Harmonic radiation contribution and X-ray transmission at the Small Quantum Systems instrument of European XFEL.

Transmission measurements of the soft X-ray beamline to the Small Quantum Systems (SQS) scientific instrument at the SASE3 undulator of European XFEL are presented. Measurements are reported for a wide range of photon energies (650 eV to 2400 eV), using X-ray gas monitors as well as a bolometric radiometer. The results are in good agreement with simulations for the beam transport and show a transmission of up to 80% over the whole photon energy range. The contribution of second- and third-harmonic radiation of the soft X-ray undulator is determined at selected photon energies by performing transmission measurements using a gas absorber to provide variable attenuation of the incoming photon flux. A comparison of the results with semi-analytic calculations for the generation of free-electron laser pulses in the SASE3 undulator reveals an influence of apertures along the beam transport on the exact harmonic content to be accounted for at the experiment. The second-harmonic content is measured to be in the range of 0.1% to 0.3%, while the third-harmonic contributed a few percent to the SASE3 emission. For experiments at the SQS instrument, these numbers can be reduced through specific selections of the mirror reflection angles.

Measurement of the absolute number of photons of the hard X-ray beamline at the Linac Coherent Light Source.

X-ray free-electron lasers provide intense pulses of coherent X-rays with a short pulse duration. These sources are chaotic by nature and therefore, to be used at their full potential, require that every X-ray pulse is characterized in terms of various relevant properties such as intensity, photon energy, position and timing. Diagnostics are for example installed on an X-ray beamline to specifically monitor the intensity of individual X-ray pulses. To date, these can however only provide a single-shot value of the relative number of photons per shot. Here are reported measurements made in January 2015 of the absolute number of photons in the hard X-ray regime at LCLS which is typically 3.5 × 1011 photons shot-1 between 6 and 9.5 keV at the X-ray Pump-Probe instrument. Moreover, an average transmission of ≉62% of the hard X-ray beamline over this energy range is measured and the third-harmonic content of ≉0.47% below 9 keV is characterized.

The utility of longitudinal slicing method for rectal specimen: pathological analysis of circumferential resection margin of intersphincteric resection for low-lying rectal cancer.

The pathological assessment of the resection margin of rectal cancer is important to predict clinical outcome. The transverse slicing method of rectal specimens is recommended in Western countries. However, in Japan the longitudinal slicing method is traditionally advocated. The aim of this study was to assess the advantages of the longitudinal slicing method. The subjects were 197 consecutive patients with primary rectal cancer who underwent curative intersphincteric resection from 2000 to 2013. The resected rectal specimens were cut into 12 slices in the direction of the long axis. Resection margin was considered positive when it was less than or equal to 1 mm. Resection margin was positive in 23 patients (12%). They were classified into two groups, namely the DEEP group (n = 16, 70%), when the resection margin corresponded to the deepest tumor invasion area, and the ENTRY group (n = 7, 30%), when resection margin was around the initial cutting point of the anal canal. It was shown that resection margin tends to be positive not only in the deepest tumor invasion area but also in the entry area of the anal canal. The longitudinal slicing method may have some advantages for accurate assessment of resection margin especially in low-lying rectal cancer.

Probing gaseous molecular structure by molecular-frame photoelectron angular distributions.

Carbon 1s photoelectron angular distributions of an iodomethane molecule were measured relative to the recoil-frame determined by the momentum correlation between I+ and CH3 + at photoelectron energies of 3, 6.1, and 12 eV. The energy dependent behavior of the recoil-frame photoelectron angular distributions is reproduced reasonably well by the time-dependent density functional theory with B-spline methods. We discuss potential applications of the fully differential photoelectron angular distribution measurements in the molecular frame to three-dimensional molecular structural determinations identifying the directions and lengths of the bonds.

Probing molecular bond-length using molecular-frame photoelectron angular distributions.

The molecular-frame photoelectron angular distributions (MFPADs) in O 1s photoemission from CO2 molecule were measured. Patterns due to photoelectron diffractions were observed in the MFPADs. The polarization-averaged MFPADs were compared with theoretical calculation and were found to be useful in determining the molecular bond-length, which is a component to determine molecular structures.

