Neoadjuvant radiochemotherapy with cisplatin/5-flourouracil or carboplatin/paclitaxel in patients with resectable cancer of the esophagus and the gastroesophageal junction - comparison of postoperative mortality and complications, toxicity, and pathological tumor response.

PURPOSE: In 2012, the CROSS trial implemented a new neoadjuvant radiochemotherapy protocol for patients with locally advanced, resectable cancer of the esophagus prior to scheduled surgery. There are only limited studies comparing the CROSS protocol with a PF-based (cisplatin/5-fluorouracil) nRCT protocol. METHODS: In this retrospective, monocentric analysis, 134 patients suffering from esophageal cancer were included. Those patients received either PF-based nRCT (PF group) or nRCT according to the CROSS protocol (CROSS group) prior to elective en bloc esophagectomy. Perioperative mortality and morbidity, nRCT-related toxicity, and complete pathological regression were compared between both groups. Logistic regression analysis was performed in order to identify independent factors for pathological complete response (pCR). RESULTS: Thirty-day/hospital mortality showed no significant differences between both groups. Postoperative complications ≥ grade 3 according to Clavien-Dindo classification were experienced in 58.8% (PF group) and 47.6% (CROSS group) (p = 0.2) respectively. nRCT-associated toxicity ≥ grade 3 was 30.8% (PF group) and 37.2% (CROSS group) (p = 0.6). There was no significant difference regarding the pCR rate between both groups (23.5% vs. 30.5%; p = 0.6). In multivariate analysis, SCC (OR 7.7; p < 0.01) and an initial grading of G1/G2 (OR 2.8; p = 0.03) were shown to be independent risk factors for higher rates of pCR. CONCLUSION: We conclude that both nRCT protocols are effective and safe. There were no significant differences regarding toxicity, pathological tumor response, and postoperative morbidity and mortality between both groups. Squamous cell carcinoma (SCC) and favorable preoperative tumor grading (G1 and G2) are independent predictors for higher pCR rate in multivariate analysis.

Hybrid laparoscopic versus fully robot-assisted minimally invasive esophagectomy: an international propensity-score matched analysis of perioperative outcome.

BACKGROUND: Currently, little is known regarding the optimal technique for the abdominal phase of RAMIE. The aim of this study was to investigate the outcome of robot-assisted minimally invasive esophagectomy (RAMIE) in both the abdominal and thoracic phase (full RAMIE) compared to laparoscopy during the abdominal phase (hybrid laparoscopic RAMIE). METHODS: This retrospective propensity-score matched analysis of the International Upper Gastrointestinal International Robotic Association (UGIRA) database included 807 RAMIE procedures with intrathoracic anastomosis between 2017 and 2021 from 23 centers. RESULTS: After propensity-score matching, 296 hybrid laparoscopic RAMIE patients were compared to 296 full RAMIE patients. Both groups were equal regarding intraoperative blood loss (median 200 ml versus 197 ml, p = 0.6967), operational time (mean 430.3 min versus 417.7 min, p = 0.1032), conversion rate during abdominal phase (2.4% versus 1.7%, p = 0.560), radical resection (R0) rate (95.6% versus 96.3%, p = 0.8526) and total lymph node yield (mean 30.4 versus 29.5, p = 0.3834). The hybrid laparoscopic RAMIE group showed higher rates of anastomotic leakage (28.0% versus 16.6%, p = 0.001) and Clavien Dindo grade 3a or higher (45.3% versus 26.0%, p < 0.001). The length of stay on intensive care unit (median 3 days versus 2 days, p = 0.0005) and in-hospital (median 15 days versus 12 days, p < 0.0001) were longer for the hybrid laparoscopic RAMIE group. CONCLUSIONS: Hybrid laparoscopic RAMIE and full RAMIE were oncologically equivalent with a potential decrease of postoperative complications and shorter (intensive care) stay after full RAMIE.

[Robot-assisted Minimally Invasive Oesophagectomy - Surgical Variants of Intrathoracic Circular Stapled Oesophagogastric Anastomosis]. / Roboterassistierte minimalinvasive Ösophagektomie ­ Varianten der intrathorakalen Ösophagogastrostomie mittels Zirkularstapler.

