Assessing lymphatic drainage of the normal splenic flexure by single-photon emission computerised tomography (SPECT) technology – A feasibility study

This is a research study looking to better understand how a specific portion of the colon functions. The aim of the study is to see how the colon situated in the left upper quarter of the abdomen, near the spleen (i.e., splenic flexure), manages to drain its tissue fluid (i.e., lymph). So far, lymphatic drainage of this part of the colon remains incompletely understood. The study is being conducted within the Department of Colorectal Surgery at Concord Hospital, Sydney Local Health District (SLHD) by Dr Krishanth Naidu, under the supervision of A/Prof Matthew Rickard, A/Prof Robert Russo and Dr Kheng-Seong Ng. A Participant Information Sheet (PIS) will inform participants about what is involved in the study and help them decide whether they wish to take part. 2. Study Procedures The study procedure will take place within the Concord Repatriation General Hospital. Participants will be included into the study only if they have a normal colonoscopy. During the test Part 1 Once a normal colonoscopy is performed (standard of care), the area of interest (i.e., splenic flexure) is explored (research component). A special tracer (described below) is placed using the scope to trace the lymphatics. Part 2 Single photon-emission computed tomography (SPECT) is a test that uses a special type of camera and a tracer (a radioactive substance in liquid form) to look at organs in the body. With this study, the tracer is injected into a small portion of the participant's colon that we are interested in (close to the spleen) to trace the lymph flow of the region. After that, in the Nuclear Medicine Department, a special camera records where the tracer has moved to. As part of the SPECT, participants are required to lie still in a scanner for at least 30 minutes. After the SPECT scan, participants will complete their recovery, if indicated, and subsequently discharged home. Participants are advised not to drive or operate heavy machinery after their colonoscopy. A follow-up phone call will be made at 1,7 and 30 days from SPECT to understand how participants are going. This will be in the form of a very brief telephone questionnaire. After the test Most of the radioactive tracer leaves the body through the urine within a few hours after the SPECT scan. We advise participants to drink more fluids, after the SPECT scan to help flush the tracer from the body. The body breaks down the remaining tracer over the next few days. Before the test No extra preparation is required before the SPECT. It is important that women participating in this study are not pregnant, breast-feeding or directly caring for young children (<5years old). Woman of child-bearing potential, may be required to perform a pregnancy (urine) test before enrolment in the study. Time commitment The total time commitment for this study is approximately 4 hours, not including the follow-up phone calls. Participants agreeing to participate in this study, you will be directed to an online platform for completion of an electronic consent (e-consent) prior to participating. Future use of non-identifiable information may be used for research purposes. In this instance approval from the relevant Human Research Ethics Committee is required to access it and any identifiable data. Description of intervention 1. Details of the colonoscopy: A. As a standard of care, a complete colonoscopy (to investigate presenting symptoms/signs) is performed prior to dedicated interrogation of the splenic flexure (SF) with submucosal radio tracer. If lesions are noted that require biopsy, tattooing, clipping or other intervention, the participant is excluded from the study. B. The standard of care colonoscopy will be performed by the treating clinician. C. The apex of the SF is defined as the highest and most angulated point of the colon between the transverse colon and the descending colon, assessed visually by the investigator. This is further supported with a visual aid by way of a scope guide that defines the real time position of the scope. A Bluetooth® link is established between the scope guide transducer in the endoscope and the receiving screen. Furthermore, the architecture of the transverse colon compared to the descending and ascending colon, adds to localisation of the SF. 2. Radio tracer placement A. Technetium-99 (Tc-99m) is reconstituted in the Nuclear Medicine Department with a nano colloid – Nanoscan (Media Radiopharma, Hungary). A Nanoscan vial contains 500mcg of nano colloidal human albumin. This is reconstituted with sodium pertechnetate (Tc-99m) solution for submucosal injection. 40MBq of Tc-99m reconstituted to 0.5ml will be injected. At colonoscopy Tc-99m nano-colloid will be injected through the standard colonoscopic working port. B. A 23gauge (0.6mm diameter) 5mm Carr-Locke injection needle (Steris Endoscopy, Device Technologies, USA) is used for instillation of the radio isotope. This needle has automatic retraction technology to limit inadvertent needle stick and spillage. This needle is housed within a 2.5mm diameter sheath. The needle is attached to a 2300mm long conduit with a fixed volume of 1.38ml. This is important as it acknowledges not only the volume of tracer to be used for luminal priming but the volume of 0.9% NaCl follow-through required following tracer administration to optimise tracer delivery and deposition. C. 0.5ml of Tc-99m nano colloid reconstituted into 1.4mls is to be injected in the submucosal plane. Injection of this volume should not impede lymphatic flow. D. After endoscopic SF localization, correct needle placement is confirmed by raising a submucosal bleb with Tc-99m directly followed by injection of the remainder of the Tc-99m. The system is flushed with 1.4 mL NaCl 0.9% post Tc-99m instillation to achieve maximal tracer administration and limit colonoscope radioactivity. E. Crucially, the time of injection is recorded. F. Injection of Tc-99m following localisation of the SF at the completion of the standard of care colonoscopy will add further 10 mins to the procedure time of approximately 30 minutes. G. The tracer will be injected by Dr Krishanth Naidu. H. A resolution clip is deployed at the site of infiltration as a further marker of SF identification on radiographic imaging. 3. Post- radio tracer placement A. The participant is nursed within the confines of the endoscopy or operating theatre recovery suite with appropriate recovery precautions. Note is also made of reaction symptoms and signs, if any. B. The nuclear medicine imaging suite is notified of the participants post-injection status. C. The participant is suitably recovered prior to being transferred to the imaging suite for the SPECT-CT scan. D. The colonoscope is submitted for appropriate cleaning and sterilization. 4. Details of SPECT-CT imaging: A. Imaging acquisition at 1 hour following Tc-99m administration is aimed for. B. Participant is assisted across to the gamma scanner bed C. Time immediately prior to the commencement of the scan is recorded. D. Dosage and radioactivity of Tc-99m is recorded in the SPECT-CT report. E. The SPECT-CT scan will be performed under the direction of A/Prof Rob Russo ( Nuclear Medicine Physician). 5. Conclusion of visit A. At the conclusion of the scan, participants are discharged to their residences, in accordance with standard post-endoscopic recovery and nuclear medicine protocol. B. Formal discharge from the hospital is from the Nuclear Medicine Department. This will mirror the standard discussion plans and discussions had with a patient who has had a diagnostic scintigraphy procedure within the department. The CI (Krishanth Naidu) will be in attendance all the way through the participant’s journey to address any questions. C. Approximately 6 hours after the injection, the radioactive tracer will be nearly all removed from your body. We would advise against caring for young children within 6 hours of the radiotracer injection. No other restrictions are necessary following discharge. D. An investigator review (Dr Krishanth Naidu) via a follow-up phone call on Day 1, 7 and 30 from SPECT-CT completion is planned. This is to assess for delayed post-colonoscopy complications and adverse reactions. It also establishes further rapport with the research team and allows the opportunity to address concerns or issues faced by participant through the stages of participation.