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The Cochrane Database of Systematic... Nov 2020Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Basal cell carcinoma (BCC) is the commonest cancer affecting white-skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First-line treatment is usually surgical excision, but alternatives are available. New published studies and the development of non-surgical treatments meant an update of our Cochrane Review (first published in 2003, and previously updated in 2007) was timely.
OBJECTIVES
To assess the effects of interventions for BCC in immunocompetent adults.
SEARCH METHODS
We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for BCC in immunocompetent adults with histologically-proven, primary BCC. Eligible comparators were placebo, active treatment, other treatments, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcome measures were recurrence at three years and five years (measured clinically) (we included recurrence data outside of these time points if there was no measurement at three or five years) and participant- and observer-rated good/excellent cosmetic outcome. Secondary outcomes included pain during and after treatment, early treatment failure within six months, and adverse effects (AEs). We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 52 RCTs (26 new) involving 6690 participants (median 89) in this update. All studies recruited from secondary care outpatient clinics. More males than females were included. Study duration ranged from six weeks to 10 years (average 13 months). Most studies (48/52) included only low-risk BCC (superficial (sBCC) and nodular (nBCC) histological subtypes). The majority of studies were at low or unclear risk of bias for most domains. Twenty-two studies were industry-funded: commercial sponsors conducted most of the studies assessing imiquimod, and just under half of the photodynamic therapy (PDT) studies. Overall, surgical interventions have the lowest recurrence rates. For high-risk facial BCC (high-risk histological subtype or located in the facial 'H-zone' or both), there may be slightly fewer recurrences with Mohs micrographic surgery (MMS) compared to surgical excision (SE) at three years (1.9% versus 2.9%, respectively) (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.16 to 2.64; 1 study, 331 participants; low-certainty evidence) and at five years (3.2% versus 5.2%, respectively) (RR 0.61, 95% CI 0.18 to 2.04; 1 study, 259 participants; low-certainty evidence). However, the 95% CI also includes the possibility of increased risk of recurrence and no difference between treatments. There may be little to no difference regarding improvement of cosmetic outcomes between MMS and SE, judged by participants and observers 18 months post-operatively (one study; low-certainty evidence); however, no raw data were available for this outcome. When comparing imiquimod and SE for nBCC or sBCC at low-risk sites, imiquimod probably results in more recurrences than SE at three years (16.4% versus 1.6%, respectively) (RR 10.30, 95% CI 3.22 to 32.94; 1 study, 401 participants; moderate-certainty evidence) and five years (17.5% versus 2.3%, respectively) (RR 7.73, 95% CI 2.81 to 21.3; 1 study, 383 participants; moderate-certainty evidence). There may be little to no difference in the number of participant-rated good/excellent cosmetic outcomes (RR 1.00, 95% CI 0.94 to 1.06; 1 study, 326 participants; low-certainty evidence). However, imiquimod may result in greater numbers of good/excellent cosmetic outcomes compared to SE when observer-rated (60.6% versus 35.6%, respectively) (RR 1.70, 95% CI 1.35 to 2.15; 1 study, 344 participants; low-certainty evidence). Both cosmetic outcomes were measured at three years. Based on one study of 347 participants with high- and low-risk primary BCC of the face, radiotherapy may result in more recurrences compared to SE under frozen section margin control at three years (5.2% versus 0%, respectively) (RR 19.11, 95% CI 1.12 to 325.78; low-certainty evidence) and at four years (6.4% versus 0.6%, respectively) (RR 11.06, 95% CI 1.44 to 84.77; low-certainty evidence). Radiotherapy probably results in a smaller number of good participant- (RR 0.76, 95% CI 0.63 to 0.91; 50.3% versus 66.1%, respectively) or observer-rated (RR 0.48, 95% CI 0.37 to 0.62; 28.9% versus 60.3%, respectively) good/excellent cosmetic outcomes compared to SE, when measured at four years, where dyspigmentation and telangiectasia can occur (both moderate-certainty evidence). Methyl-aminolevulinate (MAL)-PDT may result in more recurrences compared to SE at three years (36.4% versus 0%, respectively) (RR 26.47, 95% CI 1.63 to 429.92; 1 study; 68 participants with low-risk nBCC in the head and neck area; low-certainty evidence). There were no useable data for measurement at five years. MAL-PDT probably results in greater numbers of participant- (RR 1.18, 95% CI 1.09 to 1.27; 97.3% versus 82.5%) or observer-rated (RR 1.87, 95% CI 1.54 to 2.26; 87.1% versus 46.6%) good/excellent cosmetic outcomes at one year compared to SE (2 studies, 309 participants with low-risk nBCC and sBCC; moderate-certainty evidence). Based on moderate-certainty evidence (single low-risk sBCC), imiquimod probably results in fewer recurrences at three years compared to MAL-PDT (22.8% versus 51.6%, respectively) (RR 0.44, 95% CI 0.32 to 0.62; 277 participants) and five years (28.6% versus 68.6%, respectively) (RR 0.42, 95% CI 0.31 to 0.57; 228 participants). There is probably little to no difference in numbers of observer-rated good/excellent cosmetic outcomes at one year (RR 0.98, 95% CI 0.84 to 1.16; 370 participants). Participant-rated cosmetic outcomes were not measured for this comparison. AEs with surgical interventions include wound infections, graft necrosis and post-operative bleeding. Local AEs such as itching, weeping, pain and redness occur frequently with non-surgical interventions. Treatment-related AEs resulting in study modification or withdrawal occurred with imiquimod and MAL-PDT.
