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Author Contributions
Marilla Dickfos: Writing-original draft. Hajir Nabi: Writing-
review and editing.
References
1. Perne A. Meckel diverticulum. N. Engl. J. Med. 1959; 260: 690–6.
2. McKenzie S, Evers B. Small intestine. In: Townsend C, Beauchamp RD,
Evers BM, Mattox K (ed.). Textbook of Surgery: The Biological Bases of
Modern Surgical Practice. Philadelphia, PA: Elsevier, 2012; 1227–78.
3. Dumper J, Mackenzie S, Mithcell P, Sutherland F, Quan M, Mew D.
Complications of Meckel’s diverticula in adults. Can. J. Surg. 2006;
49: 353–7.
4. Aar T, Berger D. Adult intussusceptions. Ann. Surg. 1997; 266: 134–8.
5. Barry W, Rosenberg D, Warren M, Kim E. Small bowel intussusception
secondary to inverted Meckel’s diverticulum. J. Pediatr. Surg. Case Rep.
2017; 25: 49–51.
About face: can Vismodegib change the treatment paradigm of locally
advanced basal cell carcinoma?
A 44-year-old Caucasian male was referred to Peter MacCallum
Cancer Centre for management of numerous non-melanoma skin
carcinomas (NMSCs), but predominantly large cutaneous basal cell
carcinomas (BCCs) of his head and neck region, with rapid lesion
growth over a 6-month period. His risk factors for skin cancer
included a background of childhood sun exposure, and past history
of multiple squamous cell carcinomas (SCCs) and BCCs, and one
melanoma, from the age of 20. He had no established genetic pre-
dispositions or immunodeficiency on history or investigations. On
examination, the patient was found to have greater than 50 NMSCs,
with widespread locally eruptive exophytic head and neck nodules.
Initial biopsy demonstrated multiple synchronous BCCs and a right
forehead Merkel cell carcinoma with overlying BCC. Investigation
with computed tomography–positron emission tomography scan
demonstrated only localized disease. The right forehead Merkel cell
carcinoma was treated with intensity-modulated radiation therapy
of 30 Gy in five fractions xx. Given the extent of the BCCs, and
functionally as well as aesthetically sensitive areas of involvement,
he was discussed in our multidisciplinary meeting. Concerns relat-
ing to the morbidity associated with extensive surgical resection led
to the commencement of Vismodegib 150 mg daily.
Vismodegib produced a significant clinical response for many of
the facial tumours with marked reduction in tumour size over
3 months and the drug was well tolerated. The exception to this
was a right malar lesion, which was originally biopsied as BCC but
this continued to progress rapidly. This tumour was resected after
5 months of Vismodegib and histology showed concurrent SCC
and BCC with prominent squamous differentiation. Three months
later, he developed recurrence of this SCC over his right tragus,
which was surgically treated with right partial pinnectomy, lateral
temporal bone resection parotidectomy and temporalis flap
Images for surgeons
6. Ito T, Sato K, Maekawa H et al. Adult intussusception caused by
inverted Meckel diverticulum. Case Rep. Gastroenterol. 2011;
5: 320–4.
7. Pantongrag-Brown L, Levine M, Elsayed A, Buetow P, Agrons GA,
Buck JL. Inverted Meckel diverticulum: clinical, radiologic, and patho-
logic findings. Radiology 1996; 199: 693–6.
8. Choi S, Han J, Kim S et al. Intussusception in adults: from stomach to
rectum. AJR Am. J. Roentgenol. 2004; 183: 691–8.
Marilla Dickfos,*† MBBS
Hajir Nabi,* MBBS, FRACS
*Department of General Surgery, Logan Hospital, Logan City,
Queensland, Australia and †School of Medicine, The University of
Queensland, Brisbane, Queensland, Australia
doi: 10.1111/ans.16400
reconstruction, followed by adjuvant post-operative radiotherapy.
Vismodegib therapy has maintained ongoing significant but incom-
plete clinical response in his other BCCs (Figs 1–3).
BCC is the most common carcinoma that afflicts the Caucasian
population, with the highest global incidence in Australia, increas-
ing by 2% per year.1 Low-risk lesions are amenable to topical ther-
apies and ablative procedures, whilst surgery remains the mainstay
of treatment for large disfiguring lesions. This incurs significant
morbidity.2,3 The recent clinical introduction of sonic-hedgehog
pathway inhibitors (Vismodegib and Sonidegib) offers an alternate
treatment option.2 This case demonstrates a remarkable down-
grading of widespread locally advanced facial BCCs due to treat-
ment with Vismodegib. Vismodegib acts through selective
inhibition of smoothened signalling in the hedgehog pathway, sub-
sequently inhibiting transcription of PTCH1 genes involved in
BCC differentiation and disease progression.2,3 Vismodegib has
been found to produce an objective response of 48% to locally
advanced BCC, but less in metastatic disease, at 21-month follow-
up.4 Notably, a partial response is more common.3
Although Vismodegib is an effective treatment for BCC, it is
poorly tolerated by the majority of patients due to its common and
expected side-effect profile of muscle spasms, dysgeusia, fatigue,
weight loss, diarrhoea as well as alopecia with prolonged use.2,3,5
BCC of the head and neck region often causes disfiguring skin
changes that adversely impact on patients’ body image and health-
related quality of life outcomes.6 Accordingly, use of Vismodegib
has been found to improve health-related quality of life 6 months
after commencing treatment with the greatest improvement in
patients with face and neck BCC despite the adverse effects.5
It remains to be seen whether sonic-hedgehog pathway inhibitors
are useful in neoadjuvant settings to downgrade large locally
© 2020 Royal Australasian College of Surgeons

Images for surgeons
Fig 1. Initial presentation.
