Publications by authors named "Joseph Curry"

151 Publications

Microvascular Reconstruction of Osteonecrosis: Assessment of Long-term Quality of Life.

Otolaryngol Head Neck Surg 2021 Feb 23:194599821990682. Epub 2021 Feb 23.

School of Medicine, Oregon Health and Science University, Portland, Oregon, USA.

Objective: Review long-term clinical and quality-of-life outcomes following free flap reconstruction for osteonecrosis.

Study Design: Retrospective multi-institutional review.

Setting: Tertiary care centers.

Methods: Patients included those undergoing free flap reconstructions for osteonecrosis of the head and neck (N = 232). Data included demographics, defect, donor site, radiation history, perioperative management, diet status, recurrence rates, and long-term quality-of-life outcomes. Quality-of-life outcomes were measured using the University of Washington Quality of Life (UW-QOL) survey.

Results: Overall flap success rate was 91% (n = 212). Relative to preoperative diet, 15% reported improved diet function at 3 months following reconstruction and 26% at 5 years. Osteonecrosis recurred in 14% of patients (32/232); median time to onset was 11 months. Cancer recurrence occurred in 13% of patients (29/232); median time to onset was 34 months. Results from the UW-QOL questionnaire were as follows: no pain (45%), minor or no change in appearance (69%), return to baseline endurance level (37%), no limitations in recreation (40%), no changes in swallowing following reconstruction (28%), minor or no limitations in mastication (29%), minor or no speech difficulties (93%), no changes in shoulder function (84%), normal taste function (19%), normal saliva production (27%), generally excellent mood (44%), and no or minimal anxiety about cancer (94%).

Conclusion: The majority of patients maintained or had advancement in diet following reconstruction, with low rates of osteonecrosis or cancer recurrence and above-average scores on UW-QOL survey suggesting good return of function and quality of life.
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http://dx.doi.org/10.1177/0194599821990682DOI Listing
February 2021

Free tissue transfer for central skull base defect reconstruction: Case series and surgical technique.

Oral Oncol 2021 Feb 13;115:105220. Epub 2021 Feb 13.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, United States. Electronic address:

Objectives: Local reconstruction of central skull base defects may be inadequate for large defects or reoperative cases; free tissue transfer may be necessary. Inset of the flap and management of the pedicle can be challenging. We report our experience and approaches.

Methods: Retrospective review identifying seven patients with central skull base defects who underwent free flap reconstruction from 2016 to 2020.

Results: Four patients with recurrent nasopharyngeal carcinoma, one with recurrent craniopharyngioma, one with clival-cervical chordoma, and one with meningioma of the middle cranial fossa were analyzed. Six defects were closed with an anterolateral thigh free flap and one with a radial forearm free flap. In two patients, the flap was secured in an onlay fashion to the defect via a Caldwell-Luc transmaxillary approach. In one patient, the flap was passed transorally, and the pedicle was delivered into the neck via Penrose drain. In two patients, a parapharyngeal technique and in two others, a retropharyngeal was used for nasopharyngeal inset with endoscopic assistance. There were no flap failures, with an average follow-up time of 20.1 (range 3.2-47.1) months. One patient required flap repositioning on postoperative day three due to midline shift and intracranial contents compression. The transoral inset flap necessitated flap repositioning on postoperative day 13 to improve the nasopharyngeal airway.

Conclusion: Free flap reconstruction of the central skull base is challenging, but transmaxillary, transoral, parapharyngeal, and retropharyngeal approaches can be used with endoscopic assistance to ensure secure inset flap and avoid airway obstruction.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105220DOI Listing
February 2021

Head and neck surgery global outreach: Ethics, planning, and impact.

Head Neck 2021 Feb 14. Epub 2021 Feb 14.

Department of Head and Neck Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: Head and neck surgical oncology and reconstruction are uniquely suited to address burdens of disease in underserved areas. Since these efforts are not well known in our specialty, we sought to understand global outreach throughout our society of surgeons.

Methods: Survey distributed to members of the American Head and Neck Surgery involved in international humanitarian head and neck surgical outreach trips.

Results: Thirty surgeons reported an average of seven trips to over 70 destinations. Identification of candidates, finances, on-site patient care, complications, long-term post-surgical care, ethics, and educational goals are reported. We report a success rate of 90% on 125 free flaps performed in these settings.

Conclusions: The effort to answer the call for alleviating the global burden of surgical disease is strong within our specialty. There is a shared focus on humanitarian effort and teaching. Ethics of high resource surgeries such as free flap reconstruction remains controversial.
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http://dx.doi.org/10.1002/hed.26643DOI Listing
February 2021

Improved efficiency of sialendoscopy procedures at an ambulatory surgery center.

Am J Otolaryngol 2021 Jan 22;42(3):102927. Epub 2021 Jan 22.

Thomas Jefferson University Hospital, Department of Otolaryngology - Head and Neck Surgery, 925 Chestnut St, Philadelphia, PA 19107, United States of America.

Objectives: To compare time spent on day of surgery and post-surgical outcomes for sialendoscopy procedures at an ambulatory surgery center versus in a hospital operating room.

Methods: Retrospective chart review for patients who underwent sialendoscopy for sialadenitis or sialolithiasis from March 2017 to May 2020 were included. Surgery location (ambulatory surgery center or hospital operating room) was compared. Primary outcomes included total time in hospital, operative time, total time in operating room. and recovery time. Secondary outcomes included rate of symptoms resolutions, requiring further medical management, and requiring further surgical intervention.

Results: A total of 321 procedures were included. Sialendoscopy in an ambulatory surgery center compared to main operating room decreased median hospital time (166 min reduction, p < 0.001), operative time (18 min reduction, p < 0.001), total time in operating room (34 min reduction, p < 0.001), and recovery time (64 min reduction, p < 0.001). Sialendoscopy in an ambulatory surgery center had similar rates of post-operative resolution of symptoms and further medical or surgical intervention compared to procedures in a hospital operating room.

