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BACKGROUND AND PURPOSES: To describe current practice in the management of rectal cancer, to identify uncertainties that usually arise in the multidisciplinary team (MDT)'s discussions ('grey zones') and propose next generation studies which may provide answers to them. MATERIALS AND METHODS: A questionnaire on the areas of controversy in managing T2, T3 and T4 rectal cancer was drawn up and distributed to the Rectal-Assisi Think Tank Meeting (ATTM) Expert European Board. Less than 70% agreement on a treatment option was indicated as uncertainty and selected as a 'grey zone'. Topics with large disagreement were selected by the task force group for discussion at the Rectal-ATTM. RESULTS: The controversial clinical issues that had been identified within cT2-cT3-cT4 needed further investigation. The discussions focused on the role of (1) neoadjuvant therapy and organ preservation on cT2-3a low-middle rectal cancer; (2) neoadjuvant therapy in cT3 low rectal cancer without high risk features; (3) total neoadjuvant therapy, radiotherapy boost and the best chemo-radiotherapy schedule in T4 tumors. A description of each area of investigation and trial proposals are reported. CONCLUSION: The meeting successfully identified 'grey zones' and, in the light of new evidence, proposed clinical trials for treatment of early, intermediate and advanced stage rectal cancer. ispartof: RADIOTHERAPY AND ONCOLOGY vol:142 pages:6-16 ispartof: location:ITALY, Assisi status: published

The p21 participates in the regulation of DNA repair and replication, and modulation of apoptosis as well. After DNA damage, the p53-dependent induction of p21 results in cell cycle arrest or could trigger cell apoptosis. The objective of the study was the assessment of p21 immunoreactivity in rectal cancer and the estimation of relationships with clinical outcome especially as predictor of poor outcome. While applying the ruling in and out criteria, 102 patients were incorporated to the study, with stage I–IV rectal cancer who had undergone surgery in a planned mode during 2005–2011. The follow-up covered 5 years period from surgery date. Conventional immunohistochemistry were performed using antibody against p21 (p21WAF1 (Clone H252) to detect overexpression targeted receptor. The analysis showed no statistically significant differences in the survival curves of patients in groups with immunoreactivity of p21 protein at 0; 1; 2; 3 (p = 0.6453 in the log-rank test), also is not a significant risk factor for death (HR = 0.915, p = 0.7842) and for tumor dissemination (HR = 0.94, p = 0.9426). Our study leads to the conclusion that the probability of survival does not depend on p21 expression and do not authorize the importance of p21 immunoreactivity in the detection and monitoring of rectal cancer treatment.

Background We conducted a pilot 2-arm randomized controlled trial to assess the feasibility of a digital health intervention to increase moderate-to-vigorous physical activity in patients with colorectal cancer (CRC) during chemotherapy. Objective This study aimed to determine whether a digital health physical activity intervention is feasible and acceptable during chemotherapy for CRC. Methods Potentially eligible patients with CRC expected to receive at least 12 weeks of chemotherapy were identified in person at the University of California, San Francisco, and on the web through advertising. Eligible patients were randomized 1:1 to a 12-week intervention (Fitbit Flex, automated SMS text messages) versus usual care. At 0 and 12 weeks, patients wore an Actigraph GT3X+ accelerometer for 7 days and completed surveys, body size measurements, and an optional 6-minute walk test. Participants could not be masked to their intervention arm, but people assessing the body size and 6-minute walk test outcomes were masked. The primary outcomes were adherence (eg, Fitbit wear and text response rate) and self-assessed acceptability of the intervention. The intervention would be considered feasible if we observed at least 80% complete follow-up and 70% adherence and satisfaction, a priori. Results From 2018 to 2020, we screened 240 patients; 53.3% (128/240) of patients were ineligible and 26.7% (64/240) declined to participate. A total of 44 patients (44/240, 18%) were randomized to the intervention (n=22) or control (n=22) groups. Of these, 57% (25/44) were women; 68% (30/44) identified as White and 25% (11/44) identified as Asian American or Pacific Islander; and 77% (34/44) had a 4-year college degree. The median age at enrollment was 54 years (IQR 45-62 years). Follow-up at 12 weeks was 91% (40/44) complete. In the intervention arm, patients wore Fitbit devices on a median of 67 out of 84 (80%) study days and responded to a median of 17 out of 27 (63%) questions sent via SMS text message. Among 19 out of 22 (86%) intervention patients who completed the feedback survey, 89% (17/19) were satisfied with the Fitbit device; 63% (12/19) were satisfied with the SMS text messages; 68% (13/19) said the SMS text messages motivated them to exercise; 74% (14/19) said the frequency of SMS text messages (1-3 days) was ideal; and 79% (15/19) said that receiving SMS text messages in the morning and evening was ideal. Conclusions This pilot study demonstrated that many people receiving chemotherapy for CRC are interested in participating in digital health physical activity interventions. Fitbit adherence was high; however, participants indicated a desire for more tailored SMS text message content. Studies with more socioeconomically diverse patients with CRC are required. Trial Registration ClinicalTrials.gov NCT03524716; https://clinicaltrials.gov/ct2/show/NCT03524716

