Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial.

OBJECTIVE: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence. MATERIAL AND METHODS: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure. RESULTS: Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58-0.68; specificity, 0.75-0.76). CONCLUSION: A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation. CLINICAL RELEVANCE STATEMENT: A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone. KEY POINTS: Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation. This model for recurrence, incorporating many patient variables, had higher specificity than staging alone. Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules.

Robotic transanal minimally invasive surgery (r-TAMIS): perioperative and short-term outcomes for local excision of rectal cancers.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) is an advanced technique for excision of early rectal cancers. Robotic TAMIS (r-TAMIS) has been introduced as technical improvement and potential alternative to total mesorectal excision (TME) in early rectal cancers and in frail patients. This study reports the perioperative and short-term oncological outcomes of r-TAMIS for local excision of early-stage rectal cancers. METHODS: Retrospective analysis of a prospectively collected r-TAMIS database (July 2021-July 2023). Demographics, clinicopathological features, short-term outcomes, recurrences, and survival were investigated. RESULTS: Twenty patients were included. Median age and body mass index were 69.5 (62.0-77.7) years and 31.0 (21.0-36.5) kg/m2. Male sex was prevalent (n = 12, 60.0%). ASA III accounted for 66.7%. Median distance from anal verge was 7.5 (5.0-11.7) cm. Median operation time was 90.0 (60.0-112.5) minutes. Blood loss was minimal. There were no conversions. Median postoperative stay was 2.0 (1.0-3.0) days. Minor and major complication rates were 25.0% and 0%, respectively. Seventeen (85.0%) patients had an adenocarcinoma whilst three patients had an adenoma. R0 rate was 90.0%. Most tumours were pT1 (55.0%), followed by pT2 (25.0%). One patient (5.0%) had a pT3 tumour. Specimen and tumour maximal median diameter were 51.0 (41.0-62.0) mm and 21.5 (17.2-42.0) mm, respectively. Median specimen area was 193.1 (134.3-323.3) cm2. Median follow-up was 15.5 (10.0-24.0) months. One patient developed local recurrence (5.0%). CONCLUSIONS: r-TAMIS, with strict postoperative surveillance, is a safe and feasible approach for local excision of early rectal cancer and may have a role in surgically unfit and elderly patients who refuse or cannot undergo TME surgery. Future prospective multicentre large-scale studies are needed to report the long-term oncological outcomes.

Influence of diffusion weighted imaging and contrast enhanced T1 sequences on the diagnostic accuracy of magnetic resonance enterography for Crohn's disease.

OBJECTIVES: To evaluate the additional diagnostic benefit of diffusion weighted imaging (DWI) and contrast enhanced (CE) images during MR enterography (MRE) of Crohn's disease. METHODS: Datasets from 73 patients (mean age 32; 40 male) (28 new-diagnosis, 45 relapsed) were read independently by two radiologists selected from a pool of 13. Radiologists interpreted datasets using three sequential sequence blocks: (1) T2 weighted and steady state free precession gradient echo (SSFP) images alone (T2^); (2) T2 weighted and SSFP images with DWI (T2 + DWI^) and; (3) T2 weighted images, SSFP, DWI and post-contrast enhanced (CE) T1 images (T2 + DWI + CE^), documenting presence, location, and activity of small bowel disease. For each sequence block, sensitivity and specificity (readers combined) was calculated against an outcome-based construct reference standard. RESULTS: 59/73 patients had small bowel disease. Per-patient sensitivity for disease detection was essentially identical (80 % [95 % CI 72, 86], 81 % [73,87], and 79 % [71,86] for T2^, T2 + DWI^and T2 + DWI + CE^respectively). Specificity was identical (82 % [64 to 92]). Per patient sensitivity for disease extent was 56 % (47,65), 56 % (47,65) and 52 % (43 to 61) respectively, and specificity was 82 % (64 to 92) for all blocks. Sensitivity for active disease was 97 % (90,99), 97 % (90,99) and 98 % (92,99), and specificity was also comparable between all sequence combination reads. Results were consistent across segments and newly diagnosed/relapse patients. CONCLUSION: There is no additional diagnostic benefit of adding either DWI or CE to T2 FSE and SSFP sequences for evaluating small bowel Crohn's disease, suggesting MRE protocols can be simplified safely.