Fig 2. Five months post commencement of Vismodegib. N.B. Unresponsive lesion over the right malar prominence.
advanced BCCs and reduce surgical morbidity. Small series suggest
some feasibility, although questions about variable response rates
and poor tolerance of the drug remain.7 Whether existing well-
tolerated immunotherapies have a similar role to play is a current
area of interest.
Although NMSC is common, it is rare for BCC, SCC and Mer-
kel cell carcinoma to arise synchronously with only two similar
cases found on searching the PubMed database.8,9 These case
reports identify significant ultraviolet exposure as the common
risk factor for synchronous carcinoma development and highlight
difficulties in multiple skin carcinoma identification and treatment,
© 2020 Royal Australasian College of Surgeons
14452197, 2021, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ans.16399 by Readcube (Labtiva Inc.), Wiley Online Library on [14/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1305
and the importance of accurate tissue diagnosis. 8,9 In this case, the
patient’s aggressive and recurrent SCC was clinically thought to
be a Vismodegib-resistant BCC. Therefore, tumours not respon-
sive to hedgehog inhibitors should be treated with high clinical
suspicion for an alternative histological diagnosis or dual diagno-
sis (as shown in this case, who had combined SCC/BCC as well
as Merkel/BCC tumours). This case also highlights that there is
concern about the development of SCC in patients on Vis-
modegib, although a recent retrospective cohort study of 556 Vis-
modegib patients and 1119 controls did not find an increased risk
association.10

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Fig 3. Twelve months post commencement of Vismodegib.
Acknowledgement
We acknowledge our patient who kindly agreed to publication of
this study.
Author Contributions
Kristy Mansour: Writing-original draft; writing-review and
editing. Fergal O’Duffy: Writing-review and editing. Angela
Webb: Writing-review and editing. Michelle Goh: Writing-review
and editing. Edwin Morrison: Supervision; writing-review and
editing.
References
1. Dessinioti C, Antoniou C, Katsambas A, Stratigos AJ. Basal cell carci-
noma: what’s new under the sun. Photochem. Photobiol. 2010; 86:
481–91.
2. Kim D, Kus K, Ruiz E. Basal cell carcinoma review. Hematol. Oncol.
Clin. N. Am. 2019; 33: 13–24.
3. Therapeutic Goods Administration. Australian public assessment report
for vismodegib. Report no.: 1. 2013; 78 p.
4. Sekulic A, Migden M, Lewis K et al. Pivotal ERIVANCE basal cell
carcinoma (BCC) study: 12-month update of efficacy and safety of
vismodegib in advanced BCC. J. Am. Acad. Dermatol. 2015; 72:
1021–6.
5. Villani A, Fabbrocini G, Cappello M, Costa C, Scalvenzi M. Real-life
effectiveness of Vismodegib in patients with metastatic and advanced
BC: characterisation of adverse events and assessment of health-related
14452197, 2021, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ans.16399 by Readcube (Labtiva Inc.), Wiley Online Library on [14/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Images for surgeons
quality of life using the dermatology quality index (DLQI) test.
Dermatol. Ther. 2019; 9: 505–10.
6. Mathews B, Rhee J, Neuburg M, Burzinski M, Nattinger A. Develop-
ment of facial skin care index: a health-related outcomes index for skin
cancer patients. Dermatol. Surg. 2006; 32: 924–34.
7. Mortier L, Bertrand N, Basset-Seguin N et al. Vismodegib in neo-
adjuvant treatment of locally advanced basal cell carcinoma: first results
of a multicentre, open-label, phase 2 trial (VISMONEO study). J. Clin.
Oncol. 2018; 36: 9509.
8. Whipple K, Lombard P, Rog Oh S, Korn B, Kikkawa D. Three carcino-
mas in one eyelid. Ophthalmic Plast. Reconstr. Surg. 2011; 27: 55–5.
9. Aydin A, Kocer E, Bekerecioglu M, Sari I. Cutaneous undifferentiated
small (Merkel) cell carcinoma that developed synchronously with multi-
ple actinic keratosis, squamous cell carcinomas and basal cell carcino-
mas. J. Dermatol. 2003; 30: 241–4.
10. Bhutani T, Abrouk M, Sima C et al. Risk of cutaneous squamous cell
carcinoma after treatment of basal cell carcinoma with Vismodegib.
J. Am. Acad. Dermatol. 2017; 77: 713–8.
Kristy P. Mansour, MD
Fergal O’Duffy, FRCSI
Angela Webb, MBBS, FRACS
Michelle Goh, MBBS, FACD
Edwin Morrison, MBBS, FRACS
Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne,
Victoria, Australia
doi: 10.1111/ans.16399
© 2020 Royal Australasian College of Surgeons