Primary laparoscopic fundoplication in selected patients with gastroesophageal reflux disease.

BACKGROUND: Despite proton pump inhibitors being a powerful therapeutic tool, laparoscopic fundoplication (LF) has proven successful in the treatment of gastroesophageal reflux disease (GERD), through mechanical augmentation of a weak antireflux barrier and the advantages of minimally invasive access. A critical patient selection for LF, based on thorough preoperative assessment, is important for the management of GERD-patients. The purpose of this study is to provide an overview on the management of GERD-patients treated by primary LF in a specialized center and to illustrate the possible outcome after several years. METHODS: Patients were selected after going through diagnostic workup consisting of patient's history and physical examination, upper gastrointestinal endoscopy, assessment of gastrointestinal Quality of Life Index, screening for somatoform disorders, functional assessment by esophageal manometry, (impedance)-24-hour-pH-monitoring, and selective radiographic studies. The indication for LF was based on EAES-guidelines. Either a floppy and short Nissen fundoplication was performed or a posterior Toupet-hemifundoplication was chosen. A long-term follow-up assessment was attempted after surgery. RESULTS: In total, n = 1131 patients were evaluated (603 males; 528 females; mean age; 48.3 years; and mean body mass index: 27). The mean duration between onset of symptoms and surgery was 8 years. Nissen: n = 873, Toupet: n = 258; conversion rateerativ: 0.5%; morbidity 4%, mortality: 1 (1131). Mean follow-up (n = 898; 79%): 5.6 years; pre/post-op results: esophagitis: 66%/12.1%; Gastrointestinal Quality of Life Index: median: 92/119; daily proton pump inhibitors-intake after surgery: 8%; and operative revisions 4.3%. CONCLUSIONS: In conclusion, our data show that careful patient selection for laparoscopic fundoplication and well-established technical concepts of mechanical sphincter augmentation can provide satisfying results in the majority of patients with severe GERD.

How effective is laparoscopic redo-antireflux surgery?

BACKGROUND: The failure-rate after primary antireflux surgery ranges from 3 to 30%. Reasons for failures are multifactorial. The aim of this study is to gain insight into the complex reasons for, and management of, failure after antireflux surgery. METHODS: Patients were selected for redo-surgery after a diagnostic workup consisting of history and physical examination, upper gastrointestinal endoscopy, quality-of-life assessment, screening for somatoform disorders, esophageal manometry, 24-hour-pH-impedance monitoring, and selective radiographic studies such as Barium-sandwich for esophageal passage and delayed gastric emptying. Perioperative and follow-up data were compiled between 2004 and 2017. RESULTS: In total, 578 datasets were analyzed. The patient cohort undergoing a first redo-procedure (n = 401) consisted of 36 patients after in-house primary LF and 365 external referrals (mean age: 62.1 years [25-87]; mean BMI 26 [20-34]). The majority of patients underwent a repeated total or partial laparoscopic fundoplication. Major reasons for failure were migration and insufficient mobilization during the primary operation. With each increasing number of required redo-operations, the complexity of the redo-procedure itself increased, follow-up quality-of-life decreased (GIQLI: 106; 101; and 100), and complication rate increased (intraoperative: 6,4-10%; postoperative: 4,5-19%/first to third redo). After three redo-operations, resections were frequently necessary (morbidity: 42%). CONCLUSIONS: Providing a careful patient selection, primary redo-antireflux procedures have proven to be highly successful. It is often the final chance for a satisfying result may be achieved upon performing a second redo-procedure. A third revision may solve critical problems, such as severe pain and/or inadequate nutritional intake. When resection is required, quality of life cannot be entirely normalized.

Severity of GERD and disease progression.

