The Cleft Palate–Craniofacial Journal 51(6) pp. 686–695 November 2014 Ó Copyright 2014 American Cleft Palate–Craniofacial Association

ORIGINAL ARTICLE Submucous Cleft Palate: A Systematic Review of Surgical Management Based on Perceptual and Instrumental Analysis Onur Gilleard, M.Sc., M.R.C.S., Debbie Sell, Ph.D., F.R.C.S.L.T., Ali M. Ghanem, M.D., Ph.D., M.R.C.S., Yasemin Tavsanoglu, B.Sc., M.R.C.S., Malcolm Birch, Ph.D., Brian Sommerlad, F.R.C.S. Eng., F.R.C.P.C.H., F.R.C.S.L.T. (Hon.) Objective: Submucous cleft palate (SMCP) is a congenital condition associated with abnormal development of the soft palate musculature. In a proportion of cases, this results in velopharyngeal insufficiency (VPI), the treatment for which includes pharyngeal flap surgery, pharyngoplasty, and palate reconstruction. The aim of this paper is to determine whether there is superiority of one or more types of surgical procedure over the others in improving speech in patients with VPI secondary to SMCP. Methodology: Nine databases, including MEDLINE and EMBASE, were searched between inception and January 2013 to identify articles published relating to the surgical management of SMCP. Only studies that reported outcome measures for postoperative speech were included in the systematic review. Results: Twenty-six studies analyzing the outcomes of surgery for VPI in patients with SMCP met the inclusion criteria. In these studies, speech outcomes were measured either in a binary fashion (i.e., normal speech or evidence of VPI) or using scales of VPI severity. Of the 26 studies, only two utilized blinded speech assessment, and 12 included both preoperative and postoperative speech assessment. Conclusions: The review found little evidence to support any specific surgical intervention. This is in large part due to the inclusion of mixed etiologies within study populations and the lack of unbiased validated preoperative and postoperative speech assessment. Further methodologically rigorous studies need to be conducted to provide a secure evidence base for the surgical management of SMCP. KEY WORDS:

hypernasality, intravelar veloplasty, submucous cleft palate (SMCP), velar surgery, velocardiofacial syndrome, velopharyngeal incompetence (VPI)

Submucous cleft palate (SMCP) is a congenital condition ssociated with abnormal development of the soft palate musculature (Roux, 1825; Kelly, 1910; Calnan, 1954; Sommerlad et al., 2004). Although the initiating etiologic event in embryonic development is unknown, the result is a disorganized array of atrophic myocytes and aberrant fibrous tissue leading to an absent tensor palatine aponeurosis (Stal and Hicks, 1998). The condition is highly idiopathic, though tentative risk factors that have been

identified are maternal smoking and abnormalities of the TBX22, TGFB3 and MN1 genes (Pauws et al., 2009; Reiter et al., 2012). The primary symptom associated with SMCP is hypernasality secondary to velopharyngeal insufficiency (VPI) (McWilliams, 1991). Surgery involving palate reconstruction, mobilization of a pharyngeal flap or using a sphincter pharyngoplasty, is the current mainstay of treatment to correct VPI associated with SMCP. There is, however, controversy regarding which procedure results in the optimal outcome (Gosain et al., 1996; Nasser et al., 2008). Proponents of palate reconstruction suggest that normalizing the primary anatomic abnormality is the logical first step in improving velopharyngeal function (Pensler et al., 1988; Chen et al., 1996; Sommerlad et al., 2004; Abdel-Aziz et al., 2012). The theoretical advantage of this management strategy is that it does not compromise the integrity of the airway and if hypernasality persists, pharyngeal surgery can still be undertaken at a later date (Sommerlad et al., 2004; Sullivan et al., 2011). Options for palate reconstruction include the Furlow double opposing Z-plasty (Furlow, 1986) or radical

Drs. Gilleard and Tavsanoglu, North Thames Cleft Service, Great Ormond Street Hospital for Children NHS Trust, London, and Queen Victoria Hospital, East Grinstead, West Sussex, United Kingdom. Drs. Sell, Ghanem and Sommerlad, North Thames Cleft Service, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom. Dr. Birch, Department of Clinical Physics, Bart’s and the London NHS Trust, London, United Kingdom. Submitted March 2013; Revised June 2013; Accepted September 2013. Address correspondence to: Dr. Onur Gilleard, Department of Plastic Surgery, Queen Victoria Hospital, East Grinstead, West Sussex, U.K. DOI: 10.1597/13-046 686

