Keratinocyte cancer

7.1 Considerations before selecting a surgical treatment modality

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Guideline contents > What factors need to be considered when determining if surgical treatment modalities are optimal over non-surgical modalities for the management and/or treatment of basal cell carcinoma or cutaneous squamous cell carcinoma?

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Dr Peter Callan MBBS FRACS MBA, Annika Stollery, Chetcuti, A, James Emmett, Brian De'Ambrosis, Cancer Council Australia Keratinocyte Cancers Guideline Working Party. Clinical question:What factors need to be considered when determining if surgical treatment modalities are optimal over non-surgical modalities for the management and/or treatment of BCC or SCC? . In: Clinical practice guidelines for keratinocyte cancer. Sydney: Cancer Council Australia. [Version URL: https://wiki.cancer.org.au/australiawiki/index.php?oldid=208373, cited 2023 Oct 3]. Available from: https://wiki.cancer.org.au/australia/Guidelines:Keratinocyte_carcinoma.


Last modified:
25 November 2019 21:09:30

Background

Most keratinocyte cancers (KCs) are amenable to surgical treatment, but non-surgical treatments are also available.

While an experienced clinician may be able to make a rapid decision as to the appropriate treatment modality for any given tumour, that decision-making process is based on a list of criteria that need consideration.

Factors that must be considered before opting for surgical excision include:

  • the tumour biology
  • the tumour site
  • the general condition of the patient
  • the timing of treatment.

In some cases, it may be helpful to discuss a case in a multidisciplinary team meeting, or with a pathologist or another clinician.

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Systematic review evidence

What factors need to be considered when determining if surgical treatment modalities are optimal over non-surgical modalities for the management and/or treatment of basal cell carcinoma or cutaneous squamous cell carcinoma?

A systematic review was undertaken to answer this clinical question. The search strategy, inclusion and exclusion criteria, and quality assessment are described in detail in the Technical report.

A total of eight studies reported relevant outcomes in patients with BCC or cSCC undergoing surgical or non-surgical treatment modalities. These included four randomised controlled trials (RCTs)[1][2][3][4][5] two case control studies[6][7] and two cohort studies.[8][9]

Surgical modalities include conventional excision (most studies) and Mohs micrographic surgery (MMS; one study).[9] Nonsurgical treatment modalities included aminolevulinic acid (ALA)-photodynamic therapy (PDT),[1][2][6][7] topical imiquimod[5][4][8] carbon dioxide laser ablation,[3] cryotherapy[3] and electronic brachytherapy.[9]

Reported outcomes included completeness of excision, recurrence rates and adverse events. Of the RCTs, one had a high risk of bias,[5][4] two had an unclear risk of bias[2][1] and one had a low risk of bias.[9] Both of the case control studies had a high risk of bias.[6][7] One cohort study had a low risk of bias,[9] while the other one had a moderate risk of bias.[8]

Imiquimod versus surgical excision

A UK RCT comparing imiquimod 5% cream and surgical excision in 501 nodular or superficial BCCs located on the face, neck, trunk, arm, leg and other locations[5][4] reported that 84% of the imiquimod group and 98% of the surgical group were recurrence-free at 3 years, with similar rates at 5-year follow-up. At 5-year follow-up there was a significantly lower risk of treatment failure among the surgical group: relative risk 0.84 (95% confidence interval 0.772–0.91); p<0.001). Most of the failures in the imiquimod group occurred within the first 12 months.

Aminolevulinic acid-photodynamic therapy versus surgical excision

A RCT comparing surgical excision with ALA-PTD in 196 patients with superficial BCC reported that, while surgery achieved a better clearance rate after 1 year (100% versus 91%), cosmetic outcome was superior for ALA-PDT.[2]

Another RCT in patients with nodular BCCs on the face (52%) or body (48%) also reported higher recurrence rates with ALA-PDT than surgical excision at 60 months’ follow-up (30.7% versus 21.5%, p=0.0001).[1]

A case-control study comparing surgical excision with ALA-PTD in 94 patients with nodular or superficial BCCs reported similar 2-year recurrence rates of approximately 4%, with better cosmetic outcomes in the ALA-PDT group.[7]

Another case-control study reported similar cure rates among patients with BCCs (any type) who received ALA-PDT or surgical treatment.[6]

Electronic brachytherapy (superficial external beam radiotherapy) versus Mohs micrographic surgery

In a cohort of 369 patients with BCCs (54.3%) or cSCCs (45.7%), one tumour recurrence was seen in a patient who underwent electronic brachytherapy, and no recurrences were seen in those who underwent MMS, at approximately 3.4 years’ follow-up (non-significant difference).[9] Cosmetic outcomes were similar in both groups.

