Surgical Education.

This paper summarizes the proceedings of the joint European Surgical Association ESA/American Surgical Association symposium on Surgical Education that took place in Bordeaux, France, as part of the celebrations for 30 years of ESA scientific meetings. Three presentations on the use of quantitative metrics to understand technical decisions, coaching during training and beyond, and entrustable professional activities were presented by American Surgical Association members and discussed by ESA members in a symposium attended by members of both associations.

Career Needs Assessment for Early Career Academic Surgeons Using a Modified Accelerated Delphi Process.

INTRODUCTION: Over the past 2 decades, physicians' wellbeing has become a topic of interest. It is currently unclear what the current needs are of early career academic surgeons (ECAS). METHODS: Consensus statements on academic needs were developed during a Delphi process, including all presenters from the previous European Surgical Association (ESA) meetings (2018-2022). The Delphi involved (1) a literature review, (2) Delphi form generation, and (3) an accelerated Delphi process. The Delphi form was generated by a steering group that discussed findings identified within the literature. The modified accelerated e-consensus approach included 3 rounds over a 4-week period. Consensus was defined as >80% agreement in any round. RESULTS: Forty respondents completed all 3 rounds of the Delphi. Median age was 37 years (interquartile range 5), and 53% were female. Majority were consultant/attending (52.5%), followed by PhD (22.5%), fellowship (15%), and residency (10%). ECAS was defined as a surgeon in 'development' years of clinical and academic practice relative to their career goals (87.9% agreement). Access to split academic and clinical contracts is desirable (87.5%). Consensus on the factors contributing to ECAS underperformance included: burnout (94.6%), lack of funding (80%), lack of mentorship (80%), and excessive clinical commitments (80%). Desirable factors to support ECAS development included: access to e-learning (90.9%), face-to-face networking opportunities (95%), support for research team development (100%), and specific formal mentorship (93.9%). CONCLUSION: The evolving role and responsibilities of ECAS require increasing strategic support, mentorship, and guidance on structured career planning. This will facilitate workforce sustainability in academic surgery in the future.

The Relationship Between Cortical Activation in Response to Anorectal Stimuli and Continence Behavior in Freely Behaving Rats Before and After Application of Sacral Nerve Stimulation.

BACKGROUND: Changes in anorectal sensation have been reported in patients with fecal incontinence, and there is limited evidence that sacral nerve stimulation can restore normal sensation. OBJECTIVE: The aims of the present study were to investigate changes in the transmission of sensory anorectal stimuli in a rodent model of fecal incontinence and to study the effects of sacral nerve stimulation on defecation behavior. DESIGN: An established model of fecal incontinence was utilized for this study. INTERVENTION: Pudendal nerve stretch and compression were used in 16 adult female Wistar rats and were monitored for 3 weeks: 6 rats received sacral nerve stimulation for 1 week by using an implantable neurostimulator and 10 rats had nonfunctioning "dummy" devices inserted. Five additional rats were sham operated. Anorectal cortical evoked potentials were used as a surrogate marker for anorectal sensory function. MAIN OUTCOME MEASURES: The primary outcomes measured were fecal incontinence index, evoked potential amplitude, and latency. RESULTS: Fifty percent of rats showed behavioral signs of fecal incontinence measured by the Fecal Incontinence Index (>0.20), calculated by using the pellet distribution outside the cage's latrine area. Anorectal evoked potential amplitude was reduced in rats with a Fecal Incontinence Index >0.20 (p = 0.019). The amplitude of forepaw evoked potentials recorded as a control was not different between groups. Chronic sacral nerve stimulation using the fully implantable device and custom rodent lead was safe and stable during this chronic prospective study. Incontinent rats (n = 3) that received sacral nerve stimulation showed an improvement of Fecal Incontinence Index and an increase of evoked potential amplitude to anorectal stimulation compared with the dummy implant controls (n = 5). LIMITATIONS: The main limitation is the small number of animals that received sacral nerve stimulation. CONCLUSIONS: Chronic sacral nerve stimulation is feasible in rats when miniature telemetric devices are used. Behavioral signs of fecal incontinence were positively correlated with the latency of anorectal evoked potentials. See Video Abstract at http://links.lww.com/DCR/B712.RELACIÓN ENTRE LA ACTIVACIÓN CORTICAL EN RESPUESTA A LOS ESTÍMULOS ANORRECTALES Y EL COMPORTAMIENTO DE CONTINENCIA EN RATAS QUE SE COMPORTAN LIBREMENTE ANTES Y DESPUÉS DE LA APLICACIÓN DE ESTIMULACIÓN DEL NERVIO SACRO. ANTECEDENTES: Se han informado cambios en la sensación anorrectal en pacientes con incontinencia fecal y hay evidencia limitada de que la estimulación del nervio sacro puede restaurar la sensación normal. OBJETIVO: Los objetivos del presente estudio fueron investigar los cambios en la transmisión de estímulos anorrectales sensoriales en un modelo de roedor de incontinencia fecal y estudiar los efectos de la estimulación del nervio sacro en la conducta de defecación. DISEO: Un modelo establecido de incontinencia fecal. INTERVENCIN: Se utilizó estiramiento y compresión del nervio pudendo en 16 ratas Wistar hembras adultas y se les realizó un seguimiento durante 3 semanas: seis ratas recibieron estimulación del nervio sacro durante 1 semana utilizando un neuroestimulador implantable y diez ratas tuvieron insertados dispositivos "ficticios" no funcionantes. Se operaron simuladamente cinco ratas adicionales. Los potenciales evocados corticales anorrectales se utilizaron como marcador subrogado de la función sensorial anorrectal. PRINCIPALES MEDIDAS DE RESULTADO: Índice de incontinencia fecal, amplitud de potenciales evocados y latencia. RESULTADOS: El cincuenta por ciento de las ratas mostró signos de comportamiento de incontinencia fecal medidos por el Índice de incontinencia fecal (> 0.20), calculado utilizando la distribución de heces fuera del área de la letrina de la jaula. La amplitud del potencial evocado anorrectal se redujo en ratas con un índice de incontinencia fecal >0.20 (p = 0.019). La amplitud de los potenciales evocados de la pata delantera registrados como control no fue diferente entre los grupos. La estimulación crónica del nervio sacro utilizando un dispositivo totalmente implantable y un cable de roedor personalizado fue segura y estable durante este estudio prospectivo crónico. Las ratas con incontinencia (N = 3) que recibieron estimulación del nervio sacro mostraron una mejora del índice de incontinencia fecal y un aumento de la amplitud del potencial evocado a la estimulación anorrectal en comparación con los controles de implante ficticio (N = 5). LIMITACIONES: La principal limitación es el pequeño número de animales que recibieron estimulación del nervio sacro. CONCLUSIONES: La estimulación crónica del nervio sacro es factible en ratas cuando se utilizan dispositivos telemétricos en miniatura. Los signos conductuales de incontinencia fecal se correlacionaron positivamente con la latencia de los potenciales evocados anorrectales. Consulte Video Resumen en http://links.lww.com/DCR/B712. (Traducción-Dr. Jorge Silva Velazco).

Survey of Patient Knowledge and Awareness of "Sick Day Rules" in Rheumatology Patients on Long Term Glucocorticoid Therapy.

Aims Rheumatic disease (RMD) patients treated with long-term glucocorticoids (GC) are at risk of developing tertiary adrenal insufficiency. With this survey we aimed to assess the knowledge of RMD patients taking long-term glucocorticoid therapy regarding risk of adrenal insufficiency and understanding of the "steroid sick day rules". Methods RMD patients taking ≥2.5 mg prednisolone daily for ≥3 months were recruited from the Rheumatology outpatient department in Beaumont Hospital, Dublin. Patient knowledge and previous counselling of steroid sick day rules was determined using an 8-point questionnaire carried out face-to-face or via phone call. Results 51 RMD patients on GC therapy were recruited. 3/51 (5.9%) of patients reported that they had been counselled on the Sick Day Rules. 2/51 (3.9%) carried a steroid emergency card or MedicAlert bracelet. Few patients would increase their steroid dose appropriately in response to infection, vomiting or peri-procedure [14/51 (27.5%); 9/51 (17.7%) and 5/51 (7.2%), respectively]. Conclusion We demonstrate a significant deficit of patient knowledge around the precautions for long-term GC use in rheumatic diseases. We suspect that our results may be generalisable to many other RMD units. We are currently reviewing our procedures around healthcare professional and patient education, issuing of information leaflets, emergency cards or MedicAlert bracelets etc. to at risk patients.

