Recurrent Basal Cell Carcinoma Research Articles

Recurrent basal cell carcinoma with maxillary bone invasion

Background: Basal cell carcinoma (BCC) is a malignant, slow growing, and locally invasive skin tumor. Advanced and neglected BCC may invade adjacent structures. The 5-year recurrence rates of facial BCCs are 4.1% after excision and 2.5% after Mohs Micrographic Surgery (MMS) . The number of BCC cases invading the bones of the head and neck region is limited. Case Illustration: A 75-year-old male complained of bleeding and ulcer enlargement on the right cheek expanding to the right nasal ala for 1 month. The patient had a history of an enlarged and painful lenticular nodule with a hyperpigmented spot that appeared 10 years ago on the right cheek and was diagnosed as BCC. The patient was treated with a wide excision having a negative pathological margin 3 years ago. He noticed that the similar lesion reappeared at the same location 2.5 years ago. Post-operative histopathological results showed nodular infiltrative BCC and maxillary bone invasion. Discussion: Based on history taking, physical examination, and diagnostic evaluation, the diagnosis of the patient was recurrent nodular infiltrative BCC. The final histopathology confirmed that tumor cells invaded the maxillary bone. After considering the treatment options, the patient opted to proceed with radiotherapy. Conclusion: Recurrent nodular BCC with invasion to the maxillary bone is a rare and interesting case. Among 140 BCC cases that we treated with MMS in our hospital from June 2014 to September 2019 , this case is the first recurrent BCC with maxillary bone invasion. Keywords: basal cell carcinoma, skin tumor, MMS, bone invasion

Attributes and risk factors of positive margins on 864 excisions of basal cell carcinomas: a single-center retrospective study

Background: Residual tumors increase the likelihood of recurrence of basal cell carcinoma (BCC).Objective: We determined the attributes and risk factors for positive surgical margins (+SM) of excised BCC in a university hospital.Methods: In this cross-sectional retrospective study, we reviewed the histologic reports of BCC removed via conventional surgical excision (CSE) by specialists from different fields.Results: Among excised BCCs (n = 864), there was a predominance of nodular BCC (82.64%) in the facial H-area (72.81%; average diameter = 9.12 mm), which had the highest + SM rate (20.17%). Most cephalic (ce-BCC; 69.01%) and non-cephalic (91.11%) BCCs were excised by dermatologists, with low rates of + SM (4.53%; 1.46%, respectively); the overall + SM rate was 12.73%. Men had larger (p < .001) and more ulcerated (p = .04) BCC. An aggressive histologic pattern (Ag-P) (p < .04) and ulceration (p < .001) were correlated with tumor size on multivariate analysis. The risk for + SM increased in ulcerated ce-BCC (p = .02), BCC with Ag-P (p = .02), and in the H-area (p < .001), nasal (p = .007), and labial (p = .05) regions. ce-BCC excised by head-neck surgeons had a high chance of ulceration (p < .001) and Ag-P (p = .002).Conclusions: Ag-P and H-zone remain critical risk factors for + SM. Accordingly appropriate treatment protocols should be used to ensure low + SM rates via CSE.

Efficacy of posaconazole for treatment of basal cell carcinoma

Background: Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer, with increasing incidence each year. Although the treatment of BCC is typically surgical, a non-surgical approach is highly desirable for patients with non-aggressive BCC recurrence, multiple tumors, poor general health, or with lesions in vulnerable areas. In the last few years, advanced cancer treatment options have targeted the Hedgehog pathway, known to regulate the proliferation of cancer stem cells and increase tumor invasiveness. Preliminary studies show that posaconazole may present a safer clinical alternative than current methods in the management of BCC. Therefore, this study aims to analyze the efficacy of posaconazole as a safe therapeutic option for nodular BCC lesions. Proven efficacy may have a significant impact on public health, as well as the substantially reduced medical and economic burden resulting from this disease prevalence. Methods: This study is designed as a single center, randomized, double-blinded, placebo controlled trial. Before undergoing surgical excision, 170 patients (1:1 allocation) will be randomized to receive 800 mg daily of posaconazole or placebo for four weeks. Discussion: The main strengths of this study are the potential to increase general understanding of the therapeutic and metabolic impact of posaconazole. The results from this trial may also provide valuable insights to guide a larger clinical trial of posaconazole for inoperable BCC. The main limitations of the study consist of the limited intervention time frame of 4 weeks and the sample representativeness since it is a single-center study of patients with nodular BCC.

