George Apergis

Elevated lactic acid is a negative prognostic factor in metastatic lung cancer

BACKGROUND Hyperlactatemia with or without type B lactic acidosis is a rare complication of cancer, previously observed most often in hematological malignancies. The aim of this study was to assess the prognostic value of lactic acid (LA) in patients with metastatic lung cancer. METHODS Patients diagnosed with stage IV non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC), were included in this single center retrospective study. Arterial and venous LA level, anion gap (AG), serum LDH and presence of urine ketones were recorded for each patient and their associations with demographic and clinical data and overall survival (OS) were examined. RESULTS Eighty-five patients (43 males, median age 74, range 45-96 years) were studied. The maximal levels of arterial or venous LA were significantly associated with presence of ≥ 2 metastatic sites (p= 0.001), ICU admission or transfer (p= 0.016), intubation (p= 0.029), elevated serum anion gap (p< 0.001) and LDH levels (p< 0.001). Hyperlactatemia (≥ 1.4 mmol/L) was associated with shorter OS (log-rank p< 0.001). In a multivariate model including LA, ICU, intubation, AG as well as other known prognostic factors of NSCLC and SCLC, including age, sex, smoking status, number and location of metastases, histologic type, performance status (PS), chemotherapy and LDH, LA retained its prognostic value (OR: 1.3; 95%CI: 1.082-1.561; p= 0.005), along with PS (p= 0.039) and chemotherapy (p= 0.039). CONCLUSIONS The results of the study suggest that a high lactic acid level (≥ 1.4 mmol/L) is associated with significantly shorter overall survival in patients with metastatic non-small cell lung cancer and extensive stage small cell lung cancer. Hyperlactatemia is an independent predictor of poor survival in metastatic lung cancer patients.

Angiomyolipomas, renal cell carcinomas and pulmonary lymphangioleiomyomatosis.

A 46-year-old female presented with worsening bilateral flank and abdominal pain. Abdominal CT revealed bilateral enlarged kidneys containing lesions suggestive of multiple angiomyolipomas (AML) and bilateral enhancing solid renal masses suggestive of multifocal renal cell carcinoma (RCC) [Table/Fig-1a–b]. A chest CT disclosed multiple random pulmonary cysts and small nodules in both lungs compatible with lymphangioleiomyomatosis (LAM) and multiple micronodular pneumatosis hyperplasia [Table/Fig-1c]. Overall findings were consistent with tuberous sclerosis (TS). The patient underwent bilateral renal artery branches embolization [Table/Fig-1d,e] with resolution of symptoms. Patient had another two admissions with same symptoms and signs, during which she underwent repeat embolizations for renal artery aneurysms. Patient was lost to follow up before initiation of any further therapy. [Table/Fig-1]: Axial (a) and coronal (b) views of contrast-enhanced CT scan of abdomen showing bilateral enlarged kidneys with multiple fat-containing lesions suggestive of angiomyolipomas (white arrows) and multiple enhancing solid renal lesions suspicious of multifocal ... TS should be suspected when common manifestations are found, including renal AML (55-75%) and LAM (26-39%) [1]. AML is one of the leading causes of death in TS patients. Patients are at risk of serious complications such as life-threatening hemorrhage (25%–50%). As the disease progresses, end-stage renal disease leading to dialysis develops secondary to encroachment of AML on normal renal parenchyma [2]. Historically, treatment of TS has focused on watchful waiting and surgical procedures to reduce tumor burden. Embolization is preferred in the setting of recent or active hemorrhage, or when large or multiple aneurysms are present. At the molecular level, loss of the TS complex 1 (TSC1) or TSC2 gene has been associated with increased production of vascular endothelial growth factor (VEGF), and inhibitors of mTOR have been shown to have an inhibitory effect on production of VEGF, tumor growth, and angiogenesis, both in vitro and in vivo. Everolimus is such an mTOR inhibitor approved for the treatment of adults with renal AML and TSC not requiring immediate surgery, based on favorable results from multicenter, international, randomized, double-blind, placebo-controlled trials EXIST-1 and EXIST-2 [2]. In 2–5% of patients with TS, RCC may develop within dysplastic epithelial cysts. Intriguingly, the course of RCC in TS differs from that in the general population. The mean age of TS-associated RCC is 25 years lower than in those without TSC mutations. In addition, TS-related RCC is usually bilateral and is more often found in women. However, RCC may be over-diagnosed in this patient population given the difficulty in differentiating from fat-poor AML with imaging studies alone. Immunostaining is helpful in such cases, with human melanoma black 45 (HMB-45) stain being characteristic for TSC-associated AML and lymphangioleiomyomatosis (LAM), while cytokeratin immunopositivity is typical for RCC [3]. LAM is characterized by cystic destruction of the lung caused by infiltration of smooth muscle cells and affects predominantly women, occurring more rarely in patients without TS (sporadic LAM). Symptomatic relief of air flow obstruction with bronchodilators and oxygen support can be used, as effective treatment options for this condition are lacking [2]. However, clinical evidence suggests that mTOR targeting can benefit other TSC-associated disease manifestations, including pulmonary LAM, thus rendering it a potential systemic treatment option for this genetic multifaceted disorder [4].

Methylprednisolone-Induced Transient Ventricular Dysfunction

To the Editor: We wish to present the case of a 26-year-old woman who had a right temporo-occipital throbbing headache, vertigo, and numbness in the right hand and right side of the face. Brain images revealed no acute intracranial pathologic condition, so she was given sodium succinate-containing intravenous methylprednisolone for complicated migraine. Within 20 minutes, a diffuse erythematous urticarial rash developed on her face and chest, accompanied by respiratory distress. Her vital signs were: temperature, 98.8 °F; blood pressure, 101/59 mmHg; pulse rate, 118 beats/min; respiratory rate, 28 breaths/min; and oxygen saturation, 70% on room air. Intramuscular epinephrine and intravenous diphenhydramine were ineffective, so she was intubated. Her peak troponin I level was 0.72 ng/mL, and her B-type natriuretic peptide level was 881 pg/mL (vs 6 pg/mL at baseline). Chest images revealed substantial pulmonary edema. A transthoracic echocardiogram (TTE) showed a left ventricular ejection fraction (LVEF) of 0.20, severe global LV hypokinesis, and akinesia of the anteroseptal wall. A day earlier, her LVEF had been 0.55 with normal LV systolic function. She was given intravenous furosemide, diphenhydramine, and famotidine, and was weaned from mechanical ventilation. Five days later, TTE showed normal LV function. Our patient developed a diffuse rash in the setting of respiratory distress minutes after receiving intravenous methylprednisolone, pointing to an immediate hypersensitivity reaction. Succinate-containing intravenous corticosteroids are known to cause anaphylactic reactions.1,2 The pathogenesis is enigmatic. A few studies implicate the degradation products of corticosteroids; others point to the high protein affinity of the succinate molecule, which in turn presents the steroid as an antigen.1 Mast cells throughout the heart and mediators released by them are thought to depress cardiac function.3 The cardiac mast cells release renin, which activates the cardiac renin angiotensin system to form angiotensin II. Angiotensin II activates angiotensin1 receptors on nerve endings and promotes local noradrenalin secretion.3 A catecholamine surge might be responsible for ventricular systolic dysfunction.4,5 Stress-induced cardiomyopathy can manifest itself as global hypokinesia, different from typical apical ballooning.6 The mild elevation in our patients troponin levels was attributed to acute cardiac strain from anaphylaxis. The reversion of LV dysfunction to baseline within 5 days illustrates the reversible nature of this cardiomyopathy.