Therapeutic implications of activating noncanonical PIK3CA mutations in head and neck squamous cell carcinoma.

Alpelisib selectively inhibits the p110α catalytic subunit of PI3Kα and is approved for treatment of breast cancers harboring canonical PIK3CA mutations. In head and neck squamous cell carcinoma (HNSCC), 63% of PIK3CA mutations occur at canonical hotspots. The oncogenic role of the remaining 37% of PIK3CA noncanonical mutations is incompletely understood. We report a patient with HNSCC with a noncanonical PIK3CA mutation (Q75E) who exhibited a durable (12 months) response to alpelisib in a phase II clinical trial. Characterization of all 32 noncanonical PIK3CA mutations found in HNSCC using several functional and phenotypic assays revealed that the majority (69%) were activating, including Q75E. The oncogenic impact of these mutations was validated in 4 cellular models, demonstrating that their activity was lineage independent. Further, alpelisib exhibited antitumor effects in a xenograft derived from a patient with HNSCC containing an activating noncanonical PIK3CA mutation. Structural analyses revealed plausible mechanisms for the functional phenotypes of the majority of the noncanonical PIK3CA mutations. Collectively, these findings highlight the importance of characterizing the function of noncanonical PIK3CA mutations and suggest that patients with HNSCC whose tumors harbor activating noncanonical PIK3CA mutations may benefit from treatment with PI3Kα inhibitors.

Vulvar Crohn's Disease: Clinical Features and Outcomes.

INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

Hyperammonemic encephalopathy in a patient with fibrolamellar hepatocellular carcinoma: case report and literature review.

Fibrolamellar hepatocellular carcinoma (fHCC) is a rare primary liver cancer that affects young adults with no prior liver disease. fHCC-associated hyperammonemic encephalopathy (HAE) is an uncommon and life-threatening complication. Hyperammonemia has been reported in both typical and fHCC as a result of intrahepatic shunting, side effect from immunotherapy or chemotherapy, or as a paraneoplastic phenomenon. We present a case of a 32-year-old woman with recurrent metastatic fHCC who developed HAE in the setting of steroid administration. Her hyperammonemia was exacerbated by steroid-induced protein catabolism. She was treated with ammonia scavenging medications, a low protein diet, and was placed on chronic ammonia scavenger therapy while undergoing chemotherapy. In this case report, we discuss the proposed mechanisms of HAE, and we review the literature regarding clinical presentation and treatment.

Screening for Clostridium difficile colonization on admission to a hematopoietic stem cell transplant unit may reduce hospital-acquired C difficile infection.

Clostridium difficile infection rates are higher in patients undergoing hematopoietic stem cell transplants. In our study, patients undergoing hematopoietic stem cell transplants or chemotherapy were screened for C difficile colonization at admission and placed on contact precautions if they were positive. Patient's colonized with C difficile contribute to the overall burden of C difficile infection in hospitals.

Association between atopic dermatitis and squamous cell carcinoma: a case-control study.

BACKGROUND: Conflicting data have been published on whether an association exists between atopic dermatitis (AD) and nonmelanoma skin cancer. This study aimed to determine whether individuals with AD had an increased risk of squamous cell carcinoma (SCC) development. METHODS: We conducted a retrospective, case-control study of patients residing in Olmsted County, Minnesota. Cases were selected from patients seen at Mayo Clinic (Rochester, Minnesota) who had an initial SCC diagnosis (either invasive SCC or SCC in situ) from January 1, 1996, through December 23, 2010. Age- and sex-matched controls were selected from patients seen at Mayo Clinic with no history of SCC before the case event date. RESULTS: Three hundred ninety-nine individuals with a documented history of SCC were identified and matched with 780 controls who did not have a history of SCC. After adjusting for race, smoking history, ionizing radiation exposure, corticosteroid and cyclosporine use, and non-SCC skin cancers, the odds ratio for SCC development between patients with history of AD versus patients without history of AD was 1.75 (95% CI, 1.05-2.93). CONCLUSIONS: Our findings support an increased risk of SCC development in the setting of AD.

Therapeutic Implications of the Genetic Landscape of Head and Neck Cancer.

Large-scale sequencing studies of head and neck squamous cell carcinoma (HNSCC) have elucidated the genetic changes that characterize HNSCC. These findings have supported the development of therapeutic strategies that target key components of aberrant signaling pathways and immune dysregulation. Cumulative evidence suggests that these agents in combination with radiotherapy may have synergistic effects. This review highlights the predictive biomarkers that have been identified from HNSCC genomic studies and implications on the development of molecular-targeting agents that may effectively treat patients with HNSCC, especially when used in combination with radiation.

Role of imaging in the diagnosis of occult hernias.

IMPORTANCE: Occult hernias are symptomatic but not palpable on physical examination. This is more commonly seen with inguinal hernias. Early diagnosis and treatment of occult hernias are essential in relieving symptoms and improving patients' quality of life. OBJECTIVE: To determine the effectiveness of imaging-ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI)--in the diagnosis of occult inguinal hernia. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical records review of surgical patients with groin and pelvic pain, 2008-2013, was conducted in a single-surgeon hernia specialty practice. Thirty-six patients met the following inclusion criteria: (1) examination findings suggestive of but not necessarily diagnostic for inguinal hernia; (2) imaging of the groin and/or pelvis with US, CT, and MRI; and (3) an operation to address the groin or pelvic pain. Fifty-nine groins were included. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, and predictive values of US, CT, and MRI for detection of occult inguinal hernia. RESULTS: The number, sensitivity, specificity, positive predictive value, and negative predictive value of each modality were, respectively: US (9, 0.33, 0, 1.00, and 0), CT (39, 0.54, 0.25, 0.86, and 0.06), and MRI (34, 0.91, 0.92, 0.95, and 0.85). Among multiply imaged groins in which CT examination missed a diagnosis of hernia, MRI correctly detected an occult hernia in 10 of 11 cases (91%). CONCLUSIONS AND RELEVANCE: Ultrasonography and CT cannot reliably exclude occult groin abnormalities. Patients with clinical suspicion of inguinal hernia should undergo MRI as the definitive radiologic examination.