AUTHORS' CONCLUSIONS
Surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for high-risk facial primary BCC (low-certainty evidence). Non-surgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Of the non-surgical treatments, imiquimod has the best evidence to support its efficacy. Overall, evidence certainty was low to moderate. Priorities for future research include core outcome measures and studies with longer-term follow-up.
Topics: Adult; Aminolevulinic Acid; Antineoplastic Agents; Carcinoma, Basal Cell; Cryotherapy; Female; Humans; Imiquimod; Immunocompetence; Laser Therapy; Male; Mohs Surgery; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Radiotherapy; Randomized Controlled Trials as Topic; Skin Neoplasms; Treatment Outcome
PubMed: 33202063
DOI: 10.1002/14651858.CD003412.pub3 -
Journal of the European Academy of... Jun 2024The use of Mohs micrographic surgery (MMS) in melanoma treatment has divided opinion and evidence-based guidelines are lacking. (Review)
Review
BACKGROUND
The use of Mohs micrographic surgery (MMS) in melanoma treatment has divided opinion and evidence-based guidelines are lacking.
OBJECTIVES
This systematic review aimed to analyse clinical outcomes for patients with invasive melanomas treated with Mohs rather than wide local excision (WLE).
METHODS
Embase, MEDLINE and Cochrane databases (to 30 August 2023) were searched for studies using Mohs to treat invasive melanoma. Outcomes of interest were local recurrence and death from melanoma.
RESULTS
Thirty-five articles involving 41,499 patients with invasive melanoma treated with Mohs were identified. Sixteen studies compared Mohs with WLE and 19 were Mohs-only, non-comparative studies. Patients treated with Mohs differed significantly from those undergoing WLE, in particular Mohs patients were older and had thinner melanomas. Two comparative studies using the same data source reported adjusted hazard ratios for melanoma-specific death and both showed no significant difference between Mohs and WLE-treated patients; 0.87 (95% CI 0.55-1.35) and 1.20 (95% CI 0.71-20.36). There was also no statistically significant difference in local recurrence risk; the unadjusted risk ratio for patients treated with Mohs was 0.46 (95% CI 0.14-1.51 p = 0.20) with moderate heterogeneity (I = 62%). No studies reported multivariable analyses for risk of local recurrence. Many studies generated from relatively few and often overlapping data sets have reported the use of Mohs to treat patients with invasive melanoma. Fewer studies were comparative between Mohs and WLE and these reported substantially different baseline risks of recurrence and death from melanoma between the groups. Mohs has generally been used for thinner melanomas in older patients; therefore, comparisons based on univariable analyses are likely to have been misleading.
CONCLUSIONS
On the basis of currently available data, it is not possible to reliably assess whether outcomes differ if invasive melanomas with comparable features are treated with Mohs or WLE, and randomized trial evidence will be required for reliable conclusions to be reached.
PubMed: 38842170
DOI: 10.1111/jdv.20138 -
The Journal of Dermatological Treatment Jun 2022Verrucous carcinoma is a rare mucocutaneous malignancy characterized by slow, relentless growth and a low metastasis rate. (Review)
Review
BACKGROUND
Verrucous carcinoma is a rare mucocutaneous malignancy characterized by slow, relentless growth and a low metastasis rate.
