Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

INTRODUCTION: Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. METHODS: A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. RESULTS: Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. CONCLUSION: The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Endoscopic Sellar Defect Reconstruction with Avascular Modified Gasket Seal Technique for Sellar Tumors.

Watertight repair of the skull base defect is necessary during endonasal skull base surgery to avoid postoperative CSF leak (poCSFl) and consequent intracranial complications. Various techniques have been described for reconstructing sphenoid-sellar defects with varying success rates. We have described the immediate and long-term outcomes following the reconstruction of sphenoid-sellar defects with our technique. A retrospective analysis of the patients following transsphenoidal sellar surgery underwent barrier restoring reconstruction by multi-layered (inlay-overlay) with autologous thigh fat, fascia lata, fibrin glue, knitted collagen, and absorbable gelatin sponge (modified gasket seal technique). A total of 44 patients were included in the study (n = 44). Reconstruction with modified gasket seal technique was done for all patients. 26 (59.1%) had intraoperative CSF leak (ioCSFl), and 9 (20.4%) patients had grade 3 Esposito-Kelly ioCSFl requiring adjunct short-term pressure reducing procedure (Lumbar drain) intraoperatively. 11/44 (25%) had poCSFl, 7/11 patients with poCSFl were managed conservatively, and 4/11 patients required rescue second surgery and ventriculoperitoneal shunting. 1 (2.3%) had severe meningitis and succumbed to it. Pneumocephalus was seen in 6 (13.6%). Multivariate analysis showed that revision surgery, GH-secreting tumors, and defects extending to the suprasellar region had higher chances of poCSFl (p < 0.001). All 43 alive patients had no CSF leak on long-term follow-up. The modified gasket seal technique is a viable technique for endoscopic sellar reconstruction for ioCSFl with an immediate success rate of 79.6% and 97.72% in the long term in preventing the postoperative CSF leak with a 13.6% rate of meningitis.

Lower Rates of Hypocalcemia Following Near-Infrared Autofluorescence Use in Thyroidectomy: A Meta-Analysis of RCTs.

BACKGROUND: Iatrogenic injury of the parathyroid glands is the most frequent complication after total thyroidectomy. OBJECTIVE: To determine the effectiveness of near-infrared autofluorescence (NIRAF) in reducing postoperative hypocalcemia following total thyroidectomy. METHODS: PubMed, Scopus, and Google Scholar databases were searched. Randomised trials reporting at least one hypocalcemia outcome following total thyroidectomy using NIRAF were included. RESULTS: The qualitative data synthesis comprised 1363 patients from nine randomised studies, NIRAF arm = 636 cases and non-NIRAF arm = 637 cases. There was a statistically significant difference in the overall rate of hypocalcemia log(OR) = -0.7 [(-1.01, -0.40), M-H, REM, CI = 95%] and temporary hypocalcemia log(OR) = -0.8 [(-1.01, -0.59), M-H, REM, CI = 95%] favouring the NIRAF. The difference in the rate of permanent hypocalcemia log(OR) = -1.09 [(-2.34, 0.17), M-H, REM, CI = 95%] between the two arms was lower in the NIRAF arm but was not statistically significant. CONCLUSIONS: NIRAF during total thyroidectomy helps in reducing postoperative hypocalcemia. Level of evidence-1.

Assessment of the risk of malignancy in Bethesda III thyroid nodules: a comprehensive review.

The increasing prevalence of thyroid cancer emphasizes the need for a thorough assessment of risk of malignancy in Bethesda III nodules. Various methods ranging commercial platforms of molecular genetic testing (including Afirma® GEC, Afirma® GSC, ThyroSeq® V3, RosettaGX®, ThyGeNEXT®/ThyraMIR®, ThyroidPRINT®) to radionuclide scans and ultrasonography have been investigated to provide a more nuanced comprehension of risk estimation. The integration of molecular studies and imaging techniques into clinical practice may provide clinicians with improved and personalized risk assessment. This integrated approach we feel may enable clinicians to carefully tailor interventions, thereby minimizing the likelihood of unnecessary thyroid surgeries and overall crafting the optimal treatment. By aligning with the evolving landscape of personalized healthcare, this comprehensive strategy ensures a patient-centric approach to thyroid nodule and thyroid cancer management.