Nomogram for predicting anastomotic leakage after low anterior resection for rectal cancer.

PURPOSE: Anastomotic leakage after low anterior resection for rectal cancer is a critical problem. Many risk factors have been suggested and surgical techniques have improved, but anastomotic leakage remains a major postoperative challenge. This study sought to create a nomogram for precise prediction of anastomotic leakage after low anterior resection for rectal cancer. METHODS: We used data of 936 patients that had been prospectively collected by the Japanese Society for Colon and Rectal Cancer between June 2010 and February 2013. Risk factors for anastomotic leakage were identified by multivariate logistic regression analysis and used to create a nomogram. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots. RESULTS: Sex, preoperative serum albumin, tumor location and diameter, and simultaneous resection of other organs were identified as significantly associated factors that could be combined for accurate prediction of anastomotic leakage. We created a nomogram for anastomotic leakage by using these risk factors. The area under the curve was 0.72 (95% confidence interval 0.67-0.76). The nomogram had a bootstrapped-concordance index of 0.72 and was well calibrated. CONCLUSIONS: Our nomogram was a useful tool for precise prediction of anastomotic leakage after low anterior resection for rectal cancer.

A Proposed Molecular Mechanism for Physical Analgesia in Chronic Pain.

Although pain is indispensable for survival, chronic pain places a heavy burden on humans. As the efficacy of opioid treatment is limited, the development of alternative methods of pain relief without medication is desirable. Recently, we have developed a novel method of physical analgesia using an adhesive "pyramidal thorn patch." When we apply about 3 trials of these patches on the skin of a pain region, the pain region moves toward the spinal cord like a "cutaneous rabbit," and finally, the pain vanishes. In the present review, we propose a molecular mechanism for this analgesic method or pain relief following application of the pyramidal thorn patch where firstly the mechanoreceptors and their related nerves under the skin are activated in response to touch. Transient receptor potential (TRP) channels serve as mechanosensitive channels within these mechanoreceptors. We further propose that activation of the nerves connected with the mechanoreceptors releases oxytocin, which has an antinociceptive function and activates TRP channels to hyperpolarize the pain signal nerves. We believe that our system will pave the way for alternative pain treatment.

Compact bolometric radiometer for free-electron lasers in a wavelength range from extreme-ultraviolet to x-rays.

A reliable diagnostic device for free-electron lasers (FELs) is essential for both users and the evaluation of FEL sources and beamline optics. Here, we propose a compact bolometric radiometer (CBR) that can operate at room temperature. The CBR is mainly designed for FELs in the wavelength range from the extreme-ultraviolet (EUV) to x-rays; moreover, we confirmed that the proposed device can also be applied to synchrotron radiation. As an application of the CBR, we evaluated an FEL beamline transmission by means of bolometric technique in the EUV range for the first time, to the best of our knowledge. This indicates that the CBR is an effective diagnostic device for FELs.

Postoperative Chemoradiotherapy After Local Resection for High-Risk T1 to T2 Low Rectal Cancer: Results of a Single-Arm, Multi-Institutional, Phase II Clinical Trial.

BACKGROUND: After treatment with local excision for TNM stage I low rectal cancer, the risk of local recurrence is not only high for T2 lesions but also for T1 lesions with features of massive invasion to the submucosal layer and/or lymphovascular invasion. OBJECTIVE: The purpose of this study was to determine the efficacy of chemoradiotherapy combined with local excision in the treatment of T1 to T2 low rectal cancer. DESIGN: We conducted a prospective, single-arm, phase II trial. SETTINGS: This was a multicenter study. PATIENTS: From April 2003 to October 2010, 57 patients were treated with local excision after additional external beam irradiation (45 Gy) plus continuous 5-week intravenous injection of 5-fluorouracil (250 mg/m per day) at 10 domestic hospitals. Fifty-three patients had clinical T1N0 lesions, and 4 had T2N0 lesions in the low rectum, located below the peritoneal reflection. MAIN OUTCOMES MEASURES: The primary end point was disease-free survival at 5 years. RESULTS: The completion rate for full-dose chemoradiotherapy was 86% (49/57). Serious, nontransient treatment-related complications were not reported. With a median follow-up of 7.3 years after local excision, the 5-year disease-free survival rate was 94% for the 53 patients with T1 lesions and 75% for the 4 patients with T2 lesions. There were 2 local recurrences during the entire observation period. Anal function after local excision and chemoradiation were kept at almost the same levels as observed before treatment. LIMITATIONS: The study was limited by the small number of registered T2 rectal cancers, retrospective evaluations of quality of life, and the exclusion of poorly differentiated adenocarcinoma (a high-risk feature of T1 lesions). CONCLUSIONS: The addition of chemoradiotherapy to local excision of T1 rectal adenocarcinomas with poor prognostic features including deep submucosal invasion and lymphovascular invasion could improve on less favorable historic oncologic outcomes of local excision alone in this high-risk group for lymph node metastasis. See Video Abstract at http://links.lww.com/DCR/A421.

