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BACKGROUND: Due to a delay in diagnosis by conventional techniques and high mortality, the development of a standardised and rapid non-culture-based technique is an unmet need in pulmonary, gastrointestinal, and disseminated forms of mucormycosis. Though limited studies have been conducted for molecular diagnosis, there are no established serologic tests for this highly fatal infection. OBJECTIVE: To develop and evaluate an indirect in-house enzyme-linked immunosorbent assay (ELISA) utilising antigens of Rhizopus arrhizus for detecting anti-Rhizopus antibodies (IgG and IgM) in sera of patients with mucormycosis. METHODS: We extracted both secretory and mycelial Rhizopus antigens using standardised protocols. Bradford assay was used for protein quantification. We then standardised an indirect ELISA using R. arrhizus mycelial and secretory antigens (10.0 µg/mL in bicarbonate buffer pH 9.2) for detecting anti-Rhizopus IgG and IgM antibodies in patient sera. We included patients with mucormycosis, other fungal infections, and healthy controls. Antibody index value (E-value) was calculated for each patient sample. RESULTS: Asparagine broth culture filtrate utilising 85% ammonium sulphate salt fractionation and mycelial homogenate grown in yeast extract peptone dextrose (YPD) broth precipitated with trichloroacetic acid (TCA) yielded a large amount of good-quality protein for the assay. We included 55 patients with mucormycosis (rhino-orbito-cerebral mucormycosis [ROCM, n = 39], pulmonary [n = 15], gastrointestinal [n = 1]), 24 with other fungal infections (probable aspergillosis [n = 14], candidiasis [n = 10]), and healthy controls (n = 16). The sensitivity of the antibody test for diagnosing mucormycosis ranged from 83.6-92.7% for IgG and 72.7-87.3% for IgM, with a specificity of 91.7-92.5% for IgG and 80-82.5% for IgM. The sera from patients with other fungal infections and healthy individuals did not show significant cross-reactivity. CONCLUSION: The detection of anti-Rhizopus IgG antibody performed significantly better in comparison to IgM-based ELISA for diagnosing both ROCM (sensitivity of 84.6% vs. 69.2%) and pulmonary cases (86.6% vs. 80.0%). More extensive studies are required to confirm our findings.
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Anticorpos Antifúngicos , Antígenos de Fungos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Imunoglobulina M , Mucormicose , Rhizopus , Sensibilidade e Especificidade , Testes Sorológicos , Mucormicose/diagnóstico , Mucormicose/microbiologia , Mucormicose/imunologia , Humanos , Rhizopus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Antígenos de Fungos/imunologia , Antígenos de Fungos/análise , Testes Sorológicos/métodos , Anticorpos Antifúngicos/sangue , Imunoglobulina M/sangue , Imunoglobulina G/sangue , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
The detection of the primary site in Carcinoma of Unknown Primary (CUP) is a challenging task which can significantly alter the course of management and also prognosis. Various modalities have been assessed with varying sensitivity and specificity. Imaging and cytological diagnosis have formed a key part of the diagnostic algorithm of CUP. Trans Oral Robotic Surgery offers the advantage of being both diagnostic as well as therapeutic with promising sensitivity and specificity and can form an integral part in the management of CUP. A prospective study was carried out at a tertiary care centre over a period of one year. Patients with unilateral neck swelling which was histopathologically proven squamous cell carcinoma neck metastasis were included in the study. They were evaluated with endoscopy and radiology according to the standard algorithm. When these failed to detect the primary, the patients underwent ipsilateral radical tonsillectomy and tongue base mucosal wedge biopsy via TORS. Post-operative histopathological examination was done on the resected specimens to detect the primary site. Transoral Robotic Surgery was able to localise primary in 50% of the patients enrolled in the study. Out of the primary site identified by TORS; 55.56% were located in the tonsil and 44.4% in the tongue base. TORS can offer promising detection rates of the occult primary in CUP and should form an integral part of the diagnostic algorithm.
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Perioperative high dose rate brachytherapy involves insertion of brachytherapy catheter over the tumor bed during surgical removal of disease followed by radiation in the postoperative period. It has applications in radiotherapy dose escalation or reirradiation and for extending the surgical margins. We report here initial results of treatment in five cases of locally advanced head and neck cancers.