Effects of Primary Care-Led, Integrated Palliative Care for Medicare Patients in a Value-Based Model.

CONTEXT: Faced with a projected shortage of specialized palliative care physicians, scalable palliative solutions are required to better meet the aging population's needs. OBJECTIVES: To determine whether a multi-site, primary care-led, integrated palliative care model improves clinical, utilization, and economic outcomes. METHODS: Propensity score-matched comparison group formed from participants who were Medicare beneficiaries, died January 1, 2021-January 31, 2023, were patients of eight primary care practices that partner with agilon health, and enrolled in palliative care for at least seven days. Each practice operates in a value-based model, where primary care providers (PCPs) take on full-risk for the cost and quality of patient outcomes. Each program includes symptom management, defining goals of care/advance directives, PCP care coordination, and assistance with care transitions if patients enroll in hospice. RESULTS: Final sample included 1778 decedents, with 889 in both enrolled and matched cohorts, average age 83. Palliative care is associated with improved patient outcomes from palliative care enrollment until death, including 5.4 more days at home (p < 0.001), 0.4 fewer hospitalizations (p < 0.001), 17% fewer deaths in a hospital (p < 0.001), and $10,393 lower overall healthcare costs (p < 0.001). CONCLUSION: A primary care-led, integrated approach of delivering palliative care within a full-risk model can be an effective care delivery mechanism to meet the healthcare needs of an aging population by impacting patient outcomes and reducing avoidable utilization and cost at the end of life. These findings demonstrate that PCPs in a scaled, full-risk model can simultaneously improve care for patients while reducing costs to the healthcare system.

Comparing Mohs micrographic surgery and wide local excision in the management of head and neck dermatofibrosarcoma protuberans: a scoping review.

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma with a propensity for recurrence. Its management, particularly in the head and neck (H&N) region, presents unique challenges. This study aimed to evaluate the effectiveness of Mohs micrographic surgery (MMS) compared to wide local excision (WLE) in treating H&N DFSP and its impact on recurrence rates and tissue preservation. A comprehensive search was conducted in PubMed/MEDLINE, yielding 29 relevant studies. We included studies comparing MMS and WLE in adult patients with H&N DFSP and reporting local recurrence outcomes. Data were analyzed using random effects analysis, with a meta-analysis performed for comparative studies. Analysis of studies demonstrated a lower recurrence for MMS. Comparative analysis of five studies involving 117 patients showed a significantly lower recurrence rate in the MMS group (2%) compared to the WLE group (19%). Margin status varied between studies, with some achieving negative margins at shorter distances. In the management of H&N DFSP, MMS has emerged as a superior surgical technique, consistently associated with reduced recurrence rates and the potential for tissue preservation. The adoption of MMS should be considered for its capacity to achieve negative margins with fewer processing steps, particularly in anatomically complex regions like the H&N.

A Comparison of Harmonic Scalpel and Conventional Techniques for Thyroidectomy.

Thyroidectomy is one of the most frequently performed surgeries. Conventional techniques using electrocautery carry the risk of tissue injury. Recently, there has been increased use of harmonic scalpels in thyroid surgery. The harmonic scalpel utilizes ultrasonic shears for cutting and coagulation, thus minimizing thermal injury. The objective of our study was to determine differences in operative duration, hypocalcemia, and RLN palsy. This single-center retrospective comparative study included consecutive patients undergoing hemithyroidectomies using the harmonic scalpel and conventional technique in the past one year (n = 64, harmonic group = 28 and conventional group = 36). The mean operative duration for the harmonic scalpel group was 70.4 min, vs. 81.31 min for the conventional technique group, and the difference in mean duration was found to be 10.84 min (p = 0.027). There was no statistically significant difference in the rates of hypocalcemia (p = 0.751) or RLN palsy (p = 0.121). None of the patients in either group developed permanent hypocalcemia or RLN palsy. The use of a harmonic scalpel during thyroidectomy is safe. The overall surgical duration was reduced when the harmonic scalpel was used, and the complication rates were comparable to those of the conventional technique, making it a non-inferior technique for surgical intervention in thyroidectomy and warranting harmonic scalpel consideration as a valuable addition to the armamentarium of thyroid surgeons.