Lattice and Valence Electronic Structures of Crystalline Octahedral Molybdenum Halide Clusters-Based Compounds, Cs2[Mo6X14] (X = Cl, Br, I), Studied by Density Functional Theory Calculations.

The electronic and crystal structures of Cs2[Mo6X14] (X = Cl, Br, I) cluster-based compounds were investigated by density functional theory (DFT) simulations and experimental methods such as powder X-ray diffraction, ultraviolet-visible spectroscopy, and X-ray photoemission spectroscopy (XPS). The experimentally determined lattice parameters were in good agreement with theoretically optimized ones, indicating the usefulness of DFT calculations for the structural investigation of these clusters. The calculated band gaps of these compounds reproduced those experimentally determined by UV-vis reflectance within an error of a few tenths of an eV. Core-level XPS and effective charge analyses indicated bonding states of the halogens changed according to their sites. The XPS valence spectra were fairly well reproduced by simulations based on the projected electron density of states weighted with cross sections of Al Kα, suggesting that DFT calculations can predict the electronic properties of metal-cluster-based crystals with good accuracy.

The Impact of Anastomotic Leakage on Anal Function Following Intersphincteric Resection.

BACKGROUND: Data regarding anastomotic leakage (AL) following intersphincteric resection (ISR) are lacking. We aimed to evaluate the effect of AL on anal function in a retrospective review of patients who developed AL following ISR. METHODS: We evaluated 341 consecutive patients who underwent ISR between 2000 and 2012. Patients were classified into three groups: anastomotic dehiscence (AD), major AL (Clavien-Dindo grade III+), or control (

Anal Function after Surgery for Low-Lying Rectal Cancer: Comparison of Mechanical and Hand-Sewn Coloanal Anastomosis.

BACKGROUND/AIMS: Mechanical coloanal anastomosis (MCAA) or hand-sewn coloanal anastomosis (HCAA) are used in anus-preserving surgery for low-lying rectal cancer. Either method can be used if the lower edge of the tumor is 4-6 cm from the anal verge. The goal of this study was to evaluate differences in the anal function after MCAA or HCAA. METHODS: The subjects were 305 consecutive patients with primary rectal cancer tumors situated 4-6 cm from the anal verge who underwent curative anus-preserving surgery between 2004 and 2013. Functional assessment was performed using a questionnaire at 3, 6, 12, and 24 months after stoma closure. RESULTS: Of the 305 patients, 145 underwent MCAA and 160 underwent HCAA. The median distance of the tumor from the anal verge was 6.0 cm (range 4.0-6.0) in the MCAA group and 4.5 cm (range 4.0-6.0) in the HCAA group (p < 0.001). A total of 192 patients (73%) responded to the 1-year questionnaire. The median Wexner score was 6 (range 0-17) in the MCAA group and 11 (range 0-20) in the HCAA group (p < 0.001). CONCLUSIONS: Retention of anal function is feasible after both MCAA and HCAA. MCAA may contribute to better postoperative anal function compared to HCAA.

Analysis of a Surgical Treatment for Persistent Urorectal Fistulas after Radical Cancer Surgery: A Comparison of Prostate Cancer and Rectal Cancer.

