Seagrass Meadows: Prospective Candidates for Bioactive Molecules.

Seagrass meadows consist of angiosperms that thrive fully submerged in marine environments and form distinct ecosystems. They provide essential support for many organisms, acting as nursery grounds for species of economic importance. Beyond their ecological roles, seagrasses and their associated microbiomes are rich sources of bioactive compounds with the potential to address numerous human healthcare challenges. Seagrasses produce bioactive molecules responding to physical, chemical, and biological environmental changes. These activities can treat microbe-borne diseases, skin diseases, diabetes, muscle pain, helminthic diseases, and wounds. Seagrasses also offer potential secondary metabolites that can be used for societal benefits. Despite numerous results on their presence and bioactive derivatives, only a few studies have explored the functional and therapeutic properties of secondary metabolites from seagrass. With the increasing spread of epidemics and pandemics worldwide, the demand for alternative drug sources and drug discovery has become an indispensable area of research. Seagrasses present a reliable natural source, making this an opportune moment for further exploration of their pharmacological activities with minimal side effects. This review provides a comprehensive overview of the biochemical, phytochemical, and biomedical applications of seagrasses globally over the last two decades, highlighting the prospective areas of future research for identifying biomedical applications.

Feasibility and acceptability of a caregiver-mediated early support program, delivered online, for infants at elevated familial likelihood for autism: A feasibility randomized controlled trial.

Preliminary evidence indicates potential benefit of providing caregiver-mediated intervention, prior to diagnosis, for infants at elevated familial likelihood for autism and related developmental delays including language delay (EL-A). However, delivering such interventions online and in low-resource settings like India has not been reported. This study aimed to evaluate the feasibility and acceptability of delivering a novel manualized caregiver-mediated early support program, the "LiL' STEPS," online in India, for EL-A infants. LiL' STEPS stands for Language development & Intervention Lab's (LiL') Supporting Early social-communication and language by Promoting caregiver Sensitive responsiveness (STEPS). The program comprised 14 sessions with a focus on social-communication and language, conducted over 12-weeks using demonstration and video feedback. Families of 36 EL-A infants aged 9 to 15-months participated in this feasibility randomized controlled trial (RCT). Families were randomized in a 2:1 ratio (n = 24 LiL' STEPS and n = 12 care as usual groups). Information on feasibility and acceptability was collated following a mixed methods approach from caregiver interviews, fidelity forms, session notes, and study register. Findings indicated the LiL' STEPS study trial as feasible and acceptable with recruitment rate of 4 per month, 100% willingness for randomization, 8.3% attrition, and 3.03% loss of blinding. Interventionist and caregiver fidelity was maintained above 80%. Despite challenges like interruptions during sessions, 100% families found the program acceptable and satisfactory, 86% said they would recommend the program to others, and 71% preferred online modality. Caregivers' perspectives on beneficial components and experience attending the program have been described. Accordingly, recommendations for future definitive RCTs have been presented.

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates.

A cascade inter-intramolecular double Michael strategy for the synthesis of highly functionalized cyclohexanones from curcumins and arylidenemalonates is reported. This strategy works in the presence of aqueous KOH using TBAB as a suitable phase transfer catalyst at room temperature. The functionalized cyclohexanones are formed as major products in moderate to excellent yields with complete diastereoselectivity in most cases. A triple Michael adduct, tetrahydrochromen-4-one, is also formed as a side product in a few cases with excellent diastereoselectivity.

Intraoperative surgical navigation as a precision medicine tool in sinonasal and craniofacial oncologic surgery.

INTRODUCTION: Recent evidence supports the efficacy of surgical navigation (SN) in improving outcomes of sinonasal and craniofacial oncologic surgery. This study aims to demonstrate the utility of SN as a tool for integrating surgical, radiologic, and pathologic information. Additionally, a system for recording and mapping biopsy samples has been devised to facilitate sharing of spatial information. MATERIALS AND METHODS: SN was utilized for biopsy mapping in 10 sinonasal/craniofacial oncologic procedures. Twenty-five raters with experience in anterior skull base oncology were interviewed to identify 15 anatomical structures in preoperative imaging, relying on topographical descriptions and surgical video clips. The difference in the localization of anatomical structures by raters was analyzed, using the SN-mapped coordinates as a reference (this difference was defined as spatial error). RESULTS: The analysis revealed an average spatial error of 9.0 mm (95 % confidence interval: 8.3-9.6 mm), with significant differences between surgeons and radiation oncologists (7.9 mm vs 12.5 mm, respectively, p < 0.0001). The proposed model for transferring SN-mapped coordinates can serve as a tool for consultation in multidisciplinary discussions and radiotherapy planning. CONCLUSIONS: The current standard method to evaluate disease extension and margin status is associated with a spatial error approaching 1 cm, which could affect treatment precision and outcomes. The study emphasizes the potential of SN in increasing spatial precision and information sharing. Further research is needed to incorporate this method into a multidisciplinary workflow and measure its impact on outcomes.

