Sphincter Preservation Research Articles

Symptoms, diagnostic and therapy of perianal disease in patients with inflammatory bowel diseases

Symptoms, diagnostic and therapy of perianal disease in patients with inflammatory bowel diseases Abstract. Inflammatory bowel diseases (IBD) frequently affect the perianal region. Due to the great functional importance of the anorectum, this frequently results in a significant burden of disease for the patient. For assessment of perianal IBD symptoms, the clinical history is of great importance. Often, anorectal symptoms are not reported spontaneously by patients, and a respectful direct conversation remains crucial. More than 30 % of patients with Crohn's disease (CD) will develop perianal fistulas. Perianal fistulas can be further characterized by endoscopic ultrasound, MRI, and investigation under anesthesia. These investigations provide complementary information. Fistula therapy is based on symptoms; the short-term goal is improvement of pain and secretion; the long-term goal of treatment remains fistula closure. However, preservation of the anal sphincter is of utmost importance and incontinence needs to be avoided. Antibiotics and/ or seton drainage are the mainstay for acute fistula treatment. The anti-tumor necrosis factor antibody infliximab can improve fistula symptoms, as demonstrated in a randomized controlled study. Surgical fistula closure is only possible in a clinically stable situation without rectal inflammation or other symptoms of active CD. Several surgical strategies exist including 1) fistulotomy, 2) disconnection of the fistula, 3) filling of the fistula tract and 4) fistula ablation. The optimal strategy needs to be decided on an individual basis. Intraoperative application of mesenchymal donor stem cells into the fistula tract and surrounding tissue is possibly the most effective fistula therapy. Due to the significant logistic effort, this therapy is only available in a few selected centers. Currently, stem cell therapy for CD fistulas is limited to patients with no more than two external fistula openings. The therapy of fissures and hemorrhoids in IBD patients is similar to patients without intestinal inflammation; however, due to a high rate of complications, surgery should be avoided whenever possible in CD patients. Incontinence is a frequent problem in IBD patients leading to highly relevant restrictions in daily life. Therapy is directed against intestinal inflammation but also comprises measures for normalization of stool consistency and intestinal motility. However, there are no IBD-specific concepts for the treatment of incontinence. Functional intestinal diseases are frequent in IBD patients and can contribute to urge and incontinence. Some IBD patients might benefit from anorectal physiotherapy. IBD patients have an increased risk for colorectal carcinoma, fistula carcinoma and possibly also anal carcinoma. Therefore, malignancy needs to be excluded at reasonable intervals.

Evaluation of Laparoscopic Sphincter Saving Surgery in Management of Rectal Cancer

Evaluation of Laparoscopic Sphincter Saving Surgery in Management of Rectal Cancer

Impact of preoperative transcatheter rectal arterial chemoembolization with concurrent chemoradiotherapy on surgery and prognosis of patients with locally advanced rectal cancer.

To analyze and evaluate the impact of preoperative transcatheter rectal arterial chemoembolization (TRACE) with concurrent chemoradiotherapy on surgery and prognosis of locally advanced rectal cancer (LARC). A total of 118 patients with LARC were enrolled in this nonrandomized prospective study. They were assigned into the experimental group receiving preoperative TRACE with concurrent chemoradiotherapy (TRACE-CRT group, N = 60) and the control group receiving only neoadjuvant chemoradiotherapy (CRT group, N = 58). All patients underwent surgery after their preoperative treatments. All patients successfully completed the surgical operation. No significant differences were found in sphincter preservation rate and R0 resection rate between TRACE-CRT group and CRT group (p > 0.05). No significant differences were found between the two groups in terms of the perioperative indicators and postoperative complications except mean operation time (165.8 vs. 196.6 min, p < 0.001). Local recurrence occurred in 8 and 5 patients, respectively (p > 0.05). Distant metastasis occurred in 5 and 11 patients, respectively (p < 0.05). Adding TRACE in the preoperative standard treatment for LARC did not increase perioperative complications. In addition, it has the potential advantage of preventing distant metastasis. It is worthy of further application and promotion in clinical practice.

Laparoscopic versus open resection in locally advanced rectal cancers: a propensity matched analysis of oncological and short-term outcomes.

The aim was to compare oncological and short-term outcomes between open and laparoscopic surgery in locally advanced rectal cancers. It is a retrospective analysis conducted in a high volume tertiary centre. Matching was carried out for nine variables, including preoperative factors, neoadjuvant treatment and sphincter preservation. Both the open and laparoscopic surgery arms had 239 patients each. The distributions of pretreatment MRI T3, T4, circumferential resection margin (CRM) positive tumours, neoadjuvant long-course chemoradiation and sphincter preservation were 80.3%, 13.6%, 50%, 89% and 56.4% respectively. The mean number of nodes harvested (12.9 vs. 12.7, P=0.716), pathological CRM positivity (6.3% in open vs. 5.4% in laparoscopic, P=0.697) and distal resection margins were similar. The mean blood loss was higher in open surgeries (910ml vs. 349ml, P<0.001). Anastomotic leaks and Clavien-Dindo Grade 3-4 complications were higher in the open arm than in the laparoscopy arm (5.9% vs. 1.7%, P=0.024, and 12.5% vs. 6.7%, P=0.015 respectively). The median postoperative hospital stay was significantly shorter in the laparoscopy arm (7 vs. 6, P=0.015). In CRM positive and threatened cases, the measured outcomes were similar between the two groups except for blood loss which was significantly higher in the open surgery (872 vs. 379, P=0.000). In high volume centres, in the hands of experienced colorectal surgeons, laparoscopic rectal surgery is oncologically safe in locally advanced rectal cancers and has lesser morbidity and shorter hospital stay than open surgery. In CRM positive and threatened cases the laparoscopic surgery showed less blood loss compared to open surgery, while other outcome measures were similar to open surgery.

