TIM-3 expression induces resistance to PD-1 inhibitor in G-CSF-producing lung spindle cell carcinoma: A case report.

Lung spindle cell carcinoma is an aggressive subtype of pleomorphic lung cancer resistant to cytotoxic chemotherapy. Programmed cell death-1 (PD-1) inhibitors have been reported to have clinical effects in patients with spindle cell carcinoma; however, the resistance mechanism to PD-1 inhibitors is yet to be fully elucidated. Herein, we report the case of an 88-year-old man with G-CSF-producing spindle cell carcinoma who acquired resistance to PD-1/PD-ligand 1 (L1) inhibitor in an early setting after a remarkable response. A histopathological review of the resistant specimen revealed a low count of CD8+ T cells and a predominant presence of M2 and TIM-3+ macrophages, indicating the presence of an immunosuppressive microenvironment. Our findings suggest a novel resistance mechanism to PD-1/PD-L1 inhibitors in G-CSF-producing spindle cell carcinoma.

A case of isolated hypothalamitis with a literature review and a comparison with autoimmune hypophysitis.

Idiopathic hypothalamitis is a rare condition that can cause anterior pituitary dysfunction and central diabetes insipidus (CDI), occasionally accompanied by a disturbance of autonomic regulation known as hypothalamic syndrome. This condition has been described as a subtype of autoimmune (lymphocytic) hypophysitis; however, some cases of isolated hypothalamic involvement with no inflammatory lesions in either the pituitary gland or infundibulum have been reported. The detailed epidemiology and pathophysiology of isolated hypothalamitis have not been clarified. We herein report a case of a solitary hypothalamic lesion in a young woman who showed spontaneous development of CDI and panhypopituitarism accompanied by hyperphagia. The hypothalamic lesion increased from 11 × 7 to 17 × 7 mm over 16 months based on the sagittal slices of magnetic resonance imaging examinations. The negative results for anti-pituitary antibodies and anti-Rabphilin-3A antibodies suggested that upward extension of lymphocytic adenohypophysitis or infundibulo-neurohypophysitis was unlikely. Infectious disease, granulomatosis, Langerhans cell histiocytosis, vasculitis, and systemic neoplastic diseases were excluded by the findings of a laboratory investigation, cerebrospinal fluid examination, and imaging studies. To make a definitive diagnosis, we performed a ventriculoscopic biopsy of the hypothalamic lesion. Histology revealed an infiltration of nonspecific lymphoplasmacytes with no evidence of neoplasm, which was consistent with a diagnosis of idiopathic hypothalamitis. Subsequently, the patient was treated with methylprednisolone pulse therapy followed by oral prednisolone. The hypothalamic lesion improved and remained undetectable after withdrawal of the prednisolone, suggesting that the glucocorticoid treatment was effective for isolated hypothalamitis while the patient remains dependent on the replacement of multiple hormones.

RENAL FUNCTION AND PLASMA RENIN ACTIVITY AS POTENTIAL FACTORS CAUSING HYPERKALEMIA IN PATIENTS WITH THYROID CARCINOMA UNDERGOING THYROID HORMONE WITHDRAWAL FOR RADIOACTIVE IODINE THERAPY.

Objective: Hypothyroidism is not commonly considered a cause of hyperkalemia. We previously reported that hyperkalemia was observed mainly in elderly patients treated with renin-angiotensin-aldosterone system (RAS) inhibitors when levothyroxine treatment was withdrawn for the thyroidectomized patients with thyroid carcinoma to undergo radioactive iodine treatment. Here, we investigated whether acute hypothyroidism causes hyperkalemia in patients who were not treated with RAS inhibitors. We also investigated factors influencing potassium metabolism in hypothyroid patients. Methods: We conducted a single-center, prospective cohort study of 46 Japanese patients with thyroid carcinoma undergoing levothyroxine withdrawal prior to radioiodine therapy. All patients were normokalemic before levothyroxine withdrawal. Blood samples were analyzed 3 times: before, and at 3 and 4 weeks after levothyroxine withdrawal. We investigated factors that may be associated with the elevation of serum potassium levels from a euthyroid state to a hypothyroid state. Results: None of the patients developed symptomatic hyperkalemia. The mean serum potassium level was significantly higher at 4 weeks after levothyroxine withdrawal compared to baseline. The serum sodium levels, the estimated glomerular filtration rate (eGFR), and the plasma renin activity (PRA) decreased significantly as hypothyroidism advanced. In contrast, the plasma levels of adrenocorticotropic hormone, cortisol, aldosterone, and antidiuretic hormone were not changed, while serum thyroid hormone decreased. At 4 weeks after their levothyroxine withdrawal, the patients' serum potassium values were significantly correlated with the eGFR and the PRA. Conclusion: Acute hypothyroidism can cause a significant increase in the serum potassium level, which may be associated with a decreased eGFR and decreased circulating RAS. Abbreviations: ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ATPase = adenosine triphosphatase; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; K+ = potassium; Na+ = sodium; PRA = plasma renin activity; RAS = renin-angiotensin-aldosterone system; T4 = thyroxine; TSH = thyroid-stimulating hormone.

[Anesthetic Management of a Patient with Double Outlet Right Ventricle and Situs Inversus for Dilatation and Curettage of the Uterus].

A 30-year-old woman with a double outlet right ven- tricle and situs inversus was scheduled for dilatation and curettage of the uterus. We selected intravenous anesthesia which allowed spontaneous respiration, because of the short operation time and the low invasive surgery. We administered dexmedetomidine hydrochloride 1.1 µg · kg⁻¹ · hr⁻¹ and fentanyl (total amount 150 µg, three doses of 50 µg each) during operation. We accomplished anesthesia without appar- ent hemodynamic change or respiratory depression. We should select anesthetic method and anesthetic cautiously, considering patient's state.