A retrospective cohort study of intra-corporeal versus extra-corporeal anastomosis for right hemicolectomy with cost-effectiveness analysis.

BACKGROUND: We aimed to compare outcomes and cost effectiveness of extra-corporeal anastomosis (ECA) versus intra-corporeal anastomosis (ICA) for laparoscopic right hemicolectomy using the National Surgical Quality Improvement Programme data. METHODS: Patients who underwent elective laparoscopic right hemicolectomy for colon cancer from January 2018 to December 2022 were identified. Non-cancer diagnoses, emergency procedures or synchronous resection of other organs were excluded. Surgical characteristics, peri-operative outcomes, long-term survival and hospitalisation costs were compared. Incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness. RESULTS: A total of 223 patients (175 ECA, 48 ICA) were included in the analysis. Both cohorts exhibited comparable baseline patient, comorbidity, and tumour characteristics. Distribution of pathological TMN stage, tumour largest dimension, total lymph node harvest and resection margin lengths were statistically similar. ICA was associated with a longer median operative duration compared with ECA (255 min vs. 220 min, P < 0.001). There was a quicker time to gastrointestinal recovery, with a shorter median hospital stay in the ICA group (4.0 versus 5.0 days, P = 0.001). Overall complication rates were comparable. ICA was associated with a higher surgical procedure cost (£6301.57 versus £4998.52, P < 0.001), but lower costs for ward accommodation (£1679.05 versus £2420.15, P = 0.001) and treatment (£3774.55 versus £4895.14, P = 0.009), with a 4.5% reduced overall cost compared with ECA. The ICER of -£3323.58 showed ICA to be more cost effective than ECA, across a range of willingness-to-pay thresholds. CONCLUSION: ICA in laparoscopic right hemicolectomy is associated with quicker post-operative recovery and may be more cost effective compared with ECA, despite increased operative costs.

A case report of acquired Haemophilia A: A rare medical emergency.

Acquired Haemophilia A (AHA) is a rare potentially lifethreatening bleeding disorder caused by the presence of autoantibodies against coagulation factors. It is usually characterised by severe spontaneous haemorrhage, which can lead to high morbidity and mortality. The diagnosis is often challenging. Treatment requires vigilant and accurate laboratory investigations, control of bleeding episodes, and eradication of inhibitors using bypassing agents and/or immunosuppressive agents. Hereby, we present a case report of unusual bleeding episodes with isolated raised activated partial thromboplastin time (APTT).

Zinc-α2-glycoprotein is associated with non-albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4-year follow-up.

AIM: To investigate the association between baseline plasma zinc-α2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. METHODS: Adults with normoalbuminuria at entry (n=341; age 57±10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-α2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. RESULTS: Chronic kidney disease progression occurred in 54 participants (16%). Zinc-α2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-α2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-α2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-α2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-α2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. CONCLUSIONS: Plasma zinc-α2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.

Acute myocarditis mimicking ST-elevation myocardial infarction: A diagnostic challenge for frontline clinicians.

The clinical presentation of acute myocarditis is highly variable ranging from no symptoms to cardiogenic shock. Despite considerable progress, it remains a challenge for frontline physicians to discriminate between acute myocarditis and myocardial infarction, especially in the early phase. Our case serves as a reminder that acute presentation of myocarditis could resemble ST elevation myocardial infarction potentially misdirecting the therapeutic decision. The clinical presentation, electrocardiographic and laboratory findings of the patient are not specific enough to distinguish acute myocarditis from myocardial infarction. The gold standard tests such coronary angiography and cardiovascular magnetic resonance (CMR) can reliably differentiate the two entities.

Diagnostic value of electrocardiogram in cardiac tamponade.

