Publications by authors named "Martin Broome"

34 Publications

Three-Dimensional Printed Nasal Prostheses After Oncologic Rhinectomies: Workflow and Patients' Satisfaction.

J Craniofac Surg 2021 Apr 5. Epub 2021 Apr 5.

Department of Otorhinolaryngology-Head and Neck Surgery, Lausanne University Hospital Department of Maxillofacial Surgery, Lausanne University Hospital, Lausanne, Switzerland.

Abstract: Reconstructions after oncologic full-thickness rhinectomies are often deferred from the ablative surgery. Definitive silicone prostheses are usually not used for transitional rehabilitation, and therefore, patients may deal with major facial defects for a long time before reconstruction. The aim was to develop a time- and cost-effective digital workflow to three-dimensional print temporary nasal prostheses and to assess patients' satisfaction. This prospective study enrolled all consecutive patients after full thickness ablative surgery and deferred reconstruction, from May 2018 to October 2019, at a tertiary care academic institution. With a dedicated software, the pre- and postoperative scans were three-dimensional processed to create the prosthesis and they were directly printed in elastic transparent resin. A cross-sectional survey was conducted 4 months after the rehabilitation to assess patients' satisfaction regarding comfort, aesthetics, and security of the retaining system. Seven patients were enrolled and they were all rehabilitated using this workflow. Mean time of design was 2h48 (SD 40 minutes), and mean printing time was 5h18 (SD 1 hour). Mean cost of production was 753 U.S. Dollars (SD 144 U.S. Dollars). Median scores of the visual analog scales were 8 out of 10 for each topic with interquartile range of 4 to 7 for aesthetics, 7 to 9 for comfort, and 7 to 10 for security of the retaining system. It has shown its feasibility in terms of costs and time of production. Patients were satisfied and it can be considered as a mean to help patients to deal with treatment sequelaes before definitive reconstruction.
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http://dx.doi.org/10.1097/SCS.0000000000007659DOI Listing
April 2021

An Intrinsically-Adhesive Family of Injectable and Photo-Curable Hydrogels with Functional Physicochemical Performance for Regenerative Medicine.

Macromol Rapid Commun 2021 Apr 8:e2000660. Epub 2021 Apr 8.

Laboratory of Biomechanical Orthopedics, EPFL, Lausanne, 1015, Switzerland.

Attaching hydrogels to soft internal tissues is crucial for the development of various biomedical devices. Tough sticky hydrogel patches present high adhesion, yet with lack of injectability and the need for treatment of contacting surface. On the contrary, injectable and photo-curable hydrogels are highly attractive owing to their ease of use, flexibility of filling any shape, and their minimally invasive character, compared to their conventional preformed counterparts. Despite recent advances in material developments, a hydrogel that exhibits both proper injectability and sufficient intrinsic adhesion is yet to be demonstrated. Herein, a paradigm shift is proposed toward the design of intrinsically adhesive networks for injectable and photo-curable hydrogels. The bioinspired design strategy not only provides strong adhesive contact, but also results in a wide window of physicochemical properties. The adhesive networks are based on a family of polymeric backbones where chains are modified to be intrinsically adhesive to host tissue and simultaneously form a hydrogel network via a hybrid cross-linking mechanism. With this strategy, adhesion is achieved through a controlled synergy between the interfacial chemistry and bulk mechanical properties. The functionalities of the bioadhesives are demonstrated for various applications, such as tissue adhesives, surgical sealants, or injectable scaffolds.
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http://dx.doi.org/10.1002/marc.202000660DOI Listing
April 2021

Mucosal Melanoma of the Head and Neck: A Retrospective Review and Current Opinion.

Front Surg 2020 20;7:616174. Epub 2021 Jan 20.

ENT Department, CHUV, Lausanne, Switzerland.

