Evaluation of pharyngeal swallowing pressure using high-resolution manometry during transoral surgery for oropharyngeal cancer.

BACKGROUND: Transoral robotic surgery is frequently described, driven by the desire to offer a less morbid alternative to chemoradiation. However, the objective evaluation of post-operative function has rarely been reported. Therefore, high-resolution manometry was used in this study to evaluate the impact of changes in peri-operative swallowing function on pharyngeal pressure events. METHODS: Ten patients with various stages of oropharyngeal cancer underwent transoral surgery. High-resolution manometry and videofluoroscopic swallow studies were performed before surgery and two months afterwards. The following parameters were obtained: velopharyngeal and mesopharyngeal post-deglutitive upper oesophageal sphincter pressures, velo-meso-hypopharyngeal contractile integral, upper oesophageal sphincter relaxation pressure, and pharyngeal velocity. RESULTS: There was no significant difference in pharyngeal pressure or contractile integral pre- versus post-operatively. However, pharyngeal velocity was significantly higher post-operatively than pre-operatively. CONCLUSION: High-resolution manometry showed that transoral surgery in patients without pre-operative dysphagia preserved pharyngeal constriction. However, transoral surgery might produce scar formation in the pharynx, which could lead to narrowing of the pharynx.

Experimental Infection with Baylisascaris Potosis in Chickens.

The larvae of the genus Baylisascaris can cause larva migrans in mammals and birds. This study investigated the larval migration of Baylisascaris potosis, the roundworm of kinkajou (Potos flavus), in chickens and the associated clinical manifestations of the host. Thirty-six 3-week-old chickens divided into 6 groups were orally inoculated with 3,000 B. potosis eggs/chick. Each group of chicken was necropsied at days 1, 2, 3, 7, 30 and 90 PI (post inoculation), and the number of larvae in various organs were counted until day 90 PI. No clinical signs were observed in chickens during the study. Larvae were detected from the liver, lungs or breast-muscles of 13/36 (36.1%) chickens. The mean total number of larvae in the liver, lungs and breast-muscles at days 1, 2, 3, 7, 30 and 90 PI were 0.34, 0.17, 1.66, 1.01, 0.17 and 0, respectively. No larvae were found in the brain, eyes, hid-limb muscles, heart, kidneys and spleen. Although infectivity of larvae in egg-inoculated chickens was low, the present study demonstrated that B. potosis larvae can migrate in chickens tissues up to day 30 PI. The result suggests that chickens can serve as a paratenic host for B. potosis and may underline a public health importance of B. potosis infection as a potential foodborne disease in humans.

Baylisascaris Potosis Larvae in Mice of Different Strains and Infectivity of Tissue Larvae.

Migration of Baylisascaris potosis larvae in different mouse strains were compared, and infectivity of the persisting larvae in mice tissues were investigated. Five strains of mice, BALB/c, C57BL/6, AKR, B10.BR, and ICR were inoculated with 1,000 B. potosis eggs/mouse, and necropsied at week 13 post inoculation (PI). The other uninfected ICR mice (secondary host) were inoculated with 43 larvae/ mouse recovered from mice at week 13 PI with eggs, and necropsied at day 21 PI. Larvae in organs or tissues were counted at necropsy. One AKR mouse showed torticollis and circling at day 56 PI. At necropsy at week 13 PI, larvae were recovered from all mice. A mean total larvae recovered were 124.1 (n=40). Majority of larvae were found in the carcass (mean 113.9) and some in the viscera (mean 9.9). Zero to 1 larva were found in the brain or eyes of some mice. There were no differences among the mouse strains in the number of larvae, except in the viscera; more larvae were seen in BALB/c or ICR than in B10.BR mice. No larvae were found in the secondary host mice. Present study demonstrated that B. potosis larvae migrate well in the carcass of any strains of mice, however, the tissue larvae did not infect the secondary host. Results of our present study suggest that B. potosis larvae is less aggressive for the nervous tissue migration than that of B. procyonis larvae which is commonly known to migrate in central nervous system of mammals and birds.

