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We aim to analyze differences in compliance between colon and rectal cancer surgeries under Enhanced Recovery After Surgery (ERAS) for colorectal procedures, and to detect implementation barriers for rectal cancer surgeries. Patients who underwent elective rectal cancer surgeries under ERAS were case-matched based on gender, age, and P-POSSUM with an equal number of patients who underwent colonic surgeries. Achievements of ≥ 70% of ERAS items were considered an acceptable level of compliance. A multivariate analysis was carried out to identify independent risk factors for lower compliance. A total of 434 patients were included over a 5-year period. After matching, there were 111 patients in each group. Overall compliance was significantly lower in the rectal surgery group (73% vs 82%, p = 0.001). A good compliance rate differed from 55% in rectal vs 77.5% in colonic procedures (p = 0.000). We identified three independent risk factors for lower compliance rates: open surgical approach, the use of epidural catheter, and the presence of postoperative ileus. Our data showed that rectal cancer surgeries are more exigent to success on ERAS interventions when compared to colonic resections. There is a need to introduce specific modifications on the protocols for colorectal surgeries when applied to these particular procedures.

Data from this paper were presented as a poster at the ISCT Europe 2018, Regional Meeting in Florence, Italy, held between 12 and 14 September 2018., [Aim] Management of faecal incontinence (FI) remains challenging because no definitive optimal treatment for this condition has yet been determined. Regenerative medicine could be an attractive therapeutic alternative for treating FI. Here, we aimed to determine the safety and feasibility of autologous expanded mesenchymal stem cells derived from adipose tissue (AdMSCs) in the treatment of patients diagnosed with structural FI., [Method] This was a randomized, multicentre, triple‐blinded, placebo‐controlled pilot study conducted at four sites in Spain with 16 adults with FI and a sphincter defect. Autologous AdMSCs were obtained from patients from surgically excised adipose tissue. These patients were intralesionally infused with a single dose of 4 × 107 AdMSCs or a placebo while under anaesthesia. We assessed the safety and feasibility of the treatment as the cumulative incidence of adverse events and the treatment efficacy using the Cleveland Clinic Faecal Incontinence Score, Faecal Incontinence Quality of Life score and Starck criteria to classify sphincter defects and anorectal physiology outcomes., [Results] Adipose tissue extraction, cell isolation and intralesional infusion procedures were successful in all the patients. There was only one adverse event connected to adipose tissue extraction (a haematoma), and none was associated with the injection procedure. There were no significant differences in any of the assessed clinical, manometric or ultrasonographic parameters., [Conclusion] This study indicates that this infusion procedure in the anal sphincter is feasible and safe. However, it failed to demonstrate efficacy to treat patients with structural FI., This project received partial funding from the Andalusian Ministry of Health (grant number PI‐0424‐2013).

We evaluated the safety and feasibility of adipose‐derived mesenchymal stem cells to treat endoscopically urinary incontinence after radical prostatectomy in men or female stress urinary. We designed two prospective, nonrandomized phase I‐IIa clinical trials of urinary incontinence involving 9 men (8 treated) and 10 women to test the feasibility and safety of autologous mesenchymal stem cells for this use. Cells were obtained from liposuction containing 150 to 200 g of fat performed on every patient. After 4 to 6 weeks and under sedation, endoscopic intraurethral injection of the cells was performed. On each visit (baseline, 1, 3, 6, and 12 months), clinical parameters were measured, and blood samples, urine culture, and uroflowmetry were performed. Every patient underwent an urethrocystoscopy and urodynamic studies on the first and last visit. Data from pad test, quality‐of‐life and incontinence questionnaires, and pads used per day were collected at every visit. Statistical analysis was done by Wilcoxon signed‐rank test. No adverse effects were observed. Three men (37.5%) and five women (50%) showed an objective improvement of >50% (P, We evaluated the safety and feasibility of adipose‐derived mesenchymal stem cells (MSCs) to treat endoscopically urinary incontinence after radical prostatectomy in men or women stress urinary. Our conclusion is intraurethral application of MSCs are a safe and feasible procedure to treat urinary incontinence. A statistically significant difference was obtained for pad‐test improvement in 3/8 men and 5/10 women.

Objectives. To confirm that patients affected by colorectal cancer have the V2 region of Septin 9 (SEPT9) gene hypermethylated in the circulating free DNA from a peripheral blood sample before surgery and to determine if this hypermethylated DNA disappears from the patients after complete resection of the tumour. Methods. Plasma from 10 patients with colorectal cancer was collected preoperative and three months after surgery. The analysis of the methylation status of the promoter region of the SEPT9 gene was performed using a 7500 Fast Real-Time PCR System. Results. Hypermethylation of SEPT9 gene was detected in 8 out of 10 preoperative samples (one negative result was probed to be a Lynch syndrome) and in 4 out of 10 postoperative samples matching with the cases of recurrence or persistence of disease. This means that, in this sample, the preoperative sensitivity and specificity of the test were 88.9% and 100%, respectively, and there is 100% correlation between the positive results of the SEPT9 test and a recurrence/persistence of the disease in patients after surgical resection. Conclusions. Our study shows that circulating hypermethylated SEPT9 is a specific colorectal cancer biomarker. This hypermethylated SEPT9 DNA disappears around three months after surgery and that circulating hypermethylated SEPT9 may be the first noninvasive marker for postsurgical diagnosis; this conclusion must be confirmed with a more significant number of patients.

The use of mesenchymal stem cells has resulted in a breakthrough for the treatment of complex perianal fistulas in Crohn’s disease. This novel treatment is associated with a minimally invasive surgical technique that can be well defined. However, our previous experience has taught us that neglecting any of the critical steps in the operation can result in frequent treatment failure. We have put together a comprehensive guide, a stepwise algorithm, for our minimally invasive approach to identify common pitfalls and reduce treatment failures. Using data we have collected over the past 15 years from drug development, execution of clinical trials, and enacting an advanced educational training program, we spelt out each stage of the minimally invasive surgical intervention for stem cell delivery for perianal Crohn’s disease. In this article, we provide 21 tips for a correct approach during the five major phases of the surgical procedure. To optimize the efficacy of mesenchymal stem cells for perianal Crohn’s disease, a standardized minimally invasive technique including a reliable and reproducible series of key steps should be utilized.

In the era of personalized medicine and targeted therapies for the management of patients with cancer, ultrasensitive detection methods for tumor genotyping, such as next-generation sequencing or droplet digital polymerase chain reaction (ddPCR), play a significant role. In the search for less invasive strategies for diagnosis, prognosis and disease monitoring, the number of publications regarding liquid biopsy approaches using ddPCR has increased substantially in recent years. There is a long list of malignancies in which ddPCR provides a reliable and accurate tool for detection of nucleic acid-based markers derived from cell-free DNA, cell-free RNA, circulating tumor cells, extracellular vesicles or exosomes when isolated from whole blood, plasma and serum, helping to anticipate tumor relapse or unveil intratumor heterogeneity and clonal evolution in response to treatment. This updated review describes recent developments in ddPCR platforms and provides a general overview about the major applications of liquid biopsy in blood, including its utility for molecular response and minimal residual disease monitoring in hematological malignancies or the therapeutic management of patients with colorectal or lung cancer, particularly for the selection and monitoring of treatment with tyrosine kinase inhibitors. Although plasma is the main source of genetic material for tumor genomic profiling, liquid biopsy by ddPCR is being investigated in a wide variety of biologic fluids, such as cerebrospinal fluid, urine, stool, ocular fluids, sputum, saliva, bronchoalveolar lavage, pleural effusion, mucin, peritoneal fluid, fine needle aspirate, bile or pancreatic juice. The present review focuses on these "alternative" sources of genetic material and their analysis by ddPCR in different kinds of cancers.

