Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy

The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4^＋ and CD8^＋ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.     

Neurotoxicity of petroleum benzine compared with n-hexane

Summary Petroleum benzine is one of the mixtures of organic solvents containing n-hexane. The occurrence of polyneuropathy in the workers using petroleum benzines is attributed mainly to n-hexane, though other hydrocarbons present are also suspected of having some neurotoxicity or some potential which could modify the neurotoxicity of n-hexane. The present experiment was performed in order to clarify the toxicity of petroleum benzine to the peripheral nerve and compare it with that of n-hexane.Forty rats were randomly divided into five groups. The groups were exposed to 200 ppm n-hexane, 500 ppm n-hexane, and petroleum benzine vapor containing 200 ppm n-hexane or 500 ppm n-hexane, together with aliphatic and aromatic hydrocarbons for 12 h a day for 24 weeks. The body weight, motor nerve conduction velocity, motor distal latency, and mixed nerve conduction velocities were measured before exposure and every 4 weeks of exposure. A rat from each exposed group was histopathologically examined after 24 weeks' exposure.The function of the peripheral nerve was conspicuously impaired by 500 ppm n-hexane, slightly impaired by 200 ppm n-hexane and petroleum benzine containing 500 ppm n-hexane, and even less impaired by petroleum benzine containing 200 ppm n-hexane. Degenerations of the myelin sheaths and axons were demonstrated in all exposed groups upon examination of the raveled tail nerves. Thus, the experiment revealed that petroleum benzine could impair the peripheral nerves, while some components of petroleum benzine were considered to inhibit the neurotoxicity of n-hexane.This investigation was partly supported by a grant for scientific research from the Chiyoda Mutual Life Foundation in 1980–1981     

A comparative study of degree of colorectal distention with manual air insufflation or automated CO2 insufflation at CT colonography as a preoperative examination

Objectives

The purpose of this study was to compare the degree of colorectal distention between manual insufflation using room air and automatic insufflation using carbon dioxide for computed tomography colonography performed as a preoperative examination for patients with colon cancer.

Materials and methods

Participants comprised 200 patients who underwent computed tomography colonography immediately after colonoscopy from October 2011–2012. The first 100 patients were examined using manual insufflation, and the remaining 100 patients were examined using automated insufflation. Two radiologists independently assessed colorectal distention using a 4-point scale in six segments: cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Mean scores of the two radiologists were used to analyze whether any differences existed between techniques in terms of the degree of distention per segment.

Results

Mean distention values for the colonic lumen were better using the automated technique than with the manual technique in both positions (p < 0.05). In segments, distention was significantly better using the automated technique than using the manual technique in the sigmoid and descending colon for prone patients, and in all segments for supine patients.

Conclusions

Automated carbon dioxide insufflation offered significantly improved colorectal distention scores compared to manual room air insufflation.     

Influence of Underweight on Asthma Control

Background: Although the association between asthma control and body mass index (BMI) has been thoroughly investigated, most of this work has focused on the influence on asthma incidence or the effect of obesity on asthma control. To date, there have been no published studies on the influence of underweight on asthma control.Methods: The aim of this study was to investigate the influence of underweight, as defined by the Japan Society for the Study of Obesity (JASSO), on asthma control in Japanese asthmatic patients. Using data from questionnaire surveys administered by the Niigata Asthma Treatment Study Group, we compared asthma control, as measured by the Asthma Control Test (ACT), between a normal weight group (18.5 kg/m² =< BMI < 25 kg/ m²) and an underweight group (BMI < 18.5 kg/m²).Results: Of the asthmatic patients who completed the 2008 and 2010 surveys, 1464 and 1260 cases were classified as being in the normal weight group, and 174 and 155 cases were classified as being in the underweight group. The ACT score (median, [interquartile range]) in the underweight group in 2008 (22, [19-24]) and 2010 (23, [19-25]) was significantly lower than that in the normal group in 2008 (23, [20-25]) and in 2010 (24, [21-25]).Conclusions: This study is the first, large-scale investigation of the influence of underweight on asthma control, and we have confirmed an adverse influence in a clinical setting. A potential mechanism for this interaction was unknown. Further investigation will be required.     