Background: To evaluate the efficacy and treatment related morbidity of neoadjuvant chemoradiotherapy or radiotherapy in elderly patients (aged 75 years or older) with locally advanced rectal cancer (LARC). Methods: We reviewed clinical records of elderly patients with LARC treated with neoadjuvant chemoradiotherapy or radiotherapy between January 2008 and June 2017 at our institute. A dose of 45-50Gy in 25 fractions was delivered to pelvis. The primary tumor received a dose of 55Gy concomitantly for patients receiving intensity modulated radiotherapy (IMRT). The concurrent chemotherapy included capecitabine alone and capecitabine plus oxaliplatin (Xelox). Surgery was performed for suitable patients at least 6 weeks after neoadjuvant treatment. Overall survival (OS), disease specific survival (DSS), disease free survival (DFS) and local control (LC) were calculated with Kaplan-Meier method. Results: A total of 85 patients were enrolled in this study, the median age was 80 years old (range: 75-90 years). After neoadjuvant treatment, surgery was performed in 56 patients (65.9%). Downstaging rate was 85.7% (48/56) with T downstaging in 35 patients (62.5%) and N downstaging in 36 patients (64.3%). Twelve patients (21.4%) obtained pathological complete response (pCR). The incidence of grade 3 or greater acute hematological, gastrointestinal and genitourinary toxicities were 10.7%, 5.2% and 1.8%, respectively. Seven patients (12.5%) experienced postoperative complications. The median follow-up duration was 35.7 months (range: 4.3-100.3 months), The 3-year and 5-year OS, DSS, DFS, LC were 68.9% and 47.2%, 75.8% and 60.4%, 68.2% and 56.1%, 83.9% and 78.3%, respectively. Conclusion: In patients aged 75 years or older with LARC, neoadjuvant chemoradiotherapy followed by surgery was well tolerated with promising survival outcomes, which should be strongly suggested if medically suitable.

Introduction Anastomotic leak is a very serious complication in colorectal surgery. Tissue perfusion of the anastomosis plays an integral role in its multifactorial etiology. Fluorescence angiography using indocyanine green allows visualization of perfusion in real time. Aim To evaluate the effectiveness of intraoperative fluorescence angiography as a tool to decrease the incidence of anastomotic leak after laparoscopic or robotic low resection of the rectum for cancer. Material and methods Intraoperative fluorescence angiography was performed sequentially in 50 patients during low rectal resection for cancer with total mesorectal excision, primary anastomosis and protective ileostomy using laparoscopic or robotic technique. The results were compared to a historical control group of 50 patients with the same procedure without the use of fluorescence angiography. Results The patient sets were comparable in basic demographic and clinical parameters. Intraoperative visualization of perfusion by fluorescence angiography was achieved in all patients without unwanted side-effects. In 6 (12%) patients, the resection line was adjusted based on the fluorescence angiography. The incidence of anastomotic leak was insignificantly lower in the group with fluorescence angiography (18% vs. 10%), which led to significantly shorter hospital stay. Other postoperative complications were comparable between the two groups. Conclusions Fluorescence angiography using indocyanine green is a safe and effective method with the potential of reducing anastomotic leak during minimally invasive low resection of the rectum for cancer.

Introduction Whether complete splenic flexure mobilization (SFM) is required remains a controversial issue and there are numerous approaches regarding the performance of this procedure. Aim To investigate the effect of SFM performed with a medial-to-lateral and superior-to-inferior approach on early clinical outcomes in laparoscopic resection of rectal cancer. Material and methods The SFM procedure was initiated by the ligation of the inferior mesenteric vein followed by dissection extending from the upper border of the pancreas to the splenic hilum through the gastrocolic space. The mesocolon was dissected in a superior-to-inferior and medial-to-lateral fashion and the presacral space was entered by dividing the inferior mesenteric artery. The procedure was completed by dividing all the splenocolic, phrenicocolic, gastrocolic, and pancreaticomesocolic ligaments. Results A total of 43 patients were included in the study, comprising 26 (60.5%) men and 17 (39.5%) women with a mean age of 58.2 ±13.9 (range: 30-87) years. Of the 43 patients, 21 (48.8%) underwent neoadjuvant chemotherapy and a diversion stoma was performed in 37 (86%) patients. No adjacent organ injury occurred intraoperatively. Mean operative time was 271 ±50 min and mean blood loss was 144 ±83 ml. One (2.3%) patient might have developed anastomotic leakage secondary to bevacizumab therapy postoperatively and developed no anastomotic stenosis in the follow-up period. Mean length of hospital stay was 9.3 ±4.3 days and no mortality occurred in any patient. Conclusions Splenic flexure mobilization performed via the superior-to-inferior and medial-to-lateral approach appears to be a safe and feasible procedure.

Summary: Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525). Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval [CI], −1•3 to 9•7, p = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6, p = 0•0052), micturition symptoms (−8•0 points; 95% CI, -14•1 to −1•8, p = 0•0108), male sexual problems (−19•9 points; 95% CI, -33•1 to -6•7, p = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8, p = 0•0155), and worse urinary symptoms (−5•4 points on a 35-point scale; 95% CI, −8•0 to −2•7, p

Purpose: Computed tomography remains the first-choice modality for assessment of colorectal cancer liver metastases (CRLM). Dual-energy computed tomography (DECT) is a relatively new technique that is becoming increasingly available. One of the advantages of DECT is the ability to maximise iodine detection. Our aim was to test whether single-source, fast kVp-switching DECT can improve imaging quality of CRLM compared to conventional (polychromatic) CT. Material and methods: Twenty consecutive patients were enrolled into a preliminary prospective study. The scanning protocol consisted of four phases: non-contrast with standard 120 kV tube voltage and three post-contrast phases with rapid voltage switching. As a result, three sets of images were reconstructed: pre- and postcontrast polychromatic (PR), monochromatic (MR), and iodine concentration map (IM). To compare the sensitivity of the tested reconstructions, the number of CRLMs and the maximum diameter of the largest lesion were calculated. Objective image quality was measured as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The radiation dose was expressed as CTDIvol. Results: Imaging was successfully performed in all patients. The number of detected lesions was significantly lower on PR images than on IM and MR 50-70 keV (mean number: 4.20 and 4.45, respectively). IM and MR at 70 keV presented the highest quality. SNR was significantly higher for IM and 70 keV images than for other reconstructions. The mean radiation dose was 14.61 mGy for non-contrast 120 kV scan and 17.89 mGy for single DECT scan (p < 0.05). Conclusions: DECT is a promising tool for CRLM imaging. IM and low-photon energy MR present the highest differences in contrast between metastases and the normal liver parenchyma.

