The Association Between Gastroesophageal Reflux Disease and Non-Small Cell Lung Cancer: A Retrospective Case-Control Study.

Background: Lung cancer is a leading cause of mortality in the USA. Non-small cell lung cancer (NSCLC) contributes to 85% of all lung cancers. It is the most prevalent subtype amongst non-smokers, and its incidence has risen in the last 20 years. In addition, gastroesophageal reflux disease (GERD) has been associated with several lung pathologies, namely idiopathic pulmonary fibrosis and asthma. We aimed to investigate the association between GERD and NSCLC by performing a retrospective, multicenter, case-control study. This is the first study of this nature to be carried out in the USA. Methods: Data were retrieved from 17 Northwell health care facilities in the New York area between the years 2010 and 2018. Inclusion criteria were patients > 18 years of age with NSCLC (large cell, adenocarcinoma, and squamous cell). They were appropriately matched with controls based on age, gender, weight, comorbidities, and medication use. Our exposure group had a diagnosis of GERD based on the International Classification of Diseases, Ninth/10th Revision (ICD 9/10) codes and endoscopic, in addition to histological evidence if present. We excluded patients with secondary lung cancers, esophageal adenocarcinoma, other primary malignancies, Barrett's esophagus, and smokers. Logistic regression was conducted to determine the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between NSCLC and GERD. Results: A total of 1,083 subjects were included in our study: 543 (50%) patients were diagnosed with NSCLC. In this population, GERD was twice as prevalent compared to controls (20.4% vs. 11.6%, P < 0.001). Multivariate analysis demonstrated that GERD was associated with a higher risk of NSCLC compared to matched controls (OR = 1.86, 95% CI = 1.26 - 2.73). In addition, GERD patients treated with either antihistamines or proton pump inhibitors did not demonstrate an overall reduced risk of NSCLC (OR = 1.01, 95% CI = 0.48 - 2.12). Conclusions: Our study demonstrates that GERD is associated with a higher risk of NSCLC, irrespective of GERD treatment. We postulate that GERD patients suffer from chronic micro-aspirations leading to a prolonged inflammatory state within the lung parenchyma, triggering specific proliferative signaling pathways that may lead to malignant transformation.

Carfilzomib Induced Tumor Lysis Syndrome and Other Adverse Events.

In the area of multiple myeloma (MM) therapy, proteasome inhibitors (PI) have emerged with promising responses both in the first- and second-line setting. Carfilzomib (CFZ) is a second-generation, selective PI approved in 2012 for the treatment of relapsed/refractory multiple myeloma (RRMM) in patients who received 2 prior therapies or have evidence of disease progression within 60 days of completion of last therapy. Its safety profile reported adverse events (AEs) ranging from drug-related AEs (nausea and vomiting), hematologic AEs (neutropenia and thrombocytopenia), and nonhematologic AEs (electrolyte imbalances). As CFZ use is gaining popularity, various hematological, renal, cardiovascular, pulmonary, and neurological toxicities have been reported. We are presenting this case to describe a rare occurrence of tumor lysis syndrome (TLS) with the use of this novel targeted therapy.

Predictors of 15-Day Survival for the Intensive Care Unit Patient on Continuous Renal Replacement Therapy: A Retrospective Analysis.

Purpose In the intensive care unit (ICU), acute renal failure is mostly part of multiple organ dysfunction syndromes with mortality ranging from 28%-90%, continuous renal replacement therapy (CRRT) is the predominant mode of RRT used in ICU. The main objective of the study was to evaluate the outcomes in patients with acute kidney injury (AKI) on CRRT in the ICU. Methods A retrospective chart review was conducted for all ICU patients with acute renal failure on CRRT in a tertiary care teaching hospital. A subgroup analysis was conducted between 15 days in hospital survivors and non-survivors to look for predictors of survival for patients on CRRT. Results Two-hundred twenty-six patients underwent CRRT from January 2007 to December 2013. The overall in-hospital mortality was 84.1%. Fifty-six patients (24.77%) survived to the 15-day post-CRRT mark. Acute respiratory failure requiring mechanical ventilation was associated with significantly increased mortality; 89.2% vs. 97.6% (P=0.008), ICU length of stay was significantly longer in the survivor group than the nonsurvivor group. Median±IQR; {20±24 vs 6±7(P: <0.0001)} and so were the ventilator-associated days {16±24 vs 4±6.5 (P: <0.0001)} and duration of CRRT {4.5±5.5 vs 2±2.0(P: <0.0001)}. Patients who survived had a lower incidence of metabolic acidosis {44.6% vs 62.9% (P: 0. 016)} and uremic encephalopathy {12.5% vs 26.5%; (P: 0.031)} but a greater incidence of volume overload {28.6% vs 15.9% (P: 0.031)} as compared to the non-survivor. Acute Physiology And Chronic Health Evaluation II (APACHE II) scores were significantly higher in the non-survivor group (mean SD) 26.9±28.0 vs. 23.9±25.8 (P: 0.0136). Conclusions This observational study in patients undergoing CRRT in an ICU setting revealed that the overall mortality was 84.1%. Fluid overload as an indication of CRRT was associated with improved 15 days' survival whereas higher APACHE II scores and the use of mechanical ventilation were associated with reduced 15 days' survival.

