Tahar Benhidjeb

Intravenous administration of recombinant adenoviruses causes thrombocytopenia, anemia and erythroblastosis in rabbits

Recombinant adenoviruses are highly efficient gene transfer vehicles but their administration to mammals is accompanied by a strong inflammatory response. The present study reports additional side effects observed during adenoviral gene transfer studies in rabbits.

Cervical scarless endoscopic thyroidectomy: Axillo-bilateral-breast approach (ABBA)

BackgroundNeck surgery is one of the latest applications of minimally invasive surgery. We applied a new technique for totally endoscopic thyroidectomy, the axillo-bilateral-breast approach (ABBA). This approach does not leave a scar on the neck.MethodsBetween February 2005 and October 2005, 13 patients were treated by ABBA for uni- or multinodular goitres. Surgery is performed under general anaesthesia and in supine position. 5 mm bilateral skin incisions are made on the margin of the areola of nipple. They are used to insert and subcutaneously push forward a 20 cm long, 5 mm trocar to the jugular fossa. A further 5 mm incision is performed in the right axilla. The right breast trocar is the optical trocar. A Maryland clamp in axillary position and 5 mm harmonic scalpel via the left breast trocar permit a clear view of the further subfascial preparation. The caudal hyoidal muscles are longitudinally split along the linea alba. Using delicate blunt dissection, both thyroid lobes are exposed. After isthmus transection is performed, the upper thyroid pole is being mobilized. The upper pole vessels are isolated and divided close to the thyroid capsule. Preparation of the retrothyroidal area includes visualization of the recurrent laryngeal nerve. The resection is performed without bleeding with a harmonic scalpel. Via the axillary approach, with the incision being widened, a 20 mm trocar is inserted and advanced up to the thyroid lodge to remove the specimen.ResultsThe average operation time was 132 minutes. No patient had to be converted to a conventional approach. Hypocalcaemia or recurrent laryngeal nerve palsy were not observed postoperatively.ConclusionOur preliminary results show that the ABBA technique is a feasible, safe procedure with excellent cosmetic benefits. The small scars in the right axilla and bilateral nipple areola are almost invisible.

Perceptual phenomena after unilateral arm amputation: a pre-post-surgical comparison

Painful and non-painful phantom phenomena occur frequently after amputations but are rarely investigated in the perioperative stage. The goal of the present study was the assessment of phantom phenomena, pain and changes in primary somatosensory cortex prior to and after upper limb amputation. Two patients who suffered from metastatic carcinoma were examined 2 days prior to and 7 days after the amputation of an arm using comprehensive psychometric assessments and neuroelectric source imaging. Both patients reported phantom limb pain that was similar to their pre-amputation pain. In one patient, reorganization of the mouth area into the deafferented hand area took place immediately after the amputation. In the other patient reorganization had occurred prior to the amputation possibly related to non-use of the arm several years prior to the amputation.

The future of telesurgery: a universal system with haptic sensation.

