Clinical role of serum programmed death ligand 1 in patients with hepatocellular carcinoma: Where does it come from?

Programmed death ligand 1 (PD-L1) is a key target for the treatment of several malignancies. The present study was conducted to clarify the role of serum PD-L1 in hepatocellular carcinoma (HCC). Serum PD-L1 (sPD-L1) was examined by an enzyme-linked immunosorbent assay in 153 patients with HCC who underwent curative hepatectomy at Kumamoto University in 2011–2016. The expression of PD-L1 in tissue (tPD-L1) was investigated by immunohistochemistry. The clinical roles of the PD-L1 expression in both serum and tissue were examined. The sPD-L1 was significantly elevated in HCC patients compared to patients without any malignant or inflammatory disease (234 vs. 93 pg/mL, p < 0.0001). The percentage of the tPD-L1-positive area (%tPD-L1) in the background liver was significantly higher than in the tumor (1.52% vs. 0.48%, p < 0.0001). The %tPD-L1 in the background liver but not in the tumor was significantly correlated with the sPD-L1 level (p = 0.0079). The sPD-L1, %tPD-L1 in the tumor, and %tPD-L1 in the background liver were not correlated with the overall survival after surgery. PD-L1-expressing cells in the background liver, but not in the tumor tissue, appeared to contribute to the sPD-L1 level. The sPD-L1 level may thus not indicate the tumor burden in patients with HCC.     

Multiple excimer laser phototherapeutic keratectomies for Avellino corneal dystrophy: a case report

Dear Editor,I am Chihiro Koiwa,from the Department of Ophthalmology,Juntendo University Hospital.I am writing this letter to present a case of multiple excimer laser phototherapeutic keratectomies(PTKs)for Avellino corneal dystrophy(ACD).Corneal dystrophy is a common type of hereditary,noninflammatory,and bilateral corneal disorder that involves various pathological,histological,and clinical manifestations[1].Advanced molecular gene sequencing has identified specific mutations that are associated with most dystrophies of this type.ACD,also known as granular corneal dystrophy typeⅡ[2],is autosomal dominant and associated with the R124H mutation of the transforming growth factor beta-induced(TGFBI)gene and characterized by deposits consistent with both discrete granular and lattice corneal opacities[3-4].An analysis of the TGFBI gene is essential to differentiate ACD because heterozygous R124H mutation carriers have minimal corneal abnormalities,whereas homozygotes have severe visual impairment,starting from early childhood,and early postoperative recurrence of corneal opacity.     

Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese

Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP‐induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty‐eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age‐matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1217–1226, 2014.     

Transsphenoidal cyst cisternostomy with a keyhole dural opening for sellar arachnoid cysts: technical note

A less invasive transsphenoidal approach with a keyhole dural opening for intrasellar arachnoid cysts is described. This approach was used to address seven sellar cystic lesions with suprasellar extension; they were six intrasellar arachnoid cysts (IACs) and one Rathke’s cleft cyst (RCC). In all cases, preoperative MRI revealed cerebrospinal fluid (CSF) intensity on both T1- and T2-weighted images. On preoperative contrast-enhanced MRI, five of the six IACs manifested posterior displacement of the flattened pituitary gland toward the dorsum sellae; one of the six IACs and the RCC exhibited a flattened pituitary gland on the anterior surface of the cyst. Wide cyst cisternostomy through a keyhole dural opening was carried out safely using a microscope with the support of a thin angled endoscope (30° and/or 70°, diameter 2.7 mm). As we aimed to avoid iatrogenic injury of the pituitary function, we found it difficult to obtain a sufficiently wide and precise opening of the cyst wall when the pituitary gland was located on the anterior surface of the cyst wall. Our approach facilitates safe cyst cisternostomy as wide as that obtainable by transcranial manipulation. In addition, CSF leakage is prevented by dural plasty using the fascia lata and stitching with 6-0 monofilament sutures. This technique can be adapted to address various sellar cystic lesions. However, as the posterior or anterior displacement of the normal pituitary gland in the presence of IACs or RCCs, respectively, affects the width of the cyst opening, our technique is more suitable for IACs than RCCs.     

Pathophysiology and management of intracranial arterial stenosis around the circle of Willis associated with hyperthyroidism: case reports and literature review

Cases of moyamoya disease or intracranial arterial stenosis around the circle of Willis (M/IAS) associated with hyperthyroidism have been reported. However, most of these previous reports were of the ischemic form of M/IAS and primary hyperthyroidism. To the best of our knowledge, no studies have documented therapy for M/IAS associated with hyperthyroidism. We discuss four previously unreported cases, including those involving the intracerebral hemorrhage form and thyroid-stimulating hormone (TSH) secretion from a pituitary adenoma (secondary hyperthyroidism). We analyzed data from 52 previously reported cases, including the 4 cases presented here, and discuss M/IAS associated with hyperthyroidism, treatment options, pathophysiology, the ischemic and hemorrhagic forms, secondary hyperthyroidism, and the relevant literature. Hyperthyroidism results in thyrotoxicosis and the stimulation of the superior cervical ganglion by TSH antibodies and f-T3/f-T4. Consequently, hypercoagulability and stenosis of the cerebral artery can occur. There are many reports of ischemic M/IAS associated with hyperthyroidism. A conservative approach to treatment is important in such cases; for example, antithyroid therapy should be the first choice to treat ischemic M/IAS. There have been only a limited number of reports on hemorrhagic M/IAS. We presume that hemorrhagic M/IAS tears the weakened vasculature in a manner similar to that of normal M/IAS (with no complicating hyperthyroidism). The authors also reported M/IAS associated with secondary hyperthyroidism due to pituitary thyroid secreting hormone secreting adenoma.     

