A market for gastric NOTES closure: which path should we take?

The new approach of natural-orifice transluminal endoscopic surgery (NOTES) has excited surgeons and gastroenterologists alike. Not only is the method of passing through the gut into the peritoneal cavity with a flexible endoscope exciting, but the development of the devices necessary to work in the newly conquered space is stimulating likewise. A NOTES incision closure device is one of the most important new developments to look forward to. It needs to be a very reliable tool since as soon as a potential iatrogenic complication has been created, a robust solution to fix it should be the first requirement. Some variations of many novel devices and techniques are described in this issue of Endoscopy [1].

A NOTES incision in many ways resembles any other fresh wound, incision, or perforation in need of closure, which can be achieved with sewing, sutures, clipping, stapling, glue, or in the easiest case with sticky tape such as Steri-Strips. However, the most common method of closing the edges of a wound or incision is surgical suturing. Sewing and stapling are as old as writing and can be tracked back for at least 4000 years. Archaeological records from ancient Egypt and India show the use of animal tendons to suture or the heads of beetles or ants to staple wounds. The live creatures were affixed to the edges of the wound to clamp it together with their pincers, after which the animals were cut off, leaving their jaws in place. In the 19th and early 20th centuries catgut suture was absorbable and made sterile to avoid frequent infection. By the late 1930s nylon and polyester were introduced, bringing further improvement. Today, there are many kinds of sutures with different properties suitable for a variety of uses.

So what are the novel requirements for closure of NOTES incisions? Flexible endoscopes provide little push-force and are equipped with only one or two parallel channel(s), making it impossible to work with two opposing arms – a crucial prerequisite for surgical sewing. Endoscopic sutured repair of a full-thickness lesion of the gut is therefore impossible, making accidental iatrogenic perforation one of the most feared complications of endoscopy. With the revolutionary introduction of NOTES, the deliberate incision of and through the gut wall made a means of closure necessary. Attempts have been made to overcome the single-handedness and lack of push-force of endoscopes in various ways. Current prototypes include sewing devices, endoscopic single anchor suturing, purse string suturing, stapling, and clipping. One of the earliest devices that proved feasible for this purpose achieved suturing using two threaded T-bars, placed through an EUS-needle beyond the gut wall, one each side of the incision. The two threads were subsequently locked together by a small through-the-scope locking device to close the incision [3]. Since then, several companies have produced similar prototype devices. Stapling devices have been modified from laparoscopic surgery to meet the needs of flexible endoscopy, and clipping devices such as the Ovesco systems provide an entirely new approach.

The problem, however, is not which of them is best suited to the purpose, i. e., which path we should take, but that none of these techniques has been marketed to date. For the most part they are not even available for testing, and some have remained for many years as prototypes being used by a few in preclinical and clinical studies.

Why is that so? One would have imagined that a whole generation of endoscopists would have been waiting for a closure device, even if only to be able to close the rare unintended iatrogenic perforation rather than the fancy journey into the peritoneal cavity. The demand is obvious from the many case reports of successful closure of full-thickness lesions in patients using devices that are already on the market for other purposes in a new and different way for this indication. The use of available technology in an innovative way for NOTES incision closure has also been published, e. g., in this journal [1]. Exciting as this is, it also shows the current lack of access of most endoscopists to prototype closure devices.

So, why is there no such system available, even if imperfect and relatively expensive? Is one reason that the market is perceived to be too small, and there is a fear that incorrect usage that might harm patients would lead to litigation? In recent years a limited production run of innovative devices no longer seems to be able to satisfy the business investment required in order to generate, approve, and improve an invention. The costs of producing a new device now may run into millions, so that large-scale production is the only means of recouping the research and development costs, especially if larger companies are involved. In addition, until very recently, today’s companies expect to make large profits and may no longer be satisfied with small returns on their investments.

Even if every endoscopy unit in a developed country wanted to stock one such new closure device to fix the inevitable perforation and a few used it in NOTES, there would not be a need for more than a few hundred thousand devices per year, making it an ”orphan device.” The slow, cautious development, manufacture, and repeated improvement of a boutique device over many years to perfection may not be consistent with the rapid demands of big business. However, some companies have successfully taken that risk in the past. The invention of metal stents for the gastrointestinal tract may be an example; many of these are still hand-made for a market demand which is relatively small. Although expensive to purchase, their use has been accepted by many hospital managers over time.

Despite some success stories, however, many labor-intensive small product lines are shelved. The US Congress and the Food and Drug Administration (FDA) have realized that when there is no reasonable expectation that a drug or medical device will be developed without assistance, for infrequent diseases and conditions which affect less than 200 000 persons in the US, a so-called ”orphan drug or device” may be warranted [3]. Such devices expect to generate relatively small sales in comparison to the cost of developing, and may incur a financial loss. Congress has decided that it is in the public interest to provide incentives for the development of such orphan drugs/devices, provision for which is made in the ”Orphan drug act”[3]. If not for NOTES but for the treatment of iatrogenic perforation, an incision closure device might comply with the criteria for this concept.

The orphan drug/device problem underlines one dilemma with NOTES devices. The initial enthusiasm accompanied by large-scale funding has given way to the realization that the quick and easy marketing seen in the 1990s with laparoscopic equipment, including the prospect of the money to be made, is not easily reproduced in today’s world. All current new devices for incision closure would be produced in small numbers with relatively high development costs and would need to be passed through the FDA. Additional significant costs include the set-up of distribution and sales persons as well as the necessary training program. In addition, premature availability to the average endoscopist might produce negative experiences with attendant negative propaganda.

Is there then a marketplace at all for a small production line such as a gastric closure device? With the market and the perception of the scale of profits changing, there may indeed be a small boutique marketplace for such devices, even if they need to be hand-made and will consequently be expensive. If we could close a perforation of the gut with a device that even costs a few thousand, it would be demand from physicians and patients over time that would make it a success, as has been seen with gastrointestinal metal stents.

At the present moment it does not seem to be essential to choose which path to take in the sense of which device to choose. That will be dependent on many factors such as ease of use, reliability of performance, and costs, and will come much later. At this moment the question is: does a worthwhile market even exist? This will by and large depend on physicians being willing to request the device and to pay an appropriate price for it rather than getting it for free for testing.

Competing interests: None

References

• 1 Hookey L C, Khokhotva V, Bielawska B. et al . The Queen’s closure: a novel technique for closure of endoscopic gastrotomy for natural-orifice transluminal endoscopic surgery.  Endoscopy. 2009;  41 149-153
• 2 Fritscher-Ravens A, Mosse C A, Mills T N. et al . A through-the-scope device for suturing and tissue approximation under endoscopic ultrasound control.  Gastrointest Endosc. 2002;  56 737-742
• 3 Orphan drug act. www.fda.gov/orphan/oda.htm. Accessed: 2 January 2009.