Immune Checkpoint Inhibitor-Related Pulmonary Toxicity: A Comprehensive Review, Part II.

The development of immune checkpoint inhibitors (ICIs) has changed the treatment paradigm for cancer. The ICIs nivolumab, pembrolizumab, and cemiplimab target programmed cell death protein 1, and durvalumab, avelumab, and atezolizumab target programmed death ligand 1. Ipilimumab targets cytotoxic T lymphocyte-associated antigen-4. Used as monotherapy or in combination, they have shown remarkable efficacy in melanoma, lung cancer, and many other solid tumors, and indications continue to evolve. These checkpoint inhibitors are typically well tolerated; however, they may cause immune-mediated adverse effects, resulting in inflammation of any organ system. Pulmonary toxicity is vital to recognize, and it can be more challenging to diagnose in patients with lung cancer, given the nature of the disease course and treatment.

Iatrogenic esophageal and tracheal perforation with tracheoesophageal fistula following emergency intubation.

Iatrogenic tracheoesophageal fistula (TEF) through direct penetration of esophageal and tracheal walls is exceedingly rare. Body tissues sealing around the tube may result in delayed development of respiratory complications and diagnosis. Pneumomediastinum and pneumothorax may be absent. Maintaining the airway through TEF until tracheostomy resulted in a satisfactory outcome.

Immune Checkpoint Inhibitor-Related Pulmonary Toxicity: Focus on Nivolumab.

The development of checkpoint inhibitors has changed the treatment paradigm for cancer. Checkpoint inhibitors nivolumab, pembrolizumab, and cemiplimab target programmed death-1 (PD-1), whereas durvalumab, avelumab, and atezolizumab target PD-ligand 1. Ipilimumab targets cytotoxic T lymphocyte-associated antigen 4. Used as monotherapy or in combination, these inhibitors have shown remarkable efficacy in melanoma, lung cancer, urothelial cancer, and many other solid tumors, and indications are continuing to evolve. Checkpoint inhibitors are well tolerated when compared with traditional chemotherapy. The major adverse effect profiles are idiosyncratic immune-mediated toxicities resulting from the abnormal activation of autoreactive T cells, which can lead to inflammation in any organ system. The most commonly affected organs are bowel, lung, skin, and endocrine. Pulmonary toxicity is important to recognize, and it can be more challenging to diagnose in lung cancer patients, given the nature of the disease course and treatment. This review article focuses on all of the pulmonary adverse effects of a single PD-1 inhibitor (nivolumab) that have been described in the literature. These complications include dyspnea, pneumonitis, pleural effusion, pulmonary sarcoidosis, pulmonary tuberculosis, acute fibrinous organizing pneumonia, organizing pneumonia, eosinophilic pneumonia, adult respiratory distress syndrome, and lung cavitation. Clinicians must be aware of these toxicities and mindful when prescribing these medications in patients with known lung dysfunction due to chronic lung diseases or lung cancer.

Vitamin B12 Deficiency: A Rare Cause of Excessive Daytime Sleepiness.

None: Excessive daytime sleepiness (EDS) is one of the leading reasons that patients present to sleep clinics. Approximately 10% to 14% of the adults report that excessive sleepiness interferes with their daily lives. Common causes of EDS include obstructive sleep apnea, sleep deprivation, circadian rhythm disorders, medication effects, psychiatric conditions especially depression, and primary hypersomnia such as narcolepsy or central idiopathic hypersomnia. Vitamin B12 deficiency is a rare cause of EDS. We are presenting a case of severe vitamin B12 deficiency as an unusual and rare cause of hypersomnia. CITATION: Khawaja I, Yingling K, Bukamur H, Abusnina W. Vitamin B12 deficiency: a rare cause of excessive daytime sleepiness. J Clin Sleep Med. 2019;15(9):1365-1367.

Nivolumab-induced Third Degree Atrioventricular Block in a Patient with Stage IV Squamous Cell Lung Carcinoma.