Head and Neck Mucosal Melanoma (HNMM) is an uncommon malignancy that arises in decreasing order in the nasal cavity, the paranasal sinuses, and the oral cavity. Although radical surgery followed by eventual radiotherapy is acknowledged as the mainstay treatment, patients with advanced stages or multi-focal tumors benefit from new systemic therapies. We wish to share our experience with these treatments and review the current literature. We present a case review of every patient treated in our center for an HNMM over the past 10 years, including every patient treated in our center for an HNMM over the past 10 years. We analyzed clinical characteristics, treatment modalities, and outcomes. We included eight patients aged from 62 to 85 years old. We found six MM in the nasal cavity, one in the sphenoidal sinus, and one in the piriform sinus. Six patients underwent endoscopic surgery with negative margins, six underwent radiotherapy with variable modalities. Immunotherapy or targeted therapy was given in cases extensive tumors without the possibility of a surgical treatment or in two patient as an adjuvant treatment after R0 surgery. The three-year overall survival was 50%, and three patients (37.5%) are in remission. HNMM is associated with poor oncologic outcomes regarding the concerned patients of our review, as reported in the literature. New treatments such as immunotherapies or targeted therapies have not significantly changed the prognosis, but they may offer new interesting perspectives. Our small series of cases seems to confirm that surgical resection with negative margins improves overall survival.
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http://dx.doi.org/10.3389/fsurg.2020.616174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873938PMC
January 2021

[Anosmia and COVID-19].

Rev Med Suisse 2020 Apr;16(N° 691-2):849-851

Service d'ORL et chirurgie cervico-faciale, CHUV, 1011 Lausanne.

Anosmia associated or not with dysgeusia seems to be a frequent symptom in cases of infection with SARS-CoV-2 responsible for COVID-19. It can be the initial symptom of the disease or remain isolated in pauci-symptomatic patients. Waiting for scientific confirmation and in the context of the current pandemic, it seems essential to consider any patient with a new anosmia as being infected with SARS-CoV-2 until proven otherwise. These patients should therefore isolate themselves and remain alert to the occurrence of other symptoms suggestive of the infection and/or be tested. Topical and systemic corticosteroids and nose washes are contraindicated. The natural course of anosmia seems to be favorable in most cases.
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April 2020

[New features in the management of labio-maxillo-palatal clefts at the CHUV].

Rev Med Suisse 2020 Jan;16(679):237-240

Service de chirurgie de l'enfant et de l'adolescent, Département Femme Mère Enfant, CHUV, 1011 Lausanne.

The labio-maxillofacial cleft (LMFC) penalizes the child from birth by its aesthetic, functional, psychological and social repercussions. The prognosis is conditioned by a multidisciplinary care that starts from the antenatal period to continue until the end of growth. The treatment is long and complex. This explains the multiplicity of techniques and the variability of schedules according to the teams. The purpose of this article is to describe the protocol of management of the LMFC within the multi-disciplinary team in Lausanne and to emphasize the novelties in both surgical and organizational plan.
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January 2020

[Internal medicine, seen from the mouth].

Rev Med Suisse 2019 Nov;15(672):2131-2136

Service de médecine interne, CHUV, 1011 Lausanne.

Many diseases affect the oral cavity. Therefore, the mouth is an organ that internists should observe carefully. Hereafter we present five illustrations of oral semiology that reflect a systemic condition: a strawberry tongue, an ulceration, a labial lesion, a gingival hyperplasia and a gingival hyperpigmentation. Each time, a differential diagnosis is to be considered, potentially allowing the identification of severe diseases.
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November 2019

The Mandibular Ramus: An Alternative Donor Site for Secondary Alveolar Bone Grafting in Clefts of the Alveolus.

J Craniofac Surg 2019 Nov-Dec;30(8):2590-2592

Division of Oral and Maxillofacial Surgery.

The authors describe the use of the mandibular ramus as an autologous bone graft material for secondary alveolar bone grafting in cleft patients. This technique represents a safe and effective alternative to currently used donor sites. Furthermore, it allows to minimize patient discomfort, so that they can be treated as outpatients.
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http://dx.doi.org/10.1097/SCS.0000000000005684DOI Listing
January 2020

Composite Double-Network Hydrogels To Improve Adhesion on Biological Surfaces.

ACS Appl Mater Interfaces 2018 Nov 30;10(45):38692-38699. Epub 2018 Oct 30.

Department of Maxillofacial Surgery , Lausanne University Hospital , CH-1011 Lausanne , Switzerland.

