Alpelisib to treat CLOVES syndrome, a member of the PIK3CA-related overgrowth syndrome spectrum

CLOVES syndrome is a rare congenital overgrowth disorder caused by mutations in the phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene. It is part of the PIK3CA-related overgrowth syndrome (PROS) spectrum and its treatment is challenging. PROS malformations have traditionally been treated by surgery, but research into pharmacological treatments capable of blocking the PIK/AKT/mTOR pathway has increased over the past decade. Its favorable results in these settings suggest that its compassionate use in patients with PROS disorders could have clinical benefits. Another promising drug is Alpelisib, which is a selective inhibitor that competitively binds to the p110a subunit of PIK3 in the intracellular PI3K/AKT signaling pathway. A low dose of Alpelisib used on compassionate grounds was shown in an uncontrolled case series to have striking effects in a cohort of 19 PROS patients, several with life-threatening complications. Moreover, the low dose of Alpelisib provoked few side effects and did not impair linear growth of the often young patients. We present the case of a patient with CLOVES syndrome who was started on compassionate treatment with Alpelisib after surgical debulking of a cystic lymphangioma and treatment with sirolimus. This promising drug significantly reduced the size of the lymphangioma and prevented progression of the tissue overgrowth in the gluteal region. This case suggest that there may even be collateral benefits of low-dose PI3K inhibition beyond mitigating disease-specific features of PROS.

CHFR and Paclitaxel Sensitivity of Ovarian Cancer

The poly(ADP-ribose) binding protein CHFR regulates cellular responses to mitotic stress. The deubiquitinase UBC13, which regulates CHFR levels, has been associated with better overall survival in paclitaxel-treated ovarian cancer. Despite the extensive use of taxanes in the treatment of ovarian cancer, little is known about expression of CHFR itself in this disease. In the present study, tissue microarrays containing ovarian carcinoma samples from 417 women who underwent initial surgical debulking were stained with anti-CHFR antibody and scored in a blinded fashion. CHFR levels, expressed as a modified H-score, were examined for association with histology, grade, time to progression (TTP) and overall survival (OS). In addition, patient-derived xenografts from 69 ovarian carcinoma patients were examined for CHFR expression and sensitivity to paclitaxel monotherapy. In clinical ovarian cancer specimens, CHFR expression was positively associated with serous histology (p = 0.0048), higher grade (p = 0.000014) and higher stage (p = 0.016). After correction for stage and debulking, there was no significant association between CHFR staining and overall survival (p = 0.62) or time to progression (p = 0.91) in patients with high grade serous cancers treated with platinum/taxane chemotherapy (N = 249). Likewise, no association between CHFR expression and paclitaxel sensitivity was observed in ovarian cancer PDXs treated with paclitaxel monotherapy. Accordingly, differences in CHFR expression are unlikely to play a major role in paclitaxel sensitivity of high grade serous ovarian cancer.

PLEXIFORM NEUROFIBROMA OF THE BRACHIAL PLEXUS – A RARE CASE REPORT

Neurobroma is a common benign tumour occurring as part of an autosomal dominant disorder, neurobromatosis type 1, leading to the formation of benign tumours or neurobromas of the peripheral nervous system. Large neurobromas of the brachial plexus are rare and present a difcult challenge for surgeon due to the anatomical complexity of the brachial plexus. Dermal neurobromas usually present with swelling and occasional pain, but neurobromas associated with the brachial plexus present with pain and neurological symptoms. These plexiform neurobromas of the brachial plexus are known to undergo malignant transformation. Here, we present a case of a large plexiform neurobroma affecting the left brachial plexus and extending till the elbow, conrmed with MRI and surgical debulking was done.

Reductive Otoplasty and Facial Debulking in a Pediatric Patient With PIK3CA-Related Overgrowth

Overgrowth syndromes encompass a number of rare genetic diseases with heterogeneous clinical phenotypes. Accordingly, there is a strong imperative to collect data and classify these disorders to aid in diagnosis and management. Recent advances in the genetics of overgrowth syndromes have identified mutations in the PIK3CA gene. These somatic mutations manifest in progressive segmental overgrowth of fibrous and adipose tissue and bone, vascular malformations, and in some cases, increased risk for malignancy. Targeted medical therapy is under investigation for the management of PROS, but treatment of overgrowth relies on surgical debulking. Macrotia in PIK3CA-related overgrowth spectrum (PROS) has not been reported in the literature. In this case, we discuss a novel approach to reductive otoplasty and facial soft tissue debulking in a pediatric patient with PROS.

Surgical management of a giant abdominal wall desmoid tumour

Desmoid tumours are clonal fibroblastic proliferations in soft tissues, characterised by infiltrative growth and local recurrence, but not metastasis. Various treatment strategies for desmoid tumours exist, varying from observation, medical and systemic therapy to radiotherapy and surgery. A 25-year-old woman with a background of familial adenomatous polyposis was referred with an enlarging abdominal desmoid tumour measuring 40×40×40 cm despite repeated radiofrequency ablation, surgical debulking and hormone therapy. The patient had a two-stage operation. The first stage involved excision of the desmoid tumour with full-thickness abdominal wall. The abdominal wall was not closed, and a topical negative pressure seal was applied. After 2 days, she underwent the second stage: reconstruction of the abdominal wall defect with a large porcine mesh which was covered with anterolateral thigh flaps. Postoperative complications included ileus and a fall which required further surgery. The patient was discharged 1 month after the first operation. Abdominal MRI scans were performed at 3 and 7 months postdischarge and showed no recurrence of diseaseBackground

Rare presentation of Aspergillus as cystic swelling in pre-maxillary region

<p class="abstract">Subcutaneous fungal infections are caused by penetration of the causative fungi into the subcutaneous layer and usually present as single, localised non-tender nodular swelling. The diagnostic process is a vital dynamic process that requires effective communication and efficient collaboration. Aspergillus hyphae invade host tissues through release of various toxins like proteases, phospholipases, hemolysins, gliotoxin, aflatoxin, phthioic acid and other toxins. Under general anesthesia and proper aseptic conditions using Moure incision surgical debulking of the pre-maxillary mass was done and post-operatively oral antifungal medication was started. Multiple cystic swelling was sent for histopathological examination and found to be non-invasive Aspergillus fungal infection. Subcutaneous form of aspergillosis manifest as subcutaneous fungal infection. We presented an unusual case report of 45 years old immunocompetent female with cystic presentation of aspergillosis involving premaxillary region.</p>

Patient with systemic emboli in the setting of Klebsiella oxytoca tricuspid valve endocarditis and patent foramen ovale treated with NobleStitch and AngioVac

A 34-year-old man with a medical history of injection drug use presented with 2 weeks of weakness, nausea, vomiting and septic shock secondary to infective endocarditis of a native tricuspid valve. On admission, CT chest demonstrated multiple cavitary lesions as well as numerous small infarcts seen on MRI brain concerning for systemic septic emboli. Subsequent transthoracic echo with bubble study revealed a large patent foramen ovale (PFO). The patient later received surgical debulking of his tricuspid valve vegetation with AngioVac. Subsequently, PFO closure was performed with a NobleStitch device. The case presented here demonstrates the importance of having a high index of suspicion with right-sided endocarditis and the development of other systemic signs and symptoms. It also underscores the necessity of a multidisciplinary team of cardiologists, surgeons, infectious disease specialists and intensivists in the treatment of these complicated patients.