Conclusion: Sialendoscopy can be safely performed in an ambulatory surgery center for sialadenitis or appropriate sialolithiasis cases while decreasing hospital time, operative time, total time in operating room time, and recovery time.
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http://dx.doi.org/10.1016/j.amjoto.2021.102927DOI Listing
January 2021

Functional Swallow-Related Outcomes Following Transoral Robotic Surgery for Base of Tongue Carcinoma.

Dysphagia 2021 Jan 25. Epub 2021 Jan 25.

Division of Biostatistics, Thomas Jefferson University, 1015 Chestnut Street, Suite 520, Philadelphia, PA, 19107, USA.

In an era where the incidence of oropharyngeal cancer is growing steadily, there have been few studies exploring functional outcomes for individuals whose definitive cancer management approach includes transoral robotic surgical (TORS) resection. This study was designed to examine swallow-related outcomes in individuals newly diagnosed with base of tongue cancer whose treatment plan included surgical resection via TORS. The aims of this study were to determine whether TORS resection for early stage BOT SCCA affected: (a) lingual strength, (b) swallow safety and efficiency, (c) oral intake, and (d) swallowing-related quality of life. Nine individuals meeting the inclusion criteria were recruited to participate from March 2017 to April 2018. Each participant was evaluated at four distinct time points: (a) preoperatively, (b) 1 week postoperatively, (c) 1 month postoperatively, and (d) 3 months postoperatively. The following data were collected at each time point: (a) maximum isometric lingual pressure, (b) Penetration-Aspiration Scale score, (c) Yale Pharyngeal Residue Severity Rating Scale scores, (d) Functional Oral Intake Scale score, and (e) EAT-10 score. Data analysis revealed that a significant decline in maximum isometric lingual pressure, EAT-10 scores, and Functional Oral Intake Scale scores occurred between preoperative baseline measurements and 1 week post surgery. All participants in the study demonstrated a return to levels at or near their baseline level of function for maximum isometric lingual pressure, EAT-10 score, and Functional Oral Intake Scale score by 1 or 3 months post surgery. There were no significant changes in swallow safety or efficiency observed at any time point during the study.
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http://dx.doi.org/10.1007/s00455-021-10246-yDOI Listing
January 2021

Cytotoxic evaluation of two orthodontic silver solder materials on human periodontal ligament fibroblast cells and the effects of antioxidant and antiapoptotic reagents.

Angle Orthod 2021 Jan 25. Epub 2021 Jan 25.

Objectives: To evaluate the cytotoxicity effects of two different solder materials used for orthodontic appliances on human periodontal ligament fibroblast (HPLF) cells, and to determine whether the mechanism of toxicity may involve oxidative stress and apoptosis.

Materials And Methods: The silver solder samples (Leone and Summit) were soldered to orthodontic stainless steel bands and exposed to HPLF cells via cell culture inserts for 48 hours. Cytotoxicity effect of the soldered materials on HPLF cells was measured via tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay (n = 10/sample) and morphological observation. In addition, the mechanism of cytotoxicity of the most toxic silver solder was investigated using both a caspase inhibitor Z-VAL-Ala-Asp-flu-oromethylketone (ZVAD-fmk) and the free radical scavenger Trolox (n = 8/sample). Statistical analysis was performed using one-way analysis of variance with a Bonferroni test. P < .05 was considered statistically significant.

Results: Compared to the control (no treatment, cells only), both silver solders were cytotoxic (P < .001). The bands alone were significantly cytotoxic compared to the control. There was a significant difference in cytotoxicity between the stainless steel bands alone and the Summit silver solder (P < .001), but not the Leone silver solder. The Summit silver solder was more cytotoxic than the Leone silver solder (P < .05). MTT results were supported by the microscopic morphological changes of the HPLF cells. Neither ZVAD-fmk nor Trolox provided significant protection.

Conclusions: The two silver solder materials demonstrated different levels of cytotoxicity, and neither oxidative stress nor apoptosis is involved in the mechanism of cytotoxicity.
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http://dx.doi.org/10.2319/050620-405.1DOI Listing
January 2021

Impact of Lymph Node Yield in Patients Undergoing Total Laryngectomy and Neck Dissection.

Ann Otol Rhinol Laryngol 2020 Oct 14:3489420964824. Epub 2020 Oct 14.

Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.

Objectives: To determine the impact of lymph node yield (LNY) in patients undergoing neck dissection at the time of total laryngectomy (TL). To determine the impact of radiation therapy (RT) on LNY.

Methods: Retrospective review of LNY and clinical outcomes in 232 patients undergoing primary or salvage total laryngectomy (TL) with ND.

Results: Preoperative RT significantly decreased mean LNY from 31.7 to 23.9 nodes ( < .001). In primary TL patients, age ( < .001) and positive margins ( = .044) were associated with decreased OS. In salvage TL patients, only positive margins was associated with poorer OS ( = .009). No LNY cutoff provided significant OS or DFS benefit.

Conclusions: Radiotherapy significantly reduces LNY in patients undergoing TL and ND. Within a single institution cohort, positive margins, but not LNY, is associated with survival in both primary and salvage TL patients. 4.
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http://dx.doi.org/10.1177/0003489420964824DOI Listing
October 2020

Quality of Life Outcomes in Patients With Sinonasal Malignancy After Definitive Treatment.

Laryngoscope 2020 Dec 25. Epub 2020 Dec 25.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: To describe multidimensional quality of life (QOL) outcomes in patients with sinonasal malignancies (SNM). To elucidate factors predicting worse QOL in this population.

Study Design: Retrospective chart review at tertiary institution.

Methods: A retrospective chart review on patients treated for SNM from 2006 to 2019 at a tertiary medical center was conducted. QOL outcomes were measured using the Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment Cancer Therapy - Nasopharynx (FACT-NP) score. A stepwise multiple linear regression analysis was conducted to assess factors predicting worse QOL.