Background Infection control measures during the COVID-19 crisis modified diverticulitis treatment. Here we present the treatment applied in three large UK centres compared to the same timeframe in 2019. Methods This was a multicentre, comparative study, whereby diverticulitis cases from March 23rdto May 11th2019 acted as historical controls for cases during lockdown. Severity at presentation (SD), comorbidities, treatment modality, Length of Stay (LOS), complications and COVID-19 status (CS) were recorded. Chi-squared, ANOVA, Mann-Whitney test and linear regression were used for analyses. Results 59 patients presented with diverticulitis in 2020 compared to 130 in 2019 (M:F 27/32, 56/74 and 64vs.62 y.o.). Laparotomy was performed in 6/59 and 12/130 respectively. Comparing 2019 to 2020, there was no statistical difference for severity (p = 0.643), treatment modality (0.946), comorbidities (0.313), LOS (0.602). Linear regression demonstrated statistically significant association between treatment employed (p Conclusion Diverticulitis cases during 2020 lockdown reduced noticeably (59vs.130). There was no difference in severity, treatment, comorbidities or LOS between 2019 and 2020. Laparotomy was performed in 6/59 and 12/130 respectively. Decision about treatment and LOS in 2020 was associated with severity of disease only. There was no association with COVID status. These findings should be interpreted with caution due to small COVID positive numbers and not including ambulatory units, however, they are consistent with findings from our sister Spanish group.

Background Diagnostic tests for fecal incontinence have been improved over time. This study aims to evaluate the role of Three-dimensional endoanal ultrasound (3D-EUS) and the Starck's score in the assessment and treatment of obstetric sphincter injuries. Methods A prospective observational study was performed including primiparous women who were evaluated at 20 wk of pregnancy and 3 mo after childbirth. Sphincter defects were classified according to the Starck's and Obstetrical Anal Sphincter Injuries classifications. Patients also completed the Fecal Incontinence Quality of Life and the Wexner questionnaires before and after childbirth. Results Sphincter defects were detected in 45% of the 56 women included, although 85% had an uneventful delivery. Most defects were found isolated to the external anal sphincter except for two cases, classified by a Starck’s score >8. Fecal Incontinence Quality of Life and Wexner questionnaires showed a rate of symptomatic patients of around 46%. We observed that 30% of patients with sphincter injuries remained asymptomatic. Conclusions The 3D-EUS is a useful test in assessing sphincter defects after childbirth. This method makes it possible to detect small sphincter defects that otherwise would have gone unnoticed, as 30% of patients with sphincter injuries were asymptomatic. In addition, both the 3D-EUS and the Starck's score were valuable in establishing an algorithm for the treatment of obstetric sphincter injuries.

REDISSEC-CARESS/CCR group., [Introduction] Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening., [Study method] A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010–2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained., [Results] A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p, [Conclusions] The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups., This research was partially supported by grants from REDISSEC (RD12/0001/0010 and RD16/0001/0006), Instituto de Salud Carlos III (PI 09/00910, PI 13/00013, PI 18/01181) and the European Regional Development Fund.

The best alimentary and biliopancreatic limb (BPL) lengths in the Roux-en-Y gastric bypass (RYGB) still remain unclear. The aim of this study was to compare the effect of a BPL of 70 vs 120 cm, with a constant AL of 150 cm on long-term weight loss, remission of comorbidities, and supplementation needs after RYGB. A prospective randomized study of morbidly obese patients undergoing RYGB was performed. Patients were randomized into two groups: those patients undergoing RYGB with a BPL of 70 cm (BPL 70 cm) and those ones undergoing RYGB with a BPL of 120 cm (BPL 120 cm). BMI, excess BMI loss (EBMIL), remission of comorbidities and specific vitamin and mineral supplementation needs at 1, 2, and 5 years were analyzed. Two hundred fifty-three patients were included in each group. There were no significant differences in BMI, EBMIL and the remission of diabetes mellitus, hypertension, and dyslipidemia between groups at 1, 2, and 5 years after surgery. Patients from group BPL 120 cm required greater specific supplementation of vitamin B12, folic acid, and vitamin A during all the follow-up. A RYGB with 120 cm BPL does not achieve greater weight loss or remission of comorbidities than a RYGB with 70 cm BPL but is associated with greater deficiencies of vitamin B12, vitamin A, and folic acid. ClinicalTrials.gov Identifier NCT03607305. https://clinicaltrials.gov/.

Aim. To report our experience in a compassionate use program for complex perianal fistula. Methods. Under controlled circumstances and approved by European and Spanish laws, a compassionate use program allows the use of stem cell therapy for patients with nonhealing diseases, mostly complex fistula-in-ano, who do not meet criteria to be included in a clinical trial. Candidates had previously undergone multiple surgical interventions that had failed. The intervention consisted of surgery (with closure of the internal opening or a surgical flap performance), followed by stem cell injection. Three types of cells were used for implant: stromal vascular fraction, autologous expanded adipose-derived, or allogenic adipose-derived stem cells. Healing was evaluated at 6th month follow-up. Outcome was classified as partial response or healing. Relapse was evaluated 1 year later. Maximum follow-up period was 48 months. Results. 45 patients (24 male) were included; the mean age was 45 years, which ranged from 24 to 69 years. Since some of them received repeated doses, 52 cases were considered (42 fistula-in-ano, 7 rectovaginal fistulas, 1 urethrorectal fistula, 1 sacral fistula, and 1 hidradenitis suppurativa). Regarding fistula-in-ano, there were 18 Crohn’s-associated and 24 cryptoglandular. 49 cases (94.2%) showed partial response starting 6.5 weeks of follow-up. 24 cases (46.2%) healed in a mean time of 5.5 months. A year later, all patients cured remained healed. No adverse effects related to stem cell therapy were reported. Conclusion. Stem cells are safe and useful for treating anal fistulae. Healing can be achieved in severe cases.

Background: Can we create a technological solution to flexibly self-manage undergraduate General Surgery practices within hospitals? Before the pandemic, the management of clerkships was starting to depend less on checkerboards. This study aims to explore undergraduates’ perceptions of doing rotations in teaching hospitals using different teaching styles and elicit their views regarding the options of managing practices to design a mobile app that substitutes for checkerboards. Methods: In this sequential exploratory mixed methods study, 38 semi-structured interviews at a teaching hospital were conducted. The data was used to survey 124 students doing their rotations in four teaching hospitals during the first wave of COVID-19. Results: 21 themes highlighted concerns related to the practices, the teacher involvement in the students’ education, and the students’ adaptation to clinical culture. The students reported positive perceptions concerning self-managing and organizing practices via a mobile application. However, problems emerged regarding transparency, the lack of feedback, and the need for new tools. Regarding the teaching styles, the facilitator and personal models were perceived as optimal, but the personal style had no effect on using or not using a tool. Conclusions: A mobile-learning application designed like an educational opportunities’ manager tool can probably promote self-directed learning, flexible teaching, and bidirectional assessments. However, teachers who employ a personal teaching style may not need either checkerboards or a tool. This solution supports teaching at hospitals in pandemic times without checkerboards.

