THE PAST, THE PRESENT AND THE FUTURE OF MINIMALLY INVASIVE THERAPY IN LAPAROSCOPIC SURGERY: A REVIEW AND SPECULATIVE OUTLOOK
It took nearly a hundred years till laparoscopy overlooked the realm of general surgery, but rarely in the history of surgery we observed a similar revolution. Laparoscopic cholecystectomy has caught on very quickly at the turn of the 80s and 90s quickly becoming the gold standard in the treatment of gallbladder stones. Few surgical procedures have changed so rapidly and so profoundly the daily activities of each surgeon. The first cholecystectomy “open ” of which we have news was executed on July 15, 1882, by the German surgeon Carl Johann August Langenbuch (1846-1901) at the Lazarus Krankenhaus, Berlin, on a 43 years old man. The history of laparoscopy is not that more recent. First report are dated 1901, when the Russian gynecologist Dimitri Ott examined the peritoneal cavity of a pregnant woman using a mirror and a speculum introduced through a culdoscopic opening (1,2). In the following years the Swedish surgeon Hans Christian Jacobaeus, reported 72 patients undergoing inspection of the abdominal and thoracic cavities along 10 years, coining the terms “laparoscopy” and “thoracoscopy”, from the greek “lapara“, i.e. abdomen, “thoraco” , i.e. chest and “skopein“, i.e.to see (3). Finally, it was George Bercy, an American surgeon who first had the idea to attach a camera to the laparoscope. It was 1962 and the era of video laparoscopy was begun. This contributed consistently to transform laparoscopy from a mere simple diagnostic tool into a therapeutic technique. These were the years in which laparoscopy seemed always to be characterized more as a branch of gynecology, because this was the field that seemed to offer the greatest advantages of its application. This also explains why the leading experts in endoscopic technique in those years, almost all belong to the field of gynecology. One of the them, Kurt Semm. was the first, although gynecologist, to propose and execute on September 12, 1980 a laparoscopic appendectomy (4). There is uncertainty about the actual authorship of the first laparoscopic cholecystectomy. There are traces of a publication in 1983 by the Russian Lukichev describing the technique, but due to the use of the Russian language, the text remained unknown for years (5). Unaware of this, Erich Muhe claimed the execution of the first laparoscopic cholecystectomy on September 12, 1985 (6-8). However, his description of the technique did not accept the favours of the German scientific society, and it was ignored for months, and subjected to severe criticism. It was March 17, 1987 when Philippe Mouret performed his first laparoscopic cholecystectomy in Lyon, France (9). This is the date in which you actually trace the beginning of laparoscopy in general surgery. It actually represents a milestone in the history of surgery, although Philippe Mouret told of his experience as a quite natural, without premeditation. It was a 50 years old patient who suffered from pelvic adhesions, who was addressed to him for an intervention of laparoscopic adhesiolysis. However, the patient was also suffering from symptomatic gallstones and had asked him if it was not possible to perform both actions simultaneously. So he performed an initial exploration of the liver lodge which turned out simple for the thinness of the patient. At that time, moreover, he had already racked up over 8000 laparoscopies and over 100 laparoscopic appendectomies. After adhesiolysis he performed the preparation of the pedicle of the gallbladder rather simply, and he felt sure enough that he completed the cholecystectomy under laparoscopic conditions.Since that date, the cases began to occur with a certain continuity in the following weeks. Nevertheless, it took a few more years before the technique was recognized by the scientific world for its extraordinary importance, so as to be indicated by some as the “Second French Revolution”. It was estimated that the percentage of cholecystectomies done laparoscopically reached 80% in 1992, such a rapid acceptance of a new surgical technique that was never seen before (10). The technique described by the authors was to henceforth called “French”, different from that adopted by colleagues from overseas. In fact, the experience of laparoscopic cholecystectomy started a little later in the United States, namely by the work of Barry McKernan and William Saye who performed the first laparoscopic cholecystectomy in the U.S. on June 22, 1988 in Marietta, Georgia (11). They were soon followed by the most well-known Eddie Reddick and Douglas Olsen in Nashville, Tennessee (12), who, in addition to being known for some successful endoscopic instruments conceived by them, are those who developed the technique now known as “American“, consisting in a different positioning of trocars to achieve a different approach to the organs. This was just the beginning of a dramatic change in almost all the fields of surgery, deeply influencing the way surgeons act and think, and mostly, changing the way patients are cured. Several questions were continuously discussed during this quarter of a century, but lack of evidence did not allow to come to clear conclusions. They can be distinguished in two major classification, the one regarding the application of the concept of minimally invasiveness to the different abdominal districts, the other regarding the development and fruitful application of innovative technologies which might influence the development of novel techniques. In the following paragraphs we would like to review where we were, we are and will probably be in respect to these two different characterisations.
