Quality indicators for hyperthermia treatment: Italian survey analysis.

AIM: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field. MATERIAL AND METHODS: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches. RESULTS: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed. CONCLUSION: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.

Long-term follow-up of prostate cancer patients treated with vaccine and definitive radiation therapy.

BACKGROUND: Vaccine therapy in combination with radiation therapy may improve distant and/or local control in prostate cancer. We present long-term follow-up data on the secondary and exploratory endpoints of safety and biochemical failure, respectively, from patients with clinically localized prostate cancer treated definitively with a poxviral vector-based therapeutic vaccine combined with external beam radiation therapy (EBRT). METHODS: Thirty-six prostate cancer patients received definitive EBRT plus vaccine. A total of 18 patients were treated with adjuvant standard-dose interleukin-2 (S-IL-2) (4 MIU m(-2)) and 18 were treated with very low-dose IL-2 (M-IL-2) (0.6 MIU m(-2)). Seven patients were treated with EBRT alone. Twenty-six patients treated with EBRT plus vaccine returned for follow-up, and we reviewed the most recent labs and clinical notes of the remaining patients. RESULTS: Median follow-up for the S-IL-2, M-IL-2 and EBRT-alone groups was 98, 76 and 79 months, respectively. Actuarial 5-year PSA failure-free probability was 78%, 82% and 86% (P=0.58 overall), respectively. There were no significant differences between the actuarial overall survival and the prostate cancer-specific survival between the two vaccine arms. Of the 26 patients who returned for follow-up, Radiation Therapy Oncology Group grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicity was seen in 19% and 8%, respectively, with no difference between the arms (P=1.00 and P=0.48 for grade ≥2 GU and GI toxicity, respectively). In all, 12 patients were evaluated for PSA-specific immune responses, and 1 demonstrated a response 66 months post-enrollment. CONCLUSIONS: We demonstrate that vaccine combined with EBRT does not appear to have significant differences with regard to PSA control or late-term toxicity compared with standard treatment. We also found limited evidence of long-term immune response following vaccine therapy.

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

Radio hyperthermia for re-treatment of superficial tumours.

PURPOSE: Relapse remains an unsolved problem for previously radio-treated patients. Our purpose is to evaluate the role of radio-hyperthermia (RT-HT) in the retreatment of superficial recurrences. MATERIALS AND METHODS: From 1998 to 2007, 51 patients affected by four histological types (breast recurrences (group A), melanoma recurrences (group B), head and neck recurrences (group C), and others (group D)) of 76 superficial lesions, were enrolled at Mauriziano Hospital at the Research Institute of Cancer Care Candiolo (IRCC) in Turin. All patients had previously undergone RT except 6 patients of group B. The total mean retreatment dose was 31.8 Gy (20-60 Gy), while the mean of HT sessions was 5 (1 to 8), temperature ranged from 38.5 degrees C (T min) to 44 degrees C (T max). RESULTS: Acute cutaneous toxicity was 77.6% G1, 22.4% G2, none for G3. Forty-five days later we observed: for group A 65.9% complete response (CR), 29.5% partial response (PR), 4.5% non-response (NR); for group B 33.3% CR, 25% PR and 41.7% NR; for group C 40% CR, 13.3% PR, 46.7% NR, for group D 60% CR and 40% NR. 18 months later group A presented 72.7% local control (LC), 20.5% stable disease (SD) and 6.8% non-control (NC), group B 50% LC, 16,7% SD and 33.3% NC, group C 33.3% LC, 40% SD and 26.7% NC, group D 40% LC and 60% NC. Early response, size of lesions < or =3 cm, T max > or =42 degrees C and RT doses > or =40 Gy were predictive outcome factors. CONCLUSIONS: We confirmed that radio-hyperthermia is useful in re-irradiation with a very high patient compliance.

Infiltrating giant cell tumor in a case of Paget's disease of bone.

