Refractory metabolic acidosis in small cell cancer of the lung.

To the Editor: Lactic acidosis has been often documented in patients with hematological malignancies such as leukemia and lymphoma, but its occurrence in solid tumors has been rarely reported. (1-5) We report a patient with small cell carcinoma of the lung with extensive liver metastases who had fatal high anion gap metabolic acidosis secondary to lactic acid. A 64-year-old male was admitted to the hospital because of abdominal pain in the right upper quadrant radiating to his shoulder. The patient was not taking any medication and had no significant past medical history or surgical history. He was a chronic smoker, smoking 2 packs of cigarettes a day for more that 30 years. At admission his blood work showed a complete blood count and basic metabolic panel to be within normal limits: albumin 3.7 g/dL, total protein 6.6 g/dL, total bilirubin 2.3 mg/dL, direct bilirubin 1.7 mg/dL, alkaline phosphatase 210 IU/L, aspartate aminotransferase 247 IU/L, alanine aminotransferase 253 IU/L, prothrombin time 11.7 seconds, activated partial thromboplastin time 26.1 second, international normalized ratio 1.0. Hepatitis panel was negative. Abdominal sonogram was done and showed multiple hypoechoic nodules that were nonconclusive and a CT scan of the abdomen with contrast was recommended. A computed tomography of the thorax, abdomen and pelvis with oral and IV contrast was performed which showed subtle areas of nonspecific heterogeneity in the liver and a 1.5 cm inferior right lower lung mass. Due to the discrepancy between the abdominal sonogram and computed tomography, an MRI with contrast of the abdomen was performed which showed extensive nodularity throughout the liver. On the fifth day of admission, blood work revealed a bicarbonate of 10 mmol/L. Arterial blood gas on room air (pH 7.18 PC[O.sub.2] 24 mm Hg, P[O.sub.2] 101 mm Hg, bicarbonate 9.0 mmol/L with oxygen saturation of 96.0%) showed metabolic acidosis with an anion gap of 24 and a simultaneous serum lactic acid of 15.8. A bicarbonate drip was begun and nephrology was consulted. The following day, the patient underwent dialysis as recommended by nephrology for refractory metabolic acidosis and was placed on daily dialysis because of the intractable metabolic acidosis. CT-guided liver biopsy revealed metastatic small cell carcinoma of the lung. The patient expired a couple of days after definitive diagnosis, before chemotherapy could be administered.

The pathogenesis of lactic acidosis in malignancy is not clear. Anaerobic metabolism, direct lactate production by the neoplastic cells, and metastatic replacement of the hepatic parenchyma have been proposed as possible mechanisms of tumor-induced lactic acidosis. (5) An unexplained metabolic acidosis in a patient with underlying malignancy should prompt the physician to look for lactic acidosis. In patients with extensive hepatic metastases, one should be aware of the possibility of developing fatal lactic acidosis. Prompt treatment of the underlying malignancy can resolve the acidosis and prolong the survival. (2-5)

Betancourt Manuel, MD

Vemuri Suresh, MD

Eskaros Saphwat, MD

Wyckoff Heights Medical Center

Affiliate Weill Medical College of Cornell University

Brooklyn, NY

References

1. Sillos EM, Shenep JL, Burghen GA, et al. Lactic acidosis: a metabolic complication of hematologic malignancies. Cancer 2001;92:2237-2246.

2. Rice K, Schwartz SH. Lactic acidosis with small cell carcinoma: rapid response to chemotherapy. Am J Med 1985;79:501-503.

3. Spechler SJ, Esposito AL, Koff RS, et al. Lactic acidosis in oat cell carcinoma with extensive hepatic metastases. Arch Intern Med 1978;138:1663-1664.

4. Sheriff DS. Lactic acidosis and small cell carcinoma of the lung. Postgrad Med J 1986;62:297-298.

5. Fujimura M, Shirasaki H, Kasahara K, et al. Small cell lung cancer accompanied by lactic acidosis and syndrome of inappropriate secretion of antidiuretic hormone. Lung Cancer 1998;22:251-254.