In the era of immune checkpoint inhibitors, pulmonary and critical care physicians frequently encounter patients taking these medications, usually after being admitted to the intensive care unit with life-threatening complications. These complications are rare, present with nonspecific and vague symptoms, which may delay the treatment and have high mortality. We report a very rare complication, with only two previously reported cases of a severe and potentially fatal side effect associated with anti-programmed cell death protein 1 (PD-1) immunotherapy with nivolumab. We provide a literature review to increase physicians' awareness about this rare side effect and suggest some recommendations derived from our experience.

Non-small Cell Lung Cancer with Squamous Features Metastatic to a Colonic Polyp: A Case Report of a Very Rare Presentation.

Among all malignant diseases, lung cancer is the most common on a worldwide basis. It is usually discovered incidentally on lung imaging studies or because of symptoms. The diagnosis is confirmed on biopsy material from the primary malignancy or from metastatic deposits. This is a report of metastatic lung cancer with squamous features discovered in an endoscopically removed colonic polyp. To our knowledge, there are only two prior reports of lung cancer being diagnosed in colonic polyps. We could not find any reports of lung cancer with squamous features metastatic to a colon polyp. In this case, the carcinoma was found in a polyp removed from a patient who presented with severe anemia and melena.

A series of two cases of rare tumors: Solitary fibrous tumor of the pleura.

Solitary fibrous tumors of the pleura (SFTPs) are rare neoplasms of mesenchymal origin most commonly arising in the pleura and have a benign biological behavior in the majority of cases. Most patients with SFTPs are asymptomatic; however, symptoms are mostly related to the mass effect within the thoracic cavity. Chest computed tomography (CT) scanning is the radiographic test of choice, but findings lack specificity. Surgical resection is the treatment of choice for most patients. Long-term survival after resection of benign SFTPs is excellent. In this case series, we present two females, one presented with shortness of breath (SOB) and nonproductive cough and the other one was referred because of abnormal x-ray findings. The histological as well as the immunohistochemical examination revealed the mass to be a solitary fibrous tumor of the pleura.

Pulmonary alveolar microlithiasis diagnosed with radiography, CT, and bone scintigraphy.

Pulmonary alveolar microlithiasis is rare disease characterized by accumulation of calcium phosphate microlithis in the alveoli. The pathogenesis relates to mutation in the gene SLC34A2 (solute carrier family 34 member 2) located on chromosome 4p15.2, which produces a defective sodium-phosphate cotransporter in alveolar epithelial type-2 cells, making these cells unable to clear phosphorus released during recycling of surfactant [1].

Pneumocystis Jirovecii (carinii) pneumonia causing lung cystic lesions and pneumomediastinum in non-HIV infected patient.

Pneumomediastinum is a rare, potentially life-threatening complication of PCP that occurs in HIV-positive and HIV-negative patients. We are presenting a rare case pneumomediastinum caused by pneumocystis Jirovecii pneumonia in a HIV-negative patient with history of diffuse B-cell lymphoma on R CHOP chemotherapy. What is unique about our case is that the patient developed pneumomediastinum while in the hospital, on atovaquone that improved when switched to clindamycin and primaquine with improvement in her respiratory status. Another interesting point is that diagnosis was entertained due to the characteristic CT scan finding of ground glass opacities with cystic lung lesions and pneumomediastinum in an immunocompromised patient who was started on empirical treatment for PCP. The diagnosis was eventually confirmed with PCP PCR.

Urinothorax Caused by Xanthogranulomatous Pyelonephritis.

Xanthogranulomatous pyelonephritis is a rare form of chronic pyelonephritis that generally afflicts middle-aged women with a history of recurrent urinary tract infections. Its pathogenesis generally involves calculus obstructive uropathy and its histopathology is characterized by replacement of the renal parenchyma with lipid filled macrophages. This often manifests as an enlarged, nonfunctioning kidney that may be complicated by abscess or fistula. This case details the first reported case of xanthogranulomatous pyelonephritis complicated by urinothorax, which resolved on follow-up chest X-ray after robot-assisted nephrectomy.

Atypical rapid onset Scleroderma Renal Crisis (SRC) complicated with diffuse alveolar hemorrhage and pleuro-pericardial effusions in a patient with recently diagnosed breast cancer and a positive anti-RNA polymerase III Ab.: A case report.

