Masahito Mizuuchi

Forehead is as sensitive as finger pulse oximetry during general anesthesia

PurposeTo compare the performance of a forehead probe to a conventional finger pulse oximetry probe in anesthetized patients.MethodsEighteen patients participated in the study. Each probe was connected to a Nellcor N-550 pulse oximeter. Anesthesia was induced and maintained with propofol. After intubation, the patients received air to achieve a steady-state of peripheral arterial oxygen saturation (SpO2). Ventilation was interrupted to induce a hypoxic state. As soon as one of the two SpO2’s decreased to 90%, the patients’ lungs were ventilated with 100% oxygen. To evaluate the performance of the two pulse oximeters, time to the lowest (TL), time of recovery (TR) and lag times to beginning of SpO2 decrease (Lag) were measured.ResultsThere were no significant differences in TL and TR between forehead and finger pulse oximetry under normal perfusion conditions during general anesthesia. When the axillary artery was compressed to mimic reduced peripheral perfusion, SpO2 in the forehead decreased sooner than in the finger during hypoxia. The forehead and finger TLs were similar, however, TR was significantly longer in the finger.ConclusionThe forehead SpO2 sensor can be used as an alternative to the conventional finger sensor during general anesthesia.RésuméObjectifComparer la performance d’un capteur frontal et d’un capteur traditionnel au doigt chez des patients anesthésiés.MéthodeDix-huit patients ont participé à l’étude. Chaque capteur a été relié à un sphygmo-oxymètre Nellcor N550. L’anesthésie a été induite et maintenue avec du propofol. Après l’intubation, les patients ont reçu de l’air pour l’obtention d’un état d’équilibre de la saturation en oxygène du sang artériel périphérique (SpO2). La ventilation a été interrompue pour induire un état hypoxique. Aussitôt qu’une ou l’autre mesure de SpO2 baissait à 90 %, les patients étaient ventilés avec de l’oxygène à 100 %. La performance des deux appareils a été mesurée par le temps nécessaire pour obtenir la plus basse valeur de SpO2 (TB), le temps nécessaire à la récupération (TR) et les intervalles précédant les baisses de SpO2 (Int).RésultatsIl n’y a pas eu de différences significatives de TF et TR entre les résultats notés au front et au doigt dans des conditions normales de perfusion pendant l’anesthésie générale. Quand l’artère axillaire était compressée pour imiter une perfusion périphérique réduite, la SpO2 diminuait plus vite au front qu’au doigt pendant l’hypoxie. Les TF au front et au doigt ont été similaires, mais le TR a été significativement plus long au doigt.ConclusionLe capteur frontal de SpO2 peut remplacer un capteur traditionnel fixé au doigt pendant l’anesthésie générale.

ALDH1-High Ovarian Cancer Stem-Like Cells Can Be Isolated from Serous and Clear Cell Adenocarcinoma Cells, and ALDH1 High Expression Is Associated with Poor Prognosis

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1high) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1high cells. ALDH1high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy

Cervical cancer is a major cause of cancer death in females worldwide. Cervical cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are resistant to conventional radiotherapy and chemotherapy, and CSCs/CICs are thought to be responsible for recurrence. Eradication of CSCs/CICs is thus essential to cure cervical cancer. In this study, we isolated cervical CSCs/CICs by sphere culture, and we identified a cancer testis (CT) antigen, CTCFL/BORIS, that is expressed in cervical CSCs/CICs. BORIS has 23 mRNA isoform variants classified by 6 subfamilies (sfs), and they encode 17 different BORIS peptides. BORIS sf1 and sf4 are expressed in both CSCs/CICs and non-CSCs/CICs, whereas BORIS sf6 is expressed only in CSCs/CICs. Overexpression of BORIS sf6 in cervical cancer cells increased sphere formation and tumor-initiating ability compared with those in control cells, whereas overexpression of BORIS sf1 and BORIS sf4 resulted in only slight increases. Thus, BORIS sf6 is a cervical CSC/CIC-specific subfamily and has a role in the maintenance of cervical CSCs/CICs. BORIS sf6 contains a specific c-terminal domain (C34), and we identified a human leukocyte antigen (HLA)-A2-restricted antigenic peptide, BORIS C34_24(9) encoded by BORIS sf6. A BORIS C34_24(9)-specific cytotoxic T cell (CTL) clone showed cytotoxicity for BORIS sf6-overexpressing cervical cancer cells. Furthermore, the CTL clone significantly suppressed sphere formation of CaSki cells. Taken together, the results indicate that the CT antigen BORIS sf6 is specifically expressed in cervical CSCs/CICs, that BORIS sf6 has a role in the maintenance of CSCs/CICs, and that BORIS C34_24(9) peptide is a promising candidate for cervical CSC/CIC-targeting immunotherapy.

