Frameless stereotactic radiotherapy alone and combined with temozolomide for presumed canine gliomas.

We evaluated stereotactic volume modulated arc radiotherapy (VMAT) for canine gliomas, alone (radiotherapy [RT]) and in combination with temozolomide (RT + TMZ), compared with palliation. Overall and disease-specific survival times were estimated. Thirty dogs were palliated, 22 dogs were treated with RT and 20 with RT + TMZ. Complete and partial responses were observed in 63.2% and 90.9% of patients in the RT and RT + TMZ arms, respectively, that were alive at 1 year. Median survival in the palliation arm was 94 days (95% conformity index [CI] 87÷101). Median survivals of the RT arm (383 days, 95% CI 276÷490) and RT+TMZ arm (420 days, 95% CI 280÷560) were not significantly different (P = .61). Positive correlation with survival was found both for the ratio between target and brain (relative) volume of the tumour of <5% (P = .013) and for a clinical presentation with normal mentation (P = .032). VMAT is feasible and effective for canine brain gliomas. Combining this therapy with TMZ did not elicit any additional improvement in survival time.

Volumetric-modulated arc stereotactic radiotherapy for canine adrenocortical tumours with vascular invasion.

OBJECTIVES: To evaluate the feasibility and efficacy of hypofractionated stereotactic volumetric-modulated arc radiotherapy in treating canine adrenal tumours with vascular invasion. METHODS: A single-arm clinical study was performed. The dogs underwent total body computed tomography, brain and abdomen magnetic resonance imaging and endocrine assay. Adrenal masses were classified as cortisol-secreting adrenal tumour or non-secreting adrenal tumour. Radiotherapy treatments were delivered by hypofractionated stereotactic volumetric-modulated arc radiotherapy via a linear accelerator. The overall survival was estimated by the Kaplan-Meier method. The overall response and radio-toxicity effects were determined. RESULTS: Nine dogs were enrolled. Three dogs were affected by cortisol-secreting adrenal tumours and the remaining dogs had non-secreting adrenal tumours. The prescribed doses ranged from 30 to 45 Gy in three or five consecutive daily fractions. The median overall survival time was 1030 days, and the overall mean reduction of the diameter and volume were ~32 and 30% respectively. The endocrine profile normalised in two dogs with cortisol-secreting adrenal tumours. Radio-toxicities were mild and self-limiting. Seven deaths were recorded during the follow-up period and two dogs were censored. CLINICAL SIGNIFICANCE: Hypofractionated stereotactic volumetric-modulated arc radiotherapy should be considered as a feasible and effective therapeutic option for adrenal tumours with vascular invasion.

Quality assurance of RapidArc in clinical practice using portal dosimetry.

OBJECTIVE: Quality assurance data from five centres were analysed to assess the reliability of RapidArc radiotherapy delivery in terms of machine and dosimetric performance. METHODS: A large group of patients was treated with RapidArc radiotherapy and treatment data recorded. Machine quality assurance was performed according to Ling et al (Int J Radiat Oncol Biol Phys 2008;72:575-81). In addition, treatment to a typical clinical case was delivered biweekly as a constancy check. Pre-treatment dosimetric validation of plan delivery was performed for each patient. All measurements and computations were performed at the depth of the maximum dose in water according to the GLAaS method using electronic portal imaging device measurements. Evaluation was carried out according to a gamma agreement index (GAI, the percentage of field area passing the test); the threshold dose difference was 3% and the threshold distance to agreement was 3 mm. RESULTS: A total of 275 patients (395 arcs) were included in the study. Mean delivery parameters were 31.0±20.0° (collimator angle), 4.7±0.5° s(-1) (gantry speed), 343±134 MU min(-1) (dose rate) and 1.6±1.4 min (beam-on time) for prescription doses ranging from 1.8 to 16.7 Gy/fraction. Mean deviations from the baseline dose rate and gantry speed ranged from -0.61% to 1.75%. Mean deviations from the baseline for leaf speed variation ranged from -0.73% to 0.41%. The mean GAI of repeated clinical fields was 99.2±0.2%. GAI varied from 84.7% to 100%; the mean across all patients was 97.1±2.4%. CONCLUSION: RapidArc can provide a reliable and accurate delivery of radiotherapy for a variety of clinical conditions.

