Review of T Helper 2-Type Inflammatory Diseases Following Immune Checkpoint Inhibitor Treatment.

Immune checkpoints are mechanisms that allow cancer cells to evade immune surveillance and avoid destruction by the body's immune system. Tumor cells exploit immune checkpoint proteins to inhibit T cell activation, thus enhancing their resistance to immune attacks. Immune checkpoint inhibitors, like nivolumab, work by reactivating these suppressed T cells to target cancer cells. However, this reactivation can disrupt immune balance and cause immune-related adverse events. This report presents a rare case of prurigo nodularis that developed six months after administering nivolumab for lung adenocarcinoma. While immune-related adverse events are commonly linked to T helper-1- or T helper-17-type inflammations, T helper-2-type inflammatory reactions, as observed in our case, are unusual. The PD-1-PD-L1 pathway is typically associated with T helper-1 and 17 responses, whereas the PD-1-PD-L2 pathway is linked to T helper-2 responses. Inhibition of PD-1 can enhance PD-L1 functions, potentially shifting the immune response towards T helper-1 and 17 types, but it may also influence T helper-2-type inflammation. This study reviews T helper-2-type inflammatory diseases emerging from immune checkpoint inhibitor treatment, highlighting the novelty of our findings.

Successful erlotinib rechallenge after both gefitinib- and erlotinib-induced interstitial lung diseases.

Epidermal growth factor receptor tyrosine kinase inhibitors, gefitnib and erlotinib, are effective for advanced nonsmall-cell lung cancer with epidermal growth factor receptor gene mutation. However, interstitial lung disease induced by these drugs is sometimes fatal, and discontinuation of the medication is the principle approach once this occurs. There are, however, some reports of cases in which rechallenge of gefitinib or erlotinib was successful, and it remains unclear when or how rechallenge should be attempted. We report the first successful case of erlotinib rechallenge after both gefitinib- and erlotinib-induced interstitial lung diseases. Our case suggests that, in interstitial lung disease induced by an epidermal growth factor receptor tyrosine kinase inhibitor, rechallenge with concurrent glucocorticoid administration and gradual increase of dosage could be a clinical option if imaging does not show a diffuse alveolar damage pattern, and if no alternative therapy is available.

A case of syncope induced in the supine position.

We experienced a reproducible supine syncope followed by upper abdominal pain. A 66-year-old man was transferred to our hospital after an episode of syncope during sleep. He had a history of acute pancreatitis, diabetes, hypertension, and dyslipidemia, but no history of presyncopal attack. One night, his wife noticed he was snoring abnormally in bed, and he did not respond to her voice until after she tried many times to wake him. The same attack was reproduced three times in the same situation. One of the attacks was recorded under a continuous ECG and radial tonometry. In this case, a presyncopal attack and a sense of ill-feeling were provoked by the patient lying in a prolonged supine position. He was eventually diagnosed as metastatic liver tumor 5 months after the first attack. Because few cases of syncopal attack have been reported in the supine position, its underlying mechanisms deserve consideration.

[Case of minocycline-induced acute eosinophilic pneumonia accompanied by marked neutrophilia in the peripheral blood].

A 37-year-old woman presenting with high fever, dry cough and progressive dyspnea was admitted to our hospital. She took 100 mg of minocycline hydrochloride orally because of a common cold one day prior to her admission. A chest CT scan showed diffuse ground-glass opacities with interlobular septal thickening and thickening of bronchovascular bundles. An analysis of bronchoalveolar lavage fluid showed an increase in both the total cell counts and the number of eosinophils. The result of a lymphocyte stimulation test performed on peripheral blood lymphocytes was positive for minocycline. This patient had a history of pneumonia with similar clinical and radiographic findings, which had developed while receiving minocycline. As a result, we made a diagnosis of minocycline-induced acute eosinophilic pneumonia. Her symptoms and radiographic findings improved within a few days after admission. Corticosteroid therapy was effective. A marked increase of peripheral blood neutrophils were noted on admission. The serum levels of IL-8 and G-CSF increased at the early phase of the disease, but thereafter decreased in association with neutrophils, thus suggesting the contribution of these cytokines to the early phase neutrophilia in this case.

[Our clinical experiences of amrubicin hydrochloride monotherapy in extensive-disease small cell lung cancer].

We retrospectively investigated monotherapy of amrubicin hydrochloride in patients with extensive-disease small cell lung cancer (ED-SCLC) and assessed its efficacy and safety. Twenty-two patients were enrolled. The response rate of total, previously untreated, sensitive relapsed, and refractory relapsed cases were 59%, 50%, 100% and 46%, respectively. As for the dose of amrubicin, the response rates of 30 mg/m(2), 35 mg/m(2), 40 mg/m(2), and 45 mg/m(2) were 50%, 33%, 69% and 100%, respectively. Severe myelosuppression was frequently observed as the adverse event, but significant differences among several dosages were not recognized. Median survival time was 230 days in relapsed cases. Monotherapy of amrubicin might be effective in ED-SCLC not only as first-line but also as second-line treatment in relapsed cases. The recommended dose was above 40 mg/m(2) because of its higher response rate.

