Background: The "watch and wait" (W&W) strategy for rectal cancer offers organ preservation to patients achieving aclinical complete response (cCR) after neoadjuvant therapy. While oncologically safe, its adoption across the UK varies drastically due to non-standardised pathways, a lack of structured training, and clinician anxiety regarding local regrowth. With the rise of Total Neoadjuvant Treatment (TNT) and NICE-approved contact brachytherapy (Papillon), a shift toward "intentional" organ preservation is projected to exponentially increase service demands on multidisciplinary teams (MDTs). Aim: This protocol outlines the development of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) Position Statement. The initiative aims to mitigate MDT hesitation, standardise clinical pathways, and optimise the delivery of W&W care across the UK and Ireland. Methods: A 30-member multidisciplinary Task Force—comprising colorectal surgeons, oncologists, radiologists, trainees, andpatients—will undertake a rapid, single-round Delphi consensus process. The panel will evaluate approximately 30 statements spanning eight core domains, including response timing, endpoint definitions, service organisation, training, and follow-up. Consensus is defined as 70% or greater agreement, with any remaining disparities resolved via virtual nominal group meetings. Scope and Significance: The position statement focuses strictly on the clinical implementation of W&W following a cCR. Excluded from the scope are near-cCR management, salvage surgery, and trial frameworks. Scheduled for publication in mid-2026, this statement will provide a crucial framework to guide MDTs through an emerging clinical paradigm shift, with the aim of improving patient selection and resource allocation.

BACKGROUND:Locally advanced rectal cancer is routinely treated with neoadjuvant radiotherapy. Concomitant systemic anticancer therapy with standard fluoropyrimidines has not generally improved outcomes. Small studies reported high pathological complete response rates and acceptable toxicity using irinotecan and fluoropyrimidine chemoradiation. We aimed to explore the effect of the addition of concomitant irinotecan to standard-of-care chemoradiotherapy in patients with locally advanced rectal cancer. METHODS:ARISTOTLE is a multicentre, open-label, parallel-design, phase 3, randomised controlled trial conducted at 75 UK hospital sites treating patients with rectal cancer. Patients were eligible if they were aged at least 18 years with MRI-defined, locally advanced rectal cancer threatening or involving resection margins without metastases. Patients were randomly assigned (1:1) to preoperative radiotherapy 45 Gy in 25 daily fractions, combined with either oral capecitabine 900 mg/m2 alone twice daily on weekdays (standard-of-care group) or oral capecitabine 650 mg/m2 twice daily on weekdays plus intravenous irinotecan 60 mg/m2 once weekly in weeks 1-4 (irinotecan group). Randomisation was done centrally, with allocation concealed to investigators; masking of patients and treating clinicians was not feasible. Stratification was by radiotherapy centre, mesorectal fascia involvement, and presence or absence of equivocal metastatic disease. The primary endpoint was disease-free survival, with analysis done on a modified intention-to-treat basis (ie, all eligible patients who were randomly assigned to treatment). Safety analyses were conducted in all patients who started protocol treatment (as-treated population). For time-to-event endpoints, patients without an event were censored at the date they were last known to be alive; missing radiological and pathological response assessments were classified as non-response. The study is registered with EudraCT, 2008-005782-59, and is complete. FINDINGS:Between Oct 25, 2011, and July 5, 2018, 589 patients were randomly assigned to treatment; after exclusions, 564 were included in the modified intention-to-treat population (284 in the standard-of-care group and 280 in the irinotecan group). 370 (66%) patients were male, 194 (34%) were female, and median age was 61 years (IQR 54-68); ethnicity data were not collected. Staging in both groups was similar: 223 (79%) patients in the standard-of-care group and 212 (76%) in the irinotecan group had mrT3 tumours; 44 (15%) and 45 (16%) had mrT4 tumours, respectively. Patients in the irinotecan group were less likely to receive 45 Gy radiotherapy than in the standard-of-care group (208 [75%] of 276 vs 251 [89%] of 283) or at least 90% of the planned capecitabine dose (187 [68%] of 276 vs 253 [89%] of 283). With a median follow-up was 78 months (95% CI 75-86), 36-month disease-free survival was 68% (95% CI 63-73) in the irinotecan group versus 67% (61-72) in the standard-of-care group (hazard ratio 0·91 [95% CI 0·68-1·23]; p=0·54). Deaths occurred in 88 (31%) patients in the irinotecan group and 92 (32%) in the standard-of-care group; rectal cancer was the leading cause, occurring in 59 (67%) patients in the irinotecan group and 67 (73%) in the standard-of-care group. There were five deaths related to protocol treatment: three in the irinotecan group (two had a thromboembolic event and one had multiorgan failure plus sepsis) and two in the standard-of-care group (one cardiac arrest and one febrile neutropenia). Grade 3 or worse were more frequent in patients receiving irinotecan than those receiving standard of care (215 [78%] vs 148 [52%]), including haematological investigations (235 [85%] vs 109 [39%]) and gastrointestinal events (57 [21%] vs 35 [12%]), notably diarrhoea (38 [14%] vs ten [4%]), lymphocyte count decreased (181 [66%] vs 100 [35%]), and neutrophil count decreased (27 [10%] vs three [1%]). INTERPRETATION:For MRI-defined, high-risk, locally advanced rectal cancer, the addition of irinotecan to standard of care did not improve outcomes and should not be used in combination with radiotherapy plus capecitabine. FUNDING:Cancer Research UK.

