Tissue-free liquid biopsies combining genomic and methylation signals for minimal residual disease detection in patients with early colorectal cancer from the UK TRACC Part B study.

PURPOSE: Absence of post-operative circulating tumour DNA (ctDNA) identifies resected colorectal cancer (CRC) patients with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. We present the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection. DESIGN: TRACC included stage I-III resectable CRC patients. Prospective longitudinal plasma collection for ctDNA occurred pre- and post-surgery, post-ACT, every 3m for year 1 and every 6m in years 2 and 3 with imaging annually. The Guardant Reveal assay evaluated genomic and methylation signals. The primary endpoint was 2yr recurrence free survival (RFS) by post-operative ctDNA detection. (NCT04050345) Results: Between December 2016 and August 2022, 1203 were patients enrolled. Plasma samples (n=997) from 214 patients were analysed. 143 patients were evaluable for the primary endpoint; 92 (64.3%) colon, 51 (35.7%) rectal; 2 (1.4%) stage I, 64 (44.8%) stage II, 77 (53.8%) stage III. Median follow-up was 30.3m (95% CI: 29.5-31.3). 2yr RFS was 91.1% in patients with ctDNA not detected post-operatively and 50.4% in those with ctDNA detected (HR 6.5 [2.96-14.5] p<0.0001). Landmark negative predictive value (NPV) was 91.2% (95% CI 83.9-95.9). Longitudinal sensitivity and specificity were 62.1% (95% CI 42.2-79.3) and 85.9% (95% CI 78.9-91.3) respectively. Median lead-time from ctDNA detection to radiological recurrence was 7.3m (IQR 3.3-12.5; n=9). CONCLUSIONS: Tissue-free MRD detection with longitudinal sampling predicts recurrence in stage I-III CRC without need for tissue sequencing. NPV is high supporting ACT de-escalation in patients with ctDNA not detected post-operatively, now being investigated in the UK TRACC Part C study.

Perineal hernia repair after extralevator abdominoperineal excision, how we do it (PERineal Laparoscopic Sling: PERLS Technique).

PURPOSE: Recent shift to radical extralevator abdominoperineal excision (ELAPE) approach has seen an increased incidence of post-operative perineal hernia. However, there is no standardised surgical approach for its repair. The aim of this study was to report intra and post-operative results of the perineal hernia repair by the novel trans-abdominal PERineal Laparoscopic Sling (PERLS) Technique in patients who developed post-operative perineal hernia following ELAPE. METHODS: This is a retrospective analysis of consecutive patients who underwent perineal hernia repair by laparoscopic PERLS approach. All patients had undergone ELAPE with vertical rectus abdominis muscle (VRAM) flap reconstruction during the index surgery for treatment of rectal cancer. Post-operative complications, operative time, conversion rate to open surgery and incidence of recurrent perineal hernia were noted. RESULTS: Seven patients were operated for perineal hernia. The mean operative time was 105 min (range: 87 to 131 min). One case needed conversion to the open approach. The incidence of early complications was 57.1% including just single Clavien-Dindo I and two Clavien-Dindo II complications, while recurrence rate was 14.3%. CONCLUSION: PERLS perineal hernia repair is safe, performed in convenient time duration (mean = 105 min) and has reasonably less recurrence rate.

Population-based observational study of acute pancreatitis in southern England.