The Human Papillomavirus Enigma: A Narrative Review of Global Variations in Oropharyngeal Cancer Epidemiology and Prognosis.

Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.

N0 neck trial: Does intensification of follow-up (Ultrasound + Physical Examination) influence outcomes in early-stage oral cancer?

AIM OF THE STUDY: We previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes. METHODS: Patients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS). RESULTS: Between January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51-126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71-1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51-76.09) and PE (67.3%, 95% CI, 61.81-72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33-9.60) and 7.62 (IQR 3.22-9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%. CONCLUSION: Adding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival.

Swallowing in advanced oral cancers: A prospective observational study.

BACKGROUND: Advanced head and neck cancers are known to cause swallowing dysfunction due to anatomical and post-treatment changes. Literature is sparse on post-surgical and/or multi-modality therapy-associated swallowing function in advanced oral cancers. We conducted this study to longitudinally assess and compare the pre- and post-therapy swallowing dysfunction associated with locally advanced oral cancers. METHODS AND MATERIAL: A prospective observational longitudinal study was conducted at a tertiary cancer center from 2017 to 2018 including treatment-naive cT4a oral cancer patients (AJCC 7th edition). The assessment was done pre-surgery, post-surgery, and post-adjuvant setting as per the scales (Dysphagia score, Penetration aspiration scale, and Yale pharyngeal residue (vallecular and pyriform fossa). RESULTS: Of the 30 patients in the study, 47.4%, 47.4%, 52.6%, and 47.4% experienced deterioration of Dysphagia score, Penetration-Aspiration Scale (PAS), vallecula residue, and pyriform residue scores in the postoperative period. And 52.6%, 47.4%, 68.4%, and 57.9% had inferior dysphagia score, PAS, vallecula, and pyriform residue scores even 6 months after completion of adjuvant therapy. The dysphagia score correlated well with other objective assessment scores at different time points. CONCLUSION: Swallowing functions are significantly affected by surgery and adjuvant therapy and continue to be affected even 6 months after completion of treatment. Appropriate rehabilitation and intervention must be offered to patients to reduce this problem. Dysphagia scores can predict the swallowing status similar to other objective assessments.

Autologous Fascial Slings for Stress Urinary Incontinence: a 17-year Follow-up of a Randomised Controlled Study.

INTRODUCTION AND HYPOTHESIS: Safety concerns with the use of mesh in vaginal surgery have been ongoing. Autologous fascial slings (AFS) avoid foreign body complications. We compared the long-term (17-year) outcomes of two AFS repair methods-the standard sling and short sling (sling-on-string), and assessed durability and patient satisfaction of these for the treatment of stress urinary incontinence (SUI). METHODS: A total of 107 patients from three urogynaecology units who had participated in a randomised controlled trial assessing standard (n = 52) and short (n = 55) slings were followed up for a median period of 17 years. Primary outcomes were Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores to assess the impact on the quality of life and symptom distress. Logistic quantile regression was employed to compare the two methods. Secondary outcomes included long-term complications and patient satisfaction. RESULTS: Mean scores showed no statistically significant difference between the standard and short slings at the 17-year follow-up relating to IIQ and UDI scores, leakage or urgency (p > 0.05). Improved bladder function was observed at 17 years compared with baseline (standard sling-IIQ scores mean difference [MD] 1.22 [CI: 0.69, 1.74], UDI scores MD 0.83 [CI: 0.70, 0.97]; short sling-IIQ score MD 1.14 [CI: 0.73, 1.54], UDI scores MD 0.54 [CI: 0.40, 0.67]) with age-related deterioration over time. Re-operation rates were low and patient satisfaction rates were high (67.2%) at follow-up. CONCLUSIONS: Autologous fascial slings are an effective and durable option for management of SUI and the short sling procedure can be recommended owing to plausible surgical advantages.

Prognostic Impact of Poor Differentiation of Squamous Cell Carcinoma in Treatment Naïve Node-Negative Early Oral Cancers.