Scleroderma associated Pulmonary-Renal Syndrome is a rare but severe complication with a poor prognosis and high mortality. A high index of suspicion is needed for early recognition of this potential complication in patients with systemic sclerosis and institution of appropriate treatment. With more data showing an increased association between scleroderma and malignancy, a heightened vigilance should also be exercised in patients with malignancy and scleroderma-like presentation. We report of a case rapid onset systemic sclerosis complicated by acute renal failure and diffuse alveolar hemorrhage in a woman with stage IIB right breast cancer and elevated RNA Polymerase III IgG Ab. To our knowledge, this the first case of a patient with breast cancer associated with systemic sclerosis and pulmonary-renal syndrome.

The role and safety of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis and management of infected bronchogenic mediastinal cysts in adults.

Bronchogenic and other duplication cysts are congenital abnormalities that can present at any age including adulthood years. They are usually asymptomatic and discovered incidentally on radiological imaging of the chest. They are commonly treated by surgical resection. Recently, endobronchial ultrasound has been used to assist in diagnosis when radiologic imaging is not definitive. Endobronchial ultrasound has been used rarely to drain infected cysts, a rare complication of the bronchogenic cyst. We present a unique case of an infected large bronchogenic cyst treated with endobronchial ultrasound drainage combined with conservative medical therapy. We also review the scarce available literature describing such an approach and its potential complications and add recommendations based on our experience in managing these anomalies.

Candida krusei Empyema Thoracis: A Community-Acquired Infection Requiring a High Index of Suspicion.

Empyema thoracis is a serious condition characterized by the accumulation of purulent fluid in the pleural cavity, typically following a pneumonia, subdiaphragmatic abscess, or esophageal rupture. Fungal empyema thoracis is a rare form of this condition with especially high mortality, in which the most frequently isolated fungus is Candida spp. This article presents a 74-year-old female with Candida krusei pneumonia and a complicated hospital course, initially presenting with nausea, vomiting, and dysphagia. She was initially suspected to have community-acquired pneumonia and was started on azithromycin and ceftriaxone. Worsening respiratory function led to the diagnosis of hydropneumothorax. Pleural fluid and an independent sample of pus and pleural tissue grew Candida krusei, giving the diagnosis of fungal empyema. With further respiratory deterioration, the patient was intubated and switched to piperacillin/tazobactam and micafungin. Decortication with extensive pleural peel and removal of foul-smelling pus and food particles within the chest was performed. This further lead to confirmation of esophageal perforation, and she was started on voriconazole and meropenem. After developing septic shock, the patient was managed with phenylephrine and vasopressin. Finally, after improving she was weaned off pressors and extubated, followed by an esophagogastroduodenoscopy (EDG) with pneumatic balloon dilation and WallFlex stent placement. This patient's case demonstrated an example of empyema thoracis, which required a high index of suspicion since the presentation was with a community-acquired infection. Candida empyema thoracis may be a complication of operation, gastroesophageal fistula, and spontaneous esophageal rupture. On the other hand, the course of this patient's hospital stay progressed from esophageal perforation to Candida krusei pneumonia, empyema, and pneumothorax. Thus, community-acquired fungal empyema should be considered in patients with respiratory symptoms and suspected esophageal perforation; nevertheless, after a diagnosis of fungal empyema, esophageal perforation should also be ruled out in addition to other causes like pneumonia, subphrenic abscess, and hematogenous spread. Improved communication between clinicians and microbiologists can lead to early diagnosis and a reduction in the morbidity and mortality of this condition.

Chemotherapy-related acute respiratory distress syndrome in germ cell tumors: a literature review.

Germ cell tumors (GCTs) are one of the more curable solid cancers in men. Approximately 8500 men are diagnosed with GCTs in the USA. The majority of patients survive due to the availability of effective treatment. Fewer than 400 men are estimated to die from their disease. Among those, there is a subset of patients with metastatic GCTs receiving chemotherapy who rapidly develop progressive respiratory failure and die during the early phase of their treatment course. In this review, we searched the available literature for reported cases and retrospective series of chemotherapy-associated acute respiratory distress syndrome in GCTs. We aim to determine whether a different approach from current treatment guidelines could be considered to prevent this catastrophic chemotherapy-related event.