Gilleard et al., SUBMUCOUS CLEFT PALATE: A SYSTEMATIC REVIEW

muscle correction surgery in the manner described by Sommerlad (2004). In contrast to palate reconstruction, which aims to correct the anatomic abnormality associated with SMCP, surgery involving either the mobilization of a posterior pharyngeal flap or the utilization of a sphincter pharyngoplasty compensates for it by augmenting the posterior pharyngeal wall. The posterior pharyngeal flap acts as an obturator of the velopharyngeal port. Closure of the openings beside the sagittally orientated flap is achieved by adduction of the lateral pharyngeal walls. A sphincter pharyngoplasty, on the other hand, creates a transverse mound of tissue on the posterior pharyngeal wall leaving a small central velopharyngeal port (Jackson and Silverton, 1977). Closure of the port is therefore still dependent on elevation of the soft palate. Authors who advocate primary pharyngeal flap surgery believe that such surgery has the highest chance of success in correcting hypernasality in one operation (Park et al., 2000; Abdel-Aziz, 2007). In certain centers, imaging using nasendoscopy and/or lateral videofluoroscopy helps determine which operation to undertake (Chen et al., 1996; Bezuhly et al., 2012). For example, it has been suggested that palate reconstruction should be the primary procedure for patients with a small gap between the velum and posterior pharyngeal wall, and pharyngeal surgery should be reserved for those with larger gaps (Chen et al., 1996; Bezuhly et al., 2012). The aim of the present paper is to determine, from the published literature, whether there is evidence to support the use of a specific surgical procedure over the others to improve speech in patients with VPI secondary to SMCP. The use of imaging in the evaluation of patients with SMCP will also be examined. BACKGROUND The incidence of SMCP within the general population is thought to be between 0.02% and 0.08% (Stewart et al., 1972; Garc ´ıa Velasco et al., 1988). In 1954, Calnan defined the classic triad of physical signs associated with the condition: a bifid uvula, palate muscle diastasis, and notching of the posterior hard palate. A bifid uvula can easily be visualized during an oral examination, despite its common association with SMCP in children it is a relatively common isolated finding in the general population with an incidence of approximately 3% (Shprintzen et al., 1985; Wharton and Mowrer, 1992). Although muscle diastasis is more difficult to detect than a bifid uvula, certain signs are often visible. During an intraoral clinical examination, the normal insertion of the levator palatini muscles into the palatine aponeurosis is represented by a midline palatal eminence (Boorman and Sommerlad, 1985), whereas the visible presence of anteriorly placed palatal bundles or two lateral dimples in the soft palate during phonation of /a/ are indications of muscle diastasis (Finklestein et al., 1992). Muscle abnormality also manifests as a midline translu-

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cency, termed zona pellucida. Notching of the hard palate can be suspected by the pattern of palatal rugae (Park et al., 1994) or palpated during digital examination; however, the cause and significance of this abnormality is not clear. Subsequent to Calnan’s (1954) description of the classic triad of signs associated with SMCP, it became apparent that there is considerable anatomic variation within the condition. In about 50% of cases, the three classic stigmata appear together, while in approximately 30% to 40%, two of the three signs are present (Miguel et al., 2007). In other patients, there are no obvious intraoral clinical signs; however, muscle diastasis is evident during imaging or surgery. The term ‘‘occult SMCP,’’ was introduced by Kaplan (1975) to characterize these cases, which are thought to make up approximately 10% to 20% of the SMCP phenotype (Miguel et al., 2007; Reiter et al., 2011; Sullivan et al., 2011). In order to further quantify the spectrum of pathology within the SMCP phenotype, Sommerlad et al. (2004) developed a grading system based on the severity of abnormality of the uvula, hard palate, and musculature. This grading system supported the observations by Weatherly-White et al. (1972) that the severity of anatomic abnormality does not correlate with the severity of hypernasality. Other authors have independently examined defects of the hard palate in SMCP. Mori et al. (2013) recently categorized defects as one of three types: I ¼ absent posterior nasal spine, II ¼ V-shaped bony notch, and III ¼ bony defect extending to the incisive foramen. Type I appears to be the most common, but again these authors found that the severity of the anatomic defect did not correlate with the severity of speech abnormality. In addition to the signs described above, important anatomic characteristics of SMCP, which have been quantified and compared to normal subjects, are a short velum (mean SMCP velar length ¼ 28 mm; mean normal velar length ¼ 38 mm) and anterior insertion of the levators (mean SMCP insertion point ¼ 19 mm; mean normal insertion point ¼ 25 mm) (Hoopes et al., 1970). These abnormalities result in reduced velar excursion and the inability to close off the oropharynx from the nasopharynx during speech. Further anatomic variations may also be seen when SMCP is associated with generalized malformation syndromes (Hoopes, 1970; Williams et al., 1987; Sommerlad et al., 2004; Ruotolo et al., 2006; Milczuk et al., 2007). The most common of these is 22q11.2 deletion syndrome, which occurs in approximately 1 in 2000 live births (Shprintzen, 1978). Estimates of the prevalence of SMCP among children with this condition ranges from 21% to 90% (Golding-Kushner, 1985; Shprintzen, 2008), the variation probably associated with ascertainment bias. In addition to SMCP, it has been suggested that patients with 22q11.2 deletion may have a hypoplastic adenoid pad, pharyngeal wall hypotonia, and increased pharyngeal volume (Hoopes, 1970; Williams et al., 1987; Ruotolo et al., 2006), though the latter finding has recently been disputed (Dalben et al., 2010).