Aim of the study To analyse the influence of overweight and obesity in disease-specific survival (DSS) in rectal cancers at stages I-III in a population with high prevalence of overweight/obesity. Material and methods The population (N = 304) consisted of Mexican patients with stage I-III rectal cancer during the period between 2009 and 2015. Patients were divided based on their body mass index (BMI) into normal weight 18-25 kg/m2, overweight 25-29 kg/m2, and obesity BMI > 30 kg/m2 groups. Comparison of clinicopathologic features and survival analysis were performed. Results The median age was 58 years (interquartile range [IQR] 50-65) and the mean BMI was 26.03 ±4.06 kg/m2. Patients in the obesity and overweight groups received a lower proportion of preoperative treatment and had a higher proportion of patients in stage II. Overweight patients had a lower baseline neutrophil/lymphocyte ratio and lower survival rate than patients with normal weight and with obesity (mean survival of 69.5 months vs. 81.15 months and 86.4 months, respectively). The estimated five-year DSS was 51% for the overweight group, 81% for the normal group, and 82% for the obesity group (p = 0.026). Conclusions Patients with stage I-III rectal cancer in the overweight group showed a lower DSS compared to groups with normal weight and with obesity, with the last two being similar.

// Cory Pettit 1 , Amy Webb 1 , Steve Walston 1 , Moumita Chatterjee 1 , Wei Chen 1 , Wendy Frankel 1 , Carlo Croce 1 and Terence M. Williams 1 1 The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH 43210, USA Correspondence to: Terence M. Williams, email: terence.williams@osumc.edu Keywords: miRNA; rectal cancer; chemotherapy; radiation; biomarker Received: February 05, 2018 Accepted: April 02, 2018 Published: June 22, 2018 ABSTRACT Purpose: There has been growing interest in using chemoradiation (CRT) for non-operative management of rectal cancer, and identifying patients who might benefit most from this approach is crucial. This study identified miRNAs (miRs) associated with clinical outcomes and treatment resistance by evaluating both pre- and post-CRT expression profiles. Methods: Forty patients, 9 with pathologic complete response (pCR) and 31 with pathologic incomplete response (pIR) were included. MicroRNA was extracted from 40 pre-therapy tumor samples and 31 post-chemoradiation surgical samples with pathologic incomplete response (pIR). A generalized linear model was used to identify miRs associated with pCR. A linear mixed effects model was used to identify miRs differentially expressed before and after treatment. miR expression was dichotomized at the mean and clinical outcomes were evaluated using Cox proportional hazard modeling. Results: Nine miRs were associated with pCR (p

To explore clinical characteristics which could be applied to predict pathologic complete response (pCR) for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision (TME). 297 patients with locally advanced rectal cancer (cT3-4 or cN+) who were treated with neo-CRT followed by TME were retrospectively reviewed. Clinical characteristics including age, gender, tumor distance from anus, serum CEA, hemoglobin levels before treatment and clinical TN stage were used to investigate the association with pCR after neo-CRT. Seventy-nine (26.6%) patients achieved pCR after neo-CRT. pCR were achieved in 42 (34.4%) patients in cT1-3 stage and 37 (21.1%) in cT4 stage. pCR rate was 36.4% and 16.4% for patients with pre-treatment serum CEA ≤5.33ng/ml and >5.33ng/ml, respectively. Uni- and multi-variate analyses revealed that pre-treatment serum CEA level ≤5.33ng/ml and clinical T stage, (i.e., cT1-3 versus cT4) were highly correlated with pCR (p < 0.05). Clinical T stage and pre-treatment serum CEA level were strongly associated with pCR for patients with locally advanced rectal cancer treated with neo-CRT followed by TME which could be applied as clinical predictors for pCR.

Purpose: This study aimed at investigating the long-term outcomes of oxaliplatin and capecitabine (XELOX) administered concurrently with preoperative radiation and extended to the resting period in patients with high-risk locally advanced rectal cancer (LARC). Methods: From January 2010 to December 2013, 45 patients were recruited. Study treatment consisted two cycles of XELOX regimen concomitant with preoperative radiation and then followed by an additional cycle of XELOX regimen between completion of neoadjuvant radiotherapy and surgery. Disease-free survival (DFS) time and overall survival (OS) time were analyzed. Results: The median follow-up was 51 months. Twelve (26.7%) patients developed local recurrence or distant metastasis, including 10 (22.2%) patients developing distant metastasis only, 1 (2.2%) patient local recurrence only, and 1 (2.2%) patient both local recurrence and distant metastasis. The estimated 3-year DFS and OS was 75.5% (95% CI, 63.0%-88.0%) and 88.6% (95% CI, 98.0%-79.2%), respectively. Receiving adjuvant chemotherapy was a significant predictor for DFS, with hazard ratio 0.24 (95% CI: 0.08-0.74). Conclusion: This intensified strategy with oxaliplatin and capecitabine (XELOX) administered concomitantly with neoadjuvant radiotherapy and then extended to the resting period in high-risk LARC patients is efficient. The long-term outcome is promising. Further study of this strategy is warranted.