OBJECTIVE
Herein we summarize surgical success rates and review newer approaches to the treatment of verrucous carcinomas.
METHODS AND MATERIALS
PubMed electronic searches were performed by B.F. and C.V. using combinations of the following terms: "verrucous carcinoma," "Ackerman tumor," "Buschke Lowenstein," "epithelioma cuniculatum," "carcinoma cuniculatum," "papillomatosis cutis," "treatment," "therapeutics," "management," "mohs surgery," and "excision." A systematic review was conducted on 49 articles in accordance with PRISMA guidelines.
RESULTS
Surgical management remains first-line therapy. Wide local excision is most commonly utilized, with highly variable margins (0.5-3.0 cm) and recurrence rates (4.6-75.0%). Mohs Micrographic Surgery has also been used, especially for recurrent tumors, with an overall recurrence rate of 12.9%.
CONCLUSION
Surgery is the treatment of choice, either by Mohs Micrographic Surgery or wide local excision. However, surgical recurrence rates are high, and tissue-sparing therapies are desirable given the sensitive locations involved. Ultimately, randomized control trials are needed to develop evidence-based guidelines for the management of VCs.
Topics: Carcinoma, Verrucous; Foot Diseases; Humans; Mohs Surgery; Neoplasm Recurrence, Local; Skin; Skin Neoplasms
PubMed: 33849379
DOI: 10.1080/09546634.2021.1914312 -
Archives of Dermatological Research Nov 2023Mohs micrographic surgery (MMS) may be an effective treatment modality for oral cavity cancers (OCC) due to possibility of more effective visualization of tumor margins... (Review)
Review
Mohs micrographic surgery (MMS) may be an effective treatment modality for oral cavity cancers (OCC) due to possibility of more effective visualization of tumor margins and greater preservation of benign tissue. The objective of this study is to review the existing literature on the use of MMS for the treatment of OCC and categorize its uses and limitations. A systematic review was performed in accordance with Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines. PubMed, Scopus, and Google Scholar from inception of databases to January 20, 2023 identified all published studies on the use of MMS for OCC. Nine studies met inclusion criteria. Seventy-seven patients were treated with MMS for OCC, 74 of which (96%) were treated for squamous cell carcinoma (SCC). The tongue was the most common site (n = 57). Six out of seven studies showed no recurrence of disease during the follow-up periods, which ranged from 8 to 42 months, and one study reported significantly lower loco-regional recurrence over a 2-years follow-up period (10.5% vs 25.7%). Mohs technique did not cause a statistically significant increase in operating time. Applicability of MMS is limited by operator comfort with surgical technique and pathological interpretation of specimens in the oral cavity. The main limitation was that various studies did not report specific patient characteristics. In conclusion, MMS may be an effective treatment for OCC, especially for squamous cell carcinomas, and tumors involving the tongue.
Topics: Humans; Carcinoma, Squamous Cell; Mohs Surgery; Mouth Neoplasms; Neoplasm Recurrence, Local; Retrospective Studies; Skin Neoplasms; Systematic Reviews as Topic
PubMed: 37173597
DOI: 10.1007/s00403-023-02632-3 -
Dermatologic Surgery : Official... Jan 2017Basosquamous carcinoma is a rare cutaneous neoplasm that has caused considerable controversy as to its classification, pathogenesis, and management. (Review)
Review
BACKGROUND
Basosquamous carcinoma is a rare cutaneous neoplasm that has caused considerable controversy as to its classification, pathogenesis, and management.
OBJECTIVE
To review and summarize current literature on the definition, pathogenesis, incidence, and management of basosquamous carcinoma.
MATERIALS AND METHODS
Through December 2015, an electronic search of the Pubmed database was performed using combinations of basosquamous carcinoma and metatypical basal cell carcinoma as search terms.
RESULTS
A selection of 39 publications including case reports and series, retrospective studies, and systematic reviews of the literature were included. Descriptions of the definition of basosquamous carcinoma, clinical behavior, histopathological characteristics, current treatment therapies, and future advances are summarized.
CONCLUSION
This systematic review provides a comprehensive overview of the current understanding of basosquamous carcinoma. Further study is required to elucidate the mechanisms driving the formation of this aggressive tumor.
Topics: Anilides; Antineoplastic Agents; Carcinoma, Basosquamous; Combined Modality Therapy; Humans; Immunohistochemistry; Mohs Surgery; Pyridines; Skin Neoplasms
PubMed: 27340741
DOI: 10.1097/DSS.0000000000000815 -
Archives of Dermatological Research Sep 2023There are many articles in the literature on periorbital reconstruction after Mohs micrographic surgery (MMS) or surgical excision, however, the literature lacks a... (Review)
Review
There are many articles in the literature on periorbital reconstruction after Mohs micrographic surgery (MMS) or surgical excision, however, the literature lacks a comprehensive systematic review of these reports. We performed a systematic review of published data on periorbital defect reconstruction to identify trends in the literature. A comprehensive search of eight databases was performed. To be included in the study, articles had to be published in English between 2005 and 2020 and contain repair data for MMS or excision defects in the periorbital region. Studies with less than four patients, literature or systematic reviews, and abstract-only publications were excluded. Data extracted from eligible articles included the authors' medical specialties, study design, subject number and demographics, defect characteristics, procedure type, reconstructive methods, complications, outcome measures, and method of outcome assessment. 53 studies met the inclusion criteria. The first and last authors' specialties were ophthalmology (47%), plastic and reconstructive surgery (23%), dermatology (13%), otolaryngology (4%), or were multi-specialty collaborations (13%). Only 5 of the studies were prospective. Defects were located on the lower eyelid (55%), medial canthus (31%), upper eyelid (8%), lateral canthus (4%), or a combination of these sites (2%). Reconstructive methods were reported for 3678 cases and included linear repair (18%), advancement flap (8%), rotation flap (5%), transposition flap (3%), island pedicle flap (1%), unspecified local skin flap (21%), skin graft (23%), secondary intention (4%), tarsoconjunctival flap (3%), and combined reconstruction techniques (13%). Thirty-three of 53 articles specified the periorbital subunit for each reconstructive technique that was employed. Among these 33 articles which allowed for correlation between defect location and reconstructive technique, the most utilized repair method for lower eyelid defects was local skin flap. Defects on the upper eyelid or medial canthus were most frequently repaired with a skin graft. Forty articles commented on cosmetic outcomes, however, only 3 of these articles utilized a defined grading system, objective measurements, or independent reviewers to assess the cosmetic outcomes. The methods of reconstruction in this review were diverse, however, local skin flaps and grafts were the most utilized techniques. In future reports, increased reporting of reconstructive technique by defect location as well as increased use of standardized assessments of aesthetic outcomes can help strengthen this body of literature.
Topics: Humans; Plastic Surgery Procedures; Eyelid Neoplasms; Mohs Surgery; Prospective Studies; Surgical Flaps; Retrospective Studies
PubMed: 36646921
DOI: 10.1007/s00403-022-02523-z -
Archives of Dermatological Research May 2024The use of botulinum toxin for off-label indications has become more prevalent, but the specific benefits in Mohs micrographic surgery (MMS) have not yet been fully... (Review)
Review
The use of botulinum toxin for off-label indications has become more prevalent, but the specific benefits in Mohs micrographic surgery (MMS) have not yet been fully elucidated. A systematic review was performed of PubMed, Cochrane, EMBASE, and Scopus databases to identify all articles describing the use of botulinum toxin in MMS. Analysis was subdivided into scar minimization, parotid injury, and pain management. A total of nine articles were included. Scar minimization and treatment of parotid injury were the most reported uses. One case reported the use of botulinum toxin for pain management. Off label uses of botulinum toxin are being explored. Additional research is warranted to determine the efficacy and utility of botulinum toxin in MMS.
Topics: Humans; Mohs Surgery; Off-Label Use; Cicatrix; Skin Neoplasms; Botulinum Toxins, Type A; Botulinum Toxins; Pain Management; Parotid Gland
PubMed: 38787406
DOI: 10.1007/s00403-024-02904-6 -
Archives of Dermatological Research Apr 2023Numerous reconstructive techniques for nasal defects following skin cancer removal have been described; however, the literature lacks a comprehensive systematic review.... (Review)
Review
Numerous reconstructive techniques for nasal defects following skin cancer removal have been described; however, the literature lacks a comprehensive systematic review. Our objective was to systematically review nasal reconstruction methods after tumor removal, correlate the use of specific techniques to the nasal subunits involved, assess the quality of the available evidence, and set the stage for future research on this topic. Eight databases were searched for studies published in English from January 2004 to December 2018 containing repair data for nasal defects following Mohs or excision for four or more subjects. Recorded data included author specialties, study design, subject number, demographics, defect characteristics, procedure type, reconstructive methods, outcome measures, and complications. One-hundred and eleven studies were included. Study types included case series (73%), observational cohort studies (25%), and clinical trials (2%). Most authors were dermatologic surgeons (61%). Resection was most commonly performed via Mohs (82%). Flaps (42%), linear closures (28%) and grafts (25%) were most utilized for reconstruction. In Zones I and II, transposition flaps were the most common followed by advancement flaps. In Zone III, full thickness skin grafts were the most common repair. Most studies were case series or small cohort studies, representing low level evidence. Flaps are the most common method described in the literature for nasal reconstruction. The overall quality of the evidence available on this topic is low.