Despite the development of hydrogels with high mechanical properties, insufficient adhesion between these materials and biological surfaces significantly limits their use in the biomedical field. By controlling toughening processes, we designed a composite double-network hydrogel with ∼90% water content, which creates a dissipative interface and robustly adheres to soft tissues such as cartilage and meniscus. A double-network matrix composed of covalently cross-linked poly(ethylene glycol) dimethacrylate and ionically cross-linked alginate was reinforced with nanofibrillated cellulose. No tissue surface modification was needed to obtain high adhesion properties of the developed hydrogel. Instead, mechanistic principles were used to control interfacial crack propagation. Comparing to commercial tissue adhesives, the integration of the dissipative polymeric network on the soft tissue surfaces allowed a significant increase in the adhesion strength, such as ∼130 kPa for articular cartilage. Our findings highlight the significant role of controlling hydrogel structure and dissipation processes for toughening the interface. This research provides a promising path to the development of highly adhesive hydrogels for tissues repair.
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http://dx.doi.org/10.1021/acsami.8b10735DOI Listing
November 2018

[Sleep apnea : diagnostic and therapeutic modalities in case of failure of the CPAP].

Rev Med Suisse 2018 Oct;14(621):1751-1754

Service d'ORL et de chirurgie cervico-faciale, CHUV, 1011 Lausanne.

Obstructive sleep apnea (OSA) is a sleep disorder that affects 49 % of men and 23% of women over 40 years old. CPAP is currently the treatment of choice for severe OSAS, but there are mild to moderate cases of OSAS with poor compliance or intolerance to CPAP, for which alternative treatments should be considered. In this article, we present a tool for evaluation of the upper airways, the DISE (Drug-induced sleep endoscopy), the OAM (mandibular advancement device), the bimaxillary advancement osteotomy, the hypoglossal nerve stimulation and the positional treatment.
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October 2018

Should You Buy a Three-Dimensional Printer? A Study of an Orbital Fracture.

J Craniofac Surg 2018 Oct;29(7):1925-1927

Department of Oral & Maxillo-Facial Surgery, Lausanne University Hospital, Lausanne, Switzerland.

The use of three-dimensional (3D) printing has been growing significantly in medicine for the past 10 years, especially in maxillofacial surgery. A lot a different softwares and printers are available on the market, and it can be difficult to choose which one fits best one's needs. In the authors' institution, the authors regularly print orbits to prepare the reconstruction. The authors then compared the 3D printing of an orbital fracture between a professional and nonprofessional software and between a bottom of the range and a more elaborated printer. The results show that there is a wide variation between the quality of the printing, as well as the time used for the preparation. Costs between free or professional software must also be considered. In conclusion, an analysis of needs and what is available on the market must be studied before investing in 3D printing.
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http://dx.doi.org/10.1097/SCS.0000000000005048DOI Listing
October 2018

Factors Influencing the Incidence of Severe Complications in Head and Neck Free Flap Reconstructions.

Plast Reconstr Surg Glob Open 2016 Oct 27;4(10):e1013. Epub 2016 Oct 27.

Division of Maxillo-Facial Surgery, CHUV, University of Lausanne, Lausanne, Switzerland; Department of Otolaryngology-Head and Neck Surgery, CHUV, University of Lausanne, Lausanne, Switzerland; and Department of Otolaryngology-Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany.

Background: Complications after head and neck free-flap reconstructions are detrimental and prolong hospital stay. In an effort to identify related variables in a tertiary regional head and neck unit, the microvascular reconstruction activity over the last 5 years was captured in a database along with patient-, provider-, and volume-outcome-related parameters.

Methods: Retrospective cohort study (level of evidence 3), a modified Clavien-Dindo classification, was used to assess severe complications.