Abstract Total mesorectal excision (TME) is still the gold standard management for rectal cancer including most early-stage rectal cancer. In the UK 27% of TME operations are performed for non-irradiated T1 and T2 rectal tumours, however, morbidity from this surgery can be high, with patients experiencing bowel and sexual dysfunction and a reduced quality of life. Organ preservation aims to avoid radical surgery thereby reducing treatment related morbidity to improve patients’ quality of life. This is important especially in early asymptomatic rectal cancers and elderly comorbid patients. In this chapter, we will describe the platforms for local excision of early rectal cancers, consider patient selection and discuss the clinical and pathological outcomes of local excision without neoadjuvant therapy.

The use of interventions such as major liver and lung resection, radiofrequency ablation and transarterial chemoembolization in the management of metastatic colorectal cancer (mCRC) is now relatively commonplace in clinical practice. However, the evidence base regarding these treatments is limited with a lack of high-quality data from randomised controlled trials (RCTs). The aim of this study was to understand the challenges associated with conducting RCTs in advanced mCRC and to identify potential strategies to overcome them, with a view to improving trial design and delivery in this setting. A qualitative study was undertaken with professionals involved in mCRC trials. Participants were identified using trial registries to identify relevant trials. Individual semi-structured, in-depth qualitative interviews were undertaken online using a topic guide. The principles of thematic content analysis were used for data analysis. Twelve participants were recruited to the study from six trials; three of the trials had completed, two were either terminated or no longer recruiting and one was open to recruitment. Four major themes were identified, and themes were further subdivided to identify specific challenges and solutions to overcome them. The four themes identified were as follows: trial-related processes, organisational/structural challenges, trial design considerations, and stage IV (metastatic) colorectal cancer-specific factors. Significant challenges were described in relation to funding, ethical approval processes, equipoise, patient preferences, logistical issues in trial delivery, and the advanced nature of mCRC including disease progression and palliative care. There are a range of strategies which could be implemented to improve the delivery of future trials in this complex setting, from the initial development of a trial through to trial setup, recruitment and follow-up.

Robotic assisted surgery (RAS) has seen a global rise in adoption. Despite this, there is not a standardised training curricula nor a standardised measure of performance. We performed a systematic review across the surgical specialties in RAS and evaluated tools used to assess surgeons’ technical performance. Using the PRISMA 2020 guidelines, Pubmed, Embase and the Cochrane Library were searched systematically for full texts published on or after January 2020–January 2022. Observational studies and RCTs were included; review articles and systematic reviews were excluded. The papers’ quality and bias score were assessed using the Newcastle Ottawa Score for the observational studies and Cochrane Risk Tool for the RCTs. The initial search yielded 1189 papers of which 72 fit the eligibility criteria. 27 unique performance metrics were identified. Global assessments were the most common tool of assessment (n = 13); the most used was GEARS (Global Evaluative Assessment of Robotic Skills). 11 metrics (42