[Case of small cell lung cancer complicated with diabetes insipidus and Cushing syndrome due to ectopic adrenocorticotropic hormone secretion].

A 54-year-old woman had been given a diagnosis with scleroderma and interstitial pneumonia due to scleroderma when she was 45 years old. Thirst, with resulting polydipsia and polyuria (about 7 liters/day) were present since May, 2004, and bloody sputum appeared in June of 2004. The patient was admitted to our hospital. Chest CT examination showed multiple nodules in the bilateral lower lung field and multiple movable subcutaneous nodules on the abdomen. Small-cell lung cancer (metastases in the pituitary, subcutaneous tissue, and lungs) was diagnosed by transbronchial lung biopsy and subcutaneous nodule biopsy of the abdomen. The final diagnosis was diabetes insipidus and Cushing syndrome. Chemotherapy was done with CDDP and VP-16, which resulted in reduction of the tumor and improvement in endocrinological findings. Nevertheless, chemotherapy could not be continued because of infected bullae. The patient died of deteriorating illness after 91 sickness days. We concluded that this case was Cushing syndrome caused by ectopic adrenocorticotropic hormone-producing small cell lung cancer, and that it presented with diabetes insipidus because of pituitary metastasis. Therefore, when drastic endocrinological changes are found, it is important to examine for cancer, including lung cancer, as soon as possible.

[Case of myeloperoxidase-antineutrophil cytoplasmic antibody-associated pulmonary alveolar hemorrhage caused by propylthiouracil].

We reported the case of pulmonary alveolar hemorrhage caused by propylthiouracil (PTU) with severe respiratory failure and anemia, who improved with PTU discontinuance and steroid therapy. A 35-year-old woman presented with pyrexia, shortness of breath, and arthralgia. Her chest radiograph and CT showed diffuse ground-glass opacities, and her arterial blood gas analysis revealed severe respiratory failure. Laboratory results included a hemoglobin level of 5.2 g/dl, and a myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) level of 203 EU (normal range <9.0 EU). As bronchoalveolar lavage (BAL) fluid showed fresh blood-like fluid containing hemosiderin-laden macrophages, pulmonary alveolar hemorrhage was diagnosed. Since she had been taking PTU for 4 years, PTU was immediately discontinued. Steroid pulse therapy was performed, followed by oral prednisolone 30 mg per day, and her symptoms and chest radiograph findings rapidly improved. Based on the time-course changes, MPO-ANCA may have been involved in the development of pulmonary alveolar hemorrhage.

[A case of juvenile lung cancer with suspected progeroid syndrome and mental retardation].

A 28-year old woman developed juvenile lung cancer. Cockayne syndrome, one of the progeroid syndromes, was suspected because of mental retardation, renal disfunction, photosensitivity, and the characteristic physical appearance such as low set ears, microcephaly, senile face, short stature, and cachectic habitus. We tried chemotherapy with gefitinib and docetaxel, but they were ineffective and she was found to have multiple extraocular muscle metastasis. CT scan showed carcinomatous lymphangiosis findings, her respiratory condition worsened gradually and she died about 7 months after the diagnosis of lung cancer. Some progeroid syndromes are known for their high incidence of juvenile cancres, and the responsible genes are gradually coming to light. However, concerning the relationship between lung cancer and progeroid syndromes, our investigations revealed only one case report of Werner syndrome, one of the progeroid syndromes, accompanied by lung cancer. Progeroid syndromes with lung cancer are thought to be very rare. We expect collection of data on cases like the present case will help to clarify the mechanism of aging and carcinogenesis.

[Lung cancer in patients with chronic renal failure].

We evaluated the clinical characteristics of 18 patients with lung cancer complicated by chronic renal failure at our department between November 1983 and September 2004. The 18 patients consisted of 17 men and 1 woman aged 60-81 years (mean, 70 years). Fifteen patients had non-small cell lung cancer (NSCLC), and 3 had small cell lung cancer (SCLC). The stage of NSCLC was I in 7 patients, II in 2, and IV in 6. The stage of SCLC was localized disease (LD) in 2 patients and extensive disease (ED) in 1. The lung cancer was often detected due to symptoms such as cough and bloody sputum. Concerning treatment, surgery was mainly selected in patients with stage I NSCLC, but radiotherapy alone was often performed due to the wishes of patients in those with stage III or IV NSCLC. The outcome of patients who underwent chemotherapy with stage III or IV NSCLC was similar to patients with lung cancer not complicated by renal failure. In lung cancer patients with chronic renal failure, new hepatic excretion type anti-cancer drugs can be also used, but further evaluation is necessary.