Results: A database of 217 patients was created with consecutively reconstructed patients from 2009 to 2014. In the univariate analysis of severe complications, we found significant associations ( < 0.05) between type of flap used, American Society of Anesthesiologists classification, T-stage, microscope use, surgeon, flap frequency, and surgeon volume. Within a binomial logistic regression model, less frequently versus frequently performed flap (odds ratio [OR] = 3.2; confidence interval [CI] = 2.9-3.5; = 0.000), high-volume versus low-volume surgeon (OR = 0.52; CI = -0.22 to 0.82; = 0.007), and ASA classification (OR = 2.9; CI = 2.4-3.4; = 0.033) were retained as independent predictors of severe complications. In a Cox-regression model, surgeon ( = 0.011), site of reconstruction ( = 0.000), T-stage ( = 0.001), and presence of severe complications ( = 0.015) correlated with a prolonged hospitalization.

Conclusions: In this study, we identified a correlation of patient-related factors with severe complications (ASA score) and prolonged hospital stay (T-stage, site). More importantly, we identified several provider- (surgeon) and volume-related (frequency with which a flap was performed and high-volume surgeon) factors as predictors of severe complications. Our data indicate that provider- and volume-related parameters play an important role in the outcome of microvascular free-flap procedures in the head and neck region.
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http://dx.doi.org/10.1097/GOX.0000000000001013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096513PMC
October 2016

Jaw Immobilization for Gamma Knife Surgery in Patients with Mandibular Lesions: A Newly, Innovative Approach.

Stereotact Funct Neurosurg 2016 11;94(5):342-347. Epub 2016 Oct 11.

Neurosurgery Service and Gamma Knife Center, Department of Clinical Neurosciences, University of Lausanne, Lausanne, Switzerland.

Background: The purpose of our report is to describe an innovative system used for mandibular immobilization during Gamma Knife surgery (GKS) procedures. It is based on an approach originally developed in Marseille in extracranial lesions, close to or involving the mandible, which may imply a certain degree of movement during the therapeutic image acquisitions and/or GKS treatment.

Methods: The maxillofacial surgeon applied bone titanium self-tapping monocortical screws (4; 2 mm diameter, 10 mm length) between roots of the teeth in the fixed gingiva (upper and lower maxillae) the day before GKS (local anesthesia, 5-10 min time). Two rubber bands were sufficient for the desired tension required to undergo GKS. We further proceeded with application of the Leksell stereotactic G frame and carried out the usual GKS procedure.

Results: The mean follow-up period was 2.3 years (range 0.6-3). Three patients have been treated with this approach: 2 cases with extracranial trigeminal schwannomas involving the mandibular branch, with decrease in tumor size on MR follow-up; 1 case with residual paracondylian mandibular arteriovenous malformation following partial embolization, completely obliterated at 7 months (digital subtraction angiography programmed 1 year after treatment).

Conclusions: Jaw immobilization appears to be a quick, minimally invasive, safe and accurate adjunctive technique to enhance GKS targeting precision.
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http://dx.doi.org/10.1159/000449065DOI Listing
February 2018

In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models.

Mol Cancer Ther 2016 07 19;15(7):1568-79. Epub 2016 Apr 19.

Amgen Inc., Thousand Oaks, California.

The MET receptor tyrosine kinase is involved in cell growth, survival, and invasion. Clinical studies with small molecule MET inhibitors have shown the role of biomarkers in identifying patients most likely to benefit from MET-targeted therapy. AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor. Herein, we describe AMG 337 preclinical activity and mechanism of action in MET-dependent tumor models. These studies suggest MET is the only therapeutic target for AMG 337. In an unbiased tumor cell line proliferation screen (260 cell lines), a closely related analogue of AMG 337, Compound 5, exhibited activity in 2 of 260 cell lines; both were MET-amplified. Additional studies examining the effects of AMG 337 on the proliferation of a limited panel of cell lines with varying MET copy numbers revealed that high-level focal MET amplification (>12 copies) was required to confer MET oncogene addiction and AMG 337 sensitivity. One MET-amplified cell line, H1573 (>12 copies), was AMG 337 insensitive, possibly because of a downstream G12A KRAS mutation. Mechanism-of-action studies in sensitive MET-amplified cell lines demonstrated that AMG 337 inhibited MET and adaptor protein Gab-1 phosphorylation, subsequently blocking the downstream PI3K and MAPK pathways. AMG 337 exhibited potency in pharmacodynamic assays evaluating MET signaling in tumor xenograft models; >90% inhibition of Gab-1 phosphorylation was observed at 0.75 mg/kg. These findings describe the preclinical activity and mechanism of action of AMG 337 in MET-dependent tumor models and indicate its potential as a novel therapeutic for the treatment of MET-dependent tumors. Mol Cancer Ther; 15(7); 1568-79. ©2016 AACR.
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http://dx.doi.org/10.1158/1535-7163.MCT-15-0871DOI Listing
July 2016

Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity.