PD61-09 FINAL RESULTS OF A PROSPECTIVE, RANDOMIZED CONTROLLED TRIAL ASSESSING THE IMPACT OF EARLY DORSAL VENOUS COMPLEX (eDVC) LIGATION ON URINARY CONTINENCE RECOVERY AFTER ROBOT-ASSISTED RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD61)1 Sep 2021PD61-09 FINAL RESULTS OF A PROSPECTIVE, RANDOMIZED CONTROLLED TRIAL ASSESSING THE IMPACT OF EARLY DORSAL VENOUS COMPLEX (eDVC) LIGATION ON URINARY CONTINENCE RECOVERY AFTER ROBOT-ASSISTED RADICAL PROSTATECTOMY Francesco Montorsi, Giuseppe Cirulli, Gabriele Sorce, Andrea Gallina, Marco Moschini, Giorgio Gandaglia, Francesco Pellegrino, Luigi Nocera, Nicola Fossati, Armando Stabile, Simone Scuderi, Francesco Barletta, Elio Mazzone, Andrea Salonia, Carlo Andrea Bravi, Giuseppe Rosiello, and Alberto Briganti Francesco MontorsiFrancesco Montorsi More articles by this author , Giuseppe CirulliGiuseppe Cirulli More articles by this author , Gabriele SorceGabriele Sorce More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Francesco PellegrinoFrancesco Pellegrino More articles by this author , Luigi NoceraLuigi Nocera More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Armando StabileArmando Stabile More articles by this author , Simone ScuderiSimone Scuderi More articles by this author , Francesco BarlettaFrancesco Barletta More articles by this author , Elio MazzoneElio Mazzone More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Carlo Andrea BraviCarlo Andrea Bravi More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002098.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The ligation of the dorsal venous complex (DVC) and the approach to the prostatic apex represent crucial steps of robot-assisted radical prostatectomy (RARP) which may affect urinary continence (UC) recovery. We hypothesized that the early ligation of the DVC during RARP might allow for a better preservation of urethral sphincter and thus improved continence recovery over the traditional technique. METHODS: In this randomized controlled trial (RCT - NCT03368378) a total of 312 consecutive prostate cancer (PCa) patients were randomly assigned to the experimental group (early DVC ligation, before the bladder neck incision and nerve-sparing lateral dissection) vs. control group (standard DVC ligation after the bladder neck). The minimum number of subjects for an 80% study power has been calculated considering an alfa-error of 5% and a UC recovery of 26% at 4 weeks obtained with the standard treatment. The hypothesis was that the early DVC ligation could improve UC recovery by 15% at 4-month after RARP. Primary endpoint was continence recovery at 1 and 4 months from surgery. UC was defined as 0/1 protective pad over 24-hour. Secondary outcomes were positive surgical margins (PSM), erectile function (IIEF-6), and 30-day complications (Clavien-Dindo classification). RESULTS: The per-protocol analyses included 276 patients. At 1 and 4 months after surgery, the percentage of patients who recovered continence in the experimental vs. control group was 23% vs. 28% and 71% vs. 64%, respectively (both p ≥0.2). Similar results were found at 1-year follow-up (90% vs. 91%; p=0.6). The percentage of PSM at final pathology did not differ between the groups (22% vs 24%; p=0.7). This finding was not affected by pathologic stage (PSM rate in organ-confined for experimental vs. control group: 12% vs. 18%; non-organ confined: 29% vs. 27%; both p ≥0.4). One year after surgery, there was no significant difference in median postoperative IIEF-6 between patients receiving early DVC ligation and the control group (p=0.07). The rate of Clavien-Dindo ≥2 complications during hospital stay did not differ between the experimental vs. control group (12% vs 11%, p=0.7). CONCLUSIONS: Although an early DVC ligation during RARP is safe and not associated with an increased risk of PSM or complications, our RCT demonstrated that this approach did not improve UC recovery at 4-months. These results were maintained at 1-year follow-up. Thus, early DVC has no impact on either functional or oncological outcomes. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1069-e1070 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francesco Montorsi More articles by this author Giuseppe Cirulli More articles by this author Gabriele Sorce More articles by this author Andrea Gallina More articles by this author Marco Moschini More articles by this author Giorgio Gandaglia More articles by this author Francesco Pellegrino More articles by this author Luigi Nocera More articles by this author Nicola Fossati More articles by this author Armando Stabile More articles by this author Simone Scuderi More articles by this author Francesco Barletta More articles by this author Elio Mazzone More articles by this author Andrea Salonia More articles by this author Carlo Andrea Bravi More articles by this author Giuseppe Rosiello More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Loading ...