The effect of fibrin glue on inhibition of pericardial adhesions

The effect of fibrin glue on inhibition of pericardial adhesions was tested using 26 beagle dogs. Dacron patches were sutured to the heart and tincture of iodine was applied to promote adhesions. Fibrin glue (3 ml) was sprayed over the patches in 15 dogs (test group), and was not sprated in the remaining 11 dogs (control group). All animals in the test group had minimal adhesions between the pericardium and the epicardium or patched region, and an accumulation of gelatinous material was found in the subpericardial space. Marked fibrosis and a poor demarcation of the subpericardial space were found in the control group. The adhesion score and the visibility of coronary anatomy in the test group were significantly better than in the control group. The tension strength in the test group was significantly less than in the control group. We concluded, therefore, that fibrin glue may also be useful as an adhesion inhibitor.     

Immune responses of graft mesenteric lymph node in small bowel transplantation

BACKGROUND: The high proportions of lymphoid tissues are thought to be one of the underlying factors inducing severe allograft rejection following small bowel transplantation. Mesenteric lymph nodes (MLN) contained in the intestinal graft are not only a source of donor-derived professional antigen-presenting cells, but also offer a field for immune interaction between donor and host cells. We investigated immune responses in graft MLNs with or without FK506 to develop a novel strategy to control small bowel allograft rejection. MATERIALS AND METHODS: Heterotopic small bowel transplantations were performed from Brown Norway donors to Lewis recipients. Changes in population of lymphocytes, expressions of costimulatory molecules, apoptosis, and cytokine profiles in graft MLNs were evaluated. RESULTS: The increase in apoptotic cells and cytokine responses relating to rejection in the graft MLNs developed prior to those in graft jejunum. While donor lymphocytes in graft MLNs were rapidly replaced to host-derived lymphocytes independent of FK treatment, increase in CD8(+) T cells in host population was seen only in recipients without FK506 treatment. The expressions of B7 molecules on donor cells in graft MLNs were significantly lower in the recipients with FK treatment. CONCLUSIONS: Immune responses in graft MLNs have significant impact on the outcome of the small bowel allograft. Apoptosis of graft MLN cells was well correlated with and ahead of progression of acute rejection. Modulation of costimulatory molecules on donor-derived MLN cells in the allograft and specific suppression of host CD8(+) T cells are possible ways to control severe rejection after allogeneic small bowel transplantation.     

Bone marrow chimerism and tolerance induced by single-dose cyclophosphamide

BACKGROUND: Establishment of hematopoietic chimerism is the most stable strategy for donor-specific tolerance. Safer pretreatment regimens are needed for clinical application. We evaluated the efficacy of a simple protocol using cyclophosphamide (CYP) on induction of chimerism and organ transplant tolerance across major histocompatibility complex (MHC) barriers in the rat. MATERIALS AND METHODS: Bone marrow cells from BN (RT1(n)) donors were infused to LEW (RT1(l)) recipients on day 0 after a single injection of CYP at various doses on day -1. Donor-derived hematopoietic chimerism was evaluated by flowcytometry. The recipients received BN or third party (BUF) heart allografts on day 100. RESULTS: While pretreatment with 200 mg/kg of CYP induced high levels of hematopoietic chimerism, six of eight recipients died of severe graft-versus-host-disease (GVHD). CYP at dose of 150 mg/kg induced 36.5 +/- 24.1% of donor-derived chimerism on day 10, and sustained macrochimerism was seen until day 100 without GVHD. Pretreatment with 100 mg/kg of CYP resulted in only transient chimerism (4.8 +/- 5.2%) which disappeared by day 20. In the recipients with 50 mg/kg of CYP, donor bone marrow cells were rapidly rejected and no chimerism was observed. The recipients with 150 mg/kg of CYP accepted BN heart allografts (>100 days x 5), while rejecting BUF allografts by day 12 (n = 4). BN heart allografts were rejected in the recipients with 100 (MST: 57 days, n = 5) and 50 mg/kg (MST: 7 days, n = 5) of CYP. CONCLUSIONS: A single dose of CYP can induce hematopoietic chimerism across MHC-barriers. The dose of 150 mg/kg seems to be optimal to induce organ transplant tolerance without developing GVHD.     

