Clinical application of18F-FUdR in glioma patients — PET study of nucleic acid metabolism

Summary Positron emission tomography was used to investigate the metabolism of nucleic acids by¹⁸F-fluoro-2-deoxyuridine (¹⁸F-FUdR) in 22 patients with gliomas. Sixteen cases of high grade glioma clearly demonstrated a region of high activity with a differential absorption rate (DAR) of 0.64 ± 0.34. Six cases of low grade glioma failed to reveal a positive image of the tumor and the DAR in tumor was 0.21 ± 0.042 (p < 0.01). This PET-¹⁸F-FUdR study succeeded in differentiating high and low grade gliomas from the view point of nucleic acid metabolism.     

Giant testicular tumor: a case report

We report a case of giant testicular tumor. A 30-year-old man visited our department complaining of a painless swelling of the right scrotal contents. In chest X-ray and abdominal computerized tomography (CT) there were no abnormal findings. Serum alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase levels were normal. Right high orchiectomy was performed. The size of the removed specimen was 13.5 x 8.5 x 7.5 cm, and weight 530 g. The pathological diagnosis was immature teratoma. The patient has received no further therapy. There has been no recurrence for 7 months postoperatively.     

Intra-arterial chemotherapy via reservoir system for advanced bladder cancer and prostate cancer

A clinical study was performed on the efficacy of intra-arterial chemotherapy using a reservoir system for advanced urological malignancies. The reservoir system was indwelted in the femoral subcutaneous layer by Seldinger's method. Fifteen cases of inoperable complicated advanced bladder cancer and 10 cases of postoperative local recurrent bladder cancer were administered intra-arterial chemotherapy using a reservoir system. Then, 23 cases of local relapsed prostate cancer and two cases of endpocrine-resistant prostate cancer were administered the chemotherapy. The administered anti-cancerous agents were methotraxate, cis-platinum and adriamycin, then 5-FU or carboplatin was administered as maintenance therapy. The mean number of courses of chemotherapy was six for bladder cancer and four for prostate cancer. During stabilization of the local lesion, no distant deterioration was recognized. The overall clinical efficacy was a positive response (PR) and no change (NC): for 18 and 7 cases of bladder cancer, and 11 and 14 cases of prostate cancer, respectively. The median duration of stabilization was 23 months for bladder cancer and 12 months for prostate cancer. The adverse effects were fever than those with systemic chemotherapy.     

Malignant fibrous histiocytoma. Proliferative compartment and heterogeneity of "histiocytic" cells.

To elucidate the precise origin and characteristics of the proliferating cells in malignant fibrous histiocytoma (MFH), the authors analyzed 33 MFH tumors, using immunohistochemical techniques with a panel of 12 antibodies. All three types of MFH cells (spindle cells, polygonal cells, and bizarre giant cells) stained positively for mesenchymal antigens (FU3 and vimentin) but did not stain for macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not represent true histiocytes, although they may be mesenchymal-derived cells behaving as "facultative histiocytes" with superficial resemblance to actual histiocytes. Normal histiocytes in the stroma tested positive for macrophage/histiocyte antigens; the most common cells were HAM 56-positive cells constituting 30-80% of nonneoplastic stromal cells, followed by those positive for CD68 (10-50%), Mac 387 (less than 2%), and S-100 protein (less than 1%). Our results indicate the presence of heterogeneity of "histiocytic" cells in MFH. Proliferating-cell nuclear antigen (PCNA) was expressed not only in the spindle and polygonal MFH cells but also in the bizarre giant cells. These findings suggest that all three types of MFH cells participate in the proliferative compartment of MFH. Uneven PCNA staining of the irregular nuclear segments of the bizarre giant cells may result in abnormal DNA synthesis, possibly contributing to the marked diversity of nuclear morphology in MFH. Touton-type and osteoclast-like giant cells did not stain for PCNA but stained positively for histiocytic markers. Therefore, these giant cells may lack proliferative activity and probably result from normal histiocytes fusing together.     