Laser Management for Anal Fistulas: A Prospective study

Introduction: Laser treatment for fistula-in-ano, also known as FiLaC (fistula laser closure) or LAFT (laser ablation of fistula tract), has gained increasing attention in the last decade. The procedure consists of delivering laser energy at 360° within the lumen of fistulas by means of a radial fiber which is slowly withdrawn from the external orifice. Material &amp; Methods: The study analysed 40 patients treated for anal fistulae in Sapthagiri Institute of Medical Sciences, Bangalore between November 2020 to June 2021. Fistulae were classified in accordance with the Parks’ classification system, and all patients were preoperatively assessed by clinical examination and proctosigmoidoscopy and classified using three-dimensional (3D) endoanal ultrasonography performed by a sonographer experienced in endoanal ultrasound. Results: Of the 40 patients, 26 were female and 14 were male (overall median age 46 years; range 17–82 years). The median period of follow-up was 11 months, follow up was scheduled in the outpatient at 1 and 2 weeks and 1, 3, 6 and 11 months postoperatively. However, patients were instructed to return to the outpatient at any time should symptoms recur. In the cohort, 39 fistulae (97.5%) were cryptoglandular in origin and 1 (2.5%) were Crohn’s related. 97.5% had previously undergone surgery including abscess drainage and prior fistula operations. The mean number of operations before FiLaC treatment was 2.4 (±1.7) with a range of 1–9 previous operations. Discussion: The use of FILAC for the treatment of anorectal fistula has shown encouraging. The technique is easy to learn and fast to perform, allows exploration of curved paths and any size since the fiber is very flexible and long. The destruction of the epithelialized path and sealing is carried out by laser emission radially 360◦, thereby allowing the application of energy across the path homogeneous in a controlled manner. Conclusion: The FILAC, sphincter preservation minimally invasive surgery in the treatment of anal fistulas, looks promising although prospective and long-term follow-up studies should be conducted.

Tolerability and safety of adjuvant chemoradiotherapy with S-1 after limited surgery for T1 or T2 lower rectal cancer.

Chemo-radiotherapy (CRT) after local excision for pT1 with high-risk features or pT2 rectal cancer is recommended as an optional treatment to achieve both curability and maintenance of quality of life. The aim of this study was to evaluate the short-term safety of combining limited surgery with adjuvant CRT for T1 or T2 lower rectal cancer. This was a multicenter, single-arm, prospective phase II trial. Patients diagnosed with lower rectal or anal canal cancer (clinical T1 or T2 with a maximum diameter of 30mm and N0 and M0) underwent local excision or endoscopic resection. Patients received CRT with S-1 (tegafur/gimeracil/oteracil) after confirmation of well- or moderately differentiated adenocarcinoma, and negative margins, and/or depth of submucosal invasion ≥ 1000µm or muscularis propria, and/or positive lymphovascular invasion, and/or tumor budding grade of 2/3. The primary endpoint was relapse-free survival. Secondary endpoints included overall and local relapse-free survival, safety, anal sphincter preservation rate, and anal function. Pathological diagnosis was T1 in 36 patients and T2 in 16 patients. Serious complications after surgery were not reported. The CRT completion rate per protocol was 86.5% (45/52). Thirty-two patients developed 54 events of CRT-related adverse events, including only one patient with a grade 3 event (stomatitis). The most common CRT-related adverse event was diarrhea (n = 14). No patients showed deterioration of anal function at 3years postoperatively. CRT with S-1 after limited surgery for T1 or T2 lower rectal cancer resulted in a low incidence of toxicities and maintenance of anal function.

A randomized clinical trial to assess the effectiveness of pre- and post-surgical pelvic floor physiotherapy for bowel symptoms, pelvic floor function, and quality of life of patients with rectal cancer: CARRET protocol

BackgroundThere is scarcity of trials about preventative strategies for low anterior resection syndrome (LARS) in rectal cancer patients. The aim of this study is to evaluate the effectiveness of a pre- and post-surgical pelvic floor rehabilitation program on the bowel symptoms, pelvic floor function, and quality of life of rectal cancer patients.MethodsA randomized controlled trial with parallel groups (pelvic floor rehabilitation versus control group), with a blinded evaluator. Participants and setting: 56 stage I to III rectal cancer patients aged from 18 to 80 years old undergoing sphincter preservation surgery at Hospital del Salvador and who have a sufficient knowledge of Spanish. Main outcome measures: ICIQ-B questionnaire for intestinal symptoms, high-resolution anorectal manometry (Alacer Multiplex 24-channel manometry equipment) for anorectal function, pelvic floor muscle strength test with Oxford Modified Scale, and a quality of life test with the EORTC QLQ C30 questionnaire. The evaluations will be carried out at five stages: before surgery, before and after the pelvic floor rehabilitation, and during a 3-month and 1-year follow-up. Interventions: one pre-rehabilitation session and 9 to 12 sessions of pelvic floor rehabilitation, including patient education, pelvic floor muscle exercises, pelvic floor electromyography biofeedback, and capacitive and sensory rectal training with a balloon probe. Rehabilitation will begin 3–5 weeks before the ileostomy is removed (four sessions) and around 3 weeks after stoma removal (5–8 sessions).DiscussionWe expect the program to improve the bowel symptoms, pelvic floor function, and quality of life of rectal cancer patients.Trial registrationAustralian New Zealand Clinical Trials Register ACTRN12620000040965. Registered on 21 January 2020.

