High dose craniospinal irradiation as independent risk factor of permanent alopecia in childhood medulloblastoma survivors: cohort study and literature review.

PURPOSE: Our aim was to determine the main risk factors related to the occurrence of permanent alopecia in childhood medulloblastoma (MB) survivors. METHODS: We retrospectively analyzed the clinical features of all consecutive MB survivors treated at our institute. We divided the patients into 3 groups depending on the craniospinal irradiation (CSI) dose received and defined permanent alopecia first in terms of the skin region affected (whole scalp and nape region), then on the basis of the toxicity degree (G). Any relationship between permanent alopecia and other characteristics was investigated by a univariate and multivariate analysis and Odds ratio (OR) with confidence interval (CI) was reported. RESULTS: We included 41 patients with a mean10-year follow-up. High dose CSI resulted as an independent factor leading to permanent hair loss in both groups: alopecia of the whole scalp (G1 p-value 0.030, G2 p-value 0.003) and of the nape region (G1 p-value 0.038, G2 p-value 0.006). The posterior cranial fossa (PCF) boost volume and dose were not significant factors at multivariate analysis neither in permanent hair loss of the whole scalp nor only in the nuchal region. CONCLUSION: In pediatric patients with MB, the development of permanent alopecia seems to depend only on the CSI dose ≥ 36 Gy. Acute damage to the hair follicle is dose dependent, but in terms of late side effects, constant and homogeneous daily irradiation of a large volume may have a stronger effect than a higher but focal dose of radiotherapy.

Caries-preventive efficacy of a supervised school toothbrushing programme in Northland, New Zealand.

BACKGROUND: Toothbrushing with fluoride toothpaste reduces the incidence of dental caries. OBJECTIVE: To evaluate a supervised school toothbrushing programme to reduce dental caries experience in children. BASIC RESEARCH DESIGN: Quasi-experimental study. All children had routine dental examinations at baseline using the ICDAS to record dental caries, along with bitewing radiographs. Half of the children were involved in a supervised toothbrushing programme. Examinations were repeated at the end of the school year. CLINICAL SETTING: Northland, New Zealand. PARTICIPANTS: 335 10-13-year-old New Zealand children with high caries experience. INTERVENTIONS: Half of the children participated in the supervised toothbrushing session each school day; the other half had no intervention. MAIN OUTCOME MEASURES: Caries increment, determined by comparing the baseline and follow-up status of each tooth surface. RESULTS: At baseline, there were 335 children, of whom 240 (71.6%) were followed up. The ICDAS net caries increment for those in the toothbrushing group was a mean of 11.7 surfaces improved; the control group had a mean of 8.6 surfaces which had deteriorated. Caries incidence for those in the toothbrushing group was 7.3%; that for the control group was 71.5%. Multivariate analysis showed that membership of the brushing group was the only statistically significant predictor of a lower net caries increment. CONCLUSION: A supervised school toothbrushing programme can reduce caries increment in a population experiencing high levels of dental disease.

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee: a randomized controlled trial. 1: clinical effectiveness.

OBJECTIVE: To evaluate the clinical effectiveness of manual physiotherapy and/or exercise physiotherapy in addition to usual care for patients with osteoarthritis (OA) of the hip or knee. DESIGN: In this 2 × 2 factorial randomized controlled trial, 206 adults (mean age 66 years) who met the American College of Rheumatology criteria for hip or knee OA were randomly allocated to receive manual physiotherapy (n = 54), multi-modal exercise physiotherapy (n = 51), combined exercise and manual physiotherapy (n = 50), or no trial physiotherapy (n = 51). The primary outcome was change in the Western Ontario and McMaster osteoarthritis index (WOMAC) after 1 year. Secondary outcomes included physical performance tests. Outcome assessors were blinded to group allocation. RESULTS: Of 206 participants recruited, 193 (93.2%) were retained at follow-up. Mean (SD) baseline WOMAC score was 100.8 (53.8) on a scale of 0-240. Intention to treat analysis showed adjusted reductions in WOMAC scores at 1 year compared with the usual care group of 28.5 (95% confidence interval (CI) 9.2-47.8) for usual care plus manual therapy, 16.4 (-3.2 to 35.9) for usual care plus exercise therapy, and 14.5 (-5.2 to 34.1) for usual care plus combined exercise therapy and manual therapy. There was an antagonistic interaction between exercise therapy and manual therapy (P = 0.027). Physical performance test outcomes favoured the exercise therapy group. CONCLUSIONS: Manual physiotherapy provided benefits over usual care, that were sustained to 1 year. Exercise physiotherapy also provided physical performance benefits over usual care. There was no added benefit from a combination of the two therapies. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12608000130369.

