Extensive head and neck skin cancers: Carcinologic surgery as a cornerstone of treatment.

BACKGROUND AND OBJECTIVE: The prevalence of extensive skin cancers increases with the aging of the population. Surgical management is the gold standard of curative treatment while morbidity is not negligible. There are few data in the literature concerning extensive head and neck cutaneous cancers. The aim of this article is to report our experience of curative management of head and neck extensive skin cancers. METHOD: In this single-center retrospective observational study, we report a series of 17 patients with extensive skin facial cancers treated by surgery between 2013 and 2022 in the maxillofacial surgery department of the Pitié-Salpêtrière Hospital. We collected clinical, therapeutic, histological, and carcinologic data. RESULTS: The median age of the patients was 66 years [35-94]. There were 9 male and 8 women. Scalp (39 %) and cheek (22 %) locations were the most frequent ones. The most frequent histological types were squamous cell carcinoma (61 %) and basal cell carcinoma (17 %). Three patients received neoadjuvant treatment. The surgical treatment consisted mainly of carcinological resection followed by one-stage reconstruction by free flap for 5 (30 %) patients and without reconstruction for primary for 12 (70 %) patients, of whom 8 benefited from secondary reconstruction. Five patients received adjuvant radiotherapy or radio-chemotherapy. With a median follow-up of 40 months (2-72), the median overall survival was 40 months (12-72). CONCLUSION: We know that extensive skin cancers of the face have a good prognosis on condition that the carcinological and reconstructive requirements are respected. Surgery remains the cornerstone of treatment while the improvement of adjuvant therapies, in particular the rise of immunotherapies or other targeted therapies, may allow to limit recurrences.

Epidemiology of facial skin cancers managed in a French ambulatory surgical center.

INTRODUCTION: Approximately 80,000 cases of skin cancer are diagnosed annually in France. The management of these cancers can occur in both university hospital centers and ambulatory surgery centers. Limited data exist regarding the epidemiology of cutaneous cancers treated through ambulatory surgery centers. The objective of our study is to describe the epidemiological characteristics of cutaneous cancers managed in a tertiary ambulatory surgery center. METHODS: This is a retrospective, single-center observational study. The included patients were those who underwent surgical excision of one or more skin cancers within the maxillofacial department of a tertiary ambulatory surgery center. Clinical, therapeutic, histopathological, and follow-up data (additional surgery if margins were not clear, progression, recurrence, second cancer…) were collected. RESULTS: Among the n = 1931 patients operated for a head and neck skin tumor from September 2018 to July 2022, n = 426 (22 %) were diagnosed with cancer upon histological analysis. The median age was 76 years (31-100), with a male-to-female ratio of 1/1. The most frequent locations were the nose (23 %) and cheek (20 %). Ten percent of patients had dual-site skin cancer at initial diagnosis. The most common histological types were basal cell carcinoma (77 %) and squamous cell carcinoma (18 %). Surgical treatment primarily consisted of "excision-reconstruction with local flap" (51 %) or "excision-suture" (34 %). Resection margins were mostly clear (65 %), and only six patients (2 %) experienced local recurrence or progression during follow-up. CONCLUSIONS: Skin cancers are prevalent in ambulatory practice. Surgical treatment allows for effective control of the cancer. Photoprotection, particularly in immunocompromised patients, remains crucial for prevention.

Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1/PD-L1 inhibitors.

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.

Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.

INTRODUCTION: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. METHODS: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. RESULTS: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. CONCLUSION: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.

Management of odontogenic keratocysts of the jaws: a ten-year experience with 120 consecutive lesions.

BACKGROUND: The treatment of odontogenic keratocyst (OKC) of the jaws remains controversial. The aim of this study was to report the outcome of our conservative treatment protocol for OKC. METHODS: We collected data of all OKC patients treated in the Department of Maxillofacial Surgery, Pitié-Salpêtrière University Hospital from 1995 to 2004. Basal cell naevus syndrome (Gorlin's syndrome) patients were excluded. Recurrence data was analysed in relation to radiographic features, type of microscopic diagnosis, presence of cortical perforation, and site of involvement. RESULTS: One hundred and twenty cysts in 109 patients were examined. OKCs were more frequent in the third and the fourth decades of life (range: 11-79 years, mean: 40 years) and in men (n=71). Most of the lesions were unilocular radiolucencies in the tooth-bearing area and in the posterior part of the mandible. Histologically, 80 lesions showed parakeratosis. Most of the patients underwent uneventful enucleation. Postoperatively, infection occurred in 4 patients, and there was no jaw fracture. Recurrence was found in 28 cysts (26%), of which 7 cysts (6%) had multiple recurrences. There was no significant association between recurrences and radiographic features, histological type, cortical perforation, or site of involvement (P>0.05). Recurrences were common in the first 5 years after the operation. The average follow-up was 86 months since the last operation (range: 18-151 months). CONCLUSIONS: Despite the retrospective nature, no control group and a relatively high recurrence rate, our study suggests that enucleation with the aid of computed tomography and adequate postoperative surveillance is a conservative treatment which yields clinically acceptable results. However, the patients must strictly adhere to close follow-ups because recurrences may have serious consequences. Our algorithm for managing OKCs and cyst-like lesions of the jaws is also presented.