A European snapshot of psychosocial characteristics and patients' perspectives of faecal incontinence-do they correlate with current scoring systems?

PURPOSE: To compare the current clinical scoring systems used to quantify the severity of symptoms of faecal incontinence (FI) to patients' subjective scoring of parameters of psychosocial well-being. METHODS: Patients referred to six European centres for investigation or treatment of symptoms of FI between June 2017 and September 2019 completed a questionnaire that captured patient demographics, incontinence symptoms using St. Mark's Incontinence score (SMIS) and ICIQ-B, psychological well-being (HADS, Hospital Anxiety and Depression Scale), and social interaction (a three-item loneliness scale). RESULTS: Three hundred eighteen patients completed questionnaires (62 men, mean age 58.7). Sixty percent of the respondents were aged under 65. Median SMIS was 15 (11-18), ICIQ-B bowel pattern was 8 (6-11) and bowel control was 17 (13-22), similar across all demographic groups; however, younger patients were more likely to experience symptoms of depression and anxiety (HADS score > 10, 65.2% of patients age < 65 vs 54.9% of those ages > = 65, p = 0.03) with lower quality of life (ICIQ-B QoL, median score 19 (14-23)) vs age > = 65 (16 (11-21) (p < 0.005)). On loneliness score 25.5% reported often feeling isolated from others. One of the most significant concerns by patients was the fear and embarrassment related to unpredictable episodes of incontinence. CONCLUSION: The SMIS remains a useful tool for quantifying incontinence symptoms but may underestimate the psychosocial morbidity associated with unpredictable episodes of incontinence. Interventions aimed at decreasing anxiety and to address feelings of disgust may be helpful for a significant number of patients requiring treatment for FI.

Changing paradigm of sacral neuromodulation and external anal sphincter repair for faecal incontinence in specialist centres.

AIM: The aim of this study was to determine whether the paradigm of surgical intervention for faecal incontinence (FI) has changed between 2000 and 2013. METHOD: This was a multi-centre retrospective study of patients who had undergone either sacral neuromodulation (SNM) or delayed sphincter repair or sphincteroplasty (SR) as a primary surgical intervention for FI in five centres in Europe and one in the United States. The flow of patients according to the intervention, sustainability of the treatment at a minimum follow-up of 5 years, complications and requirement for further interventions were recorded. RESULTS: A total of 461 patients (median age 56 years, range 24-90 years, 41 men) had either SNM or SR as an index operation during the study period [SNM 284 (61.6%), SR 177 (38.4%)]. Among SNM patients, there were 169 revisional operations (change of battery and/or lead, re-siting or removal). At the time of last follow-up 203 patients (71.4%) continued to use SNM. Among SR patients, 30 (16.9%) had complications, most notably wound infection (22, 12.4%). During follow-up 32 patients (18.1%) crossed over to SNM. Comparing two 4-year periods (2000-2003 and 2007-2010), the proportion of patients operated on who had a circumferential sphincter defect of less than 90° was 48 (68%) and 45 (46%), respectively (P = 0.03), while those who had SNM as the primary intervention increased from 29% to 89% (P < 0.05). CONCLUSION: The paradigm of surgical intervention for FI has changed with increasing use of SNM.

European Society of Coloproctology guidance on the use of mesh in the pelvis in colorectal surgery.

This is a comprehensive and rigorous review of currently available data on the use of mesh in the pelvis in colorectal surgery. This guideline outlines the limitations of available data and the challenges of interpretation, followed by best possible recommendations.

Clinicopathological features and oncological outcomes of patients with young-onset rectal cancer.