A Meta-analysis of Surgical Outcomes of T4a and Infranotch T4b Oral Cancers.

OBJECTIVE: To determine the overall surgical outcomes of infranotch T4b oral cancers and compare them with T4a oral cancers. METHODS: PubMed, EMBASE and Cochrane databases from 2000 to 2022 were systematically searched. Clinical studies reporting at least one outcome following curative surgery and adjuvant therapy for comparison of patients with either infranotch T4b (IN-T4b) or T4a tumour. The heterogeneity of the included studies was determined using Tau-squared, Chi-squared, and the Higgins I2 test. The random effects model was used to determine the log odds ratio (logOR). RESULTS: The systematic review comprised 11,790 patients from 16 included studies. Seven studies were included in the meta-analysis (n = 11,381). For IN-T4b patients, the pooled 2 and 5 year overall survival (OS) were 59.3% and 53.2%, 2 and 5 year disease-free survival (DFS) 57.9% and 48.4%, 2 and 5 year disease-specific survival (DSS) 72% and 68%, and 2 and 5 year local control (LC), 47% and 56%, respectively. There was no statistically significant difference in 2 year OS [logOR = 0.28 (-0.47, 1.03), p = 0.46, confidence interval (CI) = 95%], 5 year OS [logOR = 0.7 (-0.4, 1.8), p = 0.54, CI = 95%], 2 year DFS [logOR = 0.22 (-0.35, 0.79), p = 0.45, CI = 95%], 5 year DFS [logOR = 0.17 (-0.42, 0.77), p = 0.57, CI = 95%], 2 year LC [logOR = 0.47 (-0.33, 1.26), p = 0.25, CI = 95%] and 5 year LC [logOR = 0.34 (-0.31, 0.99), p = 0.31, CI = 95%] between IN-T4b and T4a oral cancers. CONCLUSION: Results of this meta-analysis suggest that IN-T4b oral cancers have similar outcomes to T4a oral cancers, which supports down-staging IN-T4b cancers to T4a cancers.

Observational Learning in Surgical Skill Development.

Observation plays a key role in the development of surgical skills, as it allows trainees to learn from experts and improve their performance through trial-and-error practice. This process, known as motor learning, involves the creation of new neural pathways that enable precise control of surgical instruments through hand movements. In recent years, there has been a shift towards minimally invasive surgery, which requires surgeons to continually learn new motor skills to control specialized instrumentation. Motor learning can be enhanced through repetition and the observation of expert performances. Observational learning is particularly useful when it is used in combination with physical practice, as it can provide hints and clues about important aspects of the task that may not be immediately apparent through verbal instruction alone. The role of mirror neurons, which are activated both when an action is performed and when it is observed, is also important in the process of observational learning. By understanding the mechanisms behind observational learning and the factors that influence its effectiveness, trainers can optimize the use of this method in surgical training.

Emergency Tracheostomy in Locally Advanced Anaplastic Thyroid Cancer.

Over 30% of cases may present with acute airway obstruction due to anaplastic thyroid cancer (ATC). In such situations, performing an emergency tracheostomy may be mandatory to save the life. A retrospective, single-centre study at our centre was conducted between 1 January 2021 to 31 December 2022. We had included 17 patients with asphyxia due to ATC and subsequently underwent tracheostomy for stridor. The overall survival (OS) ranged from 2 days to 16 months (median = 11 months). The 30-day mortality was 17.6%. One-year overall survival was 36%. A statistically significant difference in the OS among patients with distant metastasis and Shin grade IV tracheal infiltration (p < 0.001, Log Rank (Mantel-Cox), CI:95%). The degree of tracheal deviation correlated with the patent age group (Pearson chi-square (pc), p = 0.031), type of anaesthesia used local versus general (pc, p < 0.001) and site of tracheostoma (pc, p = 0.028). The degree of tracheal infiltration correlated with the presence of distant metastasis (pc, p = 0.01) and OS (pc, p = 0.013). Tracheostomy in patients with ATC is performed in extreme circumstances to support an airway. Patients often require isthmectomy to obtain adequate access for a tracheostomy, highlighting the importance of having a highly experienced surgeon involved. An attempt to perform the tracheostomy in the ward or the emergency room under local anaesthesia should be avoided. Patients and relatives should be educated to communicate evolving issues and tracheostomy care in the patient's best interests, given the unusual context of ATC. Level of evidence, IV.