Results: Eighty-one patients met inclusion criteria. Twelve (14.8%) patients had a subscale score >11 for anxiety (HADS-A) or depression (HADS-D) indicating significant anxiety or depression, at a median of 24 (8-68.5) months post treatment. The median FACT-NP total score was 136 (110-152). On multivariable analysis, advanced T classification, single status, and worse social support survey score were significant predictors of worse HADS score. Worse social support survey score was a significant predictor of worse total FACT-NP score.

Conclusion: After adjusting for confounders, at a median of 24 months after completion of definitive therapy for SNM, advanced T classification and single relationship status were found to be significant predictors of anxiety and depression (based on HADS). A worse social support survey score was associated with worse anxiety, depression, and QOL (based on HADS and FACT-NP). Identifying these factors early may help to guide treatment and psychiatric referral to at-risk individuals after the treatment of SNM.

Level Of Evidence: 3. Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29339DOI Listing
December 2020

Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.

Front Oncol 2020 2;10:566315. Epub 2020 Dec 2.

Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, United States.

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients And Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area.

Results: Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8 T cells and CD163 macrophages, whereas stromal regulatory T cells were associated with low nodal PTE. RVR correlated with PTE at both primary tumor (slope = 0.55, < 0.001) and in LN (slope = 0.62, < 0.05). 89% (16/18) of radiographic non-responders with T1-T3 primary sites had no (n = 7) or minimal PTE (n = 9), whereas 15/17 (88%) of radiographic responders had moderate (n = 12) or complete (n = 3) PTE.

Conclusion: Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.
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http://dx.doi.org/10.3389/fonc.2020.566315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738605PMC
December 2020

Cancer-Associated Fibroblast Density, Prognostic Characteristics, and Recurrence in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis.

Front Oncol 2020 27;10:565306. Epub 2020 Nov 27.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, United States.

Introduction: The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor microenvironment (TME). Among the most abundant of these stromal cells are cancer-associated fibroblasts (CAFs). While their contribution to tumor progression is widely acknowledged, and various CAF-targeted treatments are under development, the relationship between CAF density and the clinicopathologic course of HNSCC has not been clearly defined. Here we examine the published evidence investigating the relationship of cancer-associated fibroblasts to local recurrence and indicators of prognostic significance in HNSCC.

Methods: We conducted a meta-analysis of existing publications that compare the relationship between CAF density, local recurrence, and clinically significant pathologic criteria of disease development (T stage, nodal positivity, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation). Thirteen studies met the selection criteria, providing a total study population of 926 patients. Forest plots and risk ratios were generated to illustrate overall relationships.

Results: Higher CAF density within the tumor microenvironment is associated with advanced T stage, nodal infiltration, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation (p <0.05). High CAF density is also associated with increased rates of local recurrence (p <0.001).

Conclusions: Across multiple studies, increased CAF density is correlated with histopathological criteria of poor prognosis in HNSCC. These findings highlight that CAFs may play a pivotal role in HNSCC development and progression. Staining for CAFs may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment. Understanding the mechanisms by which CAFs reciprocally interact with cancer cells will be crucial for optimization of TME-focused treatment of HNSCC.
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http://dx.doi.org/10.3389/fonc.2020.565306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729160PMC
November 2020

Incorporation of a Machine Learning Algorithm With Object Detection Within the Thyroid Imaging Reporting and Data System Improves the Diagnosis of Genetic Risk.

Front Oncol 2020 12;10:591846. Epub 2020 Nov 12.

Department of Radiology, Thomas Jefferson University, Philadelphia, PA, United States.

Background: The role of next generation sequencing (NGS) for identifying high risk mutations in thyroid nodules following fine needle aspiration (FNA) biopsy continues to grow. However, ultrasound diagnosis even using the American College of Radiology's Thyroid Imaging Reporting and Data System (TI-RADS) has limited ability to stratify genetic risk. The purpose of this study was to incorporate an artificial intelligence (AI) algorithm of thyroid ultrasound with object detection within the TI-RADS scoring system to improve prediction of genetic risk in these nodules.

Methods: Two hundred fifty-two nodules from 249 patients that underwent ultrasound imaging and ultrasound-guided FNA with NGS with or without resection were retrospectively selected for this study. A machine learning program (Google AutoML) was employed for both automated nodule identification and risk stratification. Two hundred one nodules were used for model training and 51 reserved for testing. Three blinded radiologists scored the images of the test set nodules using TI-RADS and assigned each nodule as high or low risk based on the presence of highly suspicious imaging features on TI-RADS (very hypoechoic, taller-than-wide, extra-thyroidal extension, punctate echogenic foci). Subsequently, the TI-RADS classification was modified to incorporate AI for T4 nodules while treating T1-3 as low risk and T5 as high risk. All diagnostic predictions were compared to the presence of a high-risk mutation and pathology when available.

Results: The AI algorithm correctly located all nodules in the test dataset (100% object detection). The model predicted the malignancy risk with a sensitivity of 73.9%, specificity of 70.8%, positive predictive value (PPV) of 70.8%, negative predictive value (NPV) of 73.9% and accuracy of 72.4% during the testing. The radiologists performed with a sensitivity of 52.1 ± 4.4%, specificity of 65.2 ± 6.4%, PPV of 59.1 ± 3.5%, NPV of 58.7 ± 1.8%, and accuracy of 58.8 ± 2.5% when using TI-RADS and sensitivity of 53.6 ± 17.6% (p=0.87), specificity of 83.3 ± 7.2% (p=0.06), PPV of 75.7 ± 8.5% (p=0.13), NPV of 66.0 ± 8.8% (p=0.31), and accuracy of 68.7 ± 7.4% (p=0.21) when using AI-modified TI-RADS.

Conclusions: Incorporation of AI into TI-RADS improved radiologist performance and showed better malignancy risk prediction than AI alone when classifying thyroid nodules. Employing AI in existing thyroid nodule classification systems may help more accurately identifying high-risk nodules.
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http://dx.doi.org/10.3389/fonc.2020.591846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689011PMC
November 2020

Anastomotic Revision in Head and Neck Free Flaps.