Investigating basal cell carcinoma recurrence and outcomes following surgical excision at Broomfield hospital ophthalmology department, United Kingdom

AbstractPurposeOur current practice involves 2 years follow up after periocular BCC excision. This audit aims to investigate outcomes of: BCC recurrence rate while under follow up after histologically proven complete excision. Histological findings in cases of biopsy of suspected recurrent BCCMethodsRetrospective identification of samples sent to histopathology by a single Oculoplastic consultant with suspected or confirmed BCC between 01/01/16–30/04/19. Clinic letters identified the duration from surgical excision to latest follow up and any suspicion of recurrence. Where initial surgery was incomplete, or recurrence suspected clinically, secondary surgery results were checked to determine whether residual BCC was reported. Initial diagnostic incising biopsy results were excluded.ResultsOf 115 samples, 51 were excluded as per criteria. Of the remaining 64 patients, 56 patients were reviewed post‐operatively with no suspicion of recurrence in timeframe seen (1–&gt;24 months). Of 64 patients, 8 (12.5%) warranted secondary surgery within 2 years: 5 indicated by reported margin involvement (7.8%); 3 indicated by clinical suspicion (4.7%). This audit did not identify any cases of BCC recurrence. Residual BCC was identified on one deeper resection indicated by histopathology. Patients may continue to be risk assessed, and follow‐up preserved for: persistent marginal involvement; aggressive BCC sub‐type; pre‐disposition for BCC; immunosuppression; higher risk initial BCC site (e.g. medial canthus or orbital invasion).ConclusionsNo cases of BCC recurrence were identified within this cohort. Re‐excision of involved margin tends not to a show positive result. Minimal residual BCC may have been destroyed during the initial surgical cauterisation or by the immune system. We propose to discharge patients following complete excision of low risk BCCs from the periocular area with advice to seek referral with any new lesions following self‐examination.

Facial nerve reconstruction with great auricular nerve graft following resection of recurrent basal cell carcinoma in parotidomasseteric region

Facial nerve reconstruction with great auricular nerve graft following resection of recurrent basal cell carcinoma in parotidomasseteric region

Risk factors for local recurrence of basal cell carcinoma and cutaneous squamous cell carcinoma of the middle third of the face: a 15-year retrospective analysis based on a single centre.

Non-melanoma skin cancer (NMSC) is the commonest malignancy worldwide (>80% located in the head and neck area). The aim of this study was to assess risk factors predisposing to local recurrence of NMSC of the middle third of the face (MTF). This was a single-centre retrospective analysis of patients with NMSC of the MTF treated during 1995-2010. Data on epidemiological and tumour characteristics were collected. Survival analysis was performed and log-rank tests were used to compare differences in survival for each variable. A total of 531 patients with basal cell carcinoma (BCC) of the MTF were identified. Most tumours were nodular type (28.4%), located on the nose (34.3%), and confined to the dermis (75.5%). Negative margins were achieved in 91% of cases. Median follow-up time was 35 months and 15.2% of patients developed local recurrence. Incomplete excision was the only variable predisposing to local recurrence. The cohort also included 114 patients with squamous cell carcinoma (SCC). Most tumours were well differentiated (43.9%), located at the zygomatic area (49.1%), excised with negative margins (93%), and confined to the dermis (67.8%). At a median follow-up time of 42 months, local recurrence occurred in 15.7% of patients. Tumour size, depth of invasion, and prior history of head and neck SCC were risk factors for local recurrence. The variables predictive of recurrence of BCC were incomplete excision and for SCC tumour size, depth of invasion, and a prior history of head and neck SCC.

Long-Term Efficacy of Vismodegib After its Withdrawal and Patients' Health-Related Quality of Life Using the Dermatology Life Quality Index (DLQI).