BACKGROUND: Many factors may play a role in the severity and progression of gastroesophageal reflux disease (GERD) since pathophysiology is multifactorial. Data regarding the progression of GERD are controversial: some reports of increased esophageal acid exposure (EAE) and mucosal damage were considered as evidence for a stable disease course, while others interprete these findings as disease progression. The aim of this study is to analyze a large patient-population with persisting symptoms indicative of GERD under protonpumpinhibitor-therapy and identify components characterizing disease severity and progression. METHODS: Patients with symptoms indicative of GERD were included in the study in a tertiary referral center (Frankfurt, Germany). All selected patients were under long-term protonpumpinhibitor-therapy with persistant symptoms. All patients underwent investigations to collect data on their physical status, EAE, severity of esophagitis, anatomical changes, and esophageal functional defects as well as their relation to the duration of the disease. Incidence over time was plotted as survival curves and tested with Log-rank tests for the four main disease markers. Multivariate modeling with COX-regression model was used to estimate the general impact of the four main disease markers on the time course of the disease. In order to elucidate possible causal relationships over time, a path analysis (structural equation model) was calculated. RESULTS: From the database with 1480 data sets, 972 patients were evaluated (542 males, 430 females). The mean age was 50.5 years (range18-89). The mean body mass index was 27.2(19-48). The mean time between the onset of symptoms and the diagnostic investigations was 8.2 years (1-50). A longer disease history for GERD was significantly associated with a higher risk for LES-incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES-incompetence (n = 563), compared to a mean of 6 years for those with mechanically intact LES (n = 95). A longer period from symptom onset to diagnostics was significantly associated with higher acid exposure. The pathway analysis was significant for the following model: 'history' (P < 0.001➔LES-incompetence & Hiatal Hernia➔(p < 0,001)➔pH-score (P < 0.001).Conclusion: LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD. Path modeling suggests a causal sequence overtime of the main disease-parameters, tentatively allowing for a prediction of the course of the disease.

Foregut symptoms, somatoform tendencies, and the selection of patients for antireflux surgery.

A large variety of foregut symptoms can occur in patients with gastroesophageal reflux disease (GERD), which can overlap with other disorders such as somatoform disorders and dyspepsia. Due to unclear diagnostic situations, these patients are often not adequately treated. The aim of this study was the evaluation of patients with foregut symptoms, referred for possible antireflux surgery, regarding their relationship with GERD and somatization tendencies based on control data from an unselected population. Symptom evaluation and somatization screening were initiated both in volunteers and in patients with foregut symptoms and GERD. Unselected volunteers from a village population were also evaluated by symptom analysis and for somatisation tendency. In addition, patients with foregut symptoms were diagnosed for GERD, and symptom analysis and psychodiagnostic evaluation were performed. There is no major significant difference in the symptom-spectrum in patients with foregut symptoms, whether they have a proven pathologic acid exposure from GERD or not. The probability for the risk of somatization was 5.6% in the unselected population of nonpatient volunteers (n = 267). In patients with foregut symptoms (n = 750), the probability for the presence of somatoform tendencies was approximately 20%, independent whether these patients had a documented GERD or a normal esophageal acid exposure, implicating further diagnostic work-up for the selection of patients for antireflux surgery. There is a remarkable symptom load and variety in patients with GERD, in patients with foregut symptoms, and in an unselected population of volunteers. There is no difference in the risk for somatization between patients with foregut symptoms and those with documented GERD. Therapeutic decision making especially prior to antireflux surgery requires an awareness of mental and emotional challenges.

The potential and perspective of peroral endoscopic esophageal myotomy for achalasia.

The therapeutic spectrum of this disorder consists of medical therapy, endoscopic balloon dilatation, endoscopic Botox injection, open or laparoscopic cardia myotomy, and most recently transesophageal endoscopic myotomy (POEM peroral endoscopic myotomy). The most important requirement is a well-experienced team in interventional flexible endoscopy. The endoscopist as well as the assisting staff should have experience in advanced therapeutic endoscopic techniques and hemostasis to handle all necessary endoscopic instruments such as injection needles, needle knife, triangle knife, coagulation graspers, and endoscopic clip handling and closures. In addition, advanced surgical and especially laparoscopic skills and experience as well as surgical knowledge about esophageal disease must be available in case of conversion and/or consultation. Prior to this procedure, the patient undergoes a detailed diagnostic work-up to confirm the diagnosis of achalasia. The procedures are performed in general anesthesia. The patient is brought in a supine position, and the abdomen is free for inspection and palpation during the procedure. The myotomy can be performed in different locations around the esophageal circumference. In Europe, several centers with large experience in esophageal disease, laparoscopy, and especially advanced interventional endoscopy have started to introduce this POEM-technique in their clinical practice. Initial success and low complication rates are quite promising and show a great future perspective for this technique. In the USA, POEM is a procedure with a substantial increase in numbers performed in the past years with a low complication rate. The largest series are performed in Asia with a great clinical success. The perspective of POEM may be the lesser access trauma. Its potential can be also realized in Redo cases, where experienced centers have initial experience with POEM after POEM and POEM after LHMD.

