A kinetics-based approach to amyloid PET semi-quantification.

PURPOSE: To develop and validate a semi-quantification method (time-delayed ratio, TDr) applied to amyloid PET scans, based on tracer kinetics information. METHODS: The TDr method requires two static scans per subject: one early (~ 0-10 min after the injection) and one late (typically 50-70 min or 90-100 min after the injection, depending on the tracer). High perfusion regions are delineated on the early scan and applied onto the late scan. A SUVr-like ratio is calculated between the average intensities in the high perfusion regions and the late scan hotspot. TDr was applied to a naturalistic multicenter dataset of 143 subjects acquired with [18F]florbetapir. TDr values are compared to visual evaluation, cortical-cerebellar SUVr, and to the geometrical semi-quantification method ELBA. All three methods are gauged versus the heterogeneity of the dataset. RESULTS: TDr shows excellent agreement with respect to the binary visual assessment (AUC = 0.99) and significantly correlates with both validated semi-quantification methods, reaching a Pearson correlation coefficient of 0.86 with respect to ELBA. CONCLUSIONS: TDr is an alternative approach to previously validated ones (SUVr and ELBA). It requires minimal image processing; it is independent on predefined regions of interest and does not require MR registration. Besides, it takes advantage on the availability of early scans which are becoming common practice while imposing a negligible added patient discomfort.

Topical use of phytotherapic cream (Capilen® cream) to prevent radiodermatitis in breast cancer: a prospective historically controlled clinical study.

AIM: The purpose of this study was to evaluate the ability of a topical phytotherapic product (Capilen® cream) to limit acute radiodermitis and delay the use of corticosteroids in patients with breast cancer (BC). METHODS: From January 2012 to August 2012, 30 consecutive patients, undergoing radiotherapy with adjuvant intent, were invited to use Capilen® cream two times daily two weeks before and during radiotherapy. An historical group was used as an external control. Acute skin toxicity was scored weekly according to RTOG/EORTC criteria. Time of occurrence of acute skin toxicity was taken as endpoint. RESULTS: Compliance was good. Overall, no significative statistical difference was observed in rate of acute radiation dermatitis, 46.7% in experimental arm versus 63.3% in the historical control group, although only 3.3% of Capilen® cream treated patients had a G3 acute radiation dermatitis versus 10% of the control group. A delay in the onset of radition dermatitis in patients treated with Capilen® cream (P=0.04) was showed. CONCLUSION: Our findings suggested that Capilen® cream plays a role in reducing acute radiation dermatitis in breast cancer patients treated with adjuvant radiotherapy. Further evidence is needed to confirm these results.

Radiation Therapy in Non-Melanoma Skin Cancers: An Italian Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology.

AIMS: The National Palliative Care and Interventional Radiotherapy Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) carried out a survey whose aim was to obtain a "snapshot" of the real-world practice of nonmelanoma skin cancer (NMSC) treatments in Italy. MATERIALS AND METHODS: The survey was conducted on SurveyMonkey's online interface and was sent via e-mail to our society Radiation Oncologists. RESULTS: Fifty-eight Italian radiation oncologists (ROs), representing 54 centers, answered the survey. Thirteen percent of the ROs declared they treat fewer than 10 NMSC lesions annually, 36% treat between 11 and 20, and 51% treat more than 20 lesions annually. Interventional radiotherapy (IRT) was offered by 25% of the ROs, and every case was reportedly discussed by a multidisciplinary team (71%). Electrons (74%), volumetric modulated arc therapy (V-MAT) (57%), three-dimensional conformal radiotherapy (3D-CRT) (43%), and IRT (26%) were the main treatment options. With external beam radiotherapy (EBRT), 46 and 53 different RT schedules were treated for curative and palliative intent, respectively; whereas for IRT, there were 21 and 7 for curative and palliative intent, respectively. The most popular EBRT curative options were 50-70.95/22-35 fractions (fx) and 50-70 Gy/16-20fx and for EBRT palliative settings, 30Gy/10fx, and 20-35Gy/5fx. For IRT, the most popular curative options were 32-50Gy/8-10fx and 30-54Gy/3-5fx, whereas 30Gy/6fz was the palliative option. Less than 10 re-RT cases were reported in one year in 42.5%, 11-20 cases in 42.5%, and >20 cases annually in 15%. Electrons (61%), VMAT (49%), and BRT (25%) were the most widely used approaches: 20-40Gy in 10fx and 20-25Gy in 5fx were the recommended fractionations. CONCLUSION: The survey shows a variegated reality. A national registry with more detailed data could help in undercover its causes.

