Publications by authors named "Eitan Prisman"

46 Publications

A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer.

Front Endocrinol (Lausanne) 2021 10;12:686996. Epub 2021 Jun 10.

Department of Otolaryngology and Head and Neck Surgery, University Health Network and University of Toronto, Toronto, ON, Canada.

Background: The traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.

Methods: This is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient's choice. Our primary objective is to determine the rate of 'failure' of disease management in respective AS and surgical arms as defined by: i) AS arm - surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.

Discussion: The results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.

Registration Details: This prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery.
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http://dx.doi.org/10.3389/fendo.2021.686996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237853PMC
June 2021

Proceedings of the Canadian Thyroid Cancer Active Surveillance Study Group 2019 national investigator meeting.

J Otolaryngol Head Neck Surg 2021 Jun 25;50(1):40. Epub 2021 Jun 25.

Department of Medicine, Division of Endocrinology, University Health Network, University of Toronto, Toronto, Canada.

Active surveillance (AS) in the management of small, low risk papillary thyroid cancer (PTC) as an alternative option to thyroidectomy, is an area of active research. A national Canadian study is proposed to evaluate the long-term outcomes of patients with small, low risk PTC who choose AS or surgery. This letter describes the proceedings of a national investigator meeting to plan the study.
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http://dx.doi.org/10.1186/s40463-021-00514-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228934PMC
June 2021

Versatility of a single piece scapular tip and lateral border free flap for mandibular reconstruction: A virtual study on angle correspondence.

Oral Oncol 2021 Jun 14:105379. Epub 2021 Jun 14.

Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, University of British Columbia, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.oraloncology.2021.105379DOI Listing
June 2021

Prognostic value and cost benefit of HPV testing for oropharyngeal cancer patients.

Oral Dis 2021 Jun 15. Epub 2021 Jun 15.

Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.

Objectives: High-risk human papillomavirus (HR-HPV) can cause oropharyngeal squamous cell carcinoma (OpSCC). The revised 8 edition of the AJCC Staging Manual now stages OpSCC by incorporating p16 immunohistochemistry (IHC), the surrogate marker for HPV status. This study assessed the prognostic values of p16 and HPV markers.

Methods: We identified 244 OpSCC patients diagnosed between 2000-2008 from the British Columbia Cancer Registry with enough tissue to conduct experiments. Formalin-fixed, paraffin-embedded tissue sections were stained for p16 IHC, RNA in situ hybridization (ISH) HPV 16 and 18, and DNA ISH HR-HPV. Electronic charts were reviewed to collect clinical and outcome data. Combined positive RNA and/or DNA ISH was used to denote HPV status.

Results: HPV was positive among 77.9% of samples. Using HPV as the benchmark, p16 IHC had high sensitivity (90.5%), but low specificity (68.5%). Distinct subgroups of patients were identified by sequential separation of p16 then HPV status. Among both p16-positive and p16-negative groups, HPV-positive patients were younger, more males, and had better clinical outcomes, especially 5-year overall survival. We further evaluated the technical costs associated with HPV testing.

Conclusion: HPV is more prognostic than p16 for OpSCC. Clinical laboratories can adopt HPV RNA ISH for routine analysis.
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http://dx.doi.org/10.1111/odi.13938DOI Listing
June 2021

The effect of prior radiation on the success of ventral skull base reconstruction: A systematic review and meta-analysis.

Head Neck 2021 May 11. Epub 2021 May 11.

Department of Otolaryngology - Head & Neck Surgery, M. D. Anderson Cancer Center, Houston, Texas, USA.

The incidence of cerebrospinal fluid leak after ventral skull base reconstruction is a primary outcome of interest to skull base surgeons. Exposure to pre-operative radiation may put patients at an increased risk of skull base reconstructive failure. A systematic search identified studies which included patients receiving ventral skull base reconstruction in the setting of pre-operative radiation. A meta-analysis using a random effects model was conducted to estimate an odds ratio of cerebrospinal fluid (CSF) leak in patients exposed to pre-operative radiation. A meta-analysis of 13 studies demonstrated that the odds ratio of CSF leak was 1.73 (95% CI 0.98-3.05). The majority of studies (77%) used vascularized tissue grafts for reconstruction. We identified an increased incidence of CSF leak among patients undergoing ventral skull base reconstruction after prior radiation therapy, although not of statistical significance. Skull base surgeons should exercise caution when planning reconstruction in this population.
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http://dx.doi.org/10.1002/hed.26709DOI Listing
May 2021

Maxillectomy defects: Virtually comparing fibular and scapular free flap reconstructions.

Head Neck 2021 May 7. Epub 2021 May 7.

Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Background: This study virtually compares patient-specific fibular and scapular reconstructions for maxillectomies.

Methods: Nine maxillectomy defects were created on 10 maxillas and virtually reconstructed with patient-specific fibulas and scapulas. Reconstructions were compared for restoring midface cephalometrics, dental implantability, and pedicle length.

