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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 5  |  Page : 1051-1055

Clinical efficacy of Mohs surgery combined with topical photodynamic therapy for facial basal cell carcinoma


Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Military Medical University, Chongqing, China

Date of Submission15-Nov-2019
Date of Decision22-Jan-2020
Date of Acceptance08-Mar-2020
Date of Web Publication29-Sep-2020

Correspondence Address:
Yuanyuan Wang
Department of Plastic and Cosmetic Surgery, Daping Hospital, Army Military Medical University, 10 Changjiang Branch Road, Daping, Chongqing 400042
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_987_19

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 > Abstract 


Purpose: The purpose of this study is to investigate the clinical efficacy of Mohs surgery in combination with topical photodynamic therapy (PDT) for facial basal cell carcinoma.
Patients and Methods: Eighty-six patients with facial basal cell carcinoma treated in our department from April 2011 to December 2013 were included. Mohs surgery was used to remove the lesions followed by direct suturing, skin flap grafting, or medium thickness free-skin grafting to repair the incisions. Topical PDT was performed three times, at an interval of 2 weeks, immediately after the sutures were removed. The patients were followed up for 2 years after the operation to evaluate tumor recurrence.
Results: Recurrence was not observed within 1 year after Mohs surgery combining PDT; however, one case of recurrence was found at the 2-year follow-up.
Conclusion: The efficacy of Mohs surgery combining topical PDT is a definite treatment for facial basal cell carcinomas, as it reduced the tumor recurrence rate and maintained the relative integrity of the local tissues and appearance. This method could be a new effective treatment method for the facial basal cell carcinoma.

Keywords: Basal cell carcinoma, Mohs, topical photodynamic therapy


How to cite this article:
Zhang J, Lu Y, Zhang X, Yang Y, Kou H, Wang Y. Clinical efficacy of Mohs surgery combined with topical photodynamic therapy for facial basal cell carcinoma. J Can Res Ther 2020;16:1051-5

How to cite this URL:
Zhang J, Lu Y, Zhang X, Yang Y, Kou H, Wang Y. Clinical efficacy of Mohs surgery combined with topical photodynamic therapy for facial basal cell carcinoma. J Can Res Ther [serial online] 2020 [cited 2020 Oct 30];16:1051-5. Available from: https://www.cancerjournal.net/text.asp?2020/16/5/1051/296455




 > Introduction Top


Basal cell carcinoma is a common malignant skin tumor that mainly occurs on the facial area, causing severe distortion of the appearance. Although the traditional treatment methods have some level of efficacy, the therapeutic processes are painful and have limitations with regard to cosmetic effects and side effects.[1] Mohs surgery is a classic method for the treatment of the malignant skin, which has been widely used in the field of dermatologic surgery.[2] Photodynamic therapy (PDT) is a novel phototherapy and has already been considered as one of the standard treatment methods for certain kinds of malignant skin tumors.[3],[4] Eighty-six patients with facial basal cell carcinoma underwent Mohs surgery in combination with topical PDT in our department from April 2011 to December 2013, which resulted in high treatment efficacy and low recurrence rate. The results are reported below.


 > Patients and Methods Top


Clinical characteristics

In all, 86 patients (54 male and 32 female) with facial basal cell carcinoma treated in our department from April 2011 to December 2013 were included in this study. The age of the patients ranged from 41 to 75 years, and the disease courses ranged from 8 months to 10 years. The lesions of the patients were located in the inner canthus, lower eyelid, nose, temporalis, and so on. The types of lesions were superficial and nodular basal cell carcinoma in 48 and 38 patients, respectively. In all, eighty patients exhibited single lesion, and six patients, multiple lesions; 77 patients were diagnosed with primary tumors and nine with recurrent tumors after undergoing surgeries in other hospitals. The lesion size was <2.0 cm in 57 patients, 3.0–4.0 cm in 24 patients, and 4.0 cm in 5 patients. The tumors in all the patients were confirmed by histopathological examinations. The patients with the following conditions were excluded from the topical PDT therapy: Allergy to a photosensitizer, severe systemic diseases, and/or severe immune dysfunction.

Lesion resection with Mohs surgery

The region was demarcated up to 1 mm from the tumor margin, following which disinfecting and draping were performed routinely in the surgical area. The skin was incised along the demarcation, and the lesions were excised from the fat tissue layer, superficial and deep surfaces of the deep fascia, and the surface of the periosteum. The removed tissues were appropriately marked on the margins for directionality and order before freezing them in a specimen box. The frozen section was identified for the existence of residual tumor tissues. An extended resection was performed on the patients with residual tumor tissues until the tumors were completely removed (no tumor cells on the margins of the tumor in the frozen sections). The incisions were then closed followed by direct suturing, skin flap grafting, and medium thickness free skin grafting, according to the principles of “better near than far, better simple than complex.” While for the tumors at specific locations, such as inner canthus and eyelid margin, the lesions were resected as much as possible while maintaining the critical structures.

Postoperative topical photodynamic therapy

After the suture of the incisions was removed, topical PDT was performed immediately. Further, 5-aminolevulinic acid (5-ALA, FudanZhangjiang Biomedical Co., Ltd. Shanghai, China) was selected as the photosensitizer. It was solubilized in 5% azone cream and prepared as a 10% 5-ALA emulsion before use. XD-635AB photodynamic therapeutic system (Xingda Photoelectric Medical Instrument Co., Ltd, Guilin, China) was chosen as the light source. The treatment covered the area within 2 cm from the margins of the tumors. The treatment area was cleaned and dried. Then, a piece of degreasing cotton soaked in 10% 5-ALA was used to cover the treatment area, after which a protective film and sterile gauze were covered and fixed on the treatment area. The patients were advised to stay in the dark for 4 h. Subsequently, the degreased cotton was removed, and red light at a wavelength of 635 nm was used to irradiate the treatment area, with an output power of 200 mW/cm 2, irradiation dose of 120 J/cm 2, and irradiation time of 20 min. Topical PDT was performed three times at an interval of 2 weeks.

Treatments after photodynamic therapy

After topical PDT was performed, prednisone acetate (20 mg, qd) and ketotifen fumarate (1 mg, bid) were used for anti-inflammatory treatment. The patients were advised to avoid light for 24 h strictly after the treatment.

Follow-up

All the patients were followed up every half year for 2 years after the treatment. The new abrasions after the disappearance of the original skin lesions were considered recurrence.


 > Results Top


Tumor alterations

Among the 86 patients with facial basal cell carcinoma, Mohs surgery was able to completely resect the lesions in 84 patients. For the other two patients, the tumors were at specific sites (eyelid margin and inner canthus), and they were not completely resected by Mohs surgery. However, after three treatments with PDT after the Mohs surgery, the skin lesions disappeared completely.

Adverse effects

Topical burning sensation and mild pain were reported by some patients. However, all of these adverse effects were tolerable. Some patients showed skin swelling, prickling, and itching due to the compromise in avoiding the light. These symptoms disappeared after strictly avoiding the light and undergoing symptomatic treatments. Some patients were showed pigmentation or depigmentation after the skin rashes disappeared. None of the patients were found with severe adverse effects such as treatment-related liver or renal toxicities and bone marrow suppression.

Follow-up results

All the patients underwent Mohs surgery in combination with topical PDT and were followed-up for 2 years after the treatments [Figure 1] and [Figure 2]. No recurrence was observed within 1 year after the operation. However, one recurrence was recorded at 2 years after the operation, yielding a relapse rate of 1.16%. The original tumor of the patient with recurrence was located at the left lower eyelid, which could not be entirely removed by the operation [Figure 3].
Figure 1: (a) Before surgery (b) One-year follow-up after treatment (c) Two-year follow-up after treatment

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Figure 2: (a) Before surgery (b) One-year follow-up after treatment (c) Two-year follow-up after treatment

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Figure 3: (a) Before surgery (b) One-year follow-up after treatment (c) Two-year follow-up after treatment

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 > Discussion Top


Basal cell carcinoma is a common malignant skin tumor mainly occurring at the exposed parts such as the head and face and could easily cause destruction of local appearance. The conventional operations involve resection of the tumor at 4 mm [5] to the outer margins, primarily focusing on expanding the resection area to prevent the tumor recurrence that could increase the risk of destroying the topical appearance. Therefore, the treatments not only need to clear the tumor cells completely but also consider the cosmetic effects and functional integrity.

