The role of adjuvant radiotherapy in locally advanced T4 mandible squamous cell carcinoma in the N0 patient: a single centre experience.

In locally advanced oral squamous cell carcinoma (OSCC), namely that showing invasion of the mandible, demonstrating no high-risk (e.g. extranodal extension, positive margin) or intermediate-risk histopathological features (e.g. perineural invasion, lymphovascular invasion), the additional benefit of postoperative radiotherapy (PORT) currently remains uncertain. A retrospective review covering the period between January 1, 2010 and December 31, 2019 was conducted to identify patients from a single UK centre with locally advanced invasive mandibular OSCC defined as pT4a, with no nodal or distant metastasis (N0 M0). The primary outcome was to determine the disease-free survival and overall survival rates in the surgery + PORT group, in comparison to the surgery only group. Twenty-eight eligible patients were identified, with 13 patients in the surgery + PORT group and 15 patients in the surgery only group. A single patient in the surgery + PORT group developed disease recurrence and subsequently died (1/13) (median follow-up 5.24 years, range 2.13-10.71 years). No patient in the surgery only group developed disease recurrence or died (0/15) (median follow-up 5.13 years, range 1.37-10.93 years). It may be reasonable to consider omitting PORT in pT4a pN0 M0 OSCC of the mandible in patients who demonstrate no high- or intermediate-risk histopathological features, following multidisciplinary team discussion.

Osteoradionecrosis after treatment of head and neck cancer: a comprehensive analysis of risk factors with a particular focus on role of dental extractions.

In head and neck cancer (HNC), osteoradionecrosis (ORN) is one of the most significant complications of radiotherapy (RT). With an absence of effective non-surgical treatment, prevention of the development of ORN is the best approach. The purpose of this study was to identify the risk factors for the development of ORN in HNC. Records of 1,118 patients with HNC treated with radical RT (≥55Gy) from January 2010 to December 2019 were reviewed. After applying the exclusion criteria, 935 patients were included in the final analysis. In patients with confirmed ORN, exact RT doses were mapped. In total, 91 patients were found (9.7%) with a median (range) time of eight (3-89) months to the development of ORN. Smoking, having a primary site in the oropharynx, bone surgery before adjuvant RT, the addition of concurrent chemotherapy, the presence of xerostomia, dental extraction pre-RT, the time ≤20 days between dental extraction and start of RT, and receiving >55Gy RT dose were significant factors for its development. This comprehensive analysis including the precise RT dose mapping has shown the risk factors for the development of ORN. In practice, every effort should be made to avoid these risk factors without compromising the oncology treatment. The findings of this analysis may provide a basis for future prospective research on this topic.

Episode of Hepatitis C viral infection in the people of Swat, Pakistan / Episódio de infecção viral por Hepatite C no povo de Swat, Paquistão

ABSTRACT Infectious agents cause serious diseases in humans worldwide and are responsible for the high rate of morbidity and mortality. The prevalence and epidemiology of infectious disease (HCV) in the hospital visited patients referred by the physicians through the initial findings and their associated risk factors were studied in Swat. The data of 174 infected patients were collected during the period of 2015 to 2017 from two clinical laboratories of Tehsil Matta Swat. Inform consent form was taken before blood collection. After taking informed consent blood samples were collected and ICT test was performed and then ICT positive cases were conform through PCR. A total of 174 ICT positive samples [106 male and 68 females] were included in this study. Age was considered from 10 to 72 years. Of the 174 ICT strip positive, 99 [63 males, 36 females] were confirmed through PCR. The prevalence rate was recorded 56.89%. I.V/I.M injection was recorded in 100% of the individuals. Visits to the barber shop was reported in (58%) of the individuals, married individuals were (81.0), surgical operation was reported in (44.8%), sharing toothbrush was observed in (29.9%), piercing was reported in (39.7%), family history was reported in (26.4%), dental treatment was observed in (21.8%), jaundice were (13.2%) and tattooing was (1.7%). Blood transfusion, surgical operations, Jaundice, family history and dental treatment were found significant risk factors for acquiring HCV infection. It was concluded that proper implementation of precautionary measures should be needed to control the spread of HCV in far near future.