BACKGROUND: The incidence of rectal cancer among adults aged less than 50 years is rising. Survival data are limited and conflicting, and the oncological benefit of standard neoadjuvant and adjuvant therapies is unclear. METHODS: Disease-specific outcomes of patients diagnosed with rectal cancer undergoing surgical resection with curative intent between 2006 and 2016 were analysed. RESULTS: A total of 797 patients with rectal cancer were identified, of whom 685 had surgery with curative intent. Seventy patients were younger than 50 years and 615 were aged 50 years or more. Clinical stage did not differ between the two age groups. Patients aged less than 50 years were more likely to have microsatellite instability (9 versus 1·6 per cent; P = 0·003) and Lynch syndrome (7 versus 0 per cent; P < 0·001). Younger patients were also more likely to receive neoadjuvant chemoradiotherapy (67 versus 53·3 per cent; P = 0·003) and adjuvant chemotherapy (41 versus 24·2 per cent; P = 0·006). Five-year overall survival was better in those under 50 years old (80 versus 72 per cent; P = 0·013). The 5-year disease-free survival rate was 81 per cent in both age groups (P = 0·711). There were no significant differences in the development of locoregional recurrence or distant metastases. CONCLUSION: Despite accessing more treatment, young patients have disease-specific outcomes comparable to those of their older counterparts.

ANTECEDENTES: La incidencia de cáncer de recto entre adultos menores de 50 años está aumentando. Los datos de supervivencia son limitados y contradictorios, y el beneficio oncológico de los tratamientos neoadyuvantes y adyuvantes estándares no está claro. MÉTODOS: Se analizaron los resultados específicos relacionados con la enfermedad en pacientes diagnosticados de cáncer de recto operados con intención curativa entre 2006 y 2016. RESULTADOS: Se identificaron un total de 797 pacientes con cáncer de recto, de los cuales 685 fueron intervenidos quirúrgicamente con intención curativa. Setenta tenían menos de 50 años y 615 tenían 50 años o más. No hubo diferencias en el estadio clínico entre los dos grupos de edad. Los pacientes menores de 50 años tenían más probabilidades de tener inestabilidad de microsatélites (9% versus 2%, P = 0,003) y síndrome de Lynch (7% versus 0%, P ≤ 0,001). La supervivencia global a los 5 años fue mayor en los pacientes de menos de 50 años (80% y 72%; P = 0,013). La supervivencia libre de enfermedad a los 5 años fue del 81% en ambos grupos de edad (P = 0,711). No hubo diferencias significativas en el desarrollo de recidiva locorregional o metástasis a distancia. Los pacientes más jóvenes tenían más probabilidades de recibir quimiorradioterapia neoadyuvante (67% versus 53%, P = 0,003) y quimioterapia adyuvante (41% versus 24%, P = 0,006). CONCLUSIÓN: A pesar de tener acceso a más tratamientos, los pacientes jóvenes han presentado resultados específicos relacionados con la enfermedad comparables a sus homólogos de mayor edad.

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer.

BACKGROUND: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION: A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.

