Management of systemic prostate cancer: current algorithm from castration sensitive to castration resistant setting.

In recent years, the advanced knowledge of clinical, biological and molecular features of prostate cancer have led to the introduction of new drugs and have allowed the relocation of old drugs in different settings. In this way, the new concepts of systemic disease arise: high risk or high volume vs. low risk and low volume disease castration sensitive prostate cancer (CSPC), diversifying the use of previously approved drugs (CRPC) and opening new scenarios for sequence therapy. The aim of this review is to integrate new developments into the medical management of systemic prostate cancer.

Advanced/metastatic bladder cancer: current status and future directions.

In 2015 bladder cancer was the fourth most frequent malignancy and the eighth cause of death for cancer. At diagnosis, about 30% of bladder cancer (BC) patients present a muscle-invasive bladder cancer (MIBC) and 5% a metastatic bladder carcinoma (MBC). For fit MBC patients, combination chemotherapy (CC) is the standard of care for first-line treatment. CC includes both the treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) either the classical or the dose-dense MVAC regimen, and the doublet therapy with cisplatin and gemcitabine (CG). Median progression free survival (PFS) was 7 months and median overall survival (OS) was 15 months. The present review provides an update on the management of MBC, with focus on target therapies, immune checkpoint inhibition, looking for prognostic and predictive factors.

Penile cancer: prognostic and predictive factors in clinical decision-making.

Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC.

Subthalamic nucleus deep brain stimulation on motor-symptoms of Parkinson's disease: Focus on neurochemistry.

Deep brain stimulation (DBS) has become a standard therapy for Parkinson's disease (PD) and it is also currently under investigation for other neurological and psychiatric disorders. Although many scientific, clinical and ethical issues are still unresolved, DBS delivered into the subthalamic nucleus (STN) has improved the quality of life of several thousands of patients. The mechanisms underlying STN-DBS have been debated extensively in several reviews; less investigated are the biochemical consequences, which are still under scrutiny. Crucial and only partially understood, for instance, are the complex interplays occurring between STN-DBS and levodopa (LD)-centred therapy in the post-surgery follow-up. The main goal of this review is to address the question of whether an improved motor control, based on STN-DBS therapy, is also achieved through the additional modulation of other neurotransmitters, such as noradrenaline (NA) and serotonin (5-HT). A critical issue is to understand not only acute DBS-mediated effects, but also chronic changes, such as those involving cyclic nucleotides, capable of modulating circuit plasticity. The present article will discuss the neurochemical changes promoted by STN-DBS and will document the main results obtained in microdialysis studies. Furthermore, we will also examine the preliminary achievements of voltammetry applied to humans, and discuss new hypothetical investigational routes, taking into account novel players such as glia, or subcortical regions such as the pedunculopontine (PPN) area. Our further understanding of specific changes in brain chemistry promoted by STN-DBS would further disseminate its utilisation, at any stage of disease, avoiding an irreversible lesioning approach.

Estimation of liver iron concentration by dual energy CT images: influence of X-ray energy on sensitivity.

In hemochromatosis an abnormal accumulation of iron is present in parenchymal organs and especially in liver. Among the several techniques employed to diagnose the iron overload, magnetic resonance imaging (MRI) and Computed Tomography (CT) are the most promising non-invasive ones. MRI is largely used but shows limitation including an overestimation of iron and inability to quantify iron at very high concentrations. Therefore, some research groups are focusing on the estimation of iron concentration by CT images. Single X-ray CTs are not able to accurately perform this task in case of the presence of confounding factors (e.g., fat). A potential solution to overcome this concern is the employment of Dual-Energy CT (DECT). The aim of this work is to investigate influence of the kVp and mAs on CT number sensitivity to iron concentration. A phantom with test tubes filled with homogenized porcine liver at different iron concentrations, has been scanned with DECT at different mAs. The images have been analyzed using an ad-hoc developed algorithm which allows minimizing the influence of air bubbles present in the homogenized. Data show that the sensitivity is strongly influenced by kVp (its value almost halves from 80 kVp to 140 kVp; e.g. 0.41 g·µmol(-1) and 0.19 g·µmol(-1) at 80 kVp/120 mAs and 140 kVp/60 mAs respectively), on the other hand the influence of mAs value is negligible.

