Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision.

BACKGROUND: Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1-2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84-99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. METHODS: Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. FINDINGS: Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67-80] vs 65 years [61-71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6-12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. INTERPRETATION: The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. FUNDING: Cancer Research UK.

Radical surgery versus organ preservation via short-course radiotherapy followed by transanal endoscopic microsurgery for early-stage rectal cancer (TREC): a randomised, open-label feasibility study.

BACKGROUND: Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. METHODS: TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8-10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. FINDINGS: Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months' follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. INTERPRETATION: Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. FUNDING: Cancer Research UK.

Survival following rectal cancer surgery: does the age matter?

Introduction: Information regarding rectal cancer surgery outcomes and survival benefits in the elderly is sparse. Radical rectal surgery can be associated with substantial morbidity and mortality. We investigated age-specific survival for patients undergoing radical rectal surgery to determine outcomes in elderly patients Methods: Over a 10-year period data on all patients who underwent rectal cancer surgery was performed. Patients were grouped according to age and eight other variables including cancer stage (Duke's/TNM). Data analysed using computer program R. Kaplan-Meier survival curves estimated for age groups and compared using a modified log-rank permutation test. Survival curves fitted using Cox proportional hazard models and hazard ratios obtained Results: About 374 patients underwent surgery. Survival percentages at 1 year by age group are 91.3% for age <50, and 75.5% for age >80. At 5 years these are 87.0% for age <50 and 57.1% for >80. Overall the variation among the survival curves for the age groups is significant (p < .001). The hazard ratio for over the 80+ with the age group <50 as the reference is 4.79 (95% CI: 1.44-15.92) and is significant (p = .011) Conclusion: Overall survival is significantly less in the elderly. There is a striking reduction in survival in >80 year olds in the first post-operative year. This study highlights that care must be taken in deciding whether radical surgery should be offered to those patients and careful consideration is given to allow the best overall survival and quality of life.

Early discharge following transanal endoscopic microsurgery is safe.

AIM: Transanal endoscopic microsurgery (TEM) was developed as an alternative to major surgery for rectal tumors; however, there is no consensus as to the optimal postoperative length of stay. The aim of this large series is to show that a policy of presumed early discharge is safe. PATIENTS AND METHODS: All patients undergoing TEM at a single center between 2008 and 2011 were included. Data on demographics, tumor morphology, length of stay, and complications were collected from a prospectively collected database and computer records. RESULTS: Sixty-six patients were included, with a mean tumor size of 4.6 cm (range, 0.6-10 cm). The majority were adenomas (71%). Median stay was 1 day, with most (77%) patients being discharged within the 23-hour policy. Neither age nor tumor size affected the length of stay. There were five complications (7.6%), and 2 patients (3%) required readmission following discharge. No complications arose in patients discharged within 23 hours. CONCLUSIONS: The majority of patients were safely discharged within 23 hours. No early-discharge patient suffered complications or required readmission. The overall complication rate was consistent with other published series, and neither age nor tumor size adversely affected outcome. A routine 23-hour discharge policy can thus be recommended for TEM patients.

Enhanced recovery program following colorectal resection in the elderly patient.

BACKGROUND: The enhanced recovery program (ERP) aims to reduce the metabolic response to surgery, hastening recovery and shortening hospital stay. Concerns exist regarding morbidity and hospital stay in elderly patients. The present study aimed to compare the outcomes and compliance of elderly patients managed by an ERP protocol with a younger group. METHODS: A review was performed of a prospective database of patients undergoing colorectal resection managed under the ERP protocol between 2005 and 2010. Patients were grouped into <80 years and ≥ 80 years, and perioperative data were collated. The postoperative outcomes were compared with the goals set out by the ERP protocol. RESULTS: A total of 688 patients were included, 558 were <80 years (median: 66 years; range: 17-79 years) and 130 were ≥ 80 years (median: 83 years; range: 80-95 years). Some 96% of operations were planned laparoscopically. Median total length of hospital stay was 6 days (range: 1-108 days) for the <80 year group and 8 days (range: 1-167 days; P 0.363) for the elderly group, with a 30 day readmission rate of 8.6% for the population and no significant differences between groups. The 30 day mortality was 5%, with a significant difference between the two groups (P < 0.0001). Differences in protocol adherence were identified in the discontinuation of intravenous fluids, catheter removal, and early mobilization. CONCLUSIONS: An enhanced recovery program is feasible for colorectal surgery patients ≥ 80 years of age, with similar compliance as the younger group to some aspects of the protocol and an acceptable readmission rate. Attention to improving compliance in the postoperative phase is necessary, particularly in such high-risk patients, as such improvement may reduce the morbidity and mortality.