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Overview of additional evidence (non-systematic literature review)

In general, compared with more malignant histopathological types, less aggressive surgery is required for low-grade tumour types including nodular BCCs, superficial multifocal BCCs, keratoacanthomas and well-differentiated cSCCs. Some may be suitable for non-surgical treatments.

Tumour biology

Basal cell carcinomas

Superficial multifocal BCCs are amenable to both surgical and non-surgical treatments. Potential non-surgical options include topical imiquimod, PDT (see: Topical treatments and photodynamic therapy), electrodessication and curettage, or cryotherapy (see: Cryotherapy and electrodessication and curettage). Surgery is suitable for lesions that are small, recalcitrant to or recurring after non-surgical treatments, or in anatomically sensitive areas.

Nodular or nodulocystic BCCs can often be successfully treated with excision and direct closure, or other options such as electrodessication and curettage in anatomically favourable areas (see: Tumour site below). Their margins are better defined than any other subgroup of BCC. They are less likely to recur, even in cases of close margins or incomplete excision.

Micronodular, infiltrating and fibrosing (morphoeic) BCCs are less well defined and need surgical excision with wider margins. Hence their rate of recurrence is higher if histologic margins are close or incompletely excised. Treatment for these tumours needs expert attention, including consideration of MMS, postsurgical adjuvant treatments in certain cases, and close follow-up. Poorer prognostic tumours include tumours >2cm on the trunk or extremities or >1cm on the head and neck, hands, feet, genitalia or lower leg, tumours with ill-defined borders, recurrent tumours, or tumours in sites of prior irradiation.[10]

Cutaneous squamous cell carcinomas and related tumours

Bowen’s Disease (cSCC in situ) may be treated surgically or non-surgically. Non-surgical methods can be highly effective in treating such lesions.

Well-differentiated cSCCs and keratoacanthomas are often easily treated with excision and direct closure, but nonsurgical methods can be highly effective. The diagnosis of keratoacanthoma is often clinical, based on the observation of rapid growth (see: Keratoacanthoma in Clinical features). Histological diagnosis can be difficult if the entire tumour is not submitted for histopathologic evaluation (see: Pathology of keratoacanthoma).

Moderately differentiated cSCCs can usually be treated successfully with excision and direct closure, although non-surgical treatments may have a role.

Poorly differentiated cSCCs are often less well defined and need wider excision margins. Hence their rate of recurrence is higher if histologic margins are close or incompletely excised.

Tumours with a poorer prognosis include acantholytic, adenosquamous, carcinosarcomatous, desmoplastic or spindle cell subtypes, large tumours (>2cm), rapidly growing tumours, thick tumours (>6mm) or tumours with other high-risk features such as invasion into fat or surrounding structures, perineural invasion or lymphovascular invasion (Table 5).[11] Treatment for these tumours needs expert attention with consideration of adjuvant treatment in certain cases and close follow up. Discussion in a multidisciplinary clinic or with another clinician is often helpful.[10]

Table 5. Tumour-specific factors associated with recurrence of keratinocyte cancers Table 5 KC guideline Tumour specific factors BBC cSCC.png

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Tumour site

The consequences of recurrence need to be borne in mind when discussing surgery. Favourable anatomical sites are those where local recurrence (histopathology aside) is unlikely to cause problems if monitored closely and further treatment would not cause much morbidity, either aesthetically or functionally.

However, local recurrence in sites close to apertures, or adjacent to unique structures can be devastating. Sites such as the so-called H zone (central face, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular and postauricular skin and sulci, temple, and ear) have a higher risk of recurrence and recurrence can be much more difficult to treat than the primary lesion.[12][13][14] Mohs micrographic surgery may be considered as a treatment option for these difficult-to-treat sites.

Patients have widely differing expectations of cosmetic outcome after skin cancer surgery.

A knowledge of superficial anatomy is vital in planning even minor skin tumour excisions. Care should be taken with excisions in sites where nerves and other structures may be at risk. Special care should be taken with the temporal branches of the facial nerve, which are relatively superficial and may be damaged during excision of lesions that overlie the course of the nerve over the zygoma, lateral periorbital and temple regions. The mandibular branch is at risk and it may pass below the line of the mandible. The accessory nerve after it emerges from behind the posterior border of the sternomastoid is subcutaneous and at risk when excisions are performed in the posterior triangle. The great auricular nerve is similarly at risk under the ear and over the sternomastoid.

Tumour resection that is likely to result in cosmetic or functional defects requires specialised reconstructive techniques. Patients who require this type of surgery should be referred for specialist care. Tumours on the face are best treated by trained and experienced practitioners to minimise alteration in function of the eyelids or mouth and to ensure a satisfactory cosmetic outcome. Lesions on the nose or ear present specific challenges, including the thinness of the subcutaneous tissue, proximity to bone and cartilage, and the tightness of the skin envelope, which may prevent direct closure of the defect.

Occasionally sacrifice of major structures, for example eyelid, tear duct or facial nerve, is necessary to achieve complete resection. Non-surgical treatment such as radiotherapy may be appropriate in some cases. It is therefore essential preoperatively to attempt to assess the level of tumour invasion (if any) into surrounding structures.

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General condition of the patient

Life expectancy can be an important factor in determining the appropriate aggressiveness of treatment for slow-growing tumours. Some patients may have tumours that will never cause them any trouble in the short term, but leaving such tumours can lead to later, more complex and difficult problems if patient selection is incorrect. Some BCCs and Bowen's disease, in particular, can take years to become troublesome. In some cases observation and regular review observation may be acceptable.

On the other hand, KCs in younger patients, particularly cSCC of the head and neck, can behave aggressively and need urgent and adequate treatment. Keratinocyte tumours in immunocompromised should be managed more aggressively (see: Organ transplantation and other conditions associated with immunosuppression).

One must also consider the rest of the patient’s skin. Patients who have multiple KCs need an overall treatment plan. It is clearly poor management to excise a biopsy-proven skin cancer and ignore several other obvious tumours or premalignant lesions.

See also: Prognosis.

Anticoagulant agents and surgery

Minor dermatologic surgery can be carried out safely without ceasing treatment with aspirin, warfarin or the newer oral anticoagulants.

Recent meta-analysis involving 30,000 patients showed little increase in intervention for bleeding in patients on antiplatelet therapy.[15] A systematic review of the effects of antiplatelet therapy on surgical outcomes[16] found an increase in bleeding risk in those on anticoagulants or antiplatelet agents, but the consequences were not significant enough to recommend cessation of such treatments in those that require them. Similarly, a US retrospective study[17] found that the novel oral anticoagulants (oral anticoagulants dabigatran, apixaban, and rivaroxaban) did not alter the morbidity of MMS and did not recommend their cessation. Other authors have recommended continuation of warfarin or low-dose aspirin treatment for patients undergoing skin surgery, because the risk of severe haemorrhagic complications is low.[18]

A prospective study of 2,326 consecutive patients undergoing minor dermatological excisional surgery[19] included those taking warfarin (n=28), aspirin (228) and 2073 patients taking no medication. Patients were reviewed postoperatively for bleeding and wound complications. There was no increase in complications among patients being regularly treated with either aspirin or warfarin, despite the older mean age and greater number of comorbidities in this subgroup.[19] The authors concluded that both aspirin and warfarin (provided that a clotting test is performed and international normalised ratio recorded prior to surgery) can be continued during minor dermatological excisional surgery, provided that strict surgical haemostasis is achieved.

Evidence from RCTs of perioperative aspirin for non-cardiac surgery, including a recent systematic review and meta-analysis of,[20] and a very large RCT of preoperative aspirin,[21] suggests that aspirin does not affect rates of death or nonfatal myocardial infarction, but increases the risk of major bleeding. However, these studies did not separately report outcomes in patients undergoing surgery for KCs.

While available evidence suggests that stopping aspirin is helpful in patients undergoing non-cardiac surgery, most cutaneous surgery may be an exception because bleeding is unusual and the areas are small.

Role of antibiotics in cutaneous surgery

No prospective RCTs have investigated the use of prophylactic antibiotics to prevent haematogenous prosthesis infection in patients who have undergone a dermatological procedure.[22] The Australian Therapeutic Guidelines recommend prophylactic perioperative antibiotics only for patients at the highest risk of endocarditis or prosthetic joint infections.[23]

Antibiotics are not usually indicated for minor procedures, but can be considered for larger excisions, excisions from sebaceous type of skin, or skin grafts or where the lesions are ulcerated or contaminated. A prospective observational study of patients undergoing MMS without prophylactic antibiotics[24] reported a very low rate of infection.