Indexing endoscopic surgical videos is vital in surgical data science, forming the basis for systematic retrospective analysis and clinical performance evaluation. Despite its significance, current video analytics rely on manual indexing, a time-consuming process. Advances in computer vision, particularly deep learning, offer automation potential, yet progress is limited by the lack of publicly available, densely annotated surgical datasets. To address this, we present TEMSET-24K, an open-source dataset comprising 24,306 trans-anal endoscopic microsurgery (TEMS) video micro-clips. Each clip is meticulously annotated by clinical experts using a novel hierarchical labeling taxonomy encompassing phase, task, and action triplets, capturing intricate surgical workflows. To validate this dataset, we benchmarked deep learning models, including transformer-based architectures. Our in silico evaluation demonstrates high accuracy (up to 0.99) and F1 scores (up to 0.99) for key phases like Setup and Suturing. The STALNet model, tested with ConvNeXt, ViT, and SWIN V2 encoders, consistently segmented well-represented phases. TEMSET-24K provides a critical benchmark, propelling state-of-the-art solutions in surgical data science.

Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826). Exploratory analyses were done with transcriptomic signatures for the endpoint of pathologic complete response (pCR), considering treatment regimen or CMS subtype. Relevant findings were tested for overall survival and recurrence-free survival. Immune and stromal signatures were strongly associated with pCR and lack of pCR, respectively, in RT and capecitabine (Cap)/5-fluorouracil (5FU)-treated patients (N = 387), in which the radiosensitivity signature (RSS) showed the strongest association. Upon addition of oxaliplatin (Ox; N = 123), stromal signatures switched direction and showed higher chances to achieve pCR than without Ox (p for interaction 0.02). Among Cap/5FU patients, most signatures performed similarly across CMS subtypes, except cytotoxic lymphocytes that were associated with pCR in CMS1 and CMS4 cases compared with other CMS subtypes (p for interaction 0.04). The only variables associated with survival were pCR and RSS. Although the frequency of pCR across different chemoradiation regimens is relatively similar, our data suggest that response rates may differ depending on the biological landscape of rectal cancer. Response to neoadjuvant RT in stroma-rich tumors may potentially be improved by the addition of Ox. RSS in preoperative biopsies provides predictive information for response specifically to neoadjuvant RT with 5FU. SIGNIFICANCE:Rectal cancers with stromal features may respond better to RT and 5FU/Cap with the addition of Ox. Within patients not treated with Ox, high levels of cytotoxic lymphocytes associate with response only in immune and stromal tumors. Our analyses provide biological insights about the outcome by different radiotherapy regimens in rectal cancer.

Abstract Introduction Despite the rise in use of RAS in UK surgical practice, concerns have been reported regarding the lack of standardisation in training. Little is known on the current exposure to RAS training in the UK and thoughts on how training should be delivered in the future. Methods Semi-structured interviews were completed in person/online with four stakeholder groups:(1) pan speciality surgical trainees; (2) robotic trainers; (3) leads in curriculum development; (4) RAS industry leads. Respondents were pan-speciality and from across the UK. Topic guides focussed on personal perspectives on RAS training, current barriers to accessing training and views on how RAS training can be optimally delivered in the future. Data collection ceased upon saturation in themes and were analysed thematically. Results Twenty-seven informants were interviewed, including 8 trainees, 7 curriculum developers, 6 robotic surgeons and 6 industry leads. Respondents reported multiple challenges in training including barriers to accessing the robot such as the geographical location of the systems; the consultant RAS learning needs; equality and diversity issues and challenges with delivering platform agnostic training. However, respondents reported an anticipated growth in RAS and a need for the surgical training bodies to invest in structured RAS training which should be implemented earlier in surgical training. Discussion RAS training in the UK requires overcoming several barriers to deliver equitable, standardised training. A further study is required to reach a consensus amongst stakeholders on how RAS should be delivered within the current infrastructure of both the UK health care system and surgical training climate.