Expression of ATP7B in normal human liver.

ATP7B is a copper transporting P-type ATPase, also known as Wilson disease protein, which plays a key role in copper distribution inside cells. Recent experimental data in cell culture have shown that ATP7B putatively serves a dual function in hepatocytes: when localized to the Golgi apparatus, it has a biosynthetic role, delivering copper atoms to apoceruloplasmin; when the hepatocytes are under copper stress, ATP7B translocates to the biliary pole to transport excess copper out of the cell and into the bile canaliculus for subsequent excretion from the body via the bile. The above data on ATP7B localization have been mainly obtained in tumor cell systems in vitro. The aim of the present work was to assess the presence and localization of the Wilson disease protein in the human liver. We tested immunoreactivity for ATP7B in 10 human liver biopsies, in which no significant pathological lesion was found using a polyclonal antiserum specific for ATP7B. In the normal liver, immunoreactivity for ATP7B was observed in hepatocytes and in biliary cells. In the hepatocytes, immunoreactivity for ATP7B was observed close to the plasma membrane, both at the sinusoidal and at the biliary pole. In the biliary cells, ATP7B was localized close to the cell membrane, mainly concentrated at the basal pole of the cells. The data suggest that, in human liver, ATP7B is localized to the plasma membrane of both hepatocytes and biliary epithelial cells.

[CK20 expression in the gastrointestinal tract of the embryo and fetus]. / Espressione della CK20 nel tratto gastroenterico nell'embrione e nel feto.

A novel type of cytokeratin, cytokeratin 20 (CK20), was added in 1990 to the classic catalog of human cytokeratins, a heterogeneous group of proteins present in almost all epithelia. In man, the expression of CK20 is almost entirely confined to the gastro-intestinal epithelium, to the urothelium and to Merkel cells. Since only few data are available regarding the expression of CK20 in the developing human intestinal mucosa, we studied CK20 immunoreactivity in fetal and neonatal human gut. Immunoreactivity for CK20 was tested in fetuses and newborns, from the twelfth up to the fortieth week of gestation. In each subject, a specimen from the oesophagus, stomach, small intestine, colon, appendix was studied. Tissue samples were routinely processed and paraffin sections were stained with the CK20-specific antibody IT-Ks 20.8. CK20 immunoreactivity was absent in the oesophageal epithelium and it was unevenly distributed in the gastrointestinal mucosa. Three main patterns of immunoreactivity were observed during normal development: the first, found in the stomach and in the small bowel, is characterized by a progressive increase in CK20 expression during gestation; the second pattern, found in the duodenum, shows a progressive decrease in CK20 expression during gestation; in colon and appendix (third pattern), we did not find significant changes in the degree of immunoreactivity for CK20 during gestation. CK20 is unevenly expressed in developing human intestinal mucosa. The degree of positivity for CK20 appears to be related to the epithelial maturation stage only in gastric and small bowel mucosa. Further studies are needed to verify if the uneven CK20 immunoreactivity in the gastrointestinal tract persists even in adulthood.

Alpha-1-antichymotrypsin immunoreactivity in papillary carcinoma of the thyroid gland.

