End of inclusion period

Radical endoscopic transnasal surgery associated with medical treatment with liposomal amphotericine B may increase the local control of Rhino-Sinusal Mucormycosis and the survival rate. The objective of this study is to evaluate the local control rate and survival rate at 3 months after radical endoscopic transnasal surgery extended towards the skull base in association with antifungal therapy and early surgical reevaluation of the extent of the disease.

Introduction : Treatment of Rhino-Sinusal Mucormycosis remains a challenge because of the severity of the disease with high mortality rates. Mainly involving diabetic and immunodeficient patients, first clinical presentation is a common infection of the sinuses which can extend towards deep spaces of the face, orbits, the skull base and the brain. The mortality rates range from 20 to 50%, up to 80% in case of cerebral extension. through Transnasal Endoscopic Surgery extended to the Skull Base.

Hypothesis : We hypothesize that infected tissues are devascularized and because of that antifungal therapies can hardly reach areas of infected tissues. Radical endoscopic transnasal surgery associated with medical treatment with liposomal amphotericine B may increase the local control of the disease and the survival rate. Clinical evaluation of the extent of the disease within the first 7 days following initial surgery may represent a prognosis factor.

Methods :

First national mutlicentric and multidisciplinary cohort on Rhino-Sinusal Mucormycosis Radiological staging for evaluation of the extent of the disease using CT scan, MRI and PET Scan at initial stage before surgery Radical surgery and/or endoscopic transnasal surgery extended towards the skull base associated with liposomal amphotericine B medical treatment.

At day 7 new radiological evaluation and second surgical look to adapt surgical resection of infected tissues, perform biopsies to search for mycormycosis, biofilms and dosage of the concentration of liposomal amphotericin B inside tissues. New radiological and surgical looks in case of absence of local control obtained on the second look and further.

Study of the response rate by an endoscopic & scan follow-up (with biopsies for anatomopathological et mycological studies) at 1 month, 3 months, 6 months & one year. PET scan initially & at 3 months.

Number of subjects included : Phase II type trial (exclusion of a zero hypothesis of survival rate <50% ), N= 23 patients

Total length of the study 4 years Inclusion period time : 3 years Time of participation per patient : 1 year Number of center and/or participating departments: 24 Mean number of patients included per year and per center : 0 to 3 patients

Inclusion Criteria:

• Man or woman, over 18 years old, presenting a mucormycosis on a sinus biopsy showing large filaments with non or little septae compatible with a mucoral or with a positive culture for a mucoral on a sinus sample associated to clinical head & neack anomalies (endoscopic) & scans compatible with a mucormycosis previous to the inclusion and this whatever the patient incumbent pathology.

• Patient treated by liposomal amphotericin B or just before being treated

• Signature of informed consent :

  • by the patient if he is able to express their will
  • by the family or close, if the patient is unable to consent

• Inclusion in emergency clause is possible ( CPP agreement ) if the patient is incapacitated , no close is present and that the surgery is urgent

• Person affiliated to a Health Security System (beneficiary)

Exclusion Criteria:

• Pregnancy, breastfeeding
• Disseminated Mucormycosis (involvment of one site distant from the head and neck)
• Known hypersensitivity to a polyene
• Absence of documentation of mucormycosis (histological, mycological)
• Contraindication to the completion of the surgery as provided in this protocol
• Patient is the subject of a guardianship or tutelage measure