Phosphotungstic acid (PTA) preferentially binds to collagen- rich regions of porcine carotid arteries and human atherosclerotic plaques observed using contrast enhanced micro-computed tomography (CE-µCT).

Background and aims: Atherosclerotic plaque rupture in the carotid artery can cause small emboli to travel to cerebral arteries, causing blockages and preventing blood flow leading to stroke. Contrast enhanced micro computed tomography (CEµCT) using a novel stain, phosphotungstic acid (PTA) can provide insights into the microstructure of the vessel wall and atherosclerotic plaque, and hence their likelihood to rupture. Furthermore, it has been suggested that collagen content and orientation can be related to mechanical integrity. This study aims to build on existing literature and establish a robust and reproducible staining and imaging technique to non-destructively quantify the collagen content within arteries and plaques as an alternative to routine histology. Methods: Porcine carotid arteries and human atherosclerotic plaques were stained with a concentration of 1% PTA staining solution and imaged using MicroCT to establish the in situ architecture of the tissue and measure collagen content. A histological assessment of the collagen content was also performed from picrosirius red (PSR) staining. Results: PTA stained arterial samples highlight the reproducibility of the PTA staining and MicroCT imaging technique used with a quantitative analysis showing a positive correlation between the collagen content measured from CEµCT and histology. Furthermore, collagen-rich areas can be clearly visualised in both the vessel wall and atherosclerotic plaque. 3D reconstruction was also performed showing that different layers of the vessel wall and various atherosclerotic plaque components can be differentiated using Hounsfield Unit (HU) values. Conclusion: The work presented here is unique as it offers a quantitative method of segmenting the vessel wall into its individual components and non-destructively quantifying the collagen content within these tissues, whilst also delivering a visual representation of the fibrous structure using a single contrast agent.

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.

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.

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.

Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair-deficient colorectal cancer.

BACKGROUND: Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor implicated in tumour differentiation, proliferation, cell adhesion and migration. Negative CDX2 status (CDX2-) is associated with worse prognosis in colorectal cancer and may identify high-risk stage II disease that benefits from adjuvant chemotherapy. This observational study investigated whether CDX2- is associated with prognosis or response to chemotherapy in the mismatch repair-deficient (dMMR) phenotype of colorectal cancer. METHODS: Patients with resectable dMMR colorectal cancer were eligible for inclusion. The prognostic and predictive value of CDX2 expression on the presence of lymph node metastasis (LNM) and survival was investigated. CDX2 status was determined via immunohistochemistry using the Leica Bond™ CDX2 (clone EP25) ready-to-use primary antibody. RESULTS: Some 235 of 238 consecutive dMMR tumours were assessed for CDX2 status. CDX2- was observed in 15·7 per cent of colorectal cancer. Interobserver agreement was excellent (κ = 0·863; P < 0·001). CDX2- was significantly associated with female sex, increased size, advanced stage, worse conventional and poorly differentiated cluster (PDC) grade, mucinous morphology, perineural and lymphovascular invasion, and pN status (all P ≤ 0·038). CDX2- was not associated with LNM or survival in multivariable analysis. Independent predictors of LNM were PDC grade (odds ratio (OR) 4·12, 95 per cent c.i. 1·76 to 9·63; P = 0·001) and extramural venous invasion (OR 3·79, 1·62 to 8·85; P = 0·002). Budding (hazard ratio (HR) 2·79, 95 per cent c.i. 1·60 to 4·87; P < 0·001), pT status (HR 3·59, 1·29 to 10·01; P = 0·015) and adjuvant chemotherapy (HR 2·07, 1·15 to 3·74; P = 0·016) were independently associated with worse disease-free survival. CONCLUSION: CDX2- does not confer a worse prognosis in the dMMR phenotype of colorectal cancer. The MMR status of patients with colorectal cancer should be determined before assessing CDX2 status.

