Totally laparoscopic resection of right-sided colon cancer using transvaginal specimen extraction with a 10-mm-long abdominal incision.

BACKGROUND: Natural orifice specimen extraction (NOSE) has been developed as a means of decreasing the incidence of surgical wound complications. We refined the procedure for totally laparoscopic colectomy with transvaginal specimen extraction using the reduced port surgery technique with the ultimate goal of attenuating damage to the abdominal wall. We herein report this innovative technique and its short- and long-term outcomes. METHODS: We prospectively collected data on seven patients who underwent totally laparoscopic colectomy using transvaginal specimen extraction with a 10-mm-long abdominal incision for right-sided colon cancer from January 2014 to December 2021. Two 5-mm ports were used in the procedure without laparotomy. Transverse transabdominal posterior colpotomy was then performed. We introduced a GelPOINT Mini advanced access platform (Applied Medical, Rancho Santa Margarita, CA, USA) into the transvaginal route for the insertion of a laparoscope, forceps, and stapling device. Lymph node dissection and transection of the ileum and distal colon were performed with transvaginal assistance. A specimen was then extracted transvaginally. Intracorporeal functional end-to-end anastomosis was conducted using a linear stapler through the vagina. After the removal of GelPOINT Mini, the vaginal incision was closed transvaginally. RESULTS: Seven patients successfully underwent this procedure. Median operative time was 219 min (range 174-255 min), median blood loss was 23 ml (range 10-37 ml), median number of harvested lymph nodes was 21 (range 17-35 lymph nodes) and median margins were 17.0 cm (range 9.0-25.0 cm) for the proximal margin and 9.5 cm (range 5.0-13.0 cm) for the distal margin. There were no complications more severe than Clavien-Dindo Grade II and there was no mortality. The median frequency of use intravenous analgesics from postoperative day 1 to discharge was once. Two patients did not require analgesics. A node-positive patient developed recurrence at the lung and paraaortic lymph nodes. CONCLUSIONS: This procedure appears to be feasible, safe, and oncologically acceptable for selected cases.

Prediction of a single Gaussian shape of spectral line measured with low-dispersion spectrometer by using machine learning.

We have developed a denoising autoencoder based neural network (NN) method to determine a spectral line intensity with an uncertainty lower than the uncertainty determined by fitting the spectral line. The NN method processes the measured raw spectral line shape, providing a single Gaussian shape based on the training dataset, which consists of synthetically prepared Doppler shift and broadening free spectral lines in the present work. It is found that the uncertainty reduction level significantly depends on the training dataset. Limitations originating from the training dataset are also discussed.

mTOR Inhibition Ablates Cisplatin-Resistant Salivary Gland Cancer Stem Cells.

Patients with advanced salivary gland mucoepidermoid carcinoma (MEC) are treated with surgery and radiotherapy, as current systemic therapies are largely ineffective. As such, current treatment frequently leads to poor long-term survival due to locoregional recurrence or metastases. We have shown that salivary gland cancer stem cells (CSCs) are resistant to platinum-based chemotherapy and drive tumor progression. The purpose of this study was to investigate the effect of therapeutic inhibition of mTOR (mechanistic target of rapamycin) on resistance of CSCs to cisplatin, a prototypic platinum-based chemotherapeutic agent. Viability assays determined the effect of several inhibitors of PI3k/mTOR signaling (e.g., temsirolimus, BKM120, AZD8055, PF4708671) and/or cisplatin on survival of human MEC cells. The impact of mTOR inhibitors and/or cisplatin on MEC stemness was examined with salisphere assays, flow cytometry for ALDH/CD44 (CSC markers for MEC), and Western blots for Bmi-1 expression (marker of stem cell self-renewal). Salivary gland MEC patient-derived xenografts were used to examine the effect of cisplatin and/or temsirolimus on CSCs in vivo. We observed that cisplatin induced mTOR and S6K1 phosphorylation, increased the number and size of MEC salispheres, and induced Bmi-1 expression and the fraction of CSCs in MEC models in vitro. Cisplatin also increased the fraction of CSCs in vivo. In contrast, mTOR inhibition (e.g., temsirolimus) blocked cisplatin-induced Bmi-1 expression and salisphere formation in vitro. Remarkably, temsirolimus slowed down tumor growth and decreased the fraction of CSCs (P < 0.05) even in presence of cisplatin in a short-term in vivo experiment. Collectively, these results demonstrate that therapeutic inhibition of mTOR ablates cytotoxic-resistant CSCs, and they suggest that a combination of an mTOR inhibitor and platinum-based chemotherapy might be beneficial to patients with salivary gland mucoepidermoid carcinoma.