INTRODUCTION: The study aimed to present our experience of surgical treatment for urorectal fistulas (URF) that develop after cancer surgery. MATERIALS AND METHODS: Fourteen patients with URF who were treated at our institution from 2005 through 2015 were retrospectively analyzed. Among these, 7 patients had previous surgical treatment of prostate cancer (PC) and the other 7 had been treated for rectal cancer (RC). The fistula was resected through a perineal incision, and the urinary and fecal defects were separately closed with the hinge flap method followed by interposition of a muscle flap transfer. RESULTS: The overall fistula closure rate was 79%. Although the closure rate of the URF was lower in patients with previous RC surgery compared to the PC patients (57 vs. 100%), it did not reach statistical significance. CONCLUSIONS: URF treatment using an interposition muscle flap offers a high success rate of fistula closure. However, complicated fistulas occurring after RC surgery involving the prostate or the seminal vesicle might be difficult to repair by this surgery alone.

Quantitative evaluation of 3D imaging in laparoscopic surgery.

PURPOSE: 3D images offer true depth perception, which overcomes one of the disadvantages of laparoscopic surgery. We evaluated differences in the use of 3D and 2D images in laparoscopic surgery based on the recording of traces of forceps. METHODS: Twelve surgeons at our hospital participated in the study. The task consisted of one suture and three ligations, using a training box. The completion time and number of hold errors were noted, and forceps traces were recorded using the Behavior Checker system (Miura Medical). Participants were divided into two groups based on faster and slower completion times with 2D images. RESULTS: The median completion time in seconds (s) was significantly shorter when using 3D images than when using 2D images (51 s, range 34-146 vs. 63 s, range 38-265 s; p = 0.013). The 3D/2D completion time ratio was significantly higher in the faster 2D group (0.93 vs. 0.69, p = 0.030) indicating a greater effect of the 3D images on less experienced participants. CONCLUSIONS: A quantitative evaluation showed that using 3D images enables more efficient use of laparoscopic forceps than 2D images. A system with 3D images is of particular benefit for inexperienced surgeons.

Efficacy of an additional flap operation in bladder-preserving surgery with radical prostatectomy and cystourethral anastomosis for rectal cancer involving the prostate.

PURPOSE: Sphincter-preserving operations performed with bladder-preserving surgery and a cystourethral anastomosis (CUA) do not require a urinary stoma, but leakage from the CUA may develop. The aim of this study was to evaluate the efficacy of performing an additional flap operation. METHODS: The subjects were 39 patients who underwent bladder-preserving surgery for advanced rectal cancer involving the prostate, between 2001 and 2015.32 of whom had a CUA and one of whom had a neobladder. Five of these 32 patients underwent an ileal flap operation, 2 underwent an omental flap operation, and 3 underwent an operation using both flaps. RESULTS: Leakage developed in 3 (30%) of the 10 patients who underwent additional flap operations, but in 14 (60.9%) of the 23 patients who did not undergo a flap operation. The mean periods of catheterization for the patients who suffered leakage were 31 weeks (8-108 weeks) in those without a flap and 16 weeks (8-20 weeks) in those with a flap. Four (33.3%) of the 12 patients with leakage after surgery without a flap had a period of urinary catheterization >30 weeks, and 2 (16.7%) had leakage of CTCAE grade 3. There were no cases of leakage after flap surgery. CONCLUSION: An additional flap operation may decrease the risk of leakage from a CUA.

Gene expression profile in the activation of subperitoneal fibroblasts reflects prognosis of patients with colon cancer.