Head and neck lesions of Kimura's disease: exclusion of human herpesvirus-8 and Epstein-Barr virus by in situ hybridisation and polymerase chain reaction. An immunohistochemical study.

INTRODUCTION: Kimura's disease (KD) is a chronic inflammatory disorder, characterised by tumour-like lesions in the head and neck region, producing salivary gland nodules and lymph node enlargement. Many authors suggest that KD is a reactive immunological disorder; however, its aetiology remains unknown. AIMS: To study immunohistochemical characteristics of head and neck lesions of KD (H&N-KD) and to investigate the possible role of human herpesvirus-8 (HHV-8) and Epstein-Barr virus (EBV) in the development of H&N-KD. PATIENTS AND METHODS: This study enrolled five H&N-KD specimens from three patients treated between 1995 and 2005 at Pitié-Salpêtrière University Hospital, Paris, France. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue. HHV-8 DNA was determined by polymerase chain reaction (PCR) analysis, whilst EBV sequences were identified by PCR and in situ hybridisation. RESULTS: The immunohistochemical studies revealed CD20+ germinal centres with prominent staining of CD23+ dendritic reticular cells, surrounded by numerous interfollicular CD3+, and CD4+ or CD8+ T-cells. Factor VIII-related antigen, CD31 and CD34 occurred in the thin-walled blood vessels. The reactivity of CD1a, HHV-8 and EBV-associated latent membrane protein 1-EBV (LMP1-EBV) were negative, and in situ hybridisation confirmed the lack of EBV DNA. No patient recalled an external insult or chronic irritation. CONCLUSIONS: The results of this study indicate the reactive nature of H&N-KD (or a subset of H&N-KD), and it is unlikely that HHV-8 and EBV play a role in the pathogenesis of the lesion. However, the patients in this series did not have previous history of trauma or chronic irritation; thus, a neoplastic origin could not be excluded. Further multicentre studies based on more specimens are warranted.

Statins: a new pharmacological agent for free flap surgery?

Microvascular free tissue transfer has become the standard for reconstruction in head and neck oncological surgery. Several pharmacological agents have been used in order to increase the success rate of this surgery, but there is currently no consensus for an ideal drug. We review the literature concerning the complications encountered in free flap surgery related to the ischaemia-reperfusion injury and detail the effects of statins relevant to this endothelial dysfunction. Statins, because of their pleiotropic effects such as preservation of vascular tone, anticoagulation and anti-inflammatory properties, appear to be useful in free flap surgery. This study highlights the benefits of statins in order to increase the success rate and the quality of the free flap. They should be included in the perioperative strategy, especially in patients with cardiovascular risk factors. A protocol is presented.

Florid osseous dysplasia: report of a case presenting acute cellulitis.

In this review, we examined a 45-year-old Asian man who had been diagnosed with florid osseous dysplasia (FOD) of the mandible and acute perimandibular cellulitis. This presentation occurred after a history of off-and-on swellings of the jaw and multiple treatments received at another hospital. An aggressive resection of the jaw was planned; however, the patient denied the treatment and came to our clinic to seek a second opinion. The patient was successfully treated by conservative surgery and antibiotic treatment with preservation of the jaw integrity and the mandibular neurovascular canal. Intraoperatively, a piece of a calcified mass was removed and submitted for histopathological examination. The specimen showed woven bone and densely sclerotic mass of calcified materials exhibiting reversal lines and inflammatory cell infiltration of the connective tissue. The definitive diagnosis was FOD with a secondary infection. Treatments for FOD were discussed.

Extensive ameloblastic fibroma in an adolescent patient: a case report with a follow-up of 4 years.

Ameloblastic fibroma (AF) is a rare odontogenic tumour of the jaw which usually occurs in the first 2 decades of life. The common clinical manifestation is a slow-growing swelling. We report a case of a 16-year-old male patient presenting with extensive AF of the mandible. He underwent a conservative enucleation. The tumour recurred 2 years after the initial surgery, requiring the second enucleation. The patient has continued to be followed closely and has been disease-free for 4 years. Recent evidence suggests that the recurrent rate of AF is relatively high, and malignant transformation of AF may occur after recurrences or multiple surgeries. A conservative treatment approach with close surveillance is recommended. Anatomical limitations should be taken into account, especially when enucleation of AF in the posterior portion of the jaw is performed. Current surgical pathologic issues of the tumour are also discussed.