Objective. The aims of this study are to compare 2 origins of adipose-derived mesenchymal stem cells (MSCs) (omentum and subcutaneous) from 2 pathologies (morbid obesity and cancer) vs healthy donors. Adipose tissue has revealed to be the ideal MSC source. However, in developing adipose-derived stem cells (ASCs) for clinical use, it is important to consider the effects of different fat depots and also the effect of donor variability. Methods. We isolated and characterized the membrane markers and differentiation capacities of ASCs obtained from patients with these diseases and different origin. During the culture period, we further analysed the cells’ proliferation capacity in an in vitro assay as well as their secretome. Results. Adipose-derived stem cells isolated from obese and cancer patients have mesenchymal phenotype and similar cell proliferation as ASCs derived from healthy donors, some higher in cells derived from subcutaneous fat. However, cells from these 2 types of patients do not have the same differentiation potential, especially in cancer patients from omentum, and exhibit distinct secretion of both pro-inflammatory and regulatory cytokines, which could explain the differences in use due to origin as well as pathology associated with the donor. Conclusion. Subcutaneous and omentum ASCs are slightly different; omentum generates fewer cells but with greater anti-inflammatory capacity. Adipose-derived stem cells from patients with either obesity or cancer are slightly altered, which limits their therapeutic properties.

© The Author(s) 2021., Rectal cancer (RC) appears to behave differently compared with colon cancer. We aimed to analyze existence of different subtypes of RC depending on distinct features (age of onset and the presence of synchronous primary malignant neoplasms). We compared the clinicopathological, familial and molecular features of three different populations diagnosed with RC (early-onset RC [EORC], late-onset RC, and synchronous RC [SRC]). Eighty-five RCs were identified and were evaluated according to their microsatellite instability, CpG Island Methylator Phenotype (CIMP) and chromosomal instability, as assessed by Next Generation Sequencing and microarray-based comparative genomic hybridization approaches. The results were subjected to cluster analysis. SRCs displayed the most specific characteristics including a trend for the development of multiple malignant neoplasms, a greater proportion of CIMP-High tumors (75%) and more frequent genomic alterations. These findings were confirmed by a clustering analysis that stratified RCs according to their genomic alterations. We also found that EORCs exhibited their own features including an important familial cancer component and a remarkable rate of mutations in TP53 (53%). Together, heterogeneity in RC characteristics by age of disease-onset and SRC warrants further study to optimize tailored prevention, detection and intervention strategies—particularly among young adults., This work was funded by the Spanish Ministry of Health and Consumer Affairs and FEDER, Grant number PI16/01650 to José Perea, PI16/01920 to Rogelio González-Sarmiento, and PI14/00459 to Miguel Urioste.

Introduction The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life. Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant. Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals (BMJ Open, JAMA Surgery, Annals of Surgery, British Journal of Surgery). Abstracts will be submitted to relevant national and international meetings., The present research study was awarded a Ministerio de Ciencia e Innovación health research project grant (PI19/00291) from the Carlos III Institute of the Spanish National Health Service as part of the 2019 call for Strategic Action in Health.

Background: Positive cytology has been identified as an independent negative prognostic factor in patients with peritoneal metastases (PM) of colorectal origin. Liquid biopsy in plasma may detect increasing levels of circulating tumor DNA (ctDNA) and could help predict systemic relapse in patients with colorectal cancer, but little is known about the role of liquid biopsy in peritoneal fluid. The aim of this study was to evaluate the prognostic value of peritoneal fluid and plasma liquid biopsy in patients undergoing complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CC-HIPEC). Methods: A longitudinal prospective study was designed in patients with KRAS-mutated colorectal or appendiceal primary tumor, including PM of colorectal origin, pseudomyxoma peritonei and patients at high risk of developing PM (selected for second-look surgery). Eleven patients were recruited according to inclusion and exclusion criteria. ctDNA from plasma and peritoneal fluid before and after HIPEC was studied by droplet digital PCR looking for KRAS mutation. A close follow-up was scheduled (mean of 28.5 months) to monitor for systemic and peritoneal recurrences. Results: All patients with positive plasma postHIPEC had systemic relapse and four patients died as a result, while those with negative plasma postHIPEC did not relapse. Patients with negative peritoneal ctDNA after CC-HIPEC did not present peritoneal relapse. Of six patients with positive peritoneal ctDNA postHIPEC, two presented peritoneal recurrence and four systemic relapses. Conclusions: Treatment with CC-HIPEC does not always neutralize ctDNA in peritoneal fluid, and its persistence after treatment may predict adverse outcome. Despite being a proof of concept, an adequate correlation between liquid biopsy in plasma and peritoneal fluid with both systemic and peritoneal relapse has been observed.

Venous leg ulcers (VLU) represent an uphill economic, health and social burden, aggravated in the elderly. Best-practice care interventions are often insufficient and alternative therapies need to be explored. Herein, we have treated for the first time a chronic VLU in an elderly patient by combining cell therapy and tissue engineering in the context of a compassionate use. The administration of allogeneic adipose-derived mesenchymal stromal cells (MSCs) embedded in a plasma-based bioengineered dermis covering the ulcer bed and also injected into the ulcer margins led to the complete closure of a 10-year recalcitrant VLU in an 85-year-old patient. Regenerative properties of MSCs might be boosted by the use of bioengineered matrices for their delivery.

There are several cases of liver abscesses caused by the ingestion of a foreign body, especially in the elderly. Fish bones or chicken bones are sharp foreign bodies that can migrate through the digestive tract to the liver parenchyma. We reported a 71-year-old man who presented to the emergency department with fever and epigastric pain. Computed tomography scan showed a liver abscess related to a long and sharp foreign body which is protruding from the left lobe of the liver. Systemic antibiotic treatment was initiated and later the foreign body was removed by laparoscopic surgery.Existen numerosos casos publicados en la literatura que muestran abscesos hepáticos producidos por la ingestión de un cuerpo extraño, especialmente en ancianos. Los huesos de pollo, y con mayor frecuencia las espinas de pescado, pueden perforar el tubo digestivo y migrar hasta el parénquima hepático y originar un absceso. Reportamos el caso de un paciente de 71 años que acude a urgencias por dolor epigástrico y fiebre. Se realizó tomografía computarizada abdominal, que identificó un absceso hepático junto con un cuerpo extraño puntiforme que penetraba en el hígado. El paciente fue intervenido quirúrgicamente, realizando drenaje del absceso y retirada del cuerpo extraño mediante abordaje laparoscópico.