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Purpose: Isolating circulating tumour cells (CTCs) from the blood is challenging due to their low abundance and heterogeneity. Limitations of conventional CTC detection methods highlight the need for improved strategies to detect and isolate CTCs. Currently, the Food and Drug Administration (FDA)-approved CellSearch™ and other RUO techniques are not available in India. Therefore, we wanted to develop a flexible CTC detection/isolation technique that addresses the limitation(s) of currently available techniques and is suitable for various downstream applications. Methods: We developed a novel, efficient, user-friendly CTC isolation strategy combining density gradient centrifugation and immuno-magnetic hematogenous cell depletion with fluorescence-activated cell sorting (FACS)-based positive selection using multiple CTC-specific cell-surface markers. For FACS, a stringent gating strategy was optimised to exclude debris and doublets by side scatter/forward scatter (SSC/FSC) discriminator, remove dead cells by 4',6-diamidino-2-phenylindole (DAPI) staining, and eliminate non-specific fluorescence using a "dump" channel. APC-labelled anti-CD45mAB was used to gate remaining hematogenous cells, while multiple epithelial markers (EpCAM, EGFR, and Pan-Cytokeratin) and an epithelial-mesenchymal transition (EMT) marker (Vimentin) labelled with fluorescein isothiocyanate (FITC) were used to sort cancer cells. The technique was initially developed by spiking Cal 27 cancer cells into the blood of healthy donors and then validated in 95 biopsy-proven oral squamous cell carcinoma (OSCC) patients. CTCs isolated from patients were reconfirmed by Giemsa staining, immuno-staining, and whole transcriptome amplification (WTA), followed by qRT-PCR. In vitro culture and RNA sequencing (RNA-Seq) were also performed to confirm their suitability for various downstream applications. Results: The mean detection efficiency for the Cal 27 tongue cancer cells spiked in the whole blood of healthy donors was 32.82% ± 12.71%. While ~75% of our patients (71/95) had detectable CTCs, the CTC positivity was independent of the TNM staging. The isolated potential cancer cells from OSCC patients were heterogeneous in size. They expressed different CTC-specific markers in various combinations as identified by qRT-PCR after WTA in different patients. Isolated CTCs were also found to be suitable for downstream applications like short-term CTC culture and RNA-Seq. Conclusion: We developed a sensitive, specific, flexible, and affordable CTC detection/isolation technique, which is scalable to larger patient cohorts, provides a snapshot of CTC heterogeneity, isolates live CTCs ready for downstream molecular analysis, and, most importantly, is suitable for developing countries.
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We describe a case of 27 year old male who presented with history of breathing difficulty with episodes of apnea for 8 years. He was suspected to have obstructive sleep apnea and a nocturnal polysomnography showed Apnea-Hypopnea index of 34/hour and the lowest oxygen saturation of 78% and severe snoring in the night. Continuous positive airway pressure (CPAP) machine was advised from local hospital and he used for 2 month. Indirect laryngoscopy done showed bilateral abductor cord palsy. Contrast enhanced magnetic resonance imaging (CEMRI) of brain and contrast enhanced computed tomography (CECT) of chest and neck was normal study. Posterior cordotomy of left cord was done using coblation with resolution of symptoms of OSA. Repeat nocturnal polysomnography showed apnea/hypopnea index 5 and lowest oxygen saturation of 95%.
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The cumulative survival for all stages in oral squamous cell cancers (OSCC) in the world remains poor despite the advances in management; hence, we conducted this study to evaluate the survival outcomes. This is a retrospective review and analysis of treatment, follow-up and survival records of 249 OSCC patients treated in our department from April 2010 to April 2014. Telephonic interviews were conducted for survival details for some patients who had not reported. Survival analysis was done using the Kaplan-Meier analysis, comparisons were done using log-rank test and multivariate analysis was conducted using the Cox proportional hazard model to find different variables (site, age, sex, stage and treatment) affecting overall survival (OS)/disease-free survival (DFS). Two-year and 5-year DFS for OSCC were observed to be 72.3% and 58.3% with mean survival of 63.17 months (95% CI: 58.342-68.002). Similarly, OS at 2 years and 5 years were 84.3% and 55.9% with mean survival of 65.143 months (95% CI: 60.143-69.601). Tumour site, patient age, stage of disease and treatment modality had a statistically significant hazardous effect on the overall and disease-free survival rates. The significant influence of age, site of tumour, stage of disease and modality of treatment required based on the clinic-pathologic risk factors on prognosis emphasizes the importance of early diagnosis through regular screening and early treatment which can be ensured with early referral, high clinical suspicion and awareness at the point of primary/secondary care.