When used, antibiotics should be given at least 20 minutes before surgery (an hour if oral). There is rarely any indication for postoperative antibiotics. There is no role for topical antibiotics.[25]

Metastatic disease

Although KCs infrequently metastasise, lymph node examination should be carried out, particularly in the case of high-risk tumours, cSCCs on the head and neck, and immunocompromised patients (see: Metastatic disease and Prognosis). In larger tumours computed tomography (CT) or CT-positron-emission tomography (PET) may be appropriate.

Timing

When to operate on a tumour is a common dilemma in practice. When the diagnosis is made it is best to excise the tumour promptly to minimise morbidity associated with further growth of the KC. In practice, due to the constraints of surgical schedules many tumours are not excised until days or weeks after diagnosis, often with no clinically important consequences.

It is important to triage tumours according to risk factors to ensure that tumours capable of causing greater morbidity are excised as soon as practicable. Low-grade tumours, such as nodular BCCs in favourable sites, can often safely wait until time is available.

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Evidence summary and recommendations

Evidence summary Level References
Nonsurgical treatment generally resulted in higher rates of recurrence (0.53% to 30.7%) than surgical treatment (0% to 4.34%) for mainly low-risk BCCs located on various parts of the body after 12 to 60 months’ follow-up. II, III-2 [4], [2], [1], [9], [7], [8]
A higher percentage of adverse events occurred after non-surgical treatment than surgical treatment for mainly low-risk BCCs. II, III-2 [5], [2], [7], [3], [9]
Overall clearance was lower after non-surgical treatment (mean 87.05%) than surgical treatment (mean 98.35%) for mainly low-risk BCCs on the trunk, neck, face, scalp, leg, arm and extremities after 3 months. II, III-3, IV [3], [2], [6], [7]
Evidence-based recommendationQuestion mark transparent.png Grade
EBR 7.1.1. Both surgical and nonsurgical treatment modalities can be considered for superficial and nodular basal cell carcinomas in favourable sites. 		C


Key point(s)

Both surgical and nonsurgical treatment modalities can be considered for low-risk keratinocyte cancers in favourable sites. The decision must balance the probability of achieving clearance, recurrence risk, cosmetic and functional outcome, and patient preference.

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Appendices

Jutta's magnifying glass icon.png PICO question SX1 View Evidence statement form SX1 Evidence statement form SX1 View Systematic review report SX1 Systematic review report SX1