Laryngoscope 2020 Sep 10. Epub 2020 Sep 10.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: Predictors of free tissue transfer (FTT) failure and the need for postoperative revision (POR) have been extensively studied; however, there are little data evaluating outcomes when intraoperative revision (IOR) at initial surgery is required. This study seeks to better understand the impact IOR of the pedicle has on FTT outcomes.

Study Design: Retrospective review of 2482 consecutive patients across three tertiary institutions.

Methods: Adult patients (>18) who received a FTT and underwent anastomotic revision from 2006 to 2019 were included. Logistic regression was performed to predict revision, and recursive partitioning was performed to classify risk of failure based on type of revision and vessels revised.

Results: Failure rates for IOR (19%) and POR (27%) were higher compared to a nonrevised failure rate of 2% (P < .01 and P < .01, respectively). Intraoperative venous revision (IORv, n = 13), arterial (IORa, n = 114), and both (IORb, n = 11) were associated with failure rates of 8% (odds ratio [OR] 3.5, P = .23), 18% (OR = 9.0, P < .01), 45% (OR = 35.3, P = <.01), respectively. Arterial revision was most common among IOR (83%, P < .01). Postoperative venous revision (PORv, n = 35), arterial (PORa, n = 36), and both (PORb, n = 11) were associated with failure rates of 20% (OR = 15.7, P < .01), 27% (OR = 10.6, P < .01), and 39% (OR = 27.0, P < .01), respectively. Failure rate for flaps that had POR after IOR (PORi, n = 11) was 45% (OR = 18.2, P < .01). Diabetes predicted IOR (P = .006); tobacco use, heavy alcohol use, and prior radiation predicted POR (P = .01, P = .05, and P = .01, respectively).

Conclusion: Both IOR and POR were associated with increased failure compared to nonrevised flaps. The risk of failure increases sequentially with intraoperative or POR of the vein, artery, or both vessels. Revision of both vessels and POR after IOR are strongly predictive of failure.

Level Of Evidence: 3 Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29094DOI Listing
September 2020

Comparison of general anesthesia and monitored anesthesia care for sialendoscopy procedures.

Am J Otolaryngol 2021 Jan - Feb;42(1):102809. Epub 2020 Oct 24.

Thomas Jefferson University Hospital, Department of Otolaryngology - Head and Neck Surgery, 925 Chestnut St, Philadelphia, PA 19107, United States of America.

Objectives: The literature remains scarce in terms of comparing different anesthesia modalities in sialendoscopy. Due to the lack of a standard of care or guidelines to anesthetic care, it is generally accepted that surgeons perform these surgeries under the anesthetic modality in which they are most comfortable. In this study, we evaluate time spent on the day of surgery and post-surgical outcomes for patients receiving sialendoscopy under monitored anesthesia care versus general anesthesia.

Materials And Methods: We retrospectively assessed patients who underwent sialendoscopy using a solely endoscopic approach for sialadenitis or sialolithiasis from March 2017 to December 2019. Anesthesia modality (monitored anesthesia care versus general anesthesia) was compared. Main outcomes included total time in hospital, operative time, total time in operating room, anesthesia time, and recovery time. Secondary outcomes included rate of resolution of symptoms, requiring further medical management, requiring further surgical intervention, and complications.

Results: A total of 172 procedures were included. Sialendoscopy under monitored anesthesia care center compared to general anesthesia decreased median hospital time (141 min reduction), anesthesia time (46 min reduction), operative time (24 min reduction), time in operating room (43 min reduction), and recovery time (56 min reduction). Utilizing monitored anesthesia care demonstrated similar rates of post-operative resolution of symptoms, complications, and further medical or surgical intervention compared to the general anesthesia cohort.

Conclusion: Sialendoscopy can be safely performed under monitored anesthesia care for appropriate sialadenitis or sialolithiasis cases while decreasing hospital time, operative time, time in operating room, anesthesia time, and recovery time while maintaining similar post-operative outcomes. Monitored anesthesia care should be considered for solely endoscopic cases as guided by surgeon and patient comfort.
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http://dx.doi.org/10.1016/j.amjoto.2020.102809DOI Listing
October 2020

Safety of fibula free flap in patients following total knee replacement.

Head Neck 2021 Feb 21;43(2):585-589. Epub 2020 Oct 21.

Department of Otolaryngology - Head and Neck Surgery, Oregon Health and Sciences University, Portland, Oregon, USA.

Background: Fibula free flap (FFF) is the preferred osteocutaneous flap for reconstruction of large head and neck composite defects. There is a paucity of data whether FFF can be performed safely in patients with knee replacement (total knee arthroplasty [TKA]).

Methods: Multi-institutional review of outcomes following FFF in patients who had prior TKA.

Results: Ten surgeons reported successful FFF in 53 patients with prior TKA. The most common preoperative imaging was a CT angiogram of the bilateral lower extremities. There was no evidence of intraoperative vascular abnormality. Physical therapy began between postoperative day 1 to postoperative day 3. At 1 month postoperatively, 40% of patients were using a cane or walker to ambulate, but by 3 months all had returned to baseline ambulatory status. At >1 year, there were no gait complications.

Conclusion: FFF appears safe in patients with prior knee replacement without an increased risk of complications compared to baseline.
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http://dx.doi.org/10.1002/hed.26519DOI Listing
February 2021

Outcomes of Venous End-to-Side Microvascular Anastomoses of the Head and Neck.

Laryngoscope 2020 Oct 19. Epub 2020 Oct 19.

Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: The literature on outcomes of end-to-side (ETS) anastomoses for microvascular reconstruction of the head and neck is limited. This series reviews ETS in free tissue transfer (FTT) across multiple institutions to better understand their usage and associated outcomes.

Study Design: Retrospective review of 2482 consecutive patients across three tertiary institutions.

Methods: Adult patients (> 18) who received a FTT from 2006 to 2019 were included.