Effectiveness of stereotactic body radiotherapy in the treatment of inoperable early-stage lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Stereotactic body irradiation offers a non-invasive treatment modality for patients with early stage NSCLC who are not amenable to surgery or other invasive approaches because of their poor medical condition. PATIENTS AND METHODS: Forty-three inoperable patients with NSCLC were treated with SBRT at our institution. A mean total dose of 30.5 Gy in 1-4 fractions was applied. The median follow-up duration was 14 months (range 6-36 months). RESULTS: The actuarial survival at two years was 53%: two patients died from cancer progression whereas a further 8 patients died from comorbidities. Acute toxicity was practically absent, with 7 (16.3%) patients suffering from grade 1 symptoms and two from (4.6%) grade II effects. At the time of this report, only 1 patient had grade II and 6 patients (13.9%) grade I chronic symptoms. CONCLUSION: Our results compare favourably with recently published studies and confirm that stereotactic radiotherapy has the potential to produce high local control rates with a low risk of lung toxicity in patients not amenable to curative resection. The low grade of side-effects is encouraging for shortening the treatment using a greater dose per fraction.

The combined endoscopic therapy (band ligation and sclerosis) in the eradication of the esophageal varices in the cirrhotic patient: our experience.

AIM: In course of liver cirrhosis, esophageal varices develop with an incidence of 8-15% a year, and they constitute a sign of seriousness of portal hypertension. The risk of bleeding is estimated around 10-15% a year. The varices hemorrhage causes a high rate of mortality (around 30-35% for every hemorrhagic event). It follows that it is necessary to plan prophylactic strategies for all the cirrhotic patients, who are at risk of bleeding, or have already bled. Medical treatment with beta-blockers is indicated in the prophylaxis of the first bleeding, while endoscopic treatment represents now the most effective methodology either in acute bleeding, or in the prophylaxis of hemorrhage relapses. The available endoscopic methodologies are the sclerosis or band ligation of esophageal varices. However, unanimous consent about the greater effectiveness of a methodology compared to the other one doesn't exist. As far as the varices eradication is concerned, the authors have done a research to verify if the combined techniques, proposed in various studies appeared in literature, can have some advantages, in comparison with the single methodologies. METHODS: Thirty-seven patients have been treated: 27 only with sclerosis and 10 with combined methodology (band-ligation followed by sclerosis of the small residual varices). RESULTS: The group treated with the combined therapy have shown a reduction in relapses and in the main side effects and a better patients' compliance. CONCLUSIONS: The combination of the two methodologies can have some advantages as for security, easiness of execution, reduction in complications, in varices relapse and, therefore, in the hemorrhagic relapses.

[Thyroid maltoma: report of a case without coexistent Hashimoto's thyroiditis]. / Maltoma della tiroide: presentazione di un caso non associato a tiroidite di Hashimoto.

Maltomas of the thyroid are rare neoplasms that originate from parafollicular B lymphocytes and are often associated with autoimmune thyroiditis (Hashimoto's disease). The authors describe a case of a primary thyroid lymphoma in which no evidence for a previous thyroiditis could be found during clinical evaluation (clinical progression of the tumor, diagnostic studies, preoperative cytology, histology of the surgical specimen). Noteworthy was the development of a severe form of pure red cell aplasia (PRCA) about 6 months after the operation without detectable autoantibodies or signs of previous viral infection. The aplasia resolved completely with corticosteroid therapy.

Abrikossoff's tumour: report of a rare case in anal perianal region.

