes removed was recorded. The patients were divided into five different groups according to the number of nodes removed, i.e. group 1, 1-4; group 2, 5-8; group 3, 9-12; group 4, 13-16; and group 5, >or= 17. We evaluated the factors that affected the number of lymph nodes removed with nodal dissection and the variables that influenced the incidence of nodal involvement. RESULTS: Lymphadenectomy was performed in 608 patients (83.8%); in these patients the rate of lymph node metastases was 13.6%. The median (range) number of nodes removed was 9 (1-43); there was a statistically significant correlation between the number of nodes removed and the percentage of nodal involvement (r = 0.6; P < 0.01). The rate of pN+ was significantly higher in the patients with >or= 13 than in those with < 13 nodes examined (20.8% vs 10.2%; P < 0.001). For organ-confined and locally advanced tumours there was a statistically significant difference in the pN+ rate between patients with < 13 or >or= 13 nodes examined (3.4% vs 10.5%, and 19.7% vs. 32.2%, respectively). CONCLUSIONS: The proportion of tumours classified as pN+ increased with the number of lymph nodes examined. In RCC,> 12 lymph nodes need to be assessed for optimal staging.

Opsoclonus-myoclonus syndrome as a paraneoplastic manifestation of renal cell carcinoma. a case report and review of the literature.

Opsoclonus is a rare but distinctive disorder of ocular motility, characterized by irregular, continual and conjugated chaotic saccades of the eyes. It is increased with eye closure and fixation, and it persists during sleep. Opsoclonus appears more commonly in children and in half of such cases in association with neuroblastoma. In adults the most frequent causes are idiopathic (50%) and paraneoplastic (20%). Among the second group, different types of tumors involving a wide variety of organs have been reported. Opsoclonus when accompanied by other symptoms of central nervous system involvement (head, appendicular myoclonus and truncal ataxia) constitutes a clinical picture, known as opsoclonus-myoclonus syndrome. We report the case of a young patient affected by renal cell carcinoma associated with opsoclonus-myoclonus syndrome which did not respond to medical therapy but dramatically improved after cancer ablation.

Radiolabeling approaches for cholecystokinin B receptor imaging.

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with (111)In or (99m)Tc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with (111)In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA-Glu-G-CCK8. For labeling with (99m)Tc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order--cysteine, glycine, and a diphenylphosphinopropionyl moiety--giving a 10-residue peptide derivative, Phos-GC-CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2-5 x 10(6) per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both (111)In-DTPA-Glu-G-CCK8 and (99m)Tc-Phos-GC-CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20-40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of (111)In-DTPA-Glu-G-CCK8 appears to be preferentially through the kidneys, whereas (99m)Tc-Phos-GC-CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although (99m)Tc-Phos-GC-CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity.