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keratocystic odontogenic tumour recurrence rates

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The keratocystic odontogenic tumour (KCOT, odontogenic keratocyst (OKC)) was first described in the literature in 1956 and is classified by the World Health Organization classified as a benign odontogenic tumour. It is generally accepted that they arise from the remnants of the dental lamina and are benign but locally aggressive and tend to reoccur.  They account for between 2% and 11% of all jaw cysts and can occur at any age. They are more common in males than females with a male:female ratio of approximately 2:1. This review attempted to determine the recurrence rate of KCOT following treatment.

A wide range of databases(Cochrane Library, MEDLINE, EIFL, Ovid and ISI.)  and reference lists  of the retrieved articles were searched for English language papers.  Articles related to (extraosseous) varianst of KCOT/OKC and  nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome) were excluded .

They identified 1568 articles but only 2 retrospective reviews met the inclusion criteria. These studies included 108 lesions  and six treatment modalities. The recurrence rates identified were

  •  0% for resection,
  • 0% for enucleation with peripheral ostectomy and Carnoy’s solution,
  •  18.18% for enucleation with peripheral ostectomy,
  • 26.09% for enucleation alone,
  • 40% for marsupialisation,
  • 50% for enucleation with Carnoy’s solution.

The overall recurrence rate was 23.15%.

The authors concluded

The present review discusses the methodological weaknesses of many of the studies analysed. No high quality evidence was obtained to evaluate recurrence rates related to treatment modalities of keratocystic odontogenic tumour.

 

Kaczmarzyk T, Mojsa I, Stypulkowska J. A systematic review of the recurrence rate for keratocystic odontogenic tumour in relation to treatment modalities. Int J Oral Maxillofac Surg. 2012 Mar 23. [Epub ahead of print] PubMed PMID: 22445416.

Related reviews

A Cochrane review by Sharif et al was published in 2010. The aim of that review was to assess the available evidence comparing the effectiveness of surgical interventions and adjuncts for the treatment of KCOTs.  That review was restricted to randomised controlled trials and non were found.

They concluded  at the time that

There are no published randomised controlled trials relevant to this review question, therefore no conclusions could be reached about the effectiveness or otherwise of the interventions considered in this review. There is a need for well designed and conducted randomised controlled trials to evaluate treatments for KCOTs.

An earlier review was conducted by Blanas et al in 2000 which concluded.

Although the existing literature consists of retrospective consecutive case series, it appears that resection or enucleation with adjunctive therapy is associated with recurrence rates that are lower than those associated with enucleation alone.

A quick search of the clinical trials databases find no registered RCTs on this topic so it would appear that despite 60 years knowledge of the KCOT and at least 3 systematic review we still have not conducted high quality studies to provide robust answers to managing this tumour!

Sharif FNJ, Oliver R, Sweet C, Sharif MO. Interventions for the treatment of keratocystic odontogenic tumours (KCOT, odontogenic keratocysts (OKC)). Cochrane Database of Systematic Reviews 2010, Issue 9. Art. No.: CD008464. DOI: 10.1002/14651858.CD008464.pub2.

 Blanas N, Freund B, Schwartz M, Furst IM. Systematic review of the treatment and prognosis of the odontogenic keratocyst. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Nov;90(5):553-8. Review. PubMed PMID: 11077375.


New Dental Prescribing App launched

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The Scottish Dental Clinical Effectiveness Programme (SDCEP) has launched an app for use on iPhone®, iPad® and iPod touch® based on the second edition of their Drug Prescribing for Dentistry guidance.

The app aims to facilitate drug prescribing within primary care dental practice by providing mobile access to the latest dentally relevant information compiled from the British National Formulary (BNF) and BNF for Children (BNFC).

The app provides

  • Advice on the management of a range of dental conditions presented in an easy to use, problem-oriented style
  • Drug regimens displayed in a ‘prescription-like’ format to aid prescribing for both adults and children
  • Direct links to the BNF website for information on drug interactions
  • Advice on the management of medical emergencies, including drug administration.

The app is aimed at practitioners in the primary care sector and the prescribing guidance applies to all patients, including adults, children and those with special needs, who would normally be treated in this sector.

The app is available to purchase from the App Store SM.  New editions of the BNF and BNFC wil be reviewed and  any necessary changes to drug prescribing  will be provided as a free update for at least two years.

iPad, iPhone and iPod touch are trademarks of Apple Inc., registered in the U.S. and other countries. App Store is a service mark of Apple Inc.

 

 

Daily multivitamins did not reduce risk of mouth ulcers

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Recurrent aphthous stomatitis (RAS), is one of the most common oral mucosal diseases. Minor RAS is the most common form of the disease.  The exact cause of RAS is still unknown and genetics, vitamin deficiencies, trauma, and immune dysfunction have been cited as possible causes.  The aim of this study was to see whether  a daily multivitamin supplement had any effect on the incidence and duration of RAS episodes over a 12-month period.

What did they do

160 adults who had a validated history of at least three episodes of idiopathic minor RAS within the previous 12 months were randomised to receive either , a once-daily multivitamin containing 100 percent of the U.S. reference daily intake (RDI) of essential vitamins (n = 83),   or  a once-daily placebo for up to 365 days (n = 77)

 The study protocol is available on line

 What did they find

There was no significant difference in the mean number of new RAS episodes between the two groups

Multivitamin groupPlacebo group
mean number of new RAS episodes4.19 episodes4.69 episodesP = .69
mean duration of new RAS episodes8.66 days8.99 daysP = .60

There were also no difference in relation to mouth pain, normalcy of diet or compliance with the study medication regimen.

They concluded

Daily multivitamin supplementation, with the RDI of essential vitamins, did not result in a reduction in the number or duration of RAS episodes. Clinicians should not recommend multi-vitamin supplementation routinely as prophylaxis for RAS

Lalla RV, Choquette LE, Feinn RS, Zawistowski H, Latortue MC, Kelly ET, Baccaglini L. Multivitamin therapy for recurrent aphthous stomatitis: A randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012 Apr;143(4):370-6. PubMed PMID: 22467697.

