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Skeletal remodelling is a continuous process during life and is still active also in extreme senescence. In the elderly, bone resorption often prevails over bone formation, causing bone loss and fragility. Elderly subjects are exposed to the risk of fractures, and loss of self-sufficiency, if considering that the proximal femur is the most frequently involved site. Bone remodelling can maintain circulating calcium within physiological ranges, at the expense of a substantial loss of this ion from the skeleton, particularly during senescence. Calcium metabolism is regulated at cellular/molecular level by a network of cytokines, growth factors, systemic hormones that act on bone in paracrine/autocrine/systemic fashion. Among the molecules involved in bone metabolism, parathyroid hormone (PTH) and vitamin D present some peculiar aspects during senescence. The osteometabolic features in a consistent group of centenarians have been evaluated. It results that a severe hypovitaminosis D was present in 99 out of 104 centenarians (25-OH vitamin D below 5 nmol/L), and that it plays an important role as a factor inducing a vicious circle involving hypocalcemia, secondary hyperparathyroidism, together with biochemical features indicating a consistent bone loss. Serum C-terminal cross-linking telopeptide, a specific marker of bone resorption was elevated in 92% of these subjects. Moreover, it has been found that several femoral fractures had occurred after 90 years of age. These data offer a rational for the possible prevention of elevated bone turnover, bone loss and consequently the reduction of osteoporotic fractures and fractures-induced disability, in the oldest olds, through the simple supplementation with calcium and vitamin D.

The Italian multicentric study on centenarians (IMSC) was aimed at assessing the level of preservation of the sense of taste, and at estimating to what extent the recognition of various gustative stimuli can give satisfaction and information regarding the surrounding environment for the centenarians. Taste sensitivity has been qualitatively established in a group of 126 Italian centenarians (mean age 101.9+/-1.4 years) and compared to that of a group of 100 elderly subjects (mean age 70.5+/-5.0 years). All the individuals included in the study groups had a mini mental state examination (MMSE) score larger than 19. The results revealed that taste sensitivity is significantly reduced in the centenarians; as a matter of fact, the elderly control subjects are able to perceive taste stimuli in 84.25+/-3.40% of the testing, while the centenarians were successful only in 74.23+/-6.19% of the experiments (P

Left ventricular assist device (LVAD) support in donors may contribute in preserving proper haemodynamics and systemic perfusion during organ retrieval thus decreasing the risk of multiple organ injury. This is an option to expand the current organ supply. We report on intra-abdominal organs procurement strategy in a selected LVAD recipient who suffered a fatal cerebrovascular accident at the time of COVID-19 pandemic outbreak. The liver and kidneys grafts have been successfully transplanted.

Objective 3D models are increasingly used as additional preoperative tools for renal surgery. We aim to evaluate the impact of 3D renal models in the assessment of PADUA, RENAL, Contact Surface Area (CSA) and Arterial Based Complexity (ABC) for the prediction of complications after Robot assisted Partial Nephrectomy (RAPN). Methods and materials Overall, 57 patients with T1 and 1 patient with T2 renal mass referred to RAPN, were prospectively enrolled. 3D virtual modelling was obtained from 2D computed tomography (CT). Two radiologists recorded PADUA2D, RENAL2D, CSA2D and ABC2D by evaluation of 2D images; two bioengineers recorded PADUA3D, RENAL3D, CSA3D and ABC3D by evaluation of the 3D model, using MeshMixer software. To evaluate the concordance between 2D and 3D nephrometry scores, Cohen's j coefficient was calculated. Receiver-operating characteristic (ROC) curves were generated to evaluate the accuracy of 3D and 2D nephrometry scores to predict overall complications. Finally, the impact of 3D model on clamping approach during RAPN was compared to 2D imaging. Results PADUA3D, RENAL3D, CSA3D and ABC3D scores had a significant different distribution compared to PADUA2D, RENAL2D, CSA2D and ABC2D (all p≤0.03). 2D nephrometry scores may be unchanged, reduced or increased after assessment by 3D models: CSA3D, PADUA3D, RENAL3D and ABC3D were reduced in14%, 26%, 29% and 16% and increased in 16%, 36%, 38% and 29% of cases, respectively. At ROC curve analysis, PADUA3D, RENAL3D and ABC3D showed were significantly better accuracy to predict complications compared to PADUA2D, RENAL2D and ABC2D. PADUA3D (OR: 1.66), RENAL3D (OR: 1.69) and ABC3D (OR: 2.44) revealed a significant correlation with postoperative complications (all P ≤0.03). Conclusion Nephrometry scores calculated via 3D models predict complications after RAPN with higher accuracy than conventional 2D imaging.

