The surgical anatomy of a (robot-assisted) minimally invasive transcervical esophagectomy.

BACKGROUND: Transcervical esophagectomy allows for esophagectomy through transcervical access and bypasses the thoracic cavity, thereby eliminating single lung ventilation. A challenging surgical approach demands thorough understanding of the encountered anatomy. This study aims to provide a comprehensive overview of surgical anatomy encountered during the (robot-assisted) minimally invasive transcervical esophagectomy (RACE and MICE). METHODS: To assess the surgical anatomy of the lower neck and mediastinum, MR images were made of a body donor after, which it was sliced at 24-µm intervals with a cryomacrotome. Images were made every 3 slices resulting in 3.200 images of which a digital 3D multiplanar reconstruction was made. For macroscopic verification, microscopic slices were made and stained every 5 mm (Mallory-Cason). Schematic drawings were made of the 3D reconstruction to demonstrate the course of essential anatomical structures in the operation field and identify anatomical landmarks. RESULTS: Surgical anatomy 'boxes' of three levels (superior thoracic aperture, upper mediastinum, subcarinal) were created. Four landmarks were identified: (i) the course of the thoracic duct in the mediastinum; (ii) the course of the left recurrent laryngeal nerve; (iii) the crossing of the azygos vein right and dorsal of the esophagus; and (iv) the position of the aortic arch, the pulmonary arteries, and veins. CONCLUSIONS: The presented 3D reconstruction of unmanipulated human anatomy and schematic 3D 'boxes' provide a comprehensive overview of the surgical anatomy during the RACE or MICE. Our findings provide a useful tool to aid surgeons in learning the complex anatomy of the mediastinum and the exploration of new surgical approaches such as the RACE or MICE.

Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

[Preconditioning of the lungs and circulation before visceral and thoracic surgical interventions]. / Präkonditionierung von Lunge und Kreislauf vor viszeral- oder thoraxchirurgischen Eingriffen.

BACKGROUND: Estimation of the perioperative risk plays a decisive role in the surgical indications, particularly in view of the demographic change. For this reason, prehabilitation concepts for reducing perioperative risk nowadays play an increasingly important role. OBJECTIVE: Presentation of the current recommendations for preoperative diagnostics in thoracic surgical interventions as well as existing prehabilitation concepts and their practical applicability. MATERIAL AND METHODS: A selective review of the literature was carried out by searching the electronic databases PubMed, Cochrane Library and ISRCTN, including the guidelines of the American College of Chest Physicians (ACCP) and the European Society of Thoracic Surgery (ESTS). RESULTS: Preconditioning includes the conservative treatment of underlying diseases, smoking cessation and prehabilitation. Prehabilitation is an increasingly pressing concept in routine clinical practice, even though the evidence is limited due to the very heterogeneous study situation. Overall, however, there is a tendency for positive effects on the quality of life and postoperative complications as well as convalescence. CONCLUSION: In addition to preoperative diagnostics to assess the perioperative risk, effective preconditioning of patients is also necessary. For this an interdisciplinary approach including anesthesia, pneumology, psychotherapy and physiotherapy is necessary. In addition to the conservative medicinal optimization, prehabilitation concepts are gaining in importance and will certainly become established in routine clinical practice. From the surgical perspective, minimally invasive approaches and parenchyma-sparing resections also serve to reduce risks.

[Robot-assisted vs laparoscopic gastric bypass : First experiences with the DaVinci system in bariatric surgery]. / Roboterassistierter vs. laparoskopischer Magenbypass : Erste Erfahrungen mit dem DaVinci-System in der bariatrischen Chirurgie.