We have conducted this study to understand the impact of poor differentiation (PD), as a sole poor prognostic factor, in early oral cancers. This was a retrospective analysis of a prospectively maintained database of clinically node-negative early T stage OSCC patients operated between 2012 and 2014. Impact of PD on the survival and role of adjuvant therapy in these patients was noted. Out of 1172 patients screened, 280 patients were found to be eligible for the study. 11.4% patients had PDSCC. It was found to be associated with tongue cancers and peri-neural invasion. It had a significant impact on OS and DFS (48.7 months vs 81.4 months, p < 0.00 and 44.6 months vs 73.5 months, p < 0.00 respectively. Hazard ratio for DFS: 4.08. Although patients with PDSCC had better survival with radiotherapy, but this was not statistically significant. Poor differentiation as a stand-alone factor impacts survival in patients with early oral cancer. It may be seen more often in patients with tongue cancer and may have associated PNI. The role of adjuvant therapy in such patients is not clear.

Prophylactic versus reactive feeding approach in patients undergoing adjuvant radiation therapy for oral cavity squamous cell carcinoma: A propensity score matched-pair analysis.

BACKGROUND: To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). METHODS: This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. RESULTS: Two hundred and sixty-eight in each cohort (total n = 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p = 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. CONCLUSIONS: A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.

Synthesis of Spirolactones and Functionalized Benzofurans via Addition of 3-Sulfonylphthalides to 2-Formylaryl Triflates and Conversion to Benzofuroisocoumarins.

A convenient protocol for the synthesis of spirobenzofuran-isobenzofurans and substituted benzofurans via a modified Hauser-Kraus reaction of 3-sulfonylphthalide with 2-formylaryl triflates is reported here. The initial reaction involved 1,2-addition of phthalide to the formyl group and intramolecular cyclization via substitution of triflate followed by a cascade of rearrangements leading to spirolactone or benzofuran derivatives. The electronic nature of substituents on aryl triflates affected the course and outcome of the reaction. The mechanism was supported by successful characterization of one of the intermediates by mass spectrometry. A medicinally relevant influenza virus type B inhibitor, benzofuroisocoumarin, was synthesized in a single step from the spiro compound, thus demonstrating the synthetic utility of our methodology.

Oral cavity adjuvant therapy (OCAT) -a phase III, randomized controlled trial of surgery followed by conventional RT (5 fr/wk) versus concurrent CT-RT versus accelerated RT (6fr/wk) in locally advanced, resectable, squamous cell carcinoma of oral cavity.

BACKGROUND: Limited data exists regarding the impact of intensification of adjuvant therapy in resected Oral Cavity Squamous Cell Carcinomas (OCSCC) with adverse prognostic features on histopathology. PATIENTS AND METHODS: This was a three-arm phase III, randomised trial including patients with resected advanced OCSCC. Randomisation was done in a 1:1:1 ratio: Arm-A- standard adjuvant radiation therapy (RT) 60Gy/30 fractions over 6 weeks versus Arm-B-concurrent chemoradiation versus Arm-C-accelerated radiation therapy (6 d a week). The trial was powered to detect an absolute difference of 10% in 5-year Locoregional Control (LRC). RESULTS: The trial was conducted between June 2005 and March 2013. Majority of the patients were males, had T3-T4 disease, had N2-N3 nodal status and had Extra-Capsular Extension (ECE) in nodes. The median follow-up was 95.9 months. There was no difference between the three arms (A versus B versus C) for 10-year locoregional control (LRC): 60.2% versus 61.4% versus 65.7%, p = 0.57; disease free survival (DFS): 37.4% versus 43.9% versus 39.6%, p = 0.40; or Overall Survival (OS): 39.7% versus 46.6% versus 40.4%, p = 0.40. There was no benefit of intensification with either modality in patients with any single adverse pathological factor. A benefit of intensification could be seen in patients with a combination of high-risk features: T3-T4 primary tumours with N2-N3 nodes along with ECE for DFS (Arm B versus Arm A HR) = 0.53, Arm C versus Arm A HR = 0.63) and OS (Arm B versus Arm A HR = 0.58, Arm C versus Arm A HR = 0.60). CONCLUSIONS: All optimally resected OCSCC with adverse features did not benefit from intensification of adjuvant therapy. Only a cohort of patients with a combination of high-risk features are likely candidates for intensification. CLINICAL TRIAL REGISTRATION: NCT00193843.

Nonsalivary Primary Adenocarcinomas of the Base of the Tongue: A Single Tertiary-Care Oncology Center Series of 6 Cases.