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ABSTRACT: Resection of primary in carcinoma tongue is challenging as the tumor often spreads submucosal and deep in muscles. There are various Intraoperative tools available to guide tumor resection margins. We studied the use of intraoperative ultrasound-guided resection for obtaining free deep resection margins in cases of oral carcinoma tongue. To assess the feasibility of resection of tongue tumor using intraoral ultrasound intraoperatively. 5 patients of oral tongue squamous cell carcinoma were included in this prospective pilot study. Intraoral ultrasound-guided resection of the primary tongue tumor was done. The surgeon moved the probe over the tumor and focussed on the point of maximum invasion by the tumor. A 26 G needle was passed in the tongue at a point that was 10 mm away from the deepest point of infiltration. It marked the deepest plane of resection. Following the above marking, a resection of tumor was done. Deep surgical resection margin was found to be >5 mm (free) in all the USG-guided surgically resected primary tongue tumors on histopathological examination. We have found intraoperative ultrasonography a useful tool for the surgical resection of primary tongue tumours.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Humanos , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Margens de Excisão , Projetos Piloto , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Estudos Prospectivos , Língua/diagnóstico por imagem , Língua/cirurgia , Língua/patologiaRESUMO
Introduction Establishing and maintaining a cancer registry in a tertiary high volume centre is fraught with difficulty, inaccuracy and missed data entry. Further, the raw unstructured data must be converted into a structured digital data, so that scientists can identify trends in cancer diagnoses and treatment responses. Objective We test the feasibility of establishing a cancer registry of Head and Neck malignancy patients through a research oriented artificial intelligence (AI) enabled data collection platform, using its smartphone application version. Materials and Methods This prospective observational study was conducted in the Department of Otolaryngology & Head and Neck Surgery, Post Graduate Institute of Medical Education And Research, Chandigarh in collaboration with Departments of Radiotherapy and Community Medicine. After taking due clearance from the Institute ethical committee, HNC patients, who were biopsy proven, were enrolled from October 2019 up to March 2021. The obtained data was entered, followed up and analysed through Jiyyo Research application which is a commercially available dedicated research oriented AI enabled data collection platform. Results The Jiyyo Research site was browsed and after proper registration, the patient data was entered into a proforma/questionnaire. The entered patient details were browsed for review, follow up and addition of new information. The whole process of data capture for each patient, took approximately 5-8 min, while any updates or review for the same patient required less than a minute. Search and data retrieval was very quick, and can be done in 1-2 min. Through this platform, a total of 1214 HNC patients were collected, followed and analysed during the study period. Conclusion It was feasible to establish a Head and Neck Cancer Registry using an AI based smartphone app. This AI based tumor registry could benefit in further studies with longer follow up of 5 and 10 years and in future AI studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03173-3.
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Does use of Facial nerve monitors during parotidectomy decrease incidence of facial paralysis/paresis without use of facial paresis? This study was done to compare the incidence, grade and risk factors of facial palsy in patients undergoing parotidectomy for benign parotid lesions with and without use of facial nerve monitor. This is a retrospective study. Eighty parotid patients operated for benign parotid lesions from 2013 to 2020 were retrospectively analysed. Demography details, history of the patients, history of addictions, clinical examination findings, investigation findings like the biopsy report, FNAC report, imaging i.e., CT / MRI / USG, use of intraoperative facial nerve monitor, time taken to identify the facial nerve, postoperative facial nerve palsy, facial nerve stimulation test and recovery time were analysed. Fifty patients were operated without use of facial nerve monitor, and 30 patients were operated using facial nerve monitor. Postoperative facial nerve complications were seen in 28 out of 80 patients (35%). Postoperative facial nerve complications were observed in 5 out of 30 patients (20%) in whom facial nerve monitoring was used. Marginal mandibular nerve palsy was observed in 4 patients and 1 patient had weakness of both marginal mandibular and orbital branches. While in postoperative facial nerve complications were observed in 25 out of 50 patients (50%), marginal mandibular nerve palsy was observed in 15 patients (40%), grade 3 facial palsy was observed in 3 out of 50 patients (6%), and grade 4 facial palsy were observed in 2 out of 50 patients (4%). The use of intraoperative FNM significantly lowered the incidence of paralysis.