The authors report a rare case of a 47-year old man suffered from Crohn's disease and depression with multiple prominent lesions in the anal and perianal region. The biopsy of these lesions showed the presence of Abrikossoff's tumour. This tumour is very rare in the anal region and usually the lesions are small (0.5-3 cm) and solitary. The authors report this case because they considered it an interesting case for the localization and the appearance of the lesions.

[Gastrointestinal stromal tumors: clinical considerations]. / Considerazioni cliniche sui tumori gastrointestinali stromali.

Gastrointestinal stromal tumors (61ST) are an heterogeneous group of non epithelial tumors of the gastrointestinal tract. They are peculiar to extreme cellular variability and uncertain malignancy. Gist are rare tumors that arise from primitive mesenchymal cells located in all gastrointestinal tract. Till now they are object of discussion about their origin, diagnostic standards, prognostic factors, histopathological classification. They are more frequently in over 40 years old people without difference in two sex, but they can appear in the child too and in the young man suffering from HIV. The authors relate two cases of recent observation, and discuss on the biological behaviour of these rare tumors.

[Pilonidal sinus: an retrospective analysis of 205 cases]. / Sinus Pilonidale. Analisi retrospettiva di 205 casi. Metodo chiuso versus metodo aperto.

Sinus pilonidalis or the sacrococcigea cyst, normally is considered a "small surgical pathology" and actually it is controversial disease regarding its pathogenesis and treatment. Today the congenital hypothesis of this pathology is not considered. The etiopathogenesis exclude vestigia embryonic origin and consider it an inflammatory disease. Traumatism of the sacral region, hirsutism, hormonal secretion stimulating, and furrow sacral furrow cutaneous, explain the prevalence of this pathology in the male sex and in the puberale age. It usually appears after the pubertà and extension one various frequency of presentation in males sex (1.3%) regarding females (0.11%). The symptomatology can be rare or introduce itself in violent and intense way with on abscess of the region, or with only or multiple fistulas orifices from which exit materialclarly purulent. Normally cystic cavity is one, situated in the subcutaneous tissue with annexed inflammatory phenomena. This cavity to times communicates with the skyn fistulating. The treatment of election is surgical and must weighted and be regulated in relation to the entity of the lesion and its inflammatory picture. Sometimes the medical therapy with anti-inflammatory and antibiotic is not control the symptomatology and it need the surgical treatment.

Selective inhibition of human erythrocyte Na+/K+ ATPase by cardiac glycosides and by a mammalian digitalis like factor.

Na+/K+ATPase is a transport membrane protein which contains the functional receptor for digitalis compounds. In this work we compare the inhibition curves of Na+/K+ATPase measured by the inhibition of 86Rb uptake in human red blood cells by cardiac glycosides and by an endogenous digitalis like factor (EDLF) extracted from human newborn cord blood. The curves of Na+/K+TPase inhibition show a monophasic shape for ouabain, strophantidin, digitoxin, proscillaridin and EDLF whereas a biphasic shape for ouabagenin, digoxin, digoxigenin and digitoxigenin. All the drugs are potent inhibitors of erythrocyte Na+/K+ATPase with an IC50 ranging from 1.8 x 10(-9) M to 1.4 x 10(-11) M for the higher affinity binding site and from 1.8 x 10(-6) M to 5.5 x 10(-9) M for the lower affinity site. Digitoxigenin is the most active showing the higher active site at 1.4 x 10(-11) M. Ouabain and digoxin have higher affinity compared with their corresponding genins, while digitoxigenin shows a binding site with higher affinity than the respective cardiac glycosides. The increased affinity of the drugs to Na+/K+ATPase may be related to a lipophilic region in correspondence of the carbons 10, 9, 11, 12, 13 of the steroid nucleus, situated in the opposite side with respect of the C-OH-14. The comparison of the inhibition curves and the HPLC profile of newborn EDLF and of the investigated cardenolides suggest that EDLF may be a compound identical or very similar to ouabain.

Whole-body FDG positron emission tomographic imaging for staging esophageal cancer comparison with computed tomography.