RESUMO Agentes infecciosos causam doenças graves em humanos em todo o mundo, e são responsáveis pelo alto índice de morbimortalidade. A prevalência e a epidemiologia das doenças infecciosas no hospital que atendeu pacientes encaminhados pelos médicos por meio dos achados iniciais e seus fatores de risco associados foram estudadas em Peshawar. Os dados de 174 pacientes infectados foram coletados durante o período de 2015 a 2017 oriundos de dois laboratórios clínicos de Tehsil Matta Swat. O formulário de consentimento informado foi obtido antes da coleta de sangue. Após a obtenção do consentimento informado, foram coletadas amostras de sangue e foi realizado o teste ICT e, em seguida, os casos ICT positivos foram confirmados por PCR. Um total de 174 amostras ICT positivas [106 homens e 68 mulheres] foi incluído neste estudo. A idade considerada foi de 10 a 72 anos. Das 174 tiras de ICT positivas, 99 casos [63 homens, 36 mulheres] foram confirmados por PCR. A taxa de prevalência foi de 56,89%. A injeção IV / IM foi registrada em 100% dos indivíduos. A visita à barbearia foi relatada em (58%) dos indivíduos, os números de casados foram (81,0%), e a operação cirúrgica foi relatada em (44,8%), o compartilhamento de escova de dente foi observado em (29,9%), o piercing foi relatado em (39,7%), antecedentes familiares foram relatados em (26,4%), tratamento odontológico em (21,8%), icterícia (13,2%) e tatuagem em (1,7%). Transfusão de sangue, operações cirúrgicas, icterícia, histórico familiar e tratamento odontológico foram fatores de risco significativos para adquirir infecção por Vírus da Hepatite C (VHC). Concluiu-se que a implementação adequada de medidas de precaução deve ser necessária para controlar a propagação do VHC em um futuro próximo.

Episode of Hepatitis C viral infection in the people of Swat, Pakistan.

Infectious agents cause serious diseases in humans worldwide and are responsible for the high rate of morbidity and mortality. The prevalence and epidemiology of infectious disease (HCV) in the hospital visited patients referred by the physicians through the initial findings and their associated risk factors were studied in Swat. The data of 174 infected patients were collected during the period of 2015 to 2017 from two clinical laboratories of Tehsil Matta Swat. Inform consent form was taken before blood collection. After taking informed consent blood samples were collected and ICT test was performed and then ICT positive cases were conform through PCR. A total of 174 ICT positive samples [106 male and 68 females] were included in this study. Age was considered from 10 to 72 years. Of the 174 ICT strip positive, 99 [63 males, 36 females] were confirmed through PCR. The prevalence rate was recorded 56.89%. I.V/I.M injection was recorded in 100% of the individuals. Visits to the barber shop was reported in (58%) of the individuals, married individuals were (81.0), surgical operation was reported in (44.8%), sharing toothbrush was observed in (29.9%), piercing was reported in (39.7%), family history was reported in (26.4%), dental treatment was observed in (21.8%), jaundice were (13.2%) and tattooing was (1.7%). Blood transfusion, surgical operations, Jaundice, family history and dental treatment were found significant risk factors for acquiring HCV infection. It was concluded that proper implementation of precautionary measures should be needed to control the spread of HCV in far near future.

Cetuximab in the management of nasopharyngeal carcinoma - a narrative review.

BACKGROUND: Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease. METHOD: A literature search was performed using the keywords 'nasopharyngeal neoplasm', 'cetuximab' and 'Erbitux'. RESULTS: Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting. CONCLUSION: There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.

Intensity-modulated radiotherapy (55 Gy in 20 fractions) for high-grade laryngeal dysplasia: report of acute toxicity and functional outcome.