Clinical, histological, and genetic features of fourth ventricle ependymoma in the elderly

A 71-year-old woman presented with a rare case of geriatric ependymoma originating from the fourth ventricle manifesting as progressive gait and memory disturbance. Imaging studies revealed an extraaxial mass in the fourth ventricle protruding into the right cerebellomedullary cistern, with concomitant obstructive hydrocephalus. Surgery achieved subtotal removal since the tumor tightly adhered to the right vestibular area of the fourth ventricular floor. The histological diagnosis was ependymoma, which was also confirmed by comparative genetic hybridization. Although she developed severe laryngeal edema and worsening of the hydrocephalus postoperatively which required additional treatment, she recovered with residual mild gait disturbance, and was transferred to a rehabilitation facility. Fourth ventricle ependymoma in the elderly is rare. Comparative genetic hybridization may be important in the diagnosis of geriatric ependymoma and in the choice for adjuvant therapy as well as in estimating the prognosis for patients with rare types of ependymoma.     

A model to evaluate toxic factors influencing islets during collagenase digestion: the role of serine protease inhibitor in the protection of islets

The recovery of all of the islets contained in a pancreas is the goal of islet isolation for transplantation. This study reveals an environment that injures the isolated islets during digestion and proposes a new model for optimal islet isolation. Islets were isolated from Wistar rat pancreases by stationary collagenase digestion while the digestion time was varied at 15, 30, 60, and 120 min. The digested pancreas and islets were analyzed histologically and adenosine nucleotides were measured. Overnight cultured islets (40 islets) were cocultured for 30 min with the supernatants obtained from pancreatic collagenase digestion at different digestion periods in order to assess the toxic environment. The peak yields of islets were obtained at 30 min of digestion. The histological study of digested pancreas showed that the exocrine cells lost their cellular integrity at 120 min of digestion, but the islet cells were left intact. Accordingly, the ATP levels of the pancreatic tissue decreased during the digestion period. The coculture experiment demonstrated that the islets cultured with the supernatants from the collagenase digestion showed digestion time-dependent disruption of the cellular integrity of islets in accordance with a rapid decrease of ATP levels in the islets. The addition of serine protease inhibitors into this coculture clearly showed protection of islets, which maintained high ATP levels in association with intact membrane integrity as assessed by AO/PI staining. Morphological deterioration of islets as well as a marked ATP decrease was evident in the entire digested pancreas as well as in islets cocultured in the supernatants from the collagenase digestion. Various factors toxic to the islets can therefore be analyzed in future experiments using this coculture model for obtaining a good yield of viable islets.     

A dumon stent inserted for bronchial stenosis causing a left bronchopericardial fistula: Report of a case

We present herein the case of a 59-year-old man in whom a Dumon stent, inserted as treatment for stenosis of the left main bronchus, caused a left bronchopericardial fistula. The patient initially presented with severe dyspnea caused by main bronchial stenosis of unknown origin for which a Dumon stent was inserted at a local hospital. The Dumon stent migrated to the endobronchus through the stenosis of the left main bronchus a few days later, and his dyspnea remained unresolved. He was subsequently referred to our department 6 months later, where a left pneumonectomy under supportive cardiopulmonary bypass through the femoral artery and vein was performed, and a postoperative pathological diagnosis of bronchial leiomyosarcoma was made. For this rare group of malignant tumors, early diagnosis permits complete surgical resection of the mass and offers the best prognosis. Excision of the tumor should be performed under cardiopulmonary bypass through the femoral vessels when a risk of sudden rupture of the pulmonary artery or vein exists for any reason.