RFS and OS outcomes in combined Grampian and GSE87211 cohorts (Cap+RT/5FU+RT subjects)

Introduction: Poor pain control after surgery is associated with chronic pain and opioid dependence. This study aimed to determine the incidence of patient reported pain control failure following gastrointestinal surgery, and to evaluate the impact of common preventative surgical and anaesthetic strategies. Methods: Data were extracted from an electronic health record that linked real-time, ward-based pain scores with prescribing data. Adults undergoing major elective gastrointestinal surgery in 2011-18 were included. The primary endpoint was early pain control failure (≥1 instances of moderate or severe pain on postoperative days 0-2). Secondary outcomes were late (postoperative days 3-5) and persistent (both early and late) pain control failure. Results: Of 2238 patients, half underwent planned open surgery (50.3%, 1126/2238). Patient controlled analgesia (PCA) was initially used in 49.7% (1113/2238) and epidural in 35.0% (784/2238). Early (54%, 1211/2238), late (33.7%, 755/2238), and persistent (24.9%, 557/2238) pain control failures occurred frequently. In multivariable analyses, minimally invasive surgery was associated with fewer early, late, and persistent pain control failures than open surgery. There was no association between initial epidural analgesia and early or persistent pain control failure, but there was an association with increased late failure (OR 1.37, 95% CI 1.08-1.73, p=0.009). Of patients with initial epidural analgesia, 39.3% (308/784) were subsequently converted to PCA. Conclusion: Epidural analgesia offered no advantage over PCA, with pain control failure common irrespective of analgesic strategy. Increasing the uptake of minimally invasive surgery, through medical advances to down-stage disease, may offer a path to effectively improve postoperative pain failure.

BACKGROUND: A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment. OBJECTIVE: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. DESIGN: A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI). SETTING: The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online. MAIN OUTCOME MEASURES: The main outcome was to reach consensus (80% or more agreement). RESULTS: The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response. LIMITATIONS: This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice. CONCLUSIONS: Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract. UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIÓN DE UNA RESPUESTA CLÍNICA CASI COMPLETA DESPUÉS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CÁNCER DE RECTO ANTECEDENTES: Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos. OBJETIVO: El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia. DISEÑO: Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI). AJUSTE: El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea. PRINCIPALES MEDIDAS DE RESULTADO: El resultado principal fue llegar a un consenso (≥80% de acuerdo). RESULTADOS: El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa. LIMITACIONES: Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica. CONCLUSIONES: Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción – Dr. Aurian Garcia Gonzalez)

BACKGROUND:Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig´s disease, is a rare neurological condition and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management by multidisciplinary clinics. PATIENTS AND METHODS:This prospective, single-arm, open-label phase II clinical trial of sustained weekly administration of 2 mg/kg ILB® (a low-molecular weight dextran sulphate) was conducted in a single UK hospital. Eligible patients were at least 18 years and had a definite diagnosis of ALS according to El Escorial Criteria. The co-primary outcomes were safety, tolerability, and quantity of ILB® administered. EudraCT number. 2018-000668-28. FINDINGS:Between 18-Apr-2019 and 27-Mar-2020, 11 patients were recruited and treated for up to 38 weeks. There were no treatment terminations or withdrawals. One serious adverse event was reported, which was not related to ILB® and resolved without sequalae. 270 mild/moderate adverse events were reported with no intolerable events occurring during the trial. The total number of ILB® treatments administered per patient ranged from 4 to 38, with a cumulative dose ranging from 745 to 6668 mg. As a result of the COVID-19 pandemic and the high-risk status of study participants, recruitment and treatment was suspended early in Mar-2020. At the long-term follow-up, three patients had died after the trial was halted, between 53 and 62 weeks after their final ILB® injection. INTERPRETATION:Long-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS. TRIAL REGISTRATION:EudraCT: 2018-000668-28. clinicaltrials.gov: NCT03705390. This trial adheres to the principles of GCP in the design, conduct, recording and reporting of clinical trials as listed in part 2, "Conditions and Principles which apply to all Clinical Trials" under the header "Principles based on Articles 2 to 5 of the EU GCP Directive" in the Medicines for Human Use Clinical Trials Regulations (as amended in SI 2006/1928). For clarity, the study did not conform to all aspects of the International Conference on Harmonisation (ICH) E6 R2 Guidelines for GCP (also known as 'ICH GCP'). Of note, we did not use an external database, perform 100% source data verification, and only primary outcome data were analysed in parallel by a second, independent statistician.