INTRODUCTION: Acute pancreatitis is a common surgical emergency. Identifying variations in presentation, incidence and management may assist standardisation and optimisation of care. The objective of the study was to document the current incidence management and outcomes of acute pancreatitis against international guidelines, and to assess temporal trends over the past 20 years. METHODS: A prospective four-month audit of patients with acute pancreatitis was performed across the Wessex region. The Atlanta 2012 classifications were used to define cases, severity and complications. Outcomes were recorded using validated systems and correlated against guideline standards. Case ascertainment was validated with clinical coding and hospital episode statistics data. RESULTS: A total of 283 patient admissions with acute pancreatitis were identified. Aetiology included 153 gallstones (54%), 65 idiopathic (23%), 29 alcohol (10%), 9 endoscopic retrograde cholangiopancreatography (3%), 6 drug related (2%), 5 tumour (2%) and 16 other (6%). Compliance with guidelines had improved compared with our previous regional audit. Results were 6.5% mortality, 74% severity stratification, 23% idiopathic cases, 65% definitive treatment of gallstones within 2 weeks, 39% computed tomography within 6-10 days of severe pancreatitis presentation and 82% severe pancreatitis critical care admission. The Atlanta 2012 severity criteria significantly correlated with critical care stay, length of stay, development of complications and mortality (2% vs 6% vs 36%, P < 0.0001). CONCLUSIONS: The incidence of acute pancreatitis in southern England has risen substantially. The Atlanta 2012 classification identifies patients with severe pancreatitis who have a high risk of fatal outcome. Acute pancreatitis management is seen to have evolved in keeping with new evidence and updated clinical guidelines.

Early Colostomy Formation Can Improve Independence Following Spinal Cord Injury and Increase Acceptability of Bowel Management.

Background: Colostomy formation can solve complications of bowel management following spinal cord injury (SCI). Newly injured patients at this spinal unit have chosen colostomy as a preferred option for bowel management. Objectives: To discover the reasons patients choose colostomy formation early following SCI and make comparison with those choosing it later, and to establish whether early colostomy is safe and advisable. Methods: Medical and nursing records of patients with SCI who chose to have a colostomy during the period 2005-2016 were examined retrospectively. Data were gathered concerning reasons for choosing a colostomy, early and later complications, the need for further surgery, and independence with bowel care before and after surgery. Patients were divided into two groups: those who chose a colostomy "early" during inpatient rehabilitation and those who chose it "later" as is traditional. Results: Reasons for choosing colostomy differed. Reducing reliance on caregiver and independence were of more importance to the early group; the later group chose colostomy to solve bowel care problems. Early complication rates in both groups were low. Longer term complications were higher in the early group, with the most common complication being rectal discharge. Parastomal hernia rates were low in both groups, as was the need for further surgery. Colostomy formation led to 20.8% of all patients gaining independence with bowel care. Conclusion: This study found colostomy to be a safe and effective option when performed early after SCI and demonstrates colostomy can be a means of gaining independence and making bowel care easier and more acceptable to the newly injured patient.

Development and external validation of a nomogram and online tool to predict bowel dysfunction following restorative rectal cancer resection: the POLARS score.

OBJECTIVE: Bowel dysfunction is common following a restorative rectal cancer resection, but symptom severity and the degree of quality of life impairment is highly variable. An internationally validated patient-reported outcome measure, Low Anterior Resection Syndrome (LARS) score, now enables these symptoms to be measured. The study purpose was: (1) to develop a model that predicts postoperative bowel function; (2) externally validate the model and (3) incorporate these findings into a nomogram and online tool in order to individualise patient counselling and aid preoperative consent. DESIGN: Patients more than 1 year after curative restorative anterior resection (UK, median 54 months; Denmark (DK), 56 months since surgery) were invited to complete The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 version3 (EORTC QLQ-C30 v3), LARS and Wexner incontinence scores. Demographics, tumour characteristics, preoperative/postoperative treatment and surgical procedures were recorded. Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, risk factors for bowel dysfunction were independently assessed by advanced linear regression shrinkage techniques for each dataset (UK:DK). RESULTS: Patients in the development (UK, n=463) and validation (DK, n=938) datasets reported mean (SD) LARS scores of 26 (11) and 24 (11), respectively. Key predictive factors for LARS were: age (at surgery); tumour height, total versus partial mesorectal excision, stoma and preoperative radiotherapy, with satisfactory model calibration and a Mallow's Cp of 7.5 and 5.5, respectively. CONCLUSIONS: The Pre-Operative LARS score (POLARS) is the first nomogram and online tool to predict bowel dysfunction severity prior to anterior resection. Colorectal surgeons, gastroenterologist and nurse specialists may use POLARS to help patients understand their risk of bowel dysfunction and to preoperatively highlight patients who may require additional postoperative support.

Phantom rectal sensations following abdominoperineal excision of the rectum (APER) and vertical rectus abdominis myocutaneous (VRAM) flap perineal reconstruction.