Background: Minimally-invasive approach is one of the mainstays of Enhanced Recovery After Surgery (ERAS) pathways. Robot-assisted radical cystectomy (RARC) introduction has reduced the surgical burden on patient's recovery. Accordingly, ERAS protocol benefits may be more striking in RARC patients. We evaluated the impact of surgical approach on perioperative outcomes, Fast Track (FT) recovery steps and Trifecta success rates in patients undergoing RC followed by FT protocol. Materials and methods: We considered 147 patients who underwent RC, with open (Open radical cystectomy [ORC]; 47.6%) or robotic (RARC; 52.4%) approach at 2 tertiary centers. Urinary diversions were ileal conduit or orthotopic neobladder. All patients underwent FT protocol. We analyzed perioperative surgical and functional outcomes and Trifecta success rates (namely, defecation 0.05). Conclusion: RARC has more favorable perioperative outcomes compared to ORC, with higher Trifecta success rates. Accordingly, robotic approach should be ideally included in every center where ERAS protocol is applied to RC for maximizing patient's recovery.

AIM: To assess the utility of (11)C-choline PET/CT in the restaging of prostate cancer (PC) patients who showed a single finding on bone scintigraphy (BS) that was classified as equivocal or suspected for metastatic lesion. MATERIALS AND METHODS: A total of 25 PC patients with biochemical failure (mean PSA value 11.1 ng/mL; median value 6.3 ng/mL; range 0.2-37.7 ng/mL) after primary treatment were included in this retrospective study. All of them showed a single lesion on BS reported as suspected for metastatic lesion or as equivocal finding. Patients underwent (11)C-choline PET/CT within 1-4 months from BS. Validation was established by follow-up for at least 6 months. RESULTS: On the basis of biopsy confirmation and/or 6-month follow-up, 22 of 25 patients were classified as positive for the presence of metastatic bone lesions: 13 with a single lesion and 9 with multiple lesions. (11)C-choline PET/CT was positive in 19/25 patients and, on a lesion basis, it showed 50 positive findings. BS results were confirmed in 8/25 (32%) patients. (11)C-choline PET/CT detected multiple sites of relapse in 11/25 (44%) patients: in 2/11, a single bone lesion associated with other extraosseous sites of relapse; in 6/11, multiple bone lesions; in 3/11, multiple bone lesions and other extraosseous localizations. Finally, 6/25 patients were negative on (11)C-choline PET/CT. In 3/6 patients, an osteoblastic lesion was seen on CT attenuation correction images (PET false negative; BS true positive), while in 3/6 patients only findings suggestive of the presence of degenerative disease were found (PET true negative; BS false positive). On a patient basis, (11)C-choline PET/CT showed a diagnostic sensitivity of 86% (19/22) and a specificity of 100% (19/19). CONCLUSIONS: In our study, (11)C-choline PET/CT detected unknown lesions in 11/25 patients. Patients with a single equivocal finding on BS could have important additional information from (11)C-choline PET/CT study, especially in the detection of additional metastases, to choose an appropriate treatment