Manchester triage in acute pulmonary embolism: can it unmask the grand impersonator?

BACKGROUND: Acute pulmonary embolism (PE) is associated with high mortality risk. Early diagnosis is difficult because of non-specific clinical presentation and delay in imaging confirmation. Manchester Triage (MT) prioritises patients on the basis of illness severity and potentially recognises those with higher mortality risk. No studies of the role and impact of MT on rapid PE diagnosis and in-hospital mortality (IHM) have been carried out. OBJECTIVE: To assess the appropriateness of MT in this set of patients presenting acutely to the emergency department (ED), and to determine whether it assists in a rapid diagnosis, acts as a protective triage tool and affects short-term mortality. METHODS: Single-centre retrospective study of 176 consecutive patients with PE, assessed by MT in the ED between January 2006 and October 2010 (mean age 70.5±15.7 years, 38.6% men). The primary outcome measure was all-cause IHM. RESULTS: IHM was seen in 30 (17%) patients. More than half of the patients with PE (54%) were classified as target time for first medical observation (MOb) ≤10 min. 73.3% of IHM occurred in this group (p=0.020) with several increased markers of illness severity. MOb ≤10 min was not associated with faster PE imaging confirmation. The average door-to-diagnosis time (PEDx) was 26.8±36.8 h and PEDx >17.0 h was associated with higher IHM (p=0.017). On multivariate analysis, thrombolysis and MOb ≤10 min were included in an IHM predictor model. CONCLUSION: MT has high sensitivity in identifying patients with PE at risk. Those patients assigned as MOb ≤10 min have increased markers of illness severity and higher IHM. MT acts as a protective system in this challenging set and should be used as a patient's first assessment, aiding the emergency medical team to recognise those in need of urgent assessment and treatment.

Parental history of premature myocardial infarction is a stronger predictor of increased carotid intima-media thickness than parental history of hypertension.

An increased carotid intima-media thickness (IMT) is detectable in young subjects with parental history of premature myocardial infarction (PHPMI) or hypertension (PHH). In this study we evaluated if PHPMI and PHH exert a different influence on carotid IMT and if their conjunction produces additive effects. High-resolution B-mode ultrasonographic evaluation of common carotid artery IMT was acquired from 48 subjects without PHPMI and PHH (22 males, 26 females; mean age 22.1±4.9 years; controls), 24 age- (±1 year) and sex-matched subjects with PHH without PHPMI (PHH-positive/PHPMI-negative subjects), 24 age- and sex-matched subjects with PHPMI without PHH (PHH-negative/PHPMI-positive subjects) and 24 age- and sex-matched subjects with both PHPMI and PHH (PHH/PHPMI-positive subjects). Lipid profile, resting blood pressure, smoking behaviour and body mass index (BMI) were also assessed. Carotid IMT was smaller in controls (0.41±0.07mm) compared to PHH-positive/PHPMI-negative subjects (0.47±0.10, p=0.023), to PHH-negative/PHPMI-positive subjects (0.54±0.11, p<0.001) and to PHH/PHPMI-positive subjects (0.52±0.10mm, p<0.001). Carotid IMT was greater in PHH-negative/PHPMI-positive (p=0.006) and in PHH/PHPMI-positive (p=0.031) than in PHH-positive/PHPMI-negative subjects. No difference in carotid IMT was evident between PHH-negative/PHPMI-positive and PHH/PHPMI-positive subjects (p=0.549). In the comparison among subjects using multiple regression analysis, only PHPMI, age and BMI were independently associated with carotid IMT. In healthy young subjects with PHPMI and/or PHH, carotid IMT is increased. PHPMI is a stronger predictor of increased carotid IMT than PHH. PHH in conjunction with PHPMI does not add any further detrimental effect on carotid IMT.

Subclinical atherosclerosis and genetic risk markers in healthy offspring of patients with premature myocardial infarction.