AIM: Phantom rectum is the sensation of an intact and/or functioning rectum, despite excision at surgery. Abdominoperineal excision of the rectum (APER) may be complemented by reconstructive operations and recently it was reported that patients undergoing APER and vertical rectus abdominis myocutaneous (VRAM) flap reconstruction are more prone to develop phantom sensations at an earlier timeframe and have more persistent symptoms than those who do not have perineal repairs. The aim of this study was to determine the prevalence of phantom rectal sensations in a cohort of these patients. METHOD: Patients who underwent APER and VRAM flap reconstruction for anorectal carcinomas were identified from May 2008 to July 2012. Patients completed a questionnaire evaluating their experience of rectal symptoms post-surgery. RESULTS: Thirty-four of 47 eligible patients were enrolled in the study. PR sensations were experienced by 50 % of patients, the majority of which (65 %) were present for >1 year. The commonest sensation reported was the feeling of faeces in a normal rectum (24 %). Disturbances in quality of life were apparent in 44 %; notably, sleep was affected, patients expressed increased feelings of stress/sadness, heightened levels of anxiety and limitation of daily activities as consequences of PR symptoms. Few patients sought medical advice. CONCLUSION: Fifty percent of patients experience PR sensations post-surgery, comparable with reported data for patients who have undergone APER alone. The addition of VRAM reconstruction does not significantly alter the prevalence of PR symptoms. This paper provides further evidence that phantom rectum occurs frequently and thus all patients undergoing excision of the rectum should be counselled appropriately.

Predicting the Risk of Bowel-Related Quality-of-Life Impairment After Restorative Resection for Rectal Cancer: A Multicenter Cross-Sectional Study.

BACKGROUND: Restorative anterior resection is considered the optimal procedure for most patients with rectal cancer and is frequently preceded by radiotherapy. Both surgery and preoperative radiotherapy impair bowel function, which adversely affects quality of life. OBJECTIVE: This study aimed to report symptoms associated with and key predictors for bowel-related quality-of-life impairment. DESIGN: The study included a cross-sectional cohort. SETTINGS: This was a multicenter study from 12 United Kingdom centers. PATIENTS: A total of 578 patients with rectal cancer underwent curative restorative anterior resection between 2001 and 2012 (median, 5.25 years postsurgery). MAIN OUTCOME MEASURES: Patients completed outcome measures that assessed bowel dysfunction (low anterior resection syndrome score), incontinence (Wexner score), and quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30), plus an anchor question: "Overall how does bowel function affect your quality of life?" RESULTS: The response rate was 80% (462/578). Overall, 85% (391/462) of patients reported bowel-related quality-of-life impairment, with 40% (187/462) reporting major impairment. A large difference in global quality of life (22 points; p < 0.001) was reported for "none" versus "major" impairment, with greatest symptom severity being diarrhea (25 points; p < 0.001), insomnia (24 points; p < 0.001), and fatigue (20 points; p < 0.001). Regression analysis identified major impairment in 60% and 45% of patients with low rectal cancer treated with and without preoperative radiotherapy compared with 47% and 33% of middle/upper rectal cancers with and without preoperative radiotherapy. LIMITATIONS: Advances in radiotherapy delivery and improvements in posttreatment symptom control, although currently of limited efficacy, imply that the content of this consent aid should be re-evaluated in 5 to 10 years. CONCLUSIONS: Before a restorative anterior resection, patients with rectal cancer should be informed that bowel-related quality-of-life impairment is common. The key risk factors are neoadjuvant therapy and a low tumor height. This study presents quality-of-life and functional outcome data, along with a consent aid, that will enhance this preoperative patient discussion.

Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study.

