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.

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.

Role of biopsy in low-grade laryngeal chondrosarcoma: report of two cases.

Laryngeal chondrosarcomas are rare tumours that account for less than 1% of all sarcomas and originate principally from the crycoid cartilage. We report two cases: the former arising from thyroid cartilage in an 85-year-old male presenting with a palpable neck mass and hoarseness, dyspnoea and dysphagia; the other in a 54-year-old male with a mass growing from crycoid cartilage, who underwent biopsy followed by total laryngectomy. We discuss the peculiarity of the site of origin and the role of biopsy, the clinical presentation of the former case and the diagnostic and therapeutic procedures of the latter. Since it is a rare form of sarcoma arising in the larynx, we discuss the role of biopsy as a crucial although still controversial diagnostic tool.

Radial forearm free flap surgery: a modified skin-closure technique improving donor-site aesthetic appearance.

Radial forearm free flap surgery is a versatile technique that is widely adopted for microvascular reconstruction of the oral, oropharyngeal and hypopharyngeal lining. Nowadays, the technique for harvesting is standardized, while reconstruction of the forearm donor site defect is somewhat controversial. The authors describe a modified closure technique developed to reduce skin tension that provides subsequent improvement of the cosmetic appearance of the forearm donor site. A series of 43 patients undergoing radial forearm free flap (RFFF) reconstruction is presented, carried out by our ENT department between September 2007 and December 2010. The authors used a modification of the standard triangular full-thickness skin graft (FTSG) technique to close the forearm donor site on 23 patients with a new shape similar to a dagger. Using the Stony Brook Evaluation Scale, the authors analyzed the outcomes of 23 cases employing the dagger-shaped FTSG and compared these with a standard (triangular shaped) reconstructive graft used in 20 earlier patients. The new dagger-shaped graft decreases skin tension and reduces the need of multiple slits in the graft with improved aesthetic outcome; it is an effective method for repair of the forearm donor site with low tension and without the need to harvest the skin graft from the thigh. The technique is simple, reliable and requires no more time than a standard procedure.

European consensus statement on the terminology used in the management of lupus glomerulonephritis.

Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disorder, which often involves referral to multiple medical specialists. Lupus nephritis (LN) occurs in ~35% of adults with SLE and predicts poor survival. There is currently no consensus on how to manage patients with SLE or LN across specialties and across different European countries. The Lupus Nephritis Terminology Advisory Group was formed to address this issue as it impacts upon LN treatment. It has developed consensus statements based on opinions from expert panel meetings with nephrologists, nephropathologists, rheumatologists, clinical immunologists and internal medicine specialists from many European countries, after reviewing current guidelines from the European League Against Rheumatism, the American College of Rheumatology and the participants' experience. In this article, we report consensus statements that were developed in six important areas: classification of patients with LN, how classification affects the selection of treatment options and definitions of induction, response, flare and maintenance. We have also proposed a consensus for the terminology involved in the management of LN that is consistent with clinical opinion gathered from multidisciplinary expert meetings and with existing guidelines. We believe this consensus approach provides agreed expert opinion to clinicians and will form the basis for optimising LN treatment.

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.

Apoptosis in the kidneys of patients with type II diabetic nephropathy.

The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.

Glomerular clusterin is associated with PKC-alpha/beta regulation and good outcome of membranous glomerulonephritis in humans.

Mechanisms for human membranous glomerulonephritis (MGN) remain elusive. Most up-to-date concepts still rely on the rat model of Passive Heymann Nephritis that derives from an autoimmune response to glomerular megalin, with complement activation and membrane attack complex assembly. Clusterin has been reported as a megalin ligand in immunodeposits, although its role has not been clarified. We studied renal biopsies of 60 MGN patients by immunohistochemistry utilizing antibodies against clusterin, C5b-9, and phosphorylated-protien kinase C (PKC) isoforms (pPKC). In vitro experiments were performed to investigate the role of clusterin during podocyte damage by MGN serum and define clusterin binding to human podocytes, where megalin is known to be absent. Clusterin, C5b-9, and pPKC-alpha/beta showed highly variable glomerular staining, where high clusterin profiles were inversely correlated to C5b-9 and PKC-alpha/beta expression (P=0.029), and co-localized with the low-density lipoprotein receptor (LDL-R). Glomerular clusterin emerged as the single factor influencing proteinuria at multivariate analysis and was associated with a reduction of proteinuria after a follow-up of 1.5 years (-88.1%, P=0.027). Incubation of podocytes with MGN sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, serum de-complementation, or protein-A treatment. Preliminary in vitro experiments showed podocyte binding of biotinilated clusterin, co-localization with LDL-R and specific binding inhibition with anti-LDL-R antibodies and with specific ligands. These data suggest a central role for glomerular clusterin in MGN as a modulator of inflammation that potentially influences the clinical outcome. Binding of clusterin to the LDL-R might offer an interpretative key for the pathogenesis of MGN in humans.

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.

[Post-infectious glomerulonephritis]. / Glomerulonefriti post-infettive.

