Stefan Wolter

Microsatellite DNA alterations of gastrointestinal stromal tumors are predictive for outcome

Purpose: In gastrointestinal stromal tumors (GIST), loss of heterozygosity (LOH) on chromosome 22 and its presumptive biological function has been described. The prognostic value of these and other DNA regions for patient survival remains unclear. Experimental Design: Sixty patients who underwent surgery at our institution between 1992 and 2003 for GIST were histopathologically reclassified by immunohistochemistry and the GIST consensus group criteria 2001. Twenty-one microsatellite loci on chromosomes 3, 9, 13, 17, 18, and 22 were screened for alterations in tumor and healthy DNA. Survival was calculated by Kaplan-Meier plots. Results: Eleven (18.3%) of 60 patients showed metastases at presentation. Thirteen (21.7%) of 60 were high-risk GISTs. LOH was found in all tumors. Twenty-eight (46.7%) of 60 showed more than two LOH in 21 microsatellite marker sites. The frequency of single marker LOH varied from 1.7% to 28.3% among tumors. Frequent LOH was found on chromosomes 22 and 17. The correlation of LOH positivity and the consensus scoring was significant (P = 0.005, χ2 test). After a median observation time of 33.3 months (95% confidence interval, 23.9-42.6), overall survival was best for patients with tumors of very low, low, and intermediate risks with only 6 of 36 death events, whereas 14 of 24 high-risk and metastasized patients had died (P < 0.001, log-rank test). Likewise, LOH significantly predicted survival (P = 0.013) and the effect was particularly detrimental for LOH on chromosome 17 (P < 0.001). Conclusions: LOH is a useful phenomenon for the prognosis of GIST. Rather than chromosome 22 markers, chromosome 17 markers independently predict survival.

Upper Gastrointestinal Endoscopy prior to Bariatric Surgery-Mandatory or Expendable? An Analysis of 801 Cases

BackgroundUpper gastrointestinal pathologies are common in bariatric patients. Preoperative esophagogastroduodenal endoscopy (EGD) should detect and treat pathologies that might alter the type of bariatric surgery. However, clinical consequences of these findings are often insignificant. The aim of this study was to assess the influence of preoperative endoscopy in our cohort and its clinical consequences.MethodsWe conducted a retrospective analysis of endoscopic findings in patients under evaluation for bariatric surgery. Endoscopic findings were compared to preoperative risk factors as well as postoperative complications, and its clinical consequences were analyzed.ResultsData was available for 801 patients. Abnormal endoscopic findings were found in 65.7% of all patients. The most common conditions were gastritis (32.1%) and gastroesophageal reflux (24.8%). Malignancies were observed in 0.5% of all patients. We observed early-stage adenocarcinoma of the esophagus in two patients through our routine preoperative evaluation. Helicobacter pylori infections were detected in preoperative biopsies in only 3.7% of all patients. Patients who reported reflux symptoms had a higher rate of pathological EGDs (74.2 vs. 64.9%, p .019). We did not find any other risk factors for a pathological endoscopy. The postoperative complication rate was 11.2%. Leakage rate was 1.1%. Mortality rate was 0.4%. We did not find any correlation between the incidence of postoperative complications and preoperative endoscopic findings.ConclusionsRelevant findings in routine preoperative endoscopy are rare but have significant influence on decision-making in bariatric patients and should be assessed as a necessary diagnostic tool.

Clinical Value of Loss of Heterozygosity in Serum Microsatellite DNA of Patients With Gastrointestinal Stromal Tumors

Goals To study the role of loss of heterozygosity (LOH) in serum microsatellite DNA of patients with gastrointestinal stromal tumors (GIST). Background In GIST, tumor markers from peripheral blood are missing. Study Seventy-eight patients (59 GIST, 13 leiomyomas, 2 leiomyosarcomas, and 4 schwannomas) underwent resection at our institute between 1985 and 2006. Thirty-three preoperative sera (26 GIST and 7 non-GIST) and 62 postoperative sera (47 GIST and 15 non-GIST) were available and tested for alterations in 12 representative microsatellite loci on chromosomes 22, 17, 13, 9, and 3, using fluorescence-based automated capillary electrophoresis by ABI Prism. Survival was calculated with Kaplan-Meier plots. Results Seventeen out of 26 GIST patients had a positive preoperative serum LOH score (≥2 LOH, sensitivity 65.4%), and 6 out of 7 non-GIST patients had a negative score (≤1 LOH, specificity 85.7%, P=0.030, Fisher exact test). Serum LOH in GIST were strongly correlated with Fletcher risk groups (P=0.016, χ2 test). All metastasized GIST (7/7) showed ≥2 LOH preoperatively. Postoperative sensitivity and specificity of LOH analysis for prediction of relapse in 47 GIST was 75.0% and 64.1%, respectively. After a median observation time of 51.3 months (95% confidence interval, 39.4-61.4), LOH in serum significantly predicted overall survival (P=0.007, log-rank test). Conclusions LOH serum analysis in GIST may play a role as a noninvasive, differential diagnostic, prognostic, and monitoring marker in the clinical routine.

