Jean Paul Atallah

Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis.

Background: Most acute pancreatitis risk scoring systems use total white blood cell counts (WBC) as one of the risk factors. The value of the neutrophil-lymphocyte ratio (NLR) to predict the severity of acute pancreatitis has not been previously evaluated. Methods:This observational study included 283 patients admitted to a tertiary center between 2004 and 2007. The patients were arranged into tertiles according to NLR and WBC values. The primary outcomes were intensive care unit (ICU) admission and length of stay (LOS) in the hospital. Results: According to NLR tertiles, patients in the 3rd tertile (NLR ≧7.6) had significantly more ICU admissions (17 vs. 2.2%, p < 0.0001) and longer average LOS (6.2 vs. 4.2 days, p < 0.002) compared with those in the 1st tertile (NLR <3.6). According to WBC tertiles, patients in the 3rd tertile had more ICU admissions (12.6 vs. 6.2%, p = 0.12) and a longer average LOS (5.8 vs. 4.4 days, p = 0.059) compared to patients in the 1st WBC tertile, but this did not reach statistical significance. In the multivariate model including NLR, WBC and other predictors, only NLR tertiles (p < 0.0262) and modified early warning scores (p < 0.0025) were significant predictors of ICU admission. Likewise, in the multivariate model of LOS, only NLR and glucose level were significant predictors of longer LOS (p < 0.0161 and p < 0.0053, respectively). Conclusion: NLR is superior to total WBC in predicting adverse outcomes of acute pancreatitis. According to our data, we suggest using the NLR cutoff value of >4.7 as a simple indicator of severity in patients presenting with acute pancreatitis.

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.

Antineoplastic agents and thrombotic microangiopathy

Thrombotic microangiopathy is an uncommon but reported adverse effect of a variety of antineoplastic drugs, including chemotherapy agents such as mitomycin C and gemcitabine, and newer targeted agents such as the vascular endothelial growth factor inhibitors. We present a review of thrombotic microangiopathy associated with antineoplastic agents and its implications in current cancer therapy.

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.

Alpha-fetoprotein-producing nonmetastatic gastric adenocarcinoma: a rare entity.

Alpha-fetoprotein (AFP) is a plasma protein that is produced by the liver and the yolk sac during fetal development. In adults, an elevation in this protein can be exclusive to specific malignancies such as hepatocellular carcinoma, yolk sac tumors, and metastatic disease to the liver. In the clinical setting, an elevated AFP level and a liver mass (masses) translate to a diagnosis of hepatocellular carcinoma. Gastric adenocarcinoma is an aggressive malignancy that has a poor prognosis and has a potential for early metastatic spread [1]. There have been some case reports in the literature that have described elevated AFP levels in gastric adenocarcinoma with metastasis to the liver and hepatoid adenocarcinoma of the stomach. Here, we report an unusual case of nonmetastatic gastric adenocarcinoma with local compression on the liver and elevated AFP levels in a previously healthy woman.

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.

Primary Intimal Sarcoma of the Left Atrium: An Incidental Finding on Routine Echocardiography:

Cardiac sarcomas are extremely rare primary malignant tumors of the heart. In this article, we present the case of a 70-year-old female, who was found to have a left atrial mass during a routine outpatient transthoracic echocardiography. Further investigation with cardiac magnetic resonance imaging confirmed the presence of a bilobulated mass with heterogeneous enhancement. Left atrial myxoma was the first diagnostic consideration, followed by other primary cardiac tumors, and thrombus. The patient subsequently underwent resection of the mass, utilizing cardiopulmonary bypass. Upon pathological examination, the mass was found to be an intimal sarcoma. The objective of this report is to describe a case of this rare disease entity, and to discuss its presentation, pathological findings and management.

Extraocular Muscle Metastasis from Esophageal Carcinoma: an Atypical and Rare Presentation

Esophageal cancer is an aggressive disease with detrimental prognosis. While this tumor often metastasizes to liver, lymph nodes, and lungs, skeletal muscle metastasis is extremely rare. Among the skeletal muscle metastasis, extraocular muscle invasion is even more unusual. Breast and lung carcinoma are the two most common malignancies accompanying the extra ocular muscle metastasis (EOM), but cases of melanoma and sarcoma have also been reported. Extra ocular muscle invasion represents extensive hematogenous spread and typically a highly advanced disease progression. Authors of several extant studies aimed to elucidate the factors contributing to the rarity of its invasion, as well as identify the protective mechanisms against this disease outcome [1, 2]. Their findings indicate that the interaction between cancer cells and muscle microvasculature walls results in surface membrane deformation and lysis of the former. In addition, as muscle cells have a low molecular weight, this was posited to inhibit the proliferation of tumor cells in vitro and in vivo [3]. Herein, we present a new case of esophageal adenocarcinoma that metastasized to left medial rectus muscle. Case Report

ALK-Negative Anaplastic Large Cell Lymphoma Presenting as Disseminated Intravascular Coagulation and Hemophagocytic Lymphohistiocytosis: A Potentially Fatal Presentation

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder that can be familial in etiology or a result of infections, malignancy, and autoimmune or inflammatory disorders. Disseminated intravascular coagulation (DIC) is common in patients admitted to intensive care units and can confound and delay the diagnosis of HLH. We present a case of a 69-year-old female who presented with dyspnea and malaise. Her condition declined rapidly with laboratory parameters consistent with DIC. In addition, she had a ferritin of 32,522 ng/mL, low haptoglobin, and elevated LDH, and bone marrow biopsy showed hemophagocytic lymphohistiocytes. She was started on HLH-directed therapy, and later, a diagnosis of ALK-negative anaplastic large cell lymphoma was made on an excisional inguinal lymph node biopsy specimen. Our case emphasizes the importance of prompt recognition, diagnosis, and treatment of HLH while workup for a primary disorder is still being pursued.