Extended nodal radiotherapy for prostate cancer relapse guided with [11C]-choline PET/CT: ten-year results in patients enrolled in a prospective trial.

AIMS: To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and [11C]-choline positron emission tomography (PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs). METHODS: From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8 Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5 Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months. RESULTS: Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis. CONCLUSIONS: In PC relapsed patients treated with ENRT and [11C]-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67 months and OS of 110 months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.

Management of obstructive pathology of the salivary glands in elderly patients: a preliminary study.

BACKGROUND: Obstructive pathology is a benign condition of the salivary glands that can affect elderly and co-morbid people. Sialoendoscopy is a minimally invasive surgical procedure with a success rate comparable to standard sialoadenectomy and has the advantage that it can be performed under local anaesthesia. METHODS: This study aimed to assess sialoendoscopy benefits in elderly patients unfit for general anaesthesia. A group of elderly patients (aged 65 years or more) undergoing sialoendoscopy under local anaesthesia were evaluated. Age, co-morbidities, surgical time, hospital stay, and complication and recurrence rates were assessed. RESULTS: Nineteen sialoendoscopies were performed in 18 elderly patients with a mean age of 69.7 ± 5.6 years, with some of them suffering from multiple co-morbidities. Surgery was successful in 16 patients, while surgery was unsuccessful in 2 patients because of intraglandular stones. The average surgical duration was 54.5 ± 30.1 minutes, and all patients were discharged 2-3 hours after surgery. No post-operative complications were found and only one patient had recurrence during follow up. CONCLUSION: Sialoendoscopy under local anaesthesia is a safe and effective procedure in elderly patients who are more prone to complications.

Food systems are responsible for a third of global anthropogenic GHG emissions.

We have developed a new global food emissions database (EDGAR-FOOD) estimating greenhouse gas (GHG; CO2, CH4, N2O, fluorinated gases) emissions for the years 1990-2015, building on the Emissions Database of Global Atmospheric Research (EDGAR), complemented with land use/land-use change emissions from the FAOSTAT emissions database. EDGAR-FOOD provides a complete and consistent database in time and space of GHG emissions from the global food system, from production to consumption, including processing, transport and packaging. It responds to the lack of detailed data for many countries by providing sectoral contributions to food-system emissions that are essential for the design of effective mitigation actions. In 2015, food-system emissions amounted to 18 Gt CO2 equivalent per year globally, representing 34% of total GHG emissions. The largest contribution came from agriculture and land use/land-use change activities (71%), with the remaining were from supply chain activities: retail, transport, consumption, fuel production, waste management, industrial processes and packaging. Temporal trends and regional contributions of GHG emissions from the food system are also discussed.

Parotid metastasis from renal cell carcinoma: a case report and review of the literature.

Renal cell carcinoma metastasis to the parotid gland after tumour nephrectomy is extremely rare. Herewith a review of the literature on this topic is discussed and a case report is presented of a 69-year-old man affected by parotid localization of renal clear cell carcinoma with neck lymph node metastases and involvement of the masseter muscle 2 years after nephrectomy. When an otolaryngologist encounters a parotid mass, diverse differential diagnoses have to be considered. A high level of suspicion of metastatic disease from the specific primary site will help in achieving correct diagnosis and evaluation of the extension of the disease. Surgical resection, even enlarged parotidectomy with neck dissection, should be considered as a therapeutic option for exclusive location of the disease in the head and neck.

Glial choristoma of the ventral part of the tongue: first report in an elderly patient.