Improvement in the Assessment of Response to Preoperative Chemoradiotherapy for Rectal Cancer Using Magnetic Resonance Imaging and a Multigene Biomarker.

Simple SummaryPreoperative chemoradiotherapy is now the gold standard for treating locally advanced rectal cancer and has been demonstrated to decrease local recurrence and promote sphincter preservation. Therefore, developing methods to accurately predict patients’ response to chemoradiation is imperative for choosing the best surgical option after chemoradiation and predicting the oncologic outcomes of patients. Radiological tools and endoscopy are the most commonly used tools for post-treatment response assessment. In addition, examining the expression levels of genes correlated with treatment response could provide clinicians with more power to gauge each patient’s potential to respond. In this study, we explored how biological and radiological tools can be used together to provide a more tailored and multidimensional representation of patients’ response status.The response to preoperative chemoradiotherapy (PCRT) is correlated with oncologic outcomes in patients with locally advanced rectal cancer. Accurate prediction of PCRT response before surgery can provide crucial information to aid clinicians in further treatment planning. This study aimed to develop an evaluation tool incorporating a genetic biomarker and magnetic resonance imaging (MRI) to improve the assessment of response in post-CRT patients with locally advanced rectal cancer. A total of 198 patients who underwent PCRT followed by surgical resection for locally advanced rectal cancer between 2010 and 2016 were included in this study. Each patient’s response prediction index (RPI) score, a multigene biomarker developed in our previous study, and magnetic resonance tumor regression grade (mrTRG) score were added to create a new predictive value for pathologic response after PCRT, called the combined radiation prediction value (cRPV). Based on the new value, 121 and 77 patients were predicted to be good and poor responders, respectively, showing significantly different cRPV values (p = 0.001). With an overall predictive accuracy of 84.8%, cRPV was superior to mrTRG and RPI for the prediction of pathologic chemoradiotherapy response (mrTRG, 69.2%; RPI, 77.3%). In multivariate analysis, cRPV was found to be the sole predictor of tumor response (odds ratio, 32.211; 95% confidence interval, 14.408–72.011; p = 0.001). With its good predictive value for final pathologic regression, cRPV may be a valuable tool for assessing the response to PCRT before surgery.

Hospital variation in sphincter-preservation rates in rectal cancer treatment: results of a population-based study in the Netherlands.

BackgroundThis study aimed to examine the sphincter-preservation rate variations in rectal cancer surgery. The influence of hospital volume on sphincter-preservation rates and short-term outcomes (anastomotic leakage (AL), positive circumferential resection margin (CRM), 30- and 90-day mortality rates) were also analysed.MethodsNon-metastasized rectal cancer patients treated between 2009 and 2016 were selected from the Netherlands Cancer Registry. Surgical procedures were divided into sphincter-preserving surgery and an end colostomy group. Multivariable logistic regression models were generated to estimate the probability of undergoing sphincter-preserving surgery according to the hospital of surgery and tumour height (low, 5 cm or less, mid, more than 5 cm to 10 cm, and high, more than 10 cm). The influence of annual hospital volume (less than 20, 20–39, more than 40 resections) on sphincter-preservation rate and short-term outcomes was also examined.ResultsA total of 20 959 patients were included (11 611 sphincter preservation and 8079 end colostomy) and the observed median sphincter-preservation rate in low, mid and high rectal cancer was 29.3, 75.6 and 87.9 per cent respectively. After case-mix adjustment, hospital of surgery was a significant factor for patients’ likelihood for sphincter preservation in all three subgroups (P < 0.001). In mid rectal cancer, borderline higher rates of sphincter preservation were associated with low-volume hospitals (odds ratio 1.20, 95 per cent c.i. 1.01 to 1.43). No significant association between annual hospital volume and sphincter-preservation rate in low and high rectal cancer nor short-term outcomes (AL, positive CRM rate and 30- and 90-day mortality rates) was identified.ConclusionThis population-based study showed a significant hospital variation in sphincter-preservation rates in rectal surgery. The annual hospital volume, however, was not associated with sphincter-preservation rates in low, and high rectal cancer nor with other short-term outcomes.