Euro-NOTES Status Paper: from the concept to clinical practice.

BACKGROUND: The concept of natural orifice transluminal endoscopic surgery (NOTES) consists of the reduction of access trauma by using a natural orifice access to the intra-abdominal cavity. This could possibly lead to less postoperative pain, quicker recovery from surgery, fewer postoperative complications, fewer wound infections, and fewer long-term problems such as hernias. The Euro-NOTES Foundation has organized yearly meetings to work on this concept to bring it safely into clinical practice. The aim of this Euro-NOTES status update is to assess the yearly scientific working group reports and provide an overview on the current clinical practice of NOTES procedures. METHODS: After the Euro-NOTES meeting 2011 in Frankfurt, Germany, an analysis was started regarding the most important topics of the European working groups. All prospectively documented information was gathered from Euro-NOTES and D-NOTES working groups from 2007 to 2011. The top five topics were analyzed. RESULTS: The statements of the working group activities demonstrate the growing information and changing insights. The most important selected topics were infection issue, peritoneal access, education and training, platforms and new technology, closure, suture, and anastomosis. The focus on research topics changed over time. The principle of hybrid access has overcome the technical and safety limitations of pure NOTES. Currently the following NOTES access routes are established for several indications: transvaginal access for cholecystectomy, appendectomy and colon resections; transesophageal access for myotomy; transgastric access for full-thickness small-tumor resections; and transanal/transcolonic access for rectal and colon resections. CONCLUSIONS: NOTES and hybrid NOTES techniques have emerged for all natural orifices and were introduced into clinical practice with a good safety record. There are different indications for different natural orifices. Each technique has been optimized for the purpose of finding a safe and realistic solution to perform the procedure according to the specific indication.

[Benign esophageal disorders. Gastroesophageal reflux disease, diffuse esophageal spasm, achalasia]. / Benigne Erkrankungen des Ösophagus. Refluxkrankheit, diffuser Ösophagusspasmus, Achalasie.

Gastroesophageal reflux disease (GERD) is the most frequent benign disorder of the upper gastrointestinal (GI) tract and other defined disease entities, such as achalasia and diffuse esophageal spasm, also belong to this group. In addition to surgical therapy, medicinal therapy also has an important role in all 3 of these disorders. Therefore, it is very important to follow precise indication criteria based on diagnostic evaluation and patient selection as well as to use an optimal operative technique.The therapeutic spectrum for achalasia varies from Botox injections and endoscopic dilatation to laparoscopic myotomy which achieves a success rate up to 90%.Patients with diffuse spasm suffer from severe dysphagia, thoracic pain and burning sensations and even respiratory problems. Surgical therapy consists of thoracoscopic long myotomy and in selective cases with persisting pain even esophagectomy and gastric pull-up.Therapeutic options for GERD predominantly involve conservative medicinal therapy with proton pump inhibitors and selective laparoscopic antireflux procedures. Minimally invasive techniques have led to a higher acceptance of surgical therapy. The two major procedures most frequently used are total Nissen fundoplication and posterior partial Toupet fundoplication.

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease using multiple Plicator implants: 12-month multicenter study results.