Results: Of 90 maxillectomy defects, the vertically oriented scapula provided improved orbital floor and maxillary height reconstructions (p < 0.001), albeit at the cost of dental implantability compared to the fibula (p < 0.001). In two defects crossing the midline, the fibula, allowing for more osteotomies, provided improved maxillary projection. In the remaining three defects crossing the midline, the horizontally oriented scapula was comparable to the fibula. Fibular and scapular reconstructions were amenable for dental implantation and had similar pedicle lengths, although favoring scapula in extensive defects.

Conclusion: Fibular and scapular reconstructions of maxillectomy defects provide unique strengths. This virtual analysis can guide a goal-oriented reconstruction based on defect type and patient-specific goals.
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http://dx.doi.org/10.1002/hed.26731DOI Listing
May 2021

Treatment and outcomes of nasopharyngeal carcinoma in a unique non-endemic population.

Oral Oncol 2021 03 24;114:105182. Epub 2021 Jan 24.

Division of Otolaryngology - Head and Neck Surgery, University of British Columbia, 4(th) floor, Gordon and Leslie Diamond Health Care Center, 2775 Laurel Street, Vancouver, British Columbia V5Z1M9, Canada.

Objective: Nasopharyngeal carcinoma (NPC) is common in Southeast Asia. Due to the influx of immigrants from this region, the incidence in British Columbia is increasing. Current literature from non-endemic populations encompasses heterogeneous cohorts. This study examines NPC in a North American population, with a high incidence, to understand the population's characteristics, treatment outcomes and recurrence patterns.

Methods And Materials: A retrospective analysis of patients treated for primary and recurrent NPC over 15-years. Regression analyses were used to identify predictors of disease recurrence and death. A subgroup analysis of the locoregional recurrence cohort was conducted. Five-year survival outcomes were determined.

Results: 601 patients were included. Asian ethnicity comprised 77% and the majority had non-keratinizing carcinoma (81%). In total, 19.3% of patients experienced recurrence: 58% local, 22% regional and 20% distant. Five-year overall survival was 70%. Smoking, advancing T-stage, poorer performance status and advanced overall stage were all associated with worse overall survival (p < 0.05). Asian ethnicity improved overall survival but not recurrence free survival. Similar features in addition to non-keratinizing histology were associated with increased locoregional recurrence (p < 0.05). Competing risk analysis indicated radiotherapy alone had a higher recurrence relative to chemoradiotherapy (HR 1.91, CI 1.17-3.09, p = 0.01).

Conclusions: We report the largest study evaluating treatment and outcomes of NPC in a non-endemic population. This unique population falls between described endemic and non-endemic populations. Non-keratinizing pathology and primary radiotherapy did not affect survival; however, both had a propensity for recurrence. Finally, patients experienced more locoregional and less distant recurrence, supporting that this cohort may be amenable to curative salvage therapy.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105182DOI Listing
March 2021

Muscle invasion in oropharyngeal carcinoma undergoing transoral robotic surgery.

Head Neck 2021 04 23;43(4):1194-1201. Epub 2020 Dec 23.

Division of Otolaryngology - Head & Neck Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Backgrounds: Pathologic features of oropharyngeal squamous cell carcinoma (OPSCC) treated with trans-oral robotic surgery predict prognosis and adjuvant therapy. We hypothesized that pathologic muscle invasion (pMI) is associated with poor pathological markers.

Methods: Retrospective review of surgically treated OPSCC to identify pMI and its association with poor pathologic markers.

Results: pMI was present in 12/37 patients, and compared to non-pMI, was associated with higher rates of lymphovascular invasion (75% vs. 36%, p = 0.03), perineural invasion (16.7% vs. 0%, p = 0.04), extranodal extension (66.7% vs. 20%, p < 0.01), and tumor stage (8.3% vs. 48% pT1, 75% vs. 52% pT2 and 16.7% vs. 0% pT3). pMI was associated with having a positive margin on main specimen (41.7% vs. 12%, p = 0.04) but not after considering additional margins.

Conclusions: Muscle invasion was associated with higher pathologic tumor staging, poor pathologic factors, and higher rates of positive margin on main specimen.
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http://dx.doi.org/10.1002/hed.26582DOI Listing
April 2021

Predicting the Premorbid Shape of a Diseased Mandible.

Laryngoscope 2021 03 17;131(3):E781-E786. Epub 2020 Aug 17.

Division of Otolaryngology, Department of Surgery, University of British Columbia, Gordon and Leslie Diamond Health Care Centre, Vancouver, British Columbia, Canada.

Objectives/hypothesis: Virtual surgical planning (VSP) for reconstructions of advanced mandibular neoplasms that have distorted the contour of the mandible is challenging, as the premorbid shape of the mandible is unknown. We introduce a novel modeling technique, based on a statistical shape model (SSM), that has learned the shape of a normal mandible from a set of 84 mandibles, such that given a diseased mandible, the model can determine its premorbid shape.

Methods: Eighty-four control mandibles were used to generate an SSM. Various mandibular defects were created, and the SSM was applied to predict the shape of the original mandible. The predicted and original shape of the defect were compared for accuracy using volumetric overlap and Hausdorff distance. All mandibular VSP cases in the past 2 years were reviewed to identify those that required virtual preprocessing due to significantly distorted mandibular contours. The SSM was compared to those cases requiring preprocessing and highlighted in one prospective VSP.