Robot-assisted surgery (RAS) continues to grow globally. Despite this, in the UK and Ireland, it is estimated that over 70% of surgical trainees across all specialities have no access to robot-assisted surgical training (RAST). This study aimed to provide educational stakeholders guidance on a pre-procedural core robotic surgery curriculum (PPCRC) from the perspective of the end user; the surgical trainee. The study was conducted in four Phases: P1: a steering group was formed to review current literature and summarise the evidence, P2: Pan-Specialty Trainee Panel Virtual Classroom Discussion, P3: Accelerated Delphi Process and P4: Formulation of Recommendations. Forty-three surgeons in training representing all surgical specialties and training levels contributed to the three round Delphi process. Additions to the second- and third-round surveys were formulated based on the answers and comments from previous rounds. Consensus opinion was defined as ≥ 80% agreement. There was 100% response from all three rounds. The resulting formulated guidance showed good internal consistency, with a Cronbach alpha of > 0.8. There was 97.7% agreement that a standardised PPCRC would be advantageous to training and that, independent of speciality, there should be a common approach (95.5% agreement). Consensus was reached in multiple areas: 1. Experience and Exposure, 2. Access and context, 3. Curriculum Components, 4 Target Groups and Delivery, 5. Objective Metrics, Benchmarking and Assessment. Using the Delphi methodology, we achieved multispecialty consensus among trainees to develop and reach content validation for the requirements and components of a PPCRC. This guidance will benefit from further validation following implementation.

Abstract Background Robotic-Assisted Surgery (RAS) has seen a global rise in the past 30 years. Despite the increased adoption, there is no current standardised training curricula or measure of performance. The aim of this systematic review was to define the RAS metrics used to assess technical performance across the surgical specialities. Methods Using the PRISMA 2020 guidelines, Pubmed, Embase and the Cochrane Library were searched systematically for full texts published 31st January 2020 – 31st January 2022. All randomised controlled trials (RCTs) and observational studies were considered. Review articles and systematic reviews were excluded. The papers’ quality and bias score were assessed using the Newcastle Ottawa Score for the observational studies and Cochrane Risk Tool for the RCTs. Results The initial search yielded 1189 papers of which 74 were eligible. The majority were published in urology (45% n=33). 27 unique metrics were identified and categorised as “task based”, “procedural based”, “cognitive assessments” and “global assessments”. Global assessments were the most common category of assessment (n=12); the most frequently used was GEARs (Global Evaluative Assessment of Robotic Skills). Only 4 metrics (automated, Proficiency Based Progression (PBP), pupillary measures and time to completion) used quantitative measures to assess performance whilst the remaining relied upon Likert scales thereby creating variability amongst users. Conclusion There is wide variation in tools used to assess performance in RAS. The majority of tools are subjective which increases the risk of bias amongst users and therefore accuracy in the measure of performance. A validated, objective global assessment tool that utilises quantitative measures is required.

Introduction Patients with liver disease and portal hypertension frequently require surgery carrying high morbidity and mortality. Accurately estimating surgical risk remains challenging despite improved medical and surgical management.Areas covered This review aims to outline a comprehensive approach to preoperative assessment, appraise methods used to predict surgical risk, and provide an up-to-date overview of outcomes for patients with cirrhosis undergoing non-hepatic surgery.Expert opinion Robust preoperative, individually tailored, and precise risk assessment can reduce peri- and postoperative complications in patients with cirrhosis. Established prognostic scores aid stratification, providing an estimation of postoperative mortality, albeit with limitations. VOCAL-Penn Risk Score may provide greater precision than established liver severity scores. Amelioration of portal hypertension in advance of surgery may be considered, with prospective data demonstrating hepatic venous pressure gradient as a promising surrogate marker of postoperative outcomes. Morbidity and mortality vary between types of surgery with further studies required in patients with more advanced liver disease. Patient-specific considerations and practicing precision medicine may allow for improved postoperative outcomes.

For a selected group of patients with very early rectal tumors (cT1N0, without adverse histopathological events) local excision may be an effective treatment option that reduces the risk of morbidity without jeopardizing long-term oncological outcomes.1,2 Patients with larger, but nonlocally advanced rectal cancer (cT1-3N0) are treated with total mesorectal excision (TME) alone, yielding 5-year overall survival rates >80% and local recurrence rates <5%.3,4 Although these excellent results are delivered with a single operation, the morbidity of this procedure can be substantial.