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.

[Redefinition of the International System of Units (SI) and Related Quantities in the Field of Ionizing Radiation].

The International System of Units (SI) is recommended for the practical system of units of measurement. The decision of redefining the seven base units of the SI (the second, the meter, the kilogram, the ampere, the kelvin, the mole and the candela) was made at the 26th meeting of the General Conference on Weights and Measures on 16 November 2018. This redefinition came into force starting 20 May 2019, and it became a big historic turning point for the metrology society. This is because the kilogram, the unit of mass, was defined only by an artifact as the international prototype of the kilogram, has been kept for 130 years since its determination in 1889, and was finally changed to the new definition by taking the fixed numerical value of the Planck constant on that day.It is easily imagined that the redefinition of the SI base units has a strong impact on our daily life or the field of science. The reason why the SI redefinition had to be adapted is introduced firstly. Then, how the new definitions are applied now after a year from the redefinition and future prospective of the new definitions are discussed. In the last, the impacts of the SI redefinition in the field of the ionizing radiation, especially in the fields of the medical application of the ionizing radiation, are discussed.

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.

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.

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.

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.

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.

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 (

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.

High expression of miR-181c as a predictive marker of recurrence in stage II colorectal cancer.

INTRODUCTION: A standard treatment for stage II colorectal cancer (CRC) is surgical resection without adjuvant chemotherapy. However, the recurrence rate of these patients is approximately 20%. To date, there are no robust biomarkers suitable for predicting recurrence in stage II CRC patients. In this study, microRNAs (miRNAs) extracted from CRC tissues were examined for a possible biomarker to predict recurrence in stage II CRC patients. RESULTS: From the comprehensive analysis, 15 miRNAs were selected as candidates for further study. Regarding let-7a, -7d, -7e, miR-23c, -26b, -128a, -151-5p, and -181c, recurrence rates in training cohort patients with higher expression of these miRNAs isolated from their frozen tissues samples were significantly higher than those with lower expression (P < 0.05). According to multivariate analysis, the higher expression of miR-181c was detected as an independent predictive factor of recurrence (P = 0.001, OR: 9.43, 95% CI: 2.57-34.48). Results were similar in miR-181c extracted from FFPE tissues obtained from the training cohort (P = 0.003, OR: 7.46, 95% CI: 1.97-28.57). In the validation cohort using FFPE tissues, the recurrence rate in patients with higher miR-181c expression was significantly higher than those with lower miR-181c expression (P < 0.001). MATERIALS AND METHODS: Comprehensive analysis using a highly sensitive miRNA chip was initially performed to select candidate miRNAs associated with recurrence. Candidate miRNAs were analyzed by real-time RT-PCR using RNA from frozen and formalin-fixed, paraffin-embedded (FFPE) tissues. CONCLUSIONS: Higher expression of miR-181c may be a useful recurrence predictor of stage II CRC patients.

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.

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.

Neuroendocrine Tumors of the Large Intestine: Clinicopathological Features and Predictive Factors of Lymph Node Metastasis.

A new histological classification of neuroendocrine tumors (NETs) was established in WHO 2010. ENET and NCCN proposed treatment algorithms for colorectal NET. Retrospective study of NET of the large intestine (colorectal and appendiceal NET) was performed among institutions allied with the Japanese Society for Cancer of the Colon and Rectum, and 760 neuroendocrine tumors from 2001 to 2011 were re-assessed using WHO 2010 criteria to elucidate the clinicopathological features of NET in the large intestine. Next, the clinicopathological relationship with lymph node metastasis was analyzed to predict lymph node metastasis in locally resected rectal NET. The primary site was rectum in 718/760 cases (94.5%), colon in 30/760 cases (3.9%), and appendix in 12/760 cases (1.6%). Patients were predominantly men (61.6%) with a mean age of 58.7 years. Tumor size was <10 mm in 65.4% of cases. Proportions of NET G1, G2, G3, and mixed adeno-neuroendocrine carcinoma (MANEC) were 88.4, 6.3, 3.9, and 1.3%, respectively. Of the 760 tumors, 468 were locally resected, and 292 were surgically resected with lymph node dissection. Rectal NET showed a higher proportion of NET G1, and colonic and appendiceal NET was more commonly G3 and MANEC. Of the 292 surgically resected cases, 233 NET G1 and G2 located in the rectum were used for the prediction of lymph node metastasis. Lymphatic and blood vessel invasion were independent predictive factors of lymph node metastasis. NET G2 cases showed more frequent lymph node metastasis than that seen in NET G1 cases, but this was not an independent predictor of lymph node metastasis. Of the 98 surgically resected cases <10 mm in size, we found 9 cases with lymph node metastasis (9.2%). All cases were NET G1, and eight of the nine cases were positive either for lymphatic invasion or blood vessel invasion. Using the WHO classification, we found NET in the large intestine showed a tumor-site-dependent variety of histological and clinicopathological features. Risk of lymph node metastasis in rectal NET was confirmed even in lesions smaller than 10 mm. Concordant assessment of vascular invasion will be required to estimate lymph node metastasis in small lesions.

Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer.

PURPOSE: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. METHODS AND MATERIALS: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. RESULTS: During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. CONCLUSION: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.

Relationship between tissue tension and thermal diffusion to peripheral tissue using an energy device.

The aim of the study was to assess the relationship between tissue tension and thermal diffusion to peripheral tissues using an electric scalpel, ultrasonically activated device, or a bipolar sealing system. The mesentery of pigs was excised with each energy device (ED) at three tissue tensions (0, 300, 600 g). The excision time and thermal diffusion area were monitored with thermography, measured for each ED, and then histologically examined. Correlations between tissue tension and thermal diffusion area were examined. The excision time was inversely correlated with tissue tension for all ED (electric scalpel, r = 0.718; ultrasonically activated device, r = 0.949; bipolar sealing system, r = 0.843), and tissue tension was inversely correlated with the thermal diffusion area with the electric scalpel (r = 0.718) and bipolar sealing system (r = 0.869). Histopathologically, limited deep thermal denaturation occurred at a tension of 600 g with all ED. We conclude that thermal damage can be avoided with adequate tissue tension when any ED is used.

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.

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.

Histological differences between preoperative chemoradiotherapy and chemotherapy for rectal cancer: a clinicopathological study.

Pathological studies on the different histological effects between neoadjuvant chemotherapy (NAC) and preoperative chemoradiation therapy (preoperative CRT) have not been performed. The purpose of this study is to elucidate the histological differences in tissue received from NAC and preoperative CRT for rectal cancer to evaluate whether a pathological assessment method used after CRT can be applied for NAC. One hundred and thirty-eight patients were enrolled in this study; 88 patients underwent their operations after preoperative CRT or NAC, and 50 patients underwent surgery only. Residual tumor area was measured using morphometry software and we compared the stromal component of myofibroblasts, immune cells, and vasculature to elucidate the difference of therapeutic effect between them. The grade of reduction after preoperative CRT was more prominent than that seen in NAC. Also, ypT downstaging was more prominent in preoperative CRT than in NAC, and ypN downstaging was more frequent in NAC than in preoperative CRT. Preoperative CRT showed more marked myofibroblasts and fewer immune cells than did NAC, which indicates different effects on the cancer microenvironment. Our histological results suggest different effects between NAC and preoperative CRT on tumor tissue. The best assessment method available for a variable therapeutic protocol should be further investigated.