Comment

Only the abstract of this study was available to the Elf  for assessment but we have previously  reported on a  previous publication from this study which found that stress may be involved in the initiation of new RAS episodes. The study ran for one year and not all 160 completed the trial  with a total drop out of just under 30% which may have an impact on the findings.

For more information on vitamins and health visit NHS Choices

Study shows dexamethasone ointment had positive effect on recurrent aphthous ulceration

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Yesterday we looked at a study that looked at multivitamins for the treatment of recurrent aphthous stomatitis (RAS). Today we have another study whose aim was to explore the efficacy and safety of dexamethasone ointment in the treatment of RAS.

 What did they do

This was a multi-centre trail conducted across 5 centres in China. Patients were randomised to receive either dexamethasone ( n=120) or a placebo ( n=120) ointment. Patients were instructed to apply the given agent to the identified ulcer 3 times a day (after meals) for 5 days.   Patient were included if they were not pregnant, aged between 18-60 years, had a history of recurrent aphthous ulceration longer than 6 months and expectation that the ulcers normally take more than 5 days to resolve without treatment; and they presented with of 1-3 aphthous ulcers (duration, <48 hours) with a diameter <10 mm.

The patients kept a log diary and were monitored for potential biochemical abnormalities. The primary objectives were to evaluate the size of ulcers and pain level before and after the drug management (at days 1 and 6±2 days after entering the study). Pain was assessed using a visual analogue scale no pain ( 0) to unbearable pain (10)

 What did they find

  • Nine patients were discontinued (5 because of loss to follow-up; one because of the development of a systemic rash; 3 because of combination with other drugs).
  • There was significant difference in the reduction of ulcer size between the treatment group and the control group and in the reduction of pain level between the groups with better healing in the treatment group.
DexamethasonePlacebo
Ulcer size reduction 7.167 ± 6.3415 mm24.346 ± 7.0666 mm2P=.000
Pain reduction5.623 ± 1.95704.940 ± 2.2449P=.000
Healing ratio83.33%54.70%P=.000
  • No severe adverse reactions were observed.
  • No serum dexamethasone was detected before or after the use of the agents (< 0.502 ng/mL).

They concluded

The current study revealed that dexamethasone ointment was safe and efficient in reducing ulcer size, alleviating ulcer pain, and hastening ulcer healing in patients with recurrent aphthous ulceration. In addition, the patients had a good overall assessment of the agents.

Liu C, Zhou Z, Liu G, Wang Q, Chen J, Wang L, Zhou Y, Dong G, Xu X, Wang Y,Guo Y, Lin M, Wu L, Du G, Wei C, Zeng X, Wang X, Wu J, Li B, Zhou G, Zhou H. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med. 2012 Mar;125(3):292-301. PubMed PMID: 22340928.

Comment

This is short term study, and it not clear if outcome assessors were blind to intervention. There were also some potential variations between the centres in relation to pain assessment a point noted by the authors.

 

Small study suggests that low-level laser therapy may have some benefit in treatment oral lichen planus

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Oral Lichen Planus (OLP) is a common chronic immunological disease the treatment of which remains a challenge for clinicians.  Two Cochrane reviews  have recently been published regarding the treatment of OLP (Chang et al 2012 and Thongorasom et al 2011 ). The quality of evidence for treatments for OLP is weak, but topical steroids are commonly used as the first line treatment for symptomatic OLP.  The aim of this study was to compare the efficacy of low-level laser therapy (LLLT) with CO2 laser surgery in the treatment of OLP.

28 patients (mean age 50.7 years) with and clinical and histological diagnosis of OLP were randomised to receive either LLLT (n=15) or CO2 laser treatment (n=13). Patients were examined at baseline, and after 2 weeks, 1, 2 and 3 months.  Main outcomes were reduction in; pain and discomfort (VAS); change in lesion size and clinical response. The commonest sites of lesions were on the buccal mucosa.

  • After 3 months, all patients in the LLLT showed either a partial or complete improvement in clinical response compared with only 85% in the CO2 laser group.
  • Improvement in pain scores was achieved in both groups. Amelioration in symptomatic response (pain) was significantly higher in the LLLT group in all follow-up stages

The authors concluded

 this study showed that LLLT displayed better results than CO2 laser therapy as alternative or additional therapy, but further investigations in comparison with standard treatment modalities with a prolonged follow-up period will be necessary to confirm the efficacy of laser therapy in the treatment of OLP.

Comment

It is important to note that this is a relatively small study and OLP is a chronic condition and this study only reports outcomes at 3 months. It is unclear whether the outcome assessors were blind to treatment allocation.  Also the most recent Cochrane review by Chen et al 2011 noted:-

Surgical management, such as carbon dioxide laser, cryotherapy, and excision, is not recommended due to the possibility of triggering lesions (Koebner’s phenomenon) and recurrence of the inflammatory condition.

Links

Agha-Hosseini F, Moslemi E, Mirzaii-Dizgah I. Comparative evaluation of low-level laser and CO(2) laser in treatment of patients with oral lichen planus. Int J Oral Maxillofac Surg. 2012 Jul 9. [Epub ahead of print] PubMed PMID: 22784653.

Cheng S, Kirtschig G, Cooper S, Thornhill M, Leonardi-Bee J, Murphy R. Interventions for erosive lichen planus affecting mucosal sites. Cochrane Database Syst Rev. 2012 Feb 15;2:CD008092. Review. PubMed PMID: 22336835.

Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions for treating oral  lichen planus. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD001168. Review. PubMed PMID: 21735381.

Zakrzewska JM, Chan ES, Thornhill MH. A systematic review of placebo-controlled randomized clinical trials of treatments used in oral lichen planus. Br J Dermatol. 2005 Aug;153(2):336-41. Review. PubMed PMID: 16086745.