High IL-1α Production Was Induced in the WBN/Kob-Leprfa Type 2 Diabetes Mellitus Rat Model and Inhibited by Syphacia Muris Infection.

The novel WBN/Kob-Leprfa (fa/fa) congenic rat strain is considered a useful rat model of type 2 diabetes mellitus (T2DM). Accumulating findings suggest that low-grade inflammation is a causative factor in T2DM and that circulating levels of inflammatory cytokines are associated with insulin resistance. However, inflammatory cytokine profiles and their correlations with T2DM development/ progression in fa/fa rats have not been studied. In this study, we found that the fa/fa rats had considerably high plasma levels of interleukin (IL)-1α. Abundant cecal IL-1α mRNA expression and cecal inflammation with infiltrating IL-1α-producing macrophages was observed in fa/fa rats. Bone marrow derived macrophages from fa/fa rats expressed high levels of IL-1α upon lipopolysaccharide stimulation. Furthermore, Syphacia muris infection, which delays the onset of T2DM, reduced both plasma and cecal IL-1α levels in fa/fa rats. These results suggest that macrophage infiltration and IL-1α secretion comprise an important part of T2DM development and that S. muris infection inhibits pro-inflammatory cytokine expression in fa/fa rats.

Efficacy of fluoroscopy-guided endoscopic cricopharyngeal myotomy.

BACKGROUND: In endoscopic cricopharyngeal myotomy, surgeons sometimes have concerns about performing an adequate incision with only a narrow intra-cavital view from one direction. In order to overcome these issues, fluoroscopic radiography was used during endoscopic cricopharyngeal myotomy. METHODS: Peri-operative fluoroscopic radiography was utilised to check the position of the diverticuloscope, and to confirm the extent of the incision during surgery. A balloon catheter was used to determine whether the cricopharyngeal muscle was sufficiently resected. Blood loss, peri-operative complications, and functional oral swallowing scale and penetration aspiration scale scores were evaluated. RESULTS: In 12 out of 15 patients, intra-operative fluoroscopic radiography showed the diverticuloscope positioned in the post-cricoid area, and the cricopharyngeal muscle was raised and the surgery completed without adverse effect. Swallowing functions improved following surgery. CONCLUSION: Intra-operative fluoroscopy might improve endoscopic cricopharyngeal myotomy by allowing surgeons to confirm the extent of resection, and by reducing peri-operative morbidity and complication rates.

Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G).

BACKGROUND: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. PATIENTS AND METHODS: WJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided α-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396. RESULTS: Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively [HR, 0.905; 95% confidence interval (CI) 0.723-1.133; P = 0.003 for non-inferiority]. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785-1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months. CONCLUSION: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. CLINICAL TRIALS NUMBER: UMIN000001396.

Prevalence of Baylisascaris Roundworm in Captive Kinkajous in Japan.

Baylisascaris potosis causes larva migrans in animals. The present study evaluated the prevalence of B. potosis in captive kinkajous ( Potos flavus ) and the ability of milbemycin to treat natural infections of B. potosis in 2 female wild-caught kinkajous. In 2012, fecal samples were collected from 16 kinkajous in 6 zoological gardens and 29 imported captive kinkajous from 4 pet traders in Japan. Although all samples from zoological gardens were negative, 8 kinkajous from traders were positive for Baylisascaris eggs, at least 4 of which were wild caught in the Republic of Guyana. No associated human illness was reported from any of the facilities. The 2 infected kinkajous received a single oral administration of Milbemycin® A Tablets, which delivers 0.69-0.89 mg/kg milbemycin oxime. Fecal examinations on days 14 and 30 were negative for Baylisascaris eggs. These results demonstrated that milbemycin oxime has possible anthelmintic efficacy against Baylisascaris roundworms in captive kinkajous. We conclude that Baylisascaris infections are highly prevalent in wild-caught kinkajous in Japan and that most of the infected kinkajous were imported from the Republic of Guyana.

