Intensity modulated radiation therapy and oral mucosa sparing in Head and neck cancer patients: A systematic review on behalf of Italian Association of Radiation Oncology - Head and neck working group.

Oral mucositis is a common dose-limiting toxicity during radiotherapy with or without chemotherapy in head and neck cancer patients. This potentially severe complication globally worsens quality of life and negatively impacts local control and survival's outcomes. Several studies have been published on feasibility and/or clinical benefit of intensity modulated radiotherapy (IMRT) mucosa-sparing technique. In 2017, the Italian Association of Radiation Oncology Head and Neck Cancer Working Group organized a study group to perform a systematic review. The aim was to verify if practical indications, including dose-constraints and demonstrated clinical benefit, could be proposed for oral mucosa (OM)-sparing IMRT in order to reduce the incidence of severe acute mucositis. Although dose to OM should be reduced as much as possible without compromising target volumes coverage, it is still tricky to firmly state that OM-sparing procedure should be considered the standard of care, especially due to high subjective variability in OM contour.

The morphology and activity of the extrafloral nectaries in Reynoutria × bohemica (Polygonaceae).

Reynoutria × bohemica is an invasive species causing significant damage to native ecosystems in North America and Europe. In this work, we performed an in-depth micromorphological characterisation of the extrafloral nectaries (EFN), during their secretory and post-secretory phases, in combination with field monitoring of nectary activity over time and the qualitative pool of insect visitors. EFN consist of secretory trichomes and vascularised parenchyma. Polysaccharides, lipids and proteins were histochemically detected in all trichome cells; phenolic substances were detected in parenchyma cells. Our data indicate that all nectary regions are involved in nectar production and release, constituting a functional unit. Moreover, the main compound classes of nectar and their transfer change over time: first, granulocrine secretion for sugars prevails, then eccrine secretion of the lipophilic fraction takes place. Active nectaries are mainly located in the apical portion of the stem during the growth phase (April-May), when we detected the highest number of individuals visited by ants; from mid-August onwards, during flowering, the number of active nectaries declined then ceased production (September), with a concomitant decrease in visits by the ants. The spectrum of nectar-foraging ants mainly included representatives of the genera Formica, Lasius and Camponotus. Reynoutria × bohemica produces an attractive secretion able to recruit local ants that may potentially act as 'bodyguards' for protecting young shoots, reducing secretions during the blooming stage. This defence mechanism against herbivores is the same as that displayed by the parental species in its native areas.

Efficacy and feasibility of induction chemotherapy and radiotherapy plus cetuximab in head and neck cancer.

BACKGROUND: To determine the potential activity and tolerability of sequential treatment in head and neck cancer, we conducted a phase II trial based on induction chemotherapy of two cycles of taxotere, cisplatin and 5-fluorouracil followed by radiotherapy plus weekly cetuximab. PATIENTS AND METHODS: Thirty-six patients with stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx were treated and evaluated for response and acute toxicity. RESULTS: Eighty-one percent of patients had stage IV disease and 42% had hypopharyngeal and oral cavity primaries. The overall response rate was 81.8%, with 60.6% complete response and 33.3% partial response. Severe toxicities were febrile neutropenia (6%) during induction chemotherapy and dermatitis (48%), mucositis (33%) and dysphagia (12%) during the concurrent phase. CONCLUSION: Our protocol proved to be feasible, effective and well tolerated. This sequential strategy should be further investigated.

Albumin and hemoglobin adducts as biomarkers of exposure to styrene in fiberglass-reinforced-plastics workers.