Background: Due to the varying characteristics and conflicting outcomes on the overall survival of rectal cancer patients, many studies have been undertaken to determine various prognostic and predictive factors for the mainstay treatment of CCRT followed by surgery. Cancer cell motility contributes to tumor invasion, migration and eventually metastasis. However, the genes associated with cell motility (i.e., GO:0048870) have not been systemically evaluated in rectal cancers. Methods: A comparative analysis of gene expression profiles was applied to the transcriptomic dataset (GSE35452) with a focus on genes associated with cell motility (GO:0048870), where SERPINB5 was recognized as the most significantly up-regulated gene. Tumor samples from 172 primary rectal cancer patients who underwent neoadjuvant CCRT followed by surgical resection were collected. Immunohistochemistry was used to semi-quantitatively assess the expression level of SERPINB5 protein. Statistical analyses of SERPINB5 expression and various clinicopathological features as well as survival were then performed. Results: High immunoreactivity of SERPINB5 was significantly linked to pre- and post-CCRT advanced disease, lymphovascular invasion, and poor response to CCRT (all P ≤ 0.015). SERPINB5 overexpression was not only negatively associated with disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) rates in univariate analyses but also was an independent prognostic factor for DSS and MeFS in rectal cancer patients (all P ≤ 0.043). Conclusion: SERPINB5 may play an important role in rectal cancer progression and response to neoadjuvant CCRT and serve as a novel prognostic factor.

Background: Transrectal ultrasound (TRUS) is a cost-effective test for preoperative assessment of rectal cancer. However, whether the accuracy of TRUS staging is correlated with tumor location remains obscured. This study is designed to explore their relationship and confirm an optimal application of TRUS in rectal cancer restaging. Methods: From 2005 to 2011, rectal cancer patients with TRUS data were retrospectively reviewed. Patients were divided into five groups according to tumor-involved rectal segment (SEG) above the anal verge: SEG I 1-3cm, II 3-6cm, III 6-9cm, IV 9-12cm, and V 12-16cm. The accuracy and long-term outcomes of tumor staging were compared between ultrasonographic and pathological stages. Results: 219 patients were included, with 55 (25.1%) in SEG I, 123 (56.2%) in SEG II, 32 (14.6%) in SEG III, 4 (1.8%) in SEG IV and 5 (2.3%) in SEG V. The overall accuracy of TRUS staging was remarkably superior to clinical staging by CT (64.8% vs. 34.7%, P

// Yankai Meng 1 , Chongda Zhang 1 , Shuangmei Zou 2 , Xinming Zhao 1 , Kai Xu 3 , Hongmei Zhang 1 and Chunwu Zhou 1 1 Department of Radiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2 Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 3 Department of Radiology, The Affliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China Correspondence to: Chunwu Zhou, email: cjr.zhouchunwu@vip.163.com Hongmei Zhang, email: zhanghongmei1973@163.com Keywords: rectal cancer; texture analysis; magnetic resonance imaging; response assessment; neoadjuvant chemoradiotherapy Received: July 26, 2017 Accepted: October 28, 2017 Published: December 22, 2017 ABSTRACT To evaluate the importance of MRI texture analysis in prediction and early assessment of treatment response before and early neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). This retrospective study comprised of 59 patients. The tumoral texture parameters were compared between pre- and early nCRT. Area Under receiver operating characteristic (ROC) Curves [AUCs] were used to compare the diagnostic performance of statistically significant difference parameters and logistic regression analysis predicted probabilities for discriminating responders and nonresponders. The Standard Deviation (SD), kurtosis and uniformity were statistically significantly difference between pre- and early nCRT ( p = 0.0012, 0.0001, and < 0.0001, respectively). In pathological complete response (pCR) group, pre-uniformity and pre-Energy were significantly higher than that of nonresponders ( p = 0.03 and p < 0.01, respectively), while the pre-entropy in nonresponder was reverse ( p = 0.01). The diagnostic performance of pre-kurtosis and pre-Energy were higher in tumor regression grade (TRG) and pCR group (AUC = 0.67, 0.73, respectively). Logistic regression analysis showed that diagnostic performance for prediction responder and nonresponder did not significantly improve compared with to pre-uniformity, energy and entropy in pCR group (AUC = 0.76, p = 0.2794, 0.4222 and 0.3512, respectively). Texture parameters as imaging biomarkers have the potential to prediction and early assessment of tumoral treatment response to neoadjuvant chemoradiotherapy in patients with LARC.

// Jin-Tung Liang 1 , Tzu-Chun Chen 1 , John Huang 1 , Yung-Ming Jeng 2 and Jason Chia-Hsien Cheng 3 1 Division of Colorectal Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan 2 Department of Pathology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan 3 Department of Radiation Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan Correspondence to: Jin-Tung Liang, email: jintung@ntu.edu.tw Keywords: bevacizumab; cetuximab; CCRT; rectal cancer; total mesorectal excision Abbreviations: CCRT: Concurrent chemoradiation therapy; FOLFOX: folinic acid + leucovorin + oxaliplatin; TME: Total mesorectal excision Received: April 13, 2017 Accepted: August 29, 2017 Published: October 10, 2017 ABSTRACT Background: To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). Method: A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Results: Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, p

// Jin Sook Song 1 , In Ja Park 2 , Jeong Hye Kim 3 , Hyang Ran Lee 1 , Jeong Rang Kim 1 , Jong Lyul Lee 2 , Yong Sik Yoon 2 , Chan Wook Kim 2 , Seok Byung Lim 2 , Chang Sik Yu 2 and Jin Cheon Kim 2 1 Department of Colorectal Clinic, Asan Medical Center, Seoul, Korea 2 Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 3 Department of Clinical Nursing, University of Ulsan, Seoul, Korea Correspondence to: In Ja Park, email: // Jeong Hye Kim, email: // Keywords : anorectal manometry, anorectal function, preoperative chemoradiotherapy, rectal cancer Received : March 29, 2017 Accepted : August 15, 2017 Published : August 27, 2017 Abstract Preoperative chemoradiotherapy (PCRT) is a standard treatment for locally advanced rectal cancer. The influence of PCRT on anorectal function has not been objectively assessed. We evaluated the short-term influence of PCRT on anorectal function in patients with locally advanced rectal cancer using anorectal manometry. We included 310 patients with locally advanced mid and lower rectal cancer who underwent PCRT from 2012 to 2015. We compared anorectal function based on anorectal manometry between before and after PCRT according to tumor location, clinical T (cT) stage, and tumor response after PCRT. Lower rectal cancer was common in the cohort of 310 patients ( n = 228, 73.5%). Sphincter length ( p = 0.003) and maximal resting pressure ( p < 0.001) increased and maximal tolerated volume ( p = 0.036) decreased after PCRT regardless of tumor location. Maximal squeezing pressure and rectal compliance slightly decreased, without statistical significance. Changes in manometric parameters after PCRT were not associated with changes of cT stage after PCRT. However, minimal sensory volume ( p = 0.042) and maximal tolerated volume ( p = 0.025) increased significantly in 143 patients (46.1%) with changes in the distance of the cancer from the anal verge after PCRT. PCRT did not impair the overall short-term anorectal manometric parameters in patients with locally advanced rectal cancer. Further study is required to investigate postoperative anorectal function after sphincter-preserving surgery to evaluate the long-term effects of PCRT on anorectal function.