Spontaneous Rupture of Fibrolamellar Variant Hepatocellular Carcinoma.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a unique variant of hepatocellular carcinoma. The majority of cases present with nonspecific symptoms like vague abdominal pain, weight loss and fatigue. Ruptured FL-HCC occurs rarely and mortality in the acute phase is very high. We report a rare case of a ruptured FL-HCC successfully managed with transarterial embolization for hemostasis. A 37-year-old male previously in good health presented with a severe, sharp epigastric pain that started 1 h prior to the presentation. He denied trauma, fever, nausea, vomiting, or diarrhea. Tenderness in the epigastrium was noted, with no palpable masses, guarding or rigidity. His blood pressure and pulse were 159/105 mm Hg and 105 beats/min. Platelets and coagulation parameters were within normal limits; transaminases were elevated. Abdominal computed tomography (CT) scan with contrast revealed an 8 cm lobulated mass with central hypodensity in the left hepatic lobe with perilesional blood and free pelvic fluid, indicating tumor rupture. CT angiography showed tumor neovascularization from a branch of the left hepatic artery which was embolized using transarterial gelfoam. Liver magnetic resonance imaging (MRI) and biopsy were consistent with fibrolamellar variant hepatocellular carcinoma. After 4 days, as the symptoms resolved, and the lab results were stable, patient was discharged and underwent a left hepatectomy 3 weeks later. FL-HCC occurs commonly in the left lobe of a young and non-cirrhotic liver. Typically, cross sectional imaging reveals a lobulated mass with well-defined margins, areas of hypervascularity and a central calcified scar. Histologic appearance is characterized by eosinophilic polygonal shaped cells separated by lamellar fibrosis. Surgical resection is the treatment of choice with better outcome when compared to conventional HCC. Disease recurrence after complete surgical resection is however high in the first 5 years. Tumors > 5 cm in size are at high risk for rupture with high mortality and recurrence rates secondary to significant spillage of tumor. While an emergency hepatectomy is preferred in unstable patients, those that are hemodynamically stable can undergo radiologic transarterial embolization for hemostasis followed by staged hepatectomy.

Renal Tubular Acidosis an Adverse Effect of PD-1 Inhibitor Immunotherapy.

Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis. Urine and blood studies were in favor of distal renal tubular acidosis (RTA). Following a negative workup for an underlying etiology, immunotherapy-induced RTA was suspected. Withholding of the offending agent and initiation of steroid therapy resulted in adequate response. The present report provides the first presentation of RTA as a renal immune-related adverse event secondary to nivolumab. Nephrologists and oncologists should be familiar with potentially life-threatening renal side effects induced by immune checkpoint inhibitors.

What we know about surgical therapy in early-stage non-small-cell lung cancer: a guide for the medical oncologist.

Lung cancer remains the leading cause of death in cancer patients. The gold standard for the treatment of early-stage non-small-cell lung cancer is lobectomy with mediastinal lymph-node dissection or systematic lymph-node sampling. The evidence behind this recommendation is based on the sole randomized controlled trial conducted to date, done by the Lung Cancer Study Group and published in 1995, which found a superiority for lobectomy over sublobar resection with regard to local recurrence rate and improved survival. The population studied at that time were medically fit patients at low risk for surgery with a stage IA non-small-cell lung carcinoma, ie, a solitary tumor less than 3 cm in size. In practice, however, thoracic surgeons have continued to push the limit of a more conservative surgical resection in this patient population. Since then, several retrospective studies have attempted to identify the ideal population to benefit from sublobar resection without it affecting survival or local recurrence. Several variables have been studied, including tumor size, patient age, surgical approach, histological and radiological properties, and optimal surgical resection margin, as well as promising prognostic biomarkers. In this review, we summarize the data available in the literature regarding the surgical approach to patients with stage IA non-small-cell lung cancer studying all the aforementioned variables.

Anaplastic lymphoma kinase inhibitors in elderly patients with advanced non-small cell lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in the USA and worldwide. At diagnosis, half of the patients are over 70 years of age, and most present with advanced disease for which chemotherapy provides modest benefit with significant toxicity. Older patients often have more comorbidities than their younger counterparts and tend to be excluded from clinical trials. AREAS COVERED: A small percentage (less than 7%) of patients with NSCLC have the anaplastic lymphoma kinase (ALK) rearrangement. Compared to the general NSCLC population, this clinically distinct group has a relatively younger median age of 51 years at diagnosis. As such, elderly patients with ALK-positive disease are both a minority within this group and are expected to be underrepresented in clinical trials. Expert commentary: Despite promising results in the general population, data about the efficacy and safety of ALK inhibitors in the elderly population remains scarce. In our review, we briefly discuss the current evidence of ALK inhibitors in the general population and we shed light on this subgroup of elderly patients with advanced ALK-positive disease.