Conventional laparoscopy is the gold standard in bariatric surgery. Internationally, robot-assisted surgery is gaining in importance. Up to now there are only few reports from Germany on the use of the system in bariatric surgery. Since January 2017 we have been performing robot-assisted gastric bypass surgery. It remains unclear whether the use of the robotic system has advantages over the well-established laparoscopic technique. Within a period from January to early August 2017 a total of 53 gastric bypass operations were performed. Of these 16 proximal redo Roux-en-Y gastric bypass operations were performed with the DaVinci Si system versus 29 laparoscopic procedures. A retrospective analysis of the perioperative course was carried out. Body weight, body mass index (BMI), Edmonton obesity staging system (EOSS) and American Society of Anesthesiologists (ASA) classification did not show significant differences. There were also no significant differences in terms of estimated blood loss, intraoperative complications, duration of surgery, postoperative inflammatory parameters and weight loss. There was no mortality and no need for revisional surgery in either group. After laparoscopic surgery there was a delayed occurrence of a leak of the gastrojejunostomy followed by readmission and endoscopic negative pressure wound therapy. The results show that the proximal Roux-en-Y gastric bypass can be performed safely and efficiently using the DaVinci surgical system. Significant differences to the conventional laparoscopic procedure were not found. Larger randomized controlled trials are needed to define the role of the DaVinci system in bariatric surgery.

Fully robotic da Vinci Ivor-Lewis esophagectomy in four-arm technique-problems and solutions.

The aim of this technical note is a step-by-step description of a fully robotic abdominothoracic esophagectomy with an intrathoracic esophagogastrostomy. We report on our technique and short-term results of 75 patients undergoing an Ivor-Lewis esophagectomy using a fully robotic 4-arm approach in the abdominal and thoracic phase with a hand-sewn intrathoracic anastomosis. There are several important steps and differences to consider compared to the conventional minimal invasive approach (patient's positioning, anaesthesiological set up, port placement, gastric conduit pull up, technique of esophagostrostomy). Mean operative time was 392 minutes (240-610) with a 94% R0 resection status. Conversion to open procedure occurred in 2 (2.6%) in the abdominal, and 14 (18.2%) in the thoracic phase. Main reasons for conversion were problems during the lifting of the gastric conduit and difficulties in the construction of the esophagogastrostomy. The rate dropped during the last 20 patients (1/20 (10%). Our results suggest that the reported technique is safe and feasible. It satisfies the oncological principles and provides the advantages of robotic assisted minimal invasive surgery.

Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B.

Resistance towards VEGF-centered anti-angiogenic therapy still represents a substantial clinical challenge. We report here that mast cells alter the proliferative and organizational state of endothelial cells which reduces the efficacy of anti-angiogenic therapy. Consequently, absence of mast cells sensitizes tumor vessels for anti-angiogenic therapy in different tumor models. Mechanistically, anti-angiogenic therapy only initially reduces tumor vessel proliferation, however, this treatment effect was abrogated over time as a result of mast cell-mediated restimulation of angiogenesis. We show that mast cells secrete increased amounts of granzyme b upon therapy, which mobilizes pro-angiogenic laminin- and vitronectin-bound FGF-1 and GM-CSF from the tumor matrix. In addition, mast cells also diminish efficacy of anti-angiogenic therapy by secretion of FGF-2. These pro-angiogenic factors act beside the targeted VEGFA-VEGFR2-axis and reinduce endothelial cell proliferation and angiogenesis despite the presence of anti-angiogenic therapy. Importantly, inhibition of mast cell degranulation with cromolyn is able to improve efficacy of anti-angiogenic therapy. Thus, concomitant mast cell-targeting might lead to improved efficacy of anti-angiogenic therapy.Resistance towards VEGF-centered anti-angiogenic therapy is an important clinical challenge. Here, the authors show that mast cells mediate resistance to anti-angiogenetic inhibitors by altering the proliferative and organizational state of endothelial cells through mobilization of FGF-1 and GM-CSF from the tumor matrix and secretion of FGF-2.

[Robotic pylorus-preserving pancreaticoduodenectomy : Video article]. / Roboterassistierte pyloruserhaltende Pankreaskopfresektion : Videobeitrag.