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References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Roozeboom MH, Aardoom MA, Nelemans PJ, Thissen MR, Kelleners-Smeets NW, Kuijpers DI, et al. Fractionated 5-aminolevulinic acid photodynamic therapy after partial debulking versus surgical excision for nodular basal cell carcinoma: a randomized controlled trial with at least 5-year follow-up. J Am Acad Dermatol 2013 Aug;69(2):280-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23566914.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Szeimies RM, Ibbotson S, Murrell DF, Rubel D, Frambach Y, de Berker D, et al. A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8-20 mm), with a 12-month follow-up. J Eur Acad Dermatol Venereol 2008 Nov;22(11):1302-11 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18624836.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Zane C, Facchinetti E, Arisi M, Ortel B, Calzavara-Pinton P. Pulsed CO2 Laser Ablation of Superficial Basal Cell of Limbs and Trunk: A Comparative Randomized Clinical Trial With Cryotherapy and Surgical Ablation. Dermatol Surg 2017 Jul;43(7):920-927 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28291062.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Williams HC, Bath-Hextall F, Ozolins M, Armstrong SJ, Colver GB, Perkins W, et al. Surgery Versus 5% Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year Results of the SINS Randomized Controlled Trial. J Invest Dermatol 2017 Mar;137(3):614-619 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27932240.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Bath-Hextall F, Ozolins M, Armstrong SJ, Colver GB, Perkins W, Miller PS, et al. Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial. Lancet Oncol 2014 Jan;15(1):96-105 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24332516.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Suárez Valladares MJ, Vega J, Rodríguez Prieto MA. Comparison of treatment of basal cell carcinoma between surgery and intralesional photodynamic therapy: A cross-sectional study. Photodiagnosis Photodyn Ther 2018 Mar;21:312-315 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29309849.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Cosgarea R, Susan M, Crisan M, Senila S. Photodynamic therapy using topical 5-aminolaevulinic acid vs. surgery for basal cell carcinoma. J Eur Acad Dermatol Venereol 2013 Aug;27(8):980-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22738399.
  8. ↑ 8.0 8.1 8.2 8.3 Graells J, Ojeda RM, García-Cruz A. Effect of imiquimod as compared with surgery on the cancerization field in basal cell carcinoma. Actas Dermosifiliogr 2014 Jan;105(1):53-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24139468.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 Patel R, Strimling R, Doggett S, Willoughby M, Miller K, Dardick L, et al. Comparison of electronic brachytherapy and Mohs micrographic surgery for the treatment of early-stage non-melanoma skin cancer: a matched pair cohort study. J Contemp Brachytherapy 2017 Aug;9(4):338-344 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28951753.
  10. ↑ 10.0 10.1 Nehal KS, Bichakjian CK. Update on Keratinocyte Carcinomas. N Engl J Med 2018 Jul 26;379(4):363-374 Available from: http://www.ncbi.nlm.nih.gov/pubmed/30044931.
  11. ↑ Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, et al. (Eds.). AJCC Cancer Staging Manual (8th edition). Springer International Publishing: American Joint Commission on Cancer; 2017 [cited 2016 Dec 28].
  12. ↑ Kumar P, Watson S, Brain AN, Davenport PJ, McWilliam LJ, Banerjee SS, et al. Incomplete excision of basal cell carcinoma: a prospective multicentre audit. Br J Plast Surg 2002 Dec;55(8):616-22 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12550113.
  13. ↑ Hansen C, Wilkinson D, Hansen M, Soyer HP. Factors contributing to incomplete excision of nonmelanoma skin cancer by Australian general practitioners. Arch Dermatol 2009 Nov;145(11):1253-60 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19917954.
  14. ↑ NCCN Panel. NCCN Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. National Comprehensive Cancer Network; 2018 Aug 31 [cited 2019 Mar 20]. Report No.: Version 1.2019. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.
  15. ↑ Columbo JA, Lambour AJ, Sundling RA, Chauhan NB, Bessen SY, Linshaw DL, et al. A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery. Ann Surg 2018 Jan;267(1):1-10 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28463896.
  16. ↑ Bordeaux JS, Martires KJ, Goldberg D, Pattee SF, Fu P, Maloney ME. Prospective evaluation of dermatologic surgery complications including patients on multiple antiplatelet and anticoagulant medications. J Am Acad Dermatol 2011 Sep;65(3):576-583 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21782278.
  17. ↑ Antia C, Hone N, Gloster H. Perioperative complications with new oral anticoagulants dabigatran, apixaban, and rivaroxaban in Mohs micrographic surgery: A retrospective study. J Am Acad Dermatol 2017 Nov;77(5):967-968 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29029905.
  18. ↑ Otley CC. Continuation of medically necessary aspirin and warfarin during cutaneous surgery. Mayo Clin Proc 2003 Nov;78(11):1392-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14601698.
  19. ↑ 19.0 19.1 Shalom A, Klein D, Friedman T, Westreich M. Lack of complications in minor skin lesion excisions in patients taking aspirin or warfarin products. Am Surg 2008 Apr;74(4):354-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18453305.
  20. ↑ Wolff G, Navarese EP, Brockmeyer M, Lin Y, Karathanos A, Kołodziejczak M, et al. Perioperative aspirin therapy in non-cardiac surgery: A systematic review and meta-analysis of randomized controlled trials. Int J Cardiol 2018 May 1;258:59-67 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29544957.
  21. ↑ Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, et al. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014 Apr 17;370(16):1494-503 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24679062.
  22. ↑ Lee MR, Paver R. Prophylactic antibiotics in dermatological surgery. Australas J Dermatol 2016 May;57(2):83-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25752777.
  23. ↑ Therapeutic Guidelines. Therapeutic Guidelines: Antibiotic, version 15. West Melbourne: Therapeutic Guidelines Limited; 2014 Available from: https://tgldcdp.tg.org.au/guideLine?guidelinePage=Antibiotic&frompage=etgcomplete.
  24. ↑ Rogers HD, Desciak EB, Marcus RP, Wang S, MacKay-Wiggan J, Eliezri YD. Prospective study of wound infections in Mohs micrographic surgery using clean surgical technique in the absence of prophylactic antibiotics. J Am Acad Dermatol 2010 Nov;63(5):842-51 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20800320.
  25. ↑ Saco M, Howe N, Nathoo R, Cherpelis B. Topical antibiotic prophylaxis for prevention of surgical wound infections from dermatologic procedures: a systematic review and meta-analysis. J Dermatolog Treat 2015 Apr;26(2):151-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24646178.

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