Purpose: To investigate the dosimetric results and first clinical experiences with a new designed balloon applicator with adjustable catheters for endoluminal brachytherapy for patients with locally advanced rectal cancer not undergoing surgery. Material and methods: The applicator consists of an inflatable rectal balloon with six attached Foley catheters used as guidance for the inserted brachytherapy plastic needles. The construction of the applicator and the dosimetric profile in terms of representative dose points in 0, 2, 5, 10 mm ipsilaterally and in 0 mm contralaterally are described. The first clinical outcomes in three patients are reported. Results: For all three patients, a reproducible dose gradient was achieved. The surface dose on the target side was 204 ± 19% of the normalized dose in 5 mm (100%) tissue depth, and 143 ± 8% in 2 mm and 64 ± 3% in 10 mm tissue depth, while the surface dose on the contra-lateral side was 20 ± 8%. After radiochemotherapy with 50 Gy external beam radiotherapy and concomitant administration of capecitabine, a HDR brachytherapy boost in 2-3 fractions of 7-10 Gy each was delivered. All patients achieved a clinical complete response 3 month after the treatment, and no major toxicity was observed. Conclusion: The use of the applicator was clinically feasible, and resulted in a stable and reproducible dose distribution. First clinical results are promising.

// Raquel Conde-Muino 1, * , Carlos Cano 2, * , Victoria Sanchez-Martin 3, 4 , Antonio Herrera 4, 5 , Ana Comino 1 , Pedro P. Medina 4, 5 , Pablo Palma 1, * and Marta Cuadros 3, 4, * 1 Division of Colon & Rectal Surgery, University Hospital Virgen de las Nieves, Granada, Spain 2 Department of Computer Science and Artificial Intelligence, University of Granada, Granada, Spain 3 Department of Biochemistry, Molecular Biology III and Immunology, University of Granada, Granada, Spain 4 GENYO, Centre for Genomics and Oncological Research, Pfizer/University of de Granada/Junta de Andalucia, PTS Granada, Granada, Spain 5 Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain * These authors have contributed equally to this work Correspondence to: Marta Cuadros Celorrio, email: mcuadros@ugr.es Pedro Medina, email: pedro.medina@genyo.es Pablo Palma, email: pablopalma@andaluciajunta.es Keywords: regulatory networks, chemoradiotherapy-resistance, rectal cancer, miRNAs, c-Myc Received: April 21, 2017 Accepted: June 19, 2017 Published: July 19, 2017 ABSTRACT Administration of chemoradiation before tumor resection has revolutionized the management of locally advanced rectal cancer, but many patients have proven resistant to this preoperative therapy. Our group recently reported a negative correlation between c-Myc gene expression and this resistance. In the present study, integrated analysis of miRNA and mRNA expression profiles was conducted in 45 pre-treatment rectal tumors in order to analyze the expressions of miRNAs and c-Myc and their relationship with clinicopathological factors and patient survival. Twelve miRNAs were found to be differentially expressed by responders and non-responders to the chemoradiation. Functional classification revealed an association between the differentially expressed miRNAs and c-Myc. Quantitative real-time PCR results showed that miRNA-148 and miRNA-375 levels were both significantly lower in responders than in non-responders. Notably, a significant negative correlation was found between miRNA-375 expression and c-Myc expression. According to these findings, miRNA-375 and its targeted c-Myc may be useful as a predictive biomarker of the response to neoadjuvant treatment in patients with locally advanced rectal cancer.

// Xiang Hu 1, 2 , Ya-Qi Li 1, 2 , Qing-Guo Li 1, 2 , Yan-Lei Ma 1, 2 , Jun-Jie Peng 1, 2 and San-Jun Cai 1, 2 1 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 20032, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China Correspondence to: San-Jun Cai, email: caisanjun_sh@163.com Keywords: rectal cancer, stage IIA, radiotherapy, outcomes Received: April 25, 2017 Accepted: July 19, 2017 Published: July 29, 2017 ABSTRACT This study sought to determine whether additional radiotherapy is necessary in patients after optimal surgery for stage IIA rectal cancer and how the different covariates influence the efficacy of radiotherapy. The first primary rectal cancer was identified from the 1988–December 2013 Surveillance, Epidemiology and End Results database. We identified 13647 patients with IIA rectal cancer, in which 39.6% received neo-adjuvant radiotherapy and in another 14.96% patients the adjuvant radiotherapy were performed. Neo-adjuvant or adjuvant radiotherapy group had better survival with 10-Year cancer-specific survival estimates as 75.1% and 73.8% compared to 68.4% of no radiotherapy group ( P < 0.01). Adjusted hazard ratio (HR) demonstrated neo-adjuvant and adjuvant radiotherapy (HR: 0.814 and 0.848) were all associated with significantly decreased risk for cancer death. However, radiotherapy did not seem to yield the same survival benefit in selected population. Adjusted stratified analysis demonstrated patients with increasing age, relative large tumor size, and more retrieved regional lymph nodes had no additional benefit for cancer specific survival based on radiation use. In conclusions, unselected patients with stage IIA rectal cancer receiving radiotherapy experienced better survival in comparison to patients without radiation. However, additional radiotherapy is not beneficial for all.