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The incidence of facial palsy in parotid surgeries is up to 50% transient and 17% complete facial palsy. Locating facial nerve trunk during parotid surgery can be tricky despite using the standard landmarks. During a cadaveric dissection, we came across a simple technique to identify the trunk of facial nerve which we have also tried to use it in clinical setting and found it to be useful. Parotidectomy was done in 12 cadaveric hemi-faces. The distance between the mastoid tip and the tympanic segment of facial nerve was measured. The distance of the facial nerve and mastoid tip and tympanomastoid suture and facial nerve was measured. The trunk of facial nerve was found to cross the tympanomastoid sulcus-mastoid tip at around 8-10 mm from the mastoid tip in 70% of the cases. We extrapolated this information in 5 cases of parotidectomy in operative setting. We were able to identify facial nerve trunk accurately in 4/5 cases. Imaginary line connecting the mastoid tip and tympanomastoid suture can be used to locate the probable position of the facial nerve trunk reliably during parotidectomy.
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BACKGROUND: To reduce the global burden of tobacco use, clinical guidelines support behavioral therapy and pharmacotherapy as preferred interventions for tobacco cessation. The evidence-based behavioral interventions has consistently shown to be impactful in community settings; however, its efficacy has not been established in hospital settings. The current study aims to investigate impact of trans-theoretical-based behavioral intervention package on tobacco users suffering from non-communicable diseases attending tertiary care settings of North India. METHODS/DESIGN: A two-arm randomized controlled trial (RCT) in a tertiary healthcare hospital will be performed. A total of 360 tobacco users attending NCD clinics in four departments, cardiology, neurology, pulmonary medicine, and ENT (otolaryngology), will be recruited over a period of 3 months. After ascertaining the eligibility criteria, they will be followed up to 6 months (1, 3, 6) for their tobacco use status, readiness to quit, nicotine dependence, stage of behavior change, and self-reported and biochemical validation (urine cotinine) for tobacco abstinence. Assignment of intervention including allocation concealment, sequence generation, and blinding will be done as per SPIRIT guidelines for RCT protocols. DISCUSSION: As no strong evidence exists about the effectiveness of tobacco cessation intervention in tertiary settings, the current study will build evidence about the similar interventions in such settings. TRIAL REGISTRATION: CTRI/2019/09/021406.
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Abandono do Hábito de Fumar , Abandono do Uso de Tabaco , Tabagismo , Terapia Comportamental/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Abandono do Hábito de Fumar/métodos , Atenção Terciária à Saúde , Abandono do Uso de Tabaco/métodos , Tabagismo/terapiaRESUMO
This report describes a novel and easy periosteal flap design for cochlear implantation. This technique has been used in 37 patients between June 2019 and August 2020. The patients have been followed up for a period of 2 months to 15 months. There were no flap related complications attributed to this flap. There was no wound hematoma, wound breakdown or implant migration. The flap design is safe, easy, less time consuming and results in better coverage of the receiver stimulator unit without any tension.
