Exploring methods of improving patient understanding and communication in a complex anal fistula clinic: results from a randomized controlled feasibility study.

AIM: Patient understanding of disease can guide decision-making in the management of anal fistula. This prospective feasibility study aimed to assess the acceptability and methods of assessing the impact of viewing realistic models on patients with anal fistula. METHODS: New referrals to a tertiary clinic participated in this single-centre, parallel-group randomized controlled study. Baseline characteristics, Decisional Conflict Scale and understanding of disease were assessed pre-consultation. Participants were randomized to a standard consultation, where disease and treatment options were explained using magnetic resonance images and drawn diagrams, or a similar consultation supplemented with an appropriate generic three-dimensional (3D) printed model. Understanding of disease and proposed surgery, Decisional Conflict Scale and ratings of visual aids were assessed post-consultation, along with 3D model feedback. RESULTS: All 52 patients who were approached agreed to be randomized (25 standard, 27 3D consultation). Understanding of disease increased post-consultation in both groups. Post-consultation decisional conflict (0, no; 100, high decisional conflict) was low (median 27 post-standard vs. 24 post-3D consultation). Patients scored highly on measures assessing understanding of proposed surgery. 3D models were rated highly, with 96% of patients wanting to see them again in future consultations. CONCLUSIONS: Three-dimensional printed fistula models are a welcome addition to outpatient consultations with results suggesting that understanding of surgery is improved. A future trial should be powered to detect whether 3D models result in a significant improvement in understanding beyond traditional methods of explanation and explore the conditions in which models have their maximal utility. GOV REGISTRATION ID: This study was registered on ClinicalTrials.gov (ID: NCT04069728). Registered on 23 August 2019.

Long-term outcomes of pouch surveillance and risk of neoplasia in familial adenomatous polyposis.

BACKGROUND: Long-term pouch surveillance outcomes for familial adenomatous polyposis (FAP) are unknown. We aimed to quantify surveillance outcomes and to determine which of selected possible predictive factors are associated with pouch dysplasia. METHODS: Retrospective analysis of collected data on 249 patients was performed, analyzing potential risk factors for the development of adenomas or advanced lesions ( ≥ 10 mm/high grade dysplasia (HGD)/cancer) in the pouch body and cuff using Cox proportional hazards models. Kaplan-Meier analyses included landmark time-point analyses at 10 years after surgery to predict the future risk of advanced lesions. RESULTS: Of 249 patients, 76 % developed at least one pouch body adenoma, with 16 % developing an advanced pouch body lesion; 18 % developed an advanced cuff lesion. Kaplan-Meier analysis showed a 10-year lag before most advanced lesions developed; cumulative incidence of 2.8 % and 6.4 % at 10 years in the pouch body and cuff, respectively. Landmark analysis suggested the presence of adenomas prior to the 10-year point was associated with subsequent development of advanced lesions in the pouch body (hazard ratio [HR] 4.8, 95 %CI 1.6-14.1; P = 0.004) and cuff (HR 6.8, 95 %CI 2.5-18.3; P < 0.001). There were two HGD and four cancer cases in the cuff and one pouch body cancer; all cases of cancer/HGD that had prior surveillance were preceded by ≥ 10-mm adenomas. CONCLUSIONS: Pouch adenoma progression is slow and most advanced lesions occur after 10 years. HGD and cancer were rare events. Pouch phenotype in the first decade is associated with the future risk of developing advanced lesions and may guide personalized surveillance beyond 10 years.

The Middle Rectal Artery: Revisited Anatomy and Surgical Implications of a Neglected Blood Vessel.