THE EVOLUTION OF TECHNIQUES
As for any innovation, laparoscopy represented a robust incitement to test the feasibility of its application to almost all the abdominal districts. Laparoscopy soon demonstrated its clear advantages in surgery of the spleen, adrenal gland and all the urinary tract, while possible advantages in gastric resection following oncologic criteria, as well as in liver and pancreas resections, if not of limited entity, are still debated and did not meet much favour of the scientific community. Undoubtedly, the abdominal district in which minimally invasiveness demonstrated along the years the most clear advantages is the large bowel. For a long time colorectal surgeons seemed immune to the contagious excitement which surrounded the development of laparoscopic surgery across the 80ies and 90ies, ignoring the unique patient benefits if not refuting them. Colorectal surgery lagged behind, as the challenges of working in multiple quadrants with the need for extensive vascular control within an often thick friable mesentery, the requirement of anastomosis, and the surgical indications such as inflammatory bowel disease and neoplasia dampened enthusiasm (13). Reports of port site metastases further decelerated the adoption of the techniques and the penetration of the procedures(14). Finally after the COST trial was presented at the May 2004 meeting of the American Society of Colon and Rectal Surgeons (ASCRS) and simultaneously published in the New England Journal of Medicine (15) did acceptance accelerate. Today laparoscopy has proven to actually be the most important advance also in colorectal surgery since the introduction of surgical stapling (16). Oncologic safety has now been demonstrated for laparoscopy-assisted surgery for colon adenocarcinoma after 3 and 5 years of follow-up. Pooled data from large multicenter and smaller single-center trials demonstrate that the modality conveys significant short-term benefits as compared with open surgery, although the full potential has probably not yet been reached. Currently, the data supports improvements in wound morbidity, intraoperative blood loss, narcotic analgesia requirements, time to resumption of bowel movements, and time to discharge from hospital. There is a large potential for improved short-term results when combined with current and developing enhanced-recovery programs. To be true, the concept of minimally invasiveness was first applied to the rectum even earlier than to the appendix and the gall bladder. It was 1983 when Transanal Endoscopic Microsurgery (TEM) was introduced in the clinical practice by Gerhard Buess in Germany, as a novel surgical approach for the resection of large rectal adenomas (17). This procedure encompassed general anesthesia, while now is more often performed under spinal anesthesia, and the use of expensive specialized equipment with 3D vision by Richard Wolf (Knittingen, Germany), which is now more often replaced by the cheaper and more user friendly 2D equipment by Karl Storz (Tuttlingen, Germany). Since its introduction, many surgical practices have adopted TEM as the new standard therapy for large rectal adenomas (18).Transanal Endoscopic Microsurgery (TEM) was originally conceived for the treatment of large sessile extraperitoneal rectal adenomas, step by step expanding its indications. First it proved curative for “low risk”rectal cancers, as often discovered post-operatively on the resected specimens of preoperatively assessed benign lesions (19,20). Then it deserved a role in the palliative treatment of advanced invasive cancers (21,22). In this boundary, today TEM is considered a modern platform for extended indications, such as the resection of intraperitoneal as well as circumferential lesions, it is combined with sentinel lymph node sampling techniques to determine the indication for a more extensive surgical approach in N+ cancers, and recently the transanal approach was proposed as a complementary technique in combination with the abdominal approach, for the curative treatment sphincter sparing of invasive bulky and low rectal cancer (23). While it took 30 years to asses the role of TEM for resection of benign and selected malignant neoplasms of the rectum, after more than 20 years since the first report of laparoscopic colorectal surgery (24), its employment in the treatment of rectal diseases is still debated, where TME and a systematic lymphadenectomy are considered the main step of curative therapy of rectal cancer (23), available data did not allow till now to come to almost any reliable conclusion. We recently performed a meta-analysis on available data regarding short-term morbidity after open and laparoscopic excision, and the most interesting finding was that the incidence of mortality showed a significant reduction in the laparoscopic group compared to open surgery. Furthermore, the overall incidence of post-operative complications was also significantly lower in the laparoscopic group with a RR of 0.81. The analysis of all included studies showed a clear advantage for laparoscopy also in the specific analysis of both surgical and medical complications, which translated, as already shown in the treatment of colon cancer (25-28), into a clear advantage in terms of an earlier bowel activity restoration, time to oral intake and duration of postoperative hospital stay, whereas the only clear disadvantage was represented by the relatively