ANTECEDENTES: El tratamiento estándar actual del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) consiste en quimiorradioterapia neoadyuvante de ciclo largo (neoadjuvant, long-course chemoradiation, nCRT) seguida de exéresis total del mesorrecto (total mesorectal excision, TME). De forma convencional, la cirugía se realiza a las 6-8 semanas después de la nCRT. Este estudio tuvo como objetivo determinar el efecto sobre los resultados de ampliar este intervalo. MÉTODOS: Se realizó una búsqueda sistemática de los estudios que analizaban los resultados oncológicos, comparando el intervalo clásico (< 8 semanas) desde el final de la nCRT hasta la TME con un intervalo mínimo de 8 semanas, en pacientes con LARC. El criterio de valoración principal fue la tasa de respuesta patológica completa (pathologic complete response, pCR). Los criterios de valoración secundarios fueron las tasas de supervivencia sin recidiva (recurrence-free survival, RFS), recidiva local (local recurrence, LR) y metástasis a distancia (distant metastasis, DM), tasas de resección R0, integridad (completeness) del mesorrecto, afectación del margen de resección, preservación esfinteriana, formación de estoma, fuga anastomótica y otras complicaciones. Se realizó un metaanálisis utilizando el método de Mantel-Haenszel. RESULTADOS: Se identificaron 26 publicaciones, incluidos cuatro ensayos clínicos aleatorizados, con 17.220 pacientes. Un intervalo mínimo de 8 semanas se asoció con un aumento de la razón de oportunidades (odds ratio, OR) de pCR (OR, 1,68, i.c. del 95% 1,37-2,06, P < 0,001) y de disminución del estadio tumoral (OR 1,18, i.c. del 95% 1,05-1,32, P = 0,004). Los porcentajes de resección R0, integridad del mesorrecto, ganglios linfáticos identificados, preservación esfinteriana, formación de estoma y complicaciones fueron similares entre los dos grupos. El aumento del porcentaje de pCR se tradujo en una disminución de las DM (OR 0,71, i.c. del 95% 0,54-0,93, P = 0,01) y de la recidiva global (OR 0,76, i.c. del 95% 0,58-0,98, P = 0,04), pero no de la LR (OR 0,83, i.c. del 95% 0,49-1,42, P = 0,50). CONCLUSIÓN: Un intervalo mínimo de 8 semanas entre el final de la nCRT y la TME aumenta las tasas de pCR y la reducción del estadio tumoral, así como mejora la RFS sin comprometer la morbilidad quirúrgica.

Minimally invasive approaches to the management of anastomotic leakage following restorative rectal cancer resection.

AIM: Management of anastomotic leakage (AL) following rectal resection has evolved with increasing use of less invasive techniques. The aim of this study was to review the management of AL following restorative rectal cancer resection in a tertiary referral centre. METHOD: A retrospective review of a prospectively maintained database was performed. The primary outcome was successful management of AL. The secondary outcome was the impact of AL on oncological outcome. RESULTS: Five hundred and two restorative rectal cancer resections were performed during the study period. The incidence of AL was 9.9% (n = 50). AL occurred more commonly following neoadjuvant chemoradiotherapy (n = 31/252, 12.3%) than in those who did not receive neoadjuvant chemoradiotherapy (n = 19/250, 7.6%; P = 0.107); however, this was not statistically significant. Successful minimally invasive drainage was achieved in 28 patients (56%, radiological n = 24, surgical n = 4). Trans-rectal drainage was the most common drainage method (n = 14). The median duration of drainage was longer in the neoadjuvant group (27 vs 18 days). Surgical intervention was required in 11 patients, with anastomotic takedown and end-colostomy formation was most commonly required. Successful management of AL with drainage (maintenance of the anastomosis without the need for further intervention) was achieved in 26 of the 28 patients. There were no significant differences in overall or disease-free survival when patients with AL were compared with patients without AL (69.4% vs 72.6%, P = 0.99 and 78.7% vs 71.3%, P = 0.45, respectively). CONCLUSION: In selected patients, AL following restorative rectal resection can be effectively controlled using minimally invasive radiological or surgical drainage without the need for further intervention.

IntAct: intra-operative fluorescence angiography to prevent anastomotic leak in rectal cancer surgery: a randomized controlled trial.

AIM: Anastomotic leak (AL) is a major complication of rectal cancer surgery. Despite advances in surgical practice, the rates of AL have remained static, at around 10-15%. The aetiology of AL is multifactorial, but one of the most crucial risk factors, which is mostly under the control of the surgeon, is blood supply to the anastomosis. The MRC/NIHR IntAct study will determine whether assessment of anastomotic perfusion using a fluorescent dye (indocyanine green) and near-infrared laparoscopy can minimize the rate of AL leak compared with conventional white-light laparoscopy. Two mechanistic sub-studies will explore the role of the rectal microbiome in AL and the predictive value of CT angiography/perfusion studies. METHOD: IntAct is a prospective, unblinded, parallel-group, multicentre, European, randomized controlled trial comparing surgery with intra-operative fluorescence angiography (IFA) against standard care (surgery with no IFA). The primary end-point is rate of clinical AL at 90 days following surgery. Secondary end-points include all AL (clinical and radiological), change in planned anastomosis, complications and re-interventions, use of stoma, cost-effectiveness of the intervention and quality of life. Patients should have a diagnosis of adenocarcinoma of the rectum suitable for potentially curative surgery by anterior resection. Over 3 years, 880 patients from 25 European centres will be recruited and followed up for 90 days. DISCUSSION: IntAct will rigorously evaluate the use of IFA in rectal cancer surgery and explore the role of the microbiome in AL and the predictive value of preoperative CT angiography/perfusion scanning.