Tumors can create a heterogenetic tumor microenvironment. We recently identified the pathologically unique cancer microenvironment formed by peritoneal invasion (CMPI), and revealed that subperitoneal fibroblasts (SPFs) within peritoneal tissue play a crucial role in tumor progression through their interaction with cancer cells. Therefore, the genes in SPFs altered by cancer stimulation may include some biologically important factors associated with patient prognosis. In this study, we aimed to identify new biomarkers using genes specifically upregulated in SPFs by cancer-cell-conditioned medium (CCCM) stimulation (SPFs CCCM response genes; SCR genes) in colon cancer (CC). We constructed two frameworks using SCR gene data: a publicly released microarray dataset, and validation cases with freshly frozen CC samples to identify genes related to short recurrence-free survival (RFS). In the first framework, we selected differentially expressed genes between the high and low SCR gene expression groups. In the second framework, genes significantly related to short RFS were selected by univariate analysis using all SCR genes, and multivariate analysis was performed to select robust genes associated with short RFS. We identified CTGF, CALD1, INHBA and TAGLN in the first framework, and PDLIM5, MAGI1, SPTBN1 and TAGLN in the second framework. Among these seven genes, high expression of three genes (CALD1, TAGLN and SPTBN1) showed a poor prognosis in our validation cases. In a public microarray dataset, SCR gene expression was associated with the expression of ECM component, EMT, and M2-macrophage associated genes, which was concordant with the pathological features of CMPI. Thus, we successfully identified new prognostic factors.

Prognostic and predictive value of extended RAS mutation and mismatch repair status in stage III colorectal cancer.

The prognostic and predictive value of KRAS gene mutations in stage III colorectal cancer is controversial because many recent clinical trials have not involved a surgery-alone arm. Additionally, data on the significance of extended RAS (KRAS/NRAS) mutations in stage III cancer are not available. Hence, we undertook a combined analysis of two phase III randomized trials, in which the usefulness of adjuvant chemotherapy with tegafur-uracil (UFT) was evaluated, as compared with surgery alone. We determined the association of extended RAS and mismatch repair (MMR) status with the effectiveness of adjuvant chemotherapy. Mutations in KRAS exons 2, 3, and 4 and NRAS exons 2 and 3 were detected by direct DNA sequencing. Tumor MMR status was determined by immunohistochemistry. Total RAS mutations were detected in 134/304 (44%) patients. In patients with RAS mutations, a significant benefit was associated with adjuvant UFT in relapse-free survival (RFS) (hazard ratio = 0.49; P = 0.02) and overall survival (hazard ratio = 0.51; P = 0.03). In contrast, among patients without RAS mutations, there was no difference in RFS or overall survival between the adjuvant UFT group and surgery-alone group. We detected deficient DNA MMR in 23/304 (8%) patients. The MMR status was neither prognostic nor predictive for adjuvant chemotherapy. An interaction analysis showed that there was better RFS among patients treated with UFT with RAS mutations, but not for those without RAS mutations. Extended RAS (KRAS/NRAS) mutations are proposed as predictive indicators with respect to the efficacy of adjuvant UFT chemotherapy in patients with resected stage III colorectal cancer.

Topographic Anatomy of the Anal Sphincter Complex and Levator Ani Muscle as It Relates to Intersphincteric Resection for Very Low Rectal Disease.

BACKGROUND: Intersphincteric resection has become a widely used treatment for patients with rectal cancer. However, the detailed anatomy of the anal canal related to this procedure has remained unclear. OBJECTIVE: The purpose of this study was to clarify the detailed anatomy of the anal canal. DESIGN: This is a descriptive study. SETTINGS: Histologic evaluations of paraffin-embedded tissue specimens were conducted at a tertiary referral hospital. PATIENTS: Tissue specimens were obtained from cadavers of 5 adults and from 13 patients who underwent abdominoperineal resection for rectal cancer. MAIN OUTCOME MEASURES: Sagittal sections from 9 circumferential portions of the cadaveric anal canal (histologic staining) and 3 circumferential portions from patients were studied (immunohistochemistry for smooth and skeletal muscle fibers). RESULTS: Longitudinal fibers between the internal and external anal sphincters consisted primarily of smooth muscle fibers that continued from the longitudinal muscle of the rectum. The levator ani muscle attached directly to the lateral surface of the longitudinal smooth muscle of the rectum. The length of the attachment was longer in the anterolateral portion and shorter in the posterior portion of the anal canal. In the lateral and posterior portions, the levator ani muscle partially overlapped the external anal sphincter; however, there was less overlap in the anterolateral portion. In the posterior portion, thick smooth muscle was present on the surface of the levator ani muscle and it continued to the longitudinal muscle of the rectum. LIMITATIONS: We observed only limited portions in some surgical specimens because of obstruction by tumors. CONCLUSIONS: The levator ani muscle attaches directly to the longitudinal muscle of the rectum. The spatial relationship between the smooth and skeletal muscles differed in different portions of the anal canal. For intersphincteric resection, dissection must be performed between the longitudinal muscle of the rectum and the levator ani muscle/external anal sphincter, and the appropriate surgical lines must be selected based on the specific structural characteristics of each portion.