Pylorus-preserving pancreaticoduodenectomy is one of the most complex procedures in general surgery. Laparoscopic pancreaticoduodenectomy was initially described in 1994; however, its worldwide distribution is so far limited to only a few specialist centers. Robotic surgery using the DaVinci® system can overcome many limitations of laparoscopic surgery. The system is a promising tool for a more widespread introduction of minimally invasive surgery for pancreatic diseases. Mortality rates of 0-5% and pancreatic fistula rates of 0-35% are described in the literature; therefore, thorough complication management is crucial in the postoperative course. The video presents a robotic pylorus-preserving pancreaticoduodenectomy for periampullary carcinoma in a female patient.

[Robot-assisted liver resection]. / Roboterassistierte Leberresektion.

Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.

[Robot-assisted rectal surgery: hype or progress?]. / Roboterassistierte Rektumchirurgie: Hype oder Fortschritt?

Minimally invasive laparoscopic surgery for rectal cancer has undergone a significant evolution during the last decades and has become the standard approach in specialized centers with better short-term and comparable oncological outcome to open surgery. The laparoscopic approach remains challenging and has various inherent technical challenges particularly associated with rectal cancer resection. Robotic colorectal surgery using the da Vinci® surgical system has been successfully introduced into clinical practice during recent years and provides specific technical advantages. Studies have shown that the robotic approach in colorectal surgery is safe and feasible with comparable results. It is associated with low conversion rates, more R0 situations for low rectal cancer with larger tumors and more neoadjuvant treatment compared to standard laparoscopy. Robot-assisted surgery is an attractive development of minimally invasive surgery and should also be further evaluated with mandatory monitoring of outcome parameters in registries in Germany.

[Robot-assisted Pylorus-Preserving Partial Pancreaticoduodenectomy (Kausch-Whipple Procedure)]. / Roboterassistierte, pyloruserhaltende partielle Duodenopankreatektomie nach Kausch-Whipple.

BACKGROUND: The surgical treatment of pancreatic head tumours is one of the most complex procedures in general surgery. In contrast to colorectal surgery, minimally-invasive techniques are not very commonly applied in pancreatic surgery. Both the delicate dissection along peri- and retropancreatic vessels and the extrahepatic bile ducts and subsequent reconstruction are very demanding with rigid standard laparoscopic instruments. The 4-arm robotic surgery system with angled instruments, unidirectional movement of instruments with adjustable transmission, tremor elimination and a stable, surgeon-controlled 3D-HD view is a promising platform to overcome the limitations of standard laparoscopic surgery regarding precise dissection and reconstruction in pancreatic surgery. INDICATION: Pancreatic head resection for mixed-type IPMN of the pancreatic head. PROCEDURE: Robot-assisted, minimally-invasive pylorus-preserving pancreaticoduodenectomy (Kausch-Whipple procedure). CONCLUSION: The robotic approach is particularly suited for complex procedures such as pylorus-preserving pancreatic head resections. The fully robotic Kausch-Whipple procedure is technically feasible and safe. The advantages of the robotic system are apparent in the delicate dissection near vascular structures, in lymph node dissection, the precise dissection of the uncinate process and, especially, bile duct and pancreatic anastomosis.

[Implementation of Robot-Assisted Surgery]. / Aufbau eines Roboterprogramms.

The implementation of robot-assisted surgery requires a multi disciplinary approach with appropriate training and cooperation of surgical, anesthetic and technical staff. Besides acquiring the technical skills and getting used to complex technique, patient selection and an appropriate frequency of procedures are required to avoid complications.

[Robotic-Assisted Oesophageal Surgery]. / Roboterchirurgie am Ösophagus.