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As the roof of the mouth on routine initial screening examination may appear normal, SMCP is usually diagnosed between the ages of 4 and 5 years (Reiter et al., 2011; Sullivan et al 2011). The primary reason for the majority of children with SMCP to be brought to medical attention is abnormal speech associated with VPI, which is estimated to occur in 5% to 10% of cases (Gosain et al., 1996; Isotalo et al., 2007). The speech symptoms of VPI include hypernasality, weak pressure consonants, audible nasal emission/ turbulence, and abnormal articulation. In addition to speech abnormality, there may have been a history of feeding difficulties (Rudnick and Sie, 2008) and eustachian tube dysfunction, though there are conflicting reports regarding the incidence of otitis media with effusion in the SMCP patient population (Gosain et al., 1996). Hypernasality is the predominant feature of VPI in SMCP found in 50% to 65% of cases, while weak pressure consonants are reported in about 30% (Reiter et al., 2011). In addition, abnormal articulation is a secondary problem associated with VPI, but it should be noted that not all articulation errors are attributable to the structural anomaly. As a result, speech therapy is often required for abnormal consonant production even after successful surgery (Gosain et al., 1996). The gold standard for evaluating VPI is the perceptual speech assessment. Speech is assessed at the level of syllables, single words, rote speech, sentences, and spontaneous speech (Kummer, 2011). The key components that are evaluated are resonance, nasal airflow, and articulation. Various scoring systems have been developed to quantify speech abnormality; however, there is large variability in the collection and analysis of data between centers (Kummer, 2011). As a result, though perceptual speech assessment is the primary method for diagnosing and assessing VPI, other indirect methods of evaluation, such as nasometry, can also prove useful. In addition, videofluoroscopy and/or nasendoscopy are used to visualize the characteristics of the velopharyngeal mechanism and provide objective measures of velopharyngeal function. METHODOLOGY The search term ‘‘submucous cleft palate’’ was used to identify articles in MEDLINE, EMBASE, ISI Web of Knowledge, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment Database from inception to January 2013. English language restrictions were applied. In addition, websites including National Institute of Clinical Excellence (NICE) and the Meta-Register of Controlled Trials were searched, and the references of identified studies were screened. This strategy yielded 312 results. Abstracts of these articles were reviewed. Inclusion required that studies met

the following criteria: (1) the study included patients treated for SMCP (no individual case reports), and (2) the study presented postoperative speech outcome data. Studies analyzing postoperative outcomes for VPI caused by other etiologies, such as previously repaired overt cleft palate, were excluded from the analysis when speech outcome data were not reported separately for patients with SMCP. Data extraction was undertaken independently by two authors (O.G. and Y.T.). The data extracted included the following: design of study, number of patients, number of patients with 22q11.2 deletion, methods of speech assessment, preoperative and postoperative speech results, methods of imaging, measurements made during preoperative and postoperative imaging, the use of nasometry evaluation, and complications of surgery. A previously published checklist (Table 1, Sharshar and El-Bialy, 2012) was used by two authors (O.G. and Y.T.) to evaluate the methodological quality of individual articles that met the inclusion criteria. The checklist was composed of: six categories assessing study design (A through F in Table 1), three categories assessing study measurements (G through I in Table 1), and three categories assessing statistical analysis (J through L in Table 1). Each category, A through L, was given a score of 1 (fulfilled methodological criteria), 0.5 (partially fulfilled methodological criteria), or 0 (did not fulfill methodological criteria). The mean score of the assessment of the two raters was taken resulting in a possible score of 0, 0.25, 0.5, 0.75, or 1 for each category and an overall total of 0 to 12. Cohen kappa coefficient was used to determine the interrater agreement for the assessment of methodological quality of the individual studies. RESULTS Study Design Twenty-six studies analyzing the outcomes of surgery for VPI in SMCP met the inclusion/exclusion criteria. One of these was a randomized controlled trial, 14 were comparative studies, and 11 were observational series of a single procedure. The result of the quality assessment of these studies is detailed in Table 2. Over half of the papers reviewed had a methodological quality score of 6/12 (Table 2). The mean Cohen kappa coefficient for the methodological scoring of the 26 papers was 0.63 (range 0.27 to 0.81), demonstrating substantial agreement (Landis and Koch, 1977) between the two authors’ assessment of methodological quality. Speech Analysis In the majority of studies, outcomes were measured using perceptual evaluation of speech. Most authors of recent papers explicitly stated that speech was evaluated using standardized protocols, which included repetition

Gilleard et al., SUBMUCOUS CLEFT PALATE: A SYSTEMATIC REVIEW

TABLE 1

Bauer, 1988; Chen et al., 1996; Park et al., 2000; Ysunza et al., 2001; Husein et al., 2004; Sommerlad et al., 2004; Isotalo et al., 2007; Reiter et al., 2011; Abel-Aziz et al., 2012; Bezuhly et al., 2012). One study used a parent questionnaire detailing improvement in speech as the primary outcome measure (Abdel-Aziz, 2007).

Methodological Score for Clinical Trials*

Study design A. Objective: objective clearly formulated B. Population: described; suitably comparative in case-controlled series C. Selection criteria: clearly described and adequate D. Sample size: adequate; estimated before data collection E. Timing: prospective F. Randomization or consecutive cases; stated Study measurements G. Measurement method: Preoperative and postoperative speech results H. Bind measurement: blinding I. Reliability: validated scale; adequate level of agreement Statistical analysis J. Dropouts: dropouts included in data K. Statistical analysis; appropriate for data L. Statistical significance level: P value stated

Speech Outcomes Table 3 summarizes the number and proportion of patients achieving normal speech after different types of surgery. The results were as follows; Furlow Z plasty ¼ 67% to 97% (Chen et al., 1996; Sullivan et al., 2011), muscle correction/retropositioning ¼ 30% to 33% (Sommerlad et al., 2004; Reiter et al., 2011; Sullivan et al., 2011), pharyngeal flap surgery ¼ 32% to 100% (Crikelair et al., 1970; Porterfield et al., 1976; Peat et al., 1994; Isotalo et al., 2007; Sullivan et al., 2011), and sphincter pharyngoplasty ¼ 50% to 72% (Seagle et al., 1999; Pryor et al., 2006). Five studies compared outcomes of Furlow Z palate reconstruction with pharyngeal flap surgery (Seagle et al., 1999; Park et al., 2000; Husein et al., 2004; Sullivan et al., 2011; Bezuhly et al., 2012). In three of these, postoperative hypernasality was resolved to a greater degree following pharyngeal flap surgery (Seagle et al., 1999; Park et al., 2000; Sullivan et al., 2011). In two studies, Furlow Z-palatoplasty resulted in a greater proportion of patients achieving normal speech (Husein et al., 2004; Bezuhly et al., 2012). In the latter two