longer operative time. A similar analysis was then repeated limiting the object of the study to patients affected by extra-peritoneal rectal cancer, where we also proved that laparoscopic rectal resection appears to have clinically measurable short-term advantages in patients with primary resectable rectal cancer. Although technically demanding, laparoscopic rectal resection is safe and guarantees a faster recovery. We then focused on the oncologic adequacy of the laparoscopic technique compared to open rectal resection. There is no doubt that cancer patients have as principal aim to be cured from their disease, no matter the technique, so that they are prone to banish advantages of minimally invasive treatment if they do not correspond to comparable oncologic effectiveness. For this reason, the present analysis is of even major importance than the previous, to identify the correct path to move forward in the application of the concept of minimally invasiveness in this field. The main finding of this meta-analysis was that the involvement of the circumferential margin, i.e. <1 mm, was reported in 8.0% of the patients in the laparoscopic group and in 12.7% in the open group, with an overall RR 0.68, although this result was deeply influenced by Lujan 2012 (29), nor it was confirmed both in the sensitivity analysis of RCTs and in the subgroup analysis of only extraperitoneal series, and should therefore taken with caution. Moreover, the number of lymph-nodes, the average distal margin and its involvement, the average circumferential margin, the rate of R0 resections and the mesorectal fascia integrity as assessed by the pathologist, showed no significant differences between the two groups. Even the local recurrence rate at 5 years resulted similar in the laparoscopic group and the open group, so that in conclusion although technically demanding, laparoscopic rectal resection appears to be equally effective in terms of oncologic adequacy, in selected patients with primary resectable rectal cancer.
THE EVOLUTION OF TECHNOLOGIES
In general, the introduction of laparoscopy entailed the need of selection of patients, as it represented an increase in technical difficulties, which could result in the impossibility to proceed laparoscopically in particular anatomic conditions. In all cases, in endoscopic surgery, the ability to guide the instrument is significantly decreased compared with open surgery. Rigid laparoscopic instruments offer only four of the six degrees of freedom required for the free handling of objects in space. Laparoscopy represented a worsening of tissue manipulation, which might reflect on suboptimal vision due to insufficient tissue retraction and exposure. For this reason, since the early 90ies the idea to use robotic technology to improve this limit of laparoscopy, was presented. Robotics technology can be used to restore full mobility of the endoscopic instrument. A master-slave manipulator system, named ARTEMIS, for laparoscopic surgery was presented in 1994 by the Research Center Karlsruhe, with the medical advice of Gerhard Buess and Marc Schurr of the University of Tuebingen (30). This prototype consisted of two robotic arms holding two steerable laparoscopic instruments. These two work units were controlled from a console equipped with two master arms operated by the surgeon. The systems and its components were evaluated experimentally. Laparoscopic manipulations were feasible with the ARTEMIS system. The placement of ligatures and sutures and the handling of catheters were possible in phantom models. The surgical practicability of the system was demonstrated in animal experiments. It appeared soon that robotic manipulators were realistic solutions for experimental endoscopic surgery, but their clinical application required further technical development (31). In fact, the project was first moved towards cardiac surgery applications, but even in this district, clinical applications seemed distant. As derivative projects, the group tried to offer solutions for laparoscopic assistance. In fact laparoscopic assistance often demands tiring standing positions and monotonous tasks. The use of mechanical positioning systems derived from open surgery can be unsatisfactory, being their movement often cumbersome and unsafe, since in most cases both hands of the surgeon are required to change position. The use of positioning and holding devices in laparoscopic surgery, in fact, returns direct control of the whole procedure to the operating surgeons, theoretically increasing precision of action. The Research Center in Karlsruhe led first to the design of the passive system TISKA Endoarm (32) and later to the remote-controlled FIPS Endoarm (33). Although they proved to be advantageous in ex-vivo studies, compared to human assistance, in terms of safety and cost-effectiveness, they remained at the level of prototypes. At the end of the 90ies several other laparoscopic camera-driving systems were devised: the Endoassist (Armstrong Healthcare) (34) and the AESOP system (Computer Motion) (35) were available on the market. The rapid introduction of several different architecture and interface solutions reflected the growing interest in these developments (36). But all the different systems proposed with helmet controls, infra-red pointers, visual tracking systems and the first voice controlled devices, on the market did not meet the surgeons’ interest (37). At the same time the development of robotic technology had proceeded and a further example was proposed by Intuitive Surgery (Seattle, USA), named Da Vinci. Along the different generations of the device proposed, the system on one side showed a good appeal, with almost 2000 devices installed world-wide so far, and more than 300.000 procedure performed. On the other side, the system, first proposed for cardiac surgery and general surgery applications, failed so far to prove any benefit in these restricted areas, being still under evaluation in the pelvic district both for rectal surgery and prostate surgery, with a general feeling that major technology improvement has to be achieved before it can result clinically advantageous. A further important development which influenced the diffusion of laparoscopy is related to dissection devices. First the introduction of dissectors based on ultrasound technology in the late 90ies, then on radio-frequency technology, revolutionised the application of laparoscopic techniques making it apparently easier and safer. In truth several studies demonstrated the absence of real need of sophisticated dissecting technology in the vast majority of cases, which can be treated instead by simple mono-polar and bi-polar energy dissectors. Nevertheless, the consistent interest of the industry contributed significantly to the diffusion of laparoscopic techniques, in these years, for the evident feedback. This produced a number of events and courses, and delivered a fashion of organising live events with demonstration of products, that although not always scientifically driven, reflected on a consistent spread of knowledge and adoption of novel techniques. In a similar way, but with less effort, more recently the concept of single port surgery was supported. All the majors previously involved in the challenge on the promotion of the different dissectors, faced again in promoting these novel devices. Nevertheless, here the “leit motiv” of promoting technology to make things easier could not be used. Single port surgery represents evidently a worsening of environment conditions, with doubts on clear benefits for the patients, which still lack of evidence. For this reason, this, initially addressed like the further step towards less invasiveness, still struggles to emerge and it is not clear still if it will, in the end (38).
Before disputing about the future of surgery in 25 years from now, we have to seriously focus for a while on the possible scenarios that we will face in that time frame. Economy is getting more and more importance in healthcare and is going to influence strategic social decision of governments even in industrialised and healthy countries. But other factors are going to play major roles such as the diffusion of social media, through which the vast majority of knowledge and awareness will circulate in a sort of self-made healthcare reducing the role of doctors to that of specialists consulted only on specific questions or for specific manoeuvres, or the continuous research and development of new technologies, which depending on the economic situation might concentrate on high cost or low cost solutions. In this, gastroenterology in general will see a dramatic change in diagnostic tools (39), with a significant increase in prevention through screening programs, which will lead to a vast majority of early lesions or initial diseases diagnosed. The way of treatment will be influenced as a consequence, with a consistent decrease of invasiveness. In this scenario it is difficult to foresee which will be the role played by surgeons and how will their work appear, if towards a wider application of current concepts of minimally invasiveness, so basically laparoscopy, or if towards further reduction of invasiveness, for instance with the adoption of the NOTES® (Natural Orifices Transluminal Endoscopic Surgery) concepts, or maybe a combination of the two. It is anyway likely that a consistent number of cases will be treated with different ablation techniques such as HIFU (High Intensity Focused Ultrasound) or similar, maybe in combination with more specific chemotherapy, such as those derived by molecular genetics. In truth lay literature and media focused attention on NOTES since the beginning of 2007 after the first clinical reports, having been the concept and feasibility of NOTES tested in animal experiments since 2004 (40). The initial experience of transgastric and transvaginal peritoneal access demonstrated both safety and feasibility in the animal model and has been used as the basis to further evaluate and develop the technology of natural orifice surgery (40-48). Later other possible accesses where described as the transrectal, the transvesical and finally the transesophageal ones. NOTES is a new type of surgical procedure currently being studied at research hospitals and facilities around the world. The idea of NOTES was developed several years ago in response to the concepts that patients would 1) realize the benefits of less invasive surgery by reducing the recovery time, 2) experience less physical discomfort associated with traditional procedures and, 3) have virtually no visible scarring following this type of surgery. All of these advantages have spurred research and investigation forward, encouraging physicians and researchers to develop new equipment and techniques to use during NOTES procedures. The growing