J Med Chem 2016 Mar 11;59(6):2328-42. Epub 2016 Feb 11.

Amgen Incorporated , 360 Binney Street, Cambridge, Massachusetts 02142, United States.

Deregulation of the receptor tyrosine kinase mesenchymal epithelial transition factor (MET) has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of compound 23 (AMG 337), which demonstrates nanomolar inhibition of MET kinase activity, desirable preclinical pharmacokinetics, significant inhibition of MET phosphorylation in mice, and robust tumor growth inhibition in a MET-dependent mouse efficacy model.
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http://dx.doi.org/10.1021/acs.jmedchem.5b01716DOI Listing
March 2016

Grommets and speech at three and six years in children born with total cleft or cleft palate.

Int J Pediatr Otorhinolaryngol 2015 Dec 20;79(12):2243-7. Epub 2015 Oct 20.

Department of Pediatric Surgery, University Hospital Center of the Canton of Vaud (CHUV), Lausanne, Switzerland. Electronic address:

Objective: Grommets may be considered as the treatment of choice for otitis media with effusion (OME) in children born with a cleft. But the timing and precise indications to use them are not well established. The aim of the study is to compare the results of hearing and speech controls at three and six year-old in children born with total cleft or cleft palate in the presence or not of grommets.

Methods: This retrospective study concerns non syndromic children born between 1994 and 2006 and operated for a unilateral cleft lip palate (UCLP) or a cleft palate (CP) alone, by one surgeon with the same schedule of operations (Malek procedure). We compared the results of clinical observation, tympanometry, audiometry and nasometry at three and six year-old. The Borel-Maisonny classification was used to evaluate the velar insufficiency. None of the children had preventive grommets. The Fisher Exact Test was used for statistical analysis with p<0.05 considered as significant.

Results: Seventy-seven patients were analyzed in both groups. Abnormal hearing status was statistically more frequent in children with UCLP compared to children with CP, at three and six years (respectively, 80-64%, p<0.03 and 78-60%, p<0.02), with the use of grommets at six years in 43% of cases in both groups. Improvement of hearing status between three and six year-old was present in 5% of children with UCLP and 9% with CP, without the use of grommets.

Conclusion: The use of grommets between three and six year-old was not associated to any improvement of hearing status or speech results children with UCLP or with CP, with a low risk of tympanosclerosis. These results favor the use of grommets before the age of three, taking into account the risk of long term tympanosclerosis.
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http://dx.doi.org/10.1016/j.ijporl.2015.10.012DOI Listing
December 2015

Discovery of potent and selective 8-fluorotriazolopyridine c-Met inhibitors.

J Med Chem 2015 Mar 3;58(5):2417-30. Epub 2015 Mar 3.

Amgen Inc. , 360 Binney Street, Cambridge, Massachusetts 02142, United States.

The overexpression of c-Met and/or hepatocyte growth factor (HGF), the amplification of the MET gene, and mutations in the c-Met kinase domain can activate signaling pathways that contribute to cancer progression by enabling tumor cell proliferation, survival, invasion, and metastasis. Herein, we report the discovery of 8-fluorotriazolopyridines as inhibitors of c-Met activity. Optimization of the 8-fluorotriazolopyridine scaffold through the combination of structure-based drug design, SAR studies, and metabolite identification provided potent (cellular IC50 < 10 nM), selective inhibitors of c-Met with desirable pharmacokinetic properties that demonstrate potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.
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http://dx.doi.org/10.1021/jm501913aDOI Listing
March 2015

Are virtual planning and guided surgery for head and neck reconstruction economically viable?

J Oral Maxillofac Surg 2015 Jan 1;73(1):170-5. Epub 2014 Aug 1.