BACKGROUND: Abdominothoracic oesophageal resections, also known as Ivor Lewis procedures, are complex visceral surgery procedures. In recent years, substeps have increasingly been performed using minimally invasive techniques. However, intrathoracic anastomosis is still a challenge given the instrumental and technological possibilities available to date. This article provides a detailed description of the use of the Da Vinci robotic system and our techniques in oesophageal surgery. METHODS: In a prospective data collection, we analysed the robotic-assisted oesophageal surgeries performed at the University Hospital of Schleswig-Holstein, Campus Kiel, between November 2013 and November 2015. RESULTS: A total of 56 patients underwent robotic-assisted oesophageal surgery, with 43 patients undergoing the Ivor Lewis technique, 10 patients undergoing the McKeown procedure and 3 patients undergoing enucleation of a leiomyoma. A complete tumour resection (R0 margin) was achieved in 53 patients (93.4%); the mean number of resected lymph nodes was 23 (14-75). Forty-five (80.5%) patients received an induction therapy. Mean operative time was 412 min (120-610); mean hospital stay was 19 days (4-145). A conversion to open surgery was necessary in 19 (34.1%) cases, most notably in the thoracic part of the surgical procedure (17 patients). Forty-three patients received intrathoracic oesophagogastrostomy; 4 out of 5 patients with an initial side-to-side anastomosis developed a leakage, whereupon the technique was switched to a hand-sewn procedure (leakage in 3 out of 20 patients). Other major morbidities included leakage of the gastric conduit in 2 patients (3.6%), airway fistula in 2 patients (3.6%), mesenteric ischaemia in one patient (1.8%), and peritonitis due to a dislocated feeding tube in one other patient. Pulmonary complications occurred in 19 patients (34%). Four patients (7.1%) died of pulmonary embolism, heart attack, and septic organ failure. CONCLUSION: Robotic-assisted, minimally invasive oesophagectomy is a feasible and useful approach for oncological surgery. This technique should be implemented in a structured program with an extensive and critical evaluation of the users' own results and an exchange with other experienced work teams. This helps to avoid pitfalls and to speed up the learning curve. Further technological developments and increasing experience might lead to a more widespread use of this technique.

[Interdisciplinary Diagnosis and Treatment of Deep Infiltrating Endometriosis]. / Interdisziplinäre Diagnostik und Therapie der tief infiltrierenden Endometriose.

Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the interdisciplinary approach to the treatment of deep infiltrating endometriosis. Endometriosis has been defined as the presence of endometrial glands and stroma outside the internal epithelial lining of the cavum uteri. As a consequence, endometriosis can cause a wide range of symptoms such as chronic pelvic pain, subfertility, dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms (e.g., dyschezia, bloating, constipation, rectal bleeding, diarrhoea and hematuria), abnormal menstrual bleeding, chronic fatigue or low back pain. Approx. 50 % of teenagers and up to 32 % of women of reproductive age, operated for chronic pelvic pain or dysmenorrhoea, suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, a causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The correct treatment for each patient should take into account the severity of the disease and whether the patient desires to have children. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 and > 60 % and is very much dependent on the integrated management and surgical skills of the respective hospital. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should, especially in the case of deep infiltrating endometriosis, be undertaken in appropriate centres.

[Robot-assisted minimally invasive lobectomy with systematic lymphadenectomy for lung cancer]. / Roboterassistierte minimalinvasive Lobektomie mit systematischer Lymphadenektomie zur Behandlung des Bronchialkarzinoms.

BACKGROUND AND INTRODUCTION: Lobectomy for lung cancer is the standard therapy for lung cancer in limited stages. The adoption of minimally invasive lobectomy (video-assisted thoracic surgery or VATS lobectomy) has increased worldwide since its first description more than 15 years ago. However, the VATS technique has a long learning curve and sometimes limitations in terms of precise preparation and presentability of the central structures of the lung hilus due to the limited mobility of the standard thoracoscopic instruments. By using a four-arm robotic platform (DaVinci®), not only the preparation of the hilus structures but also the central lymphadenectomy can be performed in a comfortable and safe way under a clear and precise view. INDICATION: Surgical treatment of locally limited lung cancer in the right lower lobe (squamous cell carcinoma). PROCEDURE: Robot-assisted, minimally invasive right lower lobectomy with systematic lymphadenectomy. CONCLUSION: Robot-assisted minimal invasive lobectomy is feasible with special regard to oncological and technical aspects. Especially the intrathoracic precise dissection of the tissue under a perfect view allow a comfortable and safe operation technique.