The in vivo evaluation of three modified polyethylene glycol (PEG)-anilinoquinazoline derivatives labeled with (124)I, (18)F, and (11)C as potential positron emission tomography (PET) bioprobes for visualizing epidermal growth factor receptor (EGFR) in cancer using small animal PET. PROCEDURES: Xenograft mice with the human glioblastoma cell lines U138MG (lacking EGFR expression) and U87MG.wtEGFR (transfected with an overexpressing human wild-type EGFR gene) were used. Static and dynamic PET imaging was conducted for all three PEGylated compounds. Tumor necrosis, microvessel density, and EGFR levels were evaluated by histopathology and enzyme-linked immunosorbent assay. RESULTS: Nineteen animal models were generated (two U138MG, three U87MG, 14 with both U138MG and U87MG bilateral masses). In static images, a slight increase in tracer uptake was observed in tumors, but in general, there was no retention of tracer uptake over time and no difference in uptake between U138MG and U87MG masses. In addition, no significant uptake was demonstrated in dynamic scans of the (18)F-PEG tracer. No necrosis was present except in four animals. MVD was 9.6 and 48 microvessels/×400 field in the U138GM and U87GM masses, respectively (p = 0.00008). Similarly, the microvessel grades were generally higher in the U87GM group (p = 0.002). Total EGFR amount was higher in U87MG than U138MG masses (p = 0.001), but the ratio of activated (pY1068) to total EGFR did not differ (p = 0.95). CONCLUSIONS: PEGylated tracers labeled with (11)C, (124)I, and (18)F showed no significant difference in uptake between U138MG and U87MG glioblastoma xenograft mice. The tracer binding with EGFR could be influenced by activation of the tyrosine kinase portion of the receptor which was similar in U138MG and U87MG. Despite these results, these tracers should be investigated in animal models with mutant EGFR genes to determine whether aberrant receptor function plays a role in tumor uptake

Background: Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema. Methods: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h. Results: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low. Conclusions: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.

The aim of this work was to preliminarily evaluate the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of 68Ga-citrate PET/CT in a population of patients with suspected bone infections. Methods: We enrolled 31 patients with suspected osteomyelitis or diskitis who underwent a total of forty 68Ga-citrate PET/CT scans. The results were compared with different combinations of diagnostic procedures (MRI, radiography, CT, or white blood cell scintigraphy), biopsy (when diagnostic), and follow-up data (at least 1 y) to determine the performance of 68Ga-citrate PET/CT. Results: We found a sensitivity of 100%, a specificity of 76%, a positive predictive value of 85%, a negative predictive value of 100%, and an overall accuracy of 90%. Conclusion: Although preliminary, these data confirm a possible role for 68Ga-citrate in the diagnosis of bone infections, especially in consideration of its favorable characteristics.

In the last ten years, the development of several novel targeted drugs and the refinement of state of the art technologies such as the genomics and proteomics and their introduction to clinical practice have revolutionized the management of patients affected by cancer. However, everyday practice points out several clinical questions: the difficulty of response assessment to new drugs especially using standard RECIST criteria that do not provide information on biological, vascular or metabolic variations; the inadequate selection of patients who are likely to benefit from a targeted therapy excluding those with breast cancer and gastrointestinal stromal tumours; the need to know the global biological background of diseases especially in metastatic setting using repeatable non-invasive procedures. Molecular imaging could provide information on in vivo distribution of biological markers in response to targeted therapy and could improve the selection of patients before therapies. The aim of this review is to analyze the current role of conventional and innovative positron emission tomography (PET) radiotracers in clinical practice and to explore the promising perspectives of molecular imaging in cancer research.