OBJECTIVE: The purpose of this work was to compare levels of styrene-7,8-oxide (SO) adducts of albumin (Alb) and hemoglobin (Hb) with those of two urinary metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA), among workers exposed to styrene in the reinforced-plastics industry and in unexposed subjects. We also wished to determine whether cigarette smoking influenced adduct levels among these subjects. METHODS: A group of 22 male workers was selected on basis of an expectedly high level of exposure to styrene, and a group of 15 controls was selected from hospital blood donors and hospital staff. In the exposed group, MA and PGA were quantified by high-performance liquid chromatography (HPLC) analysis of urine samples collected prior to the work shift. The SO adducts were cleaved from cysteine residues by reaction with Raney nickel to give 1-phenylethanol (1-PE) and 2-phenylethanol (2-PE), which, after derivatization, were measured using gas chromatography-mass spectrometry (GC-MS) in the negative-chemical-ionization (NCI) mode. RESULTS: The estimated mean levels of MA and MA + PGA were 74 and 159 mg/g creatinine, respectively. Using the levels of urinary metabolites, an average styrene concentration of about 100 mg/m3 in the workplace air was estimated. The mean levels of 2-PE and 1-PE adducts in exposed workers were 2.84 and 0.60 nmol/g Alb and 5.44 and 0.43 nmol/g Hb, respectively. When subjects were stratified by level of urinary metabolites [zero (controls), low-level exposure (MA + PGA < or = 159 mg/g creatinine), and high-level exposure (MA + PGA > 159 mg/g creatinine)] and smoking status (smokers versus nonsmokers), a difference in Alb adduct levels was found among the groups (2-PE P = 0.002, I-PE P = 0.052). The difference in 2-PE-Alb levels was related to exposure category, to smoking status, and to their interaction. Correlations at or near a 0.05 level of significance were observed among the workers (n = 22) between individual levels of SO-protein adducts and MA + PGA (2-PE Alb, r = 0.54, 2-PE Hb, r = 0.40). CONCLUSION: Our data suggest that only exposure to relatively high levels of styrene allows a clear relationship to be detected between styrene exposure and SO adducts, due in part to the effects of cigarette consumption and to the high background levels of these adducts observed in unexposed subjects.

Clinical stage IIb carcinoma of the uterine cervix: results in 122 patients.

122 patients affected by clinical stage IIb cervical carcinoma were referred to the Radiation Therapy Department and Obstetrics and Gynaecology Department of the University of Florence between 1977 and 1986 for either radiation therapy only (42 patients) or preoperative treatment followed by surgical resection (80 patients). Among the 42 patients receiving radiation therapy only 23 were treated with external beam therapy only (total dose ranging between 50 Gy and 70 Gy at the mid-plane of the pelvis) while 19 received an additional intracavitary boost (total dose ranging between 68 Gy and 98 Gy at Manchester point A). Higher doses of irradiation to point A were correlated with significantly improved survival (65% vs. 18.5%, p = 0.001) and lower incidence of pelvic failure (33% vs 78%). Following preoperative radiation therapy 80 patients underwent radical surgery. Reassessment of the pathologic specimens was possible in all the cases. Disease free survival was not influenced by involvement of parametria, type of surgery or dose to Manchester point A, but rather to nodal status and thickness of the residual tumour in the cervix.

Cytogenetic biomonitoring of styrene-exposed plastic boat builders.

Earlier studies have produced evidence for an association between work-related styrene exposure and cytogenetic damage, while more recent studies have failed to show such an association. In the present study, chromosome aberrations (CA) and sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes of 46 male workers employed in a fiber-reinforced plastic boat building factory and exposed to styrene. Two groups of 23 workers each, characterized by different exposure levels (ranges: 2-120 mg/m3 and 86-1389 mg/m3 ambient air) were studied, fifty-one controls matched by sex, age and smoking habits were included. Randomized blood samples were analyzed for cytogenetic damage separately in two laboratories. Interlaboratory differences in the scoring of CA and SCE were noted. However, increases of the considered cytogenetic endpoints in exposed vs control groups were consistently observed in both laboratories. Multivariate statistical analysis of pooled data revealed increases of CA ranging between 19% (RR = 1.19; 95% C.I., 0.80-1.78; chromatid-type aberrations, low exposure group) and 144% (RR = 2.44; 95% C.I., 1.26-4.70; chromosome-type aberrations, high exposure group). Parallel excess of SCE in styrene exposed workers was also observed, although at a lesser extent (RR = 1.22; 95% C.I., 1.05-1.43, low exposure group; RR = 1.26; 95% C.I., 1.07-1.47, high exposure group). These findings suggest the presence of a causal association between occupational exposure to styrene and cytogenetic damage in the plastic boat building factory that was the object of the study.

[Therapeutic implications of the peculiar clinical characteristics of Hodgkin's disease in clinical stages I-II with isolated neck presentation]. / Implicazioni terapeutiche delle peculiari caratteristiche cliniche del morbo di Hodgkin negli stadi clinici I-II con presentazione cervicale isolata.