Search for η

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ_{lab}^{ηp}<-0.9 was obtained to be 2.2 nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Tongue surface model can predict radiation tongue mucositis due to intensity-modulated radiation therapy for head and neck cancer.

Acute radiation tongue mucositis has a profound effect on talking and eating. We examined whether the dose-volume histogram obtained from the tongue surface model correlates with mucositis severity, and whether it is useful for predicting acute radiation tongue mucositis in patients with head and neck cancer treated with intensity-modulated radiation therapy. Thirty-six patients who received intensity-modulated radiation therapy for head and neck cancer were analysed for acute radiation tongue mucositis according to the Common Terminology Criteria for Adverse Events, version 4.0, as well as the Radiation Therapy Oncology Group scoring systems. The corresponding high-dose locations in anatomical sub-regions in the tongue surface model and the development of high-grade acute radiation tongue mucositis were compared. The mucositis sites coincided with the high-dose anatomical sub-regions in the tongue surface model. There was a clear dose-response relationship between the mean dose to the tongue and the acute radiation tongue mucositis Radiation Therapy Oncology Group grade. According to the dose-volume histogram, patients receiving 16.0-73.0 Gy to the tongue were susceptible to grade 2-3 toxicity. The tongue surface model can predict the site and severity of acute radiation tongue mucositis. In future, radiation treatment plans ccould be optimized using this model.

Study of twice-weekly injections of Teriparatide by comparing efficacy with once-weekly injections in osteoporosis patients: the TWICE study.

A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen of teriparatide, while also improving safety. INTRODUCTION: While a 56.5-µg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-µg teriparatide can provide comparable efficacy to the 56.5-µg once-weekly regimen while improving safety. METHODS: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-µg twice-weekly group (n = 277) or the 56.5-µg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up. RESULTS: The percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-µg twice-weekly and 56.5-µg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (- 1.6%), non-inferiority of the 28.2-µg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-µg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-µg twice-weekly group. CONCLUSIONS: A 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen while improving safety. CLINICAL TRIAL REGISTRATION: JapicCTI-163477 .

Parotid gland carcinoma: 32 years' experience from a single institute.

BACKGROUND: Parotid gland carcinoma is a rare and complicated histopathological classification. Therefore, assembling a sufficient number of cases with long-term outcomes in a single institute can present a challenge. METHOD: The medical records of 108 parotid gland carcinoma patients who were treated at Kyushu University Hospital, Fukuoka, Japan, between 1983 and 2014 were reviewed. The survival outcomes were analysed according to clinicopathological findings. RESULTS: Forty-six patients had low clinical stage tumours (I-II), and 62 patients had high clinical stage tumours (III-IV). Fifty-two, 10 and 46 patients had low-, intermediate- and high-grade tumours, respectively. Twenty-seven of 65 cases had positive surgical margins. In high clinical stage and intermediate- to high-grade tumours, adjuvant radiation therapy was correlated with local recurrence-free survival (p = 0.0244). Intermediate- to high-grade tumours and positive surgical margins were significantly associated with disease-specific survival in multivariate analysis (p = 0.0002 and p = 0.0058). CONCLUSION: The results of this study show that adjuvant radiation therapy is useful for improved local control in patients with high clinical stage and intermediate- to high-grade tumours.

UVA-activated riboflavin promotes collagen crosslinking to prevent root caries.

