Genomics of the divergence continuum in an African plant biodiversity hotspot, I: drivers of population divergence in Restio capensis (Restionaceae).

Understanding the drivers of population divergence, speciation and species persistence is of great interest to molecular ecology, especially for species-rich radiations inhabiting the world's biodiversity hotspots. The toolbox of population genomics holds great promise for addressing these key issues, especially if genomic data are analysed within a spatially and ecologically explicit context. We have studied the earliest stages of the divergence continuum in the Restionaceae, a species-rich and ecologically important plant family of the Cape Floristic Region (CFR) of South Africa, using the widespread CFR endemic Restio capensis (L.) H.P. Linder & C.R. Hardy as an example. We studied diverging populations of this morphotaxon for plastid DNA sequences and >14 400 nuclear DNA polymorphisms from Restriction site Associated DNA (RAD) sequencing and analysed the results jointly with spatial, climatic and phytogeographic data, using a Bayesian generalized linear mixed modelling (GLMM) approach. The results indicate that population divergence across the extreme environmental mosaic of the CFR is mostly driven by isolation by environment (IBE) rather than isolation by distance (IBD) for both neutral and non-neutral markers, consistent with genome hitchhiking or coupling effects during early stages of divergence. Mixed modelling of plastid DNA and single divergent outlier loci from a Bayesian genome scan confirmed the predominant role of climate and pointed to additional drivers of divergence, such as drift and ecological agents of selection captured by phytogeographic zones. Our study demonstrates the usefulness of population genomics for disentangling the effects of IBD and IBE along the divergence continuum often found in species radiations across heterogeneous ecological landscapes.

Transoral laser surgery for recurrent glottic cancer after radiotherapy: oncologic and functional outcomes.

Primary radiotherapy (RT) has been successfully employed for treatment of early glottic cancer for the past half century. However, local recurrences still occur in 5-35% of patients. Salvage options for persistent/recurrent glottic cancer include total laryngectomy, open neck partial laryngectomies (ONPLs) and transoral laser surgery (TLS). We performed a retrospective chart review of 35 patients with glottic squamous cell carcinoma previously submitted to RT and managed by TLS at the Department of Otorhinolaryngology - Head and Neck Surgery of the University of Brescia, Italy, from 1995 to 2009. Oncologic outcomes were estimated using the Kaplan-Meier method, and separately calculated for the entire cohort of patients (n = 35) and for patients with true persistent/recurrent disease (n = 30), thus excluding the second primary tumours (n = 5). Hospitalization time and complications were obtained by chart review. Functional outcomes of a subgroup of 10 patients in terms of speech and swallowing were analyzed by the Voice Handicap Index (VHI), GRBAS scale, Multi Dimensional Voice Program (MDVP), M.D. Anderson Dysphagia Inventory (MDADI) questionnaire, videoendoscopy (VEES), and videofluoroscopy (VFS) of swallowing (both graded according to Donzelli's scale), and compared to a cohort of 10 patients matched for age, gender and pT category, treated by the same team of surgeons by TLS as a primary treatment. The types of resection used were: 18 Type III, 1 Type IV, and 16 Type V cordectomies. Postoperative staging was 16 rpT1a, 17 rpT2, and 2 rpT3. The 5-year overall survival for the entire series was 91%. Five-year disease-specific survival, local control with laser alone, and organ preservation rates were 94%, 84% and 87%, respectively. Among the variables tested by univariate analysis, for the entire cohort of patients the pT category had a statistically significant impact on local control with laser alone. Anterior transcommissural extension had a borderline statistical impact on disease-specific survival, while it was clearly significant on overall survival. The status of surgical margins and presence of recurrence after TLS statistically influenced both organ preservation and local control with laser alone. The mean values of VHI, MDADI, and MDVP did not show any statistically significant difference between irradiated and non-irradiated patients. The same was true for GRBAS, VEES, and VFS. This series confirms that TLS after RT failure can be considered a successful surgical option in selected early recurrences, with functional outcomes comparable to those observed after TLS as a primary treatment, and much better than those classically described after ONPLs.

Narrow band imaging and high definition television in the endoscopic evaluation of upper aero-digestive tract cancer.