BACKGROUND: Although the middle rectal artery is a relevant anatomical landmark for rectal resection and lateral lymph node dissection, descriptions of this entity are highly divergent. OBJECTIVE: Dissection, visualization, morphometry, and 3-dimensional reconstruction of the middle rectal artery to facilitate its management in surgery. DESIGN: Macroscopic dissection, histologic study, morphometric measurements, and virtual modeling. SETTING: University laboratory of applied surgical anatomy. PATIENTS: This study includes formalin-fixed hemipelvis specimens (n=37) obtained from body donors (age, 67-97 y). MAIN OUTCOME MEASURES: The main outcome measures are photo documentation of origin, trajectory, diameter, and branching pattern; immunolabeling of lymphatics; and 3-dimensional reconstruction of the middle rectal artery. RESULTS: The middle rectal artery was present in 71.4% of body donors (21.4% bilateral, 50% unilateral), originated from the anterior division of the internal iliac artery, and branched either from the internal pudendal artery (45.5%), the inferior gluteal artery (22.7%), the gluteal-pudendal trunk (22.7%), or a trifurcation (9.1%). One to 3 branches of varying diameters (0.5-3.5 mm) entered the mesorectum from the ventrolateral (35.7%), lateral (42.9%), or dorsolateral (21.4%) aspect. The middle rectal artery was accompanied by podoplanin-immunoreactive lymphatic vessels and gave off additional branches (81.8%) to the urogenital pelvic organs. Three-dimensional reconstruction revealed the complex course of the middle rectal artery from the pelvic sidewall through the pelvic nerve plexus and parietal pelvic fascia into the mesorectum. LIMITATIONS: Findings retrieved from body donors may be prone to age- and fixation-related processes. CONCLUSIONS: The investigation disclosed the rather high prevalence of the middle rectal artery, its 3-dimensional topographic anatomy, and its proximity to the autonomic pelvic nerves. These features play a role in the surgical management of this blood vessel. The data provide the anatomical rationale for the lateral lymphatic spread of rectal cancer and an anatomical basis for nerve-preserving lateral lymph node dissection.

Differential sensing with arrays of de novo designed peptide assemblies.

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings.

The retrocolic fascial system revisited for right hemicolectomy with complete mesocolic excision based on anatomical terminology: do we need the eponyms Toldt, Gerota, Fredet and Treitz?

AIM: Right hemicolectomy with complete mesocolic excision (CME) requires the removal of an intact mesocolic envelope. The study aimed to determine, on the basis of macroscopic and microscopic anatomical studies, the optimal surgical dissection planes for CME to preserve fascial integrity. Unequivocal anatomical nomenclature was applied to describe the retrocolic fascial system and compared to frequently used eponyms (Toldt, Gerota, Fredet, Treitz). METHOD: Stepwise macroscopic dissections, cross-section studies and histological analysis were performed on body donors to identify the components of the retrocolic fascial system. Based on these anatomical findings, the optimal surgical dissection planes for CME were validated in laparoscopic training courses on body donors and in robot-assisted surgical procedures in patients. RESULTS: The mesocolic tissue and lymphovascular pedicles were enveloped by the ventral and dorsal mesocolic leaf (mesocolic fascia). The mesocolic fascia was attached to the parietal peritoneal fascia ('fascia of Toldt') along the parieto-mesocolic interface, and further cranially to the pre-duodenopancreatic fascia along the mesocolic-duodenopancreatic interface ('space of Fredet'). Dorsally, the parietal peritoneal fascia was separated from the anterior renal fascia ('fascia of Gerota') by the parieto-renal interface. Dissection along this interface in front of the anterior renal fascia followed by incision of the parietal peritoneal fascia at the duodenal border and opening the mesocolic-duodenopancreatic interface yielded the best macroscopic appearance of specimens and was considered optimal for CME. CONCLUSION: The retrocolic fascial system as well as the surgical dissection planes for CME can be described by clearly defined anatomical terms rather than potentially confusing eponyms.

The Mesentery in Complete Mesocolic Excision.

The following article summarizes technical aspects of how to operate in the mesentery during complete mesocolic excision (CME). Increasingly, CME is being adopted and as such it is important to establish the anatomical basis of the techniques involved. This review thus serves to provide that foundation and explains the surgical techniques built on it.

Methods and Applications of 3D Patient-Specific Virtual Reconstructions in Surgery.

3D modelling has been highlighted as one of the key digital technologies likely to impact surgical practice in the next decade. 3D virtual models are reconstructed using traditional 2D imaging data through either direct volume or indirect surface rendering. One of the principal benefits of 3D visualisation in surgery relates to improved anatomical understanding-particularly in cases involving highly variable complex structures or where precision is required.Workflows begin with imaging segmentation which is a key step in 3D reconstruction and is defined as the process of identifying and delineating structures of interest. Fully automated segmentation will be essential if 3D visualisation is to be feasibly incorporated into routine clinical workflows; however, most algorithmic solutions remain incomplete. 3D models must undergo a range of processing steps prior to visualisation, which typically include smoothing, decimation and colourization. Models used for illustrative purposes may undergo more advanced processing such as UV unwrapping, retopology and PBR texture mapping.Clinical applications are wide ranging and vary significantly between specialities. Beyond pure anatomical visualisation, 3D modelling offers new methods of interacting with imaging data; enabling patient-specific simulations/rehearsal, Computer-Aided Design (CAD) of custom implants/cutting guides and serves as the substrate for augmented reality (AR) enhanced navigation.3D may enable faster, safer surgery with reduced errors and complications, ultimately resulting in improved patient outcomes. However, the relative effectiveness of 3D visualisation remains poorly understood. Future research is needed to not only define the ideal application, specific user and optimal interface/platform for interacting with models but also identify means by which we can systematically evaluate the efficacy of 3D modelling in surgery.