Posterior tibial nerve stimulation (PTNS) is a minimally invasive approach with little adverse effects, but obtaining good results as shown in the different scales for the evaluation of the severity of incontinence. The aim of this study was to determine the effects of PTNS based on manometric determinations of the anal sphincter and severity during a period of treatment of 6 months (18 sessions). A prospective interventional study of patients with fecal incontinence was performed. Subjects underwent one 30-min session every week for 12 weeks, followed by 6 sessions every 2 weeks. The effect on incontinence was evaluated by means of St. Marks and defecatory urgency scales, and manometry. Seventy-three patients were included. At baseline, 28.8% of the patients had a retention time of less than 1 min. At 12 weeks, 39.7% of the patients presented a retention time to 5–10 min and at 18 weeks 37% presented it over 10 min. At baseline, mean St Marks score was 15.1 + 5.1, improving after 12 weeks of treatment to 8.9 + 5 (p

Differential presence of exons (DPE) is a method of interpretation of exome sequencing, which has been proposed to design a predictive algorithm with clinical value in patients with colorectal cancer (CRC). The goal of the present study was to examine the reproducibility in a rat model of metastatic colon cancer. DHD/K12-TRb cells were injected in syngenic immunocompetent BD-IX rats. Cells were from two stocks with low and normal metastatic potential, and injected into two separate groups of rats. Five to ten weeks after injection, blood samples were taken prior euthanasia and whole exome sequencing performed. Through DPE analysis, we identified a set of exons whose differential presence in plasma allowed us to compare both groups of tumor-bearing animals. A verification test was performed to confirm that the algorithm was able to classify extracted samples into their corresponding groups of origin. The highest mean probability was 0.8954. In conclusion, the DPE analysis in tumor-bearing animals was able to discriminate between different disease status, which fully supports previous results in CRC patients., This studywas funded by two grants from"Instituto de Salud Carlos III", Spain (FIS; refs. PS09/01815 and PI13/01924)

Background: the Enhanced Recovery After Surgery (ERAS) protocols aim to improve postoperative outcomes by obtaining a functional rehabilitation after surgery. The purpose of this study was to evaluate the impact of ERAS on the quality of life (QOL) of patients undergoing colorectal cancer surgeries. Methods: a cohort observational study was designed of patients with colorectal cancer undergoing elective surgeries during a one-year period. Patients were included when the ERAS protocol was fully achieved for all the interventions, including the expected hospital discharge day. Patient reported outcomes (PROs) were evaluated by the EORTC QLQ-C30 and the QLQ-CR29 questionnaires on three different occasions: baseline before surgery and on postoperative days 7 and 30. Results: the study included 40 patients who completed QOL evaluations with a mean age of 70 ± 11 years. There were no statistical differences between preoperative and postoperative QOL scores. By subgroups of QOL items, a significant decrease was observed in physical activity and role functioning when comparing preoperative vs postoperative status, whereas the cognitive, social and emotional functioning scales were similar or improved over time. Conclusions: in our experience, surgery under ERAS protocols did not have an impact on decreasing global QOL in patients undergoing elective colorectal cancer surgery. The use of ERAS protocols in colorectal surgery achieves a positive influence, not only by decreasing surgical-related complications but also in terms of functional recovery, by decreasing the negative effects of surgery on patient QOL.

Background: Acellular pseudomyxoma peritonei (aPMP) is a rare peritoneal malignancy characterized by the accumulation of large amounts of mucin (lacking tumor cells) in the peritoneum. Many cases account for several kilograms of mucin to be screened by the pathologist. This is a comprehensive study of three patients with aPMP, whose tumors showed KRAS mutation, allowing for the tracking of this marker by liquid biopsy. Methods: Pre and post-surgery plasma, and mucin removed during cytoreductive surgery were collected from the patients. KRAS mutations were analyzed using droplet digital polymerase chain reaction (ddPCR). Mucin was injected in mice. KRAS and cytokine levels were measured in plasma of the mice using ddPCR and a magnetic bead-based assay. Mucin microbiome was analyzed by 16S rRNA sequencing. Results: KRAS mutations were detected in mucin cell-free DNA (cfDNA) from the three patients but not in the pre or post-surgery plasma. Electron microscopy detected microparticles (diameter, The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by a grant from the ‘FIS-ISCIII-FEDER’ [Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (European Regional Development Fund)], Ministry of Health, Spain (grant number PI17/01233).

Objective There is limited information on health service use or patient-reported outcomes when comparing the effectiveness of laparoscopic with that of open surgery. The aim was to compare the effectiveness of laparoscopic with that of open surgery up to 2 years after intervention in patients with colon cancer. Methods Prospective cohort study of patients with colon cancer who underwent surgery (laparoscopic or open surgery) between June 2010 and December 2012, at 22 hospitals. Main outcomes of the study were mortality, complications, reoperation, readmission, and patient-reported outcome measures (PROMs), as measured using the Hospital Anxiety and Depression Scale, Duke-UNC, EuroQol-5D, and European Organisation for Research and Treatment of Cancer-Q30 and Q29 at baseline, and 30 days and 1 and 2 years after surgery. Multivariable multilevel logistic regression and generalized linear models were used in analyses after adjusting for specific propensity scores developed for each outcome and time point. Results In the multivariable analysis, the complication rates up to 30 days (infectious, surgical, and medical) and 1 year (surgical), and readmission rate at 30 days and at 2 years were higher among patients who underwent open surgery than among those who underwent laparoscopic surgery. There were no differences between the two surgical approaches in all other parameters assessed and in changes of all PROMs. Conclusions Though in most outcomes both surgical approaches provide similar results up to 2 years after intervention, still the rates of some complications and readmission, mainly up to 30 days, are higher in open surgery. ClinicalTrials.gov Identifier NCT02488161 .

The aim of the study was to evaluate the benefits of implementing Enhanced Recovery After Surgery (ERAS) protocols in elderly patients undergoing elective colorectal surgery. A retrospective non-randomized cohort study was conducted from September 2012 to December 2016. We included patients ≥ 70 years undergoing elective colorectal surgery. Outcome measures, compliance with interventions, and postoperative complications of patients treated under ERAS were case-matched (based on gender, age, type of surgery, and the presence/absence of a temporal stoma) to a retrospective group of patients ≥ 70 years treated under conventional care. A total of 312 patients (156 ERAS vs. 156 non-ERAS) were included in the study. The ERAS group had a significant reduction of grade III/IV Dindo-Clavien’s postoperative complications when compared with conventional care. ERAS had a positive effect in reducing anastomotic leakage (14.7% non-ERAS vs. 9%) and postoperative mortality (11.5% non-ERAS vs. 1.9% ERAS; p = 0.001). A reduction of 2 days in length of hospital stay was achieved after implementing ERAS (8 (6.75) vs. 6 (5.25); p

Introduction Radical Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC), has been proposed as the current standard of treatment for metastatic peritoneal disease by several tumors. Despite its widely utilization, there seems to be a great variability in their organization, clinical practice, and safety among centers. Aim of the study To obtain updated information on clinical practice in different perioperative areas of the CRS-HIPEC. Patients and methods All 25 members of the Spanish Surface Peritoneal Malignancy (GECOP), were invited to answer an online survey, to describe their usual practice in different perioperative areas of the CRS-HIPEC. Results Survey was responded by 100% of centers. This study represents more than 800 patients treated annually. Seventy per cent of respondents perform CRS-HIPEC for more than 5 years. The most frequent technique was Coliseum (88%). Routinely non-invasive monitoring of cardiac output is used by 92% of centers. More than 50% of centers administer oxaliplatin (74%), or mitomycin-C (65%) in colorectal cancer; cisplatin in gastric cancer (73%) and mesothelioma (74%). Ovarian cancer is treated with cisplatin and various combinations, in 64% or paclitaxel in 54.5%. Spillage protocol was available in 100% centers. Conclusions Data showed an important variability in volume of patients per center, selection of cytostatic agents, professional training and safety measures applied. The standardization of CRS/HIPEC procedures based on the best available evidence, the individualization of patients and the consensus among professionals, constitute an important part of the basis that will allow us to improve results of this complex procedure.