CONTEXT.­: Nonsalivary primary adenocarcinomas of the base of the tongue (PABOTs) are extremely rare and worth reporting. OBJECTIVE.­: To study the detailed clinicopathologic features of PABOT. DESIGN.­: Cases of PABOT diagnosed on pathology material were retrieved from the archived electronic surgical pathology records. RESULTS.­: Six cases in 4 men and 2 women (M:F ratio, 2:1), with an age range of 31 to 76 years, satisfied the criteria. The tumor epicenter was the base of the tongue in all (6 of 6; 100%), with extension to the epiglottis in 50% (3 of 6), nodal metastasis in 66.7% (4 of 6), and distant metastasis in 33.3% (2 of 6). On histology, all but one were pure adenocarcinoma. Five of 6 cases (83.3%) had a gastrointestinal (GI) phenotype, of which 2 (40%) had a colonic/lower-GI-type (small groups of cells floating in mucin, CK20+, SATB2+, and CDX2+) and 3 (60%) had an upper-GI-like adenocarcinoma (UGI-LA; malignant glands with intracellular mucin, CK7+) histology. Cystic structure suggestive of teratomatous origin was identified in 2 of 5 cases (40%), both with UGI-LA phenotype. The non-GI-type case had a unique histology with squamous differentiation in addition to adenocarcinoma areas, diffuse nuclear ß-catenin on immunohistochemistry, and a corresponding exon 3 CTNNB1 mutation. One patient succumbed to disease, and 4 are alive with disease (follow-up of 1-9 months after completion of therapy). CONCLUSIONS.­: We suggest using the broad term primary adenocarcinomas of the base of tongue (PABOTs), which can be further subdivided into colonic-type adenocarcinoma of the tongue and oral cavity, UGI-LA, and not otherwise specified categories, and reiterate a need for recognition and distinction of PABOT from salivary gland tumors. A subset originates from teratoid/duplication cysts, necessitating extensive sampling. Multicentric studies are essential to clinically and biologically prognosticate each of these categories.

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial.

BACKGROUND: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.

Comparison of Microalbuminuria Status in Type 2 Diabetes Mellitus Patients With Chronic Periodontitis: A Cross-Sectional Study.

Background Diabetes has increased the risk for various other ailments in various organs of the body. This can be contributing to periodontitis also as it is the sixth complication related to diabetes mellitus. There is a bidirectional relationship between both. Given the high global prevalence of type-2 diabetes mellitus (T2DM) with periodontitis, it is of great importance to determine the link between periodontitis and microalbuminuria in T2DM patients, which shows early renal disease. Methodology In the present study, a total of 500 patients having T2DM were assessed for periodontitis using Community Periodontal Index (CPI). Anthropometric and biochemical measurements were obtained. Blood samples were estimated for glycemic control tests such as fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and lipid profile. The subjects who participated in the study were categorized into three groups depending on the albuminuria level. The data were tabulated and analyzed using SPSS Statistics software (IBM Corp., Armonk, USA). Results Out of 500 T2DM subjects, 342 subjects had periodontitis. A statistically significant difference was found in FPG, HbA1c, total cholesterol (TC), triglycerides, and low-density lipoprotein (LDL) between subjects with periodontitis and without periodontitis using a t-test (p = <0.001). The prevalence of normoalbuminuria, micro-, and macroalbuminuria among periodontitis patients was 24.6%, 72.8%, and 2.6% respectively, and the Chi-square analysis revealed that was highly significant. In terms of albuminuria, one-way analysis of variance (ANOVA) revealed statistically significant differences among the periodontitis subjects for the following variables: inputs such as the number of teeth, diabetes mellitus (DM) duration, the level of LDL, and also the depth of the pocket. Intergroup comparison of variables among subjects with albuminuria using the statistical test of Tukey Post Hoc found that there is a significant difference between normoalbuminuria and microalbuminuria. CPI score, tooth mobility, smoking, education level, family income, tooth brushing duration, along with the use of other dental hygiene aids was also found to be statistically significant among subjects with periodontitis. Conclusion The study concluded that T2DM patients had a higher incidence of microalbuminuria among individuals with periodontitis. These subjects also had significantly higher HbA1c and FPG levels than subjects with normoalbuminuria. In addition, subjects with periodontitis exhibited a significant reduction in the total teeth numbers present in the case of albuminuria. The longitudinal correlation between DM, microalbuminuria, and periodontitis could be further investigated in detail to explore possible pathways.

Gender discrimination in surgical oncology: An in-house appraisal.