INTRODUCTION: We aim to study the diagnostic value of electrocardiogram (ECG) in cardiac tamponade. METHODS: This study was a single centre, retrospective casecontrol study. We recruited 42 patients diagnosed with cardiac tamponade of various aetiologies confirmed by transthoracic echocardiography and 100 controls between January 2011 and December 2015. The ECG criteria of cardiac tamponade we adopted was as follows: 1) Low QRS voltage in a) the limb leads alone, b) in the precordial leads alone or, c) in all leads, 2) PR segment depression, 3) Electrical alternans, and 4) Sinus tachycardia. RESULTS: Malignancy was the most common causes of cardiac tamponade, the two groups were of similar proportion of gender and ethnicity. We calculated the sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of each ECG criteria. Among the ECG abnormalities, we noted the SN of 'low voltage in all chest leads' (69%), 'low voltage in all limb leads' (67%) and 'sinus tachycardia' (69%) were higher as compared to 'PR depression' (12%) and 'electrical alternan' (5%). On the other hand, 'low voltage in all chest leads' (98%), 'low voltage in all leads' (99%), 'PR depression' (100%) and 'electrical alternans' (100%) has highest SP. CONCLUSION: Our study reaffirmed the findings of previous studies that electrocardiography cannot be used as a screening tool for diagnosing cardiac tamponade due to its low sensitivity. However, with clinical correlation, electrocardiography is a valuable adjuvant test to 'rule in' cardiac tamponade because of its high specificity.

Horizontal and vertical distribution of sea lice larvae (Lepeophtheirus salmonis) in and around salmon farms in the Bay of Fundy, Canada.

The sea louse, Lepeophtheirus salmonis, is parasitic to salmonid species in the Northern Hemisphere and has become a widespread biological and economic problem for the salmon farming industry. A better understanding is needed of their spatial distribution and early life history to disrupt the life cycle of the sea louse. In this study, sea lice larval densities within salmon farms, between salmon farms and reference sites, and at various depths were quantified using both plankton pumps and plankton nets. Farm sites exhibited significantly higher densities than reference sites; however, these densities dropped an order of magnitude at a distance of 100 m from the cages. The majority of the larvae captured in the study were nauplii (93%), and densities ranged from 0 to 10 larvae/m3 . Free-swimming sea lice larvae were found to exhibit a diel cycle where nauplii larvae were in deeper waters (10-17 m) during the day and in surface waters (1-6 m) during the night. The results of this study suggest that the early life-history stages of sea lice originate from and may remain close to active salmon farms, creating a self-sustaining population.

Gender differences for growth in North American Atlantic salmon.

An assumption in aquaculture of Atlantic salmon is that male and female growth within families is perfectly genetically correlated. That is, families would rank identically if based on male growth only or female growth only. Also, growth in freshwater and sea water is assumed to be highly correlated between males and females within families. However, structural analysis of the DNA of Atlantic salmon has found that the linkage maps of females differ significantly from that of males. Genetic variability for any trait measured on females could be greater or lesser than on males. Thus, male and female growth might be considered as separate traits giving rise to families ranking differently depending on gender. A multiple trait family model for weight and length at 3 years of age in Atlantic salmon according to gender was applied to data on North American Atlantic salmon obtained from the Oak Bay Hatchery in New Brunswick, Canada. Genetic correlations between male and female growth in both freshwater and sea water were estimated by Bayesian methods. The estimates support the possible existence of gender dimorphism in North American Atlantic salmon for growth traits.

Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation.

Previous studies have suggested that the HIF transcription factors can both activate and inhibit gene expression. Here we show that HIF1 regulates the expression of mir-210 in a variety of tumor types through a hypoxia-responsive element. Expression analysis in primary head and neck tumor samples indicates that mir-210 may serve as an in vivo marker for tumor hypoxia. By Argonaute protein immunoprecipitation, we identified 50 potential mir-210 targets and validated randomly selected ones. The majority of these 50 genes are not classical hypoxia-inducible genes, suggesting mir-210 represses genes expressed under normoxia that are no longer necessary to adapt and survive in a hypoxic environment. When human head and neck or pancreatic tumor cells ectopically expressing mir-210 were implanted into immunodeficient mice, mir-210 repressed initiation of tumor growth. Taken together, these data implicate an important role for mir-210 in regulating the hypoxic response of tumor cells and tumor growth.

Use of tantalum cones in primary arthroplasty of acute proximal tibial fractures.