Patient satisfaction with joint colorectal-urogynaecology pelvic floor surgery

Introduction Pelvic floor dysfunction is a global term used to describe conditions such as pelvic organ prolapse, and faecal or urinary incontinence. The Pelvic Floor Centre is a multi-disciplinary clinic for pelvic floor dysfunction. The aim of this study was to assess patient satisfaction following joint colorectal-urogynaecology surgery in the Pelvic Floor Centre. Methods All patients who underwent a joint procedure in the Pelvic Floor Centre from 1st October 2015 to 31st October 2016 were contacted via telephone. Patient satisfaction was assessed using the Surgical Satisfaction Questionnaire (SSQ-8). Results Fifteen patients underwent joint surgeries between 1st October 2015 and 31st October 2016. All patients consented to the questionnaire. Patients underwent a variety of combined procedures including vaginal repairs, anal sphincter repairs, mid-urethral slings, perineal injections, and stapled trans-rectal resection of the rectum. Discussion Thirteen (86.7%) patients were satisfied with their surgery, and would recommend it to other patients with a similar condition. All patients were satisfied that their pain was well controlled after discharge. Eleven (73.3%) patients were satisfied with the time taken to return to daily activities, work, and their usual exercise routine. There is a high level of satisfaction amongst patients undergoing joint colorectal-urogynaecology surgery at the Pelvic Floor Centre. Further investigation into patient satisfaction with the clinic itself and international comparison is warranted.

Trends in the treatment of rectal prolapse: a population analysis.

PURPOSE: Rectal prolapse is a common condition, with conflicting opinions on optimal surgical management. Existing literature is predominantly composed of case series, with a dearth of evidence demonstrating current, real-world practice. This study investigated recent national trends in management of rectal prolapse in the Republic of Ireland (ROI). METHODS: This population analysis used a national database to identify patients admitted in the ROI primarily for the management of rectal prolapse, as defined by the International Classification of Diseases, 10th Revision (ICD-10). Demographics, procedures, comorbidities, and outcomes were obtained for patients admitted from 2005 to 2015 inclusive. RESULTS: There were 2648 admissions with a primary diagnosis of rectal prolapse; 39.3% underwent surgical correction. The majority were treated with either a perineal resection (47.2%) or an abdominal rectopexy ± resection (45.1%). The population-adjusted rate of operative intervention increased over the study period, from 25 to 42 per million (p < 0.001), with no change in the mean age of patients over time (p = 0.229). The application of a laparoscopic approach increased over time (p = 0.001). Patients undergoing an abdominal rectopexy were younger than those undergoing a perineal procedure (64.1 ± 17.3 versus 75.2 ± 15.5 years, p < 0.001) despite having a similar Charlson Comorbidity Index (p = 0.097). The mortality rate for elective repair was 0.2%. CONCLUSIONS: Despite the popularization of ventral mesh rectopexy over the study period, perineal resection Delorme's procedure remains the most common procedure employed for the correction of rectal prolapse in the ROI, with specific approach determined by age.

The lymph node ratio does not provide additional prognostic information compared with the N1/N2 classification in Stage III colon cancer.

AIM: The ratio of positive nodes to total nodes, the lymph node ratio (LNR), is a proposed alternative to the current N1/N2 classification of nodal disease. The true clinical benefit of adopting the LNR, however, has not been definitively demonstrated. This study compared the LNR with the current N1/N2 classification of Stage III colon cancer. METHOD: Patients with Stage III colon cancer were identified from a prospectively maintained database (1996-2012). The specificity and sensitivity of the N1/N2 classification in the prediction of overall survival were determined using R. A cut-off point for the LNR was determined by setting the specificity the same as for the N1/N2 classification. The sensitivity of the two methods was then compared, and bootstrapping 1000-fold was performed. This was then repeated for disease-specific survival. RESULTS: The specificity and sensitivity of the N1/N2 classification in predicting 3-year overall survival in this cohort (n = 402) was 62.2% and 52.1%, respectively. The cut-off point for the LNR was determined to be 0.27 for these data. On comparing LNR with the N1/N2 classification showed that for a given specificity, the LNR did not provide a statistically significant improvement in sensitivity (52.8% vs 52.1%, P = 0.31). For disease-specific death at 3 years, the specificity and sensitivity were 60.8% and 54.6%, respectively. The LNR did not provide a statistically significant improvement (55.4% vs 54.6%, P = 0.44). CONCLUSION: Both the N1/N2 system and the LNR predict survival in colon cancer, but both have low specificity and sensitivity. The LNR does not provide additional prognostic value to current staging for overall or disease-specific survival for a given cut-off point.