Post-infectious glomerulonephrites (GNs) include a wide spectrum of nephropathies, with known etiological agent, bacterial, parasitic, viral. Among GNs secondary to bacterial infections, post-streptococcal GN is the most frequent; nevertheless, its incidence in developed countries has decreased during the last 20 years, while some of the characteristics such as types of infection, exposed subjects, clinical and evolutionary patterns have changed. Prognosis has worsened and is correlated with some clinical and histological parameters. The viral infection-related GNs include those associated with HBV, HCV, HIV plus other rarer forms. Membranous GN (MGN), membranoproliferative GN (MPGN) and IgA nephropathy may occur in the course of HBV infection, while different GNs can be detected in relation to HCV, the most frequent being mixed cryoglobulinemic GN, a MPGN with peculiar morphological features. Multiple glomerular involvements are seen from HIV infection, the more characteristic form being the so-called HIV associated nephropathy (HIVAN), a focal segmental glomerulosclerosis with tuft collapse affecting African subjects, which starts with a nephrotic syndrome and rapidly develops into uraemia. Other GNs derive from HIV-related immunecomplexes, some with diffuse proliferative characteristics, or lupus like, with less severe clinical manifestations compared with HIVAN. Among the rare viral infections, we ultimately, mention the association between Parvovirus B19 and "collapsing" focal segmental glomerulosclerosis.

[Borderline indications for renal biopsy]. / Indicazioni "borderline" della biopsia renale.

The Authors report 3 cases with clinical renal manifestations where the indication to perform a renal biopsy was defined as borderline. The uncertain indication was related to the clinical presentation, with a pattern of urinary abnormalities, such as isolated microscopic hematuria, microscopic hematuria associated with mild proteinuria, and isolated proteinuria. In addition, similar questions on biopsy are raised for chronic renal failure and elderly patients. In the literature, microscopic hematuria without significant proteinuria shows that 25% of adult patients have no histological abnormalities. A higher percentage is found among children. The other cases exhibit a pattern of IgA nephropathy, Alport's syndrome, thin BM nephropathy and arteriolar C3 deposition. The percentage of an abnormal histological picture increases if the patients have a family history of hematuria, and if there are concomitant episodes of macroscopic hematuria, because of an increase in IgA nephropathy and Alport's syndrome, respectively. In the last cases, therefore the indication to perform a renal biopsy increases. For those patients without these characteristics, a renal biopsy can be delayed whereas in cases of microscopic hematuria with proteinuria or isolated proteinuria the indication for a renal biopsy is stronger, because the spectrum of glomerulopathies is wider, and the possible evolution to renal failure after 10 years is higher (10-14% of cases). In patients with chronic renal failure the biopsy is contraindicated for cases where the thickness of the cortical section of the kidney is lower than 8-10 mm, because of possible technical difficulties, lower diagnostic information due to sclerosis and higher risk of complications. The prolonged bleeding time and the consequent risk of bleeding can be avoided by i.v. infusion of vasopressin 2 hours prior to biopsy. The higher indications are for those patients who may be susceptible to a medical treatment, capable to slowing down the progression of nephropathy. Finally, in elderly patients the biopsy is indicated in almost all cases because of the recently confirmed high incidence of glomerulopathies. In the aged there is a higher frequency of membranous GN, crescentic-ANCA associated GN, amyloidosis and, according to some Authors, post-infectious GN. In all cases a precise histological diagnosis can correct an erroneous diagnosis made according to clinical data alone. In the elderly the indication for biopsy aims at making an exact diagnosis of nephropathy, especially for acute renal failure: for this purpose age itself should not become an obstacle.

Idiopathic IgA nephropathy with segmental necrotizing lesions of the capillary wall.

BACKGROUND: Segmental glomerular necrosis has been described in the biopsy material in a minority of patients with idiopathic IgA nephropathy in the oldest studies on this disease, but this marker of active capillaritis has received little attention in the subsequent literature, and its significance and relevance for the clinical outcome is still unknown. METHODS: Thirty-five out of 340 patients (10.3%) biopsied in our division at the San Carlo Hospital since 1974 showed active segmental necrotizing lesions. The morphological features and the natural history of this group of patients were compared with those of a control group of 229 patients who had comparable serum creatinine and extent of glomerular sclerosis, but who lacked active segmental necrosis. RESULTS: Patients with the necrotic variant showed a significantly more marked extracapillary proliferation and interstitial accumulation of monocytes and T lymphocytes and, in the segmental areas of necrotizing and extracapillary lesions, infiltration of monocytes, deposition of fibrinogen, and expression of the adhesion molecule vascular cell adhesion molecule-1. No difference was found in the presenting clinical syndrome. The clinical course was frequently characterized by acute flare ups, and the progression to end-stage renal failure was more frequent, although actuarial renal survival was not significantly worse (P = 0.07). The aggressive treatment with steroids and cyclophosphamide, carried out in 20 of the 35 patients, has probably been beneficial, justifying the multicenter controlled trial that recently has been initiated. CONCLUSIONS: Vasculitic lesions of the glomerular capillaries, with histologic and immunohistological features similar to those of Henoch-Schönlein purpura and antineutrophil cytoplasmic antibody-positive renal vasculitis, were found in 10% of patients with idiopathic IgAN. Clinical features at presentation did not differ from those of the other patients with IgAN, and despite of the more frequent occurrences of recurrent acute flare ups, rapid progression to end-stage renal failure was a rare phenomenon, even in untreated patients.

Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis.

BACKGROUND: In kidney biopsies of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis, a variety of histopathological lesions occur, and their relationship to renal outcome is virtually unknown. This multicenter European study reports a clinicopathological analysis of biopsies from 157 patients with systemic vasculitis. METHODS: The biopsies were evaluated according to a previously standardized scoring protocol. Serum creatinine values were measured at the time of biopsy and one year later. In addition, the lowest creatinine level during follow-up was taken into account as the optimum level of renal function recovery. The clinical prognostic value of the histopathological parameters was analyzed with the Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U-test. RESULTS: The percentage of normal glomeruli correlated most significantly with renal outcome at all points of measurement (all P < 0.001). Other lesions predicting for renal function were glomerular sclerosis (P < 0.0005 at one year after the biopsy), diffuse interstitial infiltrates (P < 0.0001 at entry, P < 0.0003 at one year), tubular necrosis (P < 0.0025 at entry), and tubular atrophy (P < 0.002 at entry, P < 0.0002 at one year). CONCLUSION: Traditionally, attention is focused on the extent of active lesions in the renal biopsy in order to determine the severity of renal disease and its implication for renal outcome. Because of their significant impact on renal function, combined with their easy recognition, we recommend the use of the percentage of normal glomeruli in an adequate biopsy in predicting renal function of patients with systemic vasculitis.

Morphological features in IgA nephropathy.

The hallmark of Berger's disease is the mesangial and/or mesangioparietal deposition of IgA as the predominant or sole immunoglobulin. Despite similar appearance to the immunohistological pattern, morphological glomerular lesions differ in that they are wide ranging and variable, making precise and uniform classificatory approaches extremely difficult. The most characteristic and frequent abnormality is mesangial enlargement, which is produced by various combinations of excess of matrix and of hypercellularity, ranging from minimal to very extensive. In some cases the mesangial lesions are more severe giving a pattern of membrano-proliferative glomerulonephritis. The concomitant presence of necrotizing alterations of glomerular tuft with segmental extracapillary proliferation, similar to capillaritis of Henoch-Schönlein purpura and ANCA associated vasculitis, is now well documented and recognized by researchers. This similarity with vasculitic lesions is confirmed by the strong positivity of fibrinogen, of VCAM-1, and of the accumulation of monocytes within the same areas of segmental necrotic glomerular lesions. These active lesions appear to play a crucial role in the progression of the disease due to repeat formations of necrotizing/extracapillary alterations with subsequent glomerular sclerosis and fibrous adhesions. In the last decade, many groups of investigators have focused their attention on tubulo-interstitial lesions in IgA nephropathy, in particular, on leukocyte infiltration and intersitial fibrosis, demonstrating that the impairment of the glomerular filtration rate and the progression of the disease correlate better with tubulo-interstitial damage than with the degree of glomerular damage. This has also been confirmed by studies with repeat biopsies. Moreover, the recent availability of immunohistochemical and in situ hybridation methods that allow more precise evaluations of infiltrating cells and of numerous factors secreted by these cells (chemokines, cytokines, adhesion molecules etc ...) offers us incredible opportunities to expand our knowledge on mechanisms involved in the inflammatory process and in the progression of the disease.

[Radiation treatment of early stage supraglottic cancer]. / Le traitement radiothérapique des tumeurs sus-glottiques au stade initial.

The management of early-stage squamous cell carcinoma (SCC) of the supraglottic larynx is still controversial. Supraglottic laryngectomy as well as irradiation alone is correlated with good oncological and functional results. In order to evaluate the results and prognostic factors influencing the successful using radiotherapy (RT), the authors performed a retrospective study of 100 consecutive T1-T2 N0 M0 cases of SCC of the supraglottic larynx, treated at a single institution between 1983 and 1992. RT was delivered with 60Co or 6 MeV photons through two lateral parallel opposed portals encompassing the primary laryngeal tumor and the upper and mid-neck nodes (Robbins' levels II, III and V). Supraclavicular nodes (level IV) were electively irradiated in 54 patients with T2 N0 tumors only, using an anterior field with midline block. Sixty-three patients received conventional fractionation (2 Gy/fraction, once-a-day, five times a week), while 37 patients were irradiated according to a twice-a-day fractionation regimen (1.5 Gy/fraction, twice a day with six-hour interval, five days a week). The median total tumor dose delivered was 67 Gy. A multivariate analysis showed that performance status, tumor grade and fractionation modality were the only statistically significant variables influencing disease-free survival. Acute and late radiation reactions were relatively low. This retrospective study confirms that conservative management of T1-T2 N0 supraglottic cancer using RT can achieve good cure rates with the possibility of larynx preservation for the majority of the patients. The decision between different conservative treatment modalities may be influenced by several factors correlated to the patient's conditions, tumor characteristics, but especially treatment modalities.