Metaphyseal tantalum cones in primary total knee arthroplasty and their functional outcome is described using 3 case reports over 6 years. 3 knees in 3 elderly individuals (mean age of 70.4 years), with pre-existing osteoarthritis and complex proximal tibial fractures, were operated on. Ambulation with walking frame was achieved from post-operation day 1, with weight-bearing as tolerated. Mean range of motion was 122° and Mean Knee Society Score was 88. All showed improvement in pre-operative limb alignment. Radiological fracture union was achieved on an average of 3 months. All were independent ambulators and pain-free at the latest follow-up. Our case series shows that tantalum cones are associated with significant improvements in clinical scores, patient symptoms, range of movement, early weight-bearing and low rates of complications in complex proximal tibial fractures with poor bone stock.

Long-term outcomes after surgical or nonsurgical initial therapy for patients with T4 squamous cell carcinoma of the larynx: A 3-decade survey.

BACKGROUND: The current study was conducted to evaluate long-term disease control, survival, and functional outcomes after surgical and nonsurgical initial treatment for patients with T4 larynx cancer. METHODS: Demographics, disease stage, and treatment characteristics were reviewed for 221 sequential patients treated for T4 laryngeal squamous cell cancer at a single institution between 1983 and 2011. Survival and disease control outcomes were calculated. RESULTS: The median follow-up time was 47 months (71 months for patients still alive at the time of analysis). The overall 5-year and 10-year overall survival rates were 52% and 29%, respectively, and the corresponding disease-free survival rates were 57% and 48%, respectively. Overall 5-year and 10-year locoregional control rates were 78% and 67%, respectively, and the corresponding rates for freedom from distant metastasis were 76% and 74%, respectively. On both univariate and multivariate analyses, lymph node-positive disease at the time of presentation was associated with overall mortality (P<.0001). Patients treated with laryngectomy followed by postlaryngectomy radiotherapy (161 patients) achieved better initial locoregional control than patients treated with a laryngeal preservation (LP) approach (60 patients) throughout the follow-up period (log-rank P<.007) yet the median overall survival times were equal for both groups (64 months; 95% confidence interval 47-87 months and 38-87 months, respectively [P =.7]). Patients treated with an LP approach had a tracheostomy rate of 45% and an any-event aspiration rate of 23%. Rates of high-grade dysphagia at the time of last follow-up were worse for patients treated with an LP approach (P<.01). CONCLUSIONS: Surgery and postoperative radiotherapy can produce substantial long-term cancer control and survival rates for patients with T4 larynx cancer. Caution should be taken when selecting patients for initial nonsurgical treatment because of significant rates of functional impairment despite survival equivalence.

Large-scale two-dimensional MoS2 photodetectors by magnetron sputtering.

We report on the demonstration of photodetectors based on large scale two-dimensional molybdenum disulfide (MoS2) transition metal dichalcogenides. Excellent film uniformity and precise control of the MoS2 thickness down to a monolayer (~0.75nm) were achieved by magnetron sputtering synthesis approach. In particular, the photodetectors integrated with five MoS2 monolayers exhibit a high photoresponsivity of 1.8 A/W, an external quantum efficiency exceeding 260%, and a photodetectivity of ~5 x 10(8) Jones for a wavelength of 850 nm, surpassing the performance of mechanically exfoliated based photodetectors.

Improved survival using intensity-modulated radiation therapy in head and neck cancers: a SEER-Medicare analysis.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) is a technologically advanced, and more expensive, method of delivering radiation therapy with a goal of minimizing toxicity. It has been widely adopted for head and neck cancers; however, its comparative impact on cancer control and survival remains unknown. The goal of this analysis was to compare the cause-specific survival (CSS) for patients with head and neck cancers treated with IMRT versus non-IMRT from 1999 to 2007. METHODS: CSS was determined using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and analyzed regarding treatment details, including the use of IMRT versus non-IMRT, using claims data. Hazard ratios (HRs) were estimated by the frailty model with a propensity score matching cohort and instrumental variable analysis. RESULTS: A total of 3172 patients were identified. With a median follow-up of 40 months, patients treated with IMRT had a statistically significant improvement in CSS compared with those treated with non-IMRT (84.1% versus 66.0%; P < .001). When each anatomic subsite was analyzed separately, all respective subgroups of patients treated with IMRT had better CSS than those treated with non-IMRT. In multivariable survival analyses, patients treated with IMRT were associated with better CSS (HR = 0.72, 95% confidence interval = 0.59 to 0.90 for propensity score matching; HR = 0.60, 95% confidence interval = 0.41 to 0.88 for instrumental variable analysis). CONCLUSIONS: Patients with head and neck cancers who were treated with IMRT experienced significant improvements in CSS compared with patients treated with non-IMRT techniques. This suggests there may be benefits to IMRT in cancer outcomes, in addition to toxicity reduction, for this patient population.

