Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study).

BACKGROUND: Perianal fistulas may affect 15-50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis guidelines state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (2). OBJECTIVE: Presenting real-world effectiveness data for darvadstrocel in a Spanish population. DESIGN: Observational retrospective cohort study with prospective data gathering. SETTINGS: Fourteen institutions. PATIENTS: From November 2019-April 2022, all patients (73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; 3) absence of collections >2 cm confirmed by pelvic MRI scan at the time of surgery. INTERVENTIONS: Darvadstrocel treatment. MAIN OUTCOME MEASURES: Clinical response (closure of ≥50% of external openings), complete clinical closure (100% of external openings) and radiological closure (no fluid collection >2 cm, no edema or inflammation) evaluated 6 months after treatment. RESULTS: Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%) and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure and vice versa. No serious adverse events were reported. LIMITATIONS: Retrospective. CONCLUSIONS: Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, UK, and Japan) and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for treatment of fistulas in Crohn's disease. See Video Abstract.

Baiona's Consensus Statement for Fecal Incontinence. Spanish Association of Coloproctology.

Faecal incontinence (FI) is a major health problem, both for individuals and for health systems. It is obvious that, for all these reasons, there is widespread concern for healing it or, at least, reducing as far as possible its numerous undesirable effects, in addition to the high costs it entails. There are different criteria for the diagnostic tests to be carried out and the same applies to the most appropriate treatment, among the numerous options that have proliferated in recent years, not always based on rigorous scientific evidence. For this reason, the Spanish Association of Coloproctology (AECP) proposed to draw up a consensus to serve as a guide for all health professionals interested in the problem, aware, however, that the therapeutic decision must be taken on an individual basis: patient characteristics/experience of the care team. For its development it was adopted the Nominal Group Technique methodology. The Levels of Evidence and Grades of Recommendation were established according to the criteria of the Oxford Centre for Evidence-Based Medicine. In addition, expert recommendations were added briefly to each of the items analysed.

Influence of Preoperative Educational Intervention for Patients Undergoing Fecal Ostomy Surgery: A Comparison Cohort Study.

PURPOSE: This aim of this study was to compare the impact on hospital stay and short-term overall complications prior to and following the introduction of an outpatient preoperative ostomy education program to an existing inpatient ostomy education program. DESIGN: A comparison cohort study. SUBJECTS AND SETTING: One hundred thirty-eight consecutive patients undergoing ostomy surgery were included. One group (n = 65, 47%) was given an experimental preoperative ostomy education intervention, along with standard care including a postoperative educational intervention during the initial hospital course. A second group (n = 73, 53%) received the same standardized education in the postoperative period. Data were collected from a single tertiary center located in Seville, Spain, during a 12-month period between July 2014 and June 2015. METHODS: Data were collected in 2 phases. Data from participants undergoing postoperative (standard) education were collected retrospectively. Data for the group receiving preoperative education were collective prospectively. Outcome variables were postoperative length of stay, surgical complications (severity was assessed by the Clavien-Dindo grading system), subsequent interventions, and readmission rates. RESULTS: Analysis indicated no differences between the average length of postoperative hospital stay (12.32 days in the preoperative education group vs 12.76 days in the postoperative education group, P = .401). In contrast, overall complications, mortality, and readmission rates were significantly higher in the preoperative education program group (P = .027, P = .047, and P = .046, respectively). CONCLUSIONS: Delivering a standardized educational intervention during the preoperative period versus postoperative education delivery during the ostomy surgery hospital course did not reduce length of stay. Analysis indicated that overall complications, mortality, and readmission rates were significantly higher in the preoperative education program group but we hypothesize that intervening factors may have influenced these outcomes.

Personalized additive manufacturing of devices for the management of enteroatmospheric fistulas.

Additive manufacturing techniques allow the customized design of medical devices according to the patient's requirements. Enteroatmospheric fistula is a pathology that benefits from this personalization due to its extensive clinical variability since the size and morphology of the wound differ extensively among patients. Standard prosthetics do not achieve proper isolation of the wound, leading to a higher risk of infections. Currently, no effective personalized technique to isolate it has been described. In this work, we present the workflow for the design and manufacture of customized devices adapted to the fistula characteristics as it evolves and changes during the treatment with Negative Pressure Wound Therapy (NPWT). For each case, a device was designed with dimensions and morphology depending on each patient's requirements using white light scanning, CAD design, and additive manufacturing. The design and manufacture of the devices were performed in 230.50 min (184.00-304.75). After the placement of the device, the wound was successfully isolated from the intestinal content for 48-72 h. The therapy was applied for 27.71 ± 13.74 days, and the device was redesigned to adapt to the wound when geometrical evolutionary changes occur during the therapy. It was observed a decrease in weekly cures from 23.63 ± 10.54 to 2.69 ± 0.65 (p = 0.001). The fistulose size was reduced longitudinal and transversally by 3.25 ± 2.56 cm and 6.06 ± 3.14 cm, respectively. The wound depth also decreased by 1.94 ± 1.08 cm. In conclusion, customization through additive manufacturing is feasible and offers promising results in the generation of personalized devices for the treatment of enteroatmospheric fistula.

INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial.

BACKGROUND: The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn's disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn\'s Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. METHODS: Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. RESULTS: Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. CONCLUSIONS: Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel.

This retrospective chart review of patients treated with darvadstrocel indicates sustained remission and confirms a favorable safety profile up to 156 weeks after a single administration of stem cells for treatment of complex perianal fistulas in patients with Crohn's disease.

Clostridium septicum endophthalmitis as the first manifestation of a colon adenocarcinoma: A case report.

Clostridium septicum endophthalmitis is an extremely rare infection with only a few cases reported in the literature. It has an endogenous origin and is associated with gastrointestinal and haematological malignancies. We present the case of a 62-year-old male who presented this infection as the first manifestation of a colon adenocarcinoma.

Impact of the pandemic on surgical activity in colorectal cancer in Spain. Results of a national survey.

INTRODUCTION: The pandemic has had an impact on colorectal cancer surgery in hospitals. In 2020, up to 75% of colorectal cancer patients are estimated to require surgery. No objective data on the impact of the pandemic on the management of surgical waiting lists is available. We conducted a survey in colorectal surgery units to assess the impact on colorectal cancer surgery waiting lists. METHOD: All personnel in charge of colorectal surgery units nationwide received a survey (from February to April, 2020) with eight questions divided into three sections-cessation date of colorectal cancer surgeries, number of patients waiting for treatment, and use of neoadjuvant therapy to postpone surgery. RESULTS: Sixty-seven units participated in the study, with 79.1% of units ceasing some type of activity (32.8% total and 46.3% partial cessation) and 20.9% continuing all surgical activity. In addition, 65% of units used or prolonged neoadjuvant therapy in rectal cancer patients and 40% of units performed at least five emergency colorectal cancer surgeries. It was estimated that at least one month of intense surgical activity will be required to catch up. CONCLUSIONS: Currently, patients from units with a long waiting list must be redistributed, at least within the country. In the future, in the event of a second wave of the pandemic, an effective program to manage each unit's resources should be developed to prevent total collapse.

Urgent care practice in anorectal abscess. Still a pending task.

AIM: The aim of the study was to evaluate urgent care practice with regard to anorectal abscesses (AA) in a tertiary-level referral hospital. MATERIALS AND METHODS: this was retrospective and unicentric study. Patients who underwent surgery for AA between 2016 and 2017 were included in the study. Demographic variables were analyzed as well as the treatment performed, the need for hospitalization, use of antibiotics, and referral to the coloproctology outpatient department (COD). The recurrence risk factors were also evaluated. RESULTS: A total of 220 evaluations under anesthesia were performed, corresponding to 190 patients, 129 males (mean age 46 ± 14.9 years). The most frequent treatment in the emergency department (ED) was simple drainage (75.8%). Antibiotic therapy was prescribed in 62.9% of the cases. A total of 41.1% of the patients were referred to a specialized COD. The only risk factor associated with recurrence was the presence of an associated anal fistula. CONCLUSIONS: Anorectal abscesses are very frequent in the ED. There is great clinical variability regarding the taking of cultures, prescription of antibiotics, and referral criteria to a specialized coloproctology outpatient department, without clear impact of any of them on the recurrence of the abscess.

OBJETIVO: Evaluar el manejo de los abscesos perianales por parte del servicio de cirugía de urgencias. MÉTODO: Estudio unicéntrico retrospectivo. Se incluyeron pacientes que requirieron manejo quirúrgico de abscesos perianales de 2016 a 2017. Se analizaron variables demográficas, tratamientos realizados, necesidad de ingreso hospitalario, uso de antibióticos y necesidad de derivación a la consulta externa de coloproctología. Así mismo, se evaluaron los factores relacionados con la recurrencia del absceso. RESULTADOS: Durante el periodo de estudio se realizaron 220 exploraciones, correspondientes a 190 pacientes (129 hombres) con una edad media de 46 ± 14.9 años. El tratamiento quirúrgico más frecuentemente realizado fue el drenaje simple (75.8%). Se prescribieron antibióticos en el 62.9% de los casos. El 41.1% de los pacientes fueron remitidos a consulta externa de coloproctología. El único factor de riesgo asociado a la recurrencia fue la presencia de una fístula perianal asociada. CONCLUSIONES: Los abscesos perianales son frecuentes en los servicios de urgencias. Hay una gran variabilidad clínica en su manejo, sobre todo en lo relativo a la realización de cultivos, la prescripción de antibióticos y la derivación a unidades de coloproctología especializadas, sin que ninguna de estas medidas tenga un claro impacto en la recurrencia.