SPHINCTER CUTTING AND PRESERVING SURGERIES FOR COMPLEX FISTULA IN ANO: A COMPARATIVE STUDY AT A TERTIARY CARE CENTRE IN NORTH INDIA

INTRODUCTION: Anal stula represents an important aspect of colorectal practice, being a distressing condition for the patient and sometimes a challenge for the surgeon. Successful surgical management of anal stulas requires accurate preoperative assessment of the course of the primary stulous tract and the site of any secondary extension or abscess. Fistula-in-ano has various types of clinical presentations. With time newer techniques have also evolved. Here we comparing the various treating modalities by classifying them as sphincter preserving and sphincter cutting surgeries. AIMS AND OBJECTIVES : To compare the outcome, duration of wound healing, recurrence rate, and complications after sphincter preserving and sphincter cutting surgeries. MATERIAL AND METHODS: A total 100 patients were taken up for the study after ethical clearance and proper informed consent. Group A (n=50) patients were selected for sphincter preserving surgeries (VAAFT+FILAC+LIFT, VAAFT+FILAC, LIFT). Group B (n=50) patients were taken up for sphincter cutting procedures (stulectomy and stulotomy). Simple fistulas, and those associated with tuberculosis, IBD, carcinomas, or with perianal injury were excluded from the study. Rectovaginal and anovaginal stulas, patients with history of incontinence, or anal sphincter impairment were also excluded. RESULTS: 66% patients were males and 34% were females. (1.94:1). Mean age of patients was 41.01+12.35 between 20-70 years. Transphincteric stula was the most common type (61%, n=61) and perianal discharge was the most common presentation. (100%, n=100). Primary healing rate at 3 months in sphincter preserving surgeries was 84%, and 66% in cutting surgeries (p&lt;0.05). Recurrence (p&lt;0.05) was st more in cutting surgeries. Incontinence at 1 week (p&lt;0.05) and hospital stay (p&lt;0.05), were also more after cutting surgeries. However, there was no statistically signicant difference in the mean healing time and pain by VAS score at 48 hours. CONCLUSIONS: Sphincter preserving surgeries for complex stula in ano are better in terms of less recovery time and better healing rate, less chances of incontinence, recurrence, compared to sphincter cutting surgeries. With the advent of more sphincter sparing techniques the percentage of patients undergoing sphincter cutting techniques should continue to decrease over time.

The Outcome of Induction Chemotherapy, Followed by Neoadjuvant Chemoradiotherapy and Surgery, in Locally Advanced Rectal Cancer.

Background & Objective:Currently, neoadjuvant chemoradiotherapy, followed by surgery, is the standard treatment for locally advanced rectal cancer. The use of induction chemotherapy for this tumor is controversial. In this study, the benefits and side effects of induction chemotherapy in locally advanced rectal cancer are evaluated.Methods:Twenty-nine patients with locally advanced rectal cancer in 2018-2019 were enrolled in this study. Initially, they underwent induction chemotherapy (oxaliplatin 130 mg/m2 every 3 weeks and capecitabine 1000 mg/m2 twice a day for 14 days every 3 weeks for 2 courses). Then, neoadjuvant chemoradiotherapy (radiotherapy 50.4 Gy/28 for 5 days a week concomitant with weekly oxaliplatin 50 mg/m2, as well as capecitabine 825 mg/m2/bid on the days of radiotherapy) was administered. After 4 weeks, computed tomography (CT) scan of thorax, pelvis, and abdomen with and without contrast was performed. Total mesorectal surgery was performed 6-8 weeks after the end of radiotherapy. Four courses of adjuvant chemotherapy were applied. Pathologic complete response (pCR), margin, sphincter preservation, and adverse effects were assessed.Results:In this study, pCR was present in 6 (20.7%) patients. R0 resection was done in 96.05%. Sphincter was preserved in 44.4% of lower rectal tumors. Two patients (6.9%) did not complete adjuvant treatment. Grade 3 adverse effects were documented in 13.7% of cases during induction chemotherapy and 17.2% of cases during neoadjuvant chemoradiation. Mortality was not reported. Conclusion:Induction chemotherapy, followed by neoadjuvant chemoradiotherapy and surgery, would be an effective and safe modality in locally advanced rectal cancer.

Distal resection margins in rectal cancer specimens: differences in assessment between surgeons and pathologists and the influence of neoadjuvant chemoradiation

To investigate the discrepancy between the distal resection margin (DRM) assessed by surgeons and pathologists, and the impact of neoadjuvant chemoradiotherapy (nCRT) on DRM. This study included 67 rectal cancer patients undergoing elective surgery. DRMs were assessed through four different techniques: in vivo subjective estimative, made by the surgeon before the rectal resection (by palpation and visual estimative); in vivo objective, measured with a ruler before the rectal transection; ex vivo objective, measured right after resection of the specimen; post-fixation objective measurement, conducted by the pathologist. The DRMs subjectively and objectively assessed by the surgeons were not significantly different (3.40cm vs. 3.45cm). There was a mean reduction in the length of DRMs of 35.6%, from 3.45cm objectively measured by the surgeon to 2.20cm measured by the pathologist. This difference was significant among patients that did not receive nCRT (3.90cm vs. 2.30cm, P < 0.001), but not among those who received nCRT (2.30 vs. 2.05cm). Surgeons are accurate in assessing rectal cancer DRMs. There are significant differences between intraoperative measurements of DRMs and the final pathologic results. However, these differences are not seen when nCRT is used, a finding that may be useful when sphincter preservation is being considered.

