Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Efficacy of dupilumab in real-life settings: a STROBE study.

BACKGROUND: Dupilumab, a monoclonal antibody targeting IL-4 and IL-13, has demonstrated its efficacy in several clinical trials. However, to date, real-life data remains limited. OBJECTIVE: The aim of our study was to assess the real-life impact of dupilumab on patients with severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) quality of life. MATERIALS AND METHODS: This was a retrospective, monocentric, observational, real-life study, conducted in accordance with the STROBE guidelines. The following parameters were collected before treatment and at 1, 4, and 12 months: Sino-Nasal Outcome Test-22 (SNOT-22), nasal polyp score (NPS), Sniffin' Sticks-16 (SST-16), visual analog scale (VAS) for loss of smell, nasal congestion score (NCS), gustatory VAS, asthma control, oral corticosteroid usage, surgery rates, and occurrence of side effects. RESULTS: The study included 47 patients. SNOT-22 scores decreased from 52.4 ± 24.3 to 12.7 ± 10.5 at 12 months (p < 0.001). NPS decreased from 6.15 ± 1.71 to 1.57 ± 1.40 at 12 months (p < 0.001). SST-16 scores increased from 1.6 ± 2.83 to 9.1 ± 5.4 at 12 months (p < 0.001). NCS decreased from 2.45 ± 0.72 to 0.38 ± 0.63 at 12 months (p < 0.001). Prior to treatment, 72.3% were using oral corticosteroids, compared to 17.0% at 12 months (p < 0.01). Two patients required additional surgery, and 17% reported completely uncontrolled asthma, compared to 0% at 12 months (p < 0.01). CONCLUSION: Our real-life results confirm the efficacy of Dupilumab in the treatment of severe and uncontrolled CRSwNP.

The price tag of a potential cure for chronic hepatitis B infection: A cost threshold analysis for USA, China and Australia.

BACKGROUND & AIMS: We aim to capture the economic impact of a potential cure for chronic hepatitis B infection (CHB) in three countries (USA, China and Australia) with different health systems and epidemics to estimate the threshold drug prices below which a CHB cure would be cost-saving and/or highly cost-effective. METHODS: We simulated patients' hepatitis B progression, under three scenarios: current long-term suppressive antiviral therapy, functional cure defined as sustained undetectable HBsAg and HBV DNA, and partial cure defined as sustained undetectable HBV DNA only after a finite, 48-week treatment. RESULTS: Compared with current long-term antiviral therapy, a 30% effective functional cure among patients with and without cirrhosis in the USA, China and Australia would yield 17.50, 17.32 and 20.42 QALYs per patient, and 20.61, 20.42 and 20.62 QALYs per patient respectively. In financial terms, for CHB patients with and without cirrhosis, this would be cost-saving at a one-time treatment cost under US$11 944 and US$6694, respectively, in the USA, US$1744 and US$1001 in China, and US$12 063 and US$10 983 in Australia. CONCLUSION: We show that in purely economic terms, a CHB cure will be highly cost-effective even if effective in only 30% of treated patients. The threshold price for cure is largely determined by the current antiviral drug costs, since it will replace a daily antiviral pill that is inexpensive and effective, although not curative. The likely need for combination therapies to achieve cure will also present cost challenges. While cost-effectiveness is important, it cannot be the only consideration, as cure will provide many benefits in addition to reduced liver disease and HCC, including eliminating the need for a long-term daily pill and reducing stigma often associated with chronic viral infection.

Assessing normal values for the FACE-Q rhinoplasty module: An observational study.

OBJECTIVES: The goal of this study was to determine normal values for the FACE-Q rhinoplasty module. DESIGN: A prospective monocentric observational cohort study. SETTING: We tested FACE-Q Satisfaction with Nose and Satisfaction with Nostrils in two groups of patients, seeking or not a rhinoplasty. PARTICIPANTS: One hundred and four patients were included in the study, fifty-two in each group. MAIN OUTCOME MEASUREMENTS: Primary outcome was to identify possible cutting scores to establish normal values for each of the FQRM questionnaires. RESULTS: Regarding the Satisfaction with Nose scale, there was a statistically significant difference between the two groups (P < .001). Area under the ROC curve was 0.964 (95% CI = 0.931-0.997). Forty-seven points was the value presenting the best Youden index (sensitivity = 96.2%, specificity = 86.5%). Regarding the Satisfaction with Nostrils scale, there was a statistically significant difference between the two groups (P < .001). Area under the ROC curve was 0.820 (95% CI = 0.741-0.899). Sixty-four points was the value presenting the best Youden index (sensitivity = 94.2%, specificity = 53.8%). CONCLUSION: This is the first study to generate normative data for the FACE-Q rhinoplasty module. The findings presented here have important implications for future clinical care and research. The definition of a normal score can help practitioners to better analyse their patients and to support a therapeutic indication.