PURPOSE: Scintigraphic localisation of parathyroid glands is often unsuccessful in patients with renal failure on chronic haemodialysis who have secondary hyperparathyroidism (HPT). The purpose of this study was to investigate the use of (11)C-methionine PET/CT to detect hyperfunctioning parathyroid glands in patients with renal failure on chronic haemodialysis who had (99m)Tc-sestamibi-negative HPT. METHODS: (11)C-methionine PET/CT was performed in 18 patients (11 women and 7 men, aged 42-79 years; mean age 57.8 years) on haemodialysis for renal failure (2-14 years' duration), with normo-, hypo- or hypercalcaemia and HPT not localised by either dual-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi subtraction scans or dual-phase (99m)Tc-sestamibi scans. RESULTS: In three of ten patients with normo- or hypocalcaemic HPT there was increased (11)C-methionine accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed increased uptake: in five of these patients increased (11)C-methionine accumulation was present in one gland, while in two it was demonstrated in two glands. All patients also had high-resolution ultrasound of the neck and were treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the four glands. Regardless of their size, all glands with abnormal (11)C-methionine parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia. All patients developed post-parathyroidectomy hypoparathyroidism and one patient with normocalcaemic HPT relapsed 8 months after surgery. CONCLUSION: These data suggest that (11)C-methionine PET/CT may be used to identify hyperfunctioning parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when conventional (99m)Tc-sestamibi imaging is non-localising.

To evaluate the prevalence and scan interpretation criteria useful in identifying non-tumoural F-FDG focal uptakes (potential pitfalls) in patients who had been previously treated for a malignant lymphoma studied by positron emission tomography (PET).Nine hundred and ninety-six consecutive PET scans obtained in 706 patients with malignant lymphoma were reviewed. All patients had been previously treated by first-line chemo-radiotherapy, plus surgery when required, and were then studied by FDG PET to investigate suspected recurrence at doubtful or inconclusive conventional radiological imaging (ultrasound, computed tomography, magnetic resonance imaging). PET was obtained with patients in the fasted condition and after i.v. injection of 370 MBq of F-FDG; imaging was acquired 60-90 min later. In patients with focal FDG uptake the final diagnosis was reached on the basis of histological findings or long-term follow-up.Thirty-one of 134 PET scans (23.1%) showing focal FDG uptake were diagnosed as non-tumoural radiotracer uptake, related to the presence of brown fat in seven cases, thymic hyperplasia in five, muscles contraction in four, lymph node unspecific inflammation in four, mediastinal/pulmonary unspecific inflammation in four, gastritis in two, colitis in two, bacterial abscess in one, lactating breast in one, and herpes zoster in one. Each of the above cited situations has been reported in the literature, generally in the form of sporadic reports, as a potential cause of misinterpretation (false positive) in reading a PET scan with the potential for incorrect patient management. An accurate diagnosis in these patients was important for the following therapeutic decision making.In the whole series of patients with treated malignant lymphoma, the prevalence of non-tumoural FDG focal uptake during follow-up was relatively low (3.1%); conversely, it was relatively high when considering the sub-group of 'positive' PET only (23.1%). The importance of knowing these situations in order to avoid misinterpretation in reading PET scans needs to be emphasized. In this light, an accurate patient's history and a skilful nuclear medicine physician are very important factors. For the same purpose, it is reasonable to think that the use of hybrid PET/CT tomographs could also play an important role in helping to identify non-tumoural FDG focal uptake.

Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.

In an attempt to know the exact retrograde spread of high-dosage 5-aminosalicylic acid enemas, we have studied eight patients with active left-sided colitis, by adding a small amount of barium sulfate to the enemas and by checking the spread radiologically after 15 minutes, 1 hour, and 6 hours. Four grams of 5-aminosalicylic acid in 100-ml enemas and 4 gm in 200-ml enemas were used. The same experiment was repeated in a subsequent attack, with enemas labeled with technetium-99m and checked by scintiscans in five of these patients. We always have observed a volume-dependent spread of enemas but, interestingly, in the patients studied with technetium-99m there was always a wider spread than that which was detected with barium enemas. In all five patients, 100-ml enemas reached the splenic flexure. In two patients with total colitis, a progression of 100-ml technetium-99m enemas was performed in the transverse colon, but the maximum opacity remained in the left side. We can conclude that 4 gm of 5-aminosalicylic acid in 100-ml enemas can be suitable for treating patients with left-sided colitis, and will represent a valid addition for patients with more extensive colitis.