Aim To assess KRAS G12D mutation detection by droplet digital PCR (ddPCR) in stool-derived DNA from colorectal cancer (CRC) patients. Methods In this study, tumor tissue and stool samples were collected from 70 patients with stage I-IV CRC diagnosed by preoperative biopsy. KRAS mutational status was determined by pyrosequencing analysis of DNA obtained from formalin-fixed paraffin-embedded (FFPE) tumor tissues. The KRAS G12D mutation was then analyzed by ddPCR in FFPE tumors and stool-derived DNA from patients with this point mutation. Wild-type (WT) tumors, as determined by pyrosequencing, were included as controls; analysis of FFPE tissue and stool-derived DNA by ddPCR was performed for these patients as well. Results Among the total 70 patients included, KRAS mutations were detected by pyrosequencing in 32 (45.71%), whereas 38 (54.29%) had WT tumors. The frequency of KRAS mutations was higher in left-sided tumors (11 located in the right colon, 15 in the left, and 6 in the rectum). The predominant point mutation was KRAS G12D (14.29%, n = 10), which was more frequent in early-stage tumors (I-IIA, n = 7). In agreement with pyrosequencing results, the KRAS G12D mutation was detected by ddPCR in FFPE tumor-derived DNA, and only a residual number of mutated copies was found in WT controls. The KRAS G12D mutation was also detected in stool-derived DNA in 80% of all fecal samples from CRC patients with this point mutation. Conclusion ddPCR is a reliable and sensitive method to analyze KRAS G12D mutation in stool-derived DNA from CRC patients, especially at early stages. This non-invasive approach is potentially applicable to other relevant biomarkers for CRC management.

Despite several interventions having been adopted to reduce the incidence of incisional surgical site infection (SSI), it still remains a challenge for surgeons, because incisional SSI is a common cause of health-care-associated infection, leading to increased morbidity, prolonged hospital stay, patient discomfort, and increased sanitary costs. The aim of this study was to evaluate the effect on incisional SSI of vitamin E ointment in the subcutaneous tissue of patients undergoing a laparoscopic colorectal surgical procedure.A randomized study was performed. Patients with colorectal neoplasms undergoing an elective laparoscopic surgical procedure were included. The patients were randomized into two groups: Those patients undergoing a subcutaneous vitamin E ointment application (Group 1) and those patients who did not receive it (Group 2). Incisional SSI, post-operative pain, and analytical acute phase reactants were analyzed.There were 108 patients who were assessed for eligibility, and 101 patients were analyzed. The incisional SSI rate was 4% in Group 1 and 17.6% in Group 2 (p = 0.03). Mean post-operative pain, 24 hours after operation, was 17.3 ± 10.5 mm in Group 1 and 31.9 ± 18.9 mm in Group 2 (p 0.001). Median hospital stay was six days in Group 1 and eight days in Group 2 (p 0.001). White blood cell count was significantly lower in Group 1 (p 0.001).The subcutaneous application of sterile vitamin E acetate ointment leads to a reduction in the incisional SSI rate, lower post-operative pain, and decrease in C-reactive protein and white blood cell count.

BACKGROUND The use of plasma as a "liquid biopsy" has gained increasing attention. The purpose of the present study was to evaluate the diagnostic and prognostic utility of the perioperative detection and quantitation of mRNAs encoding human telomerase reverse transcriptase (hTERT) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in plasma from patients with cancer of the larynx or hypopharynx. METHODS We recruited 47 patients with laryngeal cancer and 2 patients with hypopharyngeal cancer, plus 27 healthy subjects. A blood sample was taken from each patient before and after surgical resection of the tumor. We quantified hTERT mRNA and GAPDH mRNA in plasma by real-time polymerase chain reaction (PCR). RESULTS Detection of hTERT mRNA before surgery had diagnostic value (sensitivity, 22%; specificity, 100%). Detection was more frequent in patients with supraglottic tumors than glottic tumors (p = .02) and was related to subsequent recurrence (p = .02). Preoperative levels of hTERT mRNA in plasma were higher in patients with subsequent recurrence (p = .046) and/or metastases (p = .047). The disease-free survival (DFS) and overall survival (OS) of patients with plasma samples positive for hTERT mRNA was poorer than that of patients with negative samples. Mean levels of plasma GAPDH mRNA in untreated patients were higher than in healthy subjects (p < .001). CONCLUSION Detection and quantitation of hTERT and GAPDH mRNA in patients' plasma might be clinically significant in cases of laryngeal and hypopharyngeal cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 647-655, 2017.

Introduction: Despite the fact that perianal fistulas are associated with significant morbidity and impaired quality of life, their prevalence in Europe is unknown. The aim of this study was to estimate the prevalence of perianal fistulas in Europe, overall and according to etiology. Methods: Two independent literature reviews were performed using different search strategies to maximize the identification of potentially relevant studies. Data from relevant articles were used to estimate the prevalence of perianal fistulas in Europe. The robustness of the estimate was evaluated using data from a large population-based database from the UK. Results: A total of 26 studies provided epidemiological data on perianal fistulas, of which 16 provided suitable data to estimate the prevalence. Estimations using these data yielded a total prevalence of 1.69 per 10,000 population. Cryptoglandular infection and Crohn’s disease (CD) were the predominant etiologies, with prevalence rates at 0.86 and 0.76 per 10,000 population, respectively. Comparison of prevalence data from the UK population-based database with the European population resulted in a standardized prevalence estimate of all perianal fistulas of 1.83 per 10,000 population, confirming the robustness of the literaturebased estimate. Conclusion: Although in terms of incidence cryptoglandular fistulas were clearly predominant, the prevalence of fistulas in CD and cryptoglandular infection appeared more balanced. This is due to the longer duration and higher frequency of relapses of fistulas in CD. The estimated prevalence implies that perianal fistulas meet the criteria to be considered as a rare condition in Europe (prevalence less than 5 per 10,000 population)., This study was funded by Takeda Pharmaceutical U.S.A., Inc. and TiGenix SAU

© The Author(s) 2019., Colorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a “unique” CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients., This work was funded by Projects PI10/00683 and PI16/01650 to J.P, and PI16/01920 to R.G.S, from the Spanish Ministry of Health and Consumer Afairs and FEDER, and by Project 2012-0036 from the Mutua Madrileña Foundation. This work was supported by R01 (CA72851, CA181572, CA184792, CA202797) and U01 (CA187956, CA214254) grants from the National Cancer Institute, NIH; RP140784 from the Cancer Prevention Research Institute of Texas; grants from the Baylor Foundation and Baylor Scott & White Research Institute, Dallas, TX, USA to AG.

For the acquisition of skills in laparoscopic surgery, practices in experimental labs are gaining increasing relevance. Activities in experimental labs include Pelvitrainers, virtual reality simulators, and experimental animals (frequently pigs). However, the best model for surgical formation is the performance of interventions on cadavers. The Thiel method gives the body elasticity, which allows the performance of laparoscopic procedures.An observational prospective study was performed on surgeons attending to two courses of laparoscopic bariatric surgery on cadavers embalmed by the Thiel method. A questionnaire was given to the participants (students and professors) when finishing the course. Similarities between the procedures performed on cadavers and on patients were investigated. The satisfaction degree was also analyzed.The students recognized that the Thiel cadaver presents elasticity and aspect similar to the patient, and the practice on cadavers is considered the best method for the formation in laparoscopic bariatric surgery. The assistants were extremely satisfied with the acquired skills and considered that these courses should be included in the formation programs for bariatric surgery. The results of the survey on professors agreed with the students in considering the practice on cadavers as the best method for the formation in laparoscopic bariatric surgery. However, they highlighted as drawbacks of the Thiel cadaver, the absence of bleeding, and excessive elasticity of the tissues.The participants (students and professors) to the courses of laparoscopic bariatric surgery on cadaver Thiel recognize that these are the most similar model to real conditions in bariatric surgery.