Root caries is an increasingly problem in aging societies with severe implications for the general health and wellbeing of large numbers of people. Strengthening type-I collagen, a major organic component of human dentin, has proved effective in preventing root caries. This study sought to determine whether exposure to riboflavin followed by UVA irradiation (RF/UVA) could promote additional collagen crosslinking, and thus improve the acid and enzymatic resistance of human dentin under simulated oral environments. If so, it could offer potential for treatment of the intractable problem of root caries. The greatest flexural strengths were found in dentin exposed to a 0.1% riboflavin solution for 1 minute followed by 1,600 mW/cm2 UVA irradiation for 10 minutes. Mineral loss and lesion depth were significantly lower in the RF/UVA group than in the control group. The microstructures of dentinal tubules and collagen networks after RF/UVA treatment retained their original forms after acidic and enzymatic degradation. In conclusion, RF/UVA treatment may be a new method for preventing root caries with promising prospects for clinical application.

Programmed death-1 ligands and tumor infiltrating T lymphocytes in primary and lymph node metastasis of esophageal cancer patients.

Neoadjuvant chemotherapy (NAC) is administered to many patients with esophageal squamous cell carcinoma (ESCC) prior to surgery, but it is also true that some of these patients demonstrated no response to the therapy following surgery. In addition, the prognosis of advanced case such as ESCC patients with lymph node metastasis has remained relatively low. Programmed death ligand-1 (PD-L1) in conjunction with tumor-infiltrating lymphocytes (TILs) has been studied as a potential mechanism of "immune escape" in several human malignancies. Therefore, in this study, we studied PD-L1 status in carcinoma cells and forkhead box protein 3 (FOXP3) and CD8 status among TILs in the residual tumors of primary and metastatic sites following NAC. We also studied the association of these factors with the clinicopathological findings in 44 patients with ESCC harboring lymph node metastasis. There was discordance in the pathological response to chemotherapy between the primary tumor and lymph node metastasis, and histologically identified resistance to NAC in lymph node metastases tended to be correlated with an adverse clinical outcome (P = 0.0765) than resistance in the primary tumor. Both univariate and multivariate analyses for disease-specific survival (DSS) revealed that the PD-L1 status of carcinoma cells in metastatic lymph nodes and a higher FOXP3/CD8 ratio in the primary tumor were both significantly correlated with an eventual adverse clinical outcome of the patients (P = 0.0178, P = 0.0463, respectively). These results all indicated that the PD-L1 status of carcinoma cells in metastatic lymph nodes and the FOXP3/CD8 ratio in primary tumors could predict eventual clinical outcomes in ESCC patients with NAC.

Thoracoscopic Esophagectomy for a Patient With Perforated Esophageal Epiphrenic Diverticulum After Kidney Transplantation: A Case Report.

A 58-year-old man who underwent cadaveric kidney transplantation twice presented to hospital with a perforated epiphrenic diverticulum. Computed tomography revealed epiphrenic diverticulitis and right pleural effusion. Upper gastrointestinal fibroscopy showed an epiphrenic diverticulum full of food residue. He was transferred to our hospital, where we performed percutaneous endoscopic gastrostomy under general anesthesia in the supine position before thoracoscopy. Thoracoscopic esophagectomy was performed in the semi-prone position under 6-10 mmHg artificial pneumothorax via the right thoracic cavity. We performed subtotal esophagectomy to remove sources of infection because the esophageal wall surrounding the diverticulum was too thick to close or to perform diverticulectomy. A cervical esophagostomy was constructed after the thoracic procedure. The patient was managed with continuous hemodiafiltration and administered immunosuppressants and steroids to preserve the transplanted kidney. Continuous hemodiafiltration was stopped on postoperative day (POD) 4. The patient was discharged from the intensive care unit on POD 10 and transferred to the original hospital on POD 24 for rehabilitation. The second operative stage was performed on POD 157 at our hospital. We performed gastric tube reconstruction via the ante-sternal route and anastomosed the tube to the cervical esophagus. The postoperative course was uneventful; the patient was transferred to the original hospital on POD 15 after the second operation. Minimally invasive surgery was sufficient to treat perforated epiphrenic diverticulum while preserving the transplanted kidney. We recommend completely removing the source of infection and reducing surgical invasiveness to preserve the transplanted kidney in cases of esophageal perforation following kidney transplantation.

