Temozolomide non-responsiveness in aggressive prolactinomas and carcinomas: management and outcomes

Purpose Temozolomide is endorsed as the treatment of choice in aggressive or malignant pituitary adenomas. Herein we describe a case of an aggressive prolactinoma which was resistant to temozolomide and performed a literature review of similar non-responsive aggressive prolactinomas. Methods A 40-year-old female presented with a giant prolactinoma which required cabergoline, transsphenoidal surgery and radiotherapy to achieve near-normal prolactin and apparently no residual tumour. A year later, she presented with multiple cranial nerve involvement due to recurrent tumour extending to the infratemporal fossa. She underwent transfrontal surgery, second radiotherapy and was started on temozolomide. Despite 8 cycles of temozolomide (200mg/m 2, 5/28 day cycle), she had progressive disease and ultimately succumbed to the disease. Pubmed/MEDLINE, Google scholar and prior review articles were searched for manuscripts with aggressive prolactinomas who had been treated with temozolomide. Data on demography, duration of therapy and management outcomes were analysed in those with progressive disease. Literature review We identified 94 cases of aggressive/malignant prolactinomas in the literature who had received temozolomide. Progressive disease despite temozolomide was present in 36 cases (38%). There was a male preponderance (65%) and 40% had aggressive prolactinomas while the rest had carcinomas. Patients received a median of 8 cycles (IQR 3.5-11.5) of temozolomide. MGMT immunostaining was negative in 35%. Overall mortality at the time of publication was 40%, at a duration varying from 2 to 20 years from diagnosis. Conclusion Temozolomide resistance in aggressive/malignant prolactinomas is challenging. Progressive disease on optimal temozolomide treatment entails the use of newer agents.

Emergence of Invasive Fungal Rhinosinusitis in Recently Recovered COVID-19 Patients

Objective: The risk of invasive fungal rhinosinusitis is increased in Coronavirus disease 2019 (COVID-19) because of its direct impact in altering innate immunity and is further exacerbated by widespread use of steroids/antibiotics/monoclonal antibodies. The study aims to describe this recently increased clinical entity in association with COVID-19. Method: A prospective, longitudinal study including patients diagnosed with acute invasive fungal rhinosinusitis (AIFRS) who recently recovered from COVID-19 infection or after an asymptomatic carrier state. A single-center, descriptive study investigating demographic details, clinical presentation, radio-pathological aspects, and advocated management. Result: A total of 21 patients were included with a mean age of 49.62 years (SD: 14.24). Diabetes mellitus (DM) was the most common underlying disorder (90.48%), and 63.16% of all patients with DM had a recent onset DM, either diagnosed during or after COVID-19 infection. Nineteen patients (90.48%) had recently recovered from active COVID-19 infection, and all had a history of prior steroid treatment (oral/parenteral). Remaining 2 patients were asymptomatic COVID-19 carriers. Surprisingly, 2 patients had no underlying disorder, and 5 (23.81%) recently received the Covishield vaccine. Fungal analysis exhibited Mucor (95.24%) and Aspergillus species (14.29%). Most common sign/symptom was headache and facial/periorbital pain (85.71%), followed by facial/periorbital swelling (61.90%). Disease involvement: sinonasal (100%), orbital (47.62%), pterygopalatine fossa (28.58%), infratemporal fossa (14.29%), intracranial (23.81%), and skin (9.52%). Exclusive endoscopic debridement and combined approach were utilized in 61.90% and 38.10%, respectively. Both liposomal amphotericin B and posaconazole were given in all patients except one. Conclusion: A high suspicion of AIFRS should be kept in patients with recent COVID-19 infection who received steroids and presenting with headache, facial pain, and/or facial swelling. Asymptomatic COVID-19 carriers and COVID-19 vaccinated candidates are also observed to develop AIFRS, although the exact immuno-pathogenesis is still unknown. Prompt diagnosis and early management are vital for a favorable outcome.