INTRODUCTION: Anastomotic insufficiency after oesophagectomy contributes significantly to morbidity and mortality of affected patients. A safe surgical technique can reduce the incidence of such anastomotic insufficiencies. INDICATION: In the treatment of oesophageal cancer, the German guideline recommends minimally invasive or hybrid surgical procedures. In most cases, Ivor-Lewis oesophagectomy and continuity reconstruction using a gastric sleeve are performed. Circular stapler anastomosis seems to be superior. METHOD: The preparation of the anastomosis starts intra-abdominally with mobilisation of the stomach and sparing of the gastroepiploic vessels. After the subsequent intrathoracic mobilisation of the oesophagus, the actual anastomosis construction can take place. Here, the oesophagus is either transected with a stapler closure or openly with scissors. This is followed by a purse-string suture on the open oesophageal stump. Alternatively, partial oesophageal opening with prior purse-string suture may later facilitate insertion of the stapler anvil. The anvil is placed in the oesophageal stump via minithoracotomy or alternatively transorally using a special gastric tube system. Subsequently, the anvil is fixated using the previously performed purse-string suture. Now the gastric sleeve can be pulled into the thorax. The oesophagus and small gastric curvature are placed extrathoracically through the minithoracotomy and a circular stapler is inserted into the gastric tube via an opening of the small curvature. The anastomosis then must be placed remotely from the gastroepiploic arcade. After construction of the anastomosis, the gastric sleeve is separated using a linear stapler. Eventually, the oesophagus and small gastric curvature can be completely recovered. Optionally, an additional suturing over the anastomosis and dissection margin of the gastric sleeve can be performed. CONCLUSION: In robot-assisted oesophagectomy, the reconstruction of continuity with a circular stapler anastomosis is quite possible and seems comparatively easier to learn. Nevertheless, variations are still possible within this procedure. However, there is no scientific evidence on the advantage for any method in a direct comparison.

Robot-assisted transthoracic hybrid esophagectomy versus open and laparoscopic hybrid esophagectomy: propensity score matched analysis of short-term outcome.

PURPOSE: Minimally invasive en-bloc esophagectomy is associated with a reduction of postoperative morbidity. This was demonstrated for both total minimally invasive and hybrid esophagectomy. However, little is known about any benefits of robotic assistance compared to the conventional minimally invasive technique, especially in hybrid procedures. METHODS: For this retrospective study, all consecutive patients who had undergone elective esophagectomy with circular stapled intrathoracic anastomosis using the open and the minimally invasive hybrid technique at the University Hospital Magdeburg, from January 2010 to March 2021 were considered for analysis. RESULTS: In total, 137 patients (60.4%) had undergone open esophagectomy. In 45 patients (19.8%), the laparoscopic hybrid technique and in 45 patients (19.8%), the robot-assisted hybrid technique were applied. In propensity score matching analysis comparing the open with the robotic hybrid technique, significant differences were found in favor of the robotic technique (postoperative morbidity, p < 0.01; hospital length of stay, p < 0.01; number of lymph nodes retrieved, p = 0.048). In propensity score matching analysis comparing the laparoscopic with the robotic hybrid technique, a significant reduction of the rate of postoperative delayed gastric emptying (p = 0.02) was found for patients who had undergone robotic esophagectomy. However, the operation time was significantly longer (p < 0.01). CONCLUSIONS: En-bloc esophagectomy using the robotic hybrid technique is associated with a significant reduction of postoperative morbidity and of the hospital length of stay when compared to the open approach. However, when compared to the laparoscopic hybrid technique, only few advantages could be demonstrated.

Worldwide Techniques and Outcomes in Robot-assisted Minimally Invasive Esophagectomy (RAMIE): Results From the Multicenter International Registry.

OBJECTIVE: This international multicenter study by the Upper GI International Robotic Association aimed to gain insight in current techniques and outcomes of RAMIE worldwide. BACKGROUND: Current evidence for RAMIE originates from single-center studies, which may not be generalizable to the international multicenter experience. METHODS: Twenty centers from Europe, Asia, North-America, and South-America participated from 2016 to 2019. Main endpoints included the surgical techniques, clinical outcomes, and early oncological results of ramie. RESULTS: A total of 856 patients undergoing transthoracic RAMIE were included. Robotic surgery was applied for both the thoracic and abdominal phase (45%), only the thoracic phase (49%), or only the abdominal phase (6%). In most cases, the mediastinal lymphadenectomy included the low paraesophageal nodes (n=815, 95%), subcarinal nodes (n = 774, 90%), and paratracheal nodes (n = 537, 63%). When paratracheal lymphadenectomy was performed during an Ivor Lewis or a McKeown RAMIE procedure, recurrent laryngeal nerve injury occurred in 3% and 11% of patients, respectively. Circular stapled (52%), hand-sewn (30%), and linear stapled (18%) anastomotic techniques were used. In Ivor Lewis RAMIE, robot-assisted hand-sewing showed the highest anastomotic leakage rate (33%), while lower rates were observed with circular stapling (17%) and linear stapling (15%). In McKeown RAMIE, a hand-sewn anastomotic technique showed the highest leakage rate (27%), followed by linear stapling (18%) and circular stapling (6%). CONCLUSION: This study is the first to provide an overview of the current techniques and outcomes of transthoracic RAMIE worldwide. Although these results indicate high quality of the procedure, the optimal approach should be further defined.