Results: The average volumetric overlap and Hausdorff distance between the defect replacement and the defect are 73.9% ± 13.3% and 4.51 mm ± 2.65 mm, respectively. The SSM is more accurate for smaller defects, and those not including the condyle. Ten out of 40 VSP cases required preprocessing using four different techniques. Qualitatively, the SSM outperformed those preprocessing techniques applied in the retrospective cases.

Conclusions: The SSM can accurately predict the premorbid shape of a distorted mandible and is superior to current preprocessing techniques. The SSM was successfully applied to a retrospective series and one prospective index case.

Level Of Evidence: 4 Laryngoscope, 131:E781-E786, 2021.
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http://dx.doi.org/10.1002/lary.29009DOI Listing
March 2021

A Unique Case of Primary EBV-Positive, HPV-Negative Nasopharyngeal Carcinoma Located in the Tonsil.

Head Neck Pathol 2020 Oct 21. Epub 2020 Oct 21.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Vancouver General Hospital, Vancouver, BC, Canada.

Nasopharyngeal carcinomas (NPC) are non-keratinizing squamous cell carcinomas of the nasopharynx associated with Epstein-Barr virus (EBV). When occurring outside of the nasopharynx, they are referred to as lymphoepithelioma-like carcinomas (LELCs) and present the same morphology as NPC. LELC have been described in other head and neck regions such as the salivary glands and the soft palate. LELC can also occur in the oropharynx, are associated with human papillomavirus (HPV) and are typically negative for EBV. We herein present a unique case of a 78-year-old Chinese male with EBV-positive, HPV-negative NPC of the left tonsil. His presenting symptom was a left-sided lymph node. There was no evidence of nasopharyngeal lesion seen on physical examination, PET and MRI. The patient was treated with curative-intent external beam radiotherapy which delivered 70 Gy (Gy) to the gross tumour and lymph nodes, and 56 Gy electively to the ipsilateral neck using a volumetric modulated arc therapy technique. This is the first case of primary tonsil EBV-positive NPC described in the literature.
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http://dx.doi.org/10.1007/s12105-020-01237-wDOI Listing
October 2020

Clinical evaluation of an automated virtual surgical planning platform for mandibular reconstruction.

Head Neck 2020 12 1;42(12):3506-3514. Epub 2020 Aug 1.

Division of Otolaryngology, Department of Surgery, University of British Columbia, Gordon and Leslie Diamond Health Care Centre, Vancouver, British Columbia, Canada.

Background: Virtual surgical planning (VSP), via commercial services or developed in-house, has been applied to facilitate head and neck reconstruction. We evaluate a custom, automated planning software.

Methods: Prospectively, VSP of 25 consecutive patients undergoing segmental mandibular reconstruction was performed. Postoperative CT was used to assess structural accuracy of VSP. Operative time, length of stay, and complication rate of the prospective cohort were compared with those of 25 consecutive retrospective historical cases.

Results: The deviations between the plan and execution in mandibular width, projection, and volumetric overlap were 2.32 ± 3.91, 2.39 ± 1.72, and 0.59 ± 0.51 mm respectively. Compared with historical data, there was a significant reduction in operative time and length of stay, and no significant difference in complication rates.

Conclusion: This is the largest prospective series evaluating an in-house VSP workflow for mandibular reconstruction and the first clinical evaluation of an automated planning platform.
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http://dx.doi.org/10.1002/hed.26404DOI Listing
December 2020

Characterizing Motor Control of Mastication With Soft Actor-Critic.

Front Hum Neurosci 2020 26;14:188. Epub 2020 May 26.

Electrical and Computer Engineering Department, University of British Columbia, Vancouver, BC, Canada.

The human masticatory system is a complex functional unit characterized by a multitude of skeletal components, muscles, soft tissues, and teeth. Muscle activation dynamics cannot be directly measured on live human subjects due to ethical, safety, and accessibility limitations. Therefore, estimation of muscle activations and their resultant forces is a longstanding and active area of research. Reinforcement learning (RL) is an adaptive learning strategy which is inspired by the behavioral psychology and enables an agent to learn the dynamics of an unknown system via policy-driven explorations. The RL framework is a well-formulated closed-loop system where high capacity neural networks are trained with the feedback mechanism of rewards to learn relatively complex actuation patterns. In this work, we are building on a deep RL algorithm, known as the Soft Actor-Critic, to learn the inverse dynamics of a simulated masticatory system, i.e., learn the activation patterns that drive the jaw to its desired location. The outcome of the proposed training procedure is a parametric neural model which acts as the brain of the biomechanical system. We demonstrate the model's ability to navigate the feasible three-dimensional (3D) envelope of motion with sub-millimeter accuracies. We also introduce a performance analysis platform consisting of a set of quantitative metrics to assess the functionalities of a given simulated masticatory system. This platform assesses the range of motion, metabolic efficiency, the agility of motion, the symmetry of activations, and the accuracy of reaching the desired target positions. We demonstrate how the model learns more metabolically efficient policies by integrating a force regularization term in the RL reward. We also demonstrate the inverse correlation between the metabolic efficiency of the models and their agility and range of motion. The presented masticatory model and the proposed RL training mechanism are valuable tools for the analysis of mastication and other biomechanical systems. We see this framework's potential in facilitating the functional analyses aspects of surgical treatment planning and predicting the rehabilitation performance in post-operative subjects.
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http://dx.doi.org/10.3389/fnhum.2020.00188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264096PMC
May 2020

Treatment for Recurrent Differentiated Thyroid Cancer: A Canadian Population Based Experience.