Diagnostic performance of sonographic activity scores for adult terminal ileal Crohn's disease compared to magnetic resonance and histological reference standards: experience from the METRIC trial.

OBJECTIVES: The simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) are promising intestinal ultrasound (IUS) indices of CD, but studied mainly in small settings with few sonographers. We compared SUS-CD and BUSS against histological and magnetic resonance enterography (MRE) reference standards in a post hoc analysis of a prospective multicentre, multireader trial. METHODS: Participants recruited to the METRIC trial (ISRCTN03982913) were studied, including those with available terminal ileal (TI) biopsies. Sensitivity and specificity of SUS-CD and BUSS for TI CD activity were calculated with 95% confidence intervals (CI), from the prospective observations of the original METRIC trial sonographers against the histological activity index (HAI) and the simplified magnetic resonance index of activity (sMARIA). RESULTS: We included 284 patients (median 31.5 years, IQR 23-46) from 8 centres, who underwent IUS and MRE. Of these, 111 patients had available terminal ileal biopsies with HAI scoring. Against histology, sensitivity and specificity for active disease were 79% (95% CI 69-86%) and 50% (31-69%) for SUS-CD, and 66% (56-75%) and 68% (47-84%) for BUSS, respectively. Compared to sMARIA, the sensitivity and specificity for active CD were 81% (74-86%) and 75% (66-83%) for SUS-CD, and 68% (61-74%) and 85% (76-91%) for BUSS, respectively. The sensitivity of SUS-CD was significantly greater than that of BUSS against HAI and sMARIA (p < 0.001), but its specificity was significantly lower than of BUSS against the MRE reference standard (p = 0.003). CONCLUSIONS: Particularly when compared to MRE activity scoring, SUS-CD and BUSS are promising tools in a real-world clinical setting. CLINICAL RELEVANCE STATEMENT: When tested using data from a multicentre, multireader diagnostic accuracy trial, the simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) were clinically viable intestinal ultrasound indices that were reasonably sensitive and specific for terminal ileal Crohn's disease, especially when compared to a magnetic resonance reference standard. KEY POINTS: The simple ultrasound activity score for Crohn's disease and bowel ultrasound score are promising intestinal ultrasound indices of Crohn's disease but to date studied mainly in small settings with few sonographers. Compared to histology and the magnetic resonance reference standard in a multicentre, multireader setting, the sensitivity of simple ultrasound activity score for Crohn's disease is significantly greater than that of bowel ultrasound score. The specificity of simple ultrasound activity score for Crohn's disease was significantly lower than that of bowel ultrasound score compared to the magnetic resonance enterography reference standard. The specificity of both indices was numerically higher when the magnetic resonance enterography reference standard was adopted.

Intra-operative ultrasound assessment of the biliary tree during robotic cholecystectomy.

Image-guided assessment of bile ducts and associated anatomy during laparoscopic cholecystectomy can be achieved with intra-operative cholangiography (IOC) or laparoscopic ultrasound (LUS). Rates of robotically assisted cholecystectomy (RC) are increasing and herein we describe the technique of intra-corporeal biliary ultrasound during RC using the Da Vinci system. For intraoperative evaluation of the biliary tree during RC, in cases of suspected choledocholithiasis, the L51K Ultrasound Probe (Hitachi, Tokyo, Japan) is used. The extrahepatic biliary tree is scanned along its length, capitalising on the benefits of the full range of motion offered by the articulated robotic instruments and integrated ultrasonic image display using TileProTM software. Additionally, this technique avoids the additional time and efforts required to undock and re-dock the robot that would otherwise be required for selective IOC or LUS. The average time taken to perform a comprehensive evaluation of the biliary tree, from the hepatic ducts to the ampulla of Vater, is 164.1 s. This assessment is supplemented by Doppler ultrasound, which is used to fully delineate anatomy of the porta hepatis, and accurate measurements of the biliary tree and any ductal stones can be taken, allowing for contemporaneous decision making and management of ductal pathologies. Biliary tract ultrasound has been shown to be equal to IOC in its ability to diagnose choledocholithiasis, but with the additional benefits of being quicker and having higher completion rates. We have described our practice of using biliary ultrasound during robotically assisted cholecystectomy, which is ergonomically superior to LUS, accurate and reproducible.