Training higher surgical trainees in laparoscopic common bile duct exploration.

BACKGROUND: Laparoscopic common bile duct (CBD) exploration is regarded as a safe, definitive procedure for ductal calculi, avoiding the complications of endoscopic retrograde cholangiopancreatography. We aimed to evaluate the outcomes of laparoscopic CBD exploration carried out by trainees compared to those of an experienced consultant (R.W.M.). METHODS: A prospective database of all cases of laparoscopic CBD exploration over a 15-year period was analyzed retrospectively. All patients underwent a four-port technique and intraoperative cholangiography. Patient demographics, operative technique, success, and complications were analyzed. RESULTS: The median age of patients undergoing laparoscopic CBD exploration was 65 years (range 14-94 years). In all, 187 (79%) of the CBD explorations were performed by one consultant and 48 (21%) by trainees. Calculi were successfully cleared in 141 (88%) and 43 (96%), respectively. There were two (<1%) conversions to an open procedure in the total group. The median operating time was 130 minutes in the consultant group versus 150 minutes in the trainee group (p < 0.05, Mann-Whitney U-test). There was no significant difference in CBD clearance rate, surgical approach, or complication rate between consultant and trainees (Fisher's exact test). CONCLUSIONS: Laparoscopic CBD exploration is a safe procedure in both consultant and trainee hands. With appropriate training, surgical trainees can achieve equivalent outcomes in CBD clearance with no significant difference in complication rates.

Spontaneous bowel perforation due to norovirus: a case report.

Norovirus is the leading cause of epidemic gastroenteritis worldwide but the disease is usually self-limiting and generally only causes serious health problems in the young, elderly and immunocompromised. The authors report a case of bowel perforation in an elderly Caucasian lady with confirmed infection with Norovirus genogroup II and no other presumptive cause. To the authors' knowledge this is the first such case of bowel perforation due to Norovirus. Viral gastroenteritis should be considered in the list of differentials when no obvious cause of bowel perforation can be identified to minimise morbidity and mortality.

Use of plasma MMP-2 and MMP-9 levels as a surrogate for tumour expression in colorectal cancer patients.

Matrix metalloproteinases, and notably the gelatinases MMP-2 and MMP-9, have important roles in tumour invasion, metastasis and angiogenesis. Our study investigates the distribution of MMP-2 and MMP-9 in colorectal cancer, the correlation with plasma levels, changes following surgical resection and whether plasma levels reflect clinical staging and disease course. MMP-2 and MMP-9 expression in 48 colorectal tumours and 13 adenomatous polyps was analysed by RT-PCR, immunohistochemistry, and quantified by ELISA of tumour lysates. Concentrations of MMP-2 and MMP-9 in plasma samples from these patients and 36 other patients who underwent curative resections were measured by ELISA prior to and 6-12 months after surgery. MMP-2 expression was significantly increased in colorectal cancer tissues compared to matched normal colon as measured by ELISA. Active MMP-2 was localised by immunohistochemistry to regions where tumour cells invaded the muscularis with little staining in more superficial areas. Plasma MMP-2 levels were also significantly elevated in patients with colorectal cancer, with significant reductions following curative resections at all stages. Similarly, MMP-9 expression was significantly increased in colorectal cancer tissues, predominantly in the tumour stroma. Plasma levels of MMP-9 were significantly elevated at all stages in colorectal cancer patients and a significant reduction was seen following curative resections. With both MMP-2 and MMP-9, the strongest correlation with clinical staging in colorectal cancer was represented by the total plasma concentration of the enzymes, both falling to within the normal range following curative surgery. Plasma levels of these enzymes may therefore have potential as a noninvasive indicator of invasion or metastasis in colorectal cancer or as a marker of disease status during follow-up.