// In Ja Park 1 , Soyeon An 5 , Sang-Yeob Kim 3, 4 , Hye Min Lim 4 , Seung-Mo Hong 2 , Mi-Ju Kim 4 , Yun Jae Kim 4 and Chang Sik Yu 1 1 Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea 2 Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea 3 Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea 4 Asan Institute for life sciences, Asan Medical Center, Seoul, Korea 5 Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea Correspondence to: Chang Sik Yu, email: csyu@amc.seoul.kr Sang-Yeob Kim, email: sykim3yk@amc.seoul.kr Keywords: rectal cancer, preoperative chemoradiotherapy, responsiveness, immune infiltrates Received: April 04, 2017 Accepted: July 14, 2017 Published: July 25, 2017 ABSTRACT We evaluate whether the tumor immune infiltrate (TIL) could be used for prediction of responsiveness to preoperative chemoradiotherapy (PCRT) in rectal cancers. Using formalin-fixed paraffin-embedded slides of pretreatment biopsies, co-stain for CD4, CD8, CD274 (PD-L1), FOXP3, cytokeratin, and DAPI was performed with Opal multi staining kit (Perkin-Elmer, Waltham, MA). Multispectral imaging and digital analysis to visualize and quantify specific immune infiltrates were performed using the Vectra imaging system (Perkin-Elmer). The density (number of cells per mm 2 ) and proportion of total TILs and specific cell types in the stroma were calculated by inForm ™ 2.2.1 software (Perkin-Elmer). The density and proportion of total TILs and specific cell types in the stroma were calculated by inForm ™ 2.2.1 software (Perkin-Elmer, Waltham, MA). Patients were classified as group with total regression (TR, n = 25) and group with residual disease (near total, moderate, and minimal regression, RD, n = 50). The mean density of T cell infiltration and CD274 (PD-L1)+ lymphocyte were significantly higher in TR ( p = 0.005, p = 0.001). The proportion of CD4+ lymphocyte (p=0.042) and CD274 (PD-L1)+ lymphocyte ( p = 0.002) were different between 2 groups. The TR group has lower CD4+ and higher CD274 (PD-L1)+ proportions than RD group. The ratio among CD4+, CD8+, CD274 (PD-L1)+, FOXP3+ T cell was different between groups. TR group showed lower CD4/ CD274 (PD-L1) ( p = 0.007), CD8/ CD274 (PD-L1) ( p = 0.02), and FOXP3/ CD274 (PD-L1) ( p = 0.003) ratio than RD group. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of responsiveness to PCRT.

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p

The cellular sarcoma gene (SRC) is a proto-oncogene encoding for a tyrosine kinase. SRC expression was determined in locally advanced rectal adenocarcinoma tissue from pretreatment biopsies and resection specimens. The expression level was correlated with clinicopathological parameters to evaluate the predictive and prognostic capacity. For this monocentric analysis 186 patients with locally advanced rectal cancer (median: 63.7 years; 130 men (69.9%), 56 women (30.1%)) were included. Patients with a carcinoma of the upper third of the rectum were treated with primary tumor resection (n=27; 14.5%). All other patients received a preoperative chemoradiotherapy (CRT) with 50.4 Gy and concomitant 5-fluorouracil (5-FU) or 5-FU+oxaliplatin followed by postoperative chemotherapy with 5-FU or 5-FU+oxaliplatin. SRC expression was determined with immunohistochemical staining from pretreatment biopsies (n=152) and residual tumor tissue from the resection specimens (n=163). The results were correlated with clinicopathological parameters and long-term follow-up. The expression of SRC was determined in pretherapeutic biopsies (mean H-Score: 229) and resection specimens (mean H-Score: 254). High SRC expression in pretherapeutic tumor samples significantly correlated with a negative postoperative nodal status (p=0.005). Furthermore an increased protein expression in residual tumor tissue was associated with fewer distant metastases (p=0.04). The overexpression of SRC in pretreatment tumor biopsies showed also a trend for a longer cancer-specific survival (CSS; p=0.05) and fewer local relapses (p=0.06) during long-term follow-up. High SRC expression in rectal cancer seems to be associated with a better long-term outcome. This finding could help in the future to stratify patients for a recurrence risk adapted postoperative treatment.

// Sung Woo Jung 1 , In Ja Park 1 , Se Heon Oh 1 , Seung-Seop Yeom 1 , Jong Lyul Lee 1 , Yong Sik Yoon 1 , Chan Wook Kim 1 , Seok-Byung Lim 1 , Jung Bok Lee 2 , Chang Sik Yu 1 and Jin Cheon Kim 1 1 Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea 2 Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea Correspondence to: In Ja Park, email: // Keywords : rectal cancer, preoperative chemoradiotherapy, neutrophil to lymphocyte ratio, tumor response, oncologic outcome Received : January 13, 2017 Accepted : February 20, 2017 Published : February 27, 2017 Abstract We investigated retrospectively whether immunologic markers from a complete blood count (CBC) are associated with the responsiveness to preoperative chemoradiotherapy (PCRT) and oncologic outcomes in 984 patients with locally advanced rectal cancer (LARC) who also underwent radical surgery from 2005 to 2013. CBC parameters including the neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) were recorded. Pathologic responses to PCRT were evaluated in the resected specimens using the tumor regression grade system. The cut-off values of the immunologic markers were calculated to analyze their association with recurrence-free survival (RFS). One hundred ninety-five patients achieved total regression of their primary tumor. By receiver operating characteristic analysis, NLR, PLR, and LMR could not distinguish total regression from residual disease after PCRT. The NLR, LMR and PLR cut-off values were 1.7, 6.8 and 92.88, respectively. By univariate analysis, low NLR (≤1.7), high LMR (>6.8) and high PLR (>92.88) were indicators of a favorable RFS outcome. By multivariate analysis, high PLR was associated with an improved RFS (HR, 0.649; 95% CI, 0.473-0.89; P =0.007). High NLR (>1.7) was an independent negative prognostic factor for RFS in stage II (HR, 1.868; 95% CI, 1.08-3.109; P =0.025) and high PLR was a positive prognostic factor in stage III (HR, 0.675; 95% CI, 0.421-0.957; P =0.03). Immunologic markers derived from CBCs are independently associated with the RFS outcome in LARC patients treated with PCRT followed by radical resection. However, these markers are not predictive of total primary tumor regression after PCRT.

