Ode to the Submucosal Fluid Cushion

Having the opportunity to prepare an editorial for this journal is both a privilege and a challenge to wax philosophic and critical on a subject of intense but focal interest. This present opportunity not only fulfills these notions, but adds an ever so subtle element of incredulity over the subject of this editorial, the submucosal fluid cushion, or as I have fondly become accustomed to referring to it as the SFC. In this moment, as I am unleashed from my daily duties and sitting quietly in the still of the evening, my thoughts on the SFC could well be assembled as an ode to this subject. I should perhaps spare you the pain.

In the present issue of Endoscopy, Fujishiro and colleagues report the results of a study comparing the various injection solutions that can be used to produce submucosal fluid cushions (SFCs) during endoscopic mucosal resection (EMR) in the stomach [1]. In contrast to their other study in this issue [2], the project was based on testing various fluids in ex-vivo sections of porcine gastric wall. Although convenient, the use of ex-vivo tissue has the disadvantage that the time it takes for the SFCs to resolve is unnaturally prolonged - as we also found some time ago when attempting to identify the ideal injection solution for producing SFCs [3] [4]. This criticism is minor. The authors’ findings emphasize one point of absolute clarity for those in search of the perfect SFC - substrate density! The greater the density of the SFC, the longer it will remain in situ and allow an EMR procedure of any extent to be performed. Hypertonicity may have a role in living perfused tissues, but in the ex-vivo model, density and viscosity prevail.

The importance of these findings lies in the fact that EMR is not a procedure reserved only for Japanese endoscopists looking for effective ways of managing early cancers, particularly in the stomach; nor should it be a procedure exclusively used by a few adventurous Western endoscopists. EMR is a practical method for precise tissue excision. In Western medicine, the procedure has become a popular topic in many postgraduate courses, but in fact it is only practiced by a few. This is because there are very few indications for it. The two most common indications are removal of sessile polyps and excision of focal dysplasia in Barrett’s esophagus.

The main reason why only a few endoscopists carry out EMR procedures is the fear of causing perforation. However, the risks of perforation and bleeding can easily be overcome by injecting a long-lasting, highly dense fluid solution to create an SFC. A long-lasting SFC is a guarantee of safe excision of mucosal tissues. The study by Fujishiro et al. [1] again shows the clear advantage provided by the densest of the injection solutions tested. Hyaluronic acid is an ideal injection solution, but it is not the most convenient or the most economical to use. The substance is available from several sources, such as rooster comb. It has special storage requirements and has to be reconstituted before use. Other, less dense solutions are also available, such as glycerin-based solutions and hypertonic solutions. These have measurable advantages over saline, but do not provide the performance of hyaluronic acid.

Safety is not just a function of the viscosity or density of the SFC. An SFC that lasts for a very long time makes it possible to carry out an EMR slowly and meticulously without the distractions of having to reinject additional material multiple times during a lengthy excision. A fluid cushion created by injecting hyaluronic acid (in our own practice, we use hydroxypropyl methylcellulose) should last at least 30 min or more. In our own experience, hydroxypropyl methylcellulose (HPMC) provides performance characteristics equivalent to those of hyaluronic acid and offers the advantages of ready access, no special storage requirements, and low cost [4]. Carrying out extensive excisions with shorter-acting SFCs involves the risk that a point may be reached during the procedure when the SFC has largely dissipated. This is the point at which there is a substantially increased risk in the EMR procedure. The risk can only be reduced by interrupting the procedure to inject more fluid - the major reason why this extra step is often not performed. It is possible to overcome this problem by simply injecting a very large amount of any solution at the start of the procedure.

There are sufficient data to support the universal use of the longest-lasting injection solution commercially available, as a standard of practice. Alternatively, a solution can be selected on the basis of the estimated time needed to carry out an EMR procedure, either for reasons of technical complexity (e. g., an unusual anatomic situation, with access difficulty and added procedure time) or the size of the lesion. In small lesions (≤ 2 cm in diameter) and simple EMRs, injection of a saline solution can be carried out, which provides the shortest duration of the SFC (2 min in the in-vivo porcine model). Intermediate complexity and medium-sized lesions may benefit from solutions such as 50 % dextrose and 10 % glycerin (providing a 4-min cushion in the in-vivo porcine model). Complex, time-consuming cases, large lesions (≥ 4 cm), and widespread EMRs may require the longest-lasting solutions (30 min in the in-vivo porcine model) [5].

In my opinion, the ideal injection solution for creating submucosal fluid cushions has yet to be identified. A fluid’s density is typically proportional to its viscosity. Highly viscous solutions can be difficult to inject, requiring more expensive and better-engineered needle catheters with larger inner diameters, and may require pressure-controlled syringes - factors that all stand in the way of widespread use of hyaluronic acid, HPMC, or comparable alternative solutions. Materials whose potential has yet to be investigated include polymers, particle-based solutions and slurries, plant extracts, and starches. Specific attributes that a future ideal submucosal injection solution would need to have would be:

Inexpensive Nontoxic Readily obtainable in bulk Storable at room temperature Not requiring any mixing other than dilution Highly fluid outside of the body Easily injected through any standard needle catheter Almost impenetrable when in place.

In addition, it might be more appropriate to modify the terminology and replace the term ”submucosal fluid cushion” with ”submucosal barrier.” It will surely be possible to identify an injection solution for use in endoscopic mucosal resection that meets the above requirements, and we can look forward to further studies on the topic.

As for the ode:

Oh, were I to see, an SFC
Through toil and drudgery
That would brighten sun, moon, and star
For any one to perform EMR
I would sing its praise
And shout for joy
That we have found
The ideal toy!

References

• 1 Fujishiro M, Yahagi N, Kashimura K. et al . Comparison of various submucosal injection solutions for maintaining mucosal elevation during endoscopic mucosal resection.  Endoscopy. 2004;  36 579-583
• 2 Fujishiro M, Yahagi N, Kashimura K. et al . Different mixtures of sodium hyaluronate and their ability to create submucosal fluid cushions for endoscopic mucosal resection.  Endoscopy. 2004;  36 584-589
• 3 Conio M, Rajan E, Sorbi D. et al . Comparative performance in the porcine esophagus of different solutions used for submucosal injection.  Gastrointest Endosc. 2002;  56 513-516
• 4 Feitoza A B, Gostout C J, Burgart L J. et al . Hydroxypropyl methylcellulose: a better submucosal fluid cushion for endoscopic mucosal resection.  Gastrointest Endosc. 2003;  57 41-47
• 5 Rajan E, Gostout C J. Future developments of endoscopic mucosal resection: techniques and devices.  Tech Gastrointest Endosc. 2002;  4 51-55