Long-term disease-free survival in surgically-resected oral tongue cancer: a 10-year retrospective study

Sopravvivenza libera da malattia a lungo termine nel tumore della lingua mobile operato: studio retrospettivo a 10 anni.PLAIN-LANGUAGE-SUMMARY: Early and loco-regionally advanced oral tongue squamous cell carcinoma (OTSCC) can be treated by surgery alone or followed by adjuvant radiotherapy or chemoradiotherapy. Nevertheless, up to 40% of patients develop tumour relapse. The aim of our study is to investigate the clinical and pathological features associated with reduced disease-free survival (DFS) in a cohort of surgically-resected OTSCC patients. One hundred and six patients surgically resected for OTSCC were retrospectively identified from clinical records. DFS was calculated according to the Kaplan\u2013Meier method and differences between variables were assessed with Log-Rank test. A multivariable Cox regression model was used to analyse the impact of different prognostic factors on DFS. After a median of follow-up of 8.9 years, 22 events, including 11 deaths, were observed. Overall, the 5-year DFS-rate was 87.4%. The presence of extra-nodal extension (p = 0.023) and perineural invasion (p = 0.003) were significantly correlated with shorter DFS (in univariate analysis). In multivariable analysis, extra-nodal extension and perineural invasion confirmed their role as independent prognostic factors associated with an increased risk of disease recurrence [hazard ratio (HR) 2.87, 95% CI 1.11-7.42, p = 0.03; HR 3.85, 95% CI 1.49-9.96, p = 0.006, respectively]. p16 and p53 expressions in tumour cells were detected in 12% (n = 9) and 46% (n = 40) of cases, respectively. No differences in DFS were observed between p16+ and p16- (p = 0.125) and between p53+ and p53- tumours (p = 0.213). In conclusion, radical surgery, eventually followed by adjuvant radiotherapy or chemo-radiotherapy, can achieve high cure rates in OTSCC. After long-term follow-up, perineural invasion and extra-nodal extension confirmed their role as prognostic factors associated with reduced DFS in OTSCC patients

Pediatric norovirus infection

Noroviruses (NoVs) are among the most frequent causes of acute pediatric gastroenteritis. Although the disease is often self-limiting and recovery is the rule, it constitutes an important health problem because of its highly contagious nature and the high rate of morbidity. NoVs are responsible for 47-96 % of outbreaks of acute pediatric gastroenteritis, and 5-36 % of sporadic cases. NoV-induced gastroenteritis is a frequent cause of hospitalization, and severe and sometimes fatal cases have been reported in immunocompromised children. The increasing recognition of NoVs as the cause of pediatric disease and the limited success in preventing outbreaks have led to consideration of vaccines. However, while awaiting the development of a vaccine, there is an urgent need for more epidemiological data concerning childhood NoV infection, including the impact of NoVs on different age groups, the possible etiological role of NoVs in infections other than gastroenteritis, and the socioeconomic impact of NoVs on households

COMBINED SURGERY AND POST-OPERATIVE RADIOTHERAPY OR CHEMORADIOTHERAPY FOR LOCALLY ADVANCED TONGUE CANCER

Background: Treatment options for locally advanced tongue squamocellular carcinoma (SCC) include surgery alone, radiotherapy alone, or multimodality treatment. These highly aggressive tumors are best treated by partial glossectomy in order to save organ function and postoperative radiotherapy (RT). When positive margins and/or extracapsular nodal extension are found, postoperative hemoradiotherapy (CRT) is warranted. We report on our experience with this approach. Methods: A total of 20 patients (pts) with primary tongue SCC were treated with surgery and postoperative RT. All pts underwent partial, hemi-, or subtotal glossectomy; 16 pts (80%) underwent ipsilateral radical or modified radical neck dissection. Ten pts received postoperative RT alone (median dose 6000 cGy) while 10 pts received postoperative CRT consisting of RT and Cisplatin 100 mg/m2 days 1-22- 43. Stage distribution was as follows: stage III, 5; stage IV, 15. Median follow-up is 23 months. Results: For the entire group of pts, the actuarial 2-year locoregional control rate was 80%; the same rate was recorded for both stage III and IV disease. The actuarial 2-year overall survival rate was 70%. There was one local failure among 10 pts with negative margins (local control 95%) and 3 among pts with positive margins (local control 85%). Four pts developed distant metastases, 2 with negative and 2 with positive margins. Postoperative treatment was well tolerated. Three pts treated by RT and 4 pts treated by CRT experienced grade 3 oral mucositis. Late major complications of RT and CRT included 3/20 pts requiring permanent G-tubes and/or tracheostomy to prevent aspiration. Conclusions: Surgery plus postoperative RT is an intensive treatment for SCC of the tongue which offers high locoregional control rate in patients with negative margins. Postoperative CRT can be safely administered to pts with positive margins and/or extracapsular nodal extension achieving satisfactory results in terms of both locoregional control and distant failure

Molecular mechanisms underlying mancozeb-induced inhibition of TNF-alpha production