The MiRa scale, a new standardised scale for evaluating nasal deformities before and after septorhinoplasty: A prospective study comparing patient satisfaction and the surgeon's assessment.

OBJECTIVES: The objective was to assess the reliability of a new standardised scale for evaluating nasal anomalies in order to compare the surgeon's assessment and patient satisfaction. DESIGN: Monocentric prospective cohort study. SETTINGS: First, we validated the reliability of the MiRa scale; then, we compared the surgeon's assessment and patient satisfaction. PARTICIPANTS: Fifty-two patients underwent septorhinoplasty surgery and gave their written consent before inclusion. MAIN OUTCOME MEASUREMENTS: Primary outcome measurement was to validate the reliability of the MiRa scale: two observers analysed all records twice. Intra-observer reproducibility and interobserver reproducibility were evaluated using the intraclass correlation coefficient (ICC). Secondary outcome measurement was to compare the surgeon's assessment and patient satisfaction: MiRa and ROE (Rhinoplasty Outcome Evaluation) scores were established for each patient prior to and 6 months after surgery. RESULTS: Using the MiRa scale, ICC for intra- and interobserver reproducibility was, respectively, 95.4% and 96%, showing no statistical difference (P=.70, P=.45). Good correlation scores were, respectively, 93% and 92%. Mean ROE scores were 7.1/24 (SD=11.3) before and 19.3/24 (SD=17.3) after surgery (P<.05). We found an increase in MiRa and ROE scores of +19.75% and +51.25% (P<.05), respectively. The average postoperative ROE score in the primary septorhinoplasty group was 20.4 (SD=14.4) and 17.2 (SD=23.1) in the secondary septorhinoplasty group (P<.05). CONCLUSION: MiRa scale is a reliable, standardised tool to evaluate surgical outcome in septorhinoplasty surgery. It provides an objective and reproducible score. The surgeon's assessment was more critical than patient satisfaction. Patient satisfaction is more difficult to achieve in cases involving a secondary septorhinoplasty.

[Lymphatic drainage of skin areas of head and neck: in vivo approach by the location of the sentinel node]. / Drainage lymphatique des territoires cutanés de la tête et du cou : approche in vivo par la localisation du ganglion sentinelle.

INTRODUCTION: The objective of the study was to determine the preferential territories of drainage of skin areas of the face and neck. This knowledge can guide the strategies of diagnostic (search for primary tumor skin to cervical lymphadenopathy) and treatment (determination of the extent of neck dissection to achieve in case of skin tumor). MATERIALS AND METHODS: This is a retrospective study of the surgical procedures of sentinel node research between January 2003 and April 2011. The lymphoscintigraphic and intraoperative localization of the initial tumor site and sentinel lymph node were collected. RESULTS AND DISCUSSION: One hundred and thirty-seven patients were included in the study. The parotid gland is a privileged territory of drainage of the head and neck skin. At cervical level, the submental region drains the lower and median part of the face (lips and chin). The posterior segments (IIb and V sector) were represented for the posterior locations of the head (ear, vertex), and cervical region.

Sentinel lymph node biopsy in head and neck melanoma: A single institution analysis.

INTRODUCTION: The aim of our study was to analyze a series of patients from our institution who underwent surgery for head and neck cutaneous melanoma and who received sentinel lymph node biopsy (SLNB). MATERIAL AND METHODS: A single-center observational cohort of 120 head and neck melanoma patients was investigated from 2002 to 2011. RESULTS: Among the 107 patients (89.2%) with lymph node identified during lymphoscintigraphy, at least one node was collected and analyzed in 96 patients (90.6%). A positive sentinel lymph node was found in 9.4% of patients. Our data showed higher failure rate of lymphoscintigraphic identification (11.7%), lower rate of SLN positivity (9.4%), and higher false-negative rate of SLNB (24.1%) than the usualfigures established for malignant melanomas in other locations. After a mean follow-up of 38.1 months, the disease-free survival (DFS) rate in the positive SLN group was 53% vs 75% for the negative SLN after 2 years of follow-up and 53% vs 48% after 5 years (p = 0.44). CONCLUSION: The complexity of lymphatic drainage and the anatomy of the cervical region probably accounts for a specificities which result in a lower predictive value of SLNB in head and neck melanoma than in MM in other locations.

[Fungal sinusitis: report of two cases of indolent form of fungus usually invasive, up treatment and care]. / Sinusites fongiques: à propos de deux cas de forme indolente de mycose habituellement invasive, place du traitement et prise en charge.