INTRODUCTION: The aims of this report are to illustrate the first case of glial and adipose tissue choristoma at the ventral part of the tongue in an elderly patient, to discuss the possible differential diagnoses and to speculate about its pathogenesis. CASE REPORT: A 65-year-old female was admitted to our hospital with a swelling at the base of the tongue. MRI revealed an oval lesion with indistinct borders without contrast enhancement. The patient underwent surgical complete excision and grossly, the specimen consisted of a gray-white mass measuring 25 mm in its great diameter. Microscopically the lesion contained fibrocollagenous stroma, mature adipose tissue and mature astrocytes. In the absence of cellular atypia, mitoses and necrosis a diagnosis of adipose and glial choristoma was performed. The patient is healthy 18 months postoperatively. DISCUSSION: Choristomas are cohesive tumor-like masses histologically composed by normal tissue occurring in an unusual anatomical location and mainly affecting children during the first years of life. Glial choristomas are considered malformations of the central nervous system and their localization in the tongue is exceptional. However they carry a favourable prognosis so it is of paramount importance to histologically diagnose them correctly.

Histopathological atlas of renal diseases: anti-glomerular basement membrane antibody disease.

The main diagnostic feature of anti-glomerular basement membrane (anti-GBM) antibody disease is represented by the immunofluorescence pattern of intense and diffuse linear IgG deposition along the glomerular basement membrane. By light microscopy several histological patterns can be observed.

Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials.

BACKGROUND: The policy of prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury is still a matter of discussion. Indeed, no consensus exists as to whether cotherapy with histamine type 2 (H2) blockers or misoprostol is cost-effective. METHODS: Placebo-controlled randomized clinical trials on the use of H2 blockers or misoprostol, as preventive agents (published between) January 1970 and December 1994), were identified through MEDLINE and reference lists from literature reviews. Crude rates of endoscopic lesions with short-term (< 2 weeks) and long-term (> 4 weeks) NSAID treatment were systematically assessed by 3 independent observers based on the intention-to-treat principle. The method of DerSimonian and Laird was used for pooling data. Heterogeneity was evaluated by using the Q statistic and the plots described by L'Abbe and colleagues. RESULTS: Twenty-four trials met the criteria for entry into the study. Gastric ulcer was found to be significantly reduced by misoprostol-both in short-term (pooled rate difference [RD], -13%, 95% confidence interval [CI], -26% to -1%) and long-term (RD, -8%; 95% CI, -18% to -1%) NSAID treatment-but not by H2 blockers. The risk for duodenal ulcer was significantly reduced by H2 blockers (RD, -2%; 95% CI, -5% to -0.2%) and by misoprostol (RD, -3%; 95% CI, -6% to -0.1%) in long-term but not in short-term administration. CONCLUSIONS: The use of misoprostol, but no that of H2 blockers, was beneficial in the prevention of NSAID-induced gastric ulcers. The number of patients to be treated to prevent 1 gastric ulcer with short- and long-term NSAID treatment is 11 and 15, respectively, for an intermediate baseline risk of 10%. Misoprostol and H2 blockers were beneficial in the long-term prevention of duodenal ulcers; misoprostol or H2 blockers in the short-term prevention of duodenal ulcers remains to be confirmed.

Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients.

Histological features and data on the natural history after 1 to 45 years (mean 6.56 +/- 8.55) of total apparent duration and 1 to 13 years (mean 3.48 +/- 5.04) of post-biopsy follow-up, are reported in 374 patients (mean age, 33.9 +/- 11.9 yrs) with idiopathic mesangial IgA nephropathy, who presented with a history of macroscopic hematuria (56%), recurrent in two-thirds of the patients, or with persistent microscopic hematuria and no previous episodes of gross hematuria (44%). Mesangial cell proliferation ranged from minimal to diffuse. Associated varying degrees of extracapillary proliferation, segmental and global glomerular sclerosis, tubulo-interstitial damage and arteriolar hyalinosis usually correlated with each other and with the extent of mesangial proliferation (P less than 0.05). The actuarial curve of progression to renal death showed a 75% survival after 20 years from apparent onset. Progression to renal failure was more rapid in patients with: an older age at onset (P = 0.0582); male sex (P = 0.0730); no history of recurrent gross hematuria (P = 0.0406); high blood pressure (P = 0.0011); more marked global (P = 0.0007) and segmental (P = 0.0026) glomerular sclerosis; more severe interstitial sclerosis (P = 0.0147); more diffuse and global mesangial proliferation (P = 0.0820); mesangio-parietal pattern at immunofluorescence (P = 0.0778). However, all these parameters showed a poor predictive value if applied to any single patient.