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification., This work was funded by Project PI10/0683 and PI13/0127 and PI16/01650 to J.P, and PI16/01920 to R.G.S, and PI17/01233 to D.G-O from the Spanish Ministry of Health and Consumer Affairs, and co-funded by the European Regional Development Fund (FEDER); and supported by grants R01 CA72851, CA18172, CA184792, and U01 CA187956 from the National Cancer Institute, National Institutes of Health to Ajay Goel

© 2019 Arriba et al., Comparative studies of colorectal cancer (CRC) according to the age of onset have found differences between early-onset CRC (EOCRC) and late-onset CRC (LOCRC). Using this as a starting point, we wished to determine whether intermediate-onset CRC (IOCRC) might also be considered as an independent group within CRC. We performed a retrospective comparative study of the clinicopathological and familial features, as well as of the symptoms and their duration, of a total of 272 subjects diagnosed with CRC classified into three groups according to the age-of-onset (98 EOCRC, 83 IOCRC and 91 LOCRC). The results show that from a clinicopathological point of view, IOCRC shared certain features with EOCRC (gender, prognosis), and with LOCRC (multiple primary CRCs), whereas it also had characteristics that were specific for IOCRC (mean number of associated polyps). A gradual progression was observed from EOCRC to LOCRC from a greater family aggregation to sporadic cases, in parallel with a change of Lynch Syndrome cases to the sporadic microsatellite instability pathway, with the IOCRC being a boundary group that is more related to EOCRC. With respect to symptoms, duration and correlation with stages, IOCRC appeared more similar to EOCRC. Clinically, IOCRC behaves as a transitional group between EOCRC and LOCRC, with features in common with both groups, but also with IOCRC-specific features. Excluding cases with familial cancer history, the awareness for EOCRC diagnosis should be extended to IOCRC., This work was funded by grants PI10/0683, PI13/0127 and PI16/01650 to J.P, PI16/01920 to R.G.S, and PI14/00459 to MU, from the Spanish Ministry of Health and Consumer Affairs, and cofunded by the European Regional Development Fund (FEDER); it was further supported by grants CA72851, CA181572, CA184792, CA187956 and CA202797 from the National Cancer Institute, National Institute of Health; RP140784 from the Cancer Prevention Research Institute of Texas; grants from the Sammons Cancer Center and Baylor Foundation, as well as funds from the Baylor Scott & White Research Institute, Dallas, TX, USA to AG.

To analyze the possible clonal origin of a part of Synchronous colorectal cancer (SCRC), we studied 104 paired‐SCRCs from 52 consecutive patients without hereditary forms of CRC. We used a Single‐Nucleotide Polymorphism array to characterize the genomic profiles, and subsequently used a statistical application to define them according to clonality within the same individual. We categorized the ensuing groups according to colonic location to identify differential phenotypes. The SCRC Monoclonal group (M) (19 cases) was divided into Monosegmental (MM) and Pancolonic (MP) groups. The SCRC Polyclonal group (P) (33 cases) was also divided into Monosegmental (PM) and Pancolonic (PP), the first exhibiting preference for left colon. The MM group showed a high rate of mucinous tumors, the lowest mean‐number of tumors and associated‐polyps, and the worst prognosis. The MP group included the largest mean‐number of associated‐polyps, best prognosis and familial cancer component. The PM group seemed to be a “frontier” group. Finally, the PP group also exhibited a mucin component, the highest mean‐number of tumors (4.6) compared with the mean‐number of polyps (7.7), poor prognosis and sporadic cases. Most relevant differential genomic regions within M groups were gains on 1q24 and 8q24, and deletions on 1p21 and 1p23 for MM, while within P were the gains on 7q36 and deletions on 1p36 for PM. The statistical application employed seems to define clonality more accurately in SCRC ‐more likely to be polyclonal in origin‐, and together with the tumor locations, helped us to configure a classification with prognostic and clinical value., This work was funded by Projects PI10/00683 and PI16/01650 to J.P, and PI16/01920 to R.G.S, from the Spanish Ministry of Health and Consumer Affairs and FEDER, by Project 2012–0036 from the Mutua Madrileña Foundation, and supported by the CA72851, CA181572, CA184792, CA187956 and CA202797 grants from the National Cancer Institute, National Institute of Health; RP140784 from the Cancer Prevention Research Institute of Texas; grants from the Sammons Cancer Center and Baylor Foundation, as well as funds from the Baylor Scott & White Research Institute, Dallas, TX, USA.

© 2019 by the authors., Early-onset colorectal cancer (EOCRC) is an increasing and worrisome entity. The aim of this study was to analyze its association with polyps concerning prognosis and surveillance. EOCRC cases were compared regarding the presence or absence of associated polyps (clinical and molecular features), during a minimum of 7 years of follow-up. Of 119 cases, 56 (47%) did not develop polyps (NP group), while 63 (53%) did (P group). The NP group showed a predominant location of the CRC in the rectum (50%), of sporadic cases (54%), and diagnosis at advanced stages: Only P53 and SMARCB1 mutations were statistically linked to this group. The P group, including mainly early-diagnosed tumors, was linked with the most frequent and differential altered chromosomal regions in the array comparative genomic hybridization. The two most frequent groups according to the follow-up were the NP group (40%), and patients developing polyps in the first 5 years of follow-up (P < 5FU) (34%) (these last groups predominantly diagnosed at the earliest stage and with adenomatous polyps (45%)). EOCRC with polyps that developed during the entire follow-up (PDFU group) were mainly located in the right colon (53%), diagnosed in earlier stages, and 75% had a familial history of CRC. Patients developing polyps after the first 5 years (P > 5FU) showed a mucinous component (50%). Our results show that the absence or presence of polyps in EOCRC is an important prognostic factor with differential phenotypes. The development of polyps during surveillance shows that it is necessary to extend the follow-up time, also in those cases with microsatellite-stable EOCRC, This work was funded by the Spanish Ministry of Health and Consumer Affairs and FEDER, grant number PI10/00683 and PI16/01650 to J.P.G., PI16/01920 to R.G.S., and PI14/00459 to M.U., and by the National Cancer Institute, National Institutes of Health, grant number R01 CA72851, CA18172, CA184792 and U01 CA187956 to A.G.

Summary Background Complex perianal fistulas in Crohn's disease are challenging to treat. Allogeneic, expanded, adipose-derived stem cells (Cx601) are a promising new therapeutic approach. We aimed to assess the safety and efficacy of Cx601 for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Methods We did this randomised, double-blind, parallel-group, placebo-controlled study at 49 hospitals in seven European countries and Israel from July 6, 2012, to July 27, 2015. Adult patients (≥18 years) with Crohn's disease and treatment-refractory, draining complex perianal fistulas were randomly assigned (1:1) using a pre-established randomisation list to a single intralesional injection of 120 million Cx601 cells or 24 mL saline solution (placebo), with stratification according to concomitant baseline treatment. Treatment was administered by an unmasked surgeon, with a masked gastroenterologist and radiologist assessing the therapeutic effect. The primary endpoint was combined remission at week 24 (ie, clinical assessment of closure of all treated external openings that were draining at baseline, and absence of collections >2 cm of the treated perianal fistulas confirmed by masked central MRI). Efficacy was assessed in the intention-to-treat (ITT) and modified ITT populations; safety was assessed in the safety population. This study is registered with ClinicalTrials.gov, number NCT01541579. Findings 212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2–30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5–31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine). Interpretation Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both. Funding TiGenix.