Risk factors for suicidal ideation, plans and attempts in Malaysia--results of an epidemiological survey.

OBJECTIVE: This is an epidemiological study to determine the prevalence of suicidal behavior and its association with generalised anxiety disorder (GAD) and major depressive disorder (MDD) in a nationally representative sample. METHOD: Suicidal ideation, plans and attempts were assessed in face-to-face interviews of respondents selected by a multistage probability sampling using items on suicidality from the WHO SUPRE-MISS questionnaire. The Mini International Neuropsychiatric Interview (MINI) was used to generate DSM-IV diagnoses of GAD and MDD. A total of 19309 subjects were studied. Multivariate regression analysis was conducted controlling for demographic characteristics such as age, gender and ethnicity. RESULTS: The prevalence estimates for suicide ideation, plans and attempts were 1.7% (95% CI: 1.4-1.9), 0.9% (CI: 0.7-1.1) and 0.5% (CI: 0.4-0.7) respectively. Younger people (16-24 years) had higher risk of suicidal behavior (OR: 2.6, CI: 1.08-6.2). Females (OR: 1.6, CI: 1.2-2.1) and Indians (OR: 3.3, CI: 2.2-4.9) also had higher risk. CONCLUSION: The prevalence of suicidal behavior in Malaysia is low, but it broadly corresponds to the pattern described in other countries. This national study confirms that Malaysians of Indian descent have much higher rates of suicidal behavior than other groups. The younger age group, females and the Indian ethnic group would need focused preventive efforts.

Human papillomavirus and survival of patients with oropharyngeal cancer.

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. RESULTS: The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. CONCLUSIONS: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)

Filtration of sea louse, Lepeophtheirus salmonis, copepodids by the blue mussel, Mytilus edulis, and the Atlantic sea scallop, Placopecten magellanicus, under different flow, light and copepodid-density regimes.

Population management of Lepeophtheirus salmonis in Canada currently relies on chemotherapeutants to remove attached stages of the ectoparasite. However, some populations of L. salmonis are developing resistance to chemotherapeutants making alternate management measures necessary. This article explores the ability of filter-feeding shellfish [i.e. blue mussels (Mytilus edulis) and Atlantic sea scallops (Placopecten magellanicus)] to consume the copepodid stages of L. salmonis in the laboratory under static and flowing water conditions, with variable copepodid densities, and with the aid of a light attractant. Mytilus edulis consumed copepodids under both static and flowing water conditions, and the proportion of individuals ingested was similar at low and high copepodid densities, suggesting that M. edulis was not saturated at the concentrations tested. Also, M. edulis consumed more copepodids when a light attractant was present, suggesting that lights may be useful to concentrate widely dispersed copepodids around cultured shellfish in the field. Finally, P. magellanicus consumed the same number of copepodids as an equivalent total wet weight of M. edulis. During each of the four separate experiments, shellfish consumed between 18 and 38% of the copepodids presented per hour, suggesting that both species are well suited for low level removal of copepodids over time.

Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial.