The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study.

BACKGROUND: The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. OBJECTIVES: To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. METHODS: In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. RESULTS: No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50% at week 4 with CIM331 compared with -20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. CONCLUSIONS: A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone. CIM331 may become a novel therapeutic option for AD by inhibiting IL-31.

Cytogenetic dosimetry by micronucleus assay using peripheral blood cells is modified by thyroid hormones.

Cytokinesis-block micronucleus (CBMN) assay is a convenient and easy method of radiation biodosimetry that uses peripheral blood (PB) cells. However, for micronuclei (MN) frequency induced by ionising radiation, a dose-response relationship in abnormal condition, such as in cancer patients, has not been assessed. To clarify the difference between the dose-response curve generated by the CBMN assay in conditions when thyroid hormone levels were normal and during thyroid hormone withdrawal (THW) prior to (131)I treatment, 12 thyroid cancer patients who underwent thyroidectomy were studied. The collected PB mononuclear cells were exposed to 0.5-3.0 Gy X-ray irradiation. Under normal conditions, dose dependency and independency of MN frequency were observed in 92 % and 8 %, respectively. In contrast, during THW, the number of patients who showed dose independency significantly increased to 42 % in comparison with control. Furthermore, a higher concentration of serum thyroglobulin in dose-independent patients was observed. These results suggest that MN frequency in cytogenetic dosimetry is affected by thyroid hormones.

Experimental infection of Mongolian gerbils with Baylisascaris potosis.

The present study evaluated the pathogenicity of Baylisascaris potosis, a newly described ascarid nematode, in Mongolian gerbils. Gerbils were infected with varying doses of either B. potosis or Baylisascaris transfuga embryonated eggs (100, 1,000, and 4,000) for 30 days postinfection (pi). Baylisascaris potosis-infected gerbils showed no clinical signs of disease; however, gerbils exposed to 1,000 and 4,000 B. transfuga eggs showed severe neurologic signs at 22-29 days and 14-15 days pi, respectively. Histopathologic examination revealed larvae and lesions in the intestine, lung, liver, and muscles of B. potosis-infected gerbils, but not in the brain, whereas B. transfuga larvae were found only in the brain and muscle. These results indicate that B. potosis larvae migrate through numerous organs and are associated with visceral larva migrans in gerbils, but less frequently migrate to the nervous system in gerbils than does B. transfuga .

Survey of Japanese encephalitis virus in pigs and wild boars on Ishigaki and Iriomote Islands in Okinawa, Japan.

SUMMARY We previously revealed that Japanese encephalitis virus (JEV) seroprevalence was 4.5% in pigs on Ishigaki Island from 2005 to 2007. However, a partial E gene sequence (151 bp) of the JEV genome (JEV/sw/Ishigaki/1/2005) was detected in one pig. Phylogenetic analysis showed that JEV/sw/Ishigaki/1/2005 belonged to genotype III and to the same lineages isolated in Taiwan from 2006 to 2008. Serum samples were collected from 128 pigs on Ishigaki from 2009 to 2010, 24 wild boars on Ishigaki from 2008 to 2010, and 117 wild boars on Iriomote Island from 2008 to 2010. Four (3.1%) pigs on Ishigaki were positive for JEV antibody, but all wild boars on the island were negative. Fifty-two (44.4%) wild boars on Iriomote were positive for JEV antibody, in contrast to a seroprevalence of 3.7% in 2000 and 2004. JEV on Iriomote and/or in Taiwan might be related to transmission on Ishigaki.

Treatment and prognosis of angiosarcoma of the scalp and face: a retrospective analysis of 48 patients.