OBJECTIVES: Unlike Aspergillus sinusitis, sinus infections by mucormycosis are often invasive and have a lethal potential. We report two cases of chronic sinusitis with unilateral uncomplicated diagnosis of mucormycosis confirmed by pathology or mycology and discuss the therapeutic strategy. PRESENTATION: Case 1) An immunocompetent patient with a right chronically sphenoid sinusitis uncomplicated underwent endonasal surgery in our institution. Rhizopus Oryzae was found on the surgical mycological specimen. The patient received no adjuvant medical therapy after surgery, because there were no invasive clinical or radiological criteria and no histopathological confirmation. Clinical, radiological and mycological follow-up was done. Case 2) A patient with a chronic maxillary sinusitis underwent endonasal surgery in our institution. Histological analysis found filaments in favor of mucormycosis without vascular emboli. We decided in agreement with the national reference center for mycology not to treat medically. CONCLUSION: A follow up of more than 3 years for both cases tends to confirm this collective decision.

[Prognostic value of sentinel lymph node in Merkel cell carcinoma of the head and neck]. / Intérêt pronostique du ganglion sentinelle dans les carcinomes a cellules de Merkel de la tête et du cou.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor. The aim of our study was to analyze the prognosis of patients operated on for CCM and having no lymph node involvement after analysis of sentinel lymph node (SLN). MATERIAL AND METHOD: This was a retrospective study of 10 cases of CCM stage I or II who received the SLN technique in our institution between 2003 and 2010. RESULTS Among the 10 patients, 7 had an identification of at least one SLN, among which the node could be surgically removed in 6 cases. In cases of failure of SLN technique, a neck dissection +/- parotidectomy was performed. No lymph node metastasis was found in our series. Mean follow-up was 38 months. The overall survival rate was 100% at 2 years and 50% at 5 years. The Disease-free survival was 85% at 2 and 5 years. CONCLUSION: Our results show that the technique of sentinel lymph node is a reliable tool for evaluating nodal status of patients with CCM and that pN0 patients have a good prognosis.

Rhinoplasty: French validation of the MiRa scale.

AIMS: The aim of this study was to translate the MiRa scale into French and validate its use for French-speaking surgeons. MATERIAL AND METHODS: ISPOR and WHO recommendations were used to carry out the translation process from English to French in five steps. The MiRa scale is a validated analysis scale of nasal dysmorphoses. Few tools are available in French for French-speaking surgeons. ISPOR and WHO recommendations were used to complete the five-step translation process from English into French. To assess the reliability of the MiRa scale-French version, we statistically compared intra-observer repeatability (comparison of scores obtained when one observer assessed each patient twice at a one-month interval) and inter-observer repeatability (comparison of scores obtained when 2 observers assessed the same patient) using the Wilcoxon test and the intraclass correlation coefficient (ICC) (α=5%). OBJECTIVES: Our goal was to obtain a translation of the idea or concept rather than a literal translation to enable good intra- and inter-observer repeatability. RESULTS: Each step allowed us to make changes gradually working towards a conceptual translation equivalent to the original version. CONCLUSION: The MiRa scale is the only aesthetic analysis scale validated in the literature for nasal dysmorphoses. The combined use of two sets of translation recommendations, with a five-step translation-back-translation process, made it possible to obtain a French version perfectly in line with the original. This version is usable by French-speakers.

A global scientific strategy to cure hepatitis B.

Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure. We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection. There is also a pressing need for the establishment of repositories of standardised HBV reagents and protocols that can be accessed by all HBV researchers throughout the world. The HBV cure research agenda outlined in this position paper will contribute markedly to the goal of eliminating HBV infection worldwide.

Outcomes of septorhinoplasty: a new approach comparing functional and aesthetic results.

The aim of this study was to compare objective and subjective functional results of septorhinoplasty with subjective aesthetic results. A prospective study was performed including global and subgroup analyses (primary versus secondary septorhinoplasty). Three instruments were used to evaluate pre- and postoperative results: rhinomanometry for the objective functional analysis, the Nasal Symptom Obstruction Evaluation (NOSE) scale for the subjective functional analysis, and the Rhinoplasty Outcome Evaluation (ROE) scale for the subjective aesthetic analysis. A septorhinoplasty was performed in all cases. Thirty-five patients were included (22 female), of whom 74% underwent primary septorhinoplasty. The correlation between rhinomanometry, NOSE and ROE scores was analysed. Mean resistance of the two nasal cavities was 4.9 (standard deviation (SD) 8.35) sPa/ml before surgery and 0.8 (SD 0.7) sPa/ml after surgery. NOSE and ROE scores were, respectively, 72.5/100 (SD 21.7) and 7.5/24 (SD 11.3) before surgery and 22/100 (SD 20.6) and 18/24 (SD 17.3) after surgery. Patients complaining of postoperative nasal obstruction had a worse aesthetic evaluation. Correction of the functional disease appears to be as important as aesthetic correction. This study comparing functional and aesthetic results after septorhinoplasty could provide a basis for future studies.