American Academy of Oral Medicine  OLP page

 

No single systemic treatment was found to be effective for treatment of mouth ulcers

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The prevalence of mouth ulcers (recurrent aphthous stomatitis , RAS) has been estimated at between 5 – 60%. They can be painful and slow to heal.  There are three recognized forms; minor, major and herpetiform.  The peak age at onset is between 10 and 19 years of age but they can persist through adulthood. The aim of this review was to determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency.

Cochrane methodology was followed with searches of the Cochrane Oral Health Group and PaPaS Trials Registers CENTRAL, Medline; Embase, CINAHL and AMED databases , reference lists and trial authors were also contacted. randomised controlled trials (RCTs) with a primary outcome of  reduction of pain, or reduction in episode duration or frequency associated with RAS were included

  • 25 trials were included, 22 of which were placebo controlled and eight made head-to-head comparisons (five trials had more than two treatment arms).
  • Twenty-one different interventions were assessed.
  • The interventions were grouped into two categories: immunomodulatory/anti-inflammatory and uncertain.
  • Only one study was assessed as being at low risk of bias. There was insufficient evidence to support or refute the use of any intervention.

The Authors concluded

No single treatment was found to be effective and therefore the results remain inconclusive in regard to the best systemic intervention for RAS. This is likely to reflect the poor methodological rigour of trials, and lack of studies for certain drugs, rather than the true effect of the intervention. It is also recognised that in clinical practice, individual drugs appear to work for individual patients and so the interventions are likely to be complex in nature. In addition, it is acknowledged that systemic interventions are often reserved for those patients who have been unresponsive to topical treatments, and therefore may represent a select group of patients.

Links

Brocklehurst P, Tickle M, Glenny AM, Lewis MA, Pemberton MN, Taylor J, Walsh T, Riley P, Yates JM. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD005411. DOI: 10.1002/14651858.CD005411.pub2.

 

New Cochrane Protocols for December 2012

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December brings two new protocols to the Cochrane Library from the Cochrane Oral Health Group. The first of these:-

 Liu JLY, Walsh T, Kerr AR, Lingen M, Brocklehurst P, Ogden G, Warnakulasuriya S, Scully C. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions (Protocol). Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD010276. DOI: 10.1002/14651858.CD010276

Aims

  • to estimate the accuracy of index tests for the detection of oral cancer and potentially malignant disorders of the lip and oral cavity in patients presenting with clinically evident lesions.
  • To estimate the relative accuracy of the different tests.

This review should nicely compliment another Cochrane review that is also being undertaken by the same group (Dental Elf Nov 16th 2012) which is looking at oral examination with or without additional tests to detect oral cancer.

The second protocol is:-

Strydom H, Pandis N, Katsaros C, Curatolo M, Fudalej P. Non-pharmacological interventions for alleviating pain during orthodontic treatment (Protocol). Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD010263. DOI: 10.1002/14651858.CD010263.

The aim of this review is to assess the effects of non-pharmacological interventions to alleviate pain associated with orthodontic treatment.

Flossing, scaling and bugs in the blood

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Some of the evidence used to in the formulation of the NICE guidance on antibiotic prophylaxis for invasive dental procedures that we discussed yesterday was the recognition that everyday oral activities cause bacteraemia (Dental Elf  10th May 2011). This new cross-sectional study by Zhang et al looked the bacteraemia caused by flossing compared with scaling and root planing (SRP)

30 volunteers with chronic periodontitis received either full mouth flossing or one quadrant of SRP at separate appointments one week apart. Flossing and SRP was performed by one of the authors. Blood samples were obtained at baseline, 5 minutes after the start of treatment and 30 seconds and 10 minutes after completion. Total bacteraemia and viridans streptococcal bacteraemia (VSB) were investigated.

  • The 30 participants included 2 males and 18 females with a mean age of 47 (±9.5) years.  5 were current smokers, 8 former smokers and 21 never smokers. All fulfilled the criteria for severe chronic periodontitis
  • Total bacteraemia incidence was 30% for flossing and 43.3% for SRP (no significant difference; p = 0.21).
  • Flossing and SRP caused the same incidence of VSB (26.7%).
  • Flossing caused a higher mean magnitude of total and VSB bacteraemia than SRP, but the difference was not significant.
  • Viridans streptococci comprised 11.4% of flossing bacteraemia isolates and 7.6% in SRP.
  • Gingival inflammation was significantly associated with incidence of total bacteraemia.

The authors concluded

No differences were found between flossing and SRP in the incidence or magnitude of total bacteraemia or VSB. This finding is important in the ongoing re-evaluation of antibiotic prophylaxis to prevent infective endocarditis.

Comment

This studies finding suggests that flossing produces the same level of bacteraemia, as does SRP. It is also worth noting that in 5 participants their baseline samples were found to be positive for bacteraemia (not VSB) of oral origin  (two prior to flossing and 3 prior to SRP) and were excluded when analysing total bacteraemia.

Links

Zhang W, Daly CG, Mitchell D, Curtis B. Incidence and magnitude of bacteraemia caused by flossing and by scaling and root planing. J Clin Periodontol. 2013 Jan;40(1):41-52. doi: 10.1111/jcpe.12029. Epub 2012 Nov 9. PubMed PMID: 23137266.

Dental Elf 10th May 2011 – Bacteraemia due to everyday oral activities.

Dental Elf 8th Jan 2013 – Costs of routine antibiotic prophylaxis prescribing to dental patients in the USA


Study shows that berberine had a positive effect on recurrent aphthous ulceration

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Recurrent aphthous stomatitis (RAS) is usually episodic and self-limiting but can produce severe ulcers that interfere with eating speaking and swallowing.  Minor RAS  (MiRAS) is the most common form.  The aim of this trial was to investigate the efficacy and safety of berberine (an isoquinoline alkaloid originally isolated from medicinal herbs) in the treatment of MiRAS

Adult patients (18-50 yrs of age) with a history of RAS for a minimum of 6 months with an average of 1 to 2 outbreaks per month and 1 to 5 minor aphthae per outbreak were recruited within 48 hrs of ulceration onset. Those with ulceration as as a manifestation of systemic disease were excluded.  Outcomes included pain level, size, erythema, and exudation of certain ulcers on days 1, 2, 4, and 6.  Patients recorded pain on a visual analog scale (VAS) .  Patients were randomised to receive either the active agent ( berberine) or placebo of similar shape colour and flavour.