Survival Outcomes in T3 Laryngeal Cancers: Primary Total Laryngectomy vs. Concurrent Chemoradiation or Radiation Therapy-A Meta-Analysis.

BACKGROUND: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. OBJECTIVE: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. METHODS: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. RESULTS: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= -0.88 (95% confidence interval (CI): -1.99 to 0.23), p = 0.12), 3-year OS (logOR = -0.6 (95% CI: -1.34 to 0.15), p = 0.11), and 5-year OS (logOR = -0.54 (95% CI: -1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= -1.2383 (95% CI: -2.1679 to -0.3087), p = 0.009), 3-year OS (-1.1262 (95% CI: -1.6166 to -0.6358), p < 0.001), and 5-year OS (-0.99 (95% CI: -1.44 to -0.53)), p < 0.001) between TL and RT alone. CONCLUSIONS AND SIGNIFICANCE: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment.

Standardizing the Head and Neck Cancer Treatment and Research.

Head and neck cancer requires a multidisciplinary approach, with standardized care being essential for consistent, high-quality treatment. Standardization involves evidence-based guidelines and protocols, and collaboration is necessary for research and improving outcomes. However, collaboration can be challenging due to various barriers. Collaboration can improve care by facilitating sharing of knowledge, access to technology, clinical trials, data sharing, funding and education. To improve collaboration, a shared vision, communication channels, guidelines, centralized database, training programs, culture of collaboration and funding should be established.

NLP AI Models for Optimizing Medical Research: Demystifying the Concerns.

Natural language processing (NLP) AI models have gained popularity in research; however, ethical considerations are necessary to avoid potential negative consequences. This paper identifies and explores the key areas of ethical concern for researchers using NLP AI models, such as bias in training data and algorithms, plagiarism, data privacy, accuracy of generated content, prompt and content generation, and training data quality. To mitigate bias, researchers should use diverse training data and regularly evaluate models for potential biases. Proper attribution and privacy protection are essential when using AI-generated content, while accuracy should be regularly tested and evaluated. Specific and appropriate prompts, algorithms, and techniques should be used for content generation, and training data quality should be high, diverse, and updated regularly. Finally, appropriate authorship credit and avoidance of conflicts of interest must be ensured. Adherence to ethical standards, such as those outlined by ICMJE, is crucial. These ethical considerations are vital for ensuring the quality and integrity of NLP AI model research and avoiding negative consequences.

Outcomes of Open Fronto-Facial Resection for Fungal Osteomyelitis of Frontal Bone.

INTRODUCTION: The second wave of coronavirus disease 2019 (COVID-19) led to the resurgence of opportunistic infections due to the injudicious use of steroids. Sinonasal mucormycosis was declared an epidemic in India during the pandemic. Mucormycosis was managed effectively by surgical debridement along with systemic amphotericin B. Currently, a resurgence of mucormycosis following initial treatment, in the form of fungal osteomyelitis of the frontal bone, is being seen in India. METHODS: This prospective study included 10 patients with fungal osteomyelitis of the frontal bone due to mucormycosis. All patients underwent surgical debridement of the sequestrum and involucrum, with systemic antifungal pharmacotherapy. RESULTS: The average duration of time until mucormycosis recurrence was 22 days following initial treatment (range 10-33 days). Patients presented with extracranial bossing following outer frontal cortex erosion (n=3), bicortical erosion (n=3), bifrontal involvement (n=2), dural involvement (n=3), and involvement of the brain parenchyma and prefrontal cortex (n=2). All cases underwent debridement of the entire sequestrous bone and involucrum until normal bone could be identified. The mean admission duration was 4 weeks (range 3-6 weeks). All treated patients are currently alive and without disease, confirmed by contrast-enhanced computed tomography. CONCLUSION: Based on our experience, the successful treatment of fungal osteomyelitis due to mucormycosis requires a four-pronged approach: early detection, multidisciplinary management of comorbidities, surgical debridement of necrotic bone, and adequate systemic antifungal therapy.