* Modified from Sharshar and El-Bialy, 2012.

of specific words and sentences as well as conversational speech (Seagle et al., 1999; Park et al., 2000; Husein et al., 2004; Sommerlad et al., 2004; Isotalo et al., 2007; Bezuhly et al., 2012). In two studies only, speech was evaluated from previously taken audio/video recordings (Ysunza et al., 2001; Sommerlad et al., 2004), while in the others it was evaluated live. Results were reported in either a binary fashion (i.e., normal speech or evidence of VPI) or by using scales of VPI severity. Of the 26 studies, only two utilized blinded speech assessment (Ysunza et al., 2001; Sommerlad et al., 2004), and 12 included both preoperative and postoperative speech assessment (Crikelair, 1970; Kaplan, 1975; Pensler and TABLE 2

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Methodological Score for Selected Articles (Mean Score Taken From Two Raters)

Article

Study Type*

A

B

C

D

E

F

G

H

I

J

K

L

Total Score (/12)

Interrater Agreement (Cohen Kappa)

Abdel-Aziz et al., 2012 Bezuhly et al., 2012 Reiter et al., 2011 Sullivan et al., 2011 Isotalo et al., 2007 Abdel-Aziz, 2007 Pryor et al., 2006 Sommerlad et al., 2004 Husein et al., 2004 Ysunza et al., 2001 Park et al., 2000 Peat et al., 1994 Seagle et al.,1999 Chen et al., 1996 Pensler et al., 1988 Lewin et al., 1980 Abyholm et al., 1976 Porterfield et al., 1976 Kaplan, 1975 Weatherly-White et al., 1972 Crikelair et al., 1970 Hoopes et al., 1970 Rees et al., 1967 Porterfield and Traube, 1965 Gylling and Soivio, 1965 Calnan, 1954

OS CS OS CS OS OS OS OS CS RCT CS CS CS OS OS CS CS CS OS CS CS OS CS OS CS OS

1 0.75 1 1 0.75 1 1 1 1 1 1 1 1 0.75 0.5 1 0.5 1 1 0.75 0.75 1 1 1 0.75 0.5

0.5 0.75 1 1 0.75 0.5 0.5 1 1 1 0.5 1 0.5 1 0.5 0 0.75 1 1 0.25 0.75 0.5 0.25 1 0.5 0.75

0.5 0.75 0.5 0.75 0.5 0.5 0.5 1 1 1 1 0.5 1 1 0.5 0.5 0.75 1 1 1 0.5 0.5 0.5 0.5 1 0.5

0.25 0.75 1 0.75 1 0 0 0.75 0.5 1 1 0.5 0.25 1 0.25 0.5 1 1 0.5 0.5 0.25 0 0.25 0.5 0.5 0

1 0 0 0 0 0 0 0 0.25 1 0 0 0 0 0 0 0 0 0 0.5 0 0 0 0 0 0

0 0 0.5 0.75 1 0 1 1 0 1 0.75 1 1 0 0 0 0 0 0 0.25 0 0 0 0 0.5 0.75

0.75 1 1 0.25 0.75 0 0 0.5 1 0.5 0.5 0.5 0 1 1 0 0 0 1 0 0 1 0 0 0 0

0 0 0 0 0 0 0 0.5 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0.75 0.75 0 1 0.5 0 0 1 1 0.5 0.75 0.5 0.75 0.5 0 0 0 0 0 0 0.25 1 0 0 0.5 0

0.5 0 0.5 0 0.5 0.5 1 0 0.75 1 1 0.5 1 0.5 0.5 0 1 0.5 0 0.5 0 0.5 0 0 0 0

0.75 1 0 1 1 0 0 1 1 1 1 1 0 0 0.5 0 0 0 0 0 0 0 0 0 0 0

1 1 0 1 1 0 0 1 1 1 1 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0

6.5 6.75 5 7.5 7.75 2.5 3.5 8.75 8 11 8.5 7.5 6 5.75 4.75 2 4 4.5 4.5 2.75 2.5 4.5 2 3 3.75 2.5

0.57 0.59 0.78 0.32 0.56 0.81 0.76 0.80 0.69 0.74 0.53 0.67 0.43 0.78 0.34 0.63 0.64 0.78 0.65 0.27 0.54 0.76 0.53 0.72 0.75 0.64

* OS ¼ observational study; CS ¼ comparative study; RCT ¼ randomized controlled study.

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TABLE 3

Summary of Studies, Meeting Inclusion Criteria, Assessing Speech Outcome Following Surgery in SMCP

Year Abdel-Aziz et al., 2012 Bezuhly et al., 2012

Number of SMCP/Total 15/15 (100%) 78/78 (100%)

Reiter et al., 224/224 2011 (100%) Sullivan et al., 58/58 (100%) 2011

Treatment Methods Z-palatoplasty (n ¼ 15)

Number of Patients With Normal Postoperative Speech

Z-palatoplasty (n ¼ 55)

Number of patients with normal postoperative speech not stated Z-palatoplasty group: n ¼ 47/55 (85%)

Pharyngeal flap (n ¼ 13)

Pharyngeal flap group: n ¼ 8/13 (62%)

Veloplasty using ‘‘butterfly suture’’

n ¼ 112/224 (50%)

Two-flap palatoplasty with muscle retropositioning (n ¼ 20)