Clinical usefulness of myocardial innervation imaging using Iodine-123-meta-iodobenzylguanidine scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure: an overview.

AIM: This study was designed to review published data regarding the clinical usefulness of iodine-123-meta-iodobenzyl-guanidine (MIBG) scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure (HF). METHODS: A comprehensive computer literature search of the PubMed/MEDLINE and Embase databases was conducted to find relevant published articles about the clinical usefulness of MIBG scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with HF. RESULTS: Thirty-three studies, comprising a total sample size of 1124 patients with HF, were included in this review. Main findings of the included studies are presented. CONCLUSIONS: Myocardial innervation imaging using MIBG scintigraphy can be successfully used to assess changes in cardiac sympathetic neuronal function caused by several pharmacological interventions in patients with HF.

Pharmacological interference with 123I-metaiodobenzylguanidine: a limitation to developing cardiac innervation imaging in clinical practice?

BACKGROUND: (123)I-metaiodo-benzylguanidine (MIBG) scintigraphy is considered a valid imaging test to evaluate the cardiac sympathetic nervous system. However, scientific literature showed that some drugs are able to or are expected to interfere with MIBG uptake. Thirty years after introduction of the method and over 15 years since the appearance of the first document on pharmacological interference with MIBG, an update on this issue has become necessary. AIM: The aims of this review paper are: (1) to identify the pharmacological basis of interference of a variety of substances with MIBG uptake; and (2) to update the list of drugs that definitely interfere with MIBG on the grounds of evidence in the literature. MATERIALS AND METHODS: A MEDLINE search was conducted. Scientific studies, case report and review articles were collected. Papers published demonstrating drugs interfering with MIBG uptake were evaluated. RESULTS: Drugs may interact with MIBG uptake by 5 mechanism: (1) type-1 uptake inhibition; (2) inhibition of active transport to vesicles; (3) competition in transport to vesicles; (4) depletion of neurosecretory vesicle content; (5) calcium-mediated mechanism. We find that drugs like cocaine, antidepressants, some antipsychotic, tramadol, labetalol, sympatho-mimetics, reserpine and some calcium antagonists (as diltiazem, verapamil and nifedipine) do interfere with MIBG uptake. On the other hand, we find that controversial data are available on scientific literature regarding digoxin and amiodarone. CONCLUSIONS: A compiled statement of MIBG interfering medicines is now recommended to help nuclear medicine physicians in clinical practice to avoid potential pitfalls and improve the efficacy of (123)I-MIBG scintigraphy as a diagnostic tool.

Comorbidity assessment and radiotherapy in elderly cancer patients.

More than 60% of all cancer patients in Europe and the USA are older than 65 years at the time of diagnosis. Despite this, elderly patients are generally under-represented in clinical trials. There is a lack of clinical trials to drive evidence-based decision making in the elderly cancer patients. In this review, we address the most important issue surrounding the treatment of older cancer patients: comorbidity assessment.

Radiotherapy and hepatocellular carcinoma: update and review of the literature.

Historically radiotherapy has always played a limited role for the treatment of HCC due to the low tolerance of the liver and the subsequent risk of radiation induced liver disease (RILD). Technologist advancements in radiation planning and treatment delivery such as Stereotactic Body Radiotherapy (SBRT) combined with Image Guided Radiotherapy (IGRT) has allowed us to further increase tumor dose while maximally sparing the surrounding not involved liver. Furthermore, together with the growing knowledge of radiobiological models in liver disease, several mono-institutional retrospective and prospective series are reporting very encouraging results. Therefore, radiotherapy might play a significant role for the treatment of unresectable HCC, alone or combined with other locoregional treatment such as transarterial chemoembolisation (TACE). The rationale for studying this technique is really strong and it should be tested in well designed prospective randomized clinical trials.

Can we decrease the acute proctitis in prostate cancer patients using hyaluronic acid during radiation therapy: a prospective historically controlled clinical study.

BACKGROUND: The purpose of this study was to evaluate the ability of rectal suppository of hyaluronic acid to limit symptoms of acute radiation proctitis in patients with prostate cancer (PC). MATERIALS AND METHODS: From January 2011 to October 2011, 50 consecutive patients, undergoing radiotherapy with radical or adjuvant intent for PC, were invited to use rectal suppository of hyaluronic acid (HA: Cicatridina suppository, Farma-Derma s.r.l., Sala Bolognese, BO, Italy) daily, before radiation delivering. An historical group was used as an external control. Acute rectal toxicity was scored weekly according to RTOG criteria. Time to occurrence of acute rectal toxicity was taken as endpoint. RESULTS: Compliance was good. Only 2% of HA treated patients had a G2 acute proctitis versus 7% of historical group, globally a difference was observed in rate of acute proctitis between the experimental arm and the control group: 32% in experimental arm versus 45% in control group (p = 0.08). A delay in the onset of acute rectal toxicity in patients treated with HA (p = 0.04) was showed. CONCLUSIONS: Our findings suggested the role of HA in reducing acute proctitis in prostate cancer patients treated with radiotherapy. Further trials are needed to confirm these results.