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BACKGROUND: The sudden surge of mucormycosis cases which happened during the second wave of COVID-19 pandemic was a significant public health problem in India. OBJECTIVES: The aim of this study was to analyse the clinico-epidemicological characteristics of the mucormycosis cases to determine the changes that had occurred due to COVID-19 pandemic. METHODOLOGY: A retrospective cross-sectional study was conducted at the Department of Otolaryngology Head and Neck Surgery, PGIMER, Chandigarh, India. Patients diagnosed with rhino-orbital mucormycosis were categorised into the following groups: Pre-pandemic(May 2019 to April 2020), Pandemic Pre-epidemic (May 2020 to April 2021) and Epidemic (1 May 2021 to 12 July 2021). The epidemiological, clinical and surgical data of all the patients were retrieved from the hospital records and analysed. RESULTS: The epidemic period had 370 cases, compared with 65 during pandemic period and 42 in the pre-pandemic period. Diabetes mellitus was seen in 87% of cases during epidemic period, 92.9% in the pre-pandemic period and 90.8% in the pre-pandemic pre-epidemic period. The proportion of patients suffering from vision loss, restricted extra-ocular movements, palatal ulcer and nasal obstruction was higher in the pre-epidemic groups, and the difference was significant (p, <.01). There was no history of oxygen use in 85.9% of patients and no steroid use in 76.5%. The death rates were the lowest during epidemic (10%). CONCLUSION: COVID-19 has caused a statistically significant increase in the number of mucormycosis infections. The mortality and morbidity which showed an increase during the first wave of COVID-19 decreased significantly during the epidemic period.
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COVID-19 , Mucormicose , COVID-19/epidemiologia , Estudos Transversais , Fungos , Humanos , Mucormicose/diagnóstico , Pandemias , Estudos RetrospectivosRESUMO
Conidiobolomycosis caused by Conidiobolus species is an uncommon infection restricted to tropical and subtropical regions, usually affecting immunocompetent individuals. More than half of pediatric cases of conidiobolomycosis across the globe are from India. We report a case of subcutaneous conidiobolomycosis in an adolescent with development delay who responded to combined therapy with itraconazole and saturated solution of potassium iodide.
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Conidiobolus , Zigomicose , Adolescente , Antifúngicos/uso terapêutico , Criança , Humanos , Itraconazol/uso terapêutico , Zigomicose/diagnóstico , Zigomicose/tratamento farmacológicoRESUMO
To find if an association could be established between Human Papilloma Virus (HPV) infection and oropharyngeal cancers (OPCs) in a group of patients known to be regular users of tobacco, and to determine the impact of HPV status on clinical outcomes.Case records of 212 patients with AJCC-7 (The American Joint Committee on Cancer 7th edition) stages II-IVB non metastatic squamous cell carcinoma of the oropharynx treated using radical radiotherapy with or without chemotherapy during the years 2015-2018 were retrieved. Formalin-fixed, paraffin-embedded blocks from oropharyngeal biopsies were available for 177 patients and were evaluated for p16 expression by immunohistochemical (IHC) staining. More than 50% nuclear staining with or without cytoplasmic staining was considered HPV+ . The association between tobacco use and HPV, as well as the influence of HPV status on survival outcomes were assessed. p16 expression was found to be positive in 23(13%) patients. Significant association was found between chewable tobacco usage and HPV positivity (p = 0.051). The median follow up was 20.5 months (range: 3-80). 5-year Overall Survival was 43.4% and 29.8% (p = 0.044) in HPV+ and HPV- patients, respectively. Local control was significantly better in HPV+ patients (38.6% vs. 25.3%, p = 0.049). There was also a trend towards improved Disease-free Survival in HPV+ patients (31 months vs. 15 months, p = 0.078). Though less in prevalence among the Indian population, improved outcomes in HPV+ OPC patients and widely available IHC HPV assays signifies the routine implementation of p16 testing in day-to-day clinical practice.
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Providing medical care using the telecommunication networks holds the promise of increased access and efficiency of healthcare particularly during global emergencies like the Coronavirus disease 2019 (COVID-19) pandemic. Most of the hospital setups worldwide have put telemedicine into practice ever since the onset of the COVID-19 pandemic. This study aimed at assessing the effectiveness of Tele-otolaryngology (TO) at a tertiary care centre during the pandemic lockdown. A validated patient feedback questionnaire was developed and distributed to 2577 patients who utilised the TO mobile health service at our institute. Patient feedback-based assessment of TO effectiveness during COVID-19 lockdown was carried out. The validated questionnaire in English and Hindi was statistically robust with Cronbach's alpha value of 0.808 and 0.886 respectively. 1751 patients completed their feedback to the questionnaire. 97.5% utilised WhatsApp for TO consultation. 15.2% patients were detected of Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection with TO guidance. Up to 75% patients had a positive response to the questionnaire and 91.1% opined of savings achieved either with travel time, cost incurred or the treatment time. With respect to patient health status, 71.5% recovered, 20.1% had no change and 8.4% deteriorated with a mortality rate of 1.65%. Telehealth in otolaryngology during the COVID-19 pandemic lockdown was indispensable in managing exigencies. Redesigning of clinical protocol and technical constraints, clinician training and a validated patient feedback questionnaire would effectively bestow upon the global emergencies.