PURPOSE: The aim of the authors in this study was to critically evaluate the role of whole-body positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) in staging esophageal cancer, and further to compare this method with conventional imaging with computed tomography (CT). MATERIALS AND METHODS: The authors performed independent, blinded retrospective evaluations of FDG PET images obtained in 47 patients referred for the initial staging of esophageal cancer before minimally invasive surgical staging. Twenty PET studies from patients with nonesophageal thoracic cancers were randomly selected for inclusion in the PET readings. In a subset of 37 of 47 cases, the PET findings were compared with independent readings of CT studies acquired within the same 6-week interval. The utility of the imaging findings was evaluated using a high-sensitivity interpretation (i.e., assigning equivocal findings as positive) and a low-sensitivity interpretation (i.e., assigning equivocal findings as negative). RESULTS: PET was less sensitive (41% in high-sensitivity mode, 35% in low-sensitivity mode) than CT (63% to 87%) for diagnosing tumor involvement in locoregional lymph nodes, which was identified by surgical assessment in 72% of patients. Notable, however, was the greater specificity of PET-determined nodal sites (to approximately 90%) compared with CT (14% to 43%). In detecting histologically proved distant metastases (n = 10), PET performed considerably better when applied in the high-sensitivity mode, with a sensitivity rate of approximately 70% and a specificity rate of more than 90% in the total group and in the subset of patients with correlative CT data. In the low-sensitivity mode, CT identified only two of seven metastatic sites, whereas the high-sensitivity mode resulted in an unacceptably high rate of false-positive readings (positive predictive value, 29%). PET correctly identified one additional site of metastasis that was not detected by CT. CONCLUSIONS: The relatively low sensitivity of PET for identifying locoregional lesions precludes its replacement of conventional CT staging. However, the primary advantage of PET imaging is its superior specificity for tumor detection and improved diagnostic value for distant metastatic sites, features that may substantially affect patient management decisions. In conclusion, PET imaging is useful in the initial staging of esophageal cancer and provides additional and complementary information to that obtained by CT imaging.

[Propofol and remifentanil in day surgery]. / Propofol e remifentanil in chirurgia di giorno.

AIM OF THE STUDY: to compare AG versus MAC using propofol & remifentanil in a day surgery setting evaluating intra and postoperative clinical conditions and emergence times. METHODS: Propofol and remifentanil, either for general anesthesia (AG) then conscious sedation (MAC), have been administered to 218 patients undergoing mainly plastic or proctologic surgery as day hospital. AG was induced with propofol 1.5-2 mg/kg followed by a continuous infusion of 10 mg/kg/h and remifentanil infused at 10 micrograms/kg/h; MAC was started with propofol 3 mg/kg/h and remifentanil 4-5 micrograms/kg/h; during the maintenance phase of both AG and MAC, infusion rates of both drugs were adjusted according to clinical needs. Diazepam (0.05-0.06 mg/kg) and/or midazolam (2-3 mg) were given as premedication or coinduction as necessary. All patients received field infiltration with local anesthetics (lidocaine or mepivacaine); patients under GA were artificially ventilated with O2/air through IOT or LMA. Surgical and anesthesiological data were collected on specially designed records, with special attention to time intervals between anesthesia (FA) and surgery (FC) end and eyes opening (EO), orientation (OR), return of spontaneous breathing (SR), extubation (EST), sitting (SED), walking (CAMM), dressing (VEST) and discharge (DIM); data were analyzed with parametric and non parametric analysis of variance. RESULTS: All emergence intervals were longer under AG than under MAC: the earlier in the range of 4-5 vs 0.5-1 min; for the late intervals; FA-SED 24 +/- 18 vs 15 +/- 8, FA-PIED 65 +/- 48 vs 34 +/- 17, FA-VEST 69 +/- 58 vs 33 +/- 17, FA-CAMM 68 +/- 42 vs 39 +/- 19. Discharge times (83 +/- 67 vs 73 +/- 60) were similar between the two groups. Drugs consumption under AG were roughly double than under MAC; total dose infused of propofol (mg/kg/min) 0.118 +/- 0.044 vs 0.06 +/- 0.036; total dose of remifentanil (microgram/kg/min): 0.106 +/- 0.049 vs 0.066 +/- 0.027. AG resulted in a higher % incidence of intraoperative hypotension and bradycardia: hypotension 61.7 vs 25.7 and bradycardia 30.3 vs 12.4. SaO2 decreased more commonly during MAC than AG (20.9% vs 10.1); intraoperative itching was referred in 20% of MAC patients. Conversions rate from MAC to AG was 2.8%. Psychomotor agitation was more frequent following AG (14%) than MAC (2%); nausea (1%), vomiting, shivering (12%), headache (2%), ortostatic hypotension (2%) were similar between the two groups. Diazepam and/or midazolam caused a significant prolongation of recovery intervals, for both AG and MAC with a mean delay of the order of 100-200%. CONCLUSIONS: Propofol- remifentanil gave excellent conditions for a wide variety of day surgery procedures, offering good anesthesia with quick emergence; the addition of bdz, even at low doses, prolongs significantly discharge times.