Purpose ERAS (enhanced recovery after surgery) programs have proven to reduce morbidity and hospital stay in colorectal surgery. However, the feasibility of these programs in elderly patients has been questioned. The aim of this study is to assess the implementation and outcomes of an ERAS program for colorectal cancer in elderly patients. Methods This is a multicenter observational study of a cohort of elderly patients undergoing colorectal surgery within an ERAS program. A total of 188 consecutive patients over 70 years who underwent elective colorectal surgery within an ERAS program at three institutions during a 2-year period were included. The compliance with the ERAS protocol interventions was measure. Complications were evaluated according to Clavien-Dindo classification. Data on length of stay and readmission rates were analyzed. Results Early intake and early mobilization were the most successfully carried out interventions. There was a global compliance rate of 56 % of patients for whom compliance was achieved with all measured interventions. The median hospital length of stay was 6 days. Almost 60 % of patients had no complications, 24 % had minor complications while 13 % had major complications; of them, 8 % patients were reoperated. The readmission rate was 6.4 %. Conclusions ERAS after colorectal surgery in elderly patients presents as safe and feasible based on good reported outcomes of compliance rates, complications, readmissions, and needs for reoperation.

Background aims In this report, we describe the successful bronchoscopic management of bronchopleural fistula in two patients, using autologous adipose-derived stromal cells. Cell therapy was considered for 2 cases of bronchopleural fistula refractory to conventional surgical treatment after control of the primary disease was confirmed and active pleural infection was ruled out. Briefly, adipose-derived stem cells were first isolated from lipoaspirate and used without cell expansion. In 24 months, we have not received more patients with bronchopleural fistula in our hospital and we have not been able to include more patients. Methods Briefly, adipose-derived stem cells were first isolated from lipo-aspirate and used without cell expansion. A bronchopleural fistula was identified through bronchoscopy, and the mucosa surrounding the fistula was ablated with an argon plasma coagulator. Isolated stem cells were then endoscopically injected into the de-epithelialized area and fistulous tract. If an open thoracostomy was present at the time of the intervention, the same procedure was performed on the pleural side. Bronchoscopic follow-up was scheduled weekly during the first month, monthly during the first year, and then yearly. The underlying etiologies were left pneumonectomy and right lower video-assisted lobectomy for non–small-cell lung cancer. The sizes of the fistulas were 6 mm and 3 mm in diameter, respectively. Results Both patients were discharged on the first postoperative day. The 3-year follow-up revealed a successful and maintained fistula closure, no treatment-related adverse reactions, nonlocal malignant recurrence and improved quality of life. Conclusions This preliminary study showed that bronchoscopic application of autologous adipose-derived stem cells is a feasible, safe and effective procedure for treating bronchopleural fistula.

Constipation in spinal cord injury patients is a frequent complication that leads to a reduction of quality of life, extensive psychological and economic strain on patients and healthcare systems. We report a 58-year-old man with an incomplete SCI secondary to L1 vertebral fracture, presented gait disorder with neurogenic bowel and bladder dysfunction. He received 300 million autologous mesenchymal stromal cells (MSC) in the subarachnoid space by lumbar puncture. After the third administration of MSC the patient had an important improvement in almost every functional scale of spinal cord injury, especially in the Krogh's Neurogenic Bowel Dysfunction scale. Our present observation supports recent clinical findings about the benefit of autologous stem cell therapy for the improvement of bowel dysfunction in patients suffering spinal cord injury.

Anal fistula is a challenging condition both for surgeons and patients. Recurrent fistula, Crohn's disease, or autoimmune disorders add further complexity to this situation. Numerous clinical trials have now demonstrated that cell-based therapy appears to be a good complement to fistulous surgery. As in any new treatment, especially that involving living cells, appropriate application is paramount to achieve optimal outcomes. As stem cell-based treatments are gaining a strong foothold in fistula management worldwide, we herein aim to share our mesenchymal stem cell surgical protocol. With the goal of optimizing results of this emerging therapy, we have improved and refined our protocol over the past 17 years of working with stem cells in clinical trials. The protocol consists of nine reproducible steps for mesenchymal stem cell application inside the fistulous tract, and has proven to be safe and effective in several studies, including international phase III clinical trials.

Background aims Recently, clinical studies show that cell therapy with mesenchymal stromal cells (MSCs) improves the sequelae chronically established in paraplegic patients, being necessary to know which of them can obtain better benefit. Methods We present here a phase 2 clinical trial that includes six paraplegic patients with post-traumatic syringomyelia who received 300 million MSCs inside the syrinx and who were followed up for 6 months. Clinical scales, urodynamic, neurophysiological, magnetic resonance (MR) and studies of ano-rectal manometry were performed to assess possible improvements. Results In all the cases, MR at the end of the study showed a clear reduction of the syrinx, and, at this time, signs of improvement in the urodynamic studies were found. Moreover, four patients improved in ano-rectal manometry. Four patients improved in neurophysiological studies, with signs of improvement in evoked potentials in three patients. In the American Spinal Injury Association (ASIA) assessment, only two patients improved in sensitivity, but clinical improvement in neurogenic bowel dysfunction was observed in four patients and three patients described improvement in bladder dysfunction. Spasms reduced in two of the five patients who had them previous to cell therapy, and spasticity was improved in the other two patients. Three patients had neuropathic pain before treatment, and it was reduced or disappeared completely during the study. Only two adverse events ocurred, without relation to the cell therapy. Conclusions Cell therapy can be considered as a new alternative to the treatment of post-traumatic syringomyelia, achieving reduction of syrinx and clinical improvements in individual patients.

[Background]: Since there is a predilection of some clinical and molecular features for a given tumor location, we assessed whether this can be confirmed in late-onset colorectal cancer (LOCRC). [Results]: Right colon cancers showed features associated with sporadic Microsatellite Instability: predominance of female cases and BRAF mutations, and an important mucinous component. Left colon cancers developed a higher number of polyps and multiple primary CRCs, showed the strongest familial component, and had better prognosis. Rectal cancers showed a predominantly sporadic phenotype, with worse prognosis and a CpG Island Methylator Phenotype (CIMP)-High. No copy number alterations (CNAs) greater than or equal to 50% were observed in this LOCRC group, and the most recurrent alterations were losses at 5q13 and 14q11, and gains at 7q11, 7q21-q22, 19p13-p12, 19q13 and 20p11-q11. KRAS and PIK3CA were the only mutated genes showing differences according to the tumor location, mainly for right colon cancers. [Materials and Methods]: We analyzed clinical and molecular characteristics of LOCRC at different tumor locations in order to determine if there are differential phenotypes related with the location in the colon. [Conclusions]: Categorizing LOCRC according to tumor location appears to be an adequate first step to resolving the heterogeneity of this subset of CRC., This work was funded by Projects PI10/0683, PI13/01741, PI13/0127 and PI14/00459 from the Spanish Ministry of Health and Consumer Affairs and FEDER, and was approved by the Ethics Committee of our Institution.