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.

Does anal sphincter injury preclude subsequent vaginal delivery?

OBJECTIVE: To assess continence and anal sphincter integrity during a subsequent pregnancy and delivery in women known to have a previous anal sphincter injury. DESIGN: Prospective observational study. SETTING: The National Maternity Hospital, Dublin, Ireland. POPULATION: Antenatal patients with a documented obstetric anal sphincter injury at a previous delivery. METHODS: Women underwent symptom scoring, endoanal ultrasound and manometry. MAIN OUTCOME MEASURES: Recommended and actual mode of delivery, continence scores and endoanal ultrasound findings after index delivery. RESULTS: 557 women were studied. 293 (53%) had no symptoms of faecal incontinence, 189 (34%) had mild symptoms and 75 (13%) moderate or severe symptoms. 408 (73%) had an endoanal ultrasound. 383(94%) had a normal or small (<1 quadrant) defect in the internal anal sphincter and 390 (96%) had a scar or small (<1e quadrant) defect in the external anal sphincter. 393 (70%) delivered vaginally. 164 (30%) were delivered by caesarean section. 197/557 (35%) returned for follow-up. There was no significant change in continence following either vaginal or caesarean delivery. 20 (5.1%) women had a recognised second anal sphincter tear during vaginal delivery. CONCLUSIONS: The majority of women who sustain a third degree tear have minimal or no symptoms of faecal incontinence when assessed antenatally in a subsequent pregnancy. 70% go on to have a vaginal delivery, with little impact on faecal continence. These findings provide reassurance for patients and clinicians about the safety of vaginal delivery following anal sphincter injury in appropriately selected patients.

Open versus laparoscopic abdominal rectopexy: an examination of early postoperative outcomes.

BACKGROUND: Abdominal rectopexy is used to treat full thickness rectal prolapse and obstructed defecation syndrome, with good outcomes. Use of a laparoscopic approach may reduce morbidity. The current study assessed short-term operative outcomes for patients undergoing laparoscopic or open rectopexy. METHODS: Rectopexy cases were identified from theater logs in two tertiary referral centers. Patient demographics, intra-operative details and early postoperative outcomes were examined. RESULTS: There were 62 patients included over 10 years, a third of whom underwent laparoscopic rectopexy. Laparoscopy was associated with a longer operative time (195.9 versus 129.6 min, p = 0.003), but this did not affect postoperative outcomes, with no significant differences found for complication rates and length of stay between the two groups. Univariable analysis found no influence of laparoscopic approach on the likelihood of postoperative complications, and no factor achieved significance with multivariable analysis. This study included the first laparoscopic cases performed in the involved institutions, and a "learning curve" existed as seen with a decreasing operative duration per case over time (p = 0.002). CONCLUSIONS: Laparoscopic rectopexy has similar short-term outcomes to open rectopexy.

Torsion of monofilament and polyfilament sutures under tension decreases suture strength and increases risk of suture fracture.