IntroductionAlthough non-melanoma skin cancers (NMSCs) are associated with a very low mortality risk, they have been reported to have a major impact on patients’ health-related quality of life (HRQoL). Vismodegib is a therapy for patients who are affected by locally advanced basal cell carcinoma (BCC) or metastatic BCC who are ineligible for surgery and/or radiotherapy. The aim of the present clinical study was to assess the long-term efficacy of vismodegib after its withdrawal by evaluating the recurrence rate of advanced BCC, assessing also patients’ HRQoL after 3 and 6 months from drug withdrawal.MethodsA retrospective study was performed to analyze patients with advanced and/or multiple BCCs that had been treated with vismodegib (150 mg daily) at the Non-Melanoma Skin Cancer Unit of the University of Naples Federico II (Italy) and had obtained a complete regression in 6 months. At the end of the 6-month treatment cycle, patients that reported total remission of the skin tumor were visited monthly in order to assess their therapeutic response. Moreover, to assess the specific impact of vismodegib on HRQoL, DLQI was administered before vismodegib treatment (baseline), at the end of the therapy cycle (6 months), as well as after 3 and 6 months from vismodegib discontinuation.ResultsThirty-five patients (27 male, 8 female), with a complete regression of their advanced BCC after vismodegib treatment, were included in the study. The duration of treatment for all patients was 6 months as set by study inclusion criteria. A BCC recurrence rate of 31% (11/35) was reported after a 6-month follow-up. The average reported Dermatology Life Quality Index (DLQI) score increased from a value of 0 at the end of the 6-month vismodegib treatment to a mean value of 2.4 after 3 months from drug withdrawal and 3.6 after 6 months from treatment discontinuation.ConclusionThe results of this exploratory analysis of vismodegib withdrawal are consistent with a substantial link between treatment response and patients’ HRQoL. Furthermore, 11 out of 35 (31%) patients that reported a complete remission of the disease after 6 months of vismodegib treatment reported BCC recurrence. These data highlight the importance of continuous follow-up and perhaps different regimens of treatment, such as an alternate dose regimen to maintain disease control and reduce the adverse events as previously described in the literature.

Needle tract seeding following endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer: a report of two cases

BackgroundEndoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful tool in pancreatic cancer diagnosis. However, the procedure itself may cause peritoneal dissemination and needle tract seeding at the puncture site. We herein report two cases of gastric wall metastasis due to needle tract seeding after EUS-FNA.Case presentationCase 1: A 68-year-old woman was admitted to our hospital for persistent cough. Computed tomography (CT) scan revealed inflammatory changes in the left lung field, and incidentally, a 15-mm hypovascular mass was detected in the pancreatic body. She underwent EUS-FNA and was diagnosed as pancreatic adenocarcinoma. She underwent distal pancreatectomy with splenectomy; however, a small hard mass was observed in the posterior gastric wall during surgery. We performed partial gastrectomy, and the resected specimen was diagnosed as a needle tract seeding following EUS-FNA. She then underwent adjuvant chemotherapy with TS-1, but the pancreatic cancer showed recurrence 6 months after surgery. She died due to peritoneal dissemination 18 months after surgery.Case 2: A 70-year-old man was incidentally detected with a pancreatic body mass on a CT scan as part of his follow-up for recurrence of basal cell carcinoma. He underwent EUS-FNA and was diagnosed as pancreatic adenocarcinoma. He had nodules in both lungs, and it was difficult to differentiate them from lung metastasis of pancreatic cancer. Therefore, he underwent neoadjuvant chemoradiotherapy, and thereafter, the lung nodules showed no changes; hence, he underwent distal pancreatectomy with splenectomy. During surgery, we observed a hard mass in the posterior gastric wall. We performed partial gastrectomy, and the resected specimen was diagnosed as needle tract seeding due to EUS-FNA. He underwent chemotherapy with TS-1, and he is still alive 18 months after surgery at the time of writing.ConclusionFor resectable pancreatic body or tail tumors, EUS-FNA should be carefully performed to prevent needle tract seeding and intraoperative as well as postoperative assessment for gastric wall metastasis is mandatory.