  • 84 out of the 87 randomised patients completed the trial (2 drop outs in berberine group 1 in placebo)
  • There were significant reductions in both pain score and ulcer size in the berberine group
  • Reduction in pain scores were greater in the on
    • day  2  ( 16.1% vs  6,56% in control )
    • day 4  ( 44.57%   vs  22.6%
    • day 6    (76.65% vs 60.87%)
  • Reduction in ulcer size
    • day  2    (35.63%, vs 14.14%)
    • day 4,  (54.07%, vs 37.66%,)
    • day 6, (70.56% vs 54.35%)
  •  No adverse events were reported.

The authors concluded

The present study findings demonstrate that the topical application of berberine gelatin could decrease pain intensity and promote ulcer healing with minimal safety concerns. Therefore, in clinical practice, berberine gelatin could be a well-tolerated and safe addition to the treatment armamentarium for MiRAS

Comment

This appears to be the first published study that has looked at using berberine for the treatment of RAS so the effects will need to be confirmed in other populations to see if similar positive effects can be demonstrated.  Recently Brocklehurst et al published a Cochrane review on systemic treatments for RAS (Dental Elf Sept 14th 2012 ) and found that no single systemic approach was effective.  A Cochrane review on topical treatments is planned as a number of different topical agents have been tried over the years. In May last year  (Dental Elf 8th & 9th May 2012) we highlighted two other trials looking at dexamethasone and multivitamins for RAS.

Links

Jiang XW, Zhang Y, Zhu YL, Zhang H, Lu K, Li FF, Peng HY. Effects of berberine gelatin on recurrent aphthous stomatitis: a randomized, placebo-controlled, double-blind trial in a Chinese cohort. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec 12. doi:pii: S2212-4403(12)01522-2. 10.1016/j.oooo.2012.09.009.  [Epub ahead of print] PubMed PMID: 23246229.

Dental Elf  Set 14 th   2012 -No single systemic treatment was found to be effective for treatment of mouth ulcer

Dental Elf  May 9th    2012 -Study shows dexamethasone ointment had positive effect on recurrent aphthous ulceration

Dental Elf  May 8th 2012 -Daily multivitamins did not reduce risk of mouth ulcers

 

Small trial suggests a potential benefit for combination of triamcinolone acetonide and salvianolic acid B for Oral submucous fibrosis patients

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Oral submucous fibrosis (OSF) is characterized by chronic inflammation and progressive subepithelial connective tissue fibrosis. This can involve the oral cavity, pharynx and upper third of the oesphagus. It is more commonly found in patients in the Asian subcontinent and the Far East.  The aetiology is considered to be multi-factorial with areca nut chewing, nutritional factors, genetic disposition, and hormonal factors being suggested as causative agents.  OSF cause significant morbidity and is considered a potential malignant condition with a malignant transformation rate as high a 7% in some populations.  The aim of this study was to investigate the effectiveness of triamcinolone acetonide (TA) and salvianolic acid B (SA-B) intralesional combined injection in the treatment of OSF.

Patents with OSF confirmed with biopsy were randomised to receive intralesional injections after topical anaesthesia at weekly intervals, Group A received  triamcinolone acetonide (TA) [n=14 ] , Group B received salvianolic acid B (SA-B) [n=14 ] and group C received TA & SA-B [n=14 ] . All patients were required to perform daily exercises and eliminate harmful oral habits (betel nut chewing, cigarette smoking, and alcohol consumption). Maximum mouth opening and burning sensations were the main outcome measures. Burning sensation was measured using a visual analogue scale (VAS)  Patients were assessed by an examiner blind to group allocations at 10, 20 and 44 weeks.

  •  All of the 42 OSF patients had a betel nut–chewing habit
  • There were improvements in mouth opening and burning sensations  in all three groups.
  • No side effects were reported
Triamcinolone acetonide (TA) Salvianolic acid B (SA-B)
Combination (TA & SA-B)
Baseline Mouth opening (mean± SD) 28.85 ± 3.66 mm27.97 ± 4.79 mm27.73 ±5.03 mm
Increase in mouth opening at 44 weeks
(mean± SD)
2.00 ±1.21 mm3.48 ± 2.23 mm5.50 ±1.80 mm
Improvement in burning sensation at 44 weeks
(mean± SD)
3.05 ± 0.764.96 ± 0.976.11 ± 0.93

The authors concluded

The findings of the present study demonstrate that a TA and SA-B intralesional combined injection improves the signs and symptoms associated with OSF without obvious side effects.

Comment

Treatment options in this are were the subject of a 2008 Cochrane review by Fedorowicz et al and we noted two other reviews in Dental Elf in January 2012. This particular study is small with 42 out of the original 44 completing the study and it is not clear from which groups the drop outs occurred. While this small trial is suggestive of some benefit it is clear that more high quality trials are needed to clarify the most effective treatment for this troublesome condition as previous reviews have found that the available evidence to support the range of drug treatments that have been tried is limited.

Links

Jiang XW, Zhang Y, Yang SK, Zhang H, Lu K, Sun GL. Efficacy of salvianolic acid B combined with triamcinolone acetonide in the treatment of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec 20. Doi:pii: S2212-4403(12)01637-9. 10.1016/j.oooo.2012.10.006. [Epub ahead of print] PubMed PMID: 23260769.

Fedorowicz Z, Chan Shih-Yen E, Dorri M, Nasser M, Newton T, Shi L. Interventions for the management of oral submucous fibrosis. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD007156. DOI: 10.1002/14651858.CD007156.pub2.