Cureus 2020 Feb 27;12(2):e7122. Epub 2020 Feb 27.

Medical Oncology, BC Cancer, Vancouver, CAN.

Introduction: Management of recurrent differentiated thyroid cancer (DTC) may include surgery, radioactive iodine (RAI), and external beam radiotherapy (EBRT). Systemic therapy may also be offered for RAI-refractory DTC. The study objective was to review patterns of practice in British Columbia (BC) for treatment of recurrent DTC, assess rates of RAI-refractory disease, and evaluate outcomes.

Methods: BC Cancer provides cancer care to a population of 4.6 million. A retrospective review of all patients with DTC stage I-IVB disease referred to BC Cancer from 2009 to 2013 was conducted. Patient and DTC characteristics, locoregional and distant recurrence, surgical management, RAI, EBRT, and systemic therapy details were retrospectively collected. Relapse-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were calculated using the Kaplan-Meier method.

Results/discussion: Some 1062 DTC patients were identified. Median follow-up was 4.1 years. Baseline characteristics: female 74%, median age 50, papillary/follicular/Hurthle cell 92%/6%/2%. Stage at presentation: I 60%, II 8%, III 22%, IVA/IVB 10%. Locoregional and/or distant recurrence occurred in 136 patients (13%). Locoregional recurrence (n=118) was treated with surgery +/- RAI or EBRT 48%, RAI +/- EBRT 40%, EBRT alone 1%, 11% were observed without treatment. Some 27 patients had a second cancer recurrence. Some 37 patients (3%) developed distant metastatic disease and common sites of distant metastases were: lung 76%, bone 30%, and liver 8%. Some 27 cases (2%) were deemed RAI-refractory. Some six patients (0.6%) received systemic therapy with a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). Five-year RFS was calculated to be 82%, OS 95%, and DSS 98% for the study population.

Conclusions: In our population-based study cohort, 87% of patients were rendered disease-free by primary disease management. Multi-modality treatment of locoregional recurrence facilitated disease-free status in the majority of patients (67%). RAI-refractory disease developed in 2% of patients and despite a significant number of metastatic recurrences, only a small number of patients received systemic therapy.
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http://dx.doi.org/10.7759/cureus.7122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105067PMC
February 2020

Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

BMC Cancer 2020 Feb 14;20(1):125. Epub 2020 Feb 14.

Department of Radiation Oncology, London Health Sciences Centre, Western University, 800 Commissioners Rd. E, London, Ontario, N6A 5W9, Canada.

Background: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches.

Methods: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity.

Discussion: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials.

Trial Registration: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.
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http://dx.doi.org/10.1186/s12885-020-6607-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023689PMC
February 2020

Predicting the Number of Fibular Segments to Reconstruct Mandibular Defects.

Laryngoscope 2020 11 30;130(11):E619-E624. Epub 2019 Dec 30.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Objectives: Several classification schemes have been proposed to categorize mandibular defects following surgical resection; however, there is a paucity of data to guide an optimal reconstruction. This study examines the feasibility of using a geometric algorithm to simplify and determine the optimal reconstruction for a given mandibular defect. This algorithm is then applied to three different mandible defect classification schemes to correlate the defect type and number of bony segments required for reconstruction.

Methods: Computed tomography (CT) scans of 48 mandibles were decomposed into curvilinear representations and analyzed using the Ramer-Douglas-Peucker algorithm. In total, 720 mandibular defects were created and subsequently analyzed utilizing three commonly referenced classification systems. For each defect, the number of bony segments required to reconstruct each defect was computed.

Results: A wide variance in the number of segments needed for optimal reconstruction was observed across existing classifications. A six-segment total mandible reconstruction best reconstituted mandibular form in all 48 mandibles.

Conclusion: Defect classification schemes are not adaptable to predicting the number of fibula segments required for a given defect. Additionally, cephalometric templates may not be applicable in all clinical settings. The Ramer-Douglas-Peucker algorithm is well suited for providing case-specific predictions of reconstruction plans in a reproducible manner.

Level Of Evidence: IV Laryngoscope, 130:E619-E624, 2020.
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http://dx.doi.org/10.1002/lary.28473DOI Listing
November 2020

Outcomes of free flap reconstructions with near-infrared spectroscopy (NIRS) monitoring: A systematic review.

Microsurgery 2020 Feb 30;40(2):268-275. Epub 2019 Oct 30.

Division of Otolaryngology-Head & Neck Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Free flap failure or vascular compromise remains a dreadful complication of microvascular free tissue transfer. Near-infrared spectroscopy (NIRS) is a novel technique for free flap monitoring that has the propensity for early detection of vascular compromise when compared to the current gold standard, clinical monitoring (CM). The objective of this review is to evaluate the efficacy of a NIRS system in the postoperative monitoring of free flaps and its effect on flap salvage.