Among 703 patients with supradiaphragmatic clinical stages I-II Hodgkin's disease consecutively treated 1960 through 1989 at the Florence Radiotherapy Department, we identified 98 cases presenting with cervical and supraclavicular nodes involvement only. The latter cases were retrospectively reviewed to assess: a) if they presented any peculiar clinicopathologic features and b) the possible prognostic and therapeutic implications (if any) of these features. The high incidence of lymphocytic predominance histology (33%) and Waldeyer's ring (WR) involvement (24%) and the very low risk of occult infradiaphragmatic involvement (observed in only 2 of 44 patients submitted to staging laparotomy with splenectomy, 4.5%) are among the distinctive features of the patients with supradiaphragmatic clinical stages I-II Hodgkin's disease. All the 98 patients were treated at presentation with irradiation alone. Actuarial cause-specific survival 20 years after the end of treatment was 87%; the corresponding value for relapse-free survival was 78%. The most frequent complications were irradiation pneumonia, most often asymptomatic, and xerostomia. Our data seem to suggest that, for the majority of these patients: a) staging laparotomy could be avoided and b) "mini mantle" irradiation is an adequate treatment. Moreover, WR irradiation could be avoided in the patients without clinical WR involvement.

Specific bronchial reactivity to toluene diisocyanate: dose-response relationship.

20 patients with toluene diisocyanate (TDI)-induced asthma were examined in order to assess their threshold of response to TDI during specific bronchial provocative tests (BPT). Specific bronchial hyperresponsiveness was evaluated by performing, on different days, specific BPT with increasing concentrations of TDI until a positive response was obtained; the threshold of response to TDI (low: 0.02-0.05 ppm; moderate: 0.1 ppm; high: 0.2-0.25 ppm) and the pattern of positive response were evaluated in comparison with some clinical features of the disease. The threshold of airway response to TDI was low in 9, moderate in 7 and high in 4 patients. No evident relationship was observed between the threshold of response to TDI and the pattern of positive response to the lower TDI concentration (immediate in 5, late in 8 and dual in 7 subjects) or other clinical features (duration of asthmatic symptoms, smoking habits, cessation of work, nonspecific bronchial hyperresponsiveness to methacholine); however, 6 out of 9 patients with low threshold had nonspecific bronchial hyperreactivity in comparison with 6 out of 11 patients with moderate or high threshold. In 10 out of 13 patients who performed two positive BPT with different TDI concentrations, the pattern of response was the same either at lower and at higher TDI concentrations; 3 subjects who had a late reaction at the lower concentration showed a dual reaction to the higher TDI concentration. A relationship between the degree of the specific bronchial reaction (% fall in FEV1 from baseline value) and TDI concentration during BPT was observed for the immediate reaction but not for the late reaction.

[Respiratory pathology caused by exposure to solvents in the shoe industry: description of 3 clinical cases]. / Patologia respiratoria da esposizione a solventi nell'industria calzaturiera: descrizione di tre casi clinici.

Clinical and functional respiratory features of three shoe factory workers exposed to organic solvents from glue or other adhesives are described. All subjects complained of chronic cough, dyspnea and wheezing when exposed to non specific bronchial stimuli, and showed a non specific bronchial hyperresponsiveness to methacholine; symptoms and bronchial hyperreactivity persisted some years after the cessation of work. In two cases the onset of the symptoms was ascribed to the occupational exposure to glue activators (containing usually a considerable percentage of chlorinated hydrocarbons as dichloromethane or methilenedichloride). We supposed that occupational exposure to large amounts of glue solvents in shoe factory might cause a chronic airway impairment with non specific bronchial hyperresponsiveness.

TDI-induced oculorhinitis and bronchial asthma.

A case of allergic oculorhinitis induced by toluene diisocyanate (TDI) exposure in a subject who two years later developed bronchial asthma due to TDI is described. A 55-year-old nonatopic spray painter developed symptoms of oculorhinitis two or three hours after direct occupational exposure to polyurethane varnish; at the first examination neither specific nor nonspecific bronchial hyperresponsiveness was present. Two years later the patient, who had remained in his job, developed episodic dyspnea, wheezing, and cough immediately after TDI exposure, with persistence of oculorhinitis; at this time a slight immediate-type response to a specific bronchial provocative test with polyurethane varnish and TDI was observed. Nonspecific bronchial hyperresponsiveness was mild. Specific IgE to TDI-HSA conjugate was present at both the first and second examinations. We conclude that, in some cases, TDI may cause "allergic" oculorhinitis and bronchial asthma, probably with an immunological IgE-mediated mechanism.