Results: Two hundred and twenty-one FTT were identified as requiring at least one ETS anastomosis. These ETS cases had a failure rate of 11.2% in comparison to 3.8% in a cohort of end-to-end (ETE) cases (P < .001). ETS cases were significantly more likely to have a prior neck dissection (P < .001), suggesting the ETS method was utilized in select circumstances. A second ETS anastomosis improved survival of the FTT (P = .006), as did utilization of a coupler over suture (P = .002). Failure due to venous thrombosis was significantly more common with one ETS anastomosis instead of two ETS anastomoses (P = .042).

Conclusions: ETS is effective but is often used as a secondary technique when ETE is not feasible; as such, in this series, ETS was associated with higher failure. A second anastomosis and the use of the coupler for completing the anastomoses were associated with lower rates of failure.

Level Of Evidence: 3 Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29134DOI Listing
October 2020

Factors impacting successful salvage of the failing free flap.

Head Neck 2020 Dec 26;42(12):3568-3579. Epub 2020 Aug 26.

Oregon Health and Science University School of Medicine, Portland, Oregon, USA.

Background: Understanding factors impacting successful salvage of a compromised free flap.

Methods: Multi-institutional review of free flap reconstructions for head and neck defects (n = 1764).

Results: Free flap compromise rate: 9% (n = 162); 46% salvaged (n = 74). Higher salvage rates in initial 48 hours (64%) vs after (30%; P < .001). Greater compromise (14%) and failure (8%) if inset challenging vs straightforward (6% compromise, 4% failure; P = .035). Greater compromise (23%) and failure (17%) following intraoperative anastomosis revision vs no revision (7% compromise, 4% failure; P < .0001). Success following arterial insufficiency was lower (60% failed, 40% salvaged) vs venous congestion (23% failed, 77% salvaged) (P < .0001). Greater flap salvage following thrombectomy (66%) vs no thrombectomy (34%; P < .0001). Greater flap salvage if operative duration ≤8 hours (57%), vs >8 hours (40%) (P = .04).

Conclusions: There were higher rates of free flap salvage if the vascular compromise occurred within 48 hours, if due to venous congestion, if operative duration ≤8 hours, and if the anastomosis did not require intraoperative revision.
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http://dx.doi.org/10.1002/hed.26427DOI Listing
December 2020

Functional and survival outcomes in elderly patients undergoing transoral robotic surgery.

Oral Oncol 2020 12 19;111:104954. Epub 2020 Aug 19.

Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University Hospitals, 6(th) floor, 925 Chestnut Street, Philadelphia, PA 19107, USA.

Objectives: To determine if elderly patients (≥70 years) have differences in functional and survival outcomes compared to non-elderly patients (<70 years) following transoral robotic surgery.

Materials And Methods: A retrospective cohort study was conducted on patients undergoing robotic surgery for head and neck cancer at a tertiary institution from 2011 to 2016. Functional status was evaluated with diet, enteric feeding status, Functional Oral Intake Scale (FOIS), tracheostomy tube placement, and unplanned readmission. Kaplan Meier method and Cox proportional hazard model were used to assess overall survival (OS) and disease-free survival (DFS) between elderly and non-elderly patients.

Results: Two hundred and forty-six patients met inclusion criteria. The mean age of the cohort was 63.5 ± 9.74 years. There were 64 patients (26.0%) that were ≥70 years. Elderly patients were more likely to be discharged with enteric access (p < 0.002). As early as 3 months, there was no significant difference in need for enteric feeds, diet, or FOIS score. There was no difference in tracheostomy tube rates and unplanned readmission between both cohorts. There was no significant difference in OS and DFS between age groups when stratified by p16 status.

Conclusions: Elderly patients are more likely to require perioperative enteric feeding, but 3-month, 1-year, and 2-year functional outcomes are comparable to younger patients. Survival outcomes are similar in both populations.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104954DOI Listing
December 2020

Lacrimal drainage apparatus melanoma remotely following treatment and resolution of conjunctival melanoma.

Orbit 2020 Aug 18:1-8. Epub 2020 Aug 18.

Department of Ophthalmology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University , Philadelphia, Pennsylvania, USA.

Lacrimal drainage apparatus melanoma is a rare entity that may arise primarily or, more commonly, as secondary involvement from melanoma originating elsewhere. Conjunctival melanoma may involve the lacrimal drainage apparatus (LDA) via spread along the canalicular epithelium, separate in situ processes, or direct invasion. Only seven cases exist in the literature where conjunctival melanoma remotely recurred in the LDA. We report three additional patients, two with invasive conjunctival melanoma and one with primary acquired melanosis (PAM) with severe atypia/melanoma in situ, who developed LDA melanoma at 5, 8, and 16 years after initial treatment of conjunctival melanoma. This report confirms the ability of conjunctival melanoma to give rise to spatially and temporally remote LDA melanoma despite adequate local treatment, and reviews the proposed mechanisms and associated characteristics of LDA recurrence in conjunctival melanoma.
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http://dx.doi.org/10.1080/01676830.2020.1808020DOI Listing
August 2020

Initial Experience Using 3-Dimensional Printed Models for Head and Neck Reconstruction in Haiti.

Ear Nose Throat J 2020 Aug 10:145561320938920. Epub 2020 Aug 10.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

This report describes the first use of a novel workflow for in-house computer-aided design (CAD) for application in a resource-limited surgical outreach setting. Preoperative computed tomography imaging obtained locally in Haiti was used to produce rapid-prototyped 3-dimensional (3D) mandibular models for 2 patients with large ameloblastomas. Models were used for patient consent, surgical education, and surgical planning. Computer-aided design and 3D models have the potential to significantly aid the process of complex surgery in the outreach setting by aiding in surgical consent and education, in addition to expected surgical applications of improved anatomic reconstruction.
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http://dx.doi.org/10.1177/0145561320938920DOI Listing
August 2020

Management of the Acute Loss of a Free Flap to the Head and Neck-A Multi-institutional Review.