Methods: A comprehensive literature review was performed including English-language articles evaluating the use of NIRS in free flap monitoring. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), OVID, and Web of Science were searched upto December 2017.

Results: A total of 590 articles were identified, and 10 articles were included for analysis. Overall, flaps with vascular compromise monitored with NIRS had a significantly higher salvage rate of 89% compared with a salvage rate of 50% in the flaps monitored by CM alone (p < .01). Partial loss occurred in 15% of the successful salvages in the NIRS group versus 80% with CM alone (p < .01). Detection of vascular compromise by NIRS preceded clinical signs on average by 82 ± 49 min. NIRS was accurate in detecting compromised flaps with a low false-positive and false-negative rate.

Conclusion: Despite lack of robust data, NIRS has the potential to be an objective, accurate, and continuous postoperative free flap monitoring technique with a greater flap salvage rate than CM alone.
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http://dx.doi.org/10.1002/micr.30526DOI Listing
February 2020

Headache Outcomes After Treatment of Unruptured Intracranial Aneurysm: A Systematic Review and Meta-Analysis.

Stroke 2019 12 14;50(12):3628-3631. Epub 2019 Oct 14.

From the Division of Neurosurgery, University of British Columbia, Vancouver, Canada (C.D., S.P., G.R., C.S.H., P.A.G.).

Background and Purpose- While unruptured intracranial aneurysms may be discovered incidentally in the workup of chronic headache, it remains unclear whether their treatment ultimately impacts headache severity. We aim to conduct a systematic review and meta-analysis assessing headache severity after treatment of unruptured intracranial aneurysm. Methods- MEDLINE and EMBASE were systematically reviewed. Results- Data from 7 studies met inclusion criteria (309 nonduplicated patients). The standard mean difference in pre- and post-intervention headache severity was estimated at -0.448 (95% CI, -0.566 to -0.329) under a random effects model. No significant heterogeneity was noted nor was any significant publication bias demonstrated. Conclusions- This is the first systematic review assessing postoperative headache severity following treatment of unruptured intracranial aneurysm. While a significant reduction in headache severity was observed, further investigation into this phenomenon is recommended before it influences clinical practice. Future study should stratify headache outcomes by aneurysm size, location, and treatment modality.
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http://dx.doi.org/10.1161/STROKEAHA.119.026864DOI Listing
December 2019

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

Lancet Oncol 2019 10 12;20(10):1349-1359. Epub 2019 Aug 12.

Department of Audiology, London Health Sciences Centre, London, ON, Canada.

Background: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment.

Methods: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting.

Findings: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS.

Interpretation: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options.

Funding: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.
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http://dx.doi.org/10.1016/S1470-2045(19)30410-3DOI Listing
October 2019

Primary organ preservation vs total laryngectomy for T4a larynx cancer.

Head Neck 2019 09 19;41(9):3265-3275. Epub 2019 Jun 19.

Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Background: There is a lack of consensus regarding the management of T4a larynx cancer. We evaluated the outcomes of organ preservation and laryngectomy for T4a laryngeal cancer.

Methods: Retrospective analysis of patients with T4a larynx cancer at BC Cancer from 1984 to 2014 was performed. Outcomes in patients treated with surgery alone (Sx) (n = 47), surgery with adjuvant radiotherapy (Sx/RT) (n = 94), radiation alone (RT) (n = 152), and radiation with concurrent chemoradiotherapy (chemoRT) (n = 36) were compared.

Results: The 5-year overall survival (OS) was 40% for chemoRT, 34% for RT, 23% for Sx, and 45% for Sx/RT. On multivariate analysis (MVA), Sx/RT (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.48-0.91) and chemoRT (HR, 0.44; 95% CI, 0.26-0.72) were associated with better OS than RT alone (P = .001). Sx had similar OS compared to RT (HR, 1.17; 95% CI, 0.82-1.68).

Conclusions: ChemoRT and Sx/RT were associated with better OS compared to single modality treatment. ChemoRT may be considered as an option for T4a larynx cancer.
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http://dx.doi.org/10.1002/hed.25838DOI Listing
September 2019

The association between the Nutrition-Related index and morbidity following head and neck microsurgery.

Laryngoscope 2020 02 6;130(2):375-380. Epub 2019 Mar 6.

Division of Otolaryngology-Head and Neck Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Objectives/hypothesis: Despite consensus that preoperative nutritional assessment is of importance in the head and neck surgical oncology population, it remains unclear how exactly malnutrition is associated with perioperative morbidity especially among those undergoing microvascular surgery. We aimed to study this association to help inform preoperative risk stratification, guide the use of nutritional interventions, and ultimately help prevent malnutrition related morbidity.

Study Design: Database analysis.

Methods: Retrospective, linked analysis of the 2011 to 2016 National Surgical Quality Improvement Program. After identifying eligible patients and stratifying according to the Nutrition-Related Index, a univariate screen of preoperative demographic and clinical covariates was performed. Subsequently, propensity score matching was utilized to control for differences in baseline covariates. Perioperative complications and mortality were then analyzed using the propensity score-matched cohorts.