Short-term outcome after robot-assisted hiatal hernia and anti-reflux surgery-is there a benefit for the patient?

PURPOSE: The robotic system was introduced to overcome the technical limitations of conventional laparoscopy. For complex oncological operations, it appears to offer further advantages. With regard to hiatal hernia repair, its role has yet to be determined. METHODS: All consecutive patients who received elective laparoscopic or robot-assisted hiatal hernia repair at a single institution between January 2016 and July 2020 were retrospectively evaluated. We compared both techniques with particular focus on their short-term outcome. A propensity score-matched comparison considering clinical and surgical covariates was also performed between the two groups. RESULTS: 140 patients were included, and 55 (39.3%) underwent a robot-assisted procedure. The baseline demographics and the frequency of previous abdominal operations were comparable for both groups. The size of the hiatal hernia did not differ significantly between the groups (p = 0.06). The mean operative time was significantly longer for the robot-assisted procedure (149 vs. 125 min; p < 0.01) but decreased markedly during the study period. By contrast, no significant differences were observed in terms of conversion rate (p = 1.0) and blood loss (p = 0.25). Likewise, the postoperative morbidity was comparable for both groups (10.9 vs. 12.9; p = 0.79). The hospital length of stay was not significantly different between the laparoscopic and robotic group (4.0 vs. 3.6 days; p = 0.2). After propensity score-matching, 48 patients were identified for each group. Except for the operative time, no other significant differences were found. Thus, the results of the univariate analysis were confirmed. CONCLUSION: Our initial results failed to demonstrate a clear advantage of the robotic technique in patients with refractory gastroesophageal reflux disease and/or symptomatic hiatal hernias.

Sleeve gastrectomy in the German Bariatric Surgery Registry from 2005 to 2016: Perioperative and 5-year results.

BACKGROUND: Recently, sleeve gastrectomy (SG) has become one of the most important procedures in bariatric surgery. Short-term results show that SG is a feasible, safe, and effective operation treating obesity and its related co-morbidities. Now, the main focus is on long-term data after SG. OBJECTIVES: The aim of this study was to analyze perioperative and long-term results after SG in the German Bariatric Surgery Registry. SETTING: National database, Germany. METHODS: Perioperative data of primary SG (n = 21525) and follow-up data for 5 years ± 6 months (n = 435, 18.3% of 2375 SG performed between 2005 and 2011) were analyzed. After a review of the literature long-term results were compared with international data. RESULTS: Mean baseline body mass index (BMI) was 51.1 kg/m2. Two hundred ninety-eight (68.5%) patients were female and 137 (31.5%) were male. Of patients, 90% had ≥1 co-morbidities. Mean operation time was 86 minutes. General postoperative complications occurred in 4.1% and special complications in 4.6% (staple-line leaks 1.6%). Mean maximum BMI loss was 18.0 ± 6.8 kg/m2 and BMI loss after 5 years was 14.3 ± 7.4 kg/m2 (P < .001). Co-morbidities, such as type 2 diabetes, hypertension, and sleep apnea, were significantly improved (P < .001). Gastroesophageal reflux was significantly impaired (P < .001). CONCLUSIONS: The current results showed that SG is a safe and effective procedure in bariatric surgery. BMI loss was significant 5 years after SG. Most co-morbidities were significantly improved, but gastroesophageal reflux has often worsened. The follow-up rate was very low, which is a persistent problem in German bariatric surgery.

Trends in Early Morbidity and Mortality after Sleeve Gastrectomy in Patients over 60 Years : Retrospective Review and Data Analysis of the German Bariatric Surgery Registry.