Does neoadjuvant treatment before oncologic esophagectomy affect the postoperative quality of life? A prospective, longitudinal outcome study.

To evaluate the cancer patients' quality of life (QoL) following esophagectomy the focus was placed on the impact of neoadjuvant treatment before surgery. For patients undergoing oncologic surgery, the QoL is generally accepted as an important outcome parameter in addition to clinical parameters. This prospective nonrandomized study evaluated QoL in patients treated by preoperative chemo(radio)therapy followed by either surgery or surgery alone with special focus on the postoperative course. QoL was assessed in 131 consecutive patients who underwent surgery for esophageal cancer. The EORTC-QLQ-C30 and a tumor-specific module were administered before surgery, at discharge, 3, 6, 12, and 24 months after surgery. Clinical data were collected prospectively and a follow up was performed every 6 months. The histological type of cancer was squamous cell carcinoma in 49.6% and adenocarcinoma in 50.4%. There was no significant difference between patients that were treated neoadjuvantly and those that were first operated on with regard to morbidity, mortality, and survival rates (5-year survival rate of 34%). Most QoL scores dropped significantly below the baseline in the early postoperative period and recovered slowly during the follow-up period to almost preoperative levels in many scores. There was no statistically significant difference in any of the QoL scales between neoadjuvantly treated or primary operated patients. Esophageal resections are associated with significant deterioration of QoL, which slowly recovers during the follow-up period to an almost preoperative level. Neoadjuvant treatment seems to not further negatively affect the QoL deterioration.

c-Rel is a critical mediator of NF-κB-dependent TRAIL resistance of pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies with an overall life expectancy of 6 months despite current therapies. NF-κB signalling has been shown to be critical for this profound cell-autonomous resistance against chemotherapeutic drugs and death receptor-induced apoptosis, but little is known about the role of the c-Rel subunit in solid cancer and PDAC apoptosis control. In the present study, by analysis of genome-wide patterns of c-Rel-dependent gene expression, we were able to establish c-Rel as a critical regulator of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in PDAC. TRAIL-resistant cells exhibited a strong TRAIL-inducible NF-κB activity, whereas TRAIL-sensitive cells displayed only a small increase in NF-κB-binding activity. Transfection with siRNA against c-Rel sensitized the TRAIL-resistant cells in a manner comparable to siRNA targeting the p65/RelA subunit. Gel-shift analysis revealed that c-Rel is part of the TRAIL-inducible NF-κB complex in PDAC. Array analysis identified NFATc2 as a c-Rel target gene among the 12 strongest TRAIL-inducible genes in apoptosis-resistant cells. In line, siRNA targeting c-Rel strongly reduced TRAIL-induced NFATc2 activity in TRAIL-resistant PDAC cells. Furthermore, siRNA targeting NFATc2 sensitized these PDAC cells against TRAIL-induced apoptosis. Finally, TRAIL-induced expression of COX-2 was diminished through siRNA targeting c-Rel or NFATc2 and pharmacologic inhibition of COX-2 with celecoxib or siRNA targeting COX-2, enhanced TRAIL apoptosis. In conclusion, we were able to delineate a novel c-Rel-, NFATc2- and COX-2-dependent antiapoptotic signalling pathway in PDAC with broad clinical implications for pharmaceutical intervention strategies.

[Robotic-assisted minimally invasive abdominothoracal oesophageal resection with intrathoracic anastomosis]. / Roboterassistierte, minimalinvasive abdominothorakale Ösophagusresektion mit intrathorakaler Anastomose.