Topics: Humans; Mohs Surgery; Retrospective Studies; Nose; Surgical Flaps; Skin Neoplasms
PubMed: 36152047
DOI: 10.1007/s00403-022-02390-8 -
Dermatologic Surgery : Official... Jan 2024Lidocaine is the most commonly used local anesthetic for Mohs micrographic surgery (MMS), but given its limited half-life, postoperative pain remains a significant...
BACKGROUND
Lidocaine is the most commonly used local anesthetic for Mohs micrographic surgery (MMS), but given its limited half-life, postoperative pain remains a significant concern for patients. Bupivacaine is used in various surgical subspecialty procedures and has demonstrated improved pain control compared with lidocaine. However, its role in MMS is insufficiently explored.
OBJECTIVE
To systematically review the current literature for reports on use of bupivacaine, traditional nonliposomal and newer liposomal formulations, for MMS.
METHODS
A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The MEDLINE, PubMed, and EMBASE databases were queried for articles presenting original data on the use of bupivacaine for MMS.
RESULTS
Of 483 potentially relevant articles, 3 studies met final inclusion criteria, capturing a total of 253 patients involved in primary investigations comparing bupivacaine to traditional local anesthesia for MMS. Bupivacaine was well-tolerated and associated with comparable or modestly reduced intraoperative and postoperative pain and opioid use.
CONCLUSION
Bupivacaine may have a role in prolonging intraoperative anesthesia, reducing acute postoperative pain, and reducing postoperative opioid use after MMS. However, large, prospective studies are needed to solidify the generalizability and clinical utility of these findings.
Topics: Humans; Bupivacaine; Mohs Surgery; Analgesics, Opioid; Anesthetics, Local; Pain, Postoperative; Lidocaine
PubMed: 37861355
DOI: 10.1097/DSS.0000000000003981 -
International Journal of Dermatology Jun 2024Sebaceous carcinoma (SC) is a rare neoplasm affecting periocular and extraocular sites. If inadequately treated, it can recur and cause morbidity. Specific management... (Review)
Review
Sebaceous carcinoma (SC) is a rare neoplasm affecting periocular and extraocular sites. If inadequately treated, it can recur and cause morbidity. Specific management guidelines have not been established. Wide local excision (WLE) has been traditionally used; however, Mohs micrographic surgery (MMS) can be advantageous because of complete margin assessment and tissue-sparing nature. This analysis aims to systematically review the surgical modalities used for the management of SC. Articles meeting eligibility criteria were identified using MEDLINE (via PubMed), Embase, Cochrane, and Scopus databases. All studies investigating surgical management of SC with WLE or MMS were considered. Seventy studies met inclusion criteria, including retrospective cohort studies, case series, and case reports. WLE was used in 32 studies, MMS in 29, and MMS and WLE in 9. Subgroup analysis showed that MMS has lower recurrence rates. For WLE, local, regional, and distant recurrence rates were 23.4%, 13.3%, and 11.0%, respectively, and for MMS, 6.8%, 4.3%, and 4.6%, respectively. Patients treated with WLE were more likely to have local recurrence than patients treated with MMS (P = 0.001). WLE cases were more likely to have a regional (P = 0.05) and distant recurrence (P = 0.001). Limitations of the study include heterogeneity of case reports, case series, and retrospective studies, variable follow-up times between the two groups, and large tumors included in the WLE category. In addition, disease-specific survival was not evaluated. MMS cases showed a superior outcome for local, regional, and distant recurrence, making it a good option for the management of SC.
PubMed: 38856083
DOI: 10.1111/ijd.17283