OBJECTIVE: This study aimed to validate a magnetic resonance imaging (MRI) staging classification that preoperatively assessed the relationship between tumor and the low rectal cancer surgical resection plane (mrLRP). BACKGROUND: Low rectal cancer oncological outcomes remain a global challenge, evidenced by high pathological circumferential resection margin (pCRM) rates and unacceptable variations in permanent colostomies. METHODS: Between 2008 and 2012, a prospective, observational, multicenter study (MERCURY II) recruited 279 patients with adenocarcinoma 6 cm or less from the anal verge. MRI assessed the following: mrLRP "safe or unsafe," venous invasion (mrEMVI), depth of spread, node status, tumor height, and tumor quadrant. MRI-based treatment recommendations were compared against final management and pCRM outcomes. RESULTS: Overall pCRM involvement was 9.0% [95% confidence interval (CI), 5.9-12.3], significantly lower than previously reported rates of 30%. Patients with no adverse MRI features and a "safe" mrLRP underwent sphincter-preserving surgery without preoperative radiotherapy, resulting in a 1.6% pCRM rate. The pCRM rate increased 5-fold for an "unsafe" compared with "safe" preoperative mrLRP [odds ratio (OR) = 5.5; 95% CI, 2.3-13.3)]. Posttreatment MRI reassessment indicated a "safe" ymrLRP in 33 of 113 (29.2%), none of whom had ypCRM involvement. In contrast, persistent "unsafe" ymrLRP posttherapy resulted in 17.5% ypCRM involvement. Further independent MRI assessed risk factors were EMVI (OR = 3.8; 95% CI, 1.5-9.6), tumors less than 4.0 cm from the anal verge (OR = 3.4; 95% CI, 1.3-8.8), and anterior tumors (OR = 2.8; 95% CI, 1.1-6.8). CONCLUSIONS: The study validated MRI low rectal plane assessment, reducing pCRM involvement and avoiding overtreatment through selective preoperative therapy and rationalized use of permanent colostomy. It also highlights the importance of posttreatment restaging.

Intrasaccular caecal adenocarcinoma presenting as enlarging right inguinoscrotal hernia.

INTRODUCTION: Colorectal cancer and inguinal hernias are both common surgical pathologies in the elderly but rarely co-exist. Where the conditions overlap, there can be difficulties in both diagnosis and treatment. PRESENTATION OF CASE: A 78 year old man with unexplained iron deficiency anaemia was investigated for gastrointestinal cancer. He was found to have enlarging bilateral inguinoscrotal hernias. CT colonoscopy revealed a herniated caecal carcinoma contained within the scrotum. An open excision was performed. DISCUSSION: Iron deficiency anaemia without obvious bleeding is associated with colorectal cancer and should be thoroughly investigated. Asymptomatic inguinal hernias are often ignored by patients. However, a change in an existing hernia may be associated with neoplasia. CONCLUSION: Dual pathology raises new difficulties in assessment, investigation and management of colorectal cancer.

An enhanced recovery programme reduces length of stay after rectal surgery.

PURPOSE: Enhanced Recovery Programmes (ERP) result in shorter hospital stay after colonic resection with no increase in complication, mortality or readmission rates. There is little data regarding the use of an ERP after rectal resection. We investigated the effect of introducing laparoscopic surgery and the ERP on outcomes in our unit. METHODS: From February 2007, elective patients undergoing rectal resection (laparoscopic or open) under the care of two colorectal surgeons were placed into the ERP. Length of stay (LOS) was recorded as total LOS, including readmissions. Comparison was made with a cohort of patients from 2004-2005 before the onset of laparoscopic surgery/ERP. RESULTS: Forty patients in the ERP group were compared with 42 patients from 2004-2005. Morbidity and mortality rates were similar. LOS was shorter in the ERP group cf. the retrospective group (median 7 days vs. 11 days; p=0.002). Median LOS was shorter in both laparoscopic ERP patients (6 days cf. 11 days; p= 0.004) and open ERP patients (7 days cf. 11 days; p=0.014) cf. the retrospective group. CONCLUSION: Patients having rectal resections benefit from a multimodal approach to surgery with significant reductions in LOS, but no change in morbidity or mortality.

Reconstruction of the perineum following anorectal cancer excision.