Prognostic Impact of Human Leukocyte Antigen Class I Expression and Association of Platinum Resistance with Immunologic Profiles in Epithelial Ovarian Cancer

Mariya and colleagues analyzed 122 cases of epithelial ovarian cancer (EOC) and identified low expression of HLA class I and low intraepithelial CTL infiltration as independent prognostic factors for poor overall survival for patients with advanced EOC; low HLA class I expression was correlated with platinum resistance. Epithelial ovarian cancer (EOC) is one of the most deadly carcinomas in females. Immune systems can recognize EOCs; however, a defect of human leukocyte antigen (HLA) class I expression is known to be a major mechanism for escape from immune systems, resulting in poor prognosis. The purpose of this study is to identify novel correlations between immunologic responses and other clinical factors. We investigated the expression of immunologic components in 122 cases of EOCs for which surgical operations were performed between 2001 and 2011. We immunohistochemically stained EOC specimens using an anti-pan HLA class I monoclonal antibody (EMR8-5) and anti-CD3, -CD4, and -CD8 antibodies, and we analyzed correlations between immunologic parameters and clinical factors. In multivariate analysis that used the Cox proportional hazards model, independent prognostic factors for overall survival in advanced EOCs included low expression level of HLA class I [risk ratio (RR), 1.97; 95% confidence interval (CI), 1.01–3.83; P = 0.046] and loss of intraepithelial cytotoxic T lymphocyte (CTL) infiltration (RR, 2.11; 95% CI, 1.06–4.20; P = 0.033). Interestingly, almost all platinum-resistant cases showed a significantly low rate of intraepithelial CTL infiltration in the χ2 test (positive vs. negative: 9.0% vs. 97.7%; P < 0.001). Results from a logistic regression model revealed that low CTL infiltration rate was an independent factor of platinum resistance in multivariate analysis (OR, 3.77; 95% CI, 1.08–13.12; P = 0.037). Platinum-resistant EOCs show poor immunologic responses. The immune escape system of EOCs may be one of the mechanisms of platinum resistance. Cancer Immunol Res; 2(12); 1220–9. ©2014 AACR.

Design of oxygen delivery systems influences both effectiveness and comfort in adult volunteers

PurposeThe aim of this investigation was to compare the efficiency of four oxygen delivery systems in healthy volunteers.MethodsThe subjects received oxygen at flow rates of 3.0 and 5.0 L·min−1 via a face mask, nasal cannulae, and two kinds of new open- and microphone-type oxygen delivery systems (OxyArm™ and Mike Cannula) in a random sequence, and values of partial arterial pressures of oxygen (RaO2) were measured. The comfort of these devices was also evaluated.ResultsA significant, oxygen flow dependent increase in PaO2 was obtained with all devices tested. PaO2 was significantly higher when the face mask was used [217.5 ± 19.9 (mean ± SD) mmHg at 5 L·min−1) than when the Mike Cannula was used (177.5 ± 14.8 mmHg). The face mask was the least comfortable and OxyArm was the most comfortable among the devices tested.ConclusionThe results of our evaluation suggest that comfort and clinical performance should be considered when using oxygen delivery devices for patients who require oxygen supplementation.RésuméObjectifLe but de la présente étude était de comparer l’efficacité de quatre systèmes de distribution d’oxygène chez des volontaires sains.MéthodeLes sujets ont reçu, suivant une séquence aléatoire, des débits d’oxygène de 3,0 et 5,0 L·min−1 au moyen d’un masque, d’une canule nasale et de deux nouveaux prototypes ouverts et de type microphone (OxyArm™ et Mike Cannula). Les pressions artérielles partielles (PaO2) ont été mesurées. Le confort a été évalué pour chacun des appareils utilisés.RésultatsUne augmentation significative de la PaO2, dépendante du débit d’oxygène, a été obtenue avec tous les appareils. La PaO2 a été significativement plus élevée avec le masque [217,5 ± 19,9 (moyenne ± écart type) mmHg à 5 L·min−1] qu’avec le Mike Cannula (177,5 ± 14,8 mmHg). Le masque était l’appareil le moins confortable et le OxyArm le plus confortable.ConclusionNos résultats indiquent que le confort et la performance clinique doivent être pris en compte au moment d’utiliser des appareils de distribution d’oxygéne pour un apport complémentaire.

Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses

The aim of this study was to establish an efficient human papilloma virus (HPV) type 16-targeting cancer immunotherapy. Persistent high-risk HPV infection causes cervical intra-epithelial neoplasia (CIN) and subsequent cervical carcinoma. HPV type16 (HPV16) is one of the common carcinogenic types and is found in about 50% of invasive cervical carcinomas. HPV16-derived viral proteins E6 and E7 are expressed in cancerous cells through the progression of the disease and have a role in carcinogenesis but are not expressed in normal cells. Thus, these proteins are regarded as ideal antigens for cervical carcinoma immunotherapy. In this study, we generated a novel HPV 16 E6 and E7 gene plasmid containing oligomannose liposomes (OML-HPV). We compared the cytotoxic T lymphocyte (CTL) induction efficiency of OML-HPV and that of standard liposome-HPV16 E6 and E7 DNA complex. HPV16 E6-specific CTLs could be generated from HPV 16-positive cervical carcinoma patients peripheral blood mononuclear cells (PBMCs) by stimulating OML-HPV, but could not by stimulating standard liposome-HPV 16 E6, E7 DNA complex. Furthermore, we screened HLA-A24-restricted HPV16 E6- and E7-derived peptides, and found that one E6-derived peptide (E6 66-74) showed the highest immunogenicity with ELISPOT assay from 100% of HPV16-positive patients (4 out of 4). On the other hand, other E6- or E7-derived peptides, including E6 49-57, E6 82-90, E6 87-95, E6 98-106 and E7 83-93, showed less frequent reactivity. These results indicate that OML-HPV is a more effective approach than DNA vaccination using standard liposomes, and that a novel HLA-A24-restricted peptide, E6 66-74, might be a suitable target of cervical cancer immunotherapy.

The infusion rate of most disposable, non-electric infusion pumps decreases under hypobaric conditions.