Association between pathologic features of peripheral nerves and postoperative anal function after neoadjuvant therapy for low rectal cancer.

PURPOSE: Neoadjuvant chemoradiotherapy (CRT) for rectal cancer improves local control but also induces severe postoperative anal dysfunction that may be related to neural degeneration. The aims of the study were to identify pathological features of neural degeneration caused by neoadjuvant CRT or neoadjuvant chemotherapy (NAC) and to evaluate the association between neural degeneration and anal function. METHODS: A retrospective study using chronologically different groups was performed in 95 patients with rectal cancer treated with curative resection with neoadjuvant CRT (n = 47), NAC (n = 27), or surgery alone (no neoadjuvant therapy) (n = 21) at National Cancer Center Hospital East from 2001 to 2014. Peripheral nerve degeneration was evaluated histopathologically using H&E stained sections, based on karyopyknosis, vacuolar or acidophilic degeneration, denucleation, adventitial neuron change, and fibrosis. Morphological analysis of peripheral nerves was compared among the three groups. The association between pathological features and anal function (Wexner Score) was evaluated. RESULTS: After CRT, the degree of fibrosis around the tumor was severe, and neural degeneration was found in peripheral neurons. With NAC and surgery alone, there was little fibrosis and neural degeneration. Pathological changes after CRT were more pronounced than those after NAC, indicating greater tissue degeneration due to CRT. There was an association between anal function and degeneration score in the CRT group, but not in the other groups. CONCLUSIONS: Peripheral nerves in patients who received neoadjuvant CRT showed characteristic pathological features indicating greater degeneration, compared with patients who received NAC. Neural degeneration is associated with anal function and several pathological factors after CRT.

Comparison of symptomatic anastomotic leakage following laparoscopic and open low anterior resection for rectal cancer: a propensity score matching analysis of 1014 consecutive patients.

BACKGROUND: This observational study was conducted to compare the rate of symptomatic anastomotic leakage (AL), as defined by precise criteria, between laparoscopic and open surgery in patients with mid-to-low rectal cancer using a relatively novel statistical technique. METHODS: A total of 1014 consecutive low anterior resection (LAR) patients were registered, of whom 936 were included in this prospective, multicenter, and cohort study (UMIN-CTR, Number 000004017). Patients with rectal cancer within 10 cm from the anal verge underwent either open or laparoscopic LAR at one of the 40 institutions in Japan from June 2010 to February 2013. The primary endpoint of this study was to compare the rate of symptomatic AL between the two groups before and after propensity score matching (PSM). The secondary endpoint was to analyze the risk factors for symptomatic AL in open and laparoscopic surgery. RESULTS: After PSM, the incidence of symptomatic AL in open and laparoscopic surgery was 12.4 and 15.3 %, respectively (p = 0.48). AL requiring relaparotomy occurred after 3.8 % of open surgeries and 6.2 % of laparoscopic surgeries (p = 0.37). Multivariate analysis identified male gender as an independent risk factor for symptomatic AL following laparoscopic surgery (p = 0.001; odds ratio 5.2; 95 % CI 2.0-13.8), and male gender (p = 0.004; odds ratio 2.6; 95 % CI 1.3-5.6), tumor size (p = 0.002; odds ratio 1.2; 95 % CI 0.7-0.9), and number of stapler firing (p = 0.04; odds ratio 4.1; 95 % CI 1.0-15.0) following open surgery. CONCLUSION: The rate of symptomatic AL was comparable following laparoscopic and open LAR in this large, multicenter, cohort study after PSM. Male gender was associated with an increased risk of symptomatic AL after laparoscopic LAR.