Diagnosis and treatment of basal cell carcinoma: European consensus–based interdisciplinary guidelines

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer collaborated to develop recommendations on diagnosis and treatment of BCC. A new classification into ‘easy-to-treat (common) BCC and ‘difficult-to-treat’ BCC is proposed. Diagnosis is based on clinicodermatoscopic features for ‘easy-to-treat’ BCCs. Histopathological confirmation is mandatory in ambiguous lesions and in BCCs located in high-risk areas. The first-line treatment of ‘easy-to-treat’ BCC is complete surgery. Microscopically controlled surgery shall be offered for high-risk BCC, recurrent BCC and BCC in critical anatomical sites. Topical therapies (5% imiquimod, 5% fluorouracil) and destructive approaches (curettage, electrocautery, cryotherapy, laser ablation) should be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial BCC and thin nodular BCC. The therapy for a ‘difficult-to-treat’ BCC should preferentially be discussed by a multidisciplinary tumour board. Hedgehog inhibitors, vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCCs. Immunotherapy with anti–programmed cell death 1 (PD-1) antibodies is a promising therapeutic option, currently being investigated in clinical trials. Radiotherapy represents a valid alternative to surgery for BCC on the face, especially in elderly patients. In patients with naevoid basal cell carcinoma syndrome (NBCCS), close surveillance and regular skin examinations are required to diagnose and treat BCCs at early stage. Long-term follow-up is recommended in patients with high-risk BCC subtypes, high-risk sites, multiple BCCs and NBCCS.

The Efficacy of HDR Brachytherapy for Patients with Recurrent or Margin-Positive Post-Operative Basal Cell Carcinoma

The Efficacy of HDR Brachytherapy for Patients with Recurrent or Margin-Positive Post-Operative Basal Cell Carcinoma

Modern methods of treatment of locally-advanced and recurrent basal cell carcinoma of the head and neck with using signal pathway inhibitor Hedgehog: сlinical cases

The study objective is to analyze the efficacy of a hedgehog signaling pathway inhibitor in locally advanced and recurrent basal-cell carcinoma (BCC) of the head and neck. Materials and methods . We compared the information from international clinical guidelines and two clinical trials (ERIVANCE and STEVIE). We also provide two case reports of a hedgehog signaling pathway inhibitor (vismodegib) use. Results . In the ERIVANCE trial, the objective response rate was 48.5 % in patients with metastatic BCC and 60.3 % in patients with locally advanced BCC. The median progression-free survival was 9.3 and 12.9 months in participants with metastatic and locally advanced BCC respectively. The overall survival reached 33.4 months in patients with metastatic BCC and was not reached in patients with inoperable BCC. According to the results of the STEVIE trial, vismodegib ensured disease control in 93 % of patients with locally advanced BCC and 72 % of patients with metastatic BCC. The median progression-free survival was 24.5 and 13.1 months in participants with locally advanced and metastatic BCC respectively. The majority of vismodegib-realted adverse events in both ERIVANCE BCC and STEVIE trials were grade I/II adverse events. In the two clinical trials, vismodegib at a dose of 150 mg per day during 3 months caused visual reduction of the bone destruction focus, which was confirmed by computed tomography. Patients were recommended to continue therapy with vismodegib. Conclusion . Until recently, there were no treatment standards for late-stage BCC. Currently, hedgehog signaling pathway inhibitors, such as vismodegib, can be considered as a method of choice for patients with inoperable and metastatic BCC, since this therapy demonstrated high efficacy.

Electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinomas

There is increasing evidence about the effectiveness of electrochemotherapy (ECT) in the treatment of basal cell carcinomas in the head and neck region, although its role in the management of eyelid-periocular skin tumors has to be clarified. The aim of the present study is to evaluate the results of ECT in the treatment of locally advanced primary and recurrent eyelid-periocular skin basal cell carcinomas. Twelve patients with basal cell carcinoma involving the eyelid-periocular skin region were treated with ECT. Three patients had locally advanced primary tumors, while 9 patients had recurrent tumors. All treatments were performed according to the ESOPE guidelines, using Cliniporator TM device. All patients received bleomycin based ECT. The route of administration was intratumoral in 3 patients and intravenous in 9 patients. Tumor response was evaluated using the RECIST 1.1. criteria. ECT resulted in complete response of the periocular skin tumors in all patients. Lower eyelid ectropion was developed in 3 patients which had to be corrected surgically. ECT can be used effectively in the treatment of locally advanced or recurrent basal cell carcinomas in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with short interval follow-up.