Metabolic responses in non-small cell lung cancer after hypofractionated stereotactic radiotherapy PET and hypofractionated radiotherapy.

BACKGROUND: The aim of our study was to evaluate the pattern of local failure after stereotactic body radiotherapy (SBRT) of non small cell lung cancer (NSCLC) lesions relating to different type of 18F-FDG positron emission tomography (PET) response. METHODS: Thirteen NSCLC patients for a total of 15 lesions (primary early or locally advanced and metastases) underwent PET before and 6 months after SBRT. Maximum standard uptake value (SUVmax) <2.5 was considered as cut off for complete response (CR) while lesion reduction > or =50% with residual value above 2.5 for partial response (PR). RESULTS: With a median follow up of 30 months pre- and post-SBRT mean SUV max values were 8.2 (range 14.2-3.7) and 2.4 (range 12.9-0), respectively. No "in field recurrence" was observed while 3 cases of "out field recurrence" occurred as regional nodes progression at 7.8 and 14 months after treatment. Three years overall survival, local control and distant metastases free survival were respectively 66.7%, 63.3% and 44.4%. Actuarial 75% and 53.3% 3-year local control, 60% and 40% 3-years distant metastases free survival were observed for complete and partial PET response, respectively, after SBRT. Thereafter, 60% and 50% 3-year overall survival were observed for complete and partial response. CONCLUSIONS: Clinical results were significantly better for "responder" than "non responder" and for "complete" than "partial response" group. Moreover, our data seem to confirm that a significant subset of patients maintain a low metabolic activity without developing local relapse on longer follow up.

Statins and coronary artery disease: clinical evidence and future perspective.

Many clinical trials have demonstrated the beneficial effects of statins on cardiovascular risk, both in patients with history of coronary heart disease and in healthy subjects with risk factors, because of a significant reduction in acute coronary events. The introduction of more powerful statins in the market offered the opportunity to study whether an intensive lipid lowering treatment could yields even better cardiovascular outcomes than a moderate statin therapy and several clinical trial confirmed this hypothesis. Statins have also pleiotropic effect behind their lipid lowering function: they reduce inflammation, which plays an important role in the atherosclerotic process.

Coronary plaque instability assessed by positron emission tomography and optical coherence tomography.

BACKGROUND: Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) are caused often by destabilization of non-flow limiting inflamed coronary artery plaques. 18F-fluorodeoxyglucose (FDG) uptake with positron emission tomography/computed tomography (PET/CT) reveals plaque inflammation, while intracoronary optical coherence tomography (OCT) reliably identifies morphological features of coronary instability, such as plaque rupture or erosion. We aimed to prospectively compare these two innovative biotechnologies in the characterization of coronary artery inflammation, which has never been attempted before. METHODS: OCT and FDG PET/CT were performed in 18 patients with single vessel coronary artery disease, treated by percutaneous coronary intervention (PCI) with stent implantation, divided into 2 groups: NSTEMI/UA (n = 10) and stable angina (n = 8) patients. RESULTS: Plaque rupture/erosion recurred more frequently [100% vs 25%, p = 0.001] and FDG uptake was greater [TBR median 1.50 vs 0.87, p = 0.004] in NSTEMI/UA than stable angina patients. FDG uptake resulted greater in patients with than without plaque rupture/erosion [1.2 (0.86-1.96) vs 0.87 (0.66-1.07), p = 0.013]. Among NSTEMI/UA patients, no significant difference in FDG uptake was found between ruptured and eroded plaques. The highest FDG uptake values were found in ruptured plaques, belonging to patients with NSTEMI/UA. OCT and PET/CT agreed in 72% of patients [p = 0.018]: 100% of patients with plaque rupture/erosion and increased FDG uptake had NSTEMI/UA. CONCLUSION: For the first time, we demonstrated that the correspondence between increased FDG uptake with PET/CT and morphology of coronary plaque instability at OCT is high.

Clinical efficacy of intravenous colistin therapy in combination with ceftazidime in severe MDR P. aeruginosa systemic infections in two haematological patients.