Retrospective Evaluation of Outcome of Rerouting Technique in Management of Horseshoe Perianal Fistula, Single Institution Experience

Abstract Background: Complex anal fistula is a topic of debate from ancient times due to its difficult treatment and its effect on patients quality of life. The most complex anal fistula is the branched transsphincteric fistula with secondary extension in the perianal spaces forming the configuration U-shaped or horseshoe fistula. Many surgical technique have been described for treatment of this fistula as fistulotomy as was described by Hanly 1965 but he noted high risk of anal incontinence despite the complete eradication of the deep post anal sepsis. Aim of Study: To evaluate retrospectively patients with complex horseshoe fistula for them re-routing technique was done with respect to operative time, occurrence of incontinence and rate of recurrence of the fistula. Patients and Methods: This study is a retrospective ob-servational study that was conducted on 30 patients who had complex horseshoe perianal fistula and underwent re-routing technique for the fistula in the last 3 years; from January 2017 to December 2019. Follow-up of the patients was for 6 months. They were recruited from General Surgery Department, Ain Shams University Hospitals (El-Demerdash), Ain Shams University, Egypt. Results: Of the 30 patients, 27 patients (90%) preserved complete and full continence. Only 3 patients (10%) developed incontinence post-operatively after the second stage, stage of rerouting. Of the 3 patients developed incontinence, 2 patients (6.7%) developed only gas incontinence which is according to wexner scoring system was sometimes that occurred less than once per week and only 1 patient (3.3%) developed gas and liquid stool incontinence which according to the wexner score system was rare that occurred less than once per month. All 3 cases developed incontinence didn't need to wear pads and there was no effect on their life style. After 6 months follow-up of the patients, recurrence occurred only in 2 patients (6.7%) at 3.5 and 5 months which was not statistically significant. Conclusion: Rerouting technique is a suitable proper sphincter preserving procedure for the management of the complex horse shoe perianal fistula with low recurrence rate, very acceptable and satisfactory magnitude of preservation of anal continence with no effect on patient's quality of life.

Can Pre-Treatment Inflammatory Parameters Predict the Probability of Sphincter-Preserving Surgery in Patients with Locally Advanced Low-Lying Rectal Cancer?

There is evidence suggesting that pre-treatment clinical parameters can predict the probability of sphincter-preserving surgery in rectal cancer; however, to date, data on the predictive role of inflammatory parameters on the sphincter-preservation rate are not available. The aim of the present cohort study was to investigate the association between inflammation-based parameters and the sphincter-preserving surgery rate in patients with low-lying locally advanced rectal cancer (LARC). A total of 848 patients with LARC undergoing radiotherapy from 2004 to 2019 were retrospectively reviewed in order to identify patients with rectal cancer localized ≤6 cm from the anal verge, treated with neo-adjuvant radiochemotherapy (nRCT) and subsequent surgery. Univariable and multivariable analyses were used to investigate the role of pre-treatment inflammatory parameters, including the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for the prediction of sphincter preservation. A total of 363 patients met the inclusion criteria; among them, 210 patients (57.9%) underwent sphincter-preserving surgery, and in 153 patients (42.1%), an abdominoperineal rectum resection was performed. Univariable analysis showed a significant association of the pre-treatment CRP value (OR = 2.548, 95% CI: 1.584–4.097, p < 0.001) with sphincter preservation, whereas the pre-treatment NLR (OR = 1.098, 95% CI: 0.976–1.235, p = 0.120) and PLR (OR = 1.002, 95% CI: 1.000–1.005, p = 0.062) were not significantly associated with the type of surgery. In multivariable analysis, the pre-treatment CRP value (OR = 2.544; 95% CI: 1.314–4.926; p = 0.006) was identified as an independent predictive factor for sphincter-preserving surgery. The findings of the present study suggest that the pre-treatment CRP value represents an independent parameter predicting the probability of sphincter-preserving surgery in patients with low-lying LARC.

Total neoadjuvant treatment versus standard chemoradiation to increase the sphincter preservation rate for distal locally advanced rectal cancer (TESS).

TPS3615 Background: Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with radiotherapy, followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant chemoradiotherapy to decrease surgical morbidity and increase quality of life. RAPIDO and PRODIGE-23 trials showed that TNT strategy could improve the pathological complete response (pCR) rateand reduce the risk of distant metastasis. The objective of this trial is to increase the proportion of sphincter preservation rate for distal rectal cancer patients by optimizing tumor response, by using TNT regimen as compared to conventional chemoradiotherapy. TESS (clinicalTrials.gov, NCT03840239), a prospective, open label, multicenter, randomized phase 2 study, is underway. Methods: Main inclusion criteria include: cT3-4aNany or cTanyN+ rectal adenocarcinoma aged 18-70y; ECOG performance 0-1; distance≤5cm from anal verge. 168 patients will be randomized 1:1. Patients in the TNT group will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplation) before, during and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as watch and wait) and adjuvant chemotherapy capecitabine 2 cycles. Patients in the standard treatment group will receive neoadjuvant radiotherapy 50Gy/25 fractions combined with capecitabine 5 weeks before TME (or other treatment decisions, such as watch and wait), and adjuvant chemotherapy Capeox 6 cycles. Primary endpoint is the rate of sphincter preservation rate (absence of stoma). Secondary endpoints include: Ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; acute toxicity; surgical complications; long-term anal function; late toxicity; ECOG standard score; disease-free survival; overall survival. First site opened in January 24, 2019. Clinical trial information: NCT03840239.