A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.

Leflunomide is one of the most promising disease-modifying antirheumatic drug now in clinical trials for the treatment of rheumatoid arthritis. Metabolic studies have indicated that leflunomide is rapidly processed in vivo to an active metabolite, A771726 (2). To identify the chemical characteristics necessary for the immunosuppressive activity of 2, configurational and conformational studies were carried out on the latter and its inactive analogues (ethyl 3-hydroxy-2-((4-(trifluoromethyl)phenyl)carbamoyl)but-2-enoate, 3a, and 3-hydroxy-2-nitro-N-(4-(trifluoromethyl)phenyl)but-2-enamide, 3b). These studies suggested that the pharmacophore responsible for the immunosuppressive activity of 2 is a beta-keto amide with the enolic hydroxy group cis to the amidic moiety. To verify this hypothesis, a new class of immunosuppressive agents was designed and synthesized. Their testing in vitro and in vivo identified compounds which were more potent than both leflunomide and 2 and above all confirmed our hypothesis as to the key structural and chemical determinants for the immunosuppressive properties of 2 and our compounds.

Electrophysiological findings in workers exposed to N-heptane fumes.

Electrophysiological examination of the peroneal nerve was performed in a group of individuals exposed for professional reasons to vapours of n-heptane. The results suggest a probably specific role of this hydrocarbon compound in provoking "minimal" peripheral nerve damage.

Acute endocapillary glomerulonephritis in adults: a histologic and clinical comparison between patients with and without initial acute renal failure.

30 renal biopsies were performed in 20 adult patients with acute diffuse endocapillary glomerulonephritis. 11 patients who presented with acute renal failure (ARF) and 9 patients who had normal or mildly altered renal function were compared in order to look for clinical or pathologic features peculiar to each group and possible differences in outcome. All patients underwent early renal biopsy, and 8 had repeat biopsies. There were no significant differences in clinical, immunologic or histologic features between the two groups. In repeat biopsies, there were no histologic nor immunohistologic differences between patients with or without initial ARF. After a mean follow-up period of 18 months, the overall clinical outcome appeared favorable and was similar in the two groups. Thus, initial ARF in patients with acute endocapillary glomerulonephritis does not imply a bad prognosis. The recognition of pure endocapillary proliferation in patients with anuric acute glomerulonephritis by means of renal biopsy may avoid unnecessary and potentially hazardous treatment.

IgA-mesangial nephropathy (Berger's disease) with rapid decline in renal function.

End-stage renal failure requiring dialysis treatment developed within 5 years in 11 patients with IgA mesangial glomerulonephritis (out of 94 affected by this nephropathy) whose serum creatinine levels were less than 2 mg/100 ml at the time of biopsy. We compared these patients (Group 1) with 10 patients (Group 2) whose serum creatinine was comparable at the time of biopsy (1.2 +/- 0.3 vs 1.4 +/- 0.3 mg/100 ml) but remained unchanged (1.1 +/- 0.4 mg/100 ml) at the end of a minimum post-biopsy follow-up of 5 years. The analysis of clinical findings, at the time of biopsy, showed that the mean duration of disease, from apparent onset, was shorter in Group 1. Recurrent macroscopic hematuria, never reported in this group, was present in 40% of patients of Group 2, whereas minimal urinary abnormalities, discovered by chance, were the only findings in 73% of patients of Group 1 and in 30% of Group 2. No difference was present between the patients in the two groups in the amount of proteinuria and in the incidence of high IgA serum levels, whereas hypertension was more frequent (45% vs 20%) in Group 1. The analysis of histological lesions demonstrated that in Group 1 there was a greater incidence of diffuse mesangial proliferation (82% vs 30%), of extensive glomerular obsolescence (64% vs 0) and of severe interstitial fibrosis (54% vs 0). Immunofluorescence findings were similar in the two groups. Although no single clinical or morphological parameter was characteristic of the patients with subsequent rapid decline of renal function, some features were more commonly observed, or more severe, in these patients, and therefore should be considered reliable predictors of an unfavourable outcome.