Results: Among 977 identified patients, 276 (28.2%) were malnourished. Malnourished patients had higher rates of comorbidity, were more likely to actively smoke, and were more likely to have primaries in the oropharynx or hypopharynx/larynx. After propensity score matching to control for confounders, malnourished patients had higher rates of pulmonary complications (21.5% vs. 11.6%, P < .01), higher rates of bleeding or need for transfusion (56.6% vs. 43.0%, P < .01), higher rates of venous thromboembolism (3.7% vs. 0.8%, P = .03), and a higher 30-day mortality rates (3.7% vs. 0.0%, P < .01).

Conclusions: This nationwide analysis finds that 28.2% of patients undergoing surgery for head and neck cancers with free flap reconstruction are malnourished. Malnourishment was found to be independently associated with postoperative pulmonary complications, bleeding or need for transfusion, and 30-day mortality.

Level Of Evidence: NA Laryngoscope, 130:375-380, 2020.
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http://dx.doi.org/10.1002/lary.27912DOI Listing
February 2020

In house virtual surgery and 3D complex head and neck reconstruction.

J Otolaryngol Head Neck Surg 2018 Dec 12;47(1):75. Epub 2018 Dec 12.

Division of Otolaryngology, Head & Neck Surgery, University of British Columbia, 2775 Laurel Street, DHCC 4th. Floor, Vancouver, BC, V5Z 1M9, Canada.

Background: 3-Dimensional (3D) printing can be applied to virtual planning and creation of surgical guides for mandibular reconstruction. Such systems are becoming increasingly prevalent in head and neck reconstruction. However, third party access to this technology is costly and removes the opportunity to design, create, and modify the bony reconstructions, as third party technology is a black box. This series is a pilot study to document the feasibility of an in-house software tool. The objectives of this study are to describe the design of an automated in house system and assess the accuracy of this in house automated software tool for mandibular reconstruction in a simulated environment.

Methods: Software was written to automate the preoperative planning and surgical guide creation process. In a simulation lab, Otolaryngology residents were tasked with resecting and reconstructing a simulated mandible using the 3D-printed cutting guides. A control group of residents performed resection and reconstruction using the traditional method without cutting guides. T-test analysis was performed to compare specific aspects of the final reconstructions including: change from native mandibular width and projection, segment gap distance, and reconstruction time.

Results: Mandibular reconstruction was successful in all participants using the 3D printed system. The guided group performed significantly better on the measurement of change in Mandibular overlap, projection, segment gap volume. There was a non-significant trend towards better mandibular width and operative time for the guided group.

Conclusions: This study confirms functionality and feasibility of using an in house automated software for planning and creating surgical guides.
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http://dx.doi.org/10.1186/s40463-018-0320-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290522PMC
December 2018

Potential clinical implications of HPV status and expressions of p53 and cyclin D1 among oropharyngeal cancer patients.

J Oral Pathol Med 2018 Nov 27;47(10):945-953. Epub 2018 Sep 27.

Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.

Background: There is increasing evidence that high-risk human papillomavirus plays significant role in oropharyngeal cancer; however, there is lack of knowledge on the interplay between the virus and its downstream-related molecules and their possible prognostic values. The objectives of the study are to better understand the interplay of the HR-HPV and its associated downstream molecules and to evaluate potential biomarkers for patient outcomes.

Methods: We conducted a retrospective study with available formalin-fixed, paraffin-embedded tissue from 244 oropharyngeal cancer patients that received curative radiotherapy or concurrent chemoradiotherapy from 2000 to 2008. In addition to chart review, we performed HPV DNA and RNA in situ hybridization and immunohistochemistry for p53, the retinoblastoma protein, p16, and cyclin D1 analysis. Cox proportional hazard and Kaplan-Meier survival analysis were used to determine the prognostic markers for clinical outcomes.

Results: Patients averaged 57.3 ± 9.4 year-old and were mostly males (76.2%) and ever-smokers (76.2%). All patients received curative radiotherapy, and 44.3% received concurrent chemoradiotherapy. We detected the human papillomavirus in 77.9% of study patients. Ever-smokers, more advanced tumor stage, and receiving radiotherapy only had poorer 5-year overall survival, disease-specific survival, and loco-regional recurrence. Cases with positive human papillomavirus and p53 overexpression had poorer disease-specific survival. Cases without human papillomavirus, but cyclin D1 overexpression, were associated with poorer 5-year overall survival.

Conclusions: Our data suggest that additional p53 and cyclin D1 testing may benefit oropharyngeal cancer patients with known human papillomavirus status.
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http://dx.doi.org/10.1111/jop.12779DOI Listing
November 2018

Analysis of readmissions after transoral robotic surgery for oropharyngeal squamous cell carcinoma.

Head Neck 2018 11 13;40(11):2416-2423. Epub 2018 Aug 13.

T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

Background: As transoral robotic surgery (TORS) is being increasingly used to treat patients with oropharyngeal squamous cell carcinoma (OPSCC), there is an interest in determining contributors to readmission.