Laryngoscope 2021 03 27;131(3):518-524. Epub 2020 Jul 27.

Department of Otolaryngology, Oregon Health and Science University, Portland, Oregon, USA.

Objectives/hypothesis: To review the management of failed free tissue transfers among four large institutions over a 13-year period to provide data and analysis for a logical, algorithmic, experience-based approach to the management of failed free flaps.

Study Design: Retrospective case series.

Methods: A multi-institutional retrospective chart review of free tissue transfers to the head and neck region between 2006 and 2019 was performed. Patients with a failed free flap during their hospitalization after surgery to the head and neck were identified and reviewed. Patient age, co-morbidities, risk factors, flap characteristics, tumor specifics, and length of hospital stay were reviewed, collected, and analyzed.

Results: One hundred eighteen flap failures met criteria. The most common failed flap in this review was the osteocutaneous flap 52/118 (44%). The recipient site of the initial free flap (P < .001) was the only statistically significant parameter strongly correlated with management. Osteocutaneous flap failures, fasciocutaneous, bowel, and muscle-only flaps tended to be managed most commonly with a second free flap. Myocutaneous flap failures were managed equally with either a second free flap or a regional flap.

Conclusions: The most important factor in management of a failed free flap is the recipient site. A second free flap is often the preferred treatment, but in the acute setting, local or regional flaps may be viable options depending on the recipient site, circumstances of flap loss, and patient- specific comorbidities. An algorithm for management of the acute flap loss is presented in this review.

Level Of Evidence: 4 Laryngoscope, 131:518-524, 2021.
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http://dx.doi.org/10.1002/lary.28886DOI Listing
March 2021

The underappreciated role of auriculotemporal nerve involvement in local failure following parotidectomy for cancer.

Head Neck 2020 Nov 20;42(11):3253-3262. Epub 2020 Jul 20.

Department of Otolaryngology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.

Background: Locoregional recurrence rates following parotidectomy for cancer remain as high as 20-30%. The auriculotemporal nerve (ATN) may allow parotid cancers to spread from the facial nerve (FN) toward the skull base, causing local recurrence.

Methods: Retrospective review of 173 parotidectomies for malignancy. Preoperative and post-recurrence imaging were reviewed by a neuroradiologist for signs of tumor adjacent to the ATN.

Results: Clinical and imaging signs of possible ATN involvement correlated with FN weakness and sacrifice. Eight patients had pathologically confirmed tumor from the ATN or V3. Forty-four percent of local recurrences had post-recurrence imaging showing tumor along the course of the ATN. Locoregional failure along the ATN was also associated with preoperative FN weakness, intraoperative FN sacrifice, and failure to complete recommended adjuvant therapy.

Conclusions: Parotid cancers may invade the FN and spread to the skull base via the ATN. If not appropriately managed, this may lead to local recurrence.
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http://dx.doi.org/10.1002/hed.26372DOI Listing
November 2020

SMARCB1 (Integrase Interactor 1)-Deficient Sinonasal Carcinoma of the Maxillary Sinus: A Newly Described Sinonasal Neoplasm.

J Oral Maxillofac Surg 2020 Oct 30;78(10):1870.e1-1870.e6. Epub 2020 May 30.

Associate Professor of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA.

SMARCB1 (integrase interactor 1) is a tumor suppressor gene encoded on chromosome 22q11.2 that encodes a core subunit of SWI/SNF chromatin remodeling complexes and plays a critical role in regulating gene expression and chromatin structure. We describe a case of SMARCB1 (integrase interactor 1)-deficient sinonasal carcinoma of the left maxillary sinus in a 63-year-old woman with an initial presentation of numbness of the maxillary teeth and facial swelling.
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http://dx.doi.org/10.1016/j.joms.2020.05.033DOI Listing
October 2020

Postoperative Anatomic Position of Mandibular Free Flap Neocondyles Affects Patient Symptoms.

Facial Plast Surg Aesthet Med 2021 Jan-Feb;23(1):36-41. Epub 2020 Jul 2.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Mandibular condyle reconstruction with vascularized free flaps can re-establish form and function after resection. However, no reports have been published regarding the postoperative anatomic seating of these reconstructions. To use postoperative axial imaging to determine whether condylar reconstructions migrate and correlate their ultimate location with postoperative symptoms. A prospectively maintained database of free flap cases performed between 2006 and 2019 at a single institution was queried. Twenty-one consecutive patients who underwent reconstructions that involved the mandibular condyle who also had postoperative axial imaging were selected for review. Distances were measured from the reconstructed condyle to the lateral, superior, and posterior aspect of the temporomandibular joint (TMJ), and correlated with postoperative symptoms and jaw function. Condyle displacement, postoperative diet, jaw pain, trismus, and malocclusion. In total, 57% of patients had 1 cm or greater displacement of the condylar reconstruction from the TMJ in at least one vector. Anterior displacement of condyle by >1 cm was associated with jaw misalignment (42.8%) and clicking (14.3%) [odds ratio (OR) 37.3, 95% confidence interval (CI) 1.6-866.9,  = 0.024]. However, 83.3% of these patients were able to return to a normal diet and denied dysphagia. All edentulous patients had acceptable anteroposterior alignment, but 42.8% of dentulous patients had anterior displacement >1 cm ( = 0.12). Inferior displacement >1 cm was associated with dysphagia (OR 23, 95% CI 1.07-494.6,  = 0.04), but not pain or trismus. Eleven patients had multiple postoperative computed tomography scans, on average 21 months apart. The reconstructed location was stable in all 11 patients. Patients undergoing free flap reconstruction of the mandibular condyle often return to normal diet, even when their reconstructions do not sit perfectly within the TMJ. Anterior displacement of the neocondyle may be more common in dentulous patients due to stress on the joint from chewing and produces some dysfunction and misalignment. Inferior displacement of the neocondyle may result in dysphagia. The reconstructed condyles are unlikely to migrate over time.
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http://dx.doi.org/10.1089/fpsam.2020.0110DOI Listing
July 2020

Natural History and Consequences of Nonunion in Mandibular and Maxillary Free Flaps.