OBJECTIVE: Radiotherapy is an option to treat high-grade laryngeal dysplasia. This study aimed to evaluate the use of intensity-modulated radiotherapy, 55 Gy in 20 daily fractions, in treating this disease. METHODS: Acute toxicity was evaluated in all 14 patients treated. In 10 patients, functional voice outcome was measured using the Voice Handicap Index, and the Grade, Roughness, Breath, Asthenia, Strain ('GRBAS') scale. These measurements were performed pre-treatment and three months after intensity-modulated radiotherapy. RESULTS: All but one patient managed to complete radiotherapy. Acute toxicity was significant (one patient developed grade 4 and three patients developed grade 3 dysphagia). Four patients required hospital admission. In 9 out of 10 patients, radiotherapy improved voice quality. CONCLUSION: This radiotherapy regimen using intensity-modulated radiotherapy for laryngeal dysplasia is feasible and provided excellent functional outcome, but acute toxicity was significant. Dose de-escalation can be considered in the framework of clinical trials.

Hypofractionated Concomitant Chemoradiation in Inoperable Locally Advanced Non-small Cell Lung Cancer: A Report on 100 Patients and a Systematic Review.

AIMS: Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation. MATERIALS AND METHODS: One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan-Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included. RESULTS: In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time. CONCLUSION: Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.

Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study.

OBJECTIVES: Famine exposure in utero can 'programme' an individual towards type 2 diabetes and obesity in later life. We sought to identify, (1) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (2) whether this programming was specific to gestational or postnatal exposure windows and (3) whether epigenetic differences were associated with famine exposure. DESIGN: A historical cohort study was performed as part of a wider cross-sectional survey. Exposure to famine was defined through birth date and historical records and participants were selected according to: (A) exposure to famine in postnatal life, (B) exposure to famine during gestation and (C) unexposed. SETTING: Matlab, a rural area in the Chittagong division of Bangladesh. PARTICIPANTS: Young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143). OUTCOME MEASURES: Primary outcome measures of weight, body mass index and oral glucose tolerance tests (0 and 120 min glucose). Secondary outcome measures included DNA methylation using genome-wide and targeted analysis of metastable epialleles sensitive to maternal nutrition. RESULTS: More young adults exposed to famine in gestation were underweight than those postnatally exposed or unexposed. In contrast, more young adults exposed to famine postnatally were overweight compared to those gestationally exposed or unexposed. Underweight adults exposed to famine in gestation in utero were hyperglycaemic following a glucose tolerance test, and those exposed postnatally had elevated fasting glucose, compared to those unexposed. Significant differences in DNA methylation at seven metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA, EXD3) known to vary with gestational famine exposure were identified. CONCLUSIONS: Famine exposure in developmental life programmed Bangladeshi offspring towards diabetes and obesity in adulthood but gestational and postnatal windows of exposure had variable effects on phenotype. DNA methylation differences were replicated at previously identified metastable epialleles sensitive to periconceptual famine exposure.

Pre-formulation Study of Salicylidine-cephalexin-Zn(II) dihydrate, a New Derivative of Cefalexin.

BACKGROUND: Salicylidine-cefalexin-Zn(II)·2H2O, a new derivative of cefalexin, has been reported to possess enhanced anti-microbial activity and lower toxicity than cefalexin. It is, therefore, desirable to carry out a pre-formulation study to determine its pharmaceutical properties which will be useful in conversion of the new molecule into various dosage forms. METHODS: The compound was synthesized by the previously reported method and characterized by elemental, Fourier-transform infrared and electronic spectral analyses. Crystallinity was determined by powder x-ray diffraction. Particle size distribution was determined by a laser-based sizer. Other properties including flow, density and compaction strength were determined by use of appropriate standard methods. The compound was also evaluated as a prodrug through dissolution study by the USP method. RESULTS: It was found that the new derivative is an amorphous powder with different bulk density, porosity, compressibility, plasticity and flow properties as compared to cefalexin. The amorphous character of the new compound suggests that it will have better bioavailability. The dissolution study indicated that this compound is hydrolyzed to produce cefalexin in water in a sustained manner, thus it will act as a prodrug in vivo. The release data fitted well into Highuchi model. CONCLUSION: Various pharmaceutical properties essentially required for formulation of salicylidine-cefalexin-Zn(II)·2H2O into dosage forms were determined. This study has shown that the new drug would behave as a prodrug for cefalexin with better bioavailability.