AIM: Papillary thyroid carcinoma (PTC) is the most common malignant tumour of the thyroid gland. The immunohistochemical profile of PTC is characterized by immunoreactivity of tumour cells for cytokeratins, thyroglobulin, vimentin, EMA and S100 protein. Recently, the presence of a serum protease inhibitor, alpha-1-antitrypsin (A1AT), has been demonstrated in tumour cells of PTC. The aim of our study was to test immunoreactivity of PTC for another inhibitor of proteases, alpha-1-antichymotrypsin (A1ACT). METHODS AND RESULTS: Serial paraffin sections of nine consecutive cases of PTC were tested with anti-A1AT and anti-A1ACT antibodies. No immunoreactivity for A1AT and A1ACT was found in the normal thyroid tissue surrounding each tumour. In seven out of nine cases, tumour cells of PTC showed cytoplasmic immunoreactivity for A1ACT. In two cases, A1ACT was detected even in the nuclei. Immunoreactivity for A1AT was found only in three cases. Two cases of PTC showed no staining for both A1ACT and A1AT. No significant correlation of A1ACT staining was found with various prognostic indices (age of patients, histological pattern, tumour size, presence of regional lymph node metastases). The two cases showing a lack of staining for both A1ACT and A1AT showed a more aggressive clinical behaviour. CONCLUSIONS: Our preliminary study shows that A1ACT is expressed by tumour cells in a large proportion of papillary carcinomas of the thyroid gland. Its significance remains, to the best of our knowledge, still unknown. The observation of a more aggressive behaviour in the two cases characterized by the absence of immunoreactivity for both A1ACT and A1AT suggests that the presence or absence of protease inhibitors could play a role in controlling tumour progression in PTC.

Transesophageal echocardiography-guided transvenous biopsy of a cardiac sarcoma.

Transvenous endomyocardial biopsy is a well established procedure to diagnose rejection after heart transplantation as well as to assess for other cardiomyopathic processes. However, it is rarely used to obtain samples of unidentified cardiac masses. We report a case of a primary cardiac sarcoma in which the histologic diagnosis was provided by transesophageal echocardiography-guided transvenous biopsy. This procedure is accurate and can avoid the potential risk of a diagnostic thoracotomy.

[Surgery for familial polyposis of the colon. A functional follow-up]. / Chirurgia per poliposi familiare del colon. Follow-up funzionale.

Functional assessment of pelvic pouch procedures for FAP is not different from that of UC and consists of clinical, manometric and radiologic investigations. Ileo-rectal anastomosis and pelvic pouch operation are equally effective for the disease, but function is still questionable after restorative proctocolectomy. Based on a personal series of 43 patients, relevant technical aspects influencing functional results are discussed and guidelines for a correct follow-up of these patients are presented.

[Rehabilitation of the colostomy patient]. / La riabilitazione del paziente stomizzato.

The Authors report their experience concerning the rehabilitation of patients with temporary or definitive colostomy. Mechanical and psychosocial implications as well as different rehabilitative methods are discussed and literature data are reviewed. Surgery should play a major role in this rehabilitation programme, either in terms of prevention or definitive treatment; nonetheless only through a multidisciplinary approach these patients will achieve a better quality of life.

Copper distribution within and between newborn livers.

Copper concentration was determined in different liver samples (blocks, needle biopsy and bile) obtained from 9 newborns and 3 infants at autopsy. Tissue blocks, sampled at ten equally spaced intervals between the left and the right lobe, revealed in newborns high copper concentrations, ranging from 93 to 335 mg/Kg of dry tissue with an upward trend from the right to the left lobe. The situation differed in infants where a lower and more evenly distributed copper content, ranging from 49 to 123 mg/Kg of dry tissue, was found, which seemed to approximate the situation found in adults. Copper concentration was generally high in bile, with an overall range from 99 to 413 mg/Kg of dry material. This fact was particularly significant in infants, considering their low hepatic copper content. Copper content determined in percutaneous biopts was significantly correlated to (P less than 0.01), though only moderately predictive of (r2 = 0.54), the average copper content calculated from the ten liver blocks.

Liver cell proliferation induced by the mitogen ethylene dibromide, unlike compensatory cell proliferation, does not achieve initiation of rat liver carcinogenesis by diethylnitrosamine.