The impact of three-dimensional reconstruction and standardised CT interpretation (AMIGO) on the anatomical understanding of mesenteric vascular anatomy for planning complete mesocolic excision surgery: A randomised crossover study.

BACKGROUND: Preoperative planning is a crucial aspect of safe complete mesocolic excision (CME) surgery. 3D models derived from imaging may help improve anatomical understanding of the complex vascular anatomy. Here, we assessed the effect of 3D models on surgeons' anatomical understanding in comparison to a systematic approach for CT scan interpretation (AMIGO). METHOD: Fifteen cases were included in the study. Two GI radiology consultants reviewed each scan to ascertain the vascular anatomy. Virtual 3D models were produced and displayed on a web-based platform (https://skfb.ly/6OZUZ). A total of 13 surgical trainees were recruited. Candidates were assessed after baseline anatomical training and subsequently using the AMIGO method and 3D models. Five cases were randomly allocated in each round of testing for each participant. The primary outcome measure was an objective vascular anatomy knowledge score. The secondary outcome measure was subjective feedback from participants. RESULTS: Both 3D and AMIGO significantly improved anatomical understanding in comparison to baseline testing. However, 3D was superior to AMIGO (3D [n = 65; median score 8/14] vs. AMIGO [n = 65; median score 6/14; p < 0.0001]. For 13/15 patient cases examined, 3D was superior to the AMIGO method. Eleven participants demonstrated better anatomical understanding using 3D models versus AMIGO. Ten participants preferred 3D models in comparison to standard CT imaging. CONCLUSIONS: 3D models improve anatomical understanding of mesenteric vascular anatomy in a group of colorectal surgical trainees in comparison to a formal CT interpretation method. 3D models may be a useful planning adjunct to 2D imaging for CME surgery.

Evolution of the management of retrorectal masses: A retrospective cohort study.

AIM: Retrorectal masses are abnormalities located anatomically in the retrorectal space. A significant proportion are asymptomatic with no malignant potential while others cause symptoms due to mechanical pressure or malignant infiltration. We reviewed and categorised the retrorectal masses encountered over a 30-year time period in a specialist colorectal hospital and describe our management algorithm for consideration by other multidisciplinary teams (MDT). METHODS: This was a retrospective analysis of consecutive patients referred between 1984-2019. A detailed review of clinical presentation, imaging features, postoperative histology and impact on morbidity and anorectal function is reported. RESULTS: A total of 143 patients with median age of 46 years and female preponderance (74%) were reviewed. The commonest presenting symptom was pain (46%) and all malignant cases had symptoms (n = 17). Over the last decade, more asymptomatic patients have presented with a retrorectal mass (33%, p = 0.04) and more patients are opting for surveillance rather than resection (33%, p = 0.013). Increasing age and lesion size were associated with malignancy (p < 0.05). Radiological features associated with malignancy included: solid/heterogeneous component, lobulated borders or locally invasive. Following surgery, complications included chronic pain (40%), poor wound healing (23%) and bowel dysfunction (10%). CONCLUSIONS: The management of retrorectal masses remains complex. There are features, both clinical and radiological, that can help determine the best management strategy. Management should be in a high-volume tertiary centre and preferably through a complex rectal cancer MDT. Long-term sequelae such as chronic pain must be highlighted to patients. We advocate the establishment of an international registry to further record and characterise these rare, potentially troublesome lesions.

De novo design of a reversible phosphorylation-dependent switch for membrane targeting.