PURPOSE: Most patients with anal cancer receive chemoradiotherapy as first-line treatment. Persistent/recurrent tumours will subsequently require an abdomino-perineal resection (APR). A proportion of the 20,000 new cases of rectal carcinoma diagnosed in the UK each year receive neo-adjuvant chemoradiation and then an APR. Healing of the irradiated perineal bed is compromised, resulting in high morbidity. Reconstruction of the perineam with well-vasularised tissue is thought to enhance healing. This study investigates a series of 18 patients who underwent APR for anorectal cancer with flap reconstruction of their perineum. MATERIALS AND METHODS: A retrospective analysis of all anorectal cancers requiring an APR and flap reconstruction was performed. Casenotes were reviewed and documentation made of risk factors putting them at increased risk of wound complications. Length of stay, morbidity and outcome variables including primary flap healing were recorded. RESULTS: Between November 2000 and October 2007, 18 cases were performed (M/F = 7:11), six for anal cancer and 12 for low rectal tumours. Pre-operative treatment was chemoradiotherapy in 14 (78%), radiotherapy alone in two (11%) and none in two (11%). Perineal reconstruction consisted of 14 vertical rectus abdominis myocutaneous flaps, three free latissimus dorsi flap and one transverse rectus abdominis myocutaneous flap. Mean hospital stay was 21.8 days (10-54 days). Complete healing was noted in 16 cases with the remaining two continuing to improve under current follow-up. There were no flap losses. CONCLUSIONS: Despite most patients being treated with pre-operative radiotherapy, we have had significant success in obtaining primary healing of the perineal defect after APR.

Prognosis after anastomotic leakage in colorectal surgery.

INTRODUCTION: Anastomotic leakage is a major complication of colorectal surgery causing a significant increase in 30-day mortality. The long-term prognosis of anastomotic leakage is poorly documented. This study was designed to assess whether anastomotic leakage affects five-year survival and local recurrence. METHODS: A total of 5,173 patients were recruited to the Wessex Colorectal Cancer Audit during the period September 1991 to August 1995 (prospective data, 5-year follow-up). The effect of anastomotic leakage on five-year survival and local recurrence was analyzed using Kaplan-Meier curves and the log-rank test. RESULTS: A total of 1,834 patients underwent a curative resection with an anastomosis (anastomotic leak = 71; 3.9 percent): 30-day mortality: 18.3 percent in the leak group, and 3.5 percent in the nonleak group (P < 0.001); local recurrence: 19 percent in the leak group, and 9.8 percent in the nonleak group (P = 0.018). A total of 1,201 patients underwent colonic anastomosis (anastomotic leak = 31; 2.6 percent). There was no significant difference in local recurrence or five-year survival between the leak and nonleak groups. A total of 633 patients underwent rectal anastomosis (anastomotic leakage = 40; 6.3 percent): 30-day mortality: 10 percent in the leak group, and 2 percent in the nonleak group (P = 0.014); cumulative five-year estimate of local recurrence: 25.1 (95 percent confidence interval, 9.6-40.5) percent in the leak group, and 10.4 (95 percent confidence interval, 7.7-13) percent in the nonleak group (P = 0.007). Cumulative five-year estimate of overall survival: 52.8 (95 percent confidence interval, 36.1-69.4) percent in the leak group, and 63.9 (95 percent confidence interval, 59.9-67.9) percent in the nonleak group (P = 0.19). CONCLUSIONS: After rectal anastomosis, an anastomotic leak is associated with a significant increase in local recurrence.

Can magnetic resonance imaging predict circumferential margins and TNM stage in rectal cancer?