interest and safe introduction for these novel techniques lead to the creation of new scientific societies and committees with the declared aim of regulating research activity through sponsorships and registries (49). About a decade after its proposal, the general impression is that after an initial explosive enthusiasm for NOTES techniques, the slowed down development of dedicated platforms and instruments and the ongoing diffusion of single access techniques has mitigated the spread diffusion and employment of the techniques. Dedicated platforms comprising all surgical instruments needed for visualization, dissection, manipulation and retraction will probably bring the advantage of reproducing a surgical environment through a single translumenal access, this way avoiding the need of transabdominal trocars, so hybrid procedures. It is difficult now to predict which the new barriers will be. But at the same time, once the techniques will be validated, appropriate training and accreditation should be provided by scientific societies through certified experts in the field. Despite this, NOTES implementation into clinical activity is going on, with excellent results although in extremely selected cases (50). Which benefit this would represent for patient is still too early to be assessed, but research on the topic should go on to provide new solutions to technical problems before a real validation is performed. Some considerations are to be done about what moved the initial enthusiasm. It was not the patients’ demand for a further reduction of invasiveness, as it would be reasonable to think. Although the prospective of a no scar surgery would be appealing for any patient, but in truth patients are in general already very much satisfied with laparoscopy results, as they are more concerned about wound pain and complications than cosmetics, so that most of the studies fail to demonstrate any advantage in patients’ satisfaction comparing laparoscopy, single-port laparoscopy and NOTES. The real driving force behind the development of this new frontier was the industry, that imagined the opening of new businesses related to this research activity. When it was soon understood that the research and development to be done to achieve a stable clinical employment of new techniques was much more than initially thought, the interest began to fade. The need generated by the expectation of a further reduction of invasiveness related to the concept of NOTES was soon satisfied with the implementation of single port techniques with the promotion of new tools. It has been calculated that in the last decade United States research investments in Health coming from Industry doubled constantly what sponsored by the Government. In a company-driven development it is difficult to believe that any advancement in health care will not be sustained by a concrete economic business, which does not necessarily correspond to a significant improvement in patients’ care. Priorities dictated by science and common sense are not necessarily interesting for Industry. If the scientific community will not be able to modify this tendency, playing a major role in driving this activity, technology improvement will be unpredictable and possibly of little relevance. In the previous chapter we discussed extensively about the current role of robotics in surgery. Today the major prospective and aim is to contribute to simplification of the surgical gesture, in order to increase its reproducibility. This is of course an important advancement, which will offer possibly to a majority of patients, the benefits of minimally invasiveness which are now restricted to a minority of patients due to the technical challenges that laparoscopy, at least in some districts, implies. Nevertheless, the benefits of the use of robotics would be even more if we would use this technology to devise less invasive procedures for common diseases, taking advantage of miniaturisation. Applications of a similar technology would be both endoluminal, such as for instance, local excision of large sessile lesions of the digestive tract, overtaking this way the evident limits of flexible endoscopy compared to surgical platforms (51), and translumenal, such as appendectomies or cholecystectomies, till bowel resections and similar. In this background, it is realistic that NOTES will not take over endoscopic surgery, and will remain as an application for very selected procedure. The vast majority of digestive surgery will be most likely performed endoscopically but through the thoracic or abdominal wall, by means of smaller incisions, with the extent of resections reduced either by the association with node sampling techniques (52,53), or with biologically tailored therapies. In this prospective it will be mandatory that gastroenterologists and surgeons blend into a new kind of specialist, and perhaps technology development may finally drive them in that direction. Factors that will determine the introduction of new technologies in the clinical armamentarium have to do not only with the value of the technical and clinical improvement, but also with coverage (reimbursement), adoption by practitioners, and competing technologies. “Inventing the future does not simply require technological innovation but is a complex intellectual exercise that begins with the identification of true unmet needs and profound insight into disease mechanisms” (54).