Interobserver variation in the interpretation of magnetic resonance enterography in Crohn's disease.

OBJECTIVES: To evaluate interobserver variability for diagnosis of disease presence and extent of small bowel and colonic Crohn's disease using MR enterography (MRE). METHODS: Data from the first 73 consecutive patients (mean age 32, 33F, 28 new diagnosis, 45 suspected relapse) recruited to a multicentre, prospective diagnostic accuracy trial evaluating MRE for small bowel Crohn's disease were each read independently by three (from a pool of 20) radiologists. Radiologists documented presence and segmental location of small bowel Crohn's disease and recorded morphological mural/extramural parameters for involved segments. Per patient percentage agreement for disease presence and extent were calculated against an outcome-based construct reference standard (averaged between pairs of readers). Prevalence-adjusted bias-adjusted κ (PABAK) was calculated. RESULTS: Agreement for small bowel disease presence for new diagnosis/relapsed patients was 68%(κ = 0.36)/ 78% (κ = 0.56) and 43%(κ = 0.14)/ 53% for disease extent (κ = 0.07), respectively. For disease presence, all three radiologists agreed correctly with the reference standard in 41/59 (69%) of patients with small bowel involvement, and in 8/14 (57%) cases of without small bowel disease. Agreement was highest for multisegment disease, greater than 5 cm in length, with mural thickness>6 mm, and increased mural T2 signal. Agreement for colonic disease presence was 61% (κ = 0.21 fair agreement) for new diagnosis/ 60% (κ = 0.20, slight agreement) for relapsed patients. CONCLUSION: There is a reasonable agreement between radiologists for small bowel disease presence using MRE for newly diagnosed Crohn's disease, and patients with suspected relapse, respectively. Agreement is lower for disease extent. ADVANCES IN KNOWLEDGE: There is reasonable agreement between radiologists for small bowel disease presence using MRE for newly diagnosed (68%) Crohn's disease, and patients with suspected relapse (78%). Agreement is lower for disease extent (43% new diagnosis and 53% suspected relapse).

Data from a large Western centre exploring the impact of COVID-19 pandemic on endoscopy services and cancer diagnosis.

OBJECTIVE: The global COVID-19 pandemic has changed healthcare across the world. Efforts have concentrated on managing this crisis, with impact on cancer care unclear. We investigated the impact on endoscopy services and gastrointestinal (GI) cancer diagnosis in the UK. DESIGN: Analysis of endoscopy procedures and cancer diagnosis at a UK Major General Hospital. Procedure rates and diagnosis of GI malignancy were examined over 8-week periods in spring, summer and autumn 2019 before the start of the crisis and were compared with rates since onset of national lockdown and restrictions on elective endoscopy. The number of CT scans performed and malignancies diagnosed in the two corresponding periods in 2019 and 2020 were also evaluated. RESULTS: 2 698 2516 and 3074 endoscopic procedures were performed in 2019, diagnosing 64, 73 and 78 cancers, respectively, the majority being in patients with alarm symptoms and fecal immunochemical test+ve bowel cancer screening population. Following initiation of new guidelines for management of endoscopy services 245 procedures were performed in a 6 week duration, diagnosing 18 cancers. This equates to potentially delayed diagnosis of 37 cancers per million population per month. Clinician triage improved, resulting in 13.6 procedures performed to diagnose one cancer. CONCLUSIONS: Our data demonstrate an 88% reduction in procedures during the first 6 weeks of COVID-19 crisis, resulting in 66% fewer GI cancer diagnoses. Triage changes reduced the number of procedures required to diagnose cancer. Our data can help healthcare planning to manage the extra workload on endoscopy departments during the recovery period from COVID-19.