Otolaryngol Head Neck Surg 2020 Nov 16;163(5):956-962. Epub 2020 Jun 16.

Department of Otolaryngology-Head & Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.

Objective: To describe the natural history of bone segment union in head and neck free flap procedures and detail the association of poor segment union with postoperative complications.

Study Design: Case series with chart review.

Setting: Single tertiary care referral center.

Subjects And Method: Patients with mandibular or maxillary defects reconstructed with osseous or osteocutaneous free flaps were analyzed (n = 104). Postoperative computed tomography or positron emission tomography/computed tomography scans were reviewed for signs of osseointegration and nonunion. Postoperative wound complications were correlated with imaging findings.

Result: Thirty-seven percent of appositions had partial union on nonunion. Appositions between osteotomized free flap segments form complete unions at a higher rate than appositions with native bone (65% vs 53%, = .0006). If an apposition shows a gap of ≥1 mm, the chances of failing to form a complete union are greatly increated (79% vs 8%, = .0009). Radiographic nonunion was associated with an increased likelihood of postoperative wound complications (40% vs 19%, = .025) and in most cases was present before development of complications.

Conclusion: Radiographic evidence of partial union or nonunion of free flap osseous segments greatly exceeds reported rates of clinically evident nonunion. Unions likely form between free flap appositions before unions to the native bone. If initial bone segments are >1-mm apart, the chance of progression to complete union is low. Incomplete osseointegration appears to be a marker for development of wound complications.
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http://dx.doi.org/10.1177/0194599820931069DOI Listing
November 2020

Long-Term Complications of Osteocutaneous Free Flaps in Head and Neck Reconstruction.

Otolaryngol Head Neck Surg 2020 May 24;162(5):641-648. Epub 2020 Mar 24.

Department of Otolaryngology-Head & Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA.

Objective: To determine the frequency at which patients with osteocutaneous free flap reconstruction of the head and neck develop long-term complications and identify predisposing perioperative factors.

Study Design: A prospectively maintained database of free flaps performed at a single institution over a 10-year period was queried.

Setting: Single tertiary care referral center.

Subjects And Methods: In total, 250 osseous or osteocutaneous free flaps (OCFFs) for mandibular or maxillary reconstruction were analyzed. Data were collected on demographics, preoperative therapy, resection location, adjuvant treatment, complications, and subsequent surgeries, and multivariate analysis was performed. Subgroup analysis based on perioperative factors was performed.

Results: The median follow-up time was 23 months. In 185 patients with at least 6 months of follow-up, 17.3% had at least 1 long-term complication, most commonly wound breakdown, fistula or plate extrusion (13.5%), osteoradionecrosis or nonunion (6.5%), and infected hardware (5.9%). Prior chemoradiotherapy and cancer diagnosis predisposed patients to long-term complications. At the 5-year follow-up, 21.7% of patients had experienced a long-term complication.

Conclusions: Long-term complications after OCFF occurred in 17% of patients. In this series, a preoperative history of chemoradiation and those undergoing maxillary reconstruction were at high risk for the development of long-term complications and thus warrant diligent follow-up. However, OCFFs can often enjoy long-term viability and survival, even in the case of perioperative complications and salvage surgery.
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http://dx.doi.org/10.1177/0194599820912727DOI Listing
May 2020

Insufflation in minimally invasive surgery: Is there any advantage in staying low?

J Pediatr Surg 2020 Jul 26;55(7):1356-1362. Epub 2020 Jan 26.

Specialist Neonatal and Paediatric Surgery, Great Ormond Street Hospital, Paediatric Surgery, London, United Kingdom; Stem Cell and Regenerative Medicine Section, DBC, University College London, Great Ormond Institute of Child Health, London, United Kingdom. Electronic address:

Aim: Minimally invasive repair of esophageal atresia with tracheoesophageal fistula (EA/TEF) and congenital diaphragmatic hernia (CDH) is feasible and confers benefits compared to thoracotomy or laparotomy. However, carbon dioxide (CO) insufflation can lead to hypercapnia and acidosis. We sought to determine the effect of lower insufflation pressures on patients' surrogate markers for CO absorption - arterial partial pressure of CO (PaCO), end tidal CO (EtCO) and pH.

Methods: Single center retrospective review, including neonates without major cardiac anomaly. Selected patients formed 2 groups: Historical pressure (HP) group and low pressure (LP) group. We reported on the patients' preoperative characteristics that potentially confound the degree of CO absorption or elimination. Outcome measures were perioperative PaCO, EtCO, arterial pH and anesthetic time.

Results: 30 patients underwent minimally invasive surgery for CDH and 24 patients for EA/TEF with similar distribution within the HP and LP group. For CDH patients as well as for EA/TEF patients, there were no significant differences in their preoperative characteristics or surgery duration comparing HP and LP groups. With a decrease in insufflation pressure in CDH patients, there were a significant decrease (p = 0.002) in peak PaCO and an improvement in nadir pH (p = 0.01). For the EA/TEF patients, the decrease in insufflation pressure was associated with a significant decrease (p = 0.03) in peak EtCO. Considering all 54 patients, we found EtCO to be highly significantly inversely correlated with pH and positively correlated with intraoperative PaCO (p < 0.001). Baseline Hb was inversely correlated with mean EtCO (p < 0.001).

Conclusion: With lower insufflation pressures, CDH patients had significantly improved hypercapnia and acidosis, while EA/TEF patients had significantly reduced EtCO. EtCO was correlated with acidosis and hypercapnia.

Type Of Study: Retrospective case control study.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.11.026DOI Listing
July 2020

Evaluating the impact of smoking on disease-specific survival outcomes in patients with human papillomavirus-associated oropharyngeal cancer treated with transoral robotic surgery.