Nosocomial infections due to MDR P. aeruginosa are an increasing problem. Therapeutical options are few. We describe two haematological patients with severe neutropenia and systemic infection due to MDR P. aeruginosa treated successfully with colistin plus ceftazidime. Severe adverse events were not described.

Morphology of afferent synapses in the Mauthner cell of larval Xenopus laevis.

The fine structure of the afferent synapses on the Mauthner cell of larval Xenopus laevis has been studied as a first step toward comparing the fine structure of the afferent synaptic apparatus before and after metamorphosis. There are various types of afferent endings on this cell, some of which are confined to specific cellular regions, while others are distributed over most of the large surface of the neuron. Four different main types of endings have been observed: club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. While the myelinated club endings and the spiral fibers endings are located at the distal end of the lateral dendrite and in the axon cap, respectively, the end bulbs are widely distributed over the whole cell. A further type of ending has been observed, although rarely, on the Mauthner cell soma and dendrites: end bulbs characterized by an unusually dense presynaptic substance. Results obtained in the present research suggest that, as in fish, different endings on the anuran Mauthner neuron correspond to different synaptic inputs. The possible origin of some of these inputs is discussed.

Cytoskeletal components and calibers in developing fish Mauthner axon (Salmo gairdneri Rich.).

In developing axons of many vertebrates, microtubular density is inversely correlated with fiber caliber. It is suggested that microtubules are causally related to axonal caliber. For this reason, cytoskeletal analysis during development of the fish Mauthner axon, which displays a giant caliber, is of particular interest. The Mauthner axon originates from the Mauthner cell in the medulla and runs in the fasciculus longitudinalis medialis in the spinal cord. At embryonic, larval and postlarval stages in trout (Salmo gairdneri Rich.), the following parameters were measured on conventional electron micrographs of Mauthner axon cross sections; axonal caliber, number of microtubules per axons, and microtubular and neurofilament densities. Results at each stage point to an inverse correlation between axonal caliber (x) and microtubular density (y) expressed by the equation y = axb (R = 0.932). Furthermore, three periods of Mauthner axon development are identified on the basis of the cytoskeletal content: (1) embryonic; the Mauthner axon has small caliber with a high microtubule density, (2) elongation period (larval stages); the axon enlarges and a transient peak of microtubules, corresponding to the caliber increment, is observed, and (3) postlarval; the axon enlarges still further (greater than 500 microns 2) but has the lowest microtubular content. During this period neurofilaments are the main axonal component.

Emergency therapeutical approach simulating ultrarapid opioid detoxification in methadone withdrawal precipitated by erroneous administration of naltrexone.

We report the case of a 30-year-old male, heroin dependent, receiving methadone treatment, who, while staying at home, ingested 50 mg of naltrexone. He immediately developed serious withdrawal symptoms and was admitted to the hospital. In the emergency department the drugs given to counteract the agitation were ineffective, and the patient developed respiratory distress. Anaesthesia with propofol was then started and the patient was intubated, ventilated and hospitalized in the intensive care unit. He was then sedated for 48 hours due to persistent withdrawal signs. When medically stable the patient was transferred to the medical ward where daily treatment with naltrexone and psychological support where started. After 4 days the patient was discharged. Afterwards he did not attend his scheduled outpatient follow-up visits. Treatment with propofol is effective in the case of a patient with a serious withdrawal syndrome secondary to naltrexone overdose during methadone therapy. Despite the actual possibility of getting through the withdrawal symptoms the patient failed to return for follow-up visits, which might be related to a lack of motivation.

Morphometric analysis of Mauthner axon cytoskeletal components in adult and subadult fish.

A previous cytoskeletal analysis on trout MA during developmental stages demonstrated, during the subadult stages, neurofilaments (NF) as main components as expressed by the high values of neurofilament to microtubules (MT) ratio which was found to be of the order of 300:1. Since the MA cytoskeletal composition is not known in the adult fish, the MA cytoskeletal composition has been compared to other axons of much smaller diameter of the fasciculus longitudinalis medialis (flm) among which the MA run in the ventral spinal cord. The following parameters were measured on conventional electron microscopy in MA and flm axons cross sections micrographs by means of a computer linked graphic tablet (Apple II): axonal caliber, number of microtubules (MT), microtubular (MT/microns2) and neurofilament (NF/microns2) densities. The analysis of these parameters demonstrated that neurofilaments are the main architectural components in the adult and subadult fish MA and flm axons. However, MA cytoskeletal composition differs from the other flm axons because of its particular very high ratio of neurofilaments to microtubules. The inverse relationship of axonal caliber to microtubular density, previously found in the trout during developmental stages and suggested also for many other vertebrate species, was further confirmed for flm axons which, with calibers 10 times smaller than MA, exhibit a microtubular density 10 times larger.