Giant cell tumor (GCT) of the bone, also called osteoclastoma, is a rare complication of Paget's bone disease. We report a patient from Southern Italy who developed a GCT infiltrating the neighboring tissues. The natural history and the therapeutic outcomes of this unique complication of Paget's bone disease are presented.

Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room.

OBJECTIVE: To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room. DESIGN: Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation. RESULTS: Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis. CONCLUSION: The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.

Reduced human lymphocyte blastogenesis and enhancement of adenosine triphosphate (ATP) by L-carnitine.

Carnitine is associated with lipid synthesis and its deficiency may lead to cardiomegaly with parenchymal lipid in the heart, kidney and liver. In our study we found that pretreatment of peripheral blood mononuclear cells (PBMC) with serial dilutions of L-Carnitine (100 micrograms/ml-1 pg/ml) inhibits, in a dose-dependent manner, lymphocyte DNA synthesis stimulated with PHA (20 micrograms/ml). L-Carnitine did not have any effect on resting PBMC. The maximum inhibition was found at 10 micrograms/ml of L-Carnitine. Moreover, in a time-course study and using an enzymatic analysis (ATP monitoring reagent), L-Carnitine enhanced ATP production on PBMC treated and untreated with PHA, reaching a maximum effect at 30 min incubation. In another set of experiments PBMC were treated with L-Carnitine alone and in combination with PHA, and the percent of receptors CD3, CD4, and CD8 were calculated with flow cytometry. After the cell incubation with L-Carnitine, the percent of all receptors studied did not change compared to L-Carnitine-untreated cells (controls). These data suggest that L-Carnitine inhibits, in a dose-dependent manner, lymphocyte blastogenesis induced by PHA, probably through the enhancement of ATP synthesis, which is considered an inhibitor of phospholipase C activity and a suppressor in lymphocyte cultures.

Pulmonary follow-up 2.5 years after a randomized, controlled, multiple dose bovine surfactant study of preterm newborn infants.

Forty-seven preterm infants, who were previously enrolled in a prospective, randomized, blinded study at birth to assess the effects of multiple doses of exogenous bovine surfactant to prevent respiratory distress syndrome, underwent lung function evaluation and review of their medical histories at 2 1/2 years of age. During their initial hospitalization there were no differences between the 17 control infants and the 30 surfactant-treated infants in the duration of ventilator or oxygen therapy and the incidence of bronchopulmonary dysplasia. At the follow-up both groups were similar in chronological and corrected ages, weights, lengths, and sex ratios and there were no differences in the occurrence of allergy, asthma, bronchiolitis, eczema, pneumonia, and wheezing. In addition, there was no significant difference regarding the incidence of chest illnesses lasting either 3 or 7 days and in the total number of required rehospitalizations. Functional residual capacity (FRC), tidal volume (VT/kg), compliance (Crs/kg), resistance (Rrs), and time constant of the respiratory system were not significantly different between the two groups at 2 1/2 years of age. We conclude that bovine surfactant, when given during the neonatal period, has little long-term effect on lung function. Neonatal bovine surfactant therapy neither improves nor produces any adverse effects on the developing respiratory system.

Side effects and long-term follow-up of corticosteroid therapy in very low birthweight infants with bronchopulmonary dysplasia.