Methods: We conducted this retrospective multivariate analysis modeling 30-day readmission using the Nationwide Readmissions Database (2012-2014).

Results: Of 950 patients, 117 (12.3%) were readmitted. Hemorrhage and diet/aspiration accounted for 32.5% and 19.7% of readmissions, respectively. Of those readmitted, 23.1% required operative bleeding control, 11.1% required transfusion, 1.7% required tracheostomy, and 18.8% required gastrostomies. Those readmitted were older (mean 63.2 years, SD 9.5 vs 60.9 mean years, SD 10.3) and had longer hospitalizations (mean 5.7 days, SD 6.8 vs mean 4.3 days, SD 4.1) and higher rates of aspiration/pneumonia (9.4% vs 2.4%, P < .01) on index admission. Multivariate analysis demonstrated that aspiration/pneumonia on index admission was independently associated with readmission (OR 3.128, 95% CI 1.178-8.302).

Conclusions: Of the patients 12.3% were readmitted within 30 days with hemorrhage and diet complications as significant contributors.
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http://dx.doi.org/10.1002/hed.25362DOI Listing
November 2018

Guide design in virtual planning for scapular tip free flap reconstruction.

Laryngoscope Investig Otolaryngol 2018 Jun 14;3(3):162-168. Epub 2018 May 14.

Department of Otolaryngology Head and Neck Surgery, Icahn School of Medicine at Mount Sinai New York New York U.S.A.

Background: Virtual surgical planning (VSP), intraoperative cutting guides and stereolithographic models, provides the head and neck reconstructive surgeon with powerful tools for complex reconstruction planning. Despite its use in fibular osteocutaneous reconstruction, application to the scapular tip has not been as widely reported.

Methods: From 2013 to 2014, four cases of either mandibular or maxillary reconstruction were completed with the scapular tip osseous free flap. All four cases underwent preoperative VSP with patient-specific guide design.

Results: Patient-specific guides were generated for scapular tip harvest. Guide placement was improved using a stabilizing flange and bracket design. With minimal disruption of the overlying periosteum a wedge osteotomy was successfully implemented in one case.

Conclusions: Unlike the fibula and iliac crest donor sites, the scapular tip has overlying muscle attachments that make intraoperative osteotomies challenging. Attention to key aspects of scapular anatomy, including the fibrous tip and extensive overlying muscle, permits effective guide design.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lio2.162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057217PMC
June 2018

Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer.

Anal Cell Pathol (Amst) 2018 11;2018:1607814. Epub 2018 Mar 11.

British Columbia Cancer Research Centre, Department of Integrative Oncology, Vancouver, BC, Canada.

The incidence of HPV-positive oropharyngeal cancer (HPV+ OPC) is increasing, thus presenting new challenges for disease detection and management. Noninvasive methods involving brush biopsies of diseased tissues were recently reported as insufficient for tumor detection in HPV+ OPC patients, likely due to differences between the site of tumor initiation at the base of involuted crypts and the site of brush biopsy at the crypt surface. We hypothesized that histologically normal surface epithelial cells in the oropharynx contain changes in nuclear morphology that arise due to tumor proximity. We analyzed the nuclear phenotype of matched tumor, tumor-adjacent normal, and contralateral normal tissues from biopsies of nine HPV+ OPC patients. Measurements of 89 nuclear features were used to train a random forest-based classifier to discriminate between normal and tumor nuclei. We then extracted voting scores from the trained classifier, which classify nuclei on a continuous scale from zero ("normal-like") to one ("tumor-like"). In each case, the average score of the adjacent normal nuclei was intermediate between the tumor and contralateral normal nuclei. These results provide evidence for the existence of phenotypic changes in histologically normal, tumor-adjacent surface epithelial cells, which could be used as brush biopsy-based biomarkers for HPV+ OPC detection.
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http://dx.doi.org/10.1155/2018/1607814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866869PMC
October 2018

Post-acute care use after major head and neck oncologic surgery with microvascular reconstruction.

Laryngoscope 2018 11 30;128(11):2532-2538. Epub 2018 Mar 30.

Division of Otolaryngology-Head and Neck Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Objectives: Post-acute care (PAC) centers, such as skilled nursing facilities, unskilled nursing facilities, lower acuity hospitals, and rehabilitation centers, serve to optimize recovery after acute care hospitalization. We aimed to identify factors associated with PAC utilization among patients undergoing head and neck cancer surgery with microvascular reconstruction because it may be helpful for patient decision making, discharge planning, and resource allocation.

Methods: Retrospective linked analysis of the 2011 to 2015 National Surgical Quality Improvement Program. Eligible patients were identified and stratified by discharge disposition (home or PAC) after their postoperative acute-care hospitalization. After an initial univariate screen of demographic and clinical variables, a multivariable logistic regression analysis was performed modelling discharge to PAC.