BACKGROUND: We aimed to improve the outcomes for locoregionally advanced nasopharyngeal carcinoma by testing the feasibility and safety of the addition of bevacizumab to chemoradiotherapy. METHODS: We enrolled patients older than 18 years with stage IIB-IVB nasopharyngeal carcinoma from 19 centres in North America and Hong Kong. Treatment consisted of three cycles of bevacizumab (15 mg/kg) and cisplatin (100 mg/m(2)) both given on days 1, 22, and 43 of radiation (70 Gy) with intensity-modulated radiation therapy delivered over 33 days on a daily basis, Monday through Friday. Patients then received three cycles of bevacizumab (15 mg/kg) and cisplatin (80 mg/m(2)), both given on days 64, 85, and 106 after radiation, and three cycles of fluorouracil (1000 mg/m(2) per day), given on days 64-67, 85-88, and 106-109 after radiation. The primary endpoint was the occurrence of treatment-related grade 4 haemorrhage or any grade 5 adverse event in the first year. Analyses were done with all eligible patients who started protocol treatment. The trial is registered at ClinicalTrials.gov, number NCT00408694. FINDINGS: From Dec 13, 2006, to Feb 5, 2009, we enrolled 46 patients, of whom 44 were eligible for analysis. We recorded no grade 3-4 haemorrhages or grade 5 adverse events; nine patients (20%) had a treatment-related grade 1-2 haemorrhage. Nine patients had one or more grade 4 blood or bone marrow-related complication (grade 4 leucopenia was noted in six patients, grade 4 lymphopenia in five, grade 4 neutrophils in five, and grade 4 anaemia in one). One patient had two grade 4 infections with grade 3-4 neutrophils. One patient reported grade 4 tinnitus, one patient reported grade 4 thrombosis, one reported grade 4 radiation mucositis, and two reported grade 4 pharyngolaryngeal pain. With a median follow-up of 2·5 years (IQR 2·1-2·9), the estimated 2 year locoregional progression-free interval was 83·7% (95% CI 72·6-94·9), the 2 year distant metastasis-free interval was 90·8% (82·2-99·5), the 2 year progression-free survival was 74·7% (61·8-87·6), and 2 year overall survival was 90·9% (82·3-99·4). INTERPRETATION: The addition of bevacizumab to standard chemoradiation treatment for patients with nasopharyngeal carcinoma is feasible, and might delay the progression of subclinical distant disease. FUNDING: National Cancer Institute, USA.

Association of Oral Health with Frailty, Malnutrition Risk and Functional Decline in Hospitalized Older Adults: A Cross-Sectional Study.

BACKGROUND: Poor oral health is known to be associated with adverse outcomes, but the frequency and impact of poor oral health on older adults in the acute inpatient setting has been less well studied. OBJECTIVES: We examined the association between oral health, frailty, nutrition and functional decline in hospitalized older adults. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: We included data from 465 inpatients (mean age 79.2±8.3 years) admitted acutely to a tertiary hospital. METHODS: We evaluated oral health using the Revised Oral Assessment Guide (ROAG), frailty using the Clinical Frailty Scale (CFS), malnutrition risk using the Nutritional Screening Tool (NST) and functional status using a modified Katz Activities of Daily Living (ADL) scale. We examined cross-sectional associations of oral health with frailty, malnutrition risk and functional decline on admission, followed by multivariate logistic regression models evaluating the association between poor oral health and the aforementioned outcomes. RESULTS: 343 (73.8%), 100 (21.5%) and 22 (4.7%) were classified as low, moderate and high risk on the ROAG, respectively. Poorer oral health was associated with greater severity of frailty, functional decline on admission and malnutrition risk. Abnormalities in ROAG domains of voice changes, swallowing difficulty, xerostomia, lips and tongue appearance were more frequently present at greater severity of frailty. Poor oral health was associated with frailty [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.05-2.97; P=0.034]; malnutrition risk [OR: 2.76, 95% CI 1.46-5.19, P=0.002] and functional decline [OR: 1.62, 95% CI 1.01-2.59, P=0.046]. CONCLUSIONS: Poor oral health is significantly associated with frailty, malnutrition risk and functional decline in older inpatients. Oral health evaluation, as part of a comprehensive geriatric assessment may be a target for interventions to improve outcomes. Further research including longitudinal outcomes and effectiveness of specific interventions targeted at oral health are warranted in older adults in the inpatient setting.

Head and neck carcinoma in the United States: first comprehensive report of the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN).