Two-flap palatoplasty with muscle retropositioning group: n ¼ 6/20 (30%) Z-palatoplasty group: n ¼ 10/15 (67%)

Z-palatoplasty (n ¼ 15) Pharyngeal flap (n ¼ 12)

Pharyngeal flap group: n ¼ 11/12 (92%)

Isotalo et al., 2007 AbdelAziz,2007 Pryor et al., 2006

58/58 (100%)

Honig pharyngeal flap

n ¼ 42/56 (75%)

9/9 (100%)

Pharyngeal flap

n ¼ 7/9 (78%)

7/61 (11%)

Sphincter pharyngoplasty

n ¼ 5/7 (72%)

Sommerlad et al., 2004 Husein et al., 2004

40/40 (100%)

Radical velar muscle correction

n ¼ 13/40 (33%)

29 (100%)

Z-palatoplasty (n ¼ 9) Pharyngeal flap (n ¼ 20)

Ysunza et al., 2001

72/72 (100%)

Park et al., 2000

50/50 (100%)

Peat et al., 1994 Seagle et al, 1999

13/116 (11%)

Chen et al, 1996 Pensler and Bauer, 1988 Lewin et al., 1980

30/30 (100%)

27/27 (100%)

15/15 (100%) 27/27 (100%) All occult SMCP

Z-palatoplasty group: n ¼ 8/9 (89%) Pharyngeal flap group: n ¼ 16/20 (80%) Minimal incision Minimal incision palatopharyngoplasty: palatopharyngoplasty (n ¼ 37) n ¼ 32/37 (87%) Minimal incision palatopharyngoplasty Minimal incision and tailored additional procedure: palatopharyngoplasty and tailored n ¼ 31/35 (89%) additional procedure (n ¼ 35), which was either pharyngoplasty (n ¼ 3) or pharyngeal flap surgery (n ¼ 32) Pushback palatoplasty (n ¼ 18) Pushback palatoplasty group: n ¼ 8/18 (44%) Pharyngeal flap (n ¼ 21) Pharyngeal flap group: n ¼ 19/21 (90%) Furlow palatoplasty (n ¼ 3) Furlow palatoplasty group: n ¼ 2/3 (67%) Palate pushback and pharyngeal Pushback combined with pharyngeal flap (n ¼ 8) flap group: n ¼ 7/8 (88%) Honig pharyngeal flap (n ¼ 3) Honig flap group: n ¼ 1/3 (33%) Hynes pharyngoplasty (n ¼ 10) Hynes group: n ¼ 9/10 (90%) Furlow palatoplasty (n ¼ 18) Furlow palatoplasty group: n ¼ 15/18 (83%) Palate pushback and pharyngeal Palate pushback and pharyngeal flap flap (n ¼ 6) group: n ¼ 6/6 (100%) Sphincter pharyngoplasty (n ¼ 2) Sphincter pharyngoplasty group: n ¼ 1/2 (50%) Pharyngeal flap (n ¼ 2) Pharyngeal flap group: n ¼ 2/2 (100%) Z-palatoplasty and sphincter Furlow palatoplasty and sphincter pharyngoplasty (n ¼ 1) pharyngoplasty group: n ¼ 1/1 (100%) Z-palatoplasty n ¼ 29/30 (97%)

Complications (Not Including Persistent Hypernasality) Nil Z-palatoplasty group: wound dehiscence (n ¼ 1/55, 2%) Pharyngeal flap group: sleep apnea (n ¼ 1/13, 8%) Nil

Z-palatoplasty group: oronasal fistula (n ¼ 1/15, 7%) Pharyngeal flap group: authors specifically state that there was no postoperative hyponasal speech, flap dehiscence, or obstructive sleep apnea Respiratory obstruction (n ¼ 1/58, 2%) Flaps necrosis (n ¼ 2/58, 4%) Nil Total population (not specifically given for SMCP) flap dehiscence (n ¼ 1/61, 2%) Nil

Pharyngeal flap group: intermittent apnea (n ¼ 1/38, 3%) Nil

Majority (numbers not stated) of pharyngeal flap group had snoring and mouth breathing but this resolved in most cases after 1 month

Honig flap group: hyponasality (n ¼ 1/3, 33%) Furlow palatoplasty group: oronasal fistula (n ¼ 1/18, 6%)

Nil

Levator repositioning and palate lengthening Teflon injection (n ¼ 6)

n ¼ 13/15 (87%)

Nil

Teflon injection group: n ¼ 5/6 (83%)

Teflon injection group: anaphylaxis (n ¼ 1/6, 17%)

Proplast injection (n ¼ 3) Pharyngeal flap (6 pushback) (n ¼ 18)

Proplast injection group: not reported Pharyngeal flap 6 pushback group: n ¼ 17/18 (94%)

Pharyngeal flap 6 pushback group: partial flap dehiscence (n ¼ 1/18, 6%)

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TABLE 3

Continued

Year

Number of SMCP/Total 47/47 (100%)

Von Langenbeck and pharyngeal flap (n ¼ 28) Von Langenbeck (n ¼ 19)

Porterfield et al., 1976

79/79 (100%)

Kaplan, 1975

62/62 (100%)

Palatoplasty (n ¼ 40) Pharyngeal flap (n ¼ 25) Palatoplasty and pharyngeal flap (n ¼ 14) Surgery: combined pushback, levator reconstruction and pharyngal flap (n ¼ 49) Speech therapy alone (n ¼ 13) Veau-Wardill pushback and pharyngeal flap (n ¼ 2) Pharyngeal flap (n ¼ 2) Von Langenbeck and pharyngeal flap (n ¼ 2)