Results: Of the 1,652 identified patients, 261 (15.8%) were discharged to PAC. Those admitted to PAC were older, had a higher burden of comorbidity, and were more likely to be functionally dependent. They also had longer surgeries, longer hospitalizations, higher rates of reoperation, and higher rates of postoperative complications. After multivariate analysis, factors independently associated with PAC discharge included increasing age (odds ratio [OR] 2.12 per 10-year increase; 95% confidence interval [CI], 1.81-2.48), active smoking status (odds ratio (OR) 1.61; 95% confidence interval (CI), 1.13-2.29), prolonged hospitalization (OR 1.04; 95% CI, 1.02-1.07), and postoperative pulmonary complications (OR 2.02; 95% CI, 1.36-2.99).

Conclusion: Of the patients undergoing surgery for head and neck cancers with microvascular reconstruction, 15.8% are discharged to PAC. Age, active smoking status, prolonged hospitalization, and postoperative pulmonary complications (vs. comorbidity, functional status, or primary tumor site) are independently associated with discharge to PAC.

Level Of Evidence: Level 2c. Laryngoscope, 2532-2538, 2018.
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http://dx.doi.org/10.1002/lary.27190DOI Listing
November 2018

Patient Choice of Nonsurgical Treatment Contributes to Disparities in Head and Neck Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2018 06 13;158(6):1057-1064. Epub 2018 Feb 13.

1 Division of Otolaryngology-Head & Neck Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Objectives There are well-established outcome disparities among different demographic groups with head and neck squamous cell carcinoma (HNSCC). We aimed to investigate the potential contribution of patient choice of nonsurgical treatment to these disparities by estimating the rate of this phenomenon, identifying its predictors, and estimating the effect on cancer-specific survival. Study Design Retrospective nationwide analysis. Settings Surveillance, Epidemiology, and End Results Database (2004-2014). Subjects and Methods Patients with HNSCC, who were recommended for primary surgery, were included. Multivariable logistic regression was used to identify demographic and clinical factors associated with patient choice of nonsurgical treatment, and Kaplan Meier/Cox regression was used to analyze survival. Results Of 114,506 patients with HNSCC, 58,816 (51.4%) were recommended for primary surgery, and of those, 1550 (2.7%) chose nonsurgical treatment. Those who chose nonsurgical treatment were more likely to be older (67.1 ± 12.6 vs 63.6 ± 13.1, P < .01), were of Black (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.28-1.74) or Asian (OR = 1.79; 95% CI, 1.46-2.20) ethnicity, were unmarried (OR married, 0.50; 95% CI, 0.44-0.58), had an advanced tumor, and had a hypopharyngeal or laryngeal primary. Choice of nonsurgical treatment imparted a 2.16-fold (95% CI, 2.02-2.30) increased risk of cancer-specific death. Conclusion Of the patients, 2.7% chose nonsurgical treatment despite a provider recommendation that impairs survival. Choice of nonsurgical treatment is associated with older age, having Black or Asian ethnicity, being unmarried, having an advanced stage tumor, and having a primary site in the hypopharynx or larynx. Knowledge of these disparities may help providers counsel patients and help patients make informed decisions.
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http://dx.doi.org/10.1177/0194599818755353DOI Listing
June 2018

Ectopic thymoma managed by neck dissection & video-assisted thoracoscopic thymectomy.

J Thorac Dis 2017 Dec;9(12):E1050-E1053

Faculty of Medicine, University of British Columbia, Vancouver, Canada.

Ectopic thymoma in the neck is a rare phenomenon, with fewer than 20 cases reported worldwide. Evidence for management of ectopic thymoma comes from literature for mediastinal thymoma despite clinical features that distinguish the two. Here we present a case of a 31-year-old female with an asymptomatic neck mass who was found to have an ectopic cervical thymoma with concomitant mediastinal thymic hyperplasia. The decision was made to perform a left-sided neck dissection and a video-assisted thoracoscopic surgery (VATS) thymectomy. We suggest that this approach be considered for a minimally invasive management of this rare but important condition.
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http://dx.doi.org/10.21037/jtd.2017.10.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757049PMC
December 2017

Customized software to optimize circumferential pharyngoesophageal free flap reconstruction.

Laryngoscope 2017 10 22;127(10):2252-2255. Epub 2017 Feb 22.

Division of Otolaryngology-Head and Neck Surgery, Vancouver General Hospital, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1002/lary.26497DOI Listing
October 2017

Revisiting the gastric pull-up for pharyngoesophageal reconstruction: A systematic review and meta-analysis of mortality and morbidity.

J Surg Oncol 2016 Dec 24;114(8):907-914. Epub 2016 Oct 24.

Division of Otolaryngology-Head and Neck Surgery, Vancouver General Hospital, Vancouver, British Columbia, Canada.

Gastric pull-up (GPU) is among the oldest techniques for reconstructing the pharyngoesophageal junction following cancer resection. This review examines morbidity and mortality rates following GPU pharyngoesophageal junction reconstruction from 1959 until present: 77 studies, 2,705 patients. The odds of mortality, anastomotic complications, and other complications decreased by 37.2% (95%CI = 28.0-45.3%; P < 0.0001), 8.0% (95%CI = -2.1 to 17.1%; P = 0.12), 21.0% (95%CI 3.5-35.2%; P = 0.021) per decade respectively. J. Surg. Oncol. 2016;114:907-914. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jso.24477DOI Listing
December 2016
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