INTRODUCTION: This study was designed to assess whether preoperative magnetic resonance imaging scans were able to predict 1) pathologic tumor and node stage, and 2) those patients with a pathologically clear circumferential resection margin. METHODS: Patients with histologically proven carcinoma of the rectum were staged preoperatively using magnetic resonance imaging. Histologic specimens from patients undergoing mesorectal excision were reported according to the Royal College of Pathologists minimum dataset. Agreement between radiologic staging of tumor, local lymph nodes and circumferential resection margin involvement, and pathologic reporting was assessed by means of the Kappa statistic. RESULTS: After exclusions (10 radiotherapy, 3 failed scans, 10 no surgery, 9 local surgery), 40 patients remained. Magnetic resonance imaging correctly staged the tumor in 20 patients, understaged in 12, and overstaged in 8. Statistically, there was poor correlation between pathologic and radiologic tumor staging (Kappa, 0.18; 95 percent confidence interval, -0.13 to 0.42). Magnetic resonance imaging correctly staged node status in 27 patients, overstaged in 9, and understaged in 4. Statistically, there was poor correlation between pathologic and radiologic node staging (Kappa, 0.38; 95 percent confidence interval, 0.08-0.64). Magnetic resonance imaging correctly reported the status of the circumferential resection margin in 39 patients and understaged 1. Statistically, there was good correlation between pathologic and radiologic reporting of circumferential resection margin involvement (Kappa, 0.66; 95 percent confidence interval, 0.03-1). CONCLUSIONS: Preoperative magnetic resonance imaging scans provide poor predictive data as to subsequent pathologic tumor and node stage. Preoperative magnetic resonance imaging does produce reliable prediction of clear circumferential resection margins and provides valuable information in assessing whether patients can proceed to surgery without the need for preoperative radiotherapy.

Published evidence favors the use of suprapubic catheters in pelvic colorectal surgery.

INTRODUCTION: Bladder catheterization is routine during pelvic colorectal surgery, and transurethral catheterization is the norm. However, in gynecologic surgery suprapubic catheters are commonly used and are reported to be superior to urethral catheters. METHODS: A review of published studies comparing urethral and suprapubic catheters in patients undergoing colorectal surgery is presented. Level one evidence from randomized, controlled trials is sparse. Five randomized, controlled trials, most with small numbers, have been published comparing urinary tract infection, urinary retention, duration of catheterization, pain and discomfort, and patient preference. RESULTS: Urinary tract infections were increased in the urethral group in three of the five articles. There were no differences between the two techniques with respect to urinary retention, but all studies commented on the ease with which this complication could be assessed and managed in the suprapubic group. There did not seem to be any difference in duration of catheterization. The suprapubic group experienced less pain and discomfort than the urethral group, and the suprapubic catheter was preferred by those patients who had experienced both. CONCLUSION: The results reported favor suprapubic over urethral catheterization in that urinary tract infections are reduced, particularly in females, and the ability to attempt normal voiding is facilitated, particularly in males.

Angelchik prosthesis revisited.

There are few long-term follow-up reports of the Angelchik prosthesis (AP). We report the longest follow-up series (66-192 months, average 145 months) to date. Between October 1983 and January 1994, 65 patients (45 men and 20 women) aged between 29 and 84 years (mean 52 years) had an AP inserted for gastro-oesophageal reflux (GOR) with or without hiatus hernia (HH). Clinical, radiological, endoscopy, and operative details were reviewed. Postoperative complications, investigations, and follow-up details were critically analyzed. All living patients (n = 53) with an AP in situ were interviewed and symptomatic assessment was carried out using a modified Visick system (I-IV). The average duration of the GOR symptoms before the operation was 5.7 years (range 10 months to 20 years). The average hospital stay was 8 days (range 5-15 days). Postoperatively, five patients developed chest infection/atelectasis, four had superficial wound infection, two had deep vein thrombosis (one with pulmonary embolism), one had urinary retention, and four developed an incisional hernia. Six patients (three with an AP in situ) died of other medical conditions. Ten (15%) patients had removal of the prosthesis. Eight (12%) and 11 (17%) had transient and persistent dysphagia, respectively. Thirteen (20%) and five (8%) patients had distal slippage and proximal migration of the prosthesis, respectively. One patient had erosion of the AP into the stomach, while in another patient, the straps of the prosthesis ruptured. Of the 53 living patients with an AP in situ, 28 (53%) were Visick I, 11 (20%) were Visick II, 11 (20%) were Visick III, and 3 (7%) were Visick IV. We conclude that the AP has poor long-term results, with only 66% attaining Visick I and II, and a prosthesis removal rate of 15% (10/65). Patients with preoperative dysphagia, hypothyroidism, and diabetes tend to do worse with an AP. Obese patients and those with failed previous fundoplication seemed to fare well with an AP. In view of poor long-term results and high incidence of complications as compared to other conventional operations for GOR, we cannot recommend the continued use of the AP.