Dental Elf  3rd Jan 2012 – Little evidence for drug treatments for oral submucous fibrosis

Small study suggests possible role for low-level laser therapy in treating recurrent oral ulcers

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Recurrent aphthous stomatitis (RAS) is the most common form of oral ulceration. Prevalence rates for the general population vary between 5-60%. Onset generally peaks between the ages of 10-19 an often persists in to adulthood. A wide range of topical and systematic treatments have been utilised including low-level laser therapy. The aim of the study was to determine whether low-level laser therapy (LLLT) has an analgesic effect in patients with recurrent aphthous stomatitis (RAS)

Patients over 10 years of age presenting with pain from RAS with a duration of 3 days or less were invited to participate. Those with systemic disease or undergoing systemic treatment for RAS were excluded. Patients were randomised to either GaAlAs (gallium- aluminum-arsenic) laser treatment wavelength, 809 nm; power, 60 mW; pulse frequency, 1800 Hz; duration, 80 seconds per treatment; and dose, 6.3 J/cm2, or the placebo group, who underwent the same procedure  but without any power. The procedure was repeated on days 1 and 2. Prior to treatment patients recorded pain on a visual analog scale (VAS) and subjective experience of eating, drinking, and brushing their teeth. Patients subjective experience questions were repeated on day 3.

  • 20 patients were recruited to each group
  • In the laser group the VAS score fell from 84.7 to 31.5 compared with 81.7 to 76.1 in the placebo group.
  • Difficulty of drinking, eating, and brushing teeth was relieved in the laser group.

The authors concluded

that LLLT has a pain-relieving effect on minor RAS compared with placebo. LLLT also reduces the pain caused by eating, drinking, and brushing teeth.

Comments

This is a small short-term study where the same individual conducted both the treatment and outcome assessment. Although the outcomes assessed using patient reported information the fact that the same individual administered them might have influenced the responses. The authors highlight 2 previous studies that used  lasers for RAS and currently a Cochrane review is underway looking at topical treatments for RAS (Dental Elf 9th Jan 2014) that will be considering laser treatments. The Cochrane topical treatments review will complement the published Cochrane review of systemic treatments for RAS (Dental Elf 14th Sept 2012).

Links

Albrektson M, Hedström L, Bergh H. Recurrent aphthous stomatitis and pain management with low-level laser therapy: a randomized controlled trial. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014 May;117(5):590-4. doi: 10.1016/j.oooo.2014.01.228. Epub 2014 Feb 6. PubMed PMID: 24725989.

Dental Elf 14th Sept 2012 – No single systemic treatment was found to be effective for treatment of mouth ulcers

Dental Elf 9th Jan 2014 – Cochrane Protocols December 2013

Another review finds limited evidence for making treatment recommendations for keratocystic odontogenic tumors

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The keratocystic odontogenic tumor (KCOT) is a benign but locally aggressive tumour and accounts for 2-11% of jaw cysts and can occur at any age. Historically they have been referred to as odontogenic keratocyst (OKC) and primordial cyst. A range of treatment approaches have been suggested for KCOTs but preferred option is still debatable. The aim of the present study was to define and evaluate the post-treatment recurrence of KCOT lesions in non-syndromic and syndromic patients.

Searches were conducted in Medline, LILACS, BBO, IBECS, ISI Web of Knowledge, Digital Dissertations and Cochrane Database of Systematic Reviews without limits . With additional searches conducted in Google Scholar and the journals Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Journal of Oral and Maxillofacial Surgery, International Journal of Oral and Maxillofacial Surgery, British Journal of Oral and Maxillofacial Surgery, and Journal of Cranio-Maxillofacial Surgery.  Study selection was carried out independently by two reviewers. Studies with KCOT diagnosed histologically at least one study arm with surgical therapy and 12 months follow up were considered. The risk of bias for studies was assessed.

  • 30 studies were included, 19 related to non-syndromic patients, 11 to syndromic patients.
  • Of the 19 studies related to non-syndromic patients only 5 were prospective studies with the majority (74%), reporting minimum follow-up periods of less than three years.
  • The overall risk of bias for these studies was considered to be moderate/high.
  • Recurrence rates for 3 treatment approaches were shown
    • Enucleation only; one study arm (n = 163) had a recurrence rate of 17.8%
    • Enucleation plus adjunctive therapy; two study arms pooled (n = 51) had a recurrence rate of 10.2%
    • Other or combination of treatment; only one study arm (n = 18) with recurrence rate of 27.8%
  • Of the 11 syndromic studies 8 were case series, 3 case reports.

The authors concluded

Based on existing evidence no clinical recommendations can be made for the treatment of KCOTs in either non-syndromic or syndromic patients. Additional prospective controlled clinical studies, ideally randomized and blinded, with adequate sample size and a follow-up of at least three years are needed for both nevoid basal cell carcinoma syndrome (NBCCS) and non-NBCCS cohorts.

Comment

Another group of authors has conducted a review of this topic and found limited evidence to recommend any of the treatment options that are currently being recommended for the management of KCOT. Previously we have reported on one of the other systematic reviews (Dental Elf -28th March 2012) and highlighted the earlier Cochrane review by Sharif et al, which focussed on randomised controlled trials,  finding none. The links section below lists a number of systematic reviews identified on a quick and dirty search on Medline. What is needed now , is not more reviews. but good high quality prospective studies of sufficient size in order to provide clearer information on how to manage this locally aggressive tumour.

Links

Antonoglou GN, Sándor GK, Koidou VP, Papageorgiou SN. Non-syndromic and syndromic keratocystic odontogenic tumors: Systematic review and meta-analysis of recurrences. J Craniomaxillofac Surg. 2014 Apr 1. pii: S1010-5182(14)00100-0. doi: 10.1016/j.jcms.2014.03.020. [Epub ahead of print] PubMed PMID: 24815763.

Dental Elf -28th March 2012 -  keratocystic odontogenic tumour recurrence rates

Sharif FNJ, Oliver R, Sweet C, Sharif MO. Interventions for the treatment of keratocystic odontogenic tumours (KCOT, odontogenic keratocysts (OKC)). Cochrane Database of Systematic Reviews 2010, Issue 9. Art. No.: CD008464. DOI: 10.1002/14651858.CD008464.pub2.