Dear editor; The 19th century will be remembered as the era of abdominal surgery, and the 20th as that of endoscopy. The 21st century has a potential to become the era of telesurgery, should the technical developments bring added value to the existing surgical methods. The optimal telesurgical system should be suitable to any kind of surgical procedure and provide tactile sensing, 3D vision as well as cost-effectiveness. The Joint Research Centre (JRC) of the European Commission, in collaboration with SOFAR S.p.A. in Milan, Italy, initiated a project to meet these demands, the Telelap Alf-x. The New European Surgical Academy is providing the academic background to such a demanding project. This system enables universal telesurgical procedures with optimal ergonomy and haptic sensation. The preclinical studies have proven an optimal outcome and it seems that the system will replace several endoscopic procedures in the 21st century. During the 19th century, along with the development of general anaesthesia (1), surgical procedures became routine, and certain novel operative methods were developed, some of which are in use even today, such as the Billroth or the Wertheim operations (2, 3). Georg Kelling, a German surgeon, was the first to perform an experimental laparoscopy (4). Throughout the 20th century, the introduction of endotracheal intubation (5), the insufflator (6), light sources (6) and other designed instruments enabled the development of many endoscopic procedures. Today, most operations can be performed endoscopically (7), especially the gynaecological ones, namely, the laparoscopically assisted vaginal hysterectomy (8) and the total abdominal hysterectomy (9). The patients undergoing endoscopic procedures need less postoperative analgesics and present decreased morbidity with shorter hospital stay (10). At the end of the 20th century, it seemed that surgery had reached its peak. The potential and vision of future remote operations in space and on other planets led to the development of telesurgical devices (11). Although we are still on Mother Earth, this idea stimulated the development of various systems. The era of telesurgery started in 1988 when the PUMA telesurgical system was used for a controlled neurosurgical biopsy (12). Other systems in use at present or in the past are the Da Vinci (13), Probot (14), Robodoc (15), and Zeus (16). The term “robotic” prevails in the literature. However, it is misleading since none of the existing telesurgical systems is equipped with artificial intelligence. The term “telesurgery” should be preferred. The accumulated advantages of the existing telesurgical systems are improved dexterity and accuracy, 3D stereo-vision, lack of tremor, and the potential of telementoring and operating from remote cities and countries. The most important disadvantage in all existing systems is the lack of haptic feedback. Exactly like musicians who use their fingers for producing the desired sound and, in case of string instruments, feel the vibrations of the strings, it is of utmost importance for a surgeon to be able to feel the consistency and anatomical structures and evaluate the tensility of the suture during knot-tying. Haptic sensation during surgery should be part of any telesurgical system, even if its relevance in telesurgical procedures is controversial, and it has been claimed that the results of visual force feedback and haptic feedback are comparable (17). In a recent study, differences between strand-to-strand knots and loop-to-strand knots were detected when telesurgical and manual knot-tying were compared (18). In the past, surgeons used their fingertips to hold and manipulate instruments. In endoscopy, the trocar as well as other instruments are manipulated with the fists or the proximal parts of the fingers. Telesurgical systems should provide safety, accuracy, optimal short and long time outcomes and optimal ergonomy. Cost-effectiveness should always be considered. Any surgical development should only be applied if it provides added value to the existing systems. To meet these demands, the EU commission, in collaboration with SOFAR S.p.A. in Milan, Italy, has initiated a different telesurgical system, the Telelap Alf-x, which has been designed in order to meet the needs of patients and surgeons with the aim to provide added value to existing procedures (Figure 1). Figure 1 The Telelap-Alf-x system in work The features of the system are as follows: 3 or 4 arms combined with 1 or 2 consoles, according to the needs. As the arms are separately moveable, immediate access to the patient is possible in case of an emergency; Fast docking: all instruments are connected to the arms with magnets - immediate exchange of needed instruments; The system detects within seconds the optimal pivot point of each inserted instrument. This point becomes the axis of the arm movement, preventing extension of the entry point; Avoidance of tremor, advanced control and limitation of applied forces; Haptic sensation and newly designed handles enabling manipulation of the instruments with the fingers; Placing the instruments at any given angle needed. The system can access the abdominal cavity from the abdomen and, in women, through the pouch of Douglas, therefore transdouglas surgery is possible with this system; A console with unobstructed view onto the screen with 3D vision and an ergonomic seat enabling a comfortable position during long operations; Cost-effectiveness: the surgeon can use low-cost disposable instruments, however, the system provides reusable instruments; Universality: any existing endoscopic instrument (articulated tip, monopolar, bipolar, laser etc. instruments) can be adapted. Therefore, surgeons do not have to change their operative habits and can even use the system for training; An unique eye-tracking system. Next to the 3D vision, the surgeon controls the insertion of instruments by looking at the corresponding icon on the screen, the picture is magnified when his/her head approaches the screen, and any point looked at moves to the centre of the screen (Figure 2). Figure 2 Eye-tracking system In the first experimental operations performed using the Telelap Alf-x, the average time for cholecystectomy was 31.75 min as compared to 91 min using a conventional telesurgical system (1). We strongly believe that haptic sensation provided more confidence to the surgeon, which explains the shorter operation time. No surgical system can provide an optimal outcome when the surgical steps are not taken according to an evidence-based programme (20). At the same time, only standardized and optimized surgical methods will allow valuable meta-analysis and enable a comparison of surgical outcome in different institutions and by different surgeons (21). Therefore, a group of internationally renowned opinion leaders was assigned to design evidence-based surgical procedures in various disciplines. The Telelap-Alf-x provides a combination of unobstructed 3D vision, haptic feedback and universality which offers all the advantages of laparotomy along with those of endoscopy. Therefore, this system will be the basis of novel surgical developments during the 21st century.

Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage.

Gene therapy of familial hypercholesterolemia (FH) requires successful transfer and lifelong expression of a functional low density lipoprotein receptor (LDLr) gene in the liver. Most of the vector systems currently employed for gene therapy use promoter elements which do not modulate transgene expression in a physiological manner.

Transoral thyroid and parathyroid surgery: still experimental!

It was with great interest that we read the report by Karakas et al. [1] on transoral thyroid and parathyroid surgery. By using a modified rigid rectoscope (oraloscope) hemithyroidectomies as well as resection of parathyroid glands could be performed in ten porcine cadavers, then in 10 living and orally intubated pigs, and finally in five human corpses. Because unfortunately many claims and statements in their report are misleading, we believe that rectifications are needed. Karakas et al. stated in the ‘‘Introduction’’ of their article that ‘‘For the first time, we describe an entirely transoral access, which allows for a hemithyroidectomy and parathyroidectomy without an accessorial incision of the skin in pigs and human cadavers.’’ Later, in the ‘‘Results’’ section, they affirm that ‘‘This is the first study to demonstrate that transoral resection of thyroid and parathyroid glands is feasible using an entirely transoral access to the thyroid region.’’ Both statements are wrong. Transoral thyroid surgery is an innovative project that was initiated in September 2007 by the New European Surgical Academy (NESA) and developed in cooperation with the Department of Neuroscience Anatomy at the Erasmus MC University in Rotterdam, The Netherlands. It is a part of the NESA’s Natural Orifice Surgery (NOS) project that includes investigation of transvaginal and transoral access for various surgical procedures [2–4]. Transoral thyroidectomy is based on the hybrid technique invented by our member Kai Witzel, who was the first to describe transoral access to the thyroid [5]. Our main goal was the investigation and introduction of a technique of totally endoscopic thyroid resection that is minimally invasive and safe for the patient and also cosmetically optimal (scarless). The first step of this project consisted of anatomic studies with instrument development performed on three human cadavers. Following these detailed studies, safety and reproducibility to reach and resect the thyroid gland were assessed according to a defined road map in two cadavers. On 14 May 2008 we succeeded in performing a totally transoral video-assisted thyroidectomy that we named TOVAT. On 31 August 2008 this method was successfully used in five living pigs. On 13 September 2008 we submitted a video paper to Surgical Endoscopy that was accepted on 8 January 2009 and published online on 5 March 2009 [6]. Karakas et al. submitted their manuscript to Surgical Endoscopy on 12 June 2009, 3 months after the online publication of our video paper in the same journal, long after our paper was available on PubMed and other search engines. Moreover, we presented TOVAT as early as 30 August 2008 at the 20th International Conference of the Society for Medical Innovation and Technology (SMIT) in Vienna [7]. The abstract of this oral presentation was also published at that time in Minimally Invasive Therapy and Allied Technologies [8]. All this makes it legitimate to raise serious concerns over Karakas’ literature search before starting their T. Benhidjeb (&) O. Mann Department of General-, Visceraland Thoracic-Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany e-mail: t.benhidjeb@uke.de

Novel technologies for natural orifice surgery: An overview

Natural Orifice Surgery (NOS) is now being elaborated with the aim to make abdominal surgery simpler and safer. The existing natural openings of the body are used for introduction of surgical instruments and thus to perform surgical procedures while avoiding to penetrate the abdominal wall. Actually, the transvaginal and transgastric approaches are the common routes used for NOS applications in humans. The transvaginal approach does not necessitate any sophisticated devices for opening and closure of the posterior colpotomy, thus being easy for the surgeon and safe for the patient. In contrast, the problem of transluminal access and closure represents significant obstacles in the transgastric approach and is still unsolved. In order to achieve this goal, various surgical prototype devices have been developed. This article aims to give an overview on the current status of techniques and technologies that are being developed and applied in conjunction with NOS procedures.