Introduction: Gender discrimination (GD) though rarely blatant, may present indirectly within a surgical department in the form of subtle inequities, differing standards, and bias. GD encompasses a wide spectrum including academic development, surgical opportunities and sexual harassment. Methods: We conducted an online survey to analyse the perceived incidence of GD in the surgical oncology department at a tertiary care cancer centre in India. The questionnaire consisted of 15 questions and was mailed to the entire department including trainees and faculty. Anonymity was maintained while collecting the data only of the participants' gender and whether they were faculty or trainee. Collated responses were analysed using proportions. Results: The questionnaire was sent out to 200 recipients of whom 56% (112/200) responded via an online survey. Respondents included 84% of faculty (42/50) and 46.6% of trainees (70/150). GD was perceived by 28% of female trainees (7/25) as compared to 6.6% of male trainees (3/45), whereas amongst faculty, GD was perceived by 26.6% of female faculty (4/15) compared to 14.8% of male faculty (3/27). Approximately 13% of our trainees and 12% of our faculty mentioned that GD affected their professional performance or mental well-being. GD was experienced in terms of work experience and opportunities by a majority of trainees (13%) and faculty (9.5%). There was a significant lack of awareness about recourse to an institutional grievance committee by trainees (47%) compared to faculty (14%). About 7% of trainees and 12% of faculty acknowledged that they may have been responsible for intentional/unintentional GD. Conclusion: Gender discrimination can present in subtle or overt fashion in surgical departments and requires active sustained efforts to allow both genders to feel equally empowered. Establishing a system to objectively evaluate gender equity while avoiding stereotyping for certain roles can help minimize GD.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Population-level Outcomes of Early Thyroid Cancers: A Need to Revisit Current Practice.

BACKGROUND: Early thyroid cancers have excellent long-term outcomes, yet the word "cancer" draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level. METHODS: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975-2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan-Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model. RESULTS: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P<0.001). Among the untreated T1a or T1b tumors, the risk of disease-specific death was 21 times lower than death due to other causes. There was no significant difference between T1a and T1b tumors nor across sex. The age-adjusted risk of death for the healthy US population was higher than for the population with thyroid cancer. Dynamic categorization demonstrated worsening outcomes up to 73 years, uninfluenced by sex or tumor size. For patients over 73 years of age, only tumors >26 mm impacted outcomes. CONCLUSION: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.

Critical Review of the Current Evidence on Sentinel Node Biopsy in Oral Cancer.

PURPOSE OF REVIEW: With contemporary surgery of the cN0 neck in early oral cancer becoming more selective, sentinel node biopsy (SNB) is gaining popularity as a possible alternate option to elective neck dissection (END). This review attempts to critically appraise the current evidence and highlight pertinent arguments for the use of SNB in early oral cancers. RECENT FINDINGS: Based on the recent randomized trials, it is imperative to perform an END at the time of primary resection in cN0 oral cancers. The much criticized false negative rate of SNB can be argued to be equal to the regional failure rate after END for pN0 necks, possibly making a case for SNB due to the reduction in number of neck dissections. There still lies ambiguity on the technique, protocols, and benefit of SNB over END. The role of extended histopathological techniques and the implications of micrometastasis and isolated tumor cells for treatment intensification remain questionable. Currently, SNB is an intermediary between routine imaging and END that needs to evolve before it can become a practice changing alternative to END itself. More efforts are needed in standardizing the protocols for SNB.

Definitive and adjuvant radiation therapy for external auditory canal and temporal bone squamous cell carcinomas: Long term outcomes.

INTRODUCTION: Primary Squamous Cell Carcinoma (SCC) of the external auditory canal (EAC) and Temporal Bone (TB) are rare entities with very few large reports on outcomes and toxicities. MATERIALS AND METHODS: A retrospective audit of all SCC of EAC/TB tumors treated with curative intent RT at our Institute between January 2007 and December 2019 was undertaken. The primary endpoint of the study was event-free survival (EFS). RESULTS: Eighty-nine patients were eligible for analysis. The median age was 54 years. The median follow-up of surviving patients was 61 months. Sixty-five patients received adjuvant RT, and 24 received definitive RT. Neoadjuvant Chemotherapy for aiding resectability was used in 12 patients, out of which 8 underwent surgery. The 5-year LRC, EFS, and OS were 66.2%, 57.8%, and 63.5%. The predominant pattern of failure was local (n = 36, 40.4%). Regional failure was seen in only five patients, none of which were in patients in whom elective nodal irradiation had been omitted post-operatively. On multivariable analysis adjuvant RT was associated with superior outcomes than definitive RT. Treatment with IMRT resulted in lower ≥ grade 2 late subcutaneous fibrosis (8.7% vs. 38.1%) compared to conventional/3D-CRT technique. CONCLUSIONS: Surgery followed by adjuvant therapy should remain the mainstay of treatment for EAC and TB SCC. IMRT should be the preferred modality for RT due to lower late morbidity. Elective nodal irradiation is routinely not warranted in the adjuvant setting for EAC and TB squamous cell carcinomas.