Sansare K, Raghav M, Mupparapu M, Mundada N, Karjodkar FR, Bansal S, Desai R. Keratocystic odontogenic tumor: systematic review with analysis of 72 additional cases from Mumbai, India. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Jan;115(1):128-39. doi: 10.1016/j.oooo.2012.10.005. Review. Erratum in: Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Jun;115(6):841-2. PubMed PMID: 23217544.

Johnson NR, Batstone MD, Savage NW. Management and recurrence of keratocystic odontogenic tumor: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Oct;116(4):e271-6. doi: 10.1016/j.oooo.2011.12.028. Epub 2012 Jul 6. Review. PubMed PMID: 22771402.

Kaczmarzyk T, Mojsa I, Stypulkowska J. A systematic review of the recurrence rate for keratocystic odontogenic tumour in relation to treatment modalities. Int J Oral Maxillofac Surg. 2012 Jun;41(6):756-67. doi: 10.1016/j.ijom.2012.02.008. Epub 2012 Mar 23. Review. PubMed PMID: 22445416.

MacDonald-Jankowski DS. Keratocystic odontogenic tumour: systematic review. Dentomaxillofac Radiol. 2011 Jan;40(1):1-23. doi: 10.1259/dmfr/29949053. Review. PubMed PMID: 21159911; PubMed Central PMCID: PMC3611466.

Blanas N, Freund B, Schwartz M, Furst IM. Systematic review of the treatment and prognosis of the odontogenic keratocyst. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Nov;90(5):553-8. Review. PubMed PMID: 11077375.

Behçet’s disease: review found insufficient evidence to support or refute interventions for oral ulceration

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Behçet’s disease is a chronic inflammatory vasculitis that can affect multiple systems and most commonly appears in the third decade. Oral ulceration, ocular and genital lesions are common. Oral ulceration in Behçet’s disease resembles recurrent aphthous stomatitis (RAS) and the vast majority of Behçet’s have oral ulceration.

The aim of this review was to determine the clinical effectiveness and safety of interventions on the pain, episode duration, and episode frequency of oral ulcers and on quality of life for patients with RAS-type ulceration associated with Behçet’s disease.

Methods

Searches were conducted in The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) ,Medline, Embase CINAHL and AMED databases. The US National Institutes of Health trials register and the World Health Organization (WHO) Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or date of publication.

Randomised controlled trials (RCTs) including cross-over designs with suitable washout period investigating the effects of interventions for the management of RAS-type ulceration in Behçet’s disease were included. Split mouth studies were also considered if there was no risk of contamination. Two reviewers independently selected studies and extracted data with all the review authors assessing risk of bias using the Cochrane risk of bias tool. Standard Cochrane data analysis approaches were adopted.

Results

  • 15 studies (888 patients randomised) were included. 14 used a parallel design and 1 a cross-over design.
  • Only 1 study was assessed as at low risk of bias.
  • 13 different interventions were assessed so it was not possible to conduct a meta-analysis.
  • Topical interventions: sucralfate, interferon-alpha (different doses), cyclosporin A, triamcinolone acetonide ointment, phenytoin syrup mouthwash.
  • Systemic interventions: aciclovir, thalidomide (different doses), corticosteroids, rebamipide, etanercept, colchicine, interferon-alpha, cyclosporin.
  • The quality of the evidence ranged from moderate to very low and there was insufficient evidence to support or refute the use of any included intervention with regard to pain, episode duration, or episode frequency associated with oral ulcers, or safety of the interventions.

Conclusions

The authors concluded

Due to the heterogeneity of trials including trial design, choice of intervention, choice and timing of outcome measures, it was not possible to carry out a meta-analysis. Several interventions show promise and future trials should be planned and reported according to the CONSORT guidelines. Whilst the primary aim of many trials for Behçet’s disease is not necessarily reduction of oral ulceration, reporting of oral ulcers in these studies should be standardised and pre-specified in the methodology. The use of a core outcome set for oral ulcer trials would be beneficial.

Commentary

A previous Cochrane review (Saenz et al 1998) considered pharmacological interventions for treating the different clinical features of Behçet’s disease not just oral ulceration. They included 5 studies on oral ulceration 4 of which are include in the current review. The review authors highlight the poor methodology of many of the trials and the heterogeneity of the studies. They rightly call for higher quality studies and highlight that appropriate pre-specified oral outcome measures should be used for all trials of interventions for Behçet’s disease. They also note that the development of a set of standardised outcome measures for oral ulcer trials is registered with COMET. The development of a common outcome set (COS) would be an important development  as it should help reduce heterogeneity in future reviews.

Links

Taylor J, Glenny AM, Walsh T, Brocklehurst P, Riley P, Gorodkin R, Pemberton MN. Interventions for the management of oral ulcers in Behçet’s disease. Cochrane Database of Systematic Reviews 2014, Issue 9. Art. No.: CD011018. DOI: 10.1002/14651858.CD011018.pub2

Cochrane Oral Health Group – No quality evidence on how to manage mouth ulcers in patients with Behçet’s disease

Saenz A, Ausejo M, Shea B, Wells GA, Welch V, Tugwell P. Pharmacotherapy for Behcet’s syndrome. Cochrane Database of Systematic Reviews 1998, Issue 2. Art. No.: CD001084. DOI: 10.1002/14651858.CD001084.

COMET

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Benign parotid tumors: Superficial or total conservative parotidectomy

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Between 3-10% of head and neck neoplasms are salivary gland tumors the majority of which (75-85%) occur in the parotid gland. Seventy to eighty percent of these parotid tumours are benign and surgical resection is the treatment of choice.

However, there is controversy over the best surgical procedure. The aim of this review is to investigate the effectiveness and complications of Total conservative parotidectomy (TCP) versus Superficial parotidectomy (SP) for the treatment of primary benign parotid tumors.

Methods

Searches were conducted in the PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Alt Health Watch, Health Source: Consumer Edition, Health Source: Nursing/Academic Edition, CINAH, Scopus, Wily Online Library, and Electronic Journal Centre databases.