AIM: Healthy young subjects with parental history of premature myocardial infarction (PHPMI) might constitute a privileged population for the study of genetic risk markers (GRM) for atherosclerosis. Aim of this study was to evaluate which, if any, GRM atherosclerosis-associated in previous studies has increased prevalence in a selected population. METHODS: Twenty-four healthy young subjects (12 males and 12 females; mean age 18.0±8.0 years) with PHPMI and 24 age- (±1 year), sex-matched healthy subjects without PHPMI were enrolled in the study. They underwent: 1) fasting measurement of lipid profile, resting blood pressure and body mass index; 2) high resolution B-mode ultrasonographic evaluation of common carotid artery intima-media thickness (IMT); 3) evaluation of Single Nucleotide Polymorphisms (SNPs) for six candidate genes associated with preclinical atherosclerosis. RESULTS: Compared to controls, subjects with PHPMI had increased IMT of common carotid arteries (mean of combined sites: 0.535±0.171 mm versus 0.432± 0.133 mm in controls, P=0.017). Offspring of coronary patients showed an increased prevalence of the unfavourable chemochine (C-X-C motif) ligand 12 (CXCL12) SNP risk genotype (P=0.047). CONCLUSION: In healthy young subjects with PHPMI there is an increased prevalence of the unfavorable CXCL12 SNP risk genotype.

A Primary Care Randomized Controlled Trial of Hall and Conventional Restorative Techniques.

OBJECTIVES: To investigate treatment outcomes of different restorative techniques undertaken by dental therapists for primary molar carious lesions in a sample of children in New Zealand primary care. METHODS: This was a randomized controlled trial with children aged 3 to 8 y in New Zealand's Whanganui region. Children meeting inclusion criteria were randomly allocated to treatment with either the Hall technique (HT), in which a stainless-steel crown (SSC) is placed without any carious tissue removal or tooth preparation, or a non-Hall conventional restorative approach (NHT), including tooth preparation with selective carious tissue removal; this included SSC, amalgam, composite, or glass ionomer cement (GIC) restorations. Restorative outcomes after 12 and 24 mo were categorized as success, minor failure, or major failure. RESULTS: Of the 295 eligible children, 149 and 146 were allocated to the HT and NHT groups, respectively, with a total of 570 carious primary molars treated by 13 dental therapists. The participant follow-up rates at 12 and 24 mo were 95% and 91%. SSCs were the most commonly used restoration in the NHT group (60%), followed by GIC (28%). SSCs were the most successful restorations regardless of whether they were placed with the HT or NHT, with success rates of 89% and 92% at 12 mo and 85% and 86% at 24 mo. In the NHT group, the treatment material was a predictor of minor failure at 12 and 24 mo, with significantly more failures with GICs. CONCLUSIONS: SSCs placed by dental therapists are a highly successful restoration for the primary dentition, regardless of whether they are placed with the HT or conventionally. The high failure rate of glass ionomer restorations means that they cannot be recommended for widespread use in New Zealand primary care (Australian New Zealand Clinical Trials Registry, ACTRN12614000844640). KNOWLEDGE TRANSFER STATEMENT: The findings of this study can be used by policy makers and clinicians when deciding on which materials and which approach to use to maximize success and to minimize retreatment rates when providing restorative treatment for carious primary molars in children's primary oral health care. Results also suggest that undertaking research in the primary care setting may enhance translation of new knowledge and techniques into clinicians' hands.

[Discharge against medical advice in Veneto Region]. / Dimissioni volontarie nella Regione Veneto.

Discharge against medical advice (DAMA) may put patients at risk of adverse health outcomes and often generate hospital readmission. A retrospective case-control study (2000-2004) of all DAMA in Veneto Region hospitals was carried out to determine the baseline characteristics of patients who leaves hospital. During the 5-years study period, the overall DAMA rates were 0.8 from ordinary hospitalization and 0.2 from daily. Prediction of patients at risk of DAMA may be possible with several defined variables and this analysis represent an instrument that should facilitate the development of successful strategies to reduce DAMA for high-risk patients.

[Feasibility of week surgery model in general surgery]. / Week surgery in Chirurgia generale: applicabilità del modello.

Progress in medical technology and the research in cost-effectiveness have provided an implementation on new general surgery models. Week Surgery model is a maximum 5 days stay surgical unit which represents an important contribution to surgical therapeutic strategies, allowing an excellent compromise between safety, convenience for the patient and economic savings for health care structures. This model represent an excellent compromise between elective and emergency care and thus allow to improve patients flow across the week, a most efficient bed utilisation and reallocating hospital workloads. With the aim of testing the feasibility of the application of Week Surgery model was carried out a seven-years retrospective study (2000-2006) among Veneto Region public hospitals. Results suggest that week surgery model can be considered a valid and achievable alternative organisation compared to conventional hospitalization: 61% of patient undenrwent elective surgery were discharged in less than 5 days.

