Dysfunctional neobladder causing pulmonary toxicity after combination chemotherapy for lymphoma
Authors: Ramya Thota, Chirayu Shah, Travis Richardson, Mark Koury
Journal: American Journal of Hematology (2015)

A 75-year-old man with transitional cell bladder carcinoma status post cystoprostatectomy with neobladder creation from the sigmoid colon was diagnosed with Stage IVA diffuse large B-cell lymphoma involving the kidney in an evaluation for acute-on-chronic renal failure. A [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) scan at presentation revealed lymphadenopathy above and below the diaphragm. Bone marrow biopsy showed no lymphoma. Worsening renal failure from lymphadenopathy prompted treatment of his lymphoma. Due to Stage IV chronic kidney disease and cardiac ejection fraction of 38%, he received renal-dose adjusted cyclophosphamide, etoposide, vincristine, rituximab, and prednisone (R-CEOP). He received a total of 2 L IV fluid volume with his chemotherapy. His usual chronic in-dwelling Foley catheter was in place before, during, and after chemotherapy. On Day 5 of chemotherapy, he developed gross hemoptysis, hypoxia, and diffuse bilateral rales. Hemoglobin decreased from 10.8 g/dL to 6.3 g/dL with normal platelets and coagulation panel. Infection evaluation was negative. A CT scan demonstrated bilateral ground glass opacities. He was diagnosed with diffuse alveolar hemorrhage and treated with supportive care. He improved slowly with complete resolution of all symptoms prior to his second cycle of chemotherapy. However, on Day 2 of the second cycle, he developed chest pain with hemoptysis and hypoxia. A FDG PET-CT scan performed to evaluate response to treatment after second cycle showed bilateral ground glass opacities, interlobular septal thickening, architectural distortion, and bronchiectasis with associated increased FDG uptake (Fig. 1B). Given that these lung findings were not apparent on FDG PET-CT done prior to the treatment (Fig. 1A), they were highly suspicious for chemotherapy-induced pulmonary toxicity. Interestingly, despite having a Foley catheter in place, he had abnormal emptying of the neobladder as evidenced by retention of FDG avid urine in the neobladder (Fig. 1C,D). This finding was not evident on the initial FDG PET-CT. A: Axial CT done as a part of the initial diagnostic FDG PET-CT shows small bilateral pleural effusions and relatively normal lung parenchyma. B: Follow-up CT after second episode of hypoxia shows bilateral ground glass opacities, interlobular septal thickening, architectural distortion, and bronchiectasis with associated increased FDG uptake (not shown). C, D: PET-CT fusion and CT images demonstrate retained FDG containing urine in the neobladder despite the presence of a Foley catheter (arrow in D). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] This case highlights the importance of closely monitoring patients with neobladders and indwelling Foley catheters prior to, during, and after the administration of chemotherapy. Cyclophosphamide and etoposide are commonly used to treat hematological malignancies. Acute lung injury related to these agents is rare 1. The active metabolites of cyclophosphamide, such as acrolein, were reported to induce pulmonary toxicity 2. The pathogenesis of cyclophosphamide- or etoposide-induced lung injury is unclear, but a few case reports suggest favorable responses to corticosteroids 3-7. However, this patient received prednisone as part of the chemotherapy. Delayed clearance due to absorption of drugs or their metabolites from the urine via a dysfunctional neobladder may lead to serious toxicity. Additionally, in patients with improper emptying of the neobladder, continuous irrigation during chemotherapy administration has been recommended to prevent toxicity 8. In the appropriate clinical setting, patients should be screened for proper neobladder drainage prior to the initiation of chemotherapy.