The treatment of choice for locally advanced rectal cancer is preoperative chemoradiotherapy. Despite half of patients do not respond and suffer unnecessary toxicities and surgery delays, there are no biomarkers to guide preoperative CRT outcome. MicroRNA-21 has been related to acquisition of 5-fluorouracil resistance; however, its potential predictive value of response to preoperative chemoradiotherapy in locally advanced rectal cancer remains unknown. Nighty-two patients diagnosed with locally advanced rectal cancer who were preoperatively treated with chemoradiotherapy were selected for this study. Moreover, microRNA-21 expression was quantified in formalin-fixed paraffin-embedded biopsies from this cohort, and the results obtained were correlated with clinical and molecular characteristics, pathological response, and outcome. MicroRNA-21 was found overexpressed in 77.6 % cases, and significantly correlated with tumor grade after preoperative chemoradiotherapy (P = 0.013) and with pathological response (P = 0.013). The odds ratio of having miR-21 overexpression and not getting a respond to chemoradiotherapy resulted in 9.75 CI 2.24 to 42. Sensitivity, specificity, negative predictive values, and positive predictive value were 86.6, 60, 42.8, and 92 %, respectively. Multivariate analysis confirmed the clinical significance of miR-21 determining preoperative chemoradiotherapy response. MicroRNA-21 expression efficiently predicts preoperative chemoradiotherapy pathological response in locally advanced rectal cancer.

Objective To assess the effectiveness of a protocol for the prevention of surgical site infection (SSI) in colorectal surgery. Patients and methods Evaluation of 2 cohorts of patients undergoing colon and rectal surgery in a tertiary public hospital: A historical cohort (2008–2011) and a prospective one (after the implementation of the programme in 2012). The main measures established were: Adequacy of preoperative antimicrobial prophylaxis, maintaining patient normothermia and appropriate glove change during the intervention. Comparability of the two cohorts was determined by a bivariate analysis of age, sex, NNIS index, ASA index, surgical time, perioperative transfusion, diagnosis, diabetes and renal failure. Results We assessed 342 patients (256 underwent colon surgery and 86 rectal surgery), divided into 2 cohorts: prior period (218), and post-implementation period (124). The cumulative incidence of SSI in the first cohort was 27.5% (95% CI, 21.6–33.4), and in the post-intervention cohort 16.9% (95% CI, 10.3–23.5, P =.03). Postoperative mortality was 9.2% (95% CI, 5.4–13) in the first cohort and 3.2% (95% CI, 0.1–6.3) in the post-intervention cohort ( P =.04). The inadequacy of prophylaxis decreased from 37.4% (95% CI, 30.4–44.6) to 18.9% (95% CI, 11.9–26.1) ( P =.001). Conclusion A significant decrease in the frequency of SSI, post-surgical mortality and inadequate antimicrobial prophylaxis is verified after the implementation of a protocol in colorectal surgery

Resumen Objetivo Evaluar la efectividad de un protocolo para la prevencion de la infeccion de localizacion quirurgica (ILQ) en cirugia colorrectal. Pacientes y metodos Evaluacion de 2 cohortes de pacientes intervenidos de colon y recto en un hospital publico de tercer nivel: una cohorte historica (2008-2011) y otra prospectiva (posterior a la implementacion del programa en 2012). Las principales medidas establecidas fueron: adecuacion de la profilaxis antimicrobiana prequirurgica, mantenimiento de la normotermia del paciente en el quirofano y adecuacion del cambio de guante durante la intervencion. Se determino la comparabilidad de ambas cohortes mediante un analisis bivariable de la edad, sexo, factores e indices de riesgo (indice NNIS, indice ASA, tiempos quirurgicos, transfusion periquirurgica, diagnostico, diabetes, insuficiencia renal). Resultados Se evaluo a 342 pacientes (256 intervenidos de colon y 86 de recto), distribuidos en 2 cohortes: periodo previo (218) y periodo postimplementacion del programa (124). La incidencia acumulada de ILQ de la primera cohorte fue del 27,5% (IC 95% = 21,6-33,4), y de la cohorte postintervencion 16,9% (IC 95% = 10,3-23,5; p = 0,03). La mortalidad postoperatoria fue del 9,2% (IC 95% = 5,4-13) en la primera cohorte y del 3,2% (IC 95% = 0,1-6,3) en la cohorte postintervencion (p = 0,04). La administracion inadecuada de la profilaxis disminuyo del 37,4% (IC 95% = 30,4-44,6) al 18,9% (IC 95% = 11,9-26,1; p = 0,001). Conclusiones Tras la implementacion de un protocolo para la prevencion de la infeccion quirurgica en cirugia colorrectal se verifica una disminucion significativa de la frecuencia de ILQ, de la mortalidad posquirurgica y de la profilaxis antimicrobiana inadecuada.

A correct preoperative strategy is crucial when surgery is needed for retrorectal tumours (RRT).[1] Surgical approaches may be purely anterior-abdominal, posterior-sacrococcygeal or combined depending on the tumour's size and location.[2] We present the case of an 18-year-old female with Currarino Syndrome who underwent surgery by a combined abdominal laparoscopic-posterior Kraske approach for the resection of a large RRT. This article is protected by copyright. All rights reserved.

Background Diabetes is one of the major risk factors for peripheral arterial disease. In patients in whom surgery cannot be performed, cell therapy may be an alternative treatment. Since time is crucial for these patients, we propose the use of allogenic mesenchymal cells. Methods We obtained mesenchymal cells derived from the fat tissue of a healthy Sprague-Dawley rat. Previous diabetic induction with streptozotocin in 40 male Sprague-Dawley rats, ligation plus left iliac and femoral artery sections were performed as a previously described model of ischemia. After 10 days of follow-up, macroscopic and histo-pathological analysis was performed to evaluate angiogenic and inflammatory parameters in the repair of the injured limb. All samples were evaluated by the same blind researcher. Statistical analysis was performed using the SPSS v.11.5 program (P Results Seventy percent of the rats treated with streptozotocin met the criteria for diabetes. Macroscopically, cell-treated rats presented better general and lower ischemic clinical status, and histologically, a better trend towards angiogenesis, greater infiltration of type 2 macrophages and a shortening of the inflammatory process. However, only the inflammatory variables were statistically significant. No immunological reaction was observed with the use of allogeneic cells. Discussion The application of allogeneic ASCs in a hind limb ischemic model in diabetic animals shows no rejection reactions and a reduction in inflammatory parameters in favor of better repair of damaged tissue. These results are consistent with other lines of research in allogeneic cell therapy. This approach might be a safe, effective treatment option that makes it feasible to avoid the time involved in the process of isolation, expansion and production of the use of autologous cells.

The clinical management of cancer has evolved in recent years towards more personalized strategies that require a comprehensive knowledge of the complex molecular features involved in tumor growth and evolution, and the development of drug resistance mechanisms leading to disease progression. Droplet digital PCR (ddPCR) has become one of the most accurate and reliable tools for the examination of genetic alterations in a wide variety of cancers because of its high sensitivity and specificity. ddPCR is currently being applied for absolute allele quantification, rare mutation detection, analysis of copy number variations, DNA methylation, and gene rearrangements in different kinds of clinical samples. This methodology has proven useful for the evaluation of archival tumor tissues, where poor DNA quality and limited sample availability are major obstacles for standard methods, providing less subjective and more automated quantitative results. However, most applications of ddPCR in cancer are focused on liquid biopsies (including cell-free DNA as well as circulating tumor cells) because these represent non-invasive alternatives to tissue biopsies that can more accurately reflect intratumoral heterogeneity and track the dynamic changes in tumor burden that occur in response to treatment at different times during follow-up. A broad spectrum of molecular markers have been interrogated in blood using ddPCR for diagnostic, predictive, and monitoring purposes in various malignancies. Emerging alternative approaches using other body fluids such as cerebrospinal fluid and urine are also currently being developed. This article aims to give a complete overview of ddPCR applications for molecular screening in oncology.