// Melanie J. McCoy 1, 4 , Chris Hemmings 2, 3 , Chidozie C. Anyaegbu 1 , Stephanie J. Austin 1, 3 , Tracey F. Lee-Pullen 1, 3 , Timothy J. Miller 1, 3 , Max K. Bulsara 5 , Nikolajs Zeps 1, 3 , Anna K. Nowak 4, 6 , Richard A. Lake 4 , Cameron F. Platell 1, 3 1 Colorectal Research Unit, St John of God Subiaco Hospital, Subiaco, WA, 6008, Australia 2 Department of Anatomic Pathology, St John of God Pathology, Wembley, WA, 6014, Australia 3 School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia 4 School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, 6009, Australia 5 Institute for Health Research, University of Notre Dame, Fremantle, WA, 6959, Australia 6 Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia Correspondence to: Melanie McCoy, email: melanie.mccoy@uwa.edu.au Keywords: rectal cancer, regulatory T cells, radiotherapy, chemotherapy, treatment response Received: September 13, 2016 Accepted: January 07, 2017 Published: February 03, 2017 ABSTRACT Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3 + regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3 + , CD8 + and CD3 + cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response.

// Jung Pil Choi 4, * , Sung Joo Kim 2, * , In Ja Park 1, Seung Mo Hong 2 , Jong Lyul Lee 1 , Yong Sik Yoon 1 , Chan Wook Kim 1 , Seok-Byung Lim 1 , Jung Bok Lee 3 , Chang Sik Yu 1 , Jin Cheon Kim 1 1 Departments of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 2 Departments of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 3 Departments of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 4 Department of Surgery, Dong Kang Medical Center, Ulsan, Korea * These authors have contributed equally to this work Correspondence to: In Ja Park, email: ipark@amc.seoul.kr Keywords: rectal cancer, preoperative chemoradiotherapy, lymph node regression, primary tumor regression, oncologic outcome Received: August 25, 2016 Accepted: December 13, 2016 Published: January 02, 2017 ABSTRACT Purpose: The oncologic impact of the lymph node (LN) regression level after preoperative chemoradiotherapy (PCRT) has not been thoroughly evaluated. Hence, this study aimed to examine whether the regression level of metastatic LNs following PCRT is associated with oncologic outcomes in rectal cancer. Results: The optimal number of cut points for LRG sum was determined to be three. The three LRG groups demonstrated different distributions according to the ypT and ypN stages (p < 0.001 for both). However, the distribution of the LRG groups was not associated with the TRG of the primary tumor (p = 0.527). The RFS significantly differed according to the LRG groups (p = 0.001). Moreover, the differences in RFS remained when the LRG groups were analyzed within each separate ypN stage. The LRG group was confirmed as a factor associated with RFS in the multivariate analysis (p=0.018), while the ypN stage was not (p=0.4). Patients and Methods: We analyzed the outcomes of 142 rectal cancer patients diagnosed with ypN1 disease after PCRT followed by radical resection. The pathological responses of the primary tumor and LNs to PCRT were evaluated using the tumor regression grade (TRG) and LN regression grade (LRG), respectively. The impact of LRG on recurrence-free survival (RFS) was analyzed. The K-adaptive partitioning for survival data method was applied to determine the optimal number of cut points for the LRG-sum and the optimal number of subgroups. Conclusion: The LRG as an indicator of response to PCRT should be considered as a prognostic determinant in rectal cancer patients. Future large-scale prospective studies are needed to confirm this finding.

// Che-Yu Hsu 1 , Chun-Wei Wang 2, 4 , Chia-Chun Kuo 3 , Yu-Hsuan Chen 2, 4 , Keng-Hsueh Lan 2, 4 , Ann-Lii Cheng 4, 5, 6 , Sung-Hsin Kuo 2, 4, 5, 6 1 Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan 2 Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan 3 Division of Radiation Oncology, Department of Oncology, Taiwan Medical University Hospital, Taipei, Taiwan 4 National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan 5 Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan 6 Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan Correspondence to: Sung-Hsin Kuo, email: shkuo101@ntu.edu.tw Keywords: rectal cancer, tumor compactness, pathologic complete remission, preoperative, chemoradiotherapy Received: March 30, 2016 Accepted: November 21, 2016 Published: December 10, 2016 ABSTRACT In addition to clinical factors (tumor and node stage) and treatment factors (equivalent radiotherapy dose and chemotherapy regimen), we assessed whether different performances of various tumor volume measurements help predict the pathological complete response (pCR) of locally advanced rectal cancer (LARC) after preoperative concurrent chemoradiotherapy (CCRT). A total of 122 patients with LARC treated with a long course of CCRT, between December 2009 and March 2015, were enrolled in this bi-institutional study. Tumor delineation was based on standard T2-weighted magnetic resonance imaging or contrast-enhanced computed tomography before CCRT. Tumor compactness was defined as the ratio of the volume and the surface area. The tumor compactness-corrected TV (TCTV) was defined as the ratio of the real TV (RTV) and tumor compactness. Twenty-three (18.9%) patients had a pCR. Areas under the curve of the receiver operating characteristic for pCR prediction calculated using the RTV, cylindrical approximated TV (CATV), and TCTV were 0.724, 0.747, and 0.780, respectively. The prediction performance of TCTV was significantly more efficient than that of both RTV ( P = 0.0057) and CATV ( P = 0.0329). Multivariate logistic regression analysis revealed tumor compactness ( P = 0.001), RTV ( P = 0.042), and preoperative clinical nodal status ( P = 0.044) as significant predictors of a pCR. In addition, poor tumor compactness was closely associated with lymphovascular space invasion ( P = 0.008) and pathological nodal status ( P = 0.003). For patients with LARC receiving preoperative CCRT, tumor compactness is a useful radiomic parameter for improving the volumetric based prediction model.