The impact of earlier intervention by an antimicrobial stewardship team for specific antimicrobials in a single weekly intervention.

OBJECTIVE: The objective of this study was to evaluate the effects of earlier intervention by an antimicrobial stewardship team (AST) on antimicrobial use, antimicrobial resistance rates, and the clinical outcomes, without changing the weekly intervention schedule. METHODS: A retrospective study was conducted at Fukuoka University Hospital between April 2013 and March 2016. The effects were compared among three study periods (SP): SP1 (patients receiving anti-methicillin-resistant Staphylococcus aureus agents and carbapenems for ≥14 days), SP2 (patients receiving specific antimicrobials for ≥14 days), and SP3 (patients receiving specific antimicrobials regardless of the duration of treatment). RESULTS: The timing of AST intervention was shortened from an average of 15.5days after administration in SP1 to 4.2 days in SP3. The antimicrobial use density (AUD) of carbapenems and piperacillin-tazobactam decreased significantly (SP2 vs. SP3, p<0.05), and the costs of specific antimicrobials decreased (SP1, US$ 1080000; SP2, US$ 944000; SP3, US$ 763000). The rates of carbapenem resistance among Pseudomonas aeruginosa isolates showed a significant reduction from 16.2% in SP2 to 8.7% in SP3 (p<0.05). The mortality rate and length of stay did not change during the study period. CONCLUSIONS: Earlier intervention by an AST could contribute to the proper use of antimicrobials without adversely affecting patient outcomes.

Differential Cross Section and Photon-Beam Asymmetry for the γ[over →]p → π

Differential cross sections and photon-beam asymmetries for the γ[over →]p→π^{-}Δ^{++}(1232) reaction have been measured for 0.7

Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel.

Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.

Vascular branches from cutaneous nerve of the forearm and hand: Application to better understanding raynaud's disease.

Cutaneous nerves have branches called vascular branches (VBs) that reach arteries. VBs are thought to be involved in arterial constriction, and this is the rationale for periarterial sympathectomy as a treatment option for Raynaud's disease. However, the branching patterns and distribution areas of the VBs remain largely unclear. The aim of the present study was to investigate the anatomical structures of the VBs of the cutaneous nerves. Forty hands and forearms were examined to assess the branching patterns and distribution areas of the VBs of the superficial branch of the radial nerve (SBRN), the lateral antebrachial cutaneous nerve (LACN), the medial antebrachial cutaneous nerve (MACN), and the palmar cutaneous branch of the ulnar nerve (PCUN). VBs reaching the radial and ulnar arteries were observed in all specimens. The branching patterns were classified into six types. The mean distance between the radial styloid process and the point where the VBs reached the radial artery was 34.3 ± 4.8 mm in the SBRN and 38.5 ± 15.8 mm in the LACN. The mean distance between the ulnar styloid process and the point where the VBs reached the ulnar artery was 60.3 ± 25.9 mm in the MACN and 43.8 ± 26.0 mm in the PCUN. This study showed that the VBs of the cutaneous nerves have diverse branching patterns. The VBs of the SBRN had a more limited distribution areas than those of the other nerves. Clin. Anat. 31:734-741, 2018. © 2017 Wiley Periodicals, Inc.

Use of PIXE/PIGE for sequential Ca and F measurements in root carious model.

The progress of caries has conventionally been evaluated by checking changes in mineral density using transverse microradiography (TMR). Recent advances have seen development of a new measurement system, using in-air micro proton induced X-ray/gamma-ray emission (PIXE/PIGE). PIXE/PIGE enables analysis of distributions and concentrations of multiple mineral elements in a carious lesion. The aim of this study was to evaluate the effectiveness of PIXE/PIGE for investigating the development of root caries. In summary, we successfully established a multi-elemental sequential measuring method using in-air micro-PIXE/PIGE to identify the dynamic distributions and concentrations of Ca and F in human root dentin. The PIXE/PIGE potentially offers a useful advantageous technique for studying carious development by using as a combination with conventional techniques such as TMR and Micro-computed tomography (µCT).