Posttraumatic stress and youth violence perpetration: A population-based cross-sectional study.

BACKGROUND: Exposure to trauma was found to increase later violent behaviours in youth but the underlying psychopathological mechanisms are unclear. This study aimed to test whether posttraumatic stress disorder (PTSD) is related to violent behaviours and whether PTSD symptoms mediate the relationship between the number of trauma experiences and violent behaviours in adolescents. METHOD: The present study is based on a nationally representative sample of 9th grade students with 3434 boys (mean age=15.5 years) and 3194 girls (mean age=15.5 years) in Switzerland. Lifetime exposure to traumatic events and current PTSD were assessed by the use of the University of California at Los Angeles Posttraumatic Stress Disorder Reaction Index (UCLA-RI). Logistic regression was used to assess associations between PTSD and violent behaviours, and structural equation modelling (SEM) was used to examine the meditation effects of PTSD. RESULTS: PTSD (boys: OR=7.9; girls: OR=5.5) was strongly related to violent behaviours. PTSD symptoms partially mediated the association between trauma exposure and violent behaviours in boys but not in girls. PTSD symptoms of dysphoric arousal were positively related to violent behaviours in both genders. Anxious arousal symptoms were negatively related to violent behaviours in boys but not in girls. CONCLUSIONS: In addition to trauma, posttraumatic stress is related to violent outcomes. However, specific symptom clusters of PTSD seem differently related to violent behaviours and they do not fully explain a trauma-violence link. Specific interventions to improve emotion regulation skills may be useful particularly in boys with elevated PTSD dysphoric arousal in order to break up the cycle of violence.

Loxoscelismo: revisión de la literatura a propósito de un caso / Loxoscelism: Literary review about a case

La mordedura de la araña de rincón es un motivo de consulta frecuente en los servicios de urgencia de Chile, que puede producir un cua-dro severo con manifestaciones cutáneas y sistémicas. En Chile, Loxocelles laeta se ubica principalmente desde la I a la VIII región, aunque se han reportado casos de loxocelismo en todo el país. El veneno de esta araña tiene efecto cutáneo-necrosante, hemolítico, vasculítico y coagulante. Podemos identificar 3 tipos de loxocelismo: cutáneo necrótico (80% de los casos), cutáneo edematoso (5%) y cutáneo visceral (10-15%). Este último tiene una letalidad entre 1 y 3% del total de casos de loxocelismo, la cual depende en gran parte de la precocidad de su diagnóstico y manejo oportuno. Se debe controlar cualquier tipo de loxocelismo durante las primeras 24 a 48 horas y vigilar la aparición de síntomas y signos sugerentes del cuadro visceral. No existe ningún examen de laboratorio que confirme el diagnóstico, los cuales sólo se alteran de modo marcado en los casos viscerales. El manejo de las lesiones cutáneas es con hielo local, antiinflamatorios, antihistamínicos y curaciones seriadas. En caso del loxocelismo visceral, el tratamiento principal es de soporte. La dapsona fue una indicación frecuente en el pasado y se asocia a efectos adversos graves, siendo el principal la exacerbación de la hemólisis, por lo que actualmente su uso no está recomendado. El suero anti-loxoceles no tiene evidencia que avale menor severidad ni mortalidad del cuadro.

The bite of the corner spider is a frequent reason for consultation in the emergency services of Chile, which can produce a severe reaction with cutaneous and systemic manifestations. In Chile, Loxocelles laeta is located mainly in the first to the eighth region, but cases of loxoscelism are reported throughout the country. The venom of this spider has cutaneous-necrotizing, hemolytic, vasculitic, and coagulant effects. Three types of loxoscelism can be identified, necrotic cutaneous (80% of cases), edematous cutaneous (5%), and visceral cutaneous (10-15%). The latter has a lethality between 1 and 3% of all cases of loxoscelism, which largely depends on the early diagnosis and timely management. Any loxoscelism should be controlled during the first 24 to 48 hours, and be alert to the appearance of symptoms and signs suggestive of visceral manifestations. There isn ́t any laboratory test to confirm the diagnosis. Laboratory tests are only markedly altered in visceral cases. The management of skin lesions is with local ice, NSAIDs, antihistamine and serial dressings. In the case of visceral loxoscelism, treatment begins with suspicion and early diagnosis. For these patients, the principal treatment is supportive care. Although it was recommended in the past, Dapsone is associated with severe adverse effects, like exacerbation of he-molysis, so its use is not currently recommended. The anti-loxocelles serum has no evidence to support less severity or mortality reduction.