4/4 (100%) WeatherlyWhite et al., 1972 Crikelair et 17/17 (100%) al., 1970

Hoopes et al., 1970 Rees et al., 1967

4/4 (100%) 12/12 (100%)

Porterfield et 13/13 (100%) al., 1965 Gylling and 76/76 (100%) Soivio, 1965

18/18 (100%)

Number of Patients With Normal Postoperative Speech

Treatment Methods

Abyholm, 1976

Calnan, 1954

691

Von Langenbeck (n ¼ 7) Pharyngeal flap (n ¼ 7) Simple closure (n ¼ 1) Island flap pushback (Millard) and pharyngeal flap Veau-Wardill pushback and pharyngeal flap (n ¼ 2) Hard palate closure and retroposition (n ¼ 10) Pushback procedure

Complications (Not Including Persistent Hypernasality)

Von Langenbeck and pharyngeal flap group: n ¼ 21/28 (75%) Von Langenbeck group: n ¼ 13/19 Von Langenbeck group: oronasal fistula (68%) (n ¼ 1/19, 5%) Palatoplasty group: n ¼ 6/40 (15%) Nil Pharyngeal flap group: n ¼ 8/25 (32%) Palatoplasty and pharyngeal flap group: n ¼ 6/14 (43%) Number of patients with normal Nil postoperative speech not stated

n ¼ 3/4 (75%)

Nil

Von Langenbeck and pharyngeal flap group: n ¼ 1/2 (50%)

Von Langenbeck and pharyngeal flap group: no details given (n ¼ 1/2, 50%)

Von Langenbeck group: n ¼ 1/7 (14%) Pharyngeal flap group: n ¼ 3/7 (43%) Simple closure group: n ¼ 1/1 (100%) n ¼ 1/4 (25%)

Nil

Number of patients with normal postoperative speech not stated

Nil

Number of patients with normal postoperative speech not stated n ¼ 41/70 (58%)

Nil

Veau-Kilner palatoplasty and staphylorrhaphy (n ¼ 65) Hynes pharyngoplasty (n ¼ 1) Palatoplasty and velopharyngoplasty combined (n ¼ 2) Dorrance retropositioning (pushback) (n ¼ 2) Surgical excision of cleft and V-Y n ¼ 13/18, 72% pushback of soft palate

studies, however, the group of patients undergoing the Furlow procedure had less severe preoperative hypernasality than those undergoing pharyngeal flap surgery (Husein et al., 2004; Bezuhly et al., 2012). In the only published randomized controlled trial investigating outcomes following surgery for VPI in patients with SMCP, a comparison between minimal incision palatopharyngoplasty and the same procedure combined with either pharyngoplasty or a pharyngeal flap was made (Ysunza et al., 2001). The authors found no additional benefit of the combined procedure. Comparisons between other surgical techniques have also been made, but these studies were found to be of poor methodological quality (Table 2).

Specific operations not stated worsening speech (n ¼ 9/76, 12%)

Nil

either the Furlow palatoplasty or pharyngeal flap, 74% had normal resonance in the 22q11 deletion group compared with 88% in the nonsyndromic group (P , .05). Complications Complications were reported in 10 studies (Table 3). These included snoring, wound dehiscence (Bezuhly et al., 2012), and oronasal fistula (Sullivan et al., 2011; Seagle et al., 1999) following palate surgery. Airway obstruction (Isotalo et al., 2007), sleep apnea (Bezuhly et al., 2012), and flap dehiscence (Lewin et al., 1980) were complications reported following pharyngeal flap surgery.

22q11 Deletion Nasometry One paper specifically compared outcomes in patients with SMCP and 22q11 deletion to those with isolated SMCP (Bezuhly et al., 2012). These authors found that the 22q11 deletion group started on average with poorer resonance scores. After surgical intervention using

Two studies measured preoperative and postoperative nasalance (Abdel-Aziz et al., 2012; Bezuhly et al., 2012). Bezuhly et al. (2012) demonstrated normal postoperative nasalance in 78% (n ¼ 61/78) of patients following

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TABLE 4

Summary of Postoperative Imaging Assessment in SMCP Surgery

Year

Number of SMCP/Total

Abdel-Aziz et al., 2012

15/15 (100%)

Abdel-Aziz, 2007

9/9 (100%)

Treatment Methods Z-palatoplasty (n ¼ 15) Pharyngeal flap

Sommerlad et al., 2004

40/40 (100%)

Radical velar muscle correction

Chen et al., 1996

30/30 (100%)

Z-palatoplasty

Hoopes et al., 1970

4/4 (100%)

Island flap pushback (Millard) and pharyngeal flap

Imaging Analysis Results* Preoperative NE findings: velopharyngeal closure ¼ 0/15 (0%) Postoperative NE findings: velopharyngeal closure ¼ 13/15 (87%) Preoperative NE findings not stated Postoperative NE findings: complete closure ¼ 8/9 (89%) Preoperative VF findings: full closure ¼ 17/40 (43%) Postoperative VF findings: full closure ¼ 25/40 (63%) Postoperative NE findings: incomplete closure ¼ 1/13 marginal closure ¼ 4/13 complete closure ¼ 8/13 Mean preoperative VF results: velar excursion ¼ 11.25 mm, length of soft palate ¼ 29 mm, levator insertion ¼ 19 mm; relative depth of nasopharynx ¼ 0.47; velopharyngeal incompetence ¼ 36% Mean postoperative VF results: velar excursion ¼ 9.5 mm, length of soft palate ¼ 39 mm, levator insertion ¼ 25 mm; relative depth of nasopharynx ¼ 0.47; velopharyngeal incompetence ¼ 16%