BACKGROUND: A continuous running suture is the preferential method for abdominal closure. In this technique the suture is secured with an initial knot and successive tissue bites are taken. At each tissue bite, the needle is rotated through the tissue; in doing so, the suture can twist around the knot which acts as an anchor. OBJECTIVE: To determine the effect of axial torsional forces on sutures used in abdominal closure. METHODS: The effect of axial twisting on polydioxanone (PDS*II), polyglactin (Vicryl), polypropylene (Prolene) and nylon (Ethilon) sutures was investigated using a uniaxial testing device. RESULTS: The maximum tensile force withstood for untwisted sutures was determined: polydioxanone failed at a tensile force of 116.4±0.84 N, polyglactin failed at 113.9±2.4 N, polypropylene failed at 71.1±1.5 N and nylon failed at 61.8±0.5 N. Twisting decreased the maximum tensile force of all sutures; one complete twist per 10 mm (i.e., 15 twists) decreased the tensile strength of polydioxanone by 21%, polyglactin by 23%, polypropylene by 16% and nylon by 13%, p<0.001. Excessive twisting caused a nonlinear decrease in suture strength, with one twist per 75 mm (i.e., 20 twists) of polydioxanone decreasing strength by 39%, P<0.001. CONCLUSION: The effect of excessive twisting on the mechanical properties of sutures is a previously unrecognised phenomenon. Surgeons should be aware that this can result in a decrease in suture strength and reduce the elasticity of the material, and therefore need to adapt their practice to reduce the torsional force placed on sutures.

Prophylactic colectomy for hyperplastic polyposis.

BACKGROUND: Hyperplastic polyposis (HP) is important to recognise as it increases the risk of adenomata which may develop dysplastic change or frank adenocarcinoma. We present the case of a 58-year-old woman with HP. CASE: Following a diagnosis of HP in this patient, it was noted that the number of polyps were progressively increasing over time, becoming pancolic and extending into the rectum. Genetic testing for a familial polypotic syndrome was negative. Histological analysis demonstrated that the majority of polyps were hyperplastic, but there were also serrated and tubular adenomata with foci of low-grade dysplasia. Whilst there was no evidence of frank malignancy or high-grade dysplasia, following a risk-benefit discussion the patient underwent a laparoscopic total colectomy with an ileal pouch formation. CONCLUSION: This case highlights the complexity in the management of HP and that even in the absence of confirmed invasive disease, patients may elect to undergo prophylactic colonic resection.

Prospective, randomized, controlled trial of thoracic epidural or patient-controlled opiate analgesia on perioperative quality of life.

BACKGROUND: Perioperative epidural analgesia provides continuous pain control and may have advantages over parenteral opiate administration. This study assessed the impact of epidural analgesia on quality of life (QOL) of patients undergoing major surgery. METHODS: Sixty patients undergoing thoracic or thoraco-abdominal surgery were studied prospectively. Patients were randomly assigned to receive either thoracic epidural analgesia or patient-controlled i.v. opiate analgesia (PCA) after operation. Visual analogue pain and sedation scores were recorded for the period of the study. QOL health surveys at 24 h (SF-8 acute form) and at 1 week (SF-36) were recorded. Results were examined by uni- and multivariate analyses corrected for the effect of multiple comparisons. RESULTS: Mean pain scores were significantly lower in the epidural group at most time points. Physical and mental scores in the epidural group were significantly better than the PCA group for both SF-8 and SF-36 QOL health surveys (P<0.001). CONCLUSIONS: Epidural analgesia with local anaesthetic and opioid improves QOL and delivers better analgesia compared with PCA in patients undergoing major thoraco-abdominal surgery.

Pap smears for men: a vision of the future?

BACKGROUND: Anal intraepithelial neoplasia (AIN) rarely receives as much publicity as its neighbouring orifice, the cervix. As in the cervix, intraepithelial neoplasias are precursors to cancer in the anal canal. AIN and cervical interstitial neoplasia (CIN) undergo dysplasia as a consequence of human papillomavirus (HPV) infection. Since the advent of screening with the Pap smear in CIN, cervical cancer has plummeted to a fifth of its initial incidence. Anal cancer, however, has been rising, with a predilection for human immunodeficiency virus-infected men. HPV causes a squamous epithelial dysplasia and converts healthy tissue into AINs of increasing severity until anal cancer manifests. CLINICAL CASE: This article describes a clinical case of anogenital HPV infection refractory to medical and surgical therapy. It also describes an effective surgical excision technique associated with a good cosmetic outcome. CONCLUSIONS: The paper concludes by briefly discussing the implications of a national screening programme against AIN in the future.