Robotic Complete Mesocolic Excision (CME) is a safe and feasible option for right colonic cancers: short and midterm results from a single-centre experience.

BACKGROUND: Complete mesocolic excision (CME) for right colon cancers has traditionally been an open procedure. Surgical adoption of minimal access CME remains limited due to the technical challenges, training gaps and lack of level-1 data for proven benefits. Currently there is limited published data regarding the clinical results with the use of robotic CME surgery. Aim To report our experience, results and techniques, highlighting a clinical and oncological results and midterm oncological outcomes for robotic CME. AIM: To report our experience, results and techniques, highlighting a clinical and oncological results and midterm oncological outcomes for robotic CME. METHODS: All patients undergoing standardised robotic CME technique with SMV first approach between January 2015 and September 2019 were included in this retrospective review of a prospectively collected database. Patient demographics, operative data and clinical and oncological outcomes were recorded. RESULTS: Seventy-seven robotic CME resections for right colonic cancers were performed over a 4-year period. Median operative time was 180 (128-454) min and perioperative blood loss was 10 (10-50) ml. There were 25 patients who had previous abdominal surgery. Median postoperative hospital stay was 5 (3-18) days. There was no conversion to open surgery in this series. Median lymph node count was 30 (10-60). Three (4%) patients had R1 resection. There was one (1%) local recurrence in stage III disease and 4(5%) distal recurrence in stage II and stage III. There was no 30- or 90-day mortality. Three-year disease-free survival was 100%, 91.7% and 92% for stages I, II and III, respectively. Overall survival was 94%. CONCLUSIONS: Robotic CME is feasible, effective and safe. Good oncological results and improved survival are seen in this cohort of patients with a standardised approach to robotic CME.

The role of imaging and biopsy in the management and staging of large non-pedunculated rectal polyps.

INTRODUCTION: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are often used for benign and Sm1 large non-pedunculated rectal polyps (LNPRPs), although other surgical techniques including transanal endoscopic microsurgery (TEMS) and transanal minimal invasive surgery remain available. This review covers the role of pre-excisional imaging and selective biopsy of LNPRPs. Areas covered: Polyps between 2 and 3 cm with favorable features (Paris 1, Kudo III/IV pit patterns, and non-lateral spreading type [LST]) may have a one-stage EMR without biopsy and imaging, provided adequate expertise is available with other technologies such as magnifying chromoendoscopy. Higher-risk polyps (moderate/severe dysplasia, 0-IIa+c morphology, nongranular LST, Kudo pit pattern V or submucosal carcinoma, or those >3 cm) should have pre-EMR/ESD imaging with magnetic resonance imaging (MRI) and/or endorectal ultrasound (ERUS) ± biopsies and photographs prior to multidisciplinary team discussion. Expert commentary: In some centers, EMR and ESD are considered the primary modality of treatment, with TEMS as a back-up, while elsewhere, TEMS is the main modality for excision of significant polyps and early colorectal cancer lesions. Likewise, the exact roles of ERUS and MRI will depend on availability of local expertise, although it is suggested that the techniques are complementary.

Hepatic haemangioma masquerading as the gallbladder in a case of gallbladder agenesis: a case report and literature review.

Gallbladder agenesis is uncommon. In contrast, liver haemangiomas are the most common type of benign liver lesions. We describe the first documented case of gallbladder agenesis where the clinical presentation was consistent with biliary colic, and radiological investigation suggested the presence of gallstones. Subsequent operative findings revealed a solitary haemangioma of the liver sited in the normal position of the gallbladder fossa but with absence of the gallbladder. It is important that clinicians should keep gallbladder agenesis in mind when the gallbladder appears abnormal on preoperative imaging studies and cannot be found at laparoscopy. As symptoms will improve in 98% of cases, it is very important to avoid unnecessary intervention in patients who have a negative laparoscopy. The clinical presentation, investigations, and operative findings are discussed with a review of other relevant reported cases in the literature.