5-aminosalicylic acid (5-ASA) is a new treatment for patients suffering from ulcerative colitis but only limited information is available about its rectal absorption. We therefore studied seven patients with ulcerative colitis in remission, and five with active disease to determine acetylated and free 5-ASA plasma concentrations and urinary acetyl 5-ASA after the administration of three different types of enemas: (2 g 5-ASA/100 ml, 4 g/100 ml, and 200 ml). In patients in remission urinary acetyl 5-ASA excretion was dose and volume dependent (p less than 0.01; p less than 0.05) but this correlation was absent in active disease. Because aminosalicylates are usually eliminated through the kidney, these low values (10% in active disease and 19% in those in remission) suggest that the beneficial action may be local. Urinary recovery was significantly lower in patients with active disease (p less than 0.01; p less than 0.02). No accumulation of 5-ASA was found in plasma after repeated daily administration.

Aims: An oral multiparticulate coated formulation of 5‐aminosalicylic acid (5‐ASA; mesalazine) has been developed to provide a controlled release of the drug, in a pH‐dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl‐5‐ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration. Methods: Three groups were investigated: six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5‐ASA and Ac‐5‐ASA were measured for 48 h. Results: In the single oral dose regimen, systemic absorption of 5‐ASA and Ac‐5‐ASA were low and did not differ between the three groups. Only about 20% of the 5‐ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5‐ASA and Ac‐5‐ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5‐ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges. Conclusions: The new oral 5‐ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about 80% of the drug being available for ileum‐colon therapeutic activity. Copyright © 1994, Wiley Blackwell. All rights reserved

Patients with Crohn's disease may become zinc‐deficient and, in such patients, an altered metabolism of radiolabelled long‐chain fatty acids has been reported. We have investigated the possible reversal by zinc supplementation of altered long‐chain fatty acid profiles of red cells in Crohn's disease. Twenty patients with long‐standing Crohn's disease in clinical remission received 200 mg of zinc sulphate daily for 6 weeks. Phospholipid fatty acid profiles of washed red cells were analysed before and after zinc treatment and compared to those of 20 unsupplemented healthy controls. Plasma zinc levels in Crohn's were 72 ± 8 μg/dL before zinc treatment and increased to 114 ± 10 μg/dl after the therapy. Prior to zinc supplementation, the percentage of palmitic, stearic and oleic acids was significantly higher in Crohn's disease, while linoleic, arachidonic and n‐3 fatty acids were reduced in Crohn's disease compared to healthy controls. Zinc supplementation abolished these pre‐treatment differences in red‐cell long‐chain fatty acid profiles but did not affect plasma fatty acid values. Further studies are needed to clarify whether these fatty acid changes can be related to the clinical course of the disease. Copyright © 1994, Wiley Blackwell. All rights reserved

Sunitinib is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic properties used for treatment of renal cell carcinoma and gastrointestinal stromal tumors at a dose of 50 mg/day consecutively for 4 weeks followed by 2 weeks off per cycle. At present, no data are available on the early prediction of sunitinib response in renal cell carcinoma. We report a clinical case of a patient with metastatic renal cell carcinoma diagnosed with 11C-acetate PET and conventional CT and treated with sunitinib. Partial and complete remission documented by CT was preceded by early functional tumor inhibition shown by 11C-acetate-PET after only 14 days of therapy. This case report highlights some interesting points related to the potential role of a novel non-FDG PET tracer, 11C-acetate, in the early prediction of the response to targeted therapies in metastatic renal cell carcinoma.

A 7-year-old girl with indolent left upper extremity edema had axillary, supraclavicular, right retrocaval, paravertebral, mesenteric, and right iliac adenopathy confirmed by ultrasound and CT. Selective axillary biopsy demonstrated epitheliomorphic malignancy with neuroendocrine/neuroectodermic differentiation. Bone scintigraphy demonstrated several thoracic spin lesions. I-123 metaiodobenzylguanidine imaging was negative. Ga-68 DOTA-NOC PET/CT demonstrated multiple lesions in her axilla, thoracic spine, and retroperitoneum. Biopsy of a palpable nodule at her left forearm revealed alveolar rhabdomyosarcoma with neuroendocrine differentiation.