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Voriconazole-induced periostitis deformans: serial imaging in a patient with ANCA vasculitis.

OBJECTIVES: A 61-year-old with acute granulomatosis and polyangiitis developed Aspergillus fumigatus pneumonia after admission to the intensive care unit with a small bowel perforation. This occurred after immunosuppression (intravenous methylprednisolone, intravenous cyclophosphamide, and plasmapheresis) for his initial presentation with stage 3 acute kidney injury. MATERIALS AND METHODS: The mycologist recommended long-term treatment with voriconazole after initial recovery. RESULTS: After 7 months of treatment, the patient complained of joint pain and swelling in his hands. Radiographs, computed tomography, and single-photon emission computed tomography appearances were consistent with periostitis. A diagnosis of Voriconazole-induced periostitis deformans was made and the voriconazole was stopped. Plasma fluoride level was 278 µg/L (normal range < 50 µg/L). Discontinuation of voriconazole led to clinical improvement. CONCLUSIONS: Periostitis deformans due to fluorosis is a rare complication of voriconazole treatment. The imaging in our case is unusually dramatic. We were able to track the evolution of periosteal reactions over serial imaging.

Correction to: Voriconazole-induced periostitis deformans: serial imaging in a patient with ANCA vasculitis.

The original version of this paper unfortunately contained mistakes in the affiliations for all authors.

Organ preservation with local excision or active surveillance following chemoradiotherapy for rectal cancer.

BACKGROUND: Organ preservation has been proposed as an alternative to radical surgery for rectal cancer to reduce morbidity and mortality, and to improve functional outcome. METHODS: Locally advanced non-metastatic rectal cancers were identified from a prospective database. Patients staged ⩾T3 or any stage N+ were referred for neoadjuvant chemoradiotherapy (CRT) (50-54 Gy and 5-fluorouracil), and were reassessed 6-8 weeks post treatment. An active surveillance programme ('watch and wait') was offered to patients who were found to have a complete endoluminal response. Transanal excision was performed in patients who were found to have an objective clinical response and in whom a residual ulcer measured ⩽3 cm. Patients were followed up clinically, endoscopically and radiologically to assess for local recurrence or disease progression. RESULTS: Of 785 patients with rectal cancer between 2005 and 2015, 362 had non-metastatic locally advanced tumours treated with neoadjuvant CRT. Sixty out of three hundred and sixty-two (16.5%) patients were treated with organ-preserving strategies - 10 with 'watch and wait' and 50 by transanal excision. Fifteen patients were referred for salvage total mesorectal excision post local excision owing to adverse pathological findings. There was no significant difference in overall survival (85.6% vs 93.3%, P=0.414) or disease-free survival rate (78.3% vs 80%, P=0.846) when the outcomes of radical surgery were compared with organ preservation. Tumour regrowth occurred in 4 out of 45 (8.9%) patients who had organ preservation. CONCLUSIONS: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve an objective endoluminal response to neoadjuvant CRT. Transanal excision defines the pathological response and refines decision-making.

BK Virus Nephropathy: Histological Evolution by Sequential Pathology.