Molecular Insights into Oral Malignancy.

Squamous cell carcinoma constitutes around 95% of malignancies in the oral cavity. The 5-year overall survival has not substantially improved for oral cancers over the last few decades, despite several advances in diagnosis, imaging, and treatment modalities. With progressive improvement in knowledge of the molecular pathways, cancer therapy can now be individualized. Understanding the genetic processes and natural history of cancer has the scope to enhance the clinical outcomes. There has been a significant improvement in our understanding of oncogenesis, advances in molecular detection methods, and novel biomarkers for oral cancers in the past decade. Indicators of genomic instability, the existence of expression regulators such as miRNA, and several genes and protein markers can predict which premalignant lesions are likely to turn into cancer. The molecular biomarkers in oncology are fast evolving. Still, integrating novel molecular tests into clinical practice will require a better understanding of the genetic pathways that lead to malignancy. Our article investigates the most recent concepts and knowledge on oral carcinogenesis, malignant transformation, and molecular markers for oral cancers.

Correction to: Molecular Insights into Oral Malignancy.

[This corrects the article DOI: 10.1007/s13193-021-01431-4.].

Revision Thyroid Surgery.

The incidence of recurrence in well-differentiated thyroid malignancies range from 10 to 30%. It is estimated that about 31-46% of patients with differentiated thyroid cancer will have the persistent disease and 1.2-6.8% will have structural recurrences during post-operative monitoring, depending on the initial therapy and prognostic variables. It is challenging to decide on treatment versus active monitoring following repeated or persistent tumour detection. The biological factors of the tumour and the patient guide us in the overall decision-making. Revision thyroid surgery is technically challenging. The morbidity encountered during the revision surgery is related to the anatomy of the region undergoing dissection, the degree of fibrosis and scarring from prior surgery and the operating surgeon's experience. Successful comprehensive management of revision thyroid surgery needs a multi-disciplinary approach. This review article highlights the definition, indications for revision surgery, identification of recurrent disease, management of parathyroid and recurrent laryngeal nerves with neuromonitoring.

Multidisciplinary Management of COVID-Associated Mucormycosis Syndemic in India.

The study aimed to determine clinical presentation, contributing factors, medical and surgical management, and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). A cross-sectional, single-center study was conducted on patients receiving multidisciplinary treatment for mucormycosis following the second wave of COVID-19 pandemic from April to June 2021 in India. Clinicoepidemiological factors were analyzed, 30-day overall survival and disease-specific survival were determined, and t-test was used to determine the statistical significance. A total of 215 patients were included in the study, the cases were stratified into sino-nasal 95 (44.2%), sino-naso-orbital 32 (14.9%), sino-naso-palatal 55 (25.6%), sino-naso-cerebral 12 (5.6%), sino-naso-orbito-cerebral 16 (7.4%), and sino-naso-orbito-palato-cerebral 5 (2.3%) based on their presentation. A multidisciplinary team treated patients by surgical wound debridement and medical therapy with broad-spectrum antibiotics and amphotericin B. Across all disease stages, cumulative 30-day disease-specific survival is 94% (p < 0.001, intergroup comparison, Breslow (generalized Wilcoxon) CI 95%) and overall 30-day survival is 87.9% (p < 0.001, intergroup comparison, Breslow (generalized Wilcoxon) CI 95%) (censored). Early identification, triaging, and proper multidisciplinary team management with systemic antifungals, surgical debridement, and control of comorbidities lead to desirable outcomes in COVID-associated mucormycosis. The patients with intracranial involvement have a higher chance of mortality compared to the other group. Supplementary Information: The online version contains supplementary material available at 10.1007/s12262-021-03134-0.