Mohs surgery is a technology combining dermatological surgery and pathological slices of specific frozen tissue.[6] This surgery improved the methods of obtaining the sample tumor slices, which could ensure removal of the whole tumor and preservation of the normal tissues as much as possible, thereby avoiding unnecessary extended resection. Mohs surgery is considered the preferred treatment for skin tumors in European countries and the USA.[7] In this procedure, the tumors are resected along 1 mm to the outer margin of the tumor, and then the extended resection is performed gradually with the guidance of the pathological results from frozen slices. Compared with conventional operations, Mohs surgery involves a small resection area, and the incision can be effortlessly closed, resulting in superior cosmetic effects and preserved functionality. However, clinical cases have shown that recurrence does occur in basal cell carcinoma patients treated solely with Mohs, indicating sub-optimal treatment efficacy.[8],[9]

PDT is an advanced methodology utilizing the high affinity between the photosensitizers and damaged tissues. The method involves the use of a specific laser to irradiate the concentrated photosensitizer in the damaged tissues, resulting in the targeted destruction of the injured tissues through photodynamic responses. This method is being widely used for the treatment of skin tumors such as Bowen's disease [10],[11],[12] and is considered one of the hotspot methods for the prevention of tumors globally.[13] Five-ALA is a precursor of a photosensitizer that is being used in recent years. After inhalation, the exogenous ALA can be absorbed and accumulated in the lesion cells that proliferate actively and transform into protoporphyrin IX in the cells. After irradiation with a laser of a specific wavelength, the photodynamic reactions could induce the generation of reactive oxygen species,[14] which kills the damaged cells without affecting the sounding normal tissue cells.[15],[16],[17] PDT is highly selective to tumor cells and thus destroys the tumor cells without damaging the normal tissues. Previous studies have shown that the tumor clearance rate by the sole use of local PDT is relatively low when treating basal cell carcinomas, and the recurrence rate is relatively high,[14] which could be associated with the insufficient depth penetrated by the laser. This is one of the reasons why nodular basal cell carcinoma is not sensitive to simple PDT. Previous studies used a laser wavelength of 635 nm, which could penetrate a maximum of 2 mm in the tissues.[18] Researchers have also compared the treatment efficacies of PDT and conventional methods for basal cell carcinoma, wherein treatment was carried out with PDT or conventional surgery, and the clinical efficacies and cosmetic effects were evaluated. The results showed that the 2-year recurrence rate was 16.6%, and the satisfaction rate of the cosmetic effects was 95.8% for the patients who underwent PDT. On the other hand, the 2-year recurrence rate was 3.8%, and the satisfaction rate of the cosmetic effects was 77.8% for the patients who underwent conventional surgery.[19] These results showed that using either PDT or surgery does not meet the treatment requirements.

Mohs surgery combining topical PDT was carried out in our department for patients with facial basal cell carcinomas since 2011. This treatment method combined the advantages of these two approaches and compensated for their disadvantages. In this combined method, the tumor was first resected completely during surgery, while the normal tissues were preserved as much as possible. Therefore, it maintained the relative integrity of the local appearance, shortened the treatment depth for PDT, and efficiently reduced the recurrence rate after PDT. Among the 86 patients included in the present study, the lesions of 84 patients were fully removed, after which topical PDT was provided. In the case of the other two patients, the tumors were at the unusual locations (inner canthus and eyelid margin); these lesions were resected as much as possible and the critical structures were preserved; the residual tumors were treated with PDT. In addition, three PDTs [20] were further performed after the operation, following which the skin tumor disappeared completely. All the operations were interrupted before extending over the areas of tumor resection, therefore avoiding the appearance of severe distortion and difficulties in treating the trauma caused by the extended resection. As this method considered both the functionality and cosmetic effects, it was better accepted by the patients. The 86 patients were followed up for 2 years, and the recurrence rate was 1.16%. We speculated that the recurrence could be attributable to the residual tumor cells after Mohs surgery and PDT in an attempt to preserve the critical structures. For patients with tumors that are not completely removed during surgery, whether intraoperative PDT can achieve a longer recovery period is one of the topics and directions of our future clinical research.

In summary, Mohs surgery combined with PDT could be an effective treatment for facial basal cell carcinomas, effectively reducing the recurrence rate of the tumor, preserving the normal tissues as much as possible, and maintaining the integrity of the local tissues and appearance. Thus, the satisfaction rate of the patients was high for this method. This study, therefore, provided an advanced and efficient method for the treatment of patients with facial basal cell carcinoma.

Acknowledgments

The study was supported by the Natural Science Foundation of China (No. 81201244, 81502371). We gratefully acknowledge the commitment and dedication of all the participants.