Diosmectite (DIOSMECTAL) in preventive anti-diarrheic therapy in patients subjected to pelvic radiation.

BACKGROUND: The radiation therapy of abdominal-pelvic tumors, determining diarrhea and cramps, could reduce the compliance of the patient and compromise his quality of life. This study attempts to assess the effects of adjuvant therapy with diosmectite (Diosmectal) on the above mentioned side effects from radiotherapy. METHODS: From August 1998 to September 1999, 40 patients (mean age 68) at the Oncological Radiotherapy Division of the Azienda Policlinico of Modena took part in the study: 21 forming the group of patients treated with diosmectite and 19 forming the control group. The radiotherapy was administered with total doses varying from 45 to 70 Gy in both groups with daily doses of 1.8-2 Gy. From the beginning of the therapy the patients in the group treated with Diosmectal, received 6 g daily doses of the drug split into two administrations. The diarrhea was assessed by referring to the Lent Soma score. RESULTS: In the group of patients not in therapy, an incidence of diarrhea was observed in 77% of subjects while in the group in therapy the incidence of diarrhea dropped to 25% of the cases (p<0.005), with an increase in the latency of the appearance of any diarrhoeic symptoms. CONCLUSIONS: Our data suggests that the administration of diosmectite in a prophylactic manner is capable of reducing the incidence of gastroenteric symptomatology (diarrhea and cramps).

[Methimazole-induced aplastic anemia]. / Anemia aplastica indotta da metimazolo.

The aplastic anemia methimazole induced is a rare event. We describe a case of a woman, affected by hyperthyroidism, who suffers from bone marrow aplasia during Tapazole treatment, and literature has been reviewed. Stopping methimazole and beginning a therapy with methylprednisolone in high dosage, intravenous IgG in high dosage, filgastrin and danatrol, medullary recover after 11 days of treatment is obtained. By analyzing our case and the 12 further cases described, we find that the prognosis of aplastic anemia during the treatment of antithyroid therapy, is rather good. Even if the pathogenetic mechanism of Tapazole induced bone marrow aplasia, it seems to be immuno-mediated in most cases, a direct toxicity in bone marrow cannot be excluded. In examined cases the antithyroid dosage was medium high (mean 40 mg/die). Therefore the use of Tapazole in low doses (15 mg/die) effective in almost all hyperthyroid patient must be considered, when possible, the best therapeutic choice, since it is safer in the incidence of important side effects such as bone marrow aplasia, especially in elderly patients or in patients with chronic renal failure.

[Chronic erythremic myelosis (or the chronic form of Di Guglielmo's disease). A case report]. / Mielosi eritremica cronica (o forma cronica della malattia di Di Guglielmo). Descrizione di un caso.

The chronic erythromyelosis (or chronic type of Di Guglielmo's disease) is a rare illness of uncertain classification. This illness shows characteristics that remember on the one hand the myeloproliferative and on the other hand the myelodysplastic diseases. The therapy is quite unsatisfactory. As a presence of erythrocytic antibodies has been detected, a therapy with steroids, danazol, splenectomy, immunosuppressive agents, plasmapheresis is advised. We have tried a cycle of therapy with high doses of intravenous gammaglobulin (0.4 g/kg/day for 4 days) also in the attempt of reduce, even if temporarily, the hemolytic component due to the reticuloendothelial system's hyperplasia. We conclude that this therapy, in our patient, has not yielded good outcomes immediately but carried out settled levels of haemoglobin as well as reduction of bilirubin and LDH after a month.

Elderly gastrointestinal cancer patients and radiochemotherapy: a review.

Gastrointestinal cancers are among the most frequently occurring cancer worldwide. Elderly patients represent a large proportion of patients diagnosed with gastrointestinal cancers. Despite this, elderly patients are generally under-represented in clinical trials, therefore a general consensus on how to treat elderly patients is still far from being achieved. In oesophageal cancer, radiochemotherapy can be administered successfully and effectively but should be administered with close monitoring because of potential toxicities especially hematological. In gastric and rectal cancer, there is no clear trade-off between efficacy and side effects and some patients may not gain a survival benefit from combined treatment. Instead, the treatment of elderly pancreatic cancer patients with a good performance status should be no different than the treatment of younger patients. Radiochemotherapy maintains its activity and feasibility in elderly gastrointestinal cancer patients. Finally, it is very important to assess co-morbidity with its severity in order to aid in the development of plans for treatment.