HbA1c-Triggered Endocrinology Electronic Consultation for Type 2 Diabetes Management.

BACKGROUND: Electronic consultation (eConsultation) offers a potential mechanism to increase access to specialty care, address knowledge gaps, and overcome therapeutic inertia in patients with type 2 diabetes (T2DM) being managed by primary care physicians (PCPs). OBJECTIVE: To develop and implement a system to provide unsolicited endocrinology eConsult for T2DM patients with HbA1c 8.5-10.5% managed by PCPs. DESIGN: Cluster-randomized matched cohort study with implementation evaluation. PARTICIPANTS: PCPs affiliated with Massachusetts General Hospital (MGH). INTERVENTIONS: Unsolicited endocrinology eConsultation. MAIN MEASURES: The primary clinical outcome was mean change in HbA1c at 6 months. Secondary process outcomes included referral completion rate, prescription rates of glucose-lowering medications, differences in rate of other management recommendations, change in all glucose-lowering medications, and number of face-to-face endocrinology visits. KEY RESULTS: 161 PCPs were randomly assigned to intervention (n=81) and control (n=80) arms. eConsultations were triggered on 130 patients from intervention arm PCPs. Intervention arm patients had a 0.89 (SD 1.45) decrease in HbA1c compared to 0.69 (SD 1.32) decrease in the control arm (p=0.28). There were significant differences in prescribing of glucose-lowering medications between arms. There was a 19.3% increase in patients prescribed GLP-1 RA or SGLT2i in the intervention arm compared to a 6.9% increase in control (p=0.003). There were also significant increases in prescription rates of metformin (3.1% vs -3.1%, p=0.03) and sulfonylureas (1.5% vs -6.9%, p=0.03). At 6-month follow-up, the intervention arm had 13 in-person endocrinology visits compared to 29 (p=0.012) in the control arm. PCPs were more likely to accept recommendations regarding adherence to or dose adjustment of current medications than initiation of new medications. CONCLUSIONS: The implementation of an unsolicited endocrinology eConsult system for patients with poorly controlled T2DM is feasible. Unsolicited eConsultation was associated with increased prescribing of glucose-lowering medications without significant difference in HbA1c. TRIAL REGISTRATION: Clinicaltrials.gov registration: NCT03542084.

Pharyngocutaneous Fistula Following Primary Total Laryngectomy: a Meta-analysis.

Pharyngocutaneous fistula (PCF) is the most common complication which significantly increases morbidity. High-level evidence is lacking that determines the PCF rates in the primary laryngectomy. The main objective of this study was to systematically identify the factors leading to the PCF formation in primary laryngectomy. Human studies reporting at least one risk factor for developing PCF in patients undergoing primary total laryngectomy for laryngeal cancer were included. PubMed, EMBASE, and Cochrane databases were searched for the data extraction. Risk of bias assessment tool for non-randomized trial tool was used. Cochrane's Q test and Higgin's I 2-heterogeneity was applied. The Mantel-Haenszel and DerSimonian Laird method was employed. Odds ratio was calculated for each risk factor, a P-value < 0.05 was considered as statistically significant. PROSPERO registration CRD42021248382. The meta-analysis comprised a total of 2446 patients in 14 included non-randomized studies. The among the analyzed risk factors-comorbidities (OR 2.781, R: 1.892-4.088, P < 0.001), site of tumor (OR 4.485, R: 3.003-6.699, P < 0.001), low pre-operative hemoglobin (OR 3.590, R: 2.130-6.050, P < 0.001), low pre-operative albumin (OR 2.833, R: 1.596-5.031, P < 0.001), utilization of surgical staplers (OR 0.172, R: 0.064-0.460, P < 0.001) (protective effect), positive mucosal margin (OR 4.92 R: 1.90-12.75, P = 0.001). The risk factors for PCF in patients undergoing primary TL included comorbidities, hypopharyngeal involvement, pre-operative hemoglobin and albumin, stapler usage, and positive mucosal margin. Level of Evidence - III. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01581-z.