[Impact of the pandemic on surgical activity in colorectal cancer in Spain. Results of a national survey]. / Impacto de la pandemia sobre la actividad quirúrgica en cáncer colorrectal en España. Resultados de una encuesta nacional.

INTRODUCTION: The pandemic has had an impact on colorectal cancer surgery in hospitals. In 2020, up to 75% of colorectal cancer patients are estimated to require surgery. No objective data on the impact of the pandemic on the management of surgical waiting lists is available. We conducted a survey in colorectal surgery units to assess the impact on colorectal cancer surgery waiting lists. METHOD: All personnel in charge of colorectal surgery units nationwide received a survey (from February to April, 2020) with eight questions divided into three sections-cessation date of colorectal cancer surgeries, number of patients waiting for treatment, and use of neoadjuvant therapy to postpone surgery. RESULTS: Sixty-seven units participated in the study, with 79.1% of units ceasing some type of activity (32.8% total and 46.3% partial cessation) and 20.9% continuing all surgical activity. In addition, 65% of units used or prolonged neoadjuvant therapy in rectal cancer patients and 40% of units performed at least five emergency colorectal cancer surgeries. It was estimated that at least one month of intense surgical activity will be required to catch up. CONCLUSIONS: Currently, patients from units with a long waiting list must be redistributed, at least within the country. In the future, in the event of a second wave of the pandemic, an effective program to manage each unit's resources should be developed to prevent total collapse.

Fecal incontinence in older patients. A narrative review. / Incontinencia fecal en el paciente anciano. Revisión de conjunto.

Fecal incontinence is one of the leading causes for the institutionalization of people in the last decades of life, associated with a great psychosocial and economic burden. The literature is scarce in this population group, due to the absence of universally accepted criteria to define "elderly patients" and difficulties in detection and diagnostic. The aim of this article was to conduct a narrative review of the main aspects related to fecal incontinence in older patients, providing management support. Toileting assistance, dietary change, controlling stool consistency and medical treatment can be used to treat these patients. Nevertheless, other therapies, such as biofeedback, neuromodulation or surgical treatment, can be considered in selected patients.

C reactive protein as a predictor of anastomotic leakage in colorectal surgery. Comparison between open and laparoscopic surgery. / Proteína C reactiva como predictor de fuga anastomótica en cirugía colorrectal. Comparación entre cirugía abierta y laparoscópica.

INTRODUCTION: Anastomotic leak (AL) is a serious complication in colorectal surgery due to its increase in morbidity and mortality. The aim of this prospective non-randomised study is to determine whether C-reactive Protein (CRP) is useful as a predictor of AL in patients undergoing open versus laparoscopic surgery. METHODS: A total of 168 patients undergoing elective colorectal surgery were included. CRP was measured daily during the first 5postoperative days. Complications, specially AL, were analysed. RESULTS: Following an open approach 32 patients (45.7%) presented complications, 15 (18.7%) in the laparoscopic group and 12 (29.4%) in the converted group (P=0.153). Following open surgery 9 patients experienced AL, 5 were detected in the laparoscopic group and none in those converted (P=0.153). There were significant differences in CRP values between the 3 groups (P=0.03). ROC Curves showed AUC for the open and laparoscopic approach of 0.731 and 0.760 respectively. On day 4 the AUC was 0.867 for the open group and 0.914 for the laparoscopic group. Cut-off points on day 4 were: Open: 159.2mg/L; sensitivity 75%, specificity 89% and NPP 96% (P<0.001). Following laparoscopic surgery the cut-off point was 67.3%; sensitivity 100%, specificity 89.5% and NPP 100% (P=0.016). CONCLUSION: CRP on day 4 is useful to diagnose AL. Different cut-off values should be taken into account depending on the approach used.

Analysis of conversion factors in robotic-assisted rectal cancer surgery.