BACKGROUND: The full-thickness Plicator (Ethicon Endosurgery, Sommerville, NJ, USA) was developed for endoscopic treatment of gastroesophageal reflux disease (GERD). The goal is to restructure the antireflux barrier by delivering transmural pledgeted sutures through the gastric cardia. To date, studies using this device have involved the placement of a single suture to create the plication. The purpose of this study was to evaluate the 12-month safety and efficacy of this procedure using multiple implants to restructure the gastroesophageal (GE) junction. METHODS: A multicenter, prospective, open-label trial was conducted at four tertiary centers. Eligibility criteria included symptomatic GERD [GERD Health-Related Quality-of-Life (GERD-HRQL) questionnaire, off of medication], and pathologic reflux (abnormal 24-h pH) requiring daily proton pump inhibitor therapy. Patients with Barrett's epithelium, esophageal dysmotility, hiatal hernia > 3 cm, and esophagitis (grade III or greater) were excluded. All patients underwent endoscopic full-thickness plication with linear placement of at least two transmural pledgeted sutures in the anterior gastric cardia. RESULTS: Forty-one patients were treated. Twelve months post treatment, 74% of patients demonstrated improvement in GERD-HRQL scores by > or = 50%, with mean decrease of 17.6 points compared with baseline (7.8 vs. 25.4, p < 0.001). Using an intention-to-treat model, 63% of patients had symptomatic improvements of > or = 50%, with mean GERD-HRQL decrease of 15.0 (11.0 vs. 26.0, p < 0.001). The need for daily proton pump inhibitor (PPI) therapy was eliminated in 69% of patients at 12 months on a per-protocol basis, and 59% on an intention-to-treat basis. Adverse events included postprocedure abdominal pain (44%), shoulder pain (24%), and chest pain (17%). No long-term adverse events occurred. CONCLUSIONS: Endoscopic full-thickness plication using multiple Plicator implants can be used safely and effectively to improve GERD symptoms and reduce medication use.

[Natural orifice transluminal endoscopic surgery in future obesity treatment]. / NOTES als Zukunftsmodel für die Adipositaschirurgie.

The current trend in surgery to minimize access trauma will continue. As experience grows, minimally invasive surgical techniques are used increasingly in major surgical procedures to treat morbid obesity. Obese patients benefit most from its low morbidity for complications. As a result transluminal endoscopic surgery via natural orifices (NOTES) is obviously of great interest due to its potential in obesity surgery. In NOTES procedures, natural orifices such as the transgastric, transvaginal, transcolonic, and transvesical routes are used. Possible advantages are faster recovery, less pain, greater patient mobility, no hernias, and better cosmesis. Endoscopic intraluminal techniques and sleeve gastrectomy are procedures which can be best transferred into NOTES and associated techniques. Obesity surgery is an important element of gastrointestinal surgery today and has an important future role in our societies. Principles of minimal access surgery, as represented by NOTES, will be developed further and play a future role in medicine.

Laparoscopic Nissen repair: indications, techniques and long-term benefits.

BACKGROUND: The Nissen fundoplication or total 360 degrees fundoplication is probably the most frequently used anti-reflux procedure throughout the world. With the advent of laparoscopic surgery the popularity among surgeons to perform a laparoscopic Nissen fundoplication has even increased. AIM: The purpose of this paper is to provide an overview of the experience of laparoscopic Nissen fundoplication over the past 15 years. METHOD: We performed an extensive review of the literature in order to ascertain the representative papers. In addition, available consensus papers, especially with regard to indication and technique, were assessed. Indication for a laparoscopic Nissen fundoplication should depend on documentation of the presence of disease as well as objective testing of the functional disorders and the complications. The technique of Nissen fundoplication is discussed controversially. Consensus exists with regard to floppiness of the wrap, necessary closure of the crurae and the use of a calibration method during the performance of the wrap. RESULTS: The laparoscopic technique creates a learning curve, which needs to be respected. Large prospective series in recent years have shown a complication rate between 5% and 10%, depending on the definition of the complication. In these last prospective series good and excellent results have been reported, of between 85% and 95%. Reflux recurrence is reported as between 1% and 8.5%, with a concomitant dysphagia rate of 0%-10%. CONCLUSIONS: The Nissen fundoplication is currently performed throughout the world, most frequently in a minimally invasive technique. Several randomized trials that have been performed in the past years document that the Nissen fundoplication is an effective procedure for the treatment of pathological gastro-oesophageal reflux disease when a critical indication is used for well-defined patients.

Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Monoamine-oxidase B (MAO-B) has been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease, since selegiline (L-deprenyl), an irreversible MAO-B inhibitor, prevents MPTP-induced neurotoxicity in numerous species including mice, goldfish and drosophyla. However, one disadvantage of this substance relates to its metabolism to (-)-methamphetamine and (-)-amphetamine. Rasagiline (R-(+)-N-propyl-1-aminoindane) is a novel irrevesible MAO-B-inhibitor, which is not metabolized to metamphetamine and/or amphetamine. The present study compared the effects of high doses of selegiline and rasagiline (10 mg/kg body weight s.c.) on MPTP-induced dopaminergic neurotoxicity in a non-human primate (Callithrix jacchus) model of PD. Groups of four monkeys were assigned to the following six experimental groups: Group I: Saline, Group II: Selegiline/Saline, Group III: Rasagiline/Saline, Group IV: MPTP/Saline, Group V: Rasagiline/MPTP, Group VI: Selegiline/MPTP. Daily treatment with MAO-B-inhibitors (either rasagiline or selegiline, 10 mg/kg body weight s.c.) was initiated four days prior to MPTP-exposure (MPTP-HCl, 2 mg/kg body weight subcutaneously, separated by an interval of 24 hours for a total of four days) and was continued until the end of the experiment, i.e. 7 days after the cessation of the MPTP-injections, when animals were sacrificed. MPTP-treatment caused distinct behavioural, histological, and biochemical alterations: 1. significant reduction of motor activity assessed by clinical rating and by computerized locomotor activity measurements; 2. substantial loss (approx. 40%) of dopaminergic (tyrosine-hydroxylase-positive) cells in the substantia nigra, pars compacta; and 3. putaminal dopamine depletion of 98% and its metabolites DOPAC (88%) and HVA (96%). Treatment with either rasagiline or selegiline markedly attenuated the neurotoxic effects of MPTP at the behavioural, histological, and at the biochemical levels. There were no significant differences between rasagiline/MPTP and selegiline/MPTP-treated animals in respect to signs of motor impairment, the number of dopaminergic cells in the substantia nigra, and striatal dopamine levels. As expected, both inhibitors decreased the metabolism of dopamine, leading to reduced levels of HVA and DOPAC (by >95% and 45% respectively). In conclusion, rasagiline and selegiline at the dosages employed equally protect against MPTP-toxicity in the common marmoset, suggesting that selegiline-derived metabolites are not important for the neuroprotective effects of high dose selegiline in the non-human MPTP-primate model in the experimental design employed. However, unexpectedly, high dose treatment with both MAO-inhibitors caused a decrease of the cell sizes of nigral tyrosine hydroxylase positive neurons. It remains to be determined, if this histological observation represents potential adverse effects of high dose treatment with monoamine oxidase inhibitors.

Chronic TVP-1012 (rasagiline) dose--activity response of monoamine oxidases A and B in the brain of the common marmoset.

The stereospecific form of the known acetylenic mechanism-based MAO-inhibitor AGN1135 (Rasagiline, TVP-1012) is devoid of sympathomimetic amphetamine-like properties. To evaluate the efficiency and selectivity of subcutaneous injections of TVP-1012 (dose range from 0.01 up to 10 mg/kg for 7 days) the activities of monoamine oxidases A and B (MAO-A,-B) were determined in different brain regions of the common marmoset. At a dose of 0.1 mg/kg TVP-1012, almost 80% of MAO-B activity is inhibited in all brain regions investigated (prefrontal and occipital cortex, cerebellum, caudate nucleus, putamen, nucleus accumbens). In contrast, MAO-A is not inhibited in putamen and nucleus accumbens. However, by increasing the TVP-1012 dose to 0.5 mg/kg, MAO-A is inhibited to a significant extent as well, concomitant to total inhibition of MAO-B. The results obtained indicate that TVP-1012 irreversibly inhibits both types of MAO in the common marmoset with selectivity for MAO-B at doses less than 0.5 mg/kg. TVP-1012 could be useful in studies requiring selective MAO-B inhibition without concomitant sympathomimetic amphetamine-like effects and could thus be of therapeutic interest for Parkinson's disease and retarded depression.