Seventy-seven very low birthweight (VLBW) infants (mean birthweight 891 +/- 209 g) with a diagnosis of bronchopulmonary dysplasia (BPD) were treated with a steroid (dexamethasone) in an attempt to wean them from mechanical ventilation. Seventeen of 77 (22%) treated infants died. Death from respiratory failure occurred in 13 infants; sepsis occurred in six infants (7.8%) and contributed to death in one. During steroid therapy systemic hypertension occurred in 18 surviving infants (30%), glucose intolerance occurred in 29 infants (38%), and marked irritability occurred in three infants (3.8%). Elevated blood pressure returned to normal and glucose intolerance resolved in all infants following discontinuation of therapy. Fifty infants were available for follow-up at a mean corrected age of 14.9 +/- 9.8 months. Twenty-two percent required rehospitalization in the first year of life for respiratory illnesses. Results of testing by Bayley Scales of Infant Development were normal in 60% of infants. Fifty percent were considered normal based on both developmental testing and physical examination. Twenty-eight percent had mild to moderate abnormalities, and 22% were severely handicapped. These follow-up results are statistically similar to those recorded in LBW infants with BPD not treated with steroids who were hospitalized during the same period. We conclude that the side effects of steroid therapy for BPD consist primarily of blood pressure elevation, glucose intolerance, and irritability. Causes of death are unchanged by steroids. The incidence of severe infection and the long-term neurologic outcome of high-risk infants with BPD are not appreciably compromised by this therapy. These data suggest that concern for steroid side effects should not prevent additional prospective investigation to determine the role of steroid therapy in the overall management of BPD.

Treatment of pulmonary manifestations of gastroesophageal reflux in children two years of age or less.

Apnea and worsening bronchopulmonary dysplasia as well as recurrent aspiration pneumonia have been found to be consequences of gastroesophageal reflux in infants and young children. Antireflux procedures are effective in preventing gastroesophageal reflux; however, the effect of this operation on the course of these respiratory problems in very young patients is not known. We reviewed the results in 51 patients 2 years of age or less who underwent an antireflux fundoplication for pulmonary problems attributable to severe gastroesophageal reflux unresponsive to medical treatment. Twenty-eight patients had recurrent episodes of aspiration pneumonia, 14 had nonimproving or worsening bronchopulmonary dysplasia, and 9 had unexplained apneic episodes. Seventy-three percent of these patients had coexisting congenital anomalies or acquired problems. No operative deaths and no major surgical complications occurred. There were eight late deaths occurring between 1 and 25 months postoperatively: three were due to associated congenital anomalies or acquired problems, three to sepsis, and two to sudden infant death syndrome. Of the 43 surviving children, 91 percent with preoperative recurrent aspiration pneumonia had no additional episodes after Nissen procedure. Eighty-eight percent of the infants with unexplained apneic episodes showed marked benefit and 83 percent of those with bronchopulmonary dysplasia had clinical improvement. There were no late problems attributed to the operation even when it was performed in preterm infants. Therefore, we recommend fundoplication for patients 2 years of age or less who have a persistent pulmonary problem attributed to gastroesophageal reflux that does not respond to medical therapy.

Monoclonal antibody identification of a type II alveolar epithelial cell antigen and expression of the antigen during lung development.

A monoclonal antibody identifying an antigen expressed by rat type II alveolar epithelial cells, but not by type I epithelial cells or other mature lung cells, was produced by immunization of mice with cells of the rat L2 cell line. The antigen recognized by the antibody was present on the microvillous luminal surface of type II epithelial cells. In adult rat lung, only type II epithelial cells bound the antibody. During fetal development the antigen was expressed by cuboidal epithelial cells lining the respiratory ducts of the first divisions of the tracheal bud, but not by epithelial cells lining the esophagus or trachea. The antigen continued to be expressed by cuboidal epithelial cells lining the larger respiratory ducts until approximately 19 days gestational age. Thereafter, expression was increasingly limited to selected single cells or clusters of two to four cuboidal cells in the smallest ducts. By the 21st postnatal day, the antigen was expressed only by type II alveolar epithelial cells. Type II alveolar epithelial cells isolated from adult lung and the L2 cell line in culture expressed the antigen on the cell surface. A protein of approximately 146,000 Mr was isolated by immunoadsorption of the antigen from non-ionic detergent extracts of type II cells and L2 cells. Preliminary studies of the binding of the antibody to other rat tissues indicate that the antibody binds to renal proximal tubular epithelial cells of the kidney and the luminal surface of the small bowel epithelial cells.