Reactivation of BK virus in renal allografts causes a destructive chronic infection. This single-center retrospective cohort study describes the evolution of BK virus allograft nephropathy (BKVAN) from 63 kidneys (from 61 patients) using sequential histopathology (454 biopsies, averaging 7.8 ± 2.6 per kidney) followed for 60.1 mo. Uninfected protocol biopsies formulated time-matched control Banff scores (n = 975). Interstitial inflammation occurred in 73% at diagnosis, correlating with viral histopathology (r = 0.413, p = 0.008) and amplifying early injury with accelerated interstitial fibrosis and tubular atrophy (IF/TA, p = 0.017) by 3 mo. Prodromal simian virus 40 large T antigen (SV40T)-negative inflammation with viremia preceded the histological diagnosis in 23.8%. Persistent subacute injury from viral cytopathic effect was associated with acute tubular necrosis and ongoing interstitial inflammation, culminating in IF/TA in 86.9%. Overall, cellular interstitial infiltration mitigated the intensity of subsequent tubular injury, SV40T, and tissue viral load, assessed by sequential paired histology (p < 0.001). Graft loss was predicted by high-level viremia (hazard ratio [HR] 4.996, 95% CI 2.19-11.396, p < 0.001), deceased donor (HR 3.201, 95% CI 1.149-8.915, p = 0.026), and late acute rejection (HR 3.124, 95% CI 1.037-9.413, p = 0.043). Transplant failure occurred in 38.1%, with uncontrolled infection (58.3%) and SV40T-negative chronic rejection (41.7%) causing losses. BKVAN is characterized by subacute virus-induced tubular injury, inflammation, and progressive nephron destruction. Effective antiviral therapy remains an unmet clinical need.

Efficacy and Safety Outcomes of Extended Criteria Donor Kidneys by Subtype: Subgroup Analysis of BENEFIT-EXT at 7 Years After Transplant.

The phase III Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors Trial (BENEFIT-EXT) study compared more or less intensive belatacept-based immunosuppression with cyclosporine (CsA)-based immunosuppression in recipients of extended criteria donor kidneys. In this post hoc analysis, patient outcomes were assessed according to donor kidney subtype. In total, 68.9% of patients received an expanded criteria donor kidney (United Network for Organ Sharing definition), 10.1% received a donation after cardiac death kidney, and 21.0% received a kidney with an anticipated cold ischemic time ≥24 h. Over 7 years, time to death or graft loss was similar between belatacept- and CsA-based immunosuppression, regardless of donor kidney subtype. In all three donor kidney cohorts, estimated mean GFR increased over months 1-84 for belatacept-based treatment but declined for CsA-based treatment. The estimated differences in GFR significantly favored each belatacept-based regimen versus the CsA-based regimen in the three subgroups (p < 0.0001 for overall treatment effect). No differences in the safety profile of belatacept were observed by donor kidney subtype.

Systematic Review of Animal Models Used in Research of Origins and Treatments of Fecal Incontinence.

BACKGROUND: Fecal incontinence is a common disorder, but its pathophysiology is not completely understood. OBJECTIVE: The aim of this review is to present animal models that have a place in the study of fecal incontinence. DATA SOURCES: A literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in August 2016 revealed 50 articles of interest. Search terms included fecal/faecal incontinence and animal model or specific species. STUDY SELECTION: Articles not describing an animal model, in vitro studies, veterinary literature, reviews, and non-English articles were excluded. MAIN OUTCOME MEASURES: The articles described models in rats (n = 31), dogs (n = 8), rabbits (n = 7), and pigs (n = 4). RESULTS: Different fecal incontinence etiologies were modeled, including anal sphincter lesions (33 articles) ranging from a single anal sphincter cut to destruction of 50% of the anal sphincter by sharp dissection, electrocautery, or diathermy. Neuropathic fecal incontinence (12 articles) was achieved by complete or incomplete pudendal, pelvic, or inferior rectal nerve damage. Mixed fecal incontinence (5 articles) was modeled either by the inflation of pelvic balloons or an array of several lesions including nervous and muscular damage. Anal fistulas (2 articles), anal sphincter resection (3 articles), and diabetic neuropathy (2 articles) were studied to a lesser extent. LIMITATIONS: Bias may have arisen from the authors' own work on fecal incontinence and the absence of blinding to the origins of articles. CONCLUSIONS: Validated animal models representing the main etiologies of fecal incontinence exist, but no animal model to date represents the whole pathophysiology of fecal incontinence. Therefore, the individual research questions still dictate the choice of model and species.