Narrow band imaging and high definition television are recent innovations in upper aero-digestive tract endoscopy. Aim of this prospective, non-randomized, unblinded study was to establish the diagnostic advantage of these procedures in the evaluation of squamous cell cancer arising from various upper aero-digestive tract sites. Between April 2007 and January 2010, 444 patients affected by upper aero-digestive tract squamous cell cancer, or previously treated for it, were evaluated by white light and narrow band imaging ± high definition television endoscopy, both in the pre-/intra-operative setting and during follow-up. Tumour resection was performed taking into account narrow band imaging and high definition television information to obtain histopathologic confirmation of their validity. Endoscopic and pathologic data were subsequently matched to obtain sensitivity, specificity, positive, negative predictive values, and accuracy. Overall, 110 (25%) patients showed adjunctive findings by narrow band imaging ± high definition television when compared to standard white light endoscopy. Of these patients, 98 (89%) received histopatological confirmation. The sensitivity, specificity, positive, negative predictive values, and accuracy for white light-high definition television were 41%, 92%, 87%, 82%, and 67%, for narrow band imaging alone 75%, 87%, 87%, 74%, and 80%, and for narrow band imaging-high definition television 97%, 84%, 88%, 96%, and 92%. The highest diagnostic gain was observed in the oral cavity and oropharynx (25%). Narrow band imaging and high definition television were of value in the definition of superficial tumour extension, and in the detection of synchronous lesions in the pre-/intra-operative settings. These technologies also played an important role during post-treatment surveillance for early detection of persistences, recurrences, and metachronous tumours.

Endoscopic treatment of Zenker's diverticulum by carbon dioxide laser.

The management of Zenker's diverticulum remains controversial, as both external and endoscopic procedures are potentially associated with post-operative complications and risks. The endoscopic approach is based on cricopharyngeal myotomy or myectomy by laser, cautery or stapling. A retrospective chart review has been made from December 1994 to April 2009 of all patients with Zenker's diverticulum treated by endoscopic cricopharyngeal myectomy using CO(2) laser at the Department of Otorhinolaryngology - Head and Neck Surgery of the University of Brescia, Italy. Of the 28 patients (19 males, 9 females; mean age, 64 years; range, 46-95) scheduled for the trans-oral procedure, 27 (96%) were endoscopically treated. Diagnosis was based on the patient's history, flexible fiberoptic examination of the larynx, hypopharynx, and oesophagus, and videofluoroscopy with barium. Exclusion criteria included severe medical co-morbidities, impossibility to endoscopically expose the diverticulum, and small (< 2 cm) or large (> 6 cm) diverticula. The endoscopic procedure was performed using a CO(2) laser to section the cricopharyngeal muscle and remove the posterior part in order to obtain partial myectomy. Major complications occurred in 2 (7%) patients. No cases of recurrent nerve paralysis, pharyngo-cutaneous fistula, neck emphysema, post-operative bleeding, mediastinitis or aspiration pneumonia were observed in the present series. A swallow survey was obtained by telephone: 85% of patients reported improved swallowing (without symptoms in 11 and with moderate dysphagia in 7). Based on the present series, endoscopic CO(2) laser cricopharyngeal myectomy for Zenker's diverticulum can be considered an effective and safe procedure, with reduced hospitalization time and complication rate.

Narrow band imaging and high definition television in evaluation of oral and oropharyngeal squamous cell cancer: a prospective study.

Narrow band imaging (NBI) is an optical technique in which filtered light enhances superficial neoplasms based on their neoangiogenic pattern. The accuracy of NBI can be augmented by combining it with high definition television (HDTV). The aim of this study was to prospectively assess the diagnostic value of NBI in combination with HDTV in evaluation of oral (O) and oropharyngeal (OP) squamous cell carcinoma (SCC). Between April 2007 and December 2009, we analyzed 96 patients who were divided into 2 groups: Group A included 35 patients previously biopsied and diagnosed with OSCC or OPSCC and subjected to pre- and intraoperative HDTV white light (WL) and HDTV NBI endoscopy; Group B included 61 subjects already treated for OSCC or OPSCC and followed-up with HDTV WL and HDTV NBI. Fourteen of 35 (40%) patients in Group A showed adjunctive findings with NBI compared to standard WL. All of these findings were histologically confirmed. Twelve of 61 (20%) patients in Group B showed positive NBI findings, which were all confirmed by histology. The sensitivity, specificity, positive, negative predictive values, and accuracy for HDTV WL were 51%, 100%, 100%, 87%, and 68%, respectively, whilst for HDTV NBI were 96%, 100%, 100%, 93%, and 97%, respectively. Overall, 26 of 96 (27%) patients had a diagnostic advantage in applying NBI and HDTV: 6 patients received a diagnosis of recurrence and 1 of persistence after previous treatments; 5 showed a metachronous tumour; in 4 a synchronous tumour was diagnosed; 9 lesions were upstaged; in 1 patient previously diagnosed with an unknown primary by fine needle aspiration cytology on the neck, an anterior tonsillar pillar cancer was identified.