Critical re-evaluation of 41 cases of "idiopathic" crescentic glomerulonephritis.

Despite the availability of different classifications for rapidly progressive glomerulonephritis (RPGN), patients with "idiopathic crescentic GN" have not been yet inserted as a precisely defined subgroup, pointing to their probable heterogenicity. Trying to better define their characteristic, we retrospectively analyzed the clinical, histological and immunopathological features of 41 patients diagnostically labelled "idiopathic RPGN" because they had no evidence of systemic disease (including systemic vasculitis), no anti-GBM mediated glomerulonephritis and no clearly defined primary glomerulopathy. Starting by a thorough morphological review, 2 subgroups were defined: group I (25 patients) with variable degrees of intraglomerular necrosis, and group II (16 patients) with no intracapillary necrotizing lesions. Group I showed no or minimal endocapillary proliferation, intense interstitial infiltrates with periglomerular localization, frequent ruptures of Bowman's capsule and mild degree of glomerular and/or interstitial sclerosis. 16 patients in this group (64%) had irregular deposits of complement C3 at immunofluorescence while the remaining 9 (36%) had no immune deposits. Clinically they had no previous history of preceding urinary abnormalities, had a mean of 1.8 g/day proteinuria and a positivity for ANCA in 92% (12/13). In group II there was frequently marked mesangial proliferation, scarce interstitial infiltrates, no ruptures of Bowman's capsule and marked degrees of glomerulosclerosis and interstitial fibrosis. All patients in this group had clearly defined immune deposits of C3 and/or IgG. Clinically 50% of these patients had a history of recurrent microhematuria and/or proteinuria, a mean of 4.5 g/day proteinuria and negativity for ANCA in all 8 patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay Standardization.

Renal granulomas are a relatively infrequent finding in the kidney biopsy. They have been described in a number of syndromes such as Wegener's granulomatosis, anti-GBM glomerulonephritis, and sarcoidosis, and are commonly believed to be indicative of a fulminant clinical course. In leading textbooks, diverse definitions of renal granulomas are presented, which has led to controversies in identifying them. This, in combination with their rare occurrence, makes it difficult for the general pathologist to identify them. We present the clinical data of 16 patients with renal granulomas, from a total group of 157 patients with systemic vasculitis. Their renal functioning was not significantly different from the other 141 patients in whose renal biopsies renal granulomas were present. Furthermore, we present two practical definitions for the recognition of renal granulomas in the kidney biopsy, and we show a number of examples of their various histopathological shapes.

Triazine herbicides and ovarian epithelial neoplasms.

The possible role of a class of herbicides, triazines, in ovarian carcinogenesis has been evaluated in a population-based case-referent study. The trade names reported by the study subjects, and the type of cultivation in which they worked, were used for the assessment of exposure. Women previously exposed to triazines showed a significant relative risk of 2.7 for ovarian neoplasms. Although none of the doses could be quantified for the study subjects, two risk trends in favor of the plausibility of the association were found: the first by duration and the second by probability of exposure. The population representativity of the study and the comparability of information between the cases and referents suggest the lack of any major bias in the results. Triazine-related risk remained consistent when the analysis was restricted to farmers and when the exposure to other herbicides and to other types of cultivation were considered. Unexposed farmers had the same risk as unexposed nonfarmers.

Rapidly progressive glomerulonephritis (RPGN): is there still an "idiopathic" subgroup?