Financial support and sponsorship

The study was supported by the Natural Science Foundation of China (No. 81201244, 81502371). We gratefully acknowledge the commitment and dedication of all the participants.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Bassukas ID, Ganiatsa A, Gaitanis G. Health-related quality of life associated with immunocryosurgery, a minimally invasive modality, for cervicofacial basal cell carcinoma. Eur J Dermatol 2019;29:234-6.  Back to cited text no. 1
    
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Bobotsis R, Guenther L. How Mohs surgery transformed into a first-line treatment of skin cancer. J Cutan Med Surg 2017;21:40-1.  Back to cited text no. 2
    
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Miller SJ, Alam M, Andersen J, Berg D, Bichakjian CK, Bowen G, et al. Basal cell and squamous cell skin cancers. J Natl Compr Canc Netw 2007;5:506-29.  Back to cited text no. 3
    
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Asadi KA, Alam M, Goldberg LH, Peterson SR, Silapunt S, Jih MH. Efficacy of narrow-margin excision of well-demarcated primary facial basal cell carcinomas. J Am Acad Dermatol 2005;53:464-8.  Back to cited text no. 5
    
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Mosterd K, Krekels GA, Nieman FH, Ostertag JU, Essers BA, Dirksen CD, et al. Surgical excision versus Mohs' micrographic surgery for primary and recurrent basal-cell carcinoma of the face: A prospective randomised controlled trial with 5-years' follow-up. Lancet Oncol 2008;9:1149-56.  Back to cited text no. 8
    
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Weesie F, Naus NC, Vasilic D, Hollestein LM, van den Bos RR, Wakkee M. Recurrence of periocular basal cell carcinoma and squamous cell carcinoma after Mohs micrographic surgery: A retrospective cohort study. Br J Dermatol 2019;180:1176-82.  Back to cited text no. 9
    
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Choudhary S, Nouri K, Elsaie ML. Photodynamic therapy in dermatology: A review. Lasers Med Sci 2009;24:971-80.  Back to cited text no. 10
    
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Cazaña GT, Salazar N, Álvarez VJ, Aguilera J, Navarro LN, Ceballos HE, et al. Clinical, histological and immunohistochemical markers of resistance to methyl-M-aminolaevulinate photodynamic therapy in Bowen disease. Br J Dermatol 2018;178:138-40.  Back to cited text no. 11
    
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Hu A, Moore C, Yu E, Mount G, Jordan K, Vujovic O, et al. Evaluation of patient-perceived satisfaction with photodynamic therapy for Bowen disease. J Otolaryngol Head Neck Surg 2010;39:688-96.  Back to cited text no. 12
    
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Selvam NP, Sadaksharam J, Singaravelu G, Ramu R. Treatment of oral leukoplakia with photodynamic therapy: A pilot study. J Cancer Res Ther 2015;11:464-7.  Back to cited text no. 13
    
14.
Wong TH, Morton CA, Collier N, Haylett A, Ibbotson S, McKenna KE, et al. British association of dermatologists and British photodermatology group guidelines for topical photodynamic therapy 2018. Br J Dermatol 2019;180:730-9.  Back to cited text no. 14
    
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Marmur ES, Nolan KA, Henry M. Intraoperative photodynamic therapy: A description of a new adjuvant technique for patients with nonmelanoma skin cancer. Dermatol Surg 2012;38:1073-6.  Back to cited text no. 15
    
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Mahmoudi K, Garvey KL, Bouras A, Cramer G, Stepp H, Jesu Raj JG, et al. 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas. J Neurooncol 2019;141:595-607.  Back to cited text no. 16
    
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Yow CM, Wong CK, Huang Z, Ho RJ. Study of the efficacy and mechanism of ALA-mediated photodynamic therapy on human hepatocellular carcinoma cell. Liver Int 2007;27:201-8.  Back to cited text no. 17
    
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Drucker AM, Adam GP, Rofeberg V, Gazula A, Smith B, Moustafa F, et al. Treatments of primary basal cell carcinoma of the skin: A systematic review and network meta-analysis. Ann Intern Med 2018;169:456-66.  Back to cited text no. 19
    
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Lu YG, Wang YY, Yang YD, Zhang XC, Gao Y, Yang Y, et al. Efficacy of topical ALA-PDT combined with excision in the treatment of skin malignant tumor. Photodiagnosis Photodyn Ther 2014;11:122-6.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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