Mancozeb, a polymeric complex of manganese ethylenebisdithiocarbamate with zinc salt, is widely used in agriculture as fungicide. Literature data indicate that ethylenebisdithiocarbamates (EBDTCs) may have immunomodulatory effects in humans. We have recently found in agricultural workers occupationally exposed to the fungicide mancozeb a statistically significant decrease in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF) production in leukocytes. TNF is an essential proinflammatory cytokine whose production is normally stimulated during an infection. The purpose of this work was to establish an in vitro model reflecting in vivo data and to characterize the molecular mechanism of action of mancozeb. The human promyelocytic cell line THP-1 was used as in vitro model to study the effects of mancozeb and its main metabolite ethylenthiourea (ETU) on LPS-induced TNF release. Mancozeb, but not ETU, at non-cytotoxic concentrations (1-100 microg/ml), induced a dose- and time-dependent inhibition of LPS-induced TNF release, reflecting in vivo data. The modulatory effect observed was not limited to mancozeb but also other EBDTCs, namely zineb and ziram, showed similar inhibitory effects. Mancozeb must be added before or simultaneously to LPS in order to observe the effect, indicating that it acts on early events triggered by LPS. It is known that nuclear factor-kappaB (NF-kappaB) tightly regulates TNF transcription. We could demonstrate that mancozeb, modulating LPS-induced reactive oxygen species generation, prevented IkappaB degradation and NF-kappaB nuclear translocation, which in turn resulted in decreased TNF production. To further understand the mechanism of the effect of mancozeb on TNF transcription, THP-1 cells were transfected with NF-kappaB promoter-luciferase construct, and the effect of mancozeb on luciferase activity was measured. Cells transfected with promoter constructs containing kappaB site showed decreased LPS-induced luciferase activity relative to control after mancozeb treatment, confirming NF-kappaB binding as an intracellular target of mancozeb. Overall, this study contributes to our understanding of the mechanism underlying mancozeb-induced immunotoxicity

Locoregionally advanced nasopharyngeal carcinoma : induction chemotherapy with cisplatin and 5-fluorouracil followed by radiotherapy and concurrent cisplatin : a phase II study

Chemoradiotherapy is the current standard of care for locoregionally advanced nasopharyngeal carcinoma. The purpose of this study was to assess the feasibility and efficacy of induction chemotherapy (CHT) followed by concomitant chemoradiotherapy in this patient population. PATIENTS AND METHODS: In this single-arm, phase II study, patients with locoregionally advanced nasopharyngeal carcinoma were treated with 3 cycles of induction CHT with cisplatin (100 mg/m(2) on day 1) and 5-fluorouracil (1,000 mg/m(2) continuous infusion on days 1-4) followed by 3 cycles of cisplatin (100 mg/m(2) on days 1, 22 and 43) and concurrent radiotherapy up to 70 Gy. The primary endpoint was objective response. RESULTS: Thirty-four patients were enrolled, and all completed both induction treatment and subsequent chemoradiotherapy. Objective response rates were 79.4% (95% CI 62.1-91.3) and 85.3% (95% CI 68.9-95.0) after induction CHT and chemoradiation, respectively. Treatment was well tolerated and toxicity was manageable. At a median follow-up of 29 months, 3-year overall survival and progression-free survival rates are 80.0% (95% CI 0.64-0.95) and 54.0% (95% CI 0.36-0.73), respectively. CONCLUSIONS: Induction CHT with cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy is a feasible and active regimen for patients with stage IIB-IVB nasopharyngeal carcinoma. This regimen resulted in excellent locoregional disease control and overall survival

Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure

Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural workers intermittently exposed to propanil and 7 healthy matched controls entered the study. Data were collected through physical examination, and laboratory investigations addressed at the main serum, cellular, and functional immune parameters. The levels of exposure were assessed by determining the urine concentration of the major propanil metabolite, 3,4-dichloroaniline. The investigation of serum, cellular, and functional immune parameters suggested that propanil exposure results in a modest immunomodulatory effect, characterized by an increase in the plasma level of IgG(1) and in LPS-induced IL-6 release and, by a reduction in PHA-induced IL-10 and IFN release, associated with a reduced IFN/IL-4 ratio. As observed, following in vivo exposure, in vitro treatment of human peripheral blood leukocytes with propanil resulted in a dose-dependent reduction in PHA-induced IFN-gamma and IL-10 production, while LPS-induced TNF-alpha production was not affected indicating a direct effect of propanil on selected immune parameters. We demonstrated that propanil interfering with PHA-induced intracellular calcium increase modulated IL-10 and IFN-gamma transcription and translation, which indicates that propanil acts on early events triggered by PHA. Overall, our results suggest that human exposure to propanil has slight immunomodulatory effects, and point out that the inhibition of the PHA-induced intracellular calcium rise is an important target of propanil. These findings improve our understanding of the mechanism underlying propanil-induced immunotoxicity

Multimodality treatment of osteosarcoma of the jaw : a single institution experience

Osteosarcomas of the jaws are rare mesenchymal tumors frequently diagnosed in the fourth decade of life which account for 6\ua0% of all osteosarcomas. This study evaluated the efficacy on the patients outcome of multimodality treatment consisting of surgery, chemotherapy and radiotherapy. The records of 22 patients affected by jaw osteosarcoma treated with a combination of surgery, poly-chemotherapy and adjuvant radiotherapy in selected cases were reviewed. Response rate, progression-free survival and overall survival were evaluated. Neoadjuvant chemotherapy resulted in an overall response rate of 83.3\ua0%, necrosis of grade I or II was obtained, respectively, in 44.4 and 55.6\ua0% of the patients, and surgery was radical in all patients. At a median follow-up of 60\ua0months, the 5-year progression-free survival and overall survival were 73.5 and 77.4\ua0%, respectively. These outcome parameters significantly correlated with age at diagnosis and grade of chemotherapy-induced necrosis. A complex multimodality approach including chemotherapy and radiotherapy, along with radical surgery, can maximize the outcome of patients affected by osteosarcoma of the jaws