Uroosa Ibrahim

Anti–PD-1/PD-L1 antibodies in non-small cell lung cancer: the era of immunotherapy

ABSTRACT Introduction: Advanced non-small cell lung cancer (NSCLC) has been conventionally treated with cytotoxic chemotherapy with short-lived responses and significant toxicities. Monoclonal antibodies to programmed death-1 receptor (PD-1) and programmed death ligand 1 (PD-L1) have shown tremendous promise in the treatment of advanced NSCLC in various clinical trials. Areas covered: In this article, we will review the outcomes of various trials of anti-PD-1/anti-PD-L1 antibodies in the treatment of NSCLC. We will also discuss their mechanism of action and toxicities. Expert commentary: Anti-PD-1/PD-L1 antibodies offer several advantages including significant antitumor activity, induction of long lasting responses, and favorable safety profile. Several trials are now being conducted to evaluate their efficacy as first line agents as well as in combination with other agents. More research is also needed to identify other biomarkers, in addition to PD-L1 expression, that could more reliably predict response to these drugs, and aid in better patient selection.

Emerging role of immunotherapy in precursor B-cell acute lymphoblastic leukemia

ABSTRACT Introduction: Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia that carries poor prognosis in adults especially in the setting of high risk cytogenetics and relapsed/refractory (R/R) disease. Advancements in immunotherapy have led to the development of several monoclonal antibodies (MoAbs) and chimeric antigen receptor (CAR) T cells that are capable of targeting certain surface antigens on leukemic cells, resulting in their destruction. Areas covered: This article reviews the mechanism of action, outcomes of various trials, and adverse effects of MoAbs and CAR-T cells used in the treatment of precursor B-cell ALL. Expert commentary: Some of the immunotherapeutic agents that have been approved for the treatment of R/R precursor B-cell ALL have shown superior efficacy and safety profile compared to chemotherapy in advanced disease. Several trials are now being conducted to evaluate the role of certain MoAbs in combination with chemotherapy in the treatment of B-cell ALL. Additionally, their use in the frontline setting with more favorable host characteristics may also result in superior outcomes compared to the current standard of care.

Mortality among high-risk patients admitted with septic shock to U.S. teaching hospitals in July: Does the ‘July Effect’ exist?

Background The ‘July effect’ is a phenomenon of inferior delivery of care at teaching hospitals during July because of relative inexperience of new physicians. Objective To study the difference in mortality among septic shock patients during July and another month. Methods Using the U.S. Nationwide Inpatient Sample, we estimated the difference in mortality among septic shock patients admitted during May and July from 2003 to 2011. Results 117,593 and 121,004 patients with septic shock were admitted to non‐teaching and teaching hospitals, respectively, in May and July. High‐risk patients had similar mortality rates in non‐teaching hospitals and teaching hospitals. Mortality rates were higher in teaching versus non‐teaching hospitals in high‐risk patients both in May and July. Overall, mortality rates were higher in teaching versus non‐teaching hospitals both in May and July. Conclusion Similar trends in mortality are observed in both settings in May and July and no “July effect” was observed.

Esophageal Granular Cell Tumor: A Case Report and Review of Literature.

Granular cell tumors (GCTs) are soft tissue neoplasms that originate from Schwann cells. They occur predominantly in the oral cavity, skin, and breast tissues. Gastrointestinal GCTs are very rare, accounting for only eight percent of all GCTs, most of which are located in the esophagus. Endoscopic ultrasound has been a breakthrough in diagnosing GCTs because it provides precise information on the depth of tumor invasion, thus narrowing the differential diagnosis of subepithelial lesions in the esophagus. However, the definitive diagnosis requires histological confirmation of the lesion. Here, we report a case of esophageal GCT that was identified incidentally and removed by endoscopic mucosal resection.

EGFR exon 18 delE709_T710insD mutated stage IV lung adenocarcinoma with response to afatinib

Epidermal Growth Factor Receptor (EGFR) targetable mutations have changed the landscape for treatment of advanced stage non-small cell lung cancer in recent years. Three generations of tyrosine kinase inhibitors are now available to target cancers harboring these mutations. The most common EGFR mutations occur in Exons 19 and 21. Exon 18 mutations are extremely rare comprising of 4.1% of all EGFR mutations and the delE709_T710insD mutation accounts for only 0.16% of mutations when occurring as a sole mutation, however, the frequency can vary with the kit utilized for testing. The rarity makes the clinical relevance of these mutations largely unknown. We report a case of a 52year old female with bilateral advanced adenocarcinoma of the lung harboring the delE709_T710insD mutation with significant clinical and radiographic response to treatment with afatinib. We discuss the reported cases of delE709_T710insD mutated non-small cell lung cancer variably treated with geftinib, erlotinib or afatinib. This particular exon 18 mutation seems to preferentially respond to afatinib as reported in two cases including the current case, and in an in vitro experimental model. These reports have implications in guiding decisions for treatment of patients harboring rare EGFR mutations.