BACKGROUND: Ivor Lewis oesophagectomy is one of the approaches used worldwide for treating oesophageal cancer. The adoption of minimally invasive oesophagectomy has increased worldwide since its first description more than 15 years ago. However, minimally invasive oesophagectomy with a chest anastomosis has advantages. By using a four-arm robotic platform, not only the preparation of the gastric tube and mobilisation of the oesophagus but also the intrathoracic anastomosis of the oesophagogastrostomy can be performed in a comfortable and safe way. INDICATION: The indication for oesophageal resection is oesophageal cancer. PROCEDURE: The operative procedure comprises robotic-assisted abdominothoracal oesophageal resection with reconstruction by a gastric tube and intrathoracic anastomosis (Ivor Lewis procedure). CONCLUSION: Robotic abdominal and thoracic minimally invasive esophagectomy is feasible, and safe with a complete lymph node dissection. Especially the intrathoracic anastomosis of the oesophagogastrostomy can be performed in a comfortable and safe way.

Site-specific gene expression and localization of growth factor ligand receptors RET, GFRα1 and GFRα2 in human adult colon.

Two of the glial-cell-line-derived neurotrophic factor (GDNF) family ligands (GFLs), namely GDNF and neurturin (NRTN), are essential neurotropic factors for enteric nerve cells. Signal transduction is mediated by a receptor complex composed of GDNF family receptor alpha 1 (GFRα1) for GDNF or GFRα2 for NRTN, together with the tyrosine kinase receptor RET (rearranged during transfection). As both factors and their receptors are crucial for enteric neuron survival, we assess the site-specific gene expression of these GFLs and their corresponding receptors in human adult colon. Full-thickness colonic specimens were obtained after partial colectomy for non-obstructing colorectal carcinoma. Samples were processed for immunohistochemistry and co-localization studies. Site-specific gene expression was determined by real-time quantitative polymerase chain reaction in enteric ganglia and in circular and longitudinal muscle harvested by microdissection. Protein expression of the receptors was mainly localized in the myenteric and submucosal plexus. Dual-label immunohistochemistry with PGP 9.5 as a pan-neuronal marker detected immunoreactivity of the receptors in neuronal somata and ganglionic neuropil. RET immunoreactivity co-localized with neuronal GFRα1 and GFRα2 signals. The dominant source of receptor mRNA expression was in myenteric ganglia, whereas both GFLs showed higher expression in smooth muscle layers. The distribution and expression pattern of GDNF and NRTN and their corresponding receptors in the human adult enteric nervous system indicate a role of both GFLs not only in development but also in the maintenance of neurons in adulthood. The data also provide a basis for the assessment of disturbed signaling components of the GDNF and NRTN system in enteric neuropathies underlying disorders of gastrointestinal motility.

Expression and function of the Transforming Growth Factor-b system in the human and rat enteric nervous system.

BACKGROUND: Transforming growth factor-betas (TGF-bs) are pleiotropic growth factors exerting neurotrophic functions upon various neuronal populations of the central nervous system. In contrast, the role of TGF-b isoforms in the enteric nervous system (ENS) is largely unknown. We therefore analyzed the gene expression pattern of the TGF-b system in the human colon and in rat myenteric plexus, and smooth muscle cell cultures and determined the effect of TGF-b isoforms on neuronal differentiation. METHODS: Human colonic samples as well as cultured rat myenteric plexus, and smooth muscle cells were assessed for mRNA expression levels of the TGF-b system (TGF-b1-3, TbR-1-3) by qPCR. The colonic wall was separated into mucosa and tunica muscularis and enteric ganglia were isolated by laser microdissection (LMD) to allow site-specific gene expression analysis. Effects of TGF-b isoforms on neurite outgrowth and branching pattern of cultured myenteric neurons were monitored. KEY RESULTS: mRNA expression of the TGF-b system was detected in all compartments of the human colonic wall as well as in LMD-isolated myenteric ganglia. Cultured myenteric neurons and smooth muscle cells of rat intestine also showed mRNA expression of all ligands and receptors. Transforming growth factor-b2 treatment increased neurite length and branching pattern in cultured myenteric neurons. CONCLUSIONS & INFERENCES: The TGF-b system is abundantly expressed in the human and rat ENS arguing for an auto-/paracrine function of this system on enteric neurons. Transforming growth factor-b2 promotes neuronal differentiation and plasticity characterizing this molecule as a relevant neurotrophic factor for the ENS.