Florid osseous dysplasia: Report of a case presenting acute cellulitis

In this review, we examined a 45-year-old Asian man who had been diagnosed with florid osseous dysplasia (FOD) ofthe mandible and acute perimandibular cellulitis. This presentation occurred after a history of off-and-on swellingsof the jaw and multiple treatments received at another hospital. An aggressive resection of the jaw was planned;however, the patient denied the treatment and came to our clinic to seek a second opinion. The patient was successfullytreated by conservative surgery and antibiotic treatment with preservation of the jaw integrity and themandibular neurovascular canal. Intraoperatively, a piece of a calcified mass was removed and submitted for histopathologicalexamination. The specimen showed woven bone and densely sclerotic mass of calcified materialsexhibiting reversal lines and inflammatory cell infiltration of the connective tissue. The definitive diagnosis wasFOD with a secondary infection. Treatments for FOD were discussed (AU)

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Postoperative complications of fibular free flaps in mandibular reconstruction: an analysis of 25 consecutive cases.

OBJECTIVE: The objective of this study was to analyze complications following fibular free flap (FFF) transfer for mandibular reconstruction using our definition of postoperative complications. STUDY DESIGN: Retrospective observational study. PATIENTS AND METHODS: This retrospective study presents our 4-year experiences with FFF for mandibular reconstruction by a single microsurgical team. Data were collected through patient record review and clinical evaluation by 2 independent assessors. We defined complications as any unwanted postoperative outcomes that compromised patient care. Early complication occurred within the first 2 weeks postoperatively; late complications occurred afterward. RESULTS: Of 25 patients included, 13 patients (56%) experienced complications. Early and late complications occurred in 13 and 9 patients, respectively. These included flap loss, malunion, skin-paddle necrosis, orocutaneous fistula, wound dehiscence, hematoma, soft tissue contracture, intraoral hair growth, facial asymmetry, osteoradionecrosis, donor-site morbidity, and medical complications. Revision surgeries were performed in 10 patients, ranging from wound dressing to flap removal. All but 2 flaps survived, yielding an overall success rate of 92%. Most of the patients were alive without disease (92%) at the end of the study. Average follow-up was 47.2 months (range: 26-77). CONCLUSION: Despite the small number of patients, these preliminary data suggest a relatively high frequency of complications following the FFF reconstruction based on our definition. Minor complications are common and should not be neglected because they may lead to devastating consequences. This should also be a part of informed consent for patients. Complications after the FFF transfer await keen evaluation to establish guidelines to improve end results.

A treatment algorithm for adult ameloblastomas according to the Pitié-Salpêtrière Hospital experience.

During a 13-year period (from 1994 to 2007), in the Oral and Maxillofacial Surgery Department of the Pitié-Salpêtrière Hospital, 116 new cases of adult ameloblastomas, were analyzed for treatment composed against radiographic presentation, size, histological type. Follow-up and recurrence were also analyzed. Treatment was surgical consisting of enucleations (82%), segmental mandibulectomy (8.3%) resections (24.7%) 85% of them underwent reconstruction. The follow-up was documented for 97%. More than two recurrences occurred in 21% of the patients after the first enucleation: 66% with a "follicular" histological diagnosis. Lenthly, a therapeutic algorithm is suggested for adult ameloblastomas that underlines the importance of the conservative enucleation treatment as far as possible.

Ewing's sarcoma of jaw bones in adult patients: 10-year experiences in a Paris university hospital.

INTRODUCTION: Despite using aggressive treatment, patients with Ewing's sarcoma (ES) always show a high recurrence and a low survival rate. Ki-67 has been used widely in surgical oncology. PATIENTS AND METHODS: This case report identified the Ki-67 expression in jaw bone ES from 4 adult patients operated upon between 1996 and 2005 in Pitié-Salpêtrière University Hospital, Paris, France. The clinical data of each patient was also reviewed. RESULTS: Ki-67 reactivity was found in 3 cases. Two of 4 patients with 50% and 80% of Ki-67 positive tumour cells had local relapse at 5 years and 8 months after treatments, respectively. Furthermore, the patient with 80% Ki-67 expression exhibited resistance to chemotherapy and died a year after resection. The other 2 cases revealed no evidence of recurrence and metastasis to date. CONCLUSION: Ki-67 expression is likely to be associated with tumour recurrence and poor prognosis in jaw bone ES in adult patients. This marker probably helps surgeons to plan and employ appropriate treatment and/or surveillance for each patient; however, the number of cases in this series is very limited. A large-scale, prospective study is, therefore, required to confirm our suggestion.