In order to clarify if "idiopathic" RPGN still exists as a distinct entity we reviewed 41 patients with histological picture of diffuse crescentic GN (60% of crescents) and no clinical evidence of systemic disease. According to the presence or absence of intraglomerular necrotizing lesions we subdivided the patients into two different morphological groups: Group I (25 pts) with necrotizing GN and massive periglomerular infiltrates; Group II (16 pts) with intra-extracapillary proliferation and no interstitial infiltrates. Our data suggest that "idiopathic" RPGN does not exist as a distinct entity, but is an expression either of renal limited vasculitis or crescentic GN complicating primary proliferative GN.

Plasma exchange in glomerulonephritis associated with systemic lupus erythematosus and essential mixed cryoglobulinemia.

Intensive plasma exchange and immunosuppression have been used in 13 patients affected by severe forms of glomerulonephritis (GN) associated with systemic lupus erythematosus (SLE) and essential mixed cryoglobulinaemia (EMC). The patients were divided into two groups.

Effect of intensive plasma exchange (PE) in rapidly progressive crescentic glomerulonephritis (RPCGN).

Ten adult patients with RPCGN (crescents in greater than 70% of glomeruli), primary in 6 and associated with systemic diseases in 4, were treated with PE, associated with oral steroids (P) and cyclophosphamide (C) in all cases and with intravenous methylprednisolone pulses (MP) in 7 cases. Four out of ten patients were anuric and needed dialysis treatment at the start of treatment. Therapeutic benefit, i.e. reversal of the trend to further deterioration and substantial improvement of GFR, was achieved in 8 out of 10 patients (80%), including 2 of 4 anuric patients, and in 7 of those (8) who had still active cellular crescents (87.5%). Similar therapeutic benefit had been achieved only in 10% of a comparable population of 10 patients with RPCGN treated before 1980 with P and C, without PE or MP pulses. It is difficult to establish whether the better therapeutic results in the more recently treated group were due to PE or to MP pulses of to both the new approaches, even though the clinical improvement obtained in all the 3 patients treated with PE without concomitant MP suggest a specific beneficial role for PE. RPCGN is a catastrophic illness characterized by progressive deterioration of kidney function, resulting in oliguria and uremia, usually within weeks or months. The most consistent histopathologic finding is the presence of extensive glomerular crescents resulting from proliferation of the extracapillary epithelial cell lining of Bowman's capsule. It is apparent that RPCGN is not a homogeneous entity, clinically, histologically or immunohistologically, but rather a clinicopathologic syndrome, the features of which may be seen in a variety of systemic disorders, including SLE, polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura, cryoglobulinemia, and subacute bacterial endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma exchange in the treatment of essential mixed cryoglobulinemia nephropathy. Long-term follow up.

Plasma exchange is increasingly used for management of Essential Mixed Cryoglobulinemia. However little is known about the long term effects of this treatment. Therefore we have reviewed the clinical and laboratory data of 20 patients with type II EMC who were followed for a mean of 24 months. 16 patients had renal involvement, which was characterized histologically in all of them: 9 had diffuse proliferative GN plus endoluminal "thrombi" in 6 and vasculitis in 5, 4 had lobular membranoproliferative GN and 3 had focal proliferative GN. 14 patients had renal failure and 13 had proteinuria greater than or equal to 2 g/24 hr. PE (combined with immunosuppressive drugs in 18) was performed for a mean of 18 procedures. The combined treatment induced prompt remission of extrarenal and renal involvement. Serum creatinine and proteinuria decreased significantly in all but 2 patients during the treatment (s. creatinine from 2.9 to 1.6 mg/dl; proteinuria from 3.5 to 1.6 g/24 hr). Analysis of long term follow up revealed that these effects were long lasting in all the cases. We conclude that PE should be used for EMC nephropathy whenever prompt remission is not obtained by conventional therapy especially in consideration of its long term beneficial effects.