Resin Infiltration of Caries in Primary Molars in a Community Setting: 24-Month Randomized Controlled Trial Findings.

This study aimed to assess whether resin infiltration of primary molar proximal lesions is more effective than noninvasive measures in radiographically controlling carious lesion progression into the dentin. A split-mouth randomized controlled trial included 90 children, each with 2 proximal lesions confined to the inner half of the enamel or ≤0.5 mm into the dentin. For each child, lesions were randomly allocated to test (infiltration: DMG Icon preproduct and fluoride varnish) or control (fluoride varnish) status. The primary outcome measure was 24-mo radiographic lesion progression. Placement of a restoration during the study period was counted as lesion progression. Proportions of teeth with progressed lesions were compared using the McNemar test. Children also reported on the treatment's acceptability to them. Children (46% female) ranged in age from 6 to 9 y. Their mean number of decayed, missing, and filled teeth (d3mft) was 2.8 (SD 2.6). At baseline, 58% and 42% of children were at moderate and low risk, respectively. Test and control lesions presented with similar radiographic lesions at baseline. At the 24-mo follow-up, 6 children had moved and 30 teeth had exfoliated. In the test and control groups, 15 of 66 lesions (22.7%) and 30 of 69 lesions (43.5%) had progressed, respectively (P < 0.05). The 2-y therapeutic effect (based on pairwise radiographic readings) of infiltration over fluoride varnish was 20.8% (95% confidence interval, 10.6%-30.2%). Nearly all children (96.7%) had enjoyed their visit to the clinic, and more than two-thirds (72.2%) were not worried about returning for treatment. Infiltration is more efficacious than fluoride varnish for controlling carious lesion progression in proximal lesions in primary molars, and most children find the treatment acceptable (Australian New Zealand Clinical Trials Registry ANZCTR.org.au ACTRN12611000827932). Knowledge Transfer Statement: These study findings can help clinicians decide which caries management approach they wish to use to prevent progression of proximal lesions in primary molars. With consideration of cost and patient preference, this information could lead to more appropriate therapeutic decisions.

Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy.

A hospital-based case-control study of upper aerodigestive tract tumors was conducted between June 1986 and June 1989 in Northern Italy. One hundred fifty-seven male cases of oral cavity cancer, 134 of pharyngeal cancer, 162 of laryngeal cancer, and 288 of esophageal cancer, and 1272 male inpatients with acute conditions unrelated to tobacco and alcohol were interviewed. Odds ratios for current smokers of cigarettes were 11.1 for oral cavity, 12.9 for pharynx, 4.6 for larynx, and 3.8 for esophagus. For all 4 sites, the risk increased with increasing number of cigarettes and duration of smoking habits and, with the exception of esophageal cancer, decreased with increasing age at the start of and years since quitting smoking. Smokers of pipes and cigars showed a more elevated risk of cancer of the oral cavity and esophagus than did cigarette smokers. Significantly increased risks emerged also in heavy drinkers (odds ratio greater than 60 versus greater than or equal to 19 drinks/week = 3.4, 3.6, 2.1, and 6.0 for oral cavity, pharynx, larynx, and esophagus, respectively), deriving predominantly from wine consumption.

Evolving role of myeloablative chemotherapy in the treatment of childhood brain tumours.

Primary brain tumours, a heterogeneous group of cancer that constitute the second most common cancer in childhood, were historically treated with neurosurgical resection and radiation therapy. Chemotherapy has proven to be beneficial for some histological types, which has since led to exploration of the role of high-dose chemotherapy and haematopoietic stem cell rescue. Patients with high-grade glial tumours, primitive neuroectodermal tumours and high-risk medulloblastoma usually fare poorly. The indicators of bad prognosis are metastatic status, extent of resection and age. Children <3 years at diagnosis carry worse prognosis. Rare cancers such as ependymoblastoma, atypical teratoid rhabdoid tumour and choroid plexus carcinoma have a dismal prognosis regardless of the above-mentioned indicators. The use of myeloablative therapy (MAT) has been investigated to improve the rate of long-term DFS, as well as to reduce and delay in the youngest children the use of the craniospinal irradiation associated with unacceptable late effects. We will overview the literature regarding patients with 'good and uncertain indications' to MAT. Ependymoma and brain stem tumours, for which the available data discourage the use of MAT, are excluded. Finally, we will summarize a single Institution experience (Giannina Gaslini Children's Hospital, Genoa) with MAT in the period 1997-2003.