Randomised controlled trials (RCTs), quasi-randomised controlled trials, or retrospective studies conducted in humans investigating primary benign parotid tumors without any metastases were considered. Study quality was assessed based on 5 criteria: random selection in the population, definition of inclusion/exclusion criteria, report of follow-up, validated measurements, and statistical analysis.

Results

  • 13 studies involving a total of 2477 patients were included.
  • 1317 patients underwent superficial parotidectomy; 391 patients underwent total conservative parotidectomy and 769 patients treated with other surgical techniques were excluded.
  • 5 studies were considered to be at high risk of bias and 8 at medium risk.
  • A narrative summary was presented.
  Superficial parotidectomy Total conservative parotidectomy
Recurrence incidence 0 – 15% (mean 4.57%) 0 – 16% (mean 2.4%)
Facial nerve paresis 0 – 23% (mean 6.75%) 0 – 45% (mean 15%)
Facial nerve paralysis 0 – 3% (mean 0.8 %) 0 – 17 % (mean 4.4%)

Conclusions

The authors concluded:

The results of this review suggest that superficial parotidectomy is superior to total conservative parotidectomy in the management of primary benign tumor in superficial lobes. In addition, superficial parotidectomy showed a minimal recurrence rate for benign tumor in superficial lobes.

Comments

A detailed search of the literature has been conducted to identify studies for this review. However, all of the included studies were retrospective and considered to be at medium to high risk of bias. This needs to be taken into consideration when interpreting the findings.

Links

El Fol HA, Beheiri MJ, Zaqri WA. Comparison of the effect of total conservative parotidectomy versus superficial parotidectomy in management of benign parotid gland tumor: A systematic review. J Craniomaxillofac Surg. 2015 Jan 15. pii: S1010-5182(15)00012-8. doi: 10.1016/j.jcms.2015.01.002. [Epub ahead of print] PubMed PMID: 25769678.

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Oral leukoplakia: malignant transformation rate highly variable

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Oral leukoplakia is the commonest of the oral potential malignant disorders (OPMDs) with a prevalence of 2.6% (95%CI; 1.72-2.74). A proportion of oral leukoplakia undergo malignant transformation with rates between 0-20% having been reported. The aim of this review was to ascertain the malignant transformation rate of oral leukoplakia (OL) and the associated risk factors.

Methods

Searches were conducted in the Medline/PubMed and Embase databases. Prospective or retrospective cohort studies were considered. Studies describing the pre-leukoplakia, proliferative verrucous leukoplakia and snuff-induced lesions were excluded as were studies reporting the same cohort at different time points. A narrative summary of the included studies and summary data are presented.

Results

  • 24 studies involving a total of 12,103 patients were included.
  • A majority (14) of the studies were retrospective.
  • Studies from 13 countries were included Sweden, Denmark, India, Hungary, UK, USA, Norway, Japan, Netherlands, Taiwan, Italy, Croatia and China.
  • The range of malignant transformation was between 0.13% and 34.0%.
  • The mean rate of transformation among all studies in patients with OL was 14.9%
  • 3 studies calculated a specific annual transformation for OL. The range was 0.3% to 6.9% with a mean of 3.8% per year with a range of follow-up time 2.4–11 years.
  • Only 11 studies reported the site of malignant transformation with only 6 indicating the number of cases per original sites of leukoplakia, which transformed into cancer. Buccal mucosa was the commonest site in these studies but had the lowest rate of transformation (3.53%), while tongue (24.22%) and tongue and floor of mouth (14.85%) had the highest rates of transformation.
  • Features that stood out as significant determinants contributing to malignant potential of OL included
    • Advanced age,
    • Female sex,
    • Leukoplakia exceeding 200 mm2,
    • Non-homogeneous type (e.g. erythroleukoplakia) and the higher grades of dysplasia.

Conclusions

The authors concluded: –

Malignant transformation rate of OL varies from 0.13 to 34% across the 24 studies reviewed here. Age, gender, clinical type of the lesion and the grade of dysplasia were found to be important risk factors for malignant transformation.

Advancing age was found to be an important risk factor. Due to the heterogeneity of the age group classification across the reviewed studies, it was difficult to derive a conclusion on the involvement of age as a risk factor. Although OL is relatively uncommon among females compared to males, the malignant transformation was found to be significantly higher among females. Non-homogenous leukoplakia was found to have a higher risk in malignant transformation. In three studies, the dysplasia grade did influence the risk for transformation. It is imperative for clinicians to have more evidence-based information to make sound decisions in clinical management of OL. For the reasons discussed, more studies with clear case definitions are required.

Comments

The reviews search was limited to only two major databases and the English language, so it is likely that relevant studies were not identified. While studies were screened by both authors for inclusion, it is not clear whether this was carried out independently. In addition, the quality of the included studies does not appear to have been assessed. Key findings from each of the included studies are provided in a narrative study and no formal pooling of the studies has been conducted with simple summary statistics provided. The authors note that annual transformation rate is an important guide for clinical practice but note that most studies did not report this or provide enough information for it to be calculated. Challenges also exist because of the use of difference criteria. As the authors note better reported higher quality studies with clear case definitions are needed to inform clinical decisions.

Links

Warnakulasuriya S, Ariyawardana A. Malignant transformation of oral leukoplakia: a systematic review of observational studies. J Oral Pathol Med. 2015 Jul 20. doi: 10.1111/jop.12339. [Epub ahead of print] PubMed PMID: 26189354.

Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A. Interventions for treating oral leukoplakia. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD001829. DOI: 10.1002/14651858.CD001829.pub3.

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Oral potentially malignant disorders and impact on quality of life

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Last week we looked at a review of the malignant transformation rate in oral leukoplakia, the commonest of the oral potentially malignant disorders (OPMDs). As OPMDs can result in pain discomfort and concern regarding the possibility of developing cancer, assessing their impact on patients quality of life is increasingly important. The aim of this review was to assess the literature on quality of life (QoL) in patients with of OPMDs.