Modules that switch protein-protein interactions on and off are essential to develop synthetic biology; for example, to construct orthogonal signaling pathways, to control artificial protein structures dynamically, and for protein localization in cells or protocells. In nature, the E. coli MinCDE system couples nucleotide-dependent switching of MinD dimerization to membrane targeting to trigger spatiotemporal pattern formation. Here we present a de novo peptide-based molecular switch that toggles reversibly between monomer and dimer in response to phosphorylation and dephosphorylation. In combination with other modules, we construct fusion proteins that couple switching to lipid-membrane targeting by: (i) tethering a 'cargo' molecule reversibly to a permanent membrane 'anchor'; and (ii) creating a 'membrane-avidity switch' that mimics the MinD system but operates by reversible phosphorylation. These minimal, de novo molecular switches have potential applications for introducing dynamic processes into designed and engineered proteins to augment functions in living cells and add functionality to protocells.

Current and future role of three-dimensional modelling technology in rectal cancer surgery: A systematic review.

BACKGROUND: Three-dimensional (3D) modelling technology translates the patient-specific anatomical information derived from two-dimensional radiological images into virtual or physical 3D models, which more closely resemble the complex environment encountered during surgery. It has been successfully applied to surgical planning and navigation, as well as surgical training and patient education in several surgical specialties, but its uptake lags behind in colorectal surgery. Rectal cancer surgery poses specific challenges due to the complex anatomy of the pelvis, which is difficult to comprehend and visualise. AIM: To review the current and emerging applications of the 3D models, both virtual and physical, in rectal cancer surgery. METHODS: Medline/PubMed, Embase and Scopus databases were searched using the keywords "rectal surgery", "colorectal surgery", "three-dimensional", "3D", "modelling", "3D printing", "surgical planning", "surgical navigation", "surgical education", "patient education" to identify the eligible full-text studies published in English between 2001 and 2020. Reference list from each article was manually reviewed to identify additional relevant papers. The conference abstracts, animal and cadaveric studies and studies describing 3D pelvimetry or radiotherapy planning were excluded. Data were extracted from the retrieved manuscripts and summarised in a descriptive way. The manuscript was prepared and revised in accordance with PRISMA 2009 checklist. RESULTS: Sixteen studies, including 9 feasibility studies, were included in the systematic review. The studies were classified into four categories: feasibility of the use of 3D modelling technology in rectal cancer surgery, preoperative planning and intraoperative navigation, surgical education and surgical device design. Thirteen studies used virtual models, one 3D printed model and 2 both types of models. The construction of virtual and physical models depicting the normal pelvic anatomy and rectal cancer, was shown to be feasible. Within the clinical context, 3D models were used to identify vascular anomalies, for surgical planning and navigation in lateral pelvic wall lymph node dissection and in management of recurrent rectal cancer. Both physical and virtual 3D models were found to be valuable in surgical education, with a preference for 3D printed models. The main limitations of the current technology identified in the studies were related to the restrictions of the segmentation process and the lack of 3D printing materials that could mimic the soft and deformable tissues. CONCLUSION: 3D modelling technology has potential to be utilised in multiple aspects of rectal cancer surgery, however, it is still at the experimental stage of application in this setting.

Bioinspired Silicification Reveals Structural Detail in Self-Assembled Peptide Cages.

Understanding how molecules in self-assembled soft-matter nanostructures are organized is essential for improving the design of next-generation nanomaterials. Imaging these assemblies can be challenging and usually requires processing, e.g., staining or embedding, which can damage or obscure features. An alternative is to use bioinspired mineralization, mimicking how certain organisms use biomolecules to template mineral formation. Previously, we have reported the design and characterization of Self-Assembled peptide caGEs (SAGEs) formed from de novo peptide building blocks. In SAGEs, two complementary, 3-fold symmetric, peptide hubs combine to form a hexagonal lattice, which curves and closes to form SAGE nanoparticles. As hexagons alone cannot tile onto spheres, the network must also incorporate nonhexagonal shapes. While the hexagonal ultrastructure of the SAGEs has been imaged, these defects have not been observed. Here, we show that positively charged SAGEs biotemplate a thin, protective silica coating. Electron microscopy shows that these SiO2-SAGEs do not collapse, but maintain their 3D shape when dried. Atomic force microscopy reveals a network of hexagonal and irregular features on the SiO2-SAGE surface. The dimensions of these (7.2 nm ± 1.4 nm across, internal angles 119.8° ± 26.1°) are in accord with the designed SAGE network and with coarse-grained modeling of the SAGE assembly. The SiO2-SAGEs are permeable to small molecules (<2 nm), but not to larger biomolecules (>6 nm). Thus, bioinspired silicification offers a mild technique that preserves soft-matter nanoparticles for imaging, revealing structural details <10 nm in size, while also maintaining desirable properties, such as permeability to small molecules.