// Panpan Hu 1, 2 , Jiazhou Wang 1, 2 , Haoyu Zhong 1, 2 , Zhen Zhou 1, 2 , Lijun Shen 1, 2 , Weigang Hu 1, 2 , Zhen Zhang 1, 2 1 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China Correspondence to: Zhen Zhang, email: zhenzhang6@gmail.com Keywords: radiomics, rectal cancer, reproducibility, textural features Received: July 26, 2016 Accepted: September 16, 2016 Published: September 22, 2016 ABSTRACT Purpose: To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. Results: Volume normalized features are much more reproducible than unnormalized features. The average value of all slices is the most reproducible feature type in rectal cancer. Different filters have little effect for the reproducibility of radiomics features. For the average type features, 496 out of 775 features showed high reproducibility (ICC ≥ 0.8), 225 out of 775 features showed medium reproducibility (0.8 > ICC ≥ 0.5) and 54 out of 775 features showed low reproducibility (ICC < 0.5). Methods: 40 rectal cancer patients with stage II were enrolled in this study, each of whom underwent two CT scans within average 8.7 days. 775 radiomics features were defined in this study. For each features, five different values (value from the largest slice, maximum value, minimum value, average value of all slices and value from superposed intermediate matrix) were extracted. Meanwhile a LOG filter with different parameters was applied to these images to find stable filter value. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) of two CT scans were calculated to assess the reproducibility, based on original features and volume normalized features. Conclusions: Features are recommended to be normalized to volume in radiomics analysis. The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and prognosis prediction.

// Martha L. Slattery 1 , Jennifer S. Herrick 1 , Daniel F. Pellatt 1 , Lila E. Mullany 1, John R. Stevens 2 , Erica Wolff 1 , Michael D. Hoffman 1 , Roger K. Wolff 1, Wade Samowitz 3 1 Department of Medicine, University of Utah, Salt Lake City, Utah 84108, USA 2 Department of Mathematics and Statistics, Utah State University, Logan, Utah 84322, USA 3 Department of Pathology, University of Utah School, Salt Lake City, Utah 84108, USA Correspondence to: Martha L. Slattery, email: marty.slattery@hsc.utah.edu Keywords: colon cancer, rectal cancer, miRNA, disease stage Received: June 04, 2016 Accepted: July 23, 2016 Published: August 10, 2016 ABSTRACT Background: MicroRNAs (miRNA) are small non-coding RNA involved in cellular processes, including cell proliferation and angiogenesis. Thus, miRNA expression may alter survival after diagnosis with colorectal cancer (CRC). Results: Individuals diagnosed with stage 1 or stage 2 rectal cancer had worse survival than colon cancer cases diagnosed at stage 1 or stage 2. After adjustment for multiple comparisons, no miRNAs were significantly associated with disease stage. Two miRNAs infrequently expressed in the population and not previously reported were associated with survival after diagnosis with colon cancer (miR-1 HR 2.17 95% CI 1.41, 3.36; and miR-101-3p HR 3.51 95% CI 1.72, 7.15). Among those diagnosed with rectal cancer, 201 miRNAs were associated with survival when the FDR q value was < 0.05. Assessment of 105 previously reported miRNAs associated with prognosis showed that four miRNAs influenced colon cancer survival and 17 influenced survival after a diagnosis with rectal cancer when raw p values were considered. Patients and Methods: This study includes data from population-based studies of CRC conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma and normal paired colorectal mucosa tissue samples were run using the Agilent Human miRNA Microarray V19.0. We assessed miRNA differential expression between paired carcinoma and normal colonic mucosa tissue with CRC- specific survival evaluating stage and site-specific associations after adjusting for age, sex, microsatellite instability tumor status, and AJCC stage. Conclusions: MiRNAs dysregulated for both colon and rectal cancer had a greater impact on survival after a diagnosis with rectal cancer.

Introduction : During laparoscopic abdominoperineal resection (APR) for low rectal cancer, it is difficult to resect the levator muscles and remove a cylindrical specimen without venturing close to the rectal wall to ensure negative circumferential resection margins (CRM). To solve this problem, we developed a needle-guided, laparoscopic, abdominoperineal resection (LAPR) technique. Aim: To present the safety and superiority of our technique, “needle-guided LAPR”. Material and methods: In 2015, we performed needle-guided LAPR in 5 patients. In brief, the procedure is performed as follows. After total mesorectum excision to the level of the levator muscles, a needle is inserted through the perineum from the dorsal side of the internal aspect of the anus toward the sacral tip. The levator muscles and fat tissue are resected laparoscopically by following the needle. After the levator muscles have been resected, the needle is followed in a similar manner to resect the specimen from the perineum, enabling easy access to the intra-abdominal space and removal of the specimen. No position change is required during the perineal operation or pelvic floor reconstruction. Results : Mean age was 68 years and 3 patients were male. There were no intraoperative complications or conversions to open surgery. The mean operation time and intraoperative blood loss were 319 min and 131 ml, respectively. All specimens were cylindrical in shape and had negative CRM. There were no postoperative complications. Conclusions : Needle-guided LAPR was easily and safely performed to achieve accurate resection of the levator muscles. This technique could contribute to standardization of LAPR.