Chief Consultant, Maxillofacial Surgery Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Purpose: Virtual planning and guided surgery with or without prebent or milled plates are becoming more and more common for mandibular reconstruction with fibular free flaps (FFFs). Although this excellent surgical option is being used more widely, the question of the additional cost of planning and cutting-guide production has to be discussed. In capped payment systems such additional costs have to be offset by other savings if there are no special provisions for extra funding. Our study was designed to determine whether using virtual planning and guided surgery resulted in time saved during surgery and whether this time gain resulted in self-funding of such planning through the time saved.

Materials And Methods: All consecutive cases of FFF surgery were evaluated during a 2-year period. Institutional data were used to determine the price of 1 minute of operative time. The time for fibula molding, plate adaptation, and insetting was recorded.

Results: During the defined period, we performed 20 mandibular reconstructions using FFFs, 9 with virtual planning and guided surgery and 11 freehand cases. One minute of operative time was calculated to cost US $47.50. Multiplying this number by the time saved, we found that the additional cost of virtual planning was reduced from US $5,098 to US $1,231.50 with a prebent plate and from US $6,980 to US $3,113.50 for a milled plate.

Conclusions: Even in capped health care systems, virtual planning and guided surgery including prebent or milled plates are financially viable.
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http://dx.doi.org/10.1016/j.joms.2014.07.038DOI Listing
January 2015

Rhinopharyngeal autologous fat injection for treatment of velopharyngeal insufficiency in patients with cleft palate.

Eur Arch Otorhinolaryngol 2015 May 20;272(5):1277-85. Epub 2014 Nov 20.

Department of Otolaryngology, Head and Neck Surgery, Lausanne University Hospital (CHUV), 1011, Lausanne, Switzerland,

Patients with cleft palate are prone to velopharyngeal insufficiency. In minor cases or when hypernasal speech does not resolve after velopharyngoplasty, an augmentation pharyngoplasty with autologous fat can be proposed. The aim of the present study is to evaluate the short-term (within 2 months) and long-term efficiency (during the 24 months following the procedure) of our procedure in the setting of velopharyngeal insufficiency related to a cleft palate. Twenty-two patients with cleft palate related velopharyngeal insufficiency were included in this retrospective study. All patients were operated following the same technique, in the same institution. The pre- and postoperative evaluations included a nasometry, a subjective evaluation using the Borel-Maisonny score, and a nasofibroscopy to assess the degree of velopharyngeal closure. Scores of Borel-Maisonny and nasometry were compared before, shortly after the procedure (within 2 months) and long term after the procedure (within 24 months). Forty-one procedures in 22 patients with a cleft palate performed in our institution between October 2004 and January 2012 were included in the study. Nine patients had a previous velopharyngoplasty with persistent rhinolalia despite intensive speech therapy. In 14 patients the procedure was repeated because of recurrent hypernasal speech after the first injection. The average number of procedures per patient was 1.8. Postoperative nasometry and Borel-Maisonny scores were statistically significantly improved and remained stable until the end of the follow-up (median 42 months postoperative) in most patients. Complications were rare and minor. Autologous fat injection is a simple procedure for treatment of minor velopharyngeal insufficiencies in patients with cleft palate, with good long-term results and few complications.
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http://dx.doi.org/10.1007/s00405-014-3380-0DOI Listing
May 2015

Facial Pain Associated with CPAP Use: Intra-Sinusal Third Molar.

Case Rep Otolaryngol 2014 5;2014:837252. Epub 2014 Jun 5.

Division de Chirurgie Maxillo-Faciale, Centre Hospitalier Universitaire Vaudois (CHUV), Switzerland.

Objective. This paper describes a patient with left hemifacial pain elicited by the use of a CPAP mask. Case Report. A 74-year-old man was referred with a history of pain in the left maxillary sinus related to the use of his CPAP interface, thereby prohibiting the use of the latter. Computed tomography revealed an intra-sinusal ectopic third molar in the left maxillary sinus floor corresponding to the painful area. After removal of the ectopic tooth under local anesthesia by a Caldwell-Luc approach, the patient was relieved of his symptoms. Conclusion. Although an ectopic tooth in the maxillary sinus is rare, this case points out the importance of actively looking for a regional problem if patients cannot tolerate the CPAP interface since this can lead to issues of incompliance and medical complications due to the untreated obstructive sleep apnoea syndrome.
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http://dx.doi.org/10.1155/2014/837252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068067PMC
July 2014

Isolated bilateral zygomatic arch fracture: an unusual pattern.