[Variations in interleukin-2 and interleukin-6 due to surgical trauma in cancer patients]. / Variazioni di interleuchina-2 e interleuchina-6 da trauma chirurgico in pazienti oncologici.

Inflammatory response after surgical trauma, which is necessary for infection control and tissue repairing, can actually produce some cytokines suppressive of the antitumoral immunity response. In this study the authors evaluate pre- and post-operative IL-2 (antitumor response activator) and IL-6 (lymphocytic response inhibitor and tumor growth factor) levels in 26 cancer patients undergoing resective surgery. Analysis of the results showed a significative IL-6 increase and a tendency to IL-2 decrease in the post-operative period. It is thus confirmed, even on the basis of the cytokines, the meaningful immunosuppressive effect of the surgical trauma on neoplastic growth control.

Chest tube insertion: a prospective evaluation of pain management.

OBJECTIVE: To evaluate pain associated with chest tube insertion in a group of patients with malignant pleural effusions. DESIGN: Prospective case series. SETTING: Acute care cancer center in an academic institution. PATIENTS: Fifty-two patients with symptomatic malignant pleural effusions. Twenty-six evaluated by conventional approach to chest tube insertion (group 1), 26 evaluated after institution of a new chest tube protocol (group 2). INTERVENTIONS: A new protocol was designed to improve pain control during chest tube insertion. The protocol included improved housestaff and nursing education, premedication, proper insertion techniques, and more liberal and precise delivery of local anesthetic. OUTCOME MEASURES: Both groups were evaluated by a verbal self-report scale (1-10) to assess pain and anxiety. RESULTS: The mean pain rating in group 1 was 6.2 (+/-0.76) compared with 3.7 (+/-5.6) in group 2 (p < 0.01). In group 1, pain or anxiety was 9 or 10 in 12 of 26 on a scale of 1 to 10, compared with 2 of 26 in group 2 (p < 0.001). Anxiety rating was 4.5 (+/-0.72) in group 1 compared with 1.5 (+/-0.54) in group 2 (p < 0.01). CONCLUSIONS: Chest tube insertion was associated with an unacceptably high level of pain and anxiety in our hospital. A new protocol, including housestaff education and changes in nursing policies, technical aspects, local anesthetic dose and delivery, and pre-medication, allowed us to approach the goal of a painless chest tube insertion.

Role of positron emission tomography in staging esophageal cancer.