Endovascular Treatment of Aneurysmal Subarachnoid Hemorrhage in Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2

To distinguish the characteristics of ruptured cerebral aneurysm that are suitable for endovascular treatment from those that are not, we evaluated factors that influenced the results of aneurysm embolization in patients with ruptured cerebral aneurysm, based on data from the Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2. The multivariate analysis revealed that young patients, patients with low modified Rankin Scale (mRS) scores before onset, and patients with low World Federation of Neurosurgical Societies (WFNS) grades had good outcome. Compared to proximal internal carotid artery (ICA) aneurysms, the odds ratio of middle cerebral artery (MCA) aneurysms was 1.67, indicating poorer outcome for MCA aneurysms, and patients with small, wide-neck cerebral aneurysms had poor outcome. Patients treated after 15 days had better outcome than during other periods. The timing of treatment, however, did not influence the outcome in patients treated within 14 days. The outcome was poorer when the responsible doctor for the treatment was a specialist or a non-specialist than a supervisory doctor. The outcome of patients treated with bare platinum coils, and three dimensional (3D) rotational angiography was better, and the outcome of patients who completed treatment with body filling was poorer than in patients with complete occlusion. Perioperative hemorrhagic complications, all ischemic complications, and rebleeding occurred in 4.5%, 6.4%, and 1.4% of patients, respectively. All these complications had poor outcome factors on day 30, with odds ratios of 2.72, 2.96, and 25.49, respectively. We must be fully aware of these risk factors and determine indications for the treatment when endovascular treatment is performed as the treatment of choice for ruptured cerebral aneurysm.     

Liposome‐Encapsulated Hemoglobin Accelerates Bronchial Healing After Pneumonectomy in the Rat With or Without Preoperative Radiotherapy

Liposome‐encapsulated hemoglobin (LEH) has been reported to accelerate wound healing in the stomach and skin in an experimental setting. LEH was tested in bronchial anastomotic healing after radiation and pneumonectomy in the rat. Sprague‐Dawley rats (n = 61) received preoperative radiation (20 Gy) to the chest and underwent left pneumonectomy with bronchial stump closure using the Sweet method 4 days later, when they were randomized to receive intravenous infusion of LEH with high O₂ affinity (P₅₀O₂ = 17 mm Hg, 10 mL/kg, n = 32) or saline (n = 29). Additional rats (n = 18) were treated in the same way without preoperative radiation. Bronchial anastomotic healing was evaluated 2 days after surgery by determining the bursting pressure and infiltration of neutrophils, monocytes, and macrophages. Bronchial bursting pressure was elevated in the rats receiving LEH both in the unirradiated group (LEH 212 ± 78 vs. saline 135 ± 63 mm Hg, P < 0.05) and in rats with preoperative radiation (LEH 162 ± 48 vs. saline 116 ± 56 mm Hg, P < 0.01). Moreover, the percentage of rats with bursting pressure <100 mm Hg tended to be smaller in the unirradiated group (LEH 1/9 [11.1%] vs. saline 4/9 [44.4%], NS) and was significantly reduced in irradiated animals (LEH 3/32 [9.4%] vs. saline 11/29 [38%], P < 0.05). There were no morphological differences except for macrophage infiltration to the anastomotic area, which was significantly prominent in the LEH‐treated rats (P < 0.05) regardless of the presence or absence of preoperative irradiation (IR). The results suggest that LEH with high O₂ affinity may improve mechanical strength and morphological findings in bronchial anastomosis in rats regardless of the presence or absence of preoperative IR. The irradiated rats later treated with LEH had equivalent or better bronchial healing than that of saline‐treated naïve animals undergoing pneumonectomy alone.     

Effects of Liposome‐Encapsulated Hemoglobin on Learning Ability in Tokai High‐Avoider Rat After Total Brain Ischemia and Reperfusion

Liposome‐encapsulated hemoglobin with low O₂‐affinity (l‐LEH) was shown to be protective in focal brain ischemia and reperfusion (I/R) in rats and primates. We tested l‐LEH in the transient whole brain ischemia in the Tokai high‐avoider rat (THA), which has been selected, mated, and bred over 77 generations for a high and consistent learning ability determined by the Sidman avoidance test (SAT). Young/naïve (before SAT) and adult/parent (after SAT) THA rats underwent acute and complete four‐vessel occlusion in the chest for 3 or 5 min, administration of 2 mL/kg of l‐LEH, saline, or homologous washed red blood cells (RBCs), reperfusion, and resuscitation. One week later, all rats underwent SAT, open‐field behavioral observation, Morris water maze tests, and morphological study. Whereas young/naïve rats treated with l‐LEH retained a rapid and consistent learning curve as in nonischemic controls, THA rats treated with RBCs or saline had retarded learning response on SAT as well as reduced cellularity in the amygdala. Adult/parent rats with established memory on SAT maintained perfect achievement even after I/R. In contrast, l‐LEH‐treated rats showed no better performance on Morris water maze (function) or cellularity of the CA1 sector of the hippocampus (morphology) compared with the rats treated with RBCs. Although task performance on SAT and Morris water maze appeared antithetical, morphological observations corresponded to the respective functions, suggesting that l‐LEH was protective only for the amygdala on SAT tasks but not for the CA1 sector of the hippocampus on spatial orientation as in our previous studies on focal brain I/R, where the cortex was preserved better than basal ganglia.