Long-term recurrence rates of whole specimen intraoperative frozen section analysis in basal cell carcinomas of the face with WIFSA.

Recent studies show that whole specimen intraoperative frozen section analysis (WIFSA) is a reliable method for margin analysis in basal cell carcinoma (BCC) and has low recurrence rates after five-years follow-up. There are no studies with longer follow-up. Our aim is to present long-term recurrence rates after WIFSA. All patients with a facial BCC receiving excision with WIFSA between 1992 and 2007 were evaluated. Recurrence rates were examined for primary BCC (pBCC), recurrent BCCs (rBCC), and the different histological subtypes. The accuracy of WIFSA was assessed by comparing with formalin-fixed paraffin-embedded section analysis. A total of 1140 patients with 1265 BCCs underwent excision with WIFSA, with a median and maximum follow-up of 10 and 25.3 years, respectively. Of all tumors, 90.0% were primary. Excisions were radical after an average of 1.4 excision rounds;5, 10, and 15-year recurrence rates for pBCCs are 3.3%, 5.1%, and 7.3%, respectively. An aggressive growth pattern and rBCCs are associated with more recurrences. The accuracy of WIFSA is 98.4%. WIFSA provides a highly accurate analysis and has a low recurrence rate for primary BCCs. The increasing recurrence rates over time imply 5 years of follow-up may be insufficient.

Patient indications for Mohs micrographic surgery: a clinical practice guideline.

The purpose of the present work was to develop evidence-based indications for Mohs micrographic surgery in patients with a diagnosis of skin cancer. The guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care, together with the Melanoma Disease Site Group and the Surgical Oncology Program, through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Given a lack of high-quality, comparative evidence, surgery (with postoperative or intraoperative margin assessment) or radiation (for those who are ineligible for surgery) should remain the standard of care for patients with skin cancer. Mohs micrographic surgery is recommended for patients with histologically confirmed recurrent basal cell carcinoma of the face and is appropriate for primary basal cell carcinomas of the face that are larger than 1 cm, have aggressive histology, or are located on the H zone of the face. Mohs micrographic surgery should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in Mohs micrographic surgery.

Recurrence rate of basal cell carcinoma in patients submitted to skin flaps or grafts

BackgroundBasal cell carcinoma is the most common type of skin cancer. Although the literature provides a great deal of information on the recurrences of basal cell carcinoma, studies about these indices addressing only the cases in which flaps and/or grafts have been performed for surgical reconstruction of the excision of this tumor are still lacking. ObjectivesTo evaluate rates of recurrence of basal cell carcinoma submitted to conventional surgery with pre-established margins and reconstruction by flaps or grafts. MethodsA retrospective and observational study was performed through the analysis of 109 patients, who met inclusion criteria with 116 basal cell carcinomas submitted to conventional surgery and pre-established safety margins, requiring reconstruction through a graft or cutaneous flap. This work was performed the small surgeries sector of Dermatology of the Specialty Outpatient Clinic of the University Hospital of the State University of Londrina, between January 1, 2011 and December 31, 2015. The following data were collected and inserted in an Excel worksheet: name, registration number of the hospital patient, sex, age, tumor location, histopathological type of BCC, procedure performed (type of flap and/or graft), follow-up time, recurrence. ResultsOf the 116 procedures, there were recurrences in 3 cases (2.6%) that were located in the nasal region and related to sclerodermiform or micronodular histological types. Study limitationsRetrospective nature of the study. ConclusionThe present study of the dermatology department of this university hospital showed a low rate of recurrence of basal cell carcinoma in cases where flaps and/or grafts were used in the surgical reconstruction.