Phase II trial of neoadjuvant mFOLFOX 6 with panitumumab (P) in T3 rectal cancer with clear mesorectal fascia (MRF) and KRAS, NRAS, BRAF, PI3KCA wild type (4WT). GEMCAD 1601 PIER trial.

3512 Background: Patients with advanced colorectal cancer with 4WT tumors achieve increased response rates with chemotherapy and anti-EGFR therapy as compared with chemotherapy alone. In clinically staged (c) T3 rectal cancer neoadjuvant oxaliplatin/fluoropyrimidine combination has shown to induce encouraging pathological complete response (pCR). We hypothesize that combining FOLFOX and P could improve outcomes in 4WT tumors. Methods: PIER was an investigator-initiated phase II, single-arm, multicentre clinical trial to evaluate the safety and efficacy of neoadjuvant mFOLFOX6 with P in pts &lt; 75-y, with 4WT rectal cancer of the middle third staged as T3 by centrally-reviewed magnetic resonance imaging (MRI) and clear MRF, who were candidate for a R0 resection with sphincter preservation surgery. Pts received 6 cycles and underwent re-staging with MRI and sigmoidoscopy. Pts without progression underwent total mesorectal excision 4 weeks after the last cycle. Patients with progression were treated with pre-op chemoradiotherapy. The primary endpoint was pCR. The study followed a 2-Stage Simon’s MiniMax design (P0 of 16%, P1 of 35%, alpha and beta of 0.1). The target sample size was 35 patients and if 9 or more achieved a pCR, the results would be compatible with efficacy. We present primary and early secondary endpoints. Results: Between 9/2017 and 6/2020, 90 patients were screened (56 excluded; 42 were excluded due to mutations, 12 were excluded due to discrepancies with central review of radiology) of whom 34 were enrolled. In the ITT population a pCR was observed in 11 pts (32.3%; [95% CI 17.39-50.53]) and a near-complete pathological response (Mandard 1+2) was observed 17 pts (52.9%). Clinical complete or near complete response was achieved in 50% and there were no progressions. R0 resection rate and pathological circumferential resection margin neg- were 100%. Full compliance with induction was 88%. Neoadjuvant G3/4 toxicity occurred in 54% and was consistent with FOLFOX/P safety profile. G3/4 postoperative related toxicity was 19% with one reoperation. Conclusions: The study met the threshold for efficacy. mFOLFOX6 with P as neoadjuvant therapy can be effective and safe without unexpected toxicities in mrT3, clear MRF and 4WT rectal cancer and resulted in a higher rate of pCR compared with our previous series (GEMCAD 0801; The Oncologist 2014) in a similar molecular-unselected population. This study was funded by Amgen S.A. Clinical trial information: NCT03000374.

Retrospective cohort of total neoadjuvant therapy (TNT) in high-risk locally advanced rectal cancer (HR-LARC): Additional sintilimab (PD-1) in tri-modality approach.

e15604 Background: TNT is an emerging practice adapted to ensure all patients (pts) receive of systemic therapy, particularly for pts with high risk recurrence. Our previous phase II trial of TNT in MRI stratified HR-LARC demonstrated high down-staging rate and improved complete response with acceptable toxicity (manuscript under review). The aim of this retrospective cohort study was to evaluate the feasibility of sintilimab in combination with chemotherapy in TNT tri-modality treatment of pts with HR-LARC. Methods: HR-LARC pts who were given 3 cycles of sintilimab (200mg, iv, q3w) in combination with CapeOx followed by sequential long-course radiotherapy (IMRT GTV50.6 Gy/CTV 41.8 Gy/22f), 2 cycles CapeOx and surgery were enrolled from Beijing Cancer Hospital, CHN. The high risk was defined as middle to low RC (≤8cm to ARJ or 12 cm per sigmoidoscopy) with ≥1 factor from MRI features: clinical stage T3c/d-T4a/b, or N2 or MRF (+) or EMVI (+). The clinical outcomes included pathological response, major response rate (cCR+MPR), R0 resection rate, and toxicity. Results: From Feb 2019 to Oct 2020, 19 cases were identified with median distal location 4 cm (3-7), T2/T3/T4 1/15/3, N1/N2a/N2b 7/4/8, MRF+ 8/11, EMVI+ 8/11. Other characteristics were pMMR/MSS 100%, age 67y (47-78), male 57.9%, PS 1 100%, c-stage III 100% (18), median diameter of primary lesion 5.1 cm (2.1-7.5). As of 30th Dec 2020, 84.2% (16/19) received neoadjuvant therapy and completed surgical resection, with R0 resection rate 100%. One pts denied surgery and two chose watch &amp; wait since achieving cCR 10.5% (2/19). Of 16 resection pts, 13 had sphincter-sparing surgery (LAR or TaTME). One had Hartmann procedure, and two had abdominal perineal resection. The sphincter preservation rate was 84.2% (16/19). The pCR was 26.3% (5/19), and MPR was 47.3% (9/13). The major response rate was 57.9% (11/19), 4/2/13 of which completed intact TNT schema, induction and RT, and induction phase only, respectively. Treatment related adverse events (TRAE) occurred in 6 pts (31.6%) in grade (gr) 1-2 (CTCAE 5.0) without any gr 3-5 events occurred. Immune-related AEs were found in 2 pts with hypothyroidism (gr 1,2). Postoperative complications included two gr2 (Clavien-Dindo) events of anastomtic bleeding and infection. Of note, 3 pts with anastomotic stenosis got stoma reversion after dilation. Conclusions: Given the impressive response rate (57.9%), this retrospective analysis suggested a potential enhanced anti-cancer activity and good tolerability in pMMR/MSS HR-LARC from sintilimab in combination with TNT. The encouraging results warrant further evaluation of this approach in prospective trial.

Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): The AVANA study.

3511 Background: Preop CTRT is considered the standard of care in the management of LARC. RT can induce antigen release from a low neoantigen-burden tumor (such as a mismatch repair proficient colorectal cancer) and activate dendritic cells leading to a CD8+ T lymphocyte-mediated anticancer immune response. In LARC patients, neoadjuvant CTRT increases PD-L1 expression in tumor cells, strongly suggesting a neoadjuvant combinatory strategy with RT and PD-1/PD-L1 pathway blockade. Based on such considerations, we have designed the AVANA study to investigate the role of Ave in combination with preop CTRT in LARC. Methods: This is an Italian multi-center, phase II study. Pts with resectable LARC, defined by the presence of at least one of the following features: cN+, cT4, high risk cT3, received standard preop CTRT (capecitabine 825 mg/sqm/bid 5 days/week+ 50.4 Gy in 28 fractions over 5.5 weeks) plus 6 cycles of Ave 10 mg/Kg every 2 weeks. Surgery with total mesorectal excision was performed at 8-10 weeks after the end of CTRT. The primary end-point was the pCR rate, defined as complete histological regression with no available tumor cells ypT0N0. Secondary end-points were R0 resection rate, tumor downstaging, local recurrence, sphincter preservation rate, progression-free survival, overall survival, safety profile, and the evaluation of exploratory predictive and/or prognostic biomarkers. Assuming as null hypothesis p0 a pCR rate of 15%, a significance level of 5% (one-side), and a power of 80%, a sample size of 101 pts was needed to detect an absolute increment of 10% in pCR rate (from 15% to 25%). The experimental regimen is considered for further studies if, in at least 22 pts, we observe a pCR. Results: From April 2019 to November 2020, a total of 101 resectable LARC pts were enrolled in 10 Italian Centers. The median age was 63 years (23-82), 62 (61.4%) pts were male, 93 (92%) had ECOG PS 0. At baseline, 94 (93%) and 16 (16%) pts had cN+ and cT4 LARC, respectively. All pts completed the induction phase. Out of 96 pts evaluable for pathological response, 22 (23%) pts achieved a pCR and 59 (61.5%) pts a major pathological response (a central review is ongoing). At this time, microsatellite status is available only in 39 pts, of which only one was instable. The rate of grade 3-4 non-immune and immune-related adverse events was 8% and 4%, respectively. Avelumab was early interrupted in 9 pts out 101, mainly due to toxicity. Conclusions: The combination of preop CTRT plus Ave showed a promising activity and a feasible safety profile. According to our statistical considerations, the experimental regimen will be considered for further studies. Updated results will be presented during the Congress. Sponsored by GONO and partially supported by Merck. EUDRACT 2017-003582-10. Clinical trial information: NCT03854799.

Neoadjuvant Сhemoradiotherapy of Locally Advanced Rectal Cancer with Local 5-Fluoracil Radiomodification

Chemoradiotherapy, along with following surgical treatment, including total mesorectal excision, is a current standard for treatment of locally advanced rectal cancer. Neoadjuvant chemoradiotherapy allows to downsize the tumor, up to complete clinical response in one third of all cases, which, in turn, allows increase in sphincter preserving operations, disease-free period and overall survivability. Derivatives of 5-fluoracil are used as basic chemotherapeutic agents. These drugs have a substantial amount of side effects, which lead to either plan corrections, or may even prevent its completion. Thus, search for new ways to increase chemotherapy agent in the tumor cells with reduction of systemic toxicity to improve neoadjuvant chemoradiotherapy results is an acute task for modern medicine. In this article authors suggest intrarectal application of sterile hydrogel material based on sodium alginate with incorporated 5-fluoracil as a method of neoadjuvant chemoradiotherapy.