Ramsay-Hunt syndrome and subsequent sensory neuropathy as potential immune-related adverse events of nivolumab: a case report.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor (ICI) and is used for the treatment of advanced non-small cell lung cancer (NSCLC). Several immune-mediated neurological adverse events associated with ICIs have been reported to date, such as Guillain-Barré syndrome. Nivolumab-associated neurological adverse events can vary, and their etiology remains unclear. CASE PRESENTATION: A 72-year-old man with NSCLC was treated with nivolumab as a second-line therapy. After 13 rounds of nivolumab therapy, he presented with Ramsay-Hunt syndrome (RHS) followed by acute ataxic sensory neuropathy. Antiviral therapy for Varicella-Zoster virus and prednisolone resulted in partial improvement of RHS, while almost no recovery was observed in the sensory neuropathy. However, the sensory ataxia significantly improved after intravenous immunoglobulin (IVIg) therapy, and interestingly, the facial palsy associated with RHS also improved. The neurological manifestations, nerve conduction study result, and imaging findings supported that dorsal root ganglia were the primary lesion site of acute ataxic sensory neuropathy. CONCLUSIONS: Our case presented with the comorbidity of RHS and subsequent ataxic sensory neuropathy after nivolumab therapy to whom IVIg was effective. Our case suggested the wide variability of possible neurological symptoms, and the potential usefulness of IVIg to sensory ataxic neuropathy, seen in cancer patients with ICI treatment.

Pneumatosis intestinalis induced by osimertinib in a patient with lung adenocarcinoma harbouring epidermal growth factor receptor gene mutation with simultaneously detected exon 19 deletion and T790 M point mutation: a case report.

BACKGROUND: Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. CASE PRESENTATION: A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. CONCLUSIONS: Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.

Gefitinib successfully administered in a lung cancer patient with leptomeningeal carcinomatosis after erlotinib-induced pneumatosis intestinalis.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare complication of chemotherapy, characterized by multiple gas accumulations within the bowel wall. CASE PRESENTATION: A 71-year-old woman with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma was admitted to our hospital because of reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was administered via a feeding tube. Her state of consciousness gradually improved, but she experienced diarrhea several times a day. After 3 weeks of erlotinib therapy, PI occurred. Erlotinib was discontinued and PI was resolved after treatment with conservative therapies. Erlotinib was re-administrated and PI occurred again. After improvement of erlotinib-induced PI, gefitinib was administered by a feeding tube and the patient did not experience PI or diarrhea. The patient survived 8 months from the diagnosis of LM. CONCLUSION: PI is one of the side effects of erlotinib, and consecutive therapies are useful for the treatment of PI. In this patient, gefitinib was successfully administered after erlotinib-induced PI.

The Efficacy and Safety of Long-term Pirfenidone Therapy in Patients with Idiopathic Pulmonary Fibrosis.

Objective Pirfenidone (PFD) is often used for years, but the efficacy and safety of long-term PFD therapy in patients with idiopathic pulmonary fibrosis (IPF) are not fully understood. Methods and Patients We retrospectively evaluated 46 patients with IPF who received PFD between February 2009 and August 2014. The efficacy and safety of PFD therapy were compared between 2 groups: long-term therapy patients who received PFD for over 1 year (group L, n=30, 65%) and short-term therapy patients who could not receive PFD for more than 1 year due to worsening of their condition or side effects (group S, n=16, 35%). Results The median age of the 46 patients was 70.5 years, and the median baseline % predicted forced vital capacity (%FVC) was 70.0%. The changes in the FVC in group L were -120 mL and -170 mL at 12 and 24 months after receiving PFD, respectively. The respective median survival times after PFD therapy in groups L and S were 1,612 days and 285 days (p<0.001). The patients in group L experienced a longer time free of acute exacerbation of IPF than those in group S (947 days vs. 145 days, p=0.001). A multivariate analysis revealed that %FVC <60% was a predictor of the inability to receive PFD for over 1 year (odds ratio 0.240, 95% confidence interval 0.060-0.958; p=0.043). With regard to grade 3-5 adverse events, only one patient exhibited grade 3 hyponatremia. Conclusion Long-term PFD therapy is effective, with few severe adverse events.

Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy in a patient with recurrent breast cancer: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare complication of advanced cancer, is histologically characterized by tumor embolisms and fibrocellular intimal proliferation of small pulmonary arteries and arterioles. PTTM usually has an extremely poor prognosis, and antemortem diagnosis is very difficult. CASE PRESENTATION: A 65-year-old woman with a 5-year history of clinical stage IIA (T2N0M0) invasive ductal carcinoma of the left breast was hospitalized for worsening shortness of breath, hemoptysis, and cough since 2 months. She had previously received neoadjuvant chemotherapy and left mastectomy. Because the cancer cells were positive for human epidermal growth factor receptor 2 (HER2), four cycles of trastuzumab had been administered as adjuvant chemotherapy. On admission, chest computed tomography (CT) showed peripheral consolidations in both the lower lobes and a mediastinal mass. Specimens obtained on video-assisted thoracoscopic surgical biopsy revealed tumor cell embolism, intimal fibrocellular proliferation of small arteries, fibrin thrombi, recanalization, and infarction in the left lower lobe, as well as metastasis to the mediastinal pleura. Immunohistochemical staining of the tumor cells revealed positivity for HER2, and a diagnosis of recurrent breast cancer with PTTM was made. Four cycles of trastuzumab resulted in rapid improvement of her symptoms and CT findings of peripheral consolidations and the mediastinal mass. CONCLUSION: An antemortem diagnosis of PTTM was made in a patient with HER2-positive recurrent breast cancer. Trastuzumab was effective for not only breast cancer but also PTTM.