The purpose of this investigation was to determine whether mitogen-induced cell proliferation is as effective as compensatory cell proliferation in achieving initiation of carcinogenesis in rat liver. Male Wistar rats were injected with a single non-necrogenic dose of the hepatocarcinogen diethylnitrosamine (DENA) during the peak of DNA synthesis following the administration of the hepatic mitogen ethylene dibromide (EDB) or a necrogenic dose of CCl4. After subjecting the animals to a promoting procedure, the rats were sacrificed and the initiated hepatocytes were monitored as gamma-glutamyltranspeptidase (gamma-GT) positive foci. The results indicate that while DENA administration during compensatory cell proliferation results in the formation of GT positive foci, no enzyme-altered foci were produced when the carcinogen was given during liver hyperplasia induced by EDB, despite the fact that at the time of carcinogen administration, the extent of cell proliferation, as monitored by thymidine incorporation into DNA, was the same in both the groups.

Uneven copper distribution in the human newborn liver.

The pattern of copper distribution in human newborn liver was investigated by histochemical methods (rhodamine, orcein and rubeanic acid) and by atomic absorption spectroscopy. A significant correlation (p less than 0.005) was found between the degree of histochemical positivity and the copper concentration found by atomic absorption spectroscopy. In the majority of the 30 livers examined (first group), the copper concentration was much higher than that of normal adult liver, although exhibiting striking individual differences. No correlation between the copper content and sex, body weight or gestational age was found. From a second group of five livers, longitudinal tissue slices 0.5 cm thick were partitioned into regular blocks of about 0.5 gm, which were individually analyzed by atomic absorption spectroscopy. Copper appeared unevenly distributed within each liver, with marked differences even between adjacent blocks. However, a consistent tendency of copper to accumulate in the left lobe more than in the right one was evident. Five additional blocks, one for each liver, were further partitioned into 10 small specimens of a final size (0.05 gm), comparable to that of a needle biopsy. Even at this sampling level, consisting of tissue fragments taken from a small tissue area, the copper concentration appeared quite irregularly distributed. These findings may be considered for two different aspects: (a) the biological implications of the pattern of copper accumulation in different lobar and lobular liver compartments and (b) the statistical inference, for diagnostic purposes, of the mean liver copper content from measurements of single percutaneous biopsy specimens.

Immunoperoxidase localization of HSV2 antigens in cervical dysplasia and carcinoma.

The AA. have evaluated by means of the immunohistochemical technique the incidence of herpetic phlogosis in 76 women with neoplastic pathologies of the uterine cervix. The patients were submitted to cytologic, colposcopic and histologic examination for CIN. The HSV2 positivity by immunohistochemical method was demonstrated in 53 (35.3%) cases of CIN and invasive carcinoma. The results confirm the frequent association between HSV2 and cervical carcinoma and they support a specific therapeutic approach to be made in the prevention and clinical management of the carcinoma.

Hepatic expression of hepatitis B and delta virus antigens in patients with acute and chronic hepatitis.

Delta antigen (delta-Ag), hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) were examined by immunofluorescence and immunoperoxidase staining in 106 deparaffinized liver biopsy samples from HBsAg-positive patients with acute and chronic hepatitis. The delta-Ag was present in 15 cases (14%), with nuclear positivity varying greatly in intensity and prevalence. Patients with chronic hepatitis associated with delta infection had a histological picture characterized by foci of intralobular inflammation, many apoptotic bodies and shrunken hepatocytes with no satellite signs of inflammation. The histological pattern of delta antigen-positive acute hepatitis was characterized by the presence of a large number of intralobular apoptotic bodies. The inflammatory reaction mainly involved the portal tracts with piecemeal necrosis, but without collagen production. In the same cases the pattern of expression of HBsAg and HBcAg was unusual: in three cases HBcAg and HBsAg were concomitantly present, whereas in one case none of the hepatitis B virus markers was detectable.