Reconstruction of Basal Cell Carcinoma over Face by Facial Flaps –Study of 30 Cases

Background: Basal cell carcinoma (BCC) is the most common skin cancer.85% of BCC are located in the head and neck area, of which 30% on the nose. After excision of BCC on the face, the options of treatment for a skin defect are variable. Many surgeons prefer to use a local flap rather than skin graft or free flap for small or moderately sized circular defects after excision of BCC on the face.Methods: All of the patients were histopathologically diagnosed as Basal cell carcinoma, thirty patients underwent various flaps like V-Y advancement flap, bilobed flap, forehead flap, nasolabial flap, glabellar flap repair over 3 years, between January 2014 to December 2016. We observed post-operative complications as flap loss either partial or complete, wound dehiscence, hematoma and wound infection and recurrence of carcinoma. The cosmetic outcome of the face also evaluated.Results: There were 19 men and 11 women. The age ranged from 48 to 73 years with a mean age of 62 years. The causes were BCC in all cases. The tumour locations were the face in all patients. All of the flaps survived, but in one case recurrence of BCC occur, which was managed surgically. Post-operative recovery was very nice.Conclusions: Our study shows facial flaps give nice result and first choice for facial reconstruction in BCC of face. Most defects can best closed by various facial flaps and outstanding functional and cosmetic results can be achieved.TAJ 2017; 30(2): 20-25

Cells to Surgery Quiz: December 2018

Cells to Surgery Quiz: December 2018

The role of EGFR overexpression on the recurrence of basal cell carcinomas with positive surgical margins

BackgroundEpidermal growth factor receptor (EGFR) expression may have role on recurrence of basal cell carcinoma (BCC) with positive surgical margin(s). ObjectiveThe aim was to investigate the role of genetic expression changes of EGFR on recurrence rates in patients in follow up with surgically excised BCC with positive surgical margin(s). MethodsThirty-four surgical margin–positive BCC lesions that were closely followed up without an immediate reoperation were included in this study. Real-time polymerase chain reaction (PCR) was performed from the both healthy and tumoral tissue samples. ResultsEGFR was expressed at a significantly higher rate in tumoral tissues compared to healthy tissues (p < 0,05). In patients with recurrence lesions, EGFR expression was 6,66 times higher compared to patients with non-recurrent. Also, there was statistically significant difference EGFR expression for infiltrative subtypes (p < 0,05). ConclusionOur study focuses on the role of EGFR overexpression specifically and outcomes for recurrent and infiltrative subtyped lesions are significant for both clinic and pathogenesis of BCC. Similar studies have to be performed with high numbered patient groups.

Staged excision of primary periocular basal cell carcinoma: absence of residual tumour in re-excised specimens: a 10-year series

AimsThe aim is to study staged periocular basal cell carcinoma (BCC) excision in a tertiary oculoplastic referral centre in Sheffield, UK. In particular, we examined patients with close or positive...

Patient Indications for Mohs Micrographic Surgery: A Systematic Review.

The purpose of the present review was to describe evidence-based indications for Mohs micrographic surgery (MMS) in patients with a diagnosis of skin cancer. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 1970 to 2017. Randomized controlled trials (RCTs), prospective and retrospective comparative studies with greater than 30 patients, and single-arm retrospective studies with multivariate analyses were included. A total of 2 RCTs, 3 prospective studies, and 16 retrospective studies (14 comparative and 2 single-arm) were included. Data on recurrence rate, cure rate, complications, cosmesis, and quality of life were extracted. Surgery (with postoperative or intraoperative marginal assessment) or radiation for those who are ineligible for surgery should remain the standard of care for patients with skin cancer given the lack of high-quality, comparative evidence. MMS is recommended for those with histologically confirmed recurrent basal cell carcinoma (BCC) of the face and is appropriate for primary BCCs of the face that are >1 cm, have aggressive histology, or are located on the H zone of the face. The available evidence is difficult to generalize to all patients with skin cancer because the evidence did not adequately cover non-BCC skin cancers; however, those skin cancers can be considered on a case-by-case basis for MMS. MMS should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in MMS.