JUVENILE NASOPHARYNGEALANGIOFIBROMA: OUR EXPERIENCE AND LITERATURE REVIEW

ABSTRACT Introduction: Juvenile nasopharyngeal angiofibroma is a benign vasculartumor.It is commonly found in teen age males. Its site of origin is sphenopalatine foramen. Exact pathogenesis of angiofibroma is not known. It has predictable natural history and growth pattern. This tumor most often involves nasopharynx, nasal cavity, paranasal sinuses, pterygopalatine fossa and infratemporal fossa. It can also involve orbit and can spread intracranially. Its very important to diagnose this tumor very early on the basis of clinical examination and imaging. As early tumor confined to nose and sinuses can be removed exclusively with endoscope. It is very helpful to do angiography before surgery to ascertain itsblood supply and then embolization can be done to reduce intraoperative bleeding. Objective: To describe our experience of Juvenile Nasopharyngeal Angiofibroma cases in ENT Unit-I of Lahore General Hospital. Study Design: Descriptive Study with retrospective analysis after approval from Institutional Review Board (IRB) of LGH/PGMI/AMC Lahore. Methods: We studied 20 patients who underwent surgery in our department from October 2019 to October 2020. We analyzed following factors: age, gender, symptoms, staging, mode of surgery and need for intraoperative blood transfusion, hospital stay, complications and recurrences. Results: Range of patient’s age was 12 to 25 years. Eight patients underwent surgery with endoscope. Mean blood loss was about 400 ml and mean operating time was 140 minutes. All the cases were embolized preoperatively. Conclusion: Endoscopic surgery is a safe and effective method in early stage JNA patients. While patients with advance stage tumors should be managed with combined endoscopic and conventional open approaches. KEYWORDS: juvenile nasopharyngeal angiofibroma, JNA, endoscopic surgery

A multicentric observational study of imaging findings in COVID-19-related rhino-orbito-cerebral mucormycosis: a new Pandora’s box

Background There is a sudden rise of fungal infection with corona virus disease. This is attributed to the immunomodulation by the disease and the drugs used, diabetes mellitus, steroid use, oxygen inhalation using dirty water, use of zinc and iron supplements, etc. Early diagnosis and prompt medical and surgical intervention is the mainstay of treatment. This can greatly reduce the high morbidity and mortality associated with this disease. The objective of the study is to describe the imaging findings of acute invasive rhino-orbito-cerebral mucormycosis (ROCM) in 25 patients with severe acute respiratory syndrome corona virus 2, from three different centers with proven mucormycosis. Special emphasis is placed on the signal enhancement patterns of sinonasal mucosa, the earliest and most common findings. Statistical analysis was performed using descriptive statistics. Results Computed tomography (CT) and magnetic resonance imaging (MRI) of 25 patients showed most commonly involved sinuses as maxillary and ethmoid sinuses (19, 76%) together. Sino-nasal mucosal thickening was the most common finding (24, 96%). Periantral infiltration (18, 72%) preceded before orbital (15, 60%), cerebral (5, 20%) and vascular (2, 8%) complications, with grossly intact bones. Sinus wall erosions were seen in only 2 patients (8%). Palatal (22%) and maxillary alveolar arch erosion (39%) were frequent findings. CT showed minimally enhancing hypodense soft tissue thickening as the predominant finding in involved areas, while MRI showed T1 and T2 iso- to hypointense mucosal thickening (62%) and intense (43%) and no (33%) contrast enhancement as the main finding. Conclusions Contrast enhanced MRI is better at demonstrating early mucosal abnormalities, turbinate necrosis, non-enhancing devitalized tissues, orbital apex involvement and intra-cerebral extension. Imaging findings of inflammatory tissue infiltration adjacent to the paranasal sinuses in premaxillary, retroantral fat, facial muscles, pterygopalatine fossa, temporal, infratemporal fossa and extraconal orbital fat along with typical patterns of sinonasal mucosal enhancement should raise the suspicion of acute invasive fungal etiology given the short duration of history and immunocompromised status. High incidence of periantral and orbital extension of the disease is suggestive of acute invasive form of fungal infection. Also the rapidly progressive inflammatory changes without much bone involvement should suggest the suspicion of ROCM. Bony, cerebral and vascular involvements are relatively late complications.