Monodomain Blue Phase Liquid Crystal Layers for Phase Modulation.

Liquid crystal "Blue Phases" (BP) have evolved, in the last years, from a scientific curiosity to emerging materials for new photonic and display applications. They possess attractive features over standard nematic liquid crystals, like submillisecond switching times and polarization- independent optical response. However, BPs still present a number of technical issues that prevent their use in practical applications: their phases are only found in limited temperature ranges, thus requiring stabilization of the layers; stabilized BP layers are inhomogeneous and not uniformly oriented, which worsen the optical performance of the devices. It would be essential for practical uses to obtain perfectly aligned and oriented monodomain BP layers, where the alignment and orientation of the cubic lattice are organized in a single 3D structure. In this work we have obtained virtually perfect monodomain BP layers and used them in devices for polarization independent phase modulation. We demonstrate that, under applied voltage, well aligned and oriented layers generate smoother and higher values of the phase shift than inhomogeneous layers, while preserving polarization independency. All BP devices were successfully stabilized in BPI phase, maintaining the layer monodomain homogeneity at room temperature, covering the entire area of the devices with a unique BP phase.

MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation.

Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1aflox/flox/Mob1b-/-; termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth. Their alveolar epithelial cells showed increased proliferation, impaired YAP1/TAZ-dependent differentiation and decreased surfactant protein production, all features characteristic of human respiratory distress syndrome. Intriguingly, mutant mice that received Dox postnatally (luMob1DKO (P21-41) mice) did not develop spontaneous lung adenocarcinomas, and urethane treatment-induced lung tumour formation was decreased (rather than increased). Lungs of luMob1DKO (P21-41) mice exhibited increased detachment of bronchiolar epithelial cells and decreased numbers of the bronchioalveolar stem cells thought to initiate lung adenocarcinomas. YAP1/TAZ-NKX2.1-dependent expression of collagen XVII, a key hemidesmosome component, was also reduced. Thus, a MOB1-YAP1/TAZ-NKX2.1 axis is essential for normal lung homeostasis and expression of the collagen XVII protein necessary for alveolar stem cell maintenance in the lung niche.

Progranulin and granulin-like protein as novel VEGF-independent angiogenic factors derived from human mesothelioma cells.

Malignant mesothelioma is an aggressive tumor arising from the mesothelial cells of serous membranes and is associated with tumor angiogenesis, which is a prerequisite for tumor progression. Vascular endothelial growth factors (VEGFs) including VEGF-A have a crucial role in tumor angiogenesis. However, bevacizumab, a monoclonal antibody to VEGF-A, has recently been reported not to improve the progression-free survival of patients with malignant mesothelioma. Cell culture supernatant contains extracellular components such as serum, which can mask the existence of unknown cell-derived factors in the supernatant and make it difficult to detect the factors by subsequent protein analysis. We tried using serum-free culture for human mesothelioma cell lines, NCI-H28, NCI-H2452 and NCI-H2052, and only NCI-H2052 cells adapted to serum-free culture. We found that serum-free culture supernatant derived from NCI-H2052 cells induces the formation of capillary-like tube structures (tube formation) in three-dimensional culture, in which endothelial cells sandwiched between two layers of collagen or embedded in collagen are incubated with various angiogenic inducers. However, neither neutralization of VEGF-A nor RNA interference of VEGF receptor 2 (VEGFR2) suppressed the supernatant-induced tube formation. Using mass spectrometry, we identified a total of 399 proteins in the supernatant, among which interleukin-8 (IL-8), growth-regulated α-protein, midkine, IL-18, IL-6, hepatoma-derived growth factor, clusterin and granulin (GRN), also known as progranulin (PGRN), were included as a candidate protein inducing angiogenesis. Neutralizing assays and RNA interference showed that PGRN, but not the above seven candidate proteins, caused the supernatant-induced tube formation. We also found that NCI-H28 and NCI-H2452 cells express PGRN. Furthermore, we demonstrate that not only PGRN but also GRN-like protein have an important role in the supernatant-induced tube formation. Thus, mesothelioma-derived GRNs induce VEGF-independent angiogenesis.