Prinzipien der kurativen Lebermetastasenresektion

Summary. For patients with liver metastases, surgery currently represents the only possibility for cure, with a mean 5-year survival rate of 25–35 %. Due to refinement in operative and anesthetic techniques and improved critical care with decreased morbidity ( < 25 %) and mortality ( < 5 %), hepatic resection is a safe and efficient procedure. Surgery has repeatedly achieved long-term disease-free survival in 20–25 % of patients. However, only 10–25 % of patients with colorectal liver metastases can undergo potentially curative liver resection. Therefore, accurate staging plays a pivotal role in selecting patients who would benefit from surgery. For metastatic colorectal cancer, resection offers the only potential for cure. For symptomatic neuroendocrine tumors, hepatic resection offers long-term palliation in many cases and cure in some. The role of hepatic resection for noncolorectal and nonneuroendocrine metastases, however, is less well defined. Recurrence of hepatic metastases after seemingly curative resection is observed in about 40–60 % of the cases. Only 20–35 % of these recurrent metastases appear to be resectable, resulting in an overall 3-year survival rate of about 30 %. The morbidity and mortality from repeat hepatectomy is similar to that of first hepatic resection. All results together demonstrate that resection and re-resection of liver metastases can provide long-term survival rates and can be beneficial in a carefully selected group of patients without extrahepatic disease.Zusammenfassung. Für Patienten mit Lebermetastasen stellt heute die chirurgische Therapie mit 5-Jahres-Überlebensraten von 25–35 % die einzige Chance auf eine Kuration dar. Verbesserungen von chirurgischen und anaesthesiologischen Techniken sowie Fortschritte auf dem Gebiet der Intensivtherapie haben zu einer deutlichen Senkung der Morbidität ( < 25 %) und Letalität ( < 5 %) geführt. Ein Langzeit-rezidivfreies Überleben kann bei 20–25 % der Patienten erzielt werden. Ein potentiell kurativer chirurgischer Eingriff ist jedoch bei nur 10–15 % der Patienten mit Lebermetastasen möglich. Es ist somit von großer Bedeutung diejenigen Patienten, die von einer Operation profitieren könnten, durch ein sorgfältiges Staging zu selektionieren. Bei colorectalen Lebermetastasen ist eine potentielle Kuration nur durch eine radikale Resektion möglich. Bei einem Großteil der Patienten mit symptomatischen Lebermetastasen neuroendokriner Tumoren kann durch Resektion im Sinne einer Tumormassenreduktion eine Langzeitpalliation erzielt werden. Von den potentiell kurativ resezierten Patienten können nur einige von ihnen geheilt werden. Die Indikationsstellung zur Resektion nicht colorectaler und nicht neuroendokriner Lebermetastasen ist aufgrund kleiner Fallzahlen und geringer Erfahrungen weniger klar definiert. Ein Rezidiv von Lebermetastasen nach einem potentiell kurativen Eingriff tritt bei mehr als 40–60 % der Patienten auf. Eine Resektion des Rezidivs ist bei nur 20–35 % dieser Patienten möglich. Hierbei beträgt die 3-Jahres-Überlebensrate um 30 %. Die Morbidität und Letalität nach Reresektion sind mit denen der ersten Leberresektion vergleichbar. Alle Ergebnisse zusammengenommen zeigen, daß die Resektion und Reresektion von Lebermetastasen bei sorgfältig selektionierten Patienten ohne extrahepatische Tumormanifestation mit einem Langzeitüberleben verbunden ist.