BACKGROUND: Robotic surgical management of rectal cancer has a series of advantages which might facilitate the surgical approach to the pelvic cavity and reduce conversion rates. The aim of the present study is to identify independent factors for conversion during robotic rectal cancer surgery. METHODS: A total of 67 patients underwent preoperative CT scan in order to obtain a three-dimensional image of the pelvis, the tumour and prostate. We measured maximum and minimum ilio-iliac, sacral promontory-pubis, coccyx-pubis diameters and maximum lateral axis. Further variables under consideration were age, BMI and use of neoadjuvant therapy. We recorded short-term follow-up outcomes of the resected tumour. RESULTS: The present study included 67 patients (39 males) with an average age of 65.11 ± 10.30 years and a BMI of 27.70 ± 3.97 kg/m(2). Operative procedures included nine abdominoperineal resections and 58 low anterior resections. There were 15 (22.38 %) conversions. Mean operating time was 192.2 ± 42.73 min. Minimum ilio-iliac, maximum ilio-iliac, promontory-pubic and coccyx-pubis diameter as well as maximum lateral axis were 100.38 ± 7.65, 107.10 ± 10.01, 109.97 ± 9.20, 105.61 ± 9.27 and 129.01 ± 9.94 mm, respectively. Mean tumour volume was 37.06 ± 44.08 cc; mean prostate volume was 42.07 ± 17.49 cc. The univariate analysis of the variables showed a correlation between conversion and BMI and minimum ilio-iliac and coccyx-pubis diameters (p = 0.004, 0.047, 0.046). In the multivariate analysis, the only independent predictive factor for conversion was the BMI (p = 0.004).No correlation was found between conversion and sex, age, tumour volume or the rest of pelvic diameters. CONCLUSION: BMI is an independent factor for conversion in robotic-assisted rectal cancer surgery.

Learning curve for robotic-assisted laparoscopic rectal cancer surgery.

INTRODUCTION: One of the main uses of robotic assisted abdominal surgery is the mesorectal excision in patients with rectal cancer. The aim of the present study is to analyse the learning curve for robotic assisted laparoscopic resection of rectal cancer. PATIENTS AND METHODS: We included in our study 43 consecutive rectal cancer resections (16 females and 27 males) performed from January 2008 through December 2010. Mean age of patients was 66 ± 9.0 years. Surgical procedures included both abdomino-perineal and anterior resections. We analysed the following parameters: demographic data of the patients included in the study, intra- and postoperative data, time taking to set up the robot for operations (set-up or docking time), operative time, intra- and postoperative complications, conversion rates and pathological specimen features. The learning curve was analysed using cumulative sum (CUSUM) methodology. RESULTS: The procedures understudied included seven abdomino-perineal resections and 36 anterior resections. In our series of patients, mean robotic set-up time was 62.9 ± 24.6 min, and the mean operative time was 197.4 ± 44.3 min. Once we applied CUSUM methodology, we obtained two graphs for CUSUM values (operating time and success), both of them showing three well-differentiated phases: phase 1 (the initial 9-11 cases), phase 2 (the middle 12 cases) and phase 3 (the remaining 20-22 cases). Phase 1 represents initial learning; phase 2 plateau represents increased competence in the use of the robotic system, and finally, phase 3 represents the period of highest skill or mastery with a reduction in docking time (p = 0.000), but a slight increase in operative time (p = 0.007). CONCLUSION: The CUSUM curve shows three phases in the learning and use of robotic assisted rectal cancer surgery which correspond to the phases of initial learning of the technique, consolidation and higher expertise or mastery. The data obtained suggest that the estimated learning curve for robotic assisted rectal cancer surgery is achieved after 21-23 cases.

[Prospective randomised study: robotic-assisted versus conventional laparoscopic surgery in colorectal cancer resection]. / Estudio prospectivo, aleatorizado: cirugía laparoscópica con asistencia robótica versus cirugía laparoscópica convencional en la resección del cáncer colorrectal.

INTRODUCTION: Robotic-assisted surgery is playing an increasingly important role in the last few years in the treatment of colorectal oncological disease. However, there are still no studies that objectively demonstrate the advantages of this type of surgery. We present a prospective randomised study in order to compare the short-term results between colorectal robotic surgery and laparoscopic surgery. MATERIAL AND METHOD: A total of 56 patients diagnosed with colorectal cancer between January 2008 and January 2009, were randomised and assigned to the robotic or laparoscopic group. Age, body mass index, tumour location, conversions in each group, complications during and after surgery, and histological characteristics of the specimens obtained, were all compared. RESULTS: There were no significant differences between age (P=.055), body mass index (P=.12), or tumour location (P=.91). Only one patient in the robotic group required a transfusion and none in the laparoscopic group. The percentage of conversions was the same in both groups, however, the preparation times and operating times were significantly longer in patients intervened using the robotic device (P=.0001 and P=.017, respectively). There were no differences as regards the rate of complications or in the percentage of re-interventions (14.2% and 7.1%). The mean hospital stay of the patients was 9.3 (8.1) days in the robotic group and 9.2 (6.8) days in the laparoscopic (P=.79). The distal resection margin was greater in the specimen obtained using robotic surgery (P =.003) as well as the number of lymph nodes obtained in the specimen (P =.23). CONCLUSION: Robotic colorectal was performed safely and effectively, and with similar clinical results. International Trial Number for this study is: ISRCTN60866560.