J Craniofac Surg 2014 May;25(3):1111-2

From the Oral and Maxillo-Facial Surgery Department, Lausanne University Hospital, Lausanne, Switzerland.

Isolated fractures of the zygomatic arch represent 5% to 14% of all zygomatic complex fractures. Bilateral isolated zygomatic arch fractures, which are defined as fractures of both zygomatic arches without any other facial fracture, are extremely rare. In this case report, we present a rare case of this facial fracture pattern.
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http://dx.doi.org/10.1097/SCS.0000000000000741DOI Listing
May 2014

Videos in clinical medicine. Repositioning dislocated temporomandibular joints.

N Engl J Med 2014 Feb;370(6):e9

From the Department of Maxillofacial Surgery, Lausanne University Hospital, Lausanne, Switzerland.

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http://dx.doi.org/10.1056/NEJMvcm1301200DOI Listing
February 2014

Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors.

Bioorg Med Chem Lett 2012 Jun 25;22(12):4089-93. Epub 2012 Apr 25.

Amgen Inc., 360 Binney St., Cambridge, MA 02142, USA.

Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of a structurally diverse series of carbon-linked quinoline triazolopyridinones, which demonstrates nanomolar inhibition of c-Met kinase activity. This novel series of inhibitors exhibits favorable pharmacokinetics as well as potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.
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http://dx.doi.org/10.1016/j.bmcl.2012.04.072DOI Listing
June 2012

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

Otolaryngol Head Neck Surg 2011 May;144(5):726-32

Otolaryngology, Head and Neck Surgery Department, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Objective: Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx.

Study Design: Case series with chart review.

Setting: University tertiary care center for head and neck oncology.

Subjects And Methods: Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses.

Results: The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002).

Conclusion: Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.
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http://dx.doi.org/10.1177/0194599810396290DOI Listing
May 2011

Retraction movement of the Frova airway intubation introducer to assist nasotracheal intubation in patients with limited mouth opening.

Anesthesiology 2010 Dec;113(6):1476-8

Department of Anesthesiology, University Hospital Center and University of Lausanne, Rue du Bugnon 11, 1011 Lausanne, Switzerland.

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http://dx.doi.org/10.1097/ALN.0b013e3181f98009DOI Listing
December 2010

Influence of the primary cleft palate closure on the future need for orthognathic surgery in unilateral cleft lip and palate patients.

J Craniofac Surg 2010 Sep;21(5):1615-8

Maxillo-Facial Surgery Department, CHUV University Hospital, Lausanne, Switzerland.

The aim of the study was to determine the influence of the dissection of the palate during primary surgery and the type of orthognathic surgery needed in cases of unilateral total cleft. The review concerns 58 children born with a complete unilateral cleft lip and palate and treated between 1994 and 2008 at the appropriate age for orthognathic surgery. This is a retrospective mixed-longitudinal study. Patients with syndromes or associated anomalies were excluded. All children were treated by the same orthodontist and by the same surgical team. Children are divided into 2 groups: the first group includes children who had conventional primary cleft palate repair during their first year of life, with extensive mucoperiosteal undermining. The second group includes children operated on according to the Malek surgical protocol. The soft palate is closed at the age of 3 months, and the hard palate at 6 months with minimal mucoperiosteal undermining. Lateral cephalograms at ages 9 and 16 years and surgical records were compared. The need for orthognathic surgery was more frequent in the first than in the second group (60% vs 47.8%). Concerning the type of orthognathic surgery performed, 2- or 3-piece Le Fort I or bimaxillary osteotomies were also less required in the first group. Palate surgery following the Malek procedure results in an improved and simplified craniofacial outcome. With a minimal undermining of palatal mucosa, we managed to reduce the amount of patients who required an orthognathic procedure. When this procedure was indicated, the surgical intervention was also greatly simplified.
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http://dx.doi.org/10.1097/SCS.0b013e3181ef2eedDOI Listing
September 2010

Selective and potent Raf inhibitors paradoxically stimulate normal cell proliferation and tumor growth.