Improved Risk Stratification by Circulating Tumor Cell Counts in Pancreatic Cancer

Purpose: Pancreatic cancer is one of the most devastating diseases with a 5-year survival rate of 3% to 5%. Here, we investigated whether circulating tumor cells (CTC) may predict metastatic spread and survival in pancreatic cancer patients. Experimental Design: In a prospective study, we enrolled 69 pancreatic cancer patients. In peripheral blood, CTCs were identified by MACS enrichment (anti-cytokeratin/anti-EpCam) and subsequent automated analysis after combined anti-cytokeratin/anti-CD45/DAPI staining. CTC results were correlated to established clinicopathologic risk factors, detection of disseminated tumor cells (DTC) in bone marrow, and clinical outcome (follow-up time: 48 months). Results: Median patient survival was 11 months (0–48 months). Thirty-eight patients were male and 31 were female, and the majority received gemcitabine (58/69). CTCs were present in 23 of 69 patients (33.3%) ranging from 1 to 19 cells (17 with >1 CTC). Although clinicopathologic parameters and DTC status did not correlate with CTC incidence, progression-free survival (PFS) and overall survival (OS) were significantly reduced in CTC-positive patients in univariate (P = 0.009, PFS; P = 0.030, OS, both log rank) and multivariate analysis [HR = 4.543; confidence interval (CI), 1.549–13.329; P = 0.006, PFS; HR = 2.093; CI, 1.081–4.050; P = 0.028, OS, both Cox regression). Also within patients receiving chemotherapy, PFS was significantly reduced in CTC-positive patients in univariate (P = 0.013) and multivariate (HR = 4.203; CI, 1.416–12.471; P = 0.010) analysis. Conclusions: CTCs affect the outcome of patients with pancreatic cancer independent from other risk factors, including patients receiving (adjuvant) cytotoxic therapy. CTC stratification may allow a better upfront identification of patients with a longer lifespan who might profit from new adjuvant therapies. Clin Cancer Res; 24(12); 2844–50. ©2018 AACR.

Mentorship Programs in Bariatric Surgery Reduce Perioperative Complication Rate at Equal Short-Term Outcome—Results from the OPTIMIZE Trial

ObjectivesThe aim of this study was to determine the efficacy of coaching on outcome in low volume centers of excellence and to evaluate the influence of mentorship programs on the center development.BackgroundThe number of bariatric procedures has increased steadily in the last years. Providing nationwide bariatric care on a high professional level needs structures to train and guide upcoming centers and ensure high quality in patient care.MethodsA prospective multicentered, observational study including laparoscopic sleeve gastrectomies (SG) and Roux-en-Y gastric bypass (RYGB) procedures was performed. Twelve emerging bariatric centers were coached by five experienced bariatric centers. Surgeons of the mentor centers gave guidance on pre- and postsurgical management of their patients including complications and proctored the first interventions. The results were compared regarding operative outcomes, percentage of excess weight loss, complications, and resolution of comorbidities.ResultsA total of 214 of 293 patients (73.0%) completed the study. The most frequently reported complications were wound infection (4.4%), disorder of emptying stomach/new reflux (2.4%), anastomotic leaks, intra-abdominal secondary hemorrhage, and dumping syndrome (2.0% each). The mortality rate was zero. We found no difference in overall complication rates or resolution of obesity-related comorbidities when comparing experienced surgeons with less experienced surgeons.ConclusionsOur results suggest that under the conditions of the practices of this study, coaching and mentoring were associated with comparable outcomes both in experienced and emerging centers. In addition, mentorship programs ensure equal outcome quality in terms of improvement of obesity-associated comorbidities.Trial RegistrationNCT Number: NCT01754194.

Operations for Morbid Obesity

The prevalence of obesity has increased dramatically over the past several decades worldwide and is currently reaching epidemic proportions. In the United States, two thirds of individuals are considered overweight. One in five Americans is currently obese. Morbid obesity, defined as body mass index (BMI) > 40 kg/m2 or BMI > 35 kg/m2 with weight-related morbidity, is associated with many diseases responsible for a high prevalence of morbidity and mortality, such as insulin-resistant diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and sleep apnea. These direct weight-related complications eventuate in enormous health care costs.

Minimalinvasive Chirurgie bei Malignomen des Gastrointestinaltrakts: Ösophagus - Pro-Position

Hintergrund: Die offene onkologische Resektion ist derzeit der Goldstandard in der Behandlung des Plattenepithel- und Adenokarzinoms des Ösophagus. Die mit den Therapieverfahren assoziierte Morbidität und Mortalität konnte in den letzten Jahren durch die Verbesserung des chirurgischen und perioperativen Managements deutlich gesenkt werden, bleibt aber im Vergleich zu anderen Eingriffen am Gastrointestinaltrakt weiterhin hoch. Methoden: Diese Übersicht basiert auf einer strukturierten Analyse der aktuellen, in MEDLINE, PubMed, EMBASE und den Cochrane Databases gelisteten Studien. Ergebnisse: In den letzten 20 Jahren sind zunehmend Arbeiten erschienen, die seit der Erstbeschreibung der minimalinvasiven Ösophagusresektion zeigen, dass in entsprechend erfahrenen Zentren die hohe Morbidität und Mortalität, insbesondere für pulmonale Komplikationen durch minimalinvasive Ösophagusresektionen, drastisch gesenkt werden konnte - ohne Verzicht auf onkologische Radikalität und ohne Verschlechterung des onkologischen Outcomes. Die postoperative Lebensqualität war ebenfalls nicht schlechter für minimalinvasiv operierte Patienten. Allerdings sind die minimalinvasiven Techniken im Bereich der Ösophaguschirurgie mit einer signifikanten Lernkurve verbunden - ein weiteres Argument für eine Zentralisierung der Ösophaguschirurgie. Schlussfolgerungen: Die bisher erhobenen Daten zur minimalinvasiven Ösophagusresektion sind zwar sehr vielversprechend, jedoch sind weitere kontrollierte randomisierte Studien erforderlich, um die bisher erhobenen Daten zu erhärten.