Cancer 2020 01 7;126(9):1873-1887. Epub 2020 Feb 7.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

Background: When treated nonsurgically with definitive chemoradiation, smokers with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a worse prognosis compared with their nonsmoking counterparts. To the authors' knowledge, the prognostic significance of smoking in surgically treated patients is unknown.

Methods: The current study is a retrospective case series of patients with HPV-positive OPSCC who underwent upfront transoral robotic surgery at a single institution from 2010 through 2017. Exclusion criteria were nonoropharyngeal primary tumors, histology other than SCC, HPV-negative tumors, previous history of head and neck cancer, and/or previous head and neck radiotherapy. Recurrence-free survival (RFS), overall survival, and disease-specific survival were compared using the Kaplan-Meier method and the log-rank test. Smoking history was categorized as never smokers (<1 pack-year), current smokers (smoking at the time of the cancer diagnosis), and former smokers.

Results: A total of 258 patients met the study criteria. The average age was 60 years, and approximately 87% of patients were male. A total of 148 patients (57.4%) were smokers whereas 110 (42.6%) reported never smoking. There were 44 active smokers (17.1%) and 104 former smokers (40.3%). The median follow-up was 3.23 years. There were 17 patients of disease recurrence. Smoking pack-year history was not found to be significant for RFS (hazard ratio, 1.01; 95% CI, 0.99-1.03 [P = .45]). There was no significant difference in RFS noted between never and ever smokers (92% vs 89.8%; P = .85) nor was there a difference observed between never, former, and current smokers (92% vs 91.5% vs 86.1%, respectively; P = .69).

Conclusions: A smoking history is common in patients with HPV-positive OPSCC. In the current study, HPV-positive smokers were found to have excellent survival and locoregional control, similar to their nonsmoking counterparts. The results of the current study do not support the exclusion of smokers with early-stage, HPV-positive OPSCC from transoral robotic surgery-based deintensification trials.
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http://dx.doi.org/10.1002/cncr.32739DOI Listing
January 2020

Virtual Surgical Planning in Subscapular System Free Flap Reconstruction of Midface Defects.

Oral Oncol 2020 02 19;101:104508. Epub 2019 Dec 19.

Thomas Jefferson University, Department of Otolaryngology - Head & Neck Surgery, Philadelphia, PA, USA.

Objectives: Reconstruction of the midface has many inherent challenges, including orbital support, skull base reconstruction, optimizing midface projection, separation of the nasal cavity and dental rehabilitation. Subscapular system free flaps (SF) have sufficient bone stock to support complex reconstruction and the option of separate soft tissue components. This study analyzes the effect of virtual surgical planning (VSP) in SF for midface on subsite reconstruction, bone segment contact and anatomic position.

Materials And Methods: Retrospective cohort of patients with midface defects that underwent SF reconstruction at a single tertiary care institution.

Results: Nine cases with VSP were compared to fourteen cases without VSP. VSP was associated with a higher number of successfully reconstructed subunits (5.9 vs 4.2, 95% CI of mean difference 0.31-3.04, p = 0.018), a higher number of successful bony contact between segments (2.2 vs 1.4, 95% CI of mean difference 0.0-1.6, p = 0.050), and a higher percent of segments in anatomic position (100% vs 71%, 95% CI of mean difference 2-55%, p = 0.035). When postoperative bone position after VSP reconstruction was compared to preoperative scans, the difference in anteroposterior, vertical and lateral projection compared to the preoperative 'ideal' bone position was <1 cm in 82% of measurements. There were no flap losses.

Conclusion: VSP may augment SF reconstruction of the midface by allowing for improved subunit reconstruction, bony segment contact and anatomically correct bone segment positioning. VSP can be a useful adjunct for complex midface reconstruction and the benefits should be weighed against cost.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104508DOI Listing
February 2020

Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Sci Rep 2019 12 17;9(1):19256. Epub 2019 Dec 17.

Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts.
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http://dx.doi.org/10.1038/s41598-019-55352-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917707PMC
December 2019

Surgically treated intractable constipation in children evaluated with colonic manometry.

J Pediatr Surg 2020 Feb 2;55(2):265-268. Epub 2019 Nov 2.

Department of Specialist Neonatal and Pediatric Surgery, Great Ormond Street Hospital, London, United Kingdom. Electronic address:

Background: 'Intractable constipation' (IC) is constipation unresponsive to 3 months of optimal conventional treatment. Colonic manometry (CM) is recommended as a diagnostic modality for evaluation of these children. This study aimed to review outcomes of children with IC who were managed surgically at a single tertiary care center.

Methods: Records of children with IC who were treated with ACE (antegrade colonic enema), colostomy, or ileostomy (2006-2018) were reviewed. "Success" was defined as adequate evacuation without need for further unplanned surgery. Data are median (range).

Results: Sixty-seven children underwent surgery, of whom 56 with preoperative CM were included. Age at surgery was 8.6 (3.3-15.1) years. Eight had normal manometry and underwent ACE with 75% success. Thirty-six had left-sided dysfunction and underwent ACE (18), colostomy (14) or ileostomy (4) as initial intervention with 61, 70, and 100% success. Twelve with pancolonic dysfunction underwent ACE (6) or ileostomy (6) with 60 and 100% success. Twenty underwent repeat manometry 2.2 years (10 months-7.6 years) after surgery. Of 18 with stoma, 8 had resolution or improvement and of these, 7 underwent stoma reversal with a simultaneous ACE. Two patients with ACE had improvement, 1 is still on ACE washouts, and 1 is off all treatment. Ten with persistent dysfunction remain diverted. At 3.2 years (4 months-9.9 years) follow-up, 18 remain on ACE washouts, 9 have colostomy, 19 ileostomy, and 10 are off treatment and doing well.

Conclusion: We present a large series of patients who were surgically managed for IC. CM may guide therapy in these children.

Type Of Study: Retrospective comparative study LEVEL OF EVIDENCE: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.10.046DOI Listing
February 2020