BACKGROUND: Conventional noninvasive staging of esophageal cancer is inaccurate. This study investigated the role of positron emission tomography (PET) in staging esophageal cancer. METHODS: Patients with potentially resectable esophageal cancer were included. A whole-body PET scan was acquired after injection of 18F-fluorodeoxyglucose and was evaluated for areas of increased focal uptake. Accuracy was determined by comparing PET with surgical staging. RESULTS: Potentially resectable esophageal cancer was identified in 35 patients. Positron emission tomography detected nine sites of distant metastases missed by conventional scanning, but one false-negative PET scan occurred in a patient with a 2-mm liver lesion. There were 11 false-negative PET scans for small, intracapsular local-regional nodal metastases (mean diameter 5.2 mm; range 2 to 10 mm). For distant metastases, the sensitivity was 88%, the specificity was 93%, and the accuracy was 91%. For local-regional nodal metastases, the sensitivity was 45%, the specificity was 100%, and the accuracy was 48%. CONCLUSIONS: Positron emission tomography improved our ability to detect distant metastases missed by conventional noninvasive staging of esophageal cancer. Small local-regional nodal metastases are not identified by current PET technology. Early use of PET in the staging of patients with esophageal cancer could facilitate treatment planning and identifying unsuspected distant metastases in up to 20% of patients with a negative metastatic survey by conventional staging.

Cell cycle control of DNA replication by a homologue from human cells of the p34cdc2 protein kinase.

The regulation of DNA replication during the eukaryotic cell cycle was studied in a system where cell free replication of simian virus 40 (SV40) DNA was used as a model for chromosome replication. A factor, RF-S, was partially purified from human S phase cells based on its ability to activate DNA replication in extracts from G1 cells. RF-S contained a human homologue of the Schizosaccharomyces pombe p34cdc2 kinase, and this kinase was necessary for RF-S activity. The limiting step in activation of the p34 kinase at the G1 to S transition may be its association with a cyclin since addition of cyclin A to a G1 extract was sufficient to start DNA replication. These observations suggest that the role of p34cdc2 in controlling the start of DNA synthesis has been conserved in evolution.

Effect of perioperative transfusions on survival in osteosarcoma treated by multimodal therapy.

We report on a retrospective study of 155 patients amputated for nonmetastatic osteosarcoma of the long bones. Among the various prognostic variables considered, a significant correlation was found only between survival and transfusions. In this report, the authors consider some hypotheses reported by others for tumors of a different nature and site and conclude that perioperative transfusion may induce depression in the immune response, which is the cause of a shorter survival in the patients reviewed.

Cellular and viral control of the initiation of DNA replication.

Cell-free replication of SV40 DNA in extracts prepared from S phase cells is at least 20-fold more efficient than in extracts from G1 cells. The increased activity of S phase extracts correlates with the presence of an S phase-specific cellular factor that enhances DNA unwinding at the replication origin. This change in origin-DNA structure during the initiation of SV40 replication proceeds through at least three discrete steps which can be distinguished by their extent of topologic unwinding (linking differences of -1, -2 and -5). Specific DNA elements flanking the core origin enhance replication in vivo and facilitate the formation of the pre-initiation complexes, indicating that formation of these underwound conformations may be the limiting step in the initiation of DNA synthesis. In addition, the factor that activates DNA replication in extracts from S phase cells also enhances the formation of the most highly underwound -5 pre-initiation complex. These observations suggest that during SV40 replication, formation of the rate-limiting pre-initiation complex is the focus of at least three regulatory elements. Two of these are DNA sequences flanking the replication origin and the third is a cellular factor specific to the S phase cell.

An origin unwinding activity regulates initiation of DNA replication during mammalian cell cycle.

An in vitro assay was developed to study the positive factors that regulate the onset of DNA replication during the mammalian cell cycle. Extracts prepared from cells at defined positions in the cell cycle were used to examine the replication of SV40 DNA in a cell free system. Extracts prepared from S phase cells were ten times more efficient at initiating replication at the SV40 origin than were extracts from G1 cells, whereas elongation rates were similar in G1 and S reactions. At a discrete point in the cell cycle, just before the cell's entry into S, an activity appeared that was required, in conjunction with SV40 T antigen, for site specific initiation at the SV40 origin. This factor had a role in unwinding DNA at the replication origin.