Methods

Searches were conducted in PubMed/Medline and CINHAL and limited to English language studies. Two reviewers independently selected studies that assessed QoL using a validated generic or oral health specific instrument in patients with OPMDs. Study quality was assessed. A narrative summary of the findings was presented.

Results

  • 14 studies (4 clinical trials, 10 cross sectional) were included.
  • 11 studies were conducted in Europe, 2 China, 1 in Iran.
  • 13 studies evaluated oral lichen planus (OLP), 1 epidermolysis bullosa.
  • 8 of the included studies were considered to be weak and 6 of moderate quality.
  • 1 study used the Dermatology Life Quality Index (DLQI) with all the other studies using an oral health related QoL instrument. Of these 11 used the Oral Health Impact Profile (OHIP) and 3 the Chronic Oral Mucosal Disease Questionnaire (COMDQ).
  • The findings differ but, overall, do not provide evidence that patients with OPMDs have a poorer QoL compared with healthy patients.

Conclusions

The authors concluded: –

There is no strong evidence that patients with OPMDs have a poorer QoL compared with healthy patients. Several things may explain this superficially surprising conclusion. First, the quality of most of the articles included in this review was moderate or weak; second, most of the studies assessed QoL only in patients with OLP, and these cannot be generalized to all patients with OPMDs; finally, direct comparisons between patients with OPMDs and healthy controls were rarely included. The validity of the QoL instrument used for patients with OLP was frequently inadequate. There is a need for improved and more widely applicable tools in this area of oral medicine.

Comments

The finding that QoL was not affected by OPMDs (leukoplakia, erythroplakia
, Palatal lesions in reverse smokers, submucous fibrosis, lichen planus
, actinic keratosis
, Discoid lupus erythematosus, dyskeratosis congenital, epidermolysis bullosa) is surprising as one would anticipate some impact with these conditions. However, the authors do highlight problems with the quality of the available literature and the fact that studies on only one of the OPMDs, Lichen planus dominated the findings. Consequently, there is clearly a gap in our understanding of the impact on OPMDs on patients’ QoL.

Links

Tadakamadla J, Kumar S, Johnson NW. Quality of life in patients with oral potentially malignant disorders: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Jun;119(6):644-55. doi: 10.1016/j.oooo.2015.01.025. Epub 2015 Mar 17. Review. PubMed PMID: 25956217.

Dental Elf – 24th July 2015 – Oral leukoplakia: malignant transformation rate highly variable

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Diode laser for fibrous hyperplasia – faster but more swelling and longer healing

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Fibrous hyperplasia can be found in any part of the mouth and are thought to affect between 5-16% of the population. They commonly present as small painless lesions and are frequently the result of trauma from an ill fitting denture. Traditionally they are removed with a scalpel but with the increasing use of surgical lasers for oral lesions. The aim of this study was to compare the effects of diode laser surgery with conventional techniques using scalpels.

Methods

Consecutive oral medicine patients presenting with fibrous hyperplasia caused either by dentures or by parafunctional habits were randomised to either conventional surgical removal (control) or 808nm diode laser removal (test). The same local anesthetic agent (2% lidocaine and adrenaline at 1:100,000) was used for both group but the test group also received topical anaesthesia. While suturing was used to close the wound in the control group, no suturing was undertaken in the test group. Paracetamol was prescribed for postoperative pain relief.

The following parameters were measured: type of anaesthesia; duration of surgery; oedema; secondary infection; postoperative pain; analgesic use; postoperative functional alterations, i.e., alterations in eating and speech; clinical healing, and patient satisfaction.

Results

  • 36 patients were randomised. 34 patients were included in the analysis.
  • The fibrous hyperplasia was caused by dentures in 26 of the patients (76.5%)
  • The duration of surgery was shorter in the study group, but these patients reported more oedema. More analgesic medicine was consumed by patients in the control group, but the time to clinical healing of the postoperative wounds was shorter in this group. These differences were statistically significant.
  • No secondary infection was observed in either group, and all patients in both groups reported total satisfaction with the treatment.
Test Control
Number of patients 17 17
Surgery duration, min (mean ± SD) 5.4 ±3.6 7.8 ± 3.2
Analgesic usage, n (%) 6 (35%) 13 (76%)
Oedema 12 (71%) 6 (35%)
Clinical healing of the postoperative wound, days (mean ±SD) 24.29 ± 4.37 21.41 ± 1.69

Conclusions

The authors concluded:

..diode laser surgery proved to be effective in the management of fibrous hyperplasia, decreasing the duration of surgery and the need for analgesic medication, minimizing bleeding, and eliminating the need for sutures. Furthermore, patients tended to tolerate this procedure quite well. Thus, diode laser surgery demonstrated less invasiveness when compared to scalpel surgery. By contrast, wound healing proved to be faster with scalpel surgery when compared to diode laser surgery.

Comments

This small study suggests that that while diode laser treatment was marginally quicker and required fewer analgesics and no sutures there was more swelling and wound healing was longer. In terms of assessing the wound healing, it is not clear whether this was undertaken by operator and owing to the different wound characteristics. It would have been difficult to blind an observer particularly during the early stages of healing, so the possibility of bias presents a fact noted by the authors. Additional studies are needed to confirm these findings.

Links

Amaral MB, de Ávila JM, Abreu MH, Mesquita RA. Diode laser surgery versus scalpel surgery in the treatment of fibrous hyperplasia: a randomized clinical trial. Int J Oral Maxillofac Surg. 2015 Jul 17. pii: S0901-5027(15)00206-4. doi: 10.1016/j.ijom.2015.05.015. [Epub ahead of print] PubMed PMID: 26194769.

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Oral lichen planus: is topical tacrolimus better than clobetasol?

Parasympathomimetic drugs for dry mouth after radiotherapy

Medication related osteonecrosis of the jaw

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Thirteen studies were included in this review of medication related osteonecrosis of the jaw. The majority were case series ( 9) with the risk of osteonecrosis after tooth extraction being higher in those taking IV bisphosphonates ( 3.2% (95% CI: 1.7–4.7%) than those on oral bisphosphonates 0.15% (95% CI: 0.0–0.36%).

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