A comparison of the joint effects of alcohol and smoking on the risk of cancer across sites in the upper aerodigestive tract.

A unified analysis of the combined effects of alcohol and smoking in cancers of the upper aerodigestive tract was conducted using polychotomous logistic regression to determine if, at the same level of exposure, risk varies significantly across pathological sites. Data from a case-control study in northern Italy include males with tumors of the oral cavity/pharynx, larynx, and esophagus and males admitted to the hospital for acute illnesses not related to alcohol and smoking. The combined alcohol and smoking risks for oral cavity/pharynx cancer in these data were significantly greater than those for either laryngeal or esophageal cancer, but esophageal cancer and laryngeal cancer could not be distinguished based on risk. The differences may lie in the presence of unspecified factors in the oral cavity and pharynx, but not in the other upper aerodigestive tract sites, which potentiate the effects of alcohol and smoking in the oral cavity/pharynx.

Colorectal cancer in northeast Italy: reproductive, menstrual and female hormone-related factors.

The role of reproductive and menstrual factors and a few medical conditions linked to female hormones in the aetiology of colorectal cancer was investigated in a case-control study conducted in Pordenone province in northeastern Italy, on 89 women with colorectal cancer and 148 controls admitted to hospital for a wide spectrum of acute, non-digestive nor neoplastic disorders. After adjustment for age and social class, parous women, as compared to nulliparous ones, were significantly protected against colorectal cancer (odds ratio, OR = 0.4, [95% confidence interval, CI:0.2-0.8]) and the risk appeared to decrease with successive pregnancies up to five or more (0.2, [0.04-0.6]). Compared to women who had their first birth at age 24 or less, the OR for those who had it at 30 or older was 2.0, but the inverse trend in risk was not significant. However, among parous women only, age at first birth, but not parity, seemed to retain a certain influence. Late age at menopause seemed to decrease colorectal cancer risk (OR for menopause at age greater than or equal to 50 vs. less than 45 = 0.4, [0.2-1.0] chi 2(1) (trend) = 3.66). Conversely, age at last birth, number of abortions, years between marriage and first birth, age at menarche, pattern of menstrual cycle and occurrence of a few medical conditions potentially linked to female hormones were similarly reported by cases and controls. Due to the very limited number of oral contraceptive (OC) users (9 controls but only 1 case), and the lack of oestrogen replacement therapy users, the influence of exogenous female hormones on colorectal cancer could not be analysed meaningfully.

Total body irradiation in acute myeloid leukemia and chronic myelogenous leukemia: influence of dose and dose-rate on leukemia relapse.

From June 1981 to March 1987, 106 patients--59 with acute myeloid leukemia (AML) and 47 with chronic myelogenous leukemia (CML)--were treated with Cyclophosphamide 60 mg/kg X 2 d and total body irradiation (TBI-990 cGy/3fr/3d described dose) before allogeneic bone marrow transplantation. Seventy-nine patients are evaluable for risk of relapse: 32 with chronic myelogenous leukemia (23 in first chronic phase, 9 in accelerated phase) and 47 with acute myeloid leukemia (38 in first complete remission, 9 in subsequent phases). Actual TBI doses delivered to these patients varied between 839 and 1250 cGy (mean 956 +/- 101)/3 fr/3d, with dose rates between 2.7 and 7.25 cGy/min (mean 4.2 +/- 1.8). Patients receiving high (greater than 990 cGy) and low (less than or equal to 990) dose and/or dose rate (greater than 4 cGy/min and less than or equal to 4, respectively) have been evaluated overall and stratified by type of leukemia and phase of disease. When the patients are considered altogether, high total dose is significantly correlated with decreased risk of relapse (p = 0.0005) as well as high dose rate (p = 0.03). When considering specific subgroups, the influence of total dose on relapse rate is evident both for "early" and "advanced" leukemias, while an impact of dose rate appears only for chronic myelogenous leukemia in 1st chronic phase. Pertinent radiobiological and clinical literature is reviewed, and a possible role of dose fractionation and dose rate in leukemic control rate is evidenced; in this TBI setting, total dose not less than 990 cGy/3fr/3d and dose rate not less than 4 cGy/min have to be guaranteed.

Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant.

PURPOSE: To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT). METHODS AND MATERIALS: Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned with the same protocol consisting of cyclophosphamide and fractionated TBI. The planned total dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period, variations in delivering TBI schedule occurred with regard to used radiation source, instantaneous dose rate, technical setting, and actual total dose received by the patient. We tested these different TBI variables as well as factors related to patient, state of disease, and transplant-induced disease to investigate their influence on transplant-related mortality, leukemia relapse, and survival. RESULTS: At median follow-up of 7 years (range 3-15 years) the probabilities of leukemia-free survival (LFS) and overall survival (OS) for the 93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p = 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors affecting overall survival. The occurrence of chronic GvHd was correlated with actually delivered TBI dose (p = 0.04). Combined stratification of prognostic factors showed that patients who received the planned total dose of TBI (12 Gy) and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients transplanted in first remission (p = 0.05). At multivariate analysis, TBI dose was an independent factor affecting overall survival (p = 0.05) as well as chronic GvHd (p = 0.001) and age (p = 0.04). CONCLUSIONS: This retrospective analysis showed that different variables involved in TBI delivery may influence the occurrence of cGvHd and affect prognosis of patients with ALL receiving allogeneic BMT. The total dose of 12 Gy, administered in six fractions over 3 days, appears to be an effective and low toxic regimen for ALL patients transplanted in first remission.

Potential doubling time in head and neck tumors treated by primary radiotherapy: preliminary evidence for a prognostic significance in local control.

PURPOSE: The aim of the study was to determine preliminarily whether cell kinetic parameters evaluated using in vivo infusion of bromodeoxyuridine (BrdUrd) and flow cytometry, play a role as prognostic factors of loco-regional control in squamous cell head and neck carcinoma treated with radiotherapy. METHODS AND MATERIALS: Between April 1989 and December 1991, 42 patients with unresectable Stage II-IV squamous cell carcinoma of the oral cavity, pharynx or larynx were given an infusion of BrdUrd solution prior to primary tumor biopsy sampling at 4-6 hr later. The simultaneous labeling S-phase fraction (LI) and duration (Ts) as well as the estimated potential doubling time (Tpot) were measured using flow cytometric analysis of BrdUrd and DNA content. Twenty-six patients received standard radiotherapy (70 Gy/35 fractions/7 weeks) whereas 15 patients were treated with the concomitant boost technique (75 Gy/40 fractions/6 weeks). RESULTS: A complete set of flow cytometric data was available for 31 patients. The median value of LI, Ts, and Tpot were 9%, 9 hr and 5 days, respectively. Univariate analysis among the patients treated homogeneously by standard radiotherapy, indicated that local control was affected by Tpot value (p = 0.02). When the same analysis was performed for the patients treated with either standard radiotherapy or concomitant boost regimen, we found a p = 0.04. Thus, patients with a tumor Tpot value < or = 5 days had a significantly lower three-year local control than patients with Tpot > 5 days. Log-rank test univariate analysis showed, in addition, that nodal status was the strongest prognostic factor of local control (p = 0.005). Age, tumor stage, tumor site, performance status, grading, radiotherapy regimen, DNA ploidy and LI value were, instead, not significantly related to loco-regional control. Finally, when comparing the type of radiotherapy for tumors with Tpot < or = 5 days, we found a trend toward a better local control after concomitant boost regimen, with respect to standard regimen (p = 0.06). CONCLUSION: The present preliminary results suggest that Tpot could play a role as additional prognostic factor influencing the disease outcome in head and neck carcinoma treated by radiotherapy.

Glucose-6-phosphate dehydrogenase (G6PD) activity in tumoral tissues of G6PD-deficient subjects affected by larynx carcinoma.

The activity of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose monophosphate (HMP) shunt pathway, was measured in both normal and tumoral larynx tissues from normal and G6PD deficient subjects. Significant increases of this enzymatic activity were found in tumoral tissues of both normal and G6PD deficient subjects, who were characterized by very low levels of G6PD activity in erythrocytes as well as in larynx tissue.