A case of primary gastric small cell carcinoma with a rare pattern of lymph node metastasis

We report a very rare case of primary gastric small cell carcinoma (GSCC) that was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an elevated tumor with a central ulceration in the middle stomach. The patient underwent a distal gastrectomy with lymph node dissection. The pathological examination showed two separated lesions of the stomach, which contained the components of primary GSCC and primary gastric tubular adenocarcinoma. Immunohistochemical (IHC) examination demonstrated that the tumor cells in the small cell carcinoma stained positive for synaptophysin, chromogranin A, and neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells independently metastasized to each regional lymph node. Further studies on the biological behavior of individual tumors may allow the development of new treatment strategies for GSCC.     

Potentially Life-threatening Arrhythmia Triggered by an Excessive Consumption of Dried Sweet Potato “Hoshi-Imo”

We herein report two cases of potentially life-threatening arrhythmia due to hyperkalemia triggered by the excessive consumption of “Hoshi-Imo” (dried sweet potato). Both patients with chronic renal disease on renin-angiotensin-aldosterone system inhibitors presented at the emergency room with non-specific symptoms. Electrocardiograms revealed potentially life-threatening arrhythmia due to hyperkalemia in both cases: sinus arrest with a ventricular escape rhythm, tall and peaked T waves; and a widened QRS complex in a nearly sine-wave configuration without discernible P wave. Both patients fully recovered after intensive care for hyperkalemia. Physicians should recognize the excessive consumption of “Hoshi-Imo” may lead to the development of life-threatening arrhythmia, especially in patients with risk factors for hyperkalemia.     

PAX5 alterations in an infant case of KMT2A‐rearranged leukemia with lineage switch

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A‐rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A‐MLLT3‐rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A‐MLLT3‐rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre‐post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia.     

Association Between the Occurrence and Spectrum of Immune-Related Adverse Events and Efficacy of Pembrolizumab in Asian Patients With Advanced Urothelial Cancer: Multicenter Retrospective Analyses and Systematic Literature Review

An association between the development of overall or specific immune-related adverse events (irAEs) and outcomes of immune checkpoint inhibitors has recently been suggested. To address this emerging association in patients with urothelial cancer receiving pembrolizumab, we conducted a multicenter retrospective analysis, which is the first and largest in an Asian cohort as well as a systematic literature review. We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab as second- or later-line treatment between January 2018 and March 2019. irAEs were categorized by the involved organs and graded using Common Terminology Criteria for Adverse Events version 5.0. Associations between irAEs and pembrolizumab efficacy, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. In our review of the literature, 28 studies, including 9 studies involving patients with urothelial cancer and 19 studies reporting the association between outcomes and spectrum of irAEs, were analyzed. Patients with irAEs had significantly higher ORR (52% vs. 16%, P < .01), longer PFS (11.0 months vs. 3.6 months, P < .01) and OS (median not reached vs. 13.1 months, P = .12) than in patients without irAEs. Endocrine (P = .02), pneumological (P = .06), and other (gastrointestinal, hematological, hepatic) (P = .04) irAEs were associated with increased ORR, whereas skin irAEs were not. Endocrine irAEs (P = .04) was associated with improved OS, whereas pneumological and skin irAEs were not. The association between the occurrence of irAEs and clinical efficacy of immune checkpoint inhibitors was consistently supported by the multiple studies we reviewed. The association between clinical outcomes and the spectrum of organs/systems affected by irAEs seems to be inconsistent and could be dependent on tumor type. irAEs were associated with a higher ORR and better survival of patients with advanced urothelial cancer treated with pembrolizumab.     

Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension

Background

A pulmonary hypertensive crisis (PHC) can be a life-threatening condition. We established a PHC model by exposing rats with monocrotaline (MCT)-induced pulmonary hypertension to acute hypoxia, and investigated the effects of vasopressin, phenylephrine, and norepinephrine on the PHC.