BACKGROUND: Detailed information about how patients with head and neck carcinoma (HNC) are treated across practice settings does not exist. The authors conducted a prospective, observational study to examine the patterns of care for a series of patients with newly diagnosed HNC in the United States and to test 2 hypotheses: 1) There is no difference in the pattern of care between community and academic settings; and 2) the results of major randomized clinical trials will change the pattern of care in both practice settings within 1 year of publication in peer-reviewed journals. METHODS: Patients aged ≥ 18 years were enrolled in the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN) after providing written informed consent if they had a confirmed diagnosis of new HNC and were scheduled to receive treatment other than surgery alone. RESULTS: Between 2005 and 2010, 100 centers enrolled 4243 patients, including 2612 patients (62%) from academic investigators and 1631 patients (38%) from community centers. Initial treatments were radiation with concurrent chemotherapy (30%) or cetuximab (9%), adjuvant radiotherapy (21%), induction chemotherapy (16%), and other (24%). Intensity modulated radiation therapy was the dominant radiation technique (84%). Single-agent cisplatin was prescribed in nearly half of patients and more often in academic centers (53% vs 43% of patients; P < .0001). Single-agent cetuximab was the next most common drug used (19%) and was prescribed more frequently in community settings (24% vs 17%; P = .0001). The data rejected the 2 prospective hypotheses. CONCLUSIONS: LORHAN documented differences in patient characteristics and treatments between community and academic settings for a large series of patients in the United States.

Tumor stage, human papillomavirus and smoking status affect the survival of patients with oropharyngeal cancer: an Italian validation study.

BACKGROUND: Tumor human papillomavirus (HPV) status strongly affects overall survival (OS) of oropharyngeal cancer (OPC) patients. Recently, three groups with different outcomes were identified based on HPV status, smoking history and tumor stage. Our objective was to validate this model using a single-institutional retrospective database. PATIENTS AND METHODS: Patients (n=120) diagnosed with OPC at our institution, treated with concomitant cisplatin plus radiotherapy (RT) (n=64), induction chemotherapy followed by concomitant chemoradiation (n=39) or RT alone (n=17), were stratified in three groups with respect to the risk of death (low 26, intermediate 46 and high 49 patients) according to tumor p16 expression as surrogate of HPV status, pack-years of tobacco smoking and nodal/tumor stage. Group-stratified Kaplan-Meier OS curves were estimated and compared using the log-rank test. RESULTS: The 2-year OS estimates were 100%, 86% and 70%, respectively. The difference between the survival curves was statistically significant (P=0.009). The Harrell's concordance index was 0.70. The calibration plot showed a good concordance between our results and those observed in the original study. CONCLUSIONS: This study validates the risk grouping previously identified. Risk-driven clinical decision making and trial designs will help in better defining the most appropriate treatment in OPC patients.

MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation.

The poly-(ADP-ribose) polymerase (PARP) inhibitor, MK-4827, is a novel potent, orally bioavailable PARP-1 and PARP-2 inhibitor currently in phase I clinical trials for cancer treatment. No preclinical data currently exist on the combination of MK-4827 with radiotherapy. The current study examined combined treatment efficacy of MK-4827 and fractionated radiotherapy using a variety of human tumor xenografts of differing p53 status: Calu-6 (p53 null), A549 (p53 wild-type [wt]) and H-460 (p53 wt) lung cancers and triple negative MDA-MB-231 human breast carcinoma. To mimic clinical application of radiotherapy, fractionated radiation (2 Gy per fraction) schedules given once or twice daily for 1 to 2 weeks combined with MK-4827, 50 mg/kg once daily or 25 mg/kg twice daily, were used. MK-4827 was found to be highly and similarly effective in both radiation schedules but maximum radiation enhancement was observed when MK-4827 was given at a dose of 50 mg/kg once daily (EF = 2.2). MK-4827 radiosensitized all four tumors studied regardless of their p53 status. MK-4827 reduced PAR levels in tumors by 1 h after administration which persisted for up to 24 h. This long period of PARP inhibition potentially adds to the flexibility of design of future clinical trials. Thus, MK-4827 shows high potential to improve the efficacy of radiotherapy.