Continuous Intravenous Morphine Infusion for Severe Dyspnea in Terminally Ill Interstitial Pneumonia Patients.

OBJECTIVE: The aims of this study were to evaluate the efficacy and safety of continuous morphine infusion for dyspnea in patients with acute exacerbation (AE) of end-stage interstitial pneumonia (IP). METHODS: We conducted a retrospective study. Based on the subjective clinical effectiveness ratings of "good," "moderate," "poor," or "unknown," the efficacy of continuous morphine infusion treatment was evaluated as defined as symptom relief that was "good" or "moderate." PATIENTS: This study included 22 consecutive opioid-naïve patients who received continuous morphine infusion in the palliative treatment of dyspnea resulting from AE-IP. RESULTS: Of 22 patients, nine achieved good dyspnea relief, eight had moderate relief, four had a poor response and one response was "unknown" within 24 hours of starting morphine infusion. Using an operational definition of dyspnea relief that was rated "good" or "moderate," the efficacy rate of morphine was 77% (n=17). There was a significant change in the respiratory rate (25 respirations per minute at baseline vs. 17 respirations per minute after 12 hours, p=0.02), however, none of the patients studied had fewer than eight respirations per minute. CONCLUSION: We conclude that continuous morphine infusion is an effective and safe therapy for severe dyspnea in terminal AE-IP patients without any serious adverse events.

Marked Improvement with Pirfenidone in a Patient with Idiopathic Pulmonary Fibrosis.

A man in his mid-60's with idiopathic pulmonary fibrosis and hepatitis B-related liver cirrhosis developed exertional dyspnea and a dry cough lasting for three months. High-resolution computed tomography (HRCT) showed increasing bilateral ground-glass opacity superimposed on the usual interstitial pneumonia pattern. Six months after starting pirfenidone therapy, the partial pressure of arterial oxygen at rest increased from 81 to 101 torr, the predicted forced vital capacity (FVC) value increased from 75% to 94% and the ground-glass opacity on HRCT improved. The FVC value was subsequently maintained near or above baseline for 43 months. We concluded that our patient was a super-responder to pirfenidone therapy.

Community-acquired pneumonia caused by macrolide-resistant Mycoplasma pneumoniae in adults.

We herein describe a case of community-acquired pneumonia caused by macrolide-resistant Mycoplasma pneumoniae (MRMP) in an adult who responded poorly to macrolide antibiotics, progressively deteriorated to acute respiratory failure and then responded effectively to a fluoroquinolone. In a series of 14 patients with M. pneumoniae pneumonia, 11 were infected with MRMP. In seven of the eight cases of MRMP initially treated with macrolides, the patients did not improve, and a marked improvement was observed only after the antibiotic regimen was modified to include fluoroquinolones or tetracyclines. Nationwide surveillance should provide important information regarding the prevalence and empirical treatment of MRMP infection in adults.

Long-term survival of a patient with extensive small cell carcinoma of unknown primary etiology complicated by nephrotic syndrome.

We experienced a case of nephrotic syndrome (membranous nephropathy) complicated by extensive small cell carcinoma of unknown primary etiology that was diagnosed based on the findings of bilateral cervical and mediastinal lymphadenopathy. A complete cancer response and proteinuria remission following radical chemoradiation therapy were documented. The status of a complete response and nephrosis remission persisted for more than three years. This is the first report to demonstrate the long-term survival of a patient with extensive small cell carcinoma of unknown primary etiology complicated by paraneoplastic nephrotic syndrome.

Miliary brain metastases in 2 cases with advanced non-small cell lung cancer harboring EGFR mutation during gefitinib treatment.

Here we report 2 cases of non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) gene mutation that developed miliary brain metastases characterized by dementia and disorientation during gefitinib therapy. One patient's therapy was switched from gefitinib to chemotherapy followed by whole brain radiotherapy (WBRT), which resulted in disease progression with coma. Gefitinib reinitiation improved the patient's symptoms. The other patient continued gefitinib during WBRT and achieved complete remission of the miliary metastases and lived 18 months longer. These results suggest that gefitinib concomitant with WBRT is an optional strategy for the treatment of patients with EGFR-mutated NSCLC with miliary metastases to prevent disease flare.

Selective cleavage of allyl and propargyl ethers to alcohols catalyzed by Ti(O-i-Pr)4/MXn/Mg.

[reaction: see text] Allyl and propargyl ethers were effectively deallylated or depropargylated to the parent alcohols via a C-O bond cleavage catalyzed by a low-valent titanium reagent (LVT), Ti(O-i-Pr)4/TMSCl/Mg or Ti(O-i-Pr)4/MgBr2/Mg, under mild reaction conditions. Differentiation between the allyl and propargyl ethers was achieved by the reaction in the presence of AcOEt as an additive. The reagent also catalyzed intra- and intermolecular cyclotrimerization reactions of alkynes to substituted benzenes.