Nissen fundoplication for gastroesophageal reflux in infants.

Some degree of gastroesophageal reflux is very common in infants and tends to reverse with time. Therefore, the indications for an antireflux operation are not well defined. Furthermore, the complication rate and the ability of the fundoplication to grow remain to be determined. To answer these questions, we reviewed the records of patients 6 months of age or younger who underwent a Nissen fundoplication with gastrostomy tube placement between 1979 and 1985. There were 45 patients (25 boys and 20 girls) with birth weights of 0.65 to 4.3 kg. The consequences of gastroesophageal reflux were more varied than in older children. Severe respiratory problems were common, including recurrent aspiration or bronchopulmonary dysplasia in 60% and frequent apneic and bradycardiac spells in 17%. Failure to gain weight was present in 20% and intractable vomiting in 2.0%. As expected, 78% of these patients had congenital anomalies or acquired problems which, in many cases, were important to the prognosis. The diagnosis was confirmed by barium swallow in all but one patient in whom gross reflux during feedings was present. Initially, medical management was tried for 3 to 4 weeks. In one patient, however, the severity of the respiratory problems precluded trial beyond 12 days. The recommendation for operation was based only on the severity of symptoms attributed to gastroesophageal reflux. All patients underwent Nissen fundoplication with gastrostomy tube placement at 2 weeks to 6 months of age and weighing 1.02 to 6.95 kg. The only surgical complication was one gastrostomy leak. Prematurity or preexisting anomalies led to a 20% incidence of late unrelated deaths between 2 weeks and 23 months postoperatively. Improvement in symptoms occurred in our survivors with follow-up of 5 to 72 months. We conclude: Significant gastroesophageal reflux in infancy most frequently produces respiratory problems that can be life threatening. Nissen fundoplication can be a safe and effective procedure in infants 6 months of age or younger. Fundoplication appears to have good growth potential, and no late complications or feeding problems have occurred. Consequently, surgical correction can be recommended for infants not responding to conservative medical therapy.

Localization and quantitation of anionic charge sites in fetal and neonatal alveolar basement membranes.

A method utilizing biopsy sized samples of lung for anionic charge site localization in alveolar and capillary basement membranes in human tissue is discussed. Tissue fixed in either paraformaldehyde-lysine-periodate or 1% paraformaldehyde with 0.05% glutaraldehyde, cut into 30 mu sections, and incubated with the cationic probe, polyethyleneimine, was processed for electron microscopic analysis using standard techniques. Anionic charge sites were identified and regularly distributed in increments of approximately 40-50 nm in the lamina rara externa of the alveolar basement membrane, with lesser amounts found in the lamina rara interna and lamina densa. Anionic charge sites were also demonstrated in the interstitial portion of the capillary basement membrane and on cell surfaces. These methods can be used to more broadly define the localization of anionic charge sites in human lung tissue in both normal and pathologic states.

Laryngeal injuries secondary to nasogastric tubes.

Laryngeal complications secondary to nasogastric intubation have been reported rarely in recent literature. Recent experience with three patients who developed laryngeal injuries related to nasogastric tubes prompted retrospective, experimental, and prospective studies to determine the mechanism of laryngeal injury. A review of the literature, as well as the clinical findings in our three patients, point to midline tube placement and the subsequent development of cricoid chondritis as the underlying etiology. An experimental study using anesthetized dogs was designed to compare histologically the effect on the larynx with nasogastric tubes placed in the midline, as opposed to nasogastric tubes in the lateral position. Results of the histologic study confirmed that midline tubes generate severe inflammation in the postcricoid region. One hundred patients were then evaluated roentgenographically to determine the incidence of midline tube placement in a random sample. Six percent of the patients had nasogastric tubes in the midline. Patients who have nasogastric tubes in place for more than three days or have a severe amount of discomfort should have an x-ray film to determine position of the tube. Midline tubes should be removed or replaced.