* NE ¼ nasendoscopy; VF¼ lateral videofluoroscopy.

either Furlow Z-palatoplasty or pharyngeal flap surgery. Abdel-Aziz et al. (2012) showed an improvement in mean nasalance score from 39 to 32 and 15 to 13 for nasal and oral sentences, respectively, following Furlow Z-palatoplasty in 15 patients with SMCP.

size of ,6 mm, measured using lateral videofluoroscopy, was a positive predictive factor for successful radical muscle correction surgery in patients with SMCP. DISCUSSION

Imaging Two studies used preoperative imaging to help determine the type of surgical procedure undertaken (Chen et al., 1996; Bezuhly et al., 2012). In one study, patients underwent Z- palatoplasty if a preoperative closure ratio of .0.7, visualized during lateral videofluoroscopy or nasendoscopy, was observed. Those with a closure ratio of ,0.7 underwent pharyngeal flap surgery (Bezuhly et al., 2012). In the other study, patients underwent Z-palatoplasty if gap size, measured using lateral videofluoroscopy, was ,5 mm (Chen et al., 1996). Five studies (Table 4) reported postoperative velopharyngeal closure visualized during either nasendoscopy or lateral videofluoroscopy (Hoopes et al., 1970; Chen et al., 1996; Ysunza et al., 2001; Sommerlad et al., 2004; Abdel-Aziz et al., 2012). The four studies that analyzed both preoperative and postoperative results (Hoopes et al., 1970; Ysunza et al., 2001; Sommerlad et al., 2004; Abdel-Aziz et al., 2012) all demonstrated improved velopharyngeal closure after surgery. Two studies investigated the predictive value of gap size on the success of palate reconstruction (Seagle et al., 1999; Sommerlad et al., 2004). Seagle et al. (1999) noted that failure in the resolution of hypernasality following Zpalatoplasty occurred more commonly in those patients with a preoperative gap size, measured using lateral videofluoroscopy, of .8 mm. However, no statistics were used to determine whether this finding was significant. Sommerlad et al. (2004) showed that a gap

Although randomized controlled trials are the gold standard in the hierarchy of medical evidence, in the field of cleft palate surgery they are often not feasible (de Ladeira and Alonso, 2012). This means that case-control and observational studies, results of which can be compared to historic controls, need to be conducted to the highest methodological standard (Baker and Lindeman, 2001). One methodological issue that resulted in a substantial number of articles being excluded from the review was the inclusion in study populations of patients who had VPI without SMCP together with those who did have SMCP. In addition, many of the reports assessing the success of surgical techniques to treat SMCP that are included in this review are confounded by significant bias. The most notable is the absence of blinded preoperative and postoperative speech assessment using a validated scoring system by independent listeners. In all but two studies (Ysunza et al., 2001; Sommerlad et al., 2004), live speech was evaluated, as opposed to recordings. This is a serious methodological flaw as it precluded ensuring the reliability of the primary outcome measure. In this review, ‘‘normal’’ postoperative speech was the outcome measure used to analyze the success of surgery. However, some rating systems assessing VPI in patients with SMCP have four points on the scale (Sommerlad et al., 2004; Reiter et al., 2011; Bezuhly et al., 2012), while others have only three (Porterfield et al., 1976; Abyholm, 1976; Park et al., 2000; Pryor et al., 2006) or two (Ysunza et al., 2001). This suggests that normal speech on one scale may not correspond to normal speech on another. In addition,

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certain authors reported ‘‘acceptable’’ speech, which included both normal speech and mild hypernasality, as the only outcome measure (Husein et al., 2004). Such variability in the way outcomes are reported make meaningful comparisons between studies difficult (Kummer et al., 2012). In light of the inconsistencies with perceptual speech analysis, the use of nasometry can be helpful in providing quantitative evidence of improvement in hypernasality after surgery. Nasometry measures oral and nasal acoustic sound signals to determine a score, which represents the ratio of the energy in the two signals (Fletcher et al., 1989). Two recent studies (Abdel-Aziz et al., 2012; Bezuhly et al., 2012) included in this review reported nasalance scores preoperatively and postoperatively, and both found an improvement following surgery. As protocols to improve the reliability of nasometry are being established (Sweeney and Sell, 2008), the utilization of this investigation to help provide quantitative outcome data should increase. Lateral videofluoroscopy can be used to objectively analyze velopharyngeal closure before and after surgery (Hoopes et al., 1970; Sommerlad et al., 2004). This investigation can be used to measure the space between the velum and the posterior pharyngeal wall during speech (Golding-Kushner et al., 1985; Birch et al., 1999; Lam et al., 2006). This distance is often given the term ‘‘velopharyngeal gap size.’’ Two studies included in this review measured velopharyngeal gap size preoperatively and postoperatively, and both showed it to be reduced after surgery (Hoopes et al., 1970; Sommerlad et al., 2004). Sommerlad et al. (2004) also demonstrated that a gap size ,6 mm was a positive predictive factor for successful radical muscle correction surgery in patients with SMCP. This finding supported the observation made by Seagle et al. (1999) that patients with a preoperative gap size ,8 mm tended to have a higher rate of success following Z-palatoplasty. The studies included in this review demonstrate the changes in the surgical management of SMCP that have occurred over the last 60 years. Prior to the 1970s, the most commonly undertaken procedure was the palate pushback. In his landmark paper, Calnan (1954) used V-Y retropositioning of the palate to achieve normal speech in 13 of 18 patients (72%). The decline in the use of pushback operations to treat SMCP followed results from studies comparing outcomes of this procedure with pharyngeal flap surgery, which showed speech improvement to be greater with the latter (Rees et al., 1967; Crikelair et al., 1970; Massengill et al., 1973; Porterfield et al., 1976). In the last decade pharyngeal flap surgery and palate reconstruction have been the most commonly used techniques to treat VPI associated with SMCP. Studies included in this review, which have investigated outcomes following pharyngeal flap surgery in patients with SMCP, have shown that normal speech is achieved in 33% to 100% of patients (Rees et al., 1967; Crikelair et al., 1970; Porterfield et al., 1976; Peat et al., 1994; Isotalo et al.,