OBJECTIVE: The objective of this study was to retrospectively analyse the treatment results of clinically localised angiosarcoma of the scalp and face. METHODS: The records of 48 patients who were treated between 1987 and 2009 were reviewed. single modality or a combination of surgery, radiotherapy, chemotherapy and immunotherapy were administered. The median follow-up of all 48 patients was 13.7 months (range 2.5-105.9 months). RESULTS: At the time of analysis, 45 of 48 patients (93.8%) had disease recurrences, and the lung was the most frequent site for recurrence (37 patients). In multivariate analysis, performance status (PS) and number of tumours were significant predictors of lung-metastasis-free (LMF) rate. For patients with multifocal tumours, chemotherapy use significantly decreased the LMF rate (p=0.0072). The 2-year actuarial overall survival (OS), progression-free survival and local control rates in all 48 patients were 22.1%, 10.7% and 46.3%, respectively. In multivariate analysis, PS, number of tumours, surgery and radiotherapy were significant prognostic factors for OS. Patients treated with both surgery and radiotherapy (2-year OS: 45.8%) had a significantly more favourable OS (p<0.0001) than patients treated with either surgery or radiotherapy (2-year OS: 11.1%) and patients treated with neither surgery nor radiotherapy (2-year OS: 0%). CONCLUSIONS: Our results indicated that PS and number of tumours were significant predictors for developing lung metastases. Our results also indicated that PS, number of tumours, surgery use and radiotherapy use were independent prognostic factors for OS. Multimodal treatments including surgery and radiotherapy were effective in improving OS for patients with these tumours. Advances in knowledge Multimodal treatments including surgery and radiotherapy are effective in improving overall survival for patients with angiosarcoma of the scalp and face.

Tissue rinse liquid-based cytology: a feasible tool for the intraoperative pathological evaluation of sentinel lymph nodes in breast cancer patients.

OBJECTIVES: A unique diagnostic method was designed for the intraoperative pathological evaluation of sentinel lymph nodes (SLNs) in breast cancer patients, and the results were verified with 2 years of experience. METHODS: Excised lymph nodes were cut into 2-mm-thick slices and rinsed thoroughly in CytoRich Red(®). The sliced tissues were embedded in a paraffin block. Three cytological glass slides of the cells exfoliated in CytoRich Red(®) were prepared by the SurePath(®) liquid-based cytology (LBC) technique. Two slides were stained by the Papanicolaou method, and the remaining slide was immunostained with an anti-keratin antibody. This process is called tissue rinse liquid-based cytology (TRLBC). The results of TRLBC were compared with those of the final pathological diagnoses, including immunostaining with an anti-keratin antibody on paraffin blocks (PB). RESULTS: This study analysed 444 SLNs from 247 consecutive breast cancer patients. It required 35 minutes to complete the intraoperative diagnosis on a single node, and it took an additional 5 minutes per node if more than one node was submitted. When the results of PB were assumed to be the gold standard, the sensitivity and specificity of TRLBC were 81.9% and 96.1%, respectively. TRLBC detected all nodes with macrometastasis and 23 of 24 nodes with micrometastasis. Fifteen false-negative TRLBC results were 'isolated tumour cell clusters' on PB, but there was one with micrometastasis histologically. Four of 14 false-positive TRLBC results were proven to be true positive by supplementary examination using step sectioning of the paraffin blocks of the nodes. CONCLUSION: TRLBC is a feasible and promising intraoperative cytopathological tool showing a comparable efficacy to PB while still allowing the conventional postoperative histological examination.

Cytodiagnosis through use of a z-axis video by volunteer observers: a promising tool for external quality assessment.

OBJECTIVE: This study examined whether cytological diagnosis through the use of a video, which shows the changing depth of focus in the microscopic field, described as a z-axis video, is useful compared with a still image. METHODS: From 17 cytology preparations of fine needle aspiration of the breast, we made six z-axis videos per case. A frame exhibiting the characteristic features was then extracted from each video and saved as a representative still image. One hundred and twenty-eight volunteer cytotechnologists were randomly divided into two groups of video observers and still image observers. The participants were asked to make a diagnosis of benign, indeterminate, suspicious or malignant without having any clinical information other than the age of the patient. Diagnoses were categorized as 'recommended' or 'unacceptable' according to degree of correlation with histology. RESULTS: The number of definitive diagnoses of 'benign' or 'malignant' were increased in video observers, and indeterminate or suspicious categories were decreased (P = 0.013). The distribution of diagnostic categories in three of the 17 cases was significantly different; the distribution in the remaining cases was similar between the two groups. The z-axis video observers may have selected the definite diagnoses with confidence because they observed valuable microscopic findings by 'focusing through observation'. The average number of 'recommended' diagnoses by individual observers was significantly higher in the video observer group than in the still image observer group (P = 0.016). In contrast, the average number of 'unacceptable' diagnoses was significantly lower (P = 0.019). CONCLUSIONS: A z-axis video is easy to obtain and is therefore expected to become a powerful diagnostic modality for the external quality assessment of clinical cytology and even in the field of primary cytodiagnosis.