PurposeTo examine the delivery rates of four disposable, nonelectric infusion pumps during hypobaric conditions.MethodsFour models categorized by three different driving forces, one vacuum unit (Coopdech Syringector), one spring unit (Linear-fuser), and two elastomeric balloon-powered units (Multirate Infuser LV and Large DIB), were tested. Each infusion pump was placed in an airtight container, and the pressure in the container was decreased to 1,000, 900, and 800 hPa. The catheter tip of each pump was exposed either to atmospheric pressure (1,000 hPa) or to similar hypobaric conditions (800–1,000 hPa).ResultsUnder normal atmospheric pressure, each pump showed an accurate delivery rate in the range of −2% to +8% of the set infusion rate (4.0–5.0 mL·hr−1). With the catheter tip exposed to atmospheric pressure, the infusion rate of each pump was reduced from 35% in the case of the Large DIB to 64% in the case of the Coopdech Syringector, depending on the magnitude of change in hypobaric pressure. When the pressure acting on the catheter tip was reduced to a level similar to that exerted on the pump body, infusion rate was reduced (by 19%–27%) in all three types of pump, and the Large DIB showed no significant difference in performance compared to normal atmospheric pressure.ConclusionThe infusion rates of disposable infusion pumps are reduced under hypobaric conditions. Even though we still do not know how the epidural pressure changes under hypobaric conditions, clinicians should be aware that the infusion rate of disposable infusion pumps is decreased under hypobaric conditions.RésuméObjectifVérifier les vitesses d’administration de quatre pompes à perfusion non électriques jetables utilisées dans des conditions hypobares.MéthodeNous avons testé quatre modèles classés selon trois différentes catégories d’éléments moteurs, un appareil à aspiration (Coopdech Syringector), un appareil à charnière (Linearfuser) et deux appareils élastomères à ballonnet d’entraînement (Multirate Infuser LV et Large DIB). Chaque pompe a été placée dans un contenant hermétique dont la pression interne a été abaissée à 1 000, 900 et 800 hPa. La pointe du cathéter de chacune des pompes a été exposée soit à la pression atmosphérique (1 000 hPa) soit à des conditions hypobares similaires (800– 1 000 hPa).RésultatsSoumise à une pression atmosphérique normale, chaque pompe a affiché une vitesse d’administration précise allant de −2 % à +8 % de la vitesse de perfusion préalablement définie (4,0– 5,0 mL·hr− 1). Si la pointe du cathéter était exposée à la pression atmosphérique, la vitesse de perfusion de chaque pompe était réduite de 35 %, dans le cas du Large DIB,jusqu’à 64 %, pour le Coopdech Syringector, en fonction de l’importance du changement de pression hypobare. Si la pression sur la pointe du cathéter était réduite au niveau de celle qui était exercée sur le corps de la pompe, la vitesse de perfusion était réduite (de 19 % à 27 %) pour les trois types de pompes. La performance du Large DIB n’a pas présenté de différence significative, comparée à la performance sous pression atmosphérique normale.ConclusionLes vitesses de perfusion des pompes jetables sont réduites dans des conditions hypobares. Même si nous ne pouvons encore expliquer les changements de pression péridurale observés dans des conditions hypobares, il faut savoir que la vitesse de perfusion des pompes jetables diminue dans de telles conditions.

Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer

Epithelial ovarian cancer (EOC) is one of the most lethal cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) have been reported to be origin of primary and recurrent cancers and to be resistant to several treatments. In this study, we identified matrix metalloproteinase-10 (MMP10) is expressed in CSCs/CICs of EOC. An immunohistochemical study revealed that a high expression level of MMP10 is a marker for poor prognosis and platinum resistance in multivariate analysis. MMP10 gene overexpression experiments and MMP10 gene knockdown experiments using siRNAs revealed that MMP10 has a role in the maintenance of CSCs/CICs in EOC and resistance to platinum reagent. Furthermore, MMP10 activate canonical Wnt signaling by inhibiting noncanonical Wnt signaling ligand Wnt5a. Therefore, MMP10 is a novel marker for CSCs/CICs in EOC and that targeting MMP10 is a novel promising approach for chemotherapy-resistant CSCs/CICs in EOC.

Successful Uterus-Preserving Surgery for Treatment of Chemotherapy-Resistant Placenta Increta

Treatment of placenta increta often entails abdominal total hysterectomy. We present a case of placenta increta in which 3-dimensional computed tomography shows very high blood flow to the placenta, even after chemotherapy with methotrexate. Nonetheless, we were able to remove the region of the uterus that had been invaded by chorionic villi. Massive bleeding during the operation was prevented by ligation of the hypogastric artery and local injection of vasopressin. The combination of chemotherapy and partial resection of the uterus is quite a unique treatment for placenta increta patients. This approach enabled preservation of the uterus and the patient’s fertility. We suggest this procedure could be one of the treatments for patients who have placenta increta and wish to retain their fertility.

Possibility of less radical treatment for patients with early invasive uterine cervical cancer

Radical trachelectomy (RT) with lymphadenectomy has become a standard treatment modality for patients with early invasive uterine cervical cancer who hope to preserve fertility. However, pregnancy after RT has high risks of preterm birth. The possibility of more conservative RT and the application of RT for patients with higher clinical stages were studied.