Mol Cancer Ther 2010 Aug 27;9(8):2399-410. Epub 2010 Jul 27.

Department of Hematology, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.

Raf inhibitors are under clinical investigation, specifically in patients with tumor types harboring frequent activating mutations in B-Raf. Here, we show that cell lines and tumors harboring mutant B-Raf were sensitive to a novel series of Raf inhibitors (e.g., (V600E)B-Raf A375, IC(50) on cells = 2 nmol/L; ED(50) on tumor xenografts = 1.3 mg/kg). However, in cells and tumors with wild-type B-Raf, exposure to Raf inhibitors resulted in a dose-dependent and sustained activation of mitogen-activated protein kinase signaling. In some of these cell lines, Raf inhibition led to entry into the cell cycle, enhanced proliferation, and significantly stimulated tumor growth in vivo. Inhibition with structurally distinct Raf inhibitors or isoform-specific small interfering RNA knockdown of Raf showed that these effects were mediated directly through Raf. Either A-Raf or C-Raf mediated the Raf inhibitor-induced mitogen-activated protein kinase pathway activation in an inhibitor-specific manner. These paradoxical effects of Raf inhibition were seen in malignant and normal cells in vitro and in vivo. Hyperplasia of normal epithelial cells in the esophagus and the stomach was evident in mice with all efficacious Raf inhibitors (n = 8) tested. An implication of these results is that Raf inhibitors may induce unexpected normal cell and tumor tissue proliferation in patients.
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http://dx.doi.org/10.1158/1535-7163.MCT-10-0181DOI Listing
August 2010

Accuracy and predictability in use of AO three-dimensionally preformed titanium mesh plates for posttraumatic orbital reconstruction: a pilot study.

J Craniofac Surg 2009 Jul;20(4):1108-13

Service of Oral and Maxillofacial Surgery, Departments of Surgery, Hôpitaux Universitaire de Genève, Geneva, Switzerland.

The aim of this study was to prospectively evaluate the accuracy and predictability of new three-dimensionally preformed AO titanium mesh plates for posttraumatic orbital wall reconstruction.We analyzed the preoperative and postoperative clinical and radiologic data of 10 patients with isolated blow-out orbital fractures. Fracture locations were as follows: floor (N = 7; 70%), medial wall (N = 1; 1%), and floor/medial wall (N = 2; 2%). The floor fractures were exposed by a standard transconjunctival approach, whereas a combined transcaruncular transconjunctival approach was used in patients with medial wall fractures. A three-dimensional preformed AO titanium mesh plate (0.4 mm in thickness) was selected according to the size of the defect previously measured on the preoperative computed tomographic (CT) scan examination and fixed at the inferior orbital rim with 1 or 2 screws. The accuracy of plate positioning of the reconstructed orbit was assessed on the postoperative CT scan. Coronal CT scan slices were used to measure bony orbital volume using OsiriX Medical Image software. Reconstructed versus uninjured orbital volume were statistically correlated.Nine patients (90%) had a successful treatment outcome without complications. One patient (10%) developed a mechanical limitation of upward gaze with a resulting handicapping diplopia requiring hardware removal. Postoperative orbital CT scan showed an anatomic three-dimensional placement of the orbital mesh plates in all of the patients. Volume data of the reconstructed orbit fitted that of the contralateral uninjured orbit with accuracy to within 2.5 cm(3). There was no significant difference in volume between the reconstructed and uninjured orbits.This preliminary study has demonstrated that three-dimensionally preformed AO titanium mesh plates for posttraumatic orbital wall reconstruction results in (1) a high rate of success with an acceptable rate of major clinical complications (10%) and (2) an anatomic restoration of the bony orbital contour and volume that closely approximates that of the contralateral uninjured orbit.
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http://dx.doi.org/10.1097/SCS.0b013e3181abb44bDOI Listing
July 2009

[Treatment with bisphosphonates and previous dental health].

Rev Med Suisse 2009 Apr;5(200):909-10; author reply 910-1

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April 2009