Endoscopic Minimally Invasive Thyroidectomy (eMIT): Safety First!

Dear Editor, We read with great interest the report entitled ‘‘Endoscopic Minimally Invasive Thyroidectomy (eMIT): A Prospective Proof-of-Concept Study in Humans’’ by Thomas Wilhelm and Andreas Metzig [1]. Because the Totally Transoral Video-Assisted Thyroidectomy (TOVAT) started as a project of the New European Surgical Academy (NESA), we feel that it is our responsibility to bring some facts to light that are important before a recommendation for any clinical application can be made. Although we could demonstrate the surgical feasibility of TOVAT as early as 2008 [2], we still had concerns about its clinical application, e.g., floor of mouth and specimen volume, triangulation and manipulation of instruments, difficulties in visualization of the recurrent laryngeal nerve, and risk of mental nerve lesion by lateral vestibulum trocar. All of these difficulties, which also were raised by Miccoli and colleagues as reaction to our video paper, were discussed and enlightened last year in a letter to the editor [3, 4]. Therefore, the NESA decided at that time not to proceed to clinical application before designed instrumentation and further preclinical investigation results were available. Unfortunately, the authors did not share our view. All details concerning this matter have already been published in another journal [5, 6]. Because in almost all hospitals in Germany thyroid surgery is performed by surgeons, this paper presented transoral thyroid resections performed by Dr. Metzig; the part of Dr. Wilhelm was solely the placement of trocars. It is noteworthy that Dr. Metzig did not participate in any of the preclinical trials, neither theoretically in the project conception nor practically on cadavers and living animals. The approval of the local regulatory authorities (Ethics Committee of the Saxon Chamber of Physicians/Germany, reference number EK-allg-03/10-1) to perform such ‘‘human experiment’’ is therefore not understandable. The authors encountered in their clinical application all above-cited difficulties and concerns, which are reflected in their presented results, such as paresthesia of the mental nerve in varying degrees in six of eight cases (75%), conversion to open surgery due to specimen size in three of eight cases (37.5%), palsy of the recurrent laryngeal nerve in two of eight cases (25%), and one permanent (12.5%) and local streptococci infection at the vestibular incision site necessitating incision and irrigation in one case (12.5%). Morbidity in the highly standardized thyroid surgery is as low as 4% and palsy of the recurrent laryngeal nerve occurs in less than 3% of patients. If the outcomes of these trials were monitored and evaluated continuously by the local institutional review board, why did it not intervene, because these severe adverse events already occurred from the first patient forward? In the meantime, this human ‘‘experiment’’ has been stopped and the involved surgical community in Germany is informed about these severe complications. All of these facts need to be communicated to guard against misunderstandings and to point out the complex and experimental character of TOVAT. To conclude, we are still convinced that the TOVAT method is a promising approach that needs further T. Benhidjeb (&) Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany e-mail: t.benhidjeb@uke.de

Surgical and Multimodality Treatment of Colorectal Liver Metastases

For patients with colorectal liver metastases, surgery offers the only possibility for cure. The achievable mean 5-year survival rate is 30%, and the 5-year disease-free survival rate approximately 15%. Due to refinement in operative and anesthetic techniques, improved critical care with a decrease in morbidity (< 30%) and mortality (< 5%), hepatic resection is a safe and efficient procedure. However, only 10–15% of patients with colorectal liver metastases can undergo potentially curative liver resection. Therefore, accurate staging is an important prerequisite in selecting patients who would benefit from surgery. Today, the most generally accepted contraindication for liver resection is the presence of discontinuous extra-hepatic spread and more than 4 metastases. Recurrence of hepatic metastases after potentially curative resection is observed in over 50% of cases. Re-resection of recurrent liver metastases can be beneficial in a carefully selected group of patients with limited disease. Multimodal neoadjuvant therapy is a promising tool for patients with colorectal liver metastases initially considered not R0-resectable. Cryosurgery and laser-induced thermotherapy are additive methods that may help to improve surgical treatment results in the future. Improvement in clinical outcome and survival can be achieved.