Performance enhancement of semiconductor devices by control of discrete dopant distribution.

As semiconductor devices are scaled down to the nanometre level, random dopant fluctuation in the conducting channel caused by the small number of dopant atoms will significantly affect device performance. We fabricated semiconductor devices with random discrete dopant distribution in the drain side and then evaluated how well we could control the drain current of the devices. The results showed that the drain current in devices with the dopant distribution in the drain side was several per cent higher than that in devices with the dopant distribution in the source side. We believe that this increase in current is caused by the suppression of injection velocity degradation in the source side. The capability to control the location of individual dopant atoms enhances drain current and, therefore, the performance of nanodevices. Accurately controlling both the amount and the positioning of dopant atoms is critical for the advancement of true nanoelectronics.

Cytomegalovirus infection with perineal pain after living donor liver transplantation: report of four cases.

We report on 4 adult cases of presumptive cytomegalovirus (CMV) disease with perineal pain after living donor liver transplantation. Patients presented with severe perineal pain without any other symptoms related to CMV infection, except pyrexia. All patients had an episode of acute cellular rejection (ACR) before the onset of perineal pain, and 1 patient needed OKT3 therapy. The severe perineal pain was not well controlled with medication, and 1 patient needed epidural anesthesia. In the first 3 patients, pp65 CMV antigenemia (pp65CMV-Ag) test results were positive and intravenous administration of ganciclovir (GCV) therapy was initiated. In the last patient, GCV therapy was preemptively administered before a positive pp65CMV-Ag test result was confirmed. After administration of GCV, the pain gradually disappeared and all patients had negative pp65CMV-Ag test results. In conclusion, unusual perineal pain can be a symptom related to CMV infection. CMV infection needs to be kept in mind when a liver transplant recipient has severe perineal pain, especially after receiving treatment for ACR.

Roles of cyclooxygenase-2 and prostaglandin E receptors in gastric mucosal defense in Helicobacter pylori-infected mice.

BACKGROUND/AIM: Helicobacter pylori (H. pylori) induces cyclooxygenase-2 (COX-2) expression. The aim of this study was to assess the roles of COX-2 and PGE2 receptors (EPs) in gastric defense in H. pylori-infected mice. METHODS: Gastric lesions were induced by oral administration of 0.15N HCl in 60% ethanol (HCl/EtOH) to mice infected with H. pylori, and macroscopically evaluated 30 min later. Mice were administered NS-398 (COX-2 selective inhibitor) concomitantly with selective EP agonists 4 hours before HCl/EtOH challenge. RESULTS: H. pylori infection prevented the gastric damage induced by HCl/ EtOH, and this protective effect was abolished by NS-398. Selective agonists of EP1, EP2, and EP4, but not the EP3 agonist, reversed the inhibitory effect of NS-398 on prevention of damage by H. pylori infection. The EP4 agonist and EP2/EP4 agonists inhibited the increase in TNF-alpha mRNA expression and neutrophilic infiltration caused by NS-398, respectively. CONCLUSION: COX-2-derived PGE2 may play an important role in resistance to HCl/EtOH damage in H. pylori-infected mice by activating EP1, EP2, and EP4.

Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin.

BACKGROUND: Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes. OBJECTIVES: To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope. RESULTS: Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.