Endoscopic surgery for sinonasal tumors: The transcribriform approach.

Over the past 10 to 20 years, endoscopic endonasal surgery has become for many teams the preferred treatment for sinonasal tumors. Technical advances in the field of surgical instrumentation (good visualization, hemostasis…) and the progress of imaging guidance (to avoid neurovascular complication) has made those procedures simpler and safer. Nevertheless, endonasal endoscopic procedures require a trained surgical team of ENT specialist and neurosurgeon. Endoscopic endonasal surgery has been reported to be feasible for all types of sinonasal tumors whether benign tumors such as inverted papillomas, or malignant tumors. In this paper, we mostly focus on the principles underlying the transcribriform approach, which is dedicated to the surgery of CSF leaks, encephaloceles/meningoceles, access to benign intracranial tumors such as olfactory groove meningiomas, and the resection of sinonasal malignancies with skull base invasion such as olfactory neuroblastomas.

Sinonasal adenocarcinoma: clinical outcomes and predictive factors.

A retrospective study of 39 patients treated for sinonasal adenocarcinoma between 1995 and 2010 was performed. Epidemiological, clinical, histological, and therapeutic aspects of this series of patients were analyzed statistically and their impact in terms of overall and disease-free survival established using the Kaplan-Meier method. A search for prognostic factors was made using a log-rank test. The male to female sex ratio was 6.8 to 1. The average age at diagnosis was 65.7 years (range 40.2-85.6 years). An occupational risk factor (wood dust, leather) was found for 19 patients (48.7%). The median patient follow-up was 51.9 months (range 8-180 months). Tumours were classified as T1 in 20.5%, T2 in 25.6%, T3 in 23.1%, and T4 in 30.8% of cases. Disease-free survival rates at 1, 5, and 10 years were 87.9%, 44.8%, and 39.2%, respectively; overall survival rates were 86.1%, 72.2%, and 50.3%, respectively. Overall survival was correlated with tumour status (TNM, American Joint Committee on Cancer) (P=0.004). Surgery followed by radiotherapy improved overall survival (P=0.012) and disease-free survival (P=0.028) when compared to other treatment modalities. When compared to surgery alone, surgery followed by radiotherapy improved disease-free survival regardless of tumour stage (P=0.049).

Fine-needle aspiration cytology in the management of parotid masses: evaluation of 249 patients.

INTRODUCTION: The role of fine-needle aspiration cytology (FNAC) in the management of parotid tumours is still the subject of controversy. The purpose of this study was to determine the diagnostic value of FNAC in our institution in order to define its place in the diagnostic strategy. PATIENTS AND METHODS: This retrospective study was based on 249 patients who had undergone preoperative FNAC before being operated in our institution between 2001 and 2008. All examinations were performed and interpreted by the same experienced pathologist. RESULTS: Among the 249 patients included in this study, 187 (75%) had a benign tumour and 62 (25%) had a malignant tumour. No complications of FNAC were observed. Cytological findings were non-contributory in 47 patients (18%). The sensitivity of FNAC for the diagnosis of malignancy was 80% with a specificity of 89.5%. Among the 11 false-negative results, lymphomas and low-grade mucoepidermoid carcinomas were the most common histological types. Among the 16 false-positive results, Warthin's tumours, pleomorphic adenomas and lymphoepithelial lesions were the most common histological types. Accurate histological classification of the tumour was reported in 79.5% of cases (86% for benign tumours and 44% for malignant tumours). CONCLUSION: FNAC is a reliable examination providing important information to the surgeon in the preoperative diagnostic assessment.

Development of a novel continuous culture device for experimental evolution of bacterial populations.

The availability of a robust and reliable continuous culture apparatus that eliminates wall growth problems would lead to many applications in the microbial field, including allowing genetically engineered strains to recover high fitness, improving biodegradation strains, and predicting likely antibiotic resistance mechanisms. We describe the design and implementation of a novel automated continuous culture machine that can be used both in time-dependent mode (similar to a chemostat) and turbidostat modes, in which wall growth is circumvented through the use of a long, variably divisible tube of growth medium. This tube can be restricted with clamps to create a mobile growth chamber region in which static portions of the tube and the associated medium are replaced together at equal rates. To functionally test the device as a tool for re-adaptation of engineered strains, we evolved a strain carrying a highly deleterious deletion of Elongation Factor P, a gene involved in translation. In 200 generations over 2 weeks of dilution cycles, the evolved strain improved in generation time by a factor of three, with no contaminations and easy manipulation.