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Perioperative high dose rate brachytherapy is a radiotherapy treatment technique which involves intraoperative insertions of brachytherapy catheters into the tumor bed during the surgical resection followed by treatment in the post-operative period. We report here two cases to highlight its use in the primary treatment and reirradiation of head and neck cancers.
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INTRODUCTION: Despite good surgical knowledge of the anatomy of parotid gland and meticulous surgical technique, the incidence of facial palsy in parotid surgeries is up to 26.7% transient and 1.7% complete facial palsy(1). The risk of facial palsy increases further in malignant and revision cases. METHOD: Superficial parotidectomy was done in 14 cadaveric hemi faces in 10 cadavers. Posterior auricular artery and its stylomastoid branch was dissected and facial nerve trunk was identified in all cases. The relationship of posterior auricular artery along with its stylomastoid branch with the facial nerve trunk was studied and recorded. RESULT: Posterior auricular artery was found running inferior to the facial nerve trunk in 12 cadaveric dissection while the posterior auricular artery was found crossing below the main trunk of facial in 2 cadaver dissection. The average distance between PAA and facial nerve trunk was 7 mm (2-14âmm) Stylomastoid artery was found arising from Posterior auricular artery in 12 of 14 and it was found running medial to the facial nerve trunk in all the 8 cadavers. CONCLUSION: Post auricular artery can be used as another landmark for identification of the main trunk of facial nerve in parotid surgeries.
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Nervo Facial , Glândula Parótida , Artérias , Cadáver , Nervo Facial/anatomia & histologia , Estudos de Viabilidade , Humanos , Glândula Parótida/cirurgiaRESUMO
Despite widespread popularity of navigation and angled endoscopes in endonasal endoscopy, there are hardly few studies on their efficacy with the extent of resection or retreatment. This is probably the first study to assess the independent impact of these adjuncts among pituitary tumors. Patients with pituitary tumors undergoing endonasal endoscopy were prospectively studied for their demographics, clinico-radiological features, intraoperative use of navigation, and angled endoscopes, in relation to gross total resection (GTR), near total resection (NTR), endocrine remission, and retreatment. Pertinent statistical analyses were performed. Among a total of 139 patients, navigation and angled endoscopes could be used in 54 and 48 patients, respectively, depending upon their availability rather than chosen as per the case. There was no significant difference in baseline characteristics in relation to their use. The surgeon's perception of immediate benefit was noted among 51.9% while using navigation. The use of angled endoscopes towards the end of resection could help with additional tumor removal in 62.5% of patients. Overall, the use of navigation resulted in a significantly higher GTR (80.8% vs. 59.7%, OR 2.83, p = 0.01), a higher GTR/NTR (86.5% vs. 70.8%, OR 2.65, p = 0.04), and a lower retreatment rate (7.7% vs. 20.8%, OR 3.15, p = 0.05) than the others. In functioning tumors with cavernous sinus invasion, navigation had significantly increased remission rates (69.2% vs. 0%, p = 0.03). The use of angled endoscopes yielded a significantly higher GTR/NTR (91.7% vs. 70.6%, p = 0.04) and a lower retreatment rate (0% vs. 15.7%, p = 0.05) among only non-functioning adenomas. In multivariate analyses, the use of neuronavigation had a significant association with both GTR and retreatment rates (p values 0.005 and 0.02 respectively), independent of other confounding factors. The elective intraoperative use of navigation has a significant independent impact on the extent of resection and retreatment overall. While navigation results in better remission rates among functioning tumors with cavernous sinus invasion, angled endoscopy has a significant association with surgical outcomes in non-functioning tumors.