Rasburicase-induced methemoglobinemia: The eyes do not see what the mind does not know:

Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise. Treatment is indicated at levels above 20% and at lower levels if the patient is significantly anemic. We present a case of a 60-year-old male with diffuse large B cell lymphoma at high risk of tumor lysis syndrome. Rasburicase was administered to prevent renal failure and further rise in uric acid. Twenty-four hours later, a bedside pulse oximetry showed an oxygen saturation ranging from 60 to 65% with minimal cyanosis. Co-oximetry revealed a methemoglobin level of 9.8%. Methylene blue was administered and the methemoglobin level decreased to 2.6%. However, the patient developed hemolysis several hours later, likely secondary to rasburicase and methylene blue, requiring transfusion support. We discuss this potentially fatal and initially asymptomatic adverse effect of rasburicase along with diagnostic and treatment considerations, and review the cases described in the current literature.

Antiphospholipid Syndrome: Multiple Manifestations in a Single Patient—A High Suspicion Is Still Needed

Antiphospholipid Syndrome (APS) is an autoimmune disorder with clinical and laboratory features of vascular thrombosis, pregnancy loss, and persistent antiphospholipid antibodies (aPLs). The pathophysiology is thought to involve the activation of endothelial cells, monocytes, platelets, and complement by aPLs. Disease can range from asymptomatic to rapidly fatal catastrophic APS. We present a case of a 34-year-old male referred for pancytopenia and splenomegaly. On examination, he had decreased sensation and 4/5 power in the left upper extremity. A lacy, purplish rash was noted on the trunk and upper extremity. MRI of brain showed acute/subacute lacunar infarctions. Laboratory studies revealed an elevated lactate dehydrogenase level, bilirubin and ferritin, decreased haptoglobin, and positive Coombs test. Antinuclear antibody test was negative and antiphospholipid antibody panel revealed positivity for anti-cardiolipin IgG and IgM, antiphosphatidylserine IgG, and anti-β2-glycoprotein IgG. The patient was diagnosed with primary APS. Pancytopenia is relatively rare in primary APS and is more often seen in secondary APS. Our patient demonstrated involvement of multiple organ systems as well as livedo reticularis and autoimmune-related findings such as Raynaud phenomenon and Coombs positive hemolytic anemia. We discuss the various clinical and laboratory findings in patients with APS that aid in diagnosis, as well as important management considerations.

Sarcomatoid Carcinoma of the Lung Presenting as Localized Bronchiectasis: A Case Report and Review of Literature

Sarcomatoid carcinoma (SC) of the lung is a rare and aggressive biphasic lung tumor with a 5-year survival of 20%. Early detection and treatment is the only way to improve outcomes in patients with SC of the lung. We present a case of primary SC identified early based on high suspicion. A 56-year-old female with a history of chronic obstructive pulmonary disease (COPD) presented with hemoptysis and exertional dyspnea. Chest X-ray revealed right upper lobe (RUL) opacity and patient was started on antibiotics for pneumonia. Due to the persistence of hemoptysis, a computed tomography scan was performed which showed RUL bronchiectasis with scattered nodular opacities suggestive of an infectious process. The patient underwent bronchoscopy which revealed a pedunculated mass in the RUL biopsy of which was consistent with poorly differentiated SC. Positron-emission tomography scan revealed Flourdeoxyglucose-avid right peri-hilar mass and another nodule in the RUL. The patient was not a surgical candidate because of severe COPD and was started on chemoradiation therapy. SC of the lung can have various presentations and is usually detected at a later stage and hence, difficult to treat. Our case highlights the importance of critical thinking and prompt diagnostic evaluation in high-risk patients with localized bronchiectasis even without an obvious lung mass on imaging.

An unusual complication of pigtail catheter insertion

Thoracostomy tubes are indicated for management of air or fluid in the pleural cavity. Pigtail catheters have emerged as an effective and less morbid alternative to traditional large bore chest tubes for evacuation of pleural air or fluid. However, they do not come without complications which commonly include pneumothorax and hemothorax. Rare complications in the literature such as left ventricular penetration, subclavian artery laceration and cerebral air embolism have been reported. We report a case of a 72-year-old male who presented with dyspnea and was found to have a right-sided pleural effusion requiring thoracentesis and subsequent pigtail catheter placement because of re-accumulation of the fluid. After accidental dislodgement of the catheter, it was replaced and the following day a chest X-ray (CXR) demonstrated diffuse subcutaneous emphysema. Computed tomography (CT) scan of the chest demonstrated the pigtail catheter tracking through the right middle and lower lobes reaching the posterior pleural space. We discuss the implications of this occurrence and recommended management based on our experience.

Concomitant Presence of EGFR and ALK Fusion Gene Mutation in Adenocarcinoma of Lung: A Case Report and Review of the Literature.

Empirical evidence has long suggested that oncogenic driver mutations in non-small-cell lung cancer are mutually independent. However, recent studies reported in pertinent literature reveal that concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement can occur in a subset of patients with NSCLC. In order to shed further light on this issue, we report a case of adenocarcinoma of lung harboring both EGFR mutation in exon 21 (L861Q) and ALK rearrangement. This allows us to speculate on likely molecular mechanisms underlying this uncommon phenomenon, while also offering some practical guidelines on the therapeutic options that could benefit patients diagnosed with this dual-positive tumor.