"The Great Mimicker": An Unusual Etiology of Cytopenia, Diffuse Lymphadenopathy, and Massive Splenomegaly.

Sarcoidosis is an idiopathic multisystem disease characterized by the formation of noncaseating granulomas. It frequently presents with pulmonary infiltrates and bilateral hilar and mediastinal lymphadenopathy. Splenic involvement is common, but massive splenomegaly is a rare occurrence. Sarcoidosis is known as "the great mimicker" (or "the great imitator") since it exhibits a myriad of symptoms, mimicking other inflammatory, infectious, and neoplastic conditions, including lymphoma. Herein, we report the case of a 44-year-old male patient who was found to have bicytopenia, hypercalcemia, diffuse lymphadenopathy, and massive splenomegaly, a constellation of findings suggestive of underlying lymphoma. Interestingly, lymph node biopsy showed noncaseating granulomas suggestive of sarcoidosis, without evidence of malignancy.

Epidermal growth factor receptor tyrosine kinase inhibitors in elderly patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. At diagnosis, half of the patients are over 70 years of age, and most present with advanced disease, for which chemotherapy is recommended as first-line treatment. However, the benefit from such therapy is modest and it is at times poorly tolerated. The discovery of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has significantly impacted the treatment of patients with EGFR mutation-positive advanced NSCLC. These novel agents demonstrate efficacy and a favorably mild toxicity profile. Despite limited data in elderly patients, the largest subpopulation in NSCLC, EGFR-TKIs are considered the standard of care therapy for advanced EGFR-positive disease in the elderly. In this review, we seek to compile the available data about the EGFR-TKIs use in elderly patients with advanced NSCLC, with the hope to better understand its role in this major yet, underrepresented, group of patients.

Spontaneous Tumor Lysis Syndrome in Small-Cell Lung Cancer: A Rare Complication.

Tumor lysis syndrome (TLS) is a life-threatening condition which consists of a constellation of electrolyte imbalances, acute renal failure, seizure, and arrhythmias. It is most commonly seen with hematologic malignancies after the initiation of chemotherapy. However, it can also occur spontaneously, prior to treatment with cytotoxic agents. TLS has been rarely described with non-hematologic solid tumors, and it is even more uncommon to have spontaneous tumor lysis syndrome (STLS) in solid tumors. To our knowledge, only two cases of STLS in small-cell lung cancer (SCLC) were reported in the literature. Herein, we present the case of a patient with metastatic SCLC who developed STLS. Our case highlights that in the setting of metastatic solid tumors, STLS must be in the differential diagnosis, to allow prompt initiation of prophylaxis and treatment.

Hypoalbuminemia in colorectal cancer prognosis: Nutritional marker or inflammatory surrogate?

Albumin is the single most abundant protein in the human serum. Its roles in physiology and pathology are diverse. Serum albumin levels have been classically thought to reflect the nutritional status of patients. This concept has been challenged in the last two decades as multiple factors, such as inflammation, appeared to affect albumin levels independent of nutrition. In general, cancer patients have a high prevalence of hypoalbuminemia. As such, the role of hypoalbuminemia in patients with colorectal cancer has received significant interest. We reviewed the English literature on the prognostic value of pretreatment albumin levels in colorectal cancer. We also consolidated the evidence that led to the current understanding of hypoalbuminemia as an inflammatory marker rather than as a nutritional one among patients with colorectal cancer.

An Overlapping Case of Lupus Nephritis and IgG4-Related Kidney Disease.

We report a case of a 71-year-old Filipino female who was admitted to the hospital for abdominal pain, vomiting and diarrhea of 8 days duration. The patient was found to have marked acute kidney injury (AKI), which required hemodialysis in the next 3 days. Extensive workup revealed hematuria, subnephrotic range proteinuria, elevated anti-nuclear antibody (ANA) and elevated total immunoglobulin G (IgG) levels, with normal IgG4 and anti-dsDNA levels. On kidney biopsy, mild membranous glomerulonephritis was found, along with autoimmune tubulointerstitial nephritis (TIN) with a "full-house" pattern of immune deposits. These findings were suggestive of lupus interstitial nephritis. However, IgG4+ plasma cells were detected in the interstitium by immunostaining, favoring a diagnosis of IgG4-related kidney disease (IgG4-RKD). Our case highlights the difficulty in differentiating lupus nephritis (LN) from IgG4-RKD in some patients, raising the suspicion that these two entities can co-exist.