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2007; Sullivan et al., 2011). The main drawback of such surgery is the potential for airway obstruction (Wells et al., 1999; Isotalo et al., 2007). In addition, sleep apnea, flap necrosis, flap dehiscence, and hyponasal speech have also been reported (Lewin et al., 1980; Peat et al., 1994; Husein et al., 2004; Isotalo et al., 2007; Bezuhly et al., 2012). Options for palate reconstruction include the Furlow double opposing Z-plasty (Furlow, 1986) or radical muscle correction surgery (Sommerlad et al., 2004). The benefit of the Furlow palatoplasty is that retropositioning of the levators in a more anatomically correct transverse position is achieved without the creation of a midline scar which reduces the potential for velar shortening. Quantitative increases in velar length and thickness have been demonstrated using this technique in both cleft palate re-repairs and SMCP (D’Antonio et al., 2000). Reported rates of achieving normal speech for VPI in patients with SMCP following Z-palatoplasty vary between 67% (Sullivan et al., 2011) and 97% (Chen et al., 1996). Of note, this procedure is not without its own risks, and postoperative oronasal fistulas rates of 7% and 6% were reported in two recent studies, Sullivan et al., 2011 and Seagle et al., 1999, respectively. When comparisons between pharyngeal flap surgery and Z-palatoplasty have been made within individual studies, results have been conflicting (Seagle et al., 1999; Park et al., 2000; Husein et al., 2004; Sullivan et al., 2011; Bezuhly et al., 2012). Using an operation similar to that used for palate rerepair, Sommerlad et al. (2004) reported outcomes following radical muscle correction in 40 patients with SMCP. Thirteen patients (33%) had complete postoperative resolution of hypernasality with a further 12 patients (30%) showing only mild residual hypernasality. Outcomes following this technique have not, however, been reported by others for the treatment of SMCP. Other authors who have utilized muscle retropositioning but obtained unsatisfactory results (Reiter et al., 2011; Sullivan et al., 2011) had performed the procedure prior to the description of radical muscle correction (Sommerlad et al., 2004) and have acknowledged that the technique used did not dissect and reposition the levators to the same extent (Sullivan et al., 2011). A specific group of patients with SMCP who are particularly challenging to treat are those with 22q11.2 deletion syndrome (Mehendale et al., 2004). Whether this is mainly due to anatomic, physiological, or developmental differences is presently unclear (Hoopes, 1970; Williams et al., 1987; Ruotolo et al., 2006; Dalben et al., 2010). Only one paper included in this review specifically compared outcomes in patients with SMCP and 22q11.2 deletion to those with isolated SMCP (Bezuhly et al., 2012). These authors found that the 22q11.2 deletion group started, on average, with more severe hypernasality. After surgical intervention using either a Furlow palatoplasty or pharyngeal flap, 74% had normal resonance compared with 88% in the nonsyndromic group. The finding that VPI in

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22q11.2 deletion is more difficult to correct than in nonsyndromic patients is in keeping with reports from other authors that were excluded from this systematic review due to the fact that non-SMCP patients were grouped together with SMCP patients (D’Antonio et al., 2001; Losken et al., 2003). CONCLUSIONS

AND

RECOMMENDATIONS

Pharyngeal flap surgery and palate reconstruction are currently the most commonly used techniques to treat VPI associated with SMCP. However, due to significant variability in methods of speech outcome reporting and diverse patient populations with varying anatomic profiles in which subgroup analysis was not reported, this review was unable to demonstrate the superiority of one surgical technique over the other. In addition, when the two techniques are compared within individual studies, some show higher rates of normal postoperative speech following pharyngeal flap surgery, while others show the opposite. With regard to imaging, though it has been suggested that patients with smaller preoperative gap sizes are more likely to have successful results following palate reconstruction, the evidence to support this is sparse (Chen et al., 1996; Seagle et al., 1999; Sommerlad et al., 2004). More methodologically sound research is needed before a consensus can be reached regarding the optimal management of VPI associated with SMCP. Recommendations for this to be achieved are: 



 



Studies investigating the management of SMCP may include patients with associated syndromes, such as 22q11.2 deletion (though subgroup analysis should be undertaken in these cases), but should not include patients with VPI who do not have SMCP. Preoperative and postoperative speech results should be assessed by independent blinded listeners using high quality audio/video speech recordings of a comprehensive speech sample on a validated standardized scale. Preoperative and postoperative nasalance scores should be obtained where possible. Preoperative and postoperative lateral videofluoroscopy using calibrated images should be undertaken and blindly analyzed, and gap size should be reported in millimeters. Case-control studies should be adequately powered and compare patients with a similar degree of preoperative VPI severity. REFERENCES

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