BACKGROUND: The population are getting older and obesity is growing. Laparoscopic sleeve gastrectomy (LSG) is increasingly used worldwide but is still used with skepticism in the elderly. The purpose of our analysis is to judge the security of LSG in patients older than 60 years compared to patients younger than 60 years. METHODS: This retrospective review included data of all patients in Germany who underwent LSG between January 2005 and December 2016.The data were published online in the German Bariatric Surgery Registry. A total of 21,571 operations were gathered and divided into two groups: group I, patients < 60 years old; and group II, patients ≥ 60 years old. RESULTS: The total number of patients and the mean body mass index of group I and group II was 19,786, 51.7 ± 9.5 kg/m2 and 1771, 49.2 ± 8.1 kg/m2, respectively. Regarding comorbidities, group II suffered statistically significantly more comorbidities than group I (p < 0.001). The general postoperative complications were 4.9% in group I and 7.8% in group II (p < 0.001). There was no significant difference in special postoperative complications (p = 0.048) and a slightly higher intraoperative complication rate in group II (2.2% vs. 1.6%, p = 0.048). Thirty-day mortality rate for group I versus II was 0.22% and 0.23% (p = 0.977), respectively. CONCLUSIONS: LSG is a low-risk operation and safe surgical method with acceptable, not elevated perioperative morbidity and mortality rates in patients ≥ 60 years of age.

[Roux-Y-Gastric Bypass for Morbid Obesity in Adolescents: Is it as Safe and Effective as in Obese Adults?] / Der Roux-Y-Magenbypass zur Therapie der Adipositas bei Jugendlichen: Analyse des Gewichtsverlaufs und des Einflusses auf Komorbiditäten im Vergleich zu adipösen Erwachsenen.

BACKGROUND: Obesity is one of the major challenges of the 21st century. There is also an increasing incidence of obesity in adolescents. Bariatric surgery has been proven safe and effective in obese adults. In adolescents, these operations are still subject to controversy. Current evidence is limited regarding its safety and outcome in this age group. METHODS: Within the German Bariatric Surgery Registry, data from obese patients that underwent bariatric procedures in Germany are prospectively registered. The current analysis includes all adolescent and adult subjects that underwent primary Roux-Y-gastric bypass (RYGB) surgery from 2005 to 2014. RESULTS: Overall, 370 adolescents (≤ 21 years) and 16,840 obese adults were enrolled. In 2014, RYGB was the second most common bariatric procedure in Germany. In the adolescent group, initial BMI was higher (49.2 vs. 47.9 kg/m2, p < 0.01); the proportion of associated comorbidities was lower (67.8 vs. 87.4%, p < 0.01). Operation time (104.9 vs. 113.0 min, p < 0.01) and hospital stay (5.2 vs. 5.9 days; p < 0.01) differed significantly between both groups. The leakage rate in adults was 1.6%; none of the adolescents experienced a postoperative anastomotic leak (p = 0.04). No mortalities were reported in adolescents; the mortality rate in adults was 0.2%. The mean percentage of excess weight loss (% EWL) did not differ between both groups at 12 (69.9 vs. 68.2%; p = 0.97) and 24 months (72.6 vs. 72.1% p = 1.0). The remission rate for hypertension was higher in the adolescent group. CONCLUSION: RYGB can be performed in obese adolescents with lower morbidity and mortality. Despite all limitations of a multicentre registry and the low follow-up rate, the results show that weight change and resolution of comorbidities in the short term were at least comparable to those achieved in adults. The evaluation of safety and efficiency in the long run should now be in the focus of future studies.

Metabolic surgery and nutritional deficiencies.

The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered as the main risks of metabolic surgery with its malabsorptive but also restrictive procedures. The aim of this review was to characterize the most relevant metabolic complications specific for the various bariatric procedures, which, subsequently, require a permanent surveillance and supplementation, respectively. Furthermore, we aimed to identify if there are diagnostic and therapeutic measures that can prevent those complications. Restrictive bariatric surgery such as "gastric banding" and "sleeve gastrectomy" can be associated with deficiencies related to B-vitamins whereas iron, folate, vitamin B1, B12 and D deficiencies are associated with the malabsorptive procedure such as "biliopancreatic diversion," "duodenal switch" and "Roux-en-Y gastric bypass". Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical and dietetic surveillance. The recently published guidelines of the "American Association of Bariatric and Metabolic Surgery" are the basis for recommendations on supplementation and treatment following weight loss surgery.

Risk factors for delayed gastric emptying after esophagectomy.

PURPOSE: Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy with gastric tube reconstruction. Little is known about risk factors that can predict this debilitating complication. METHODS: Patients who underwent elective esophagectomy from 2008 to 2016 in a single center were retrospectively reviewed. Diagnosis of DGE was based on clinical, radiological, and endoscopic findings. Uni- and multivariate analyses were performed to identify patient-, tumor-, and procedure-related factors that increase the risk of DGE. RESULTS: One hundred eighty-two patients were included. Incidence of DGE was 39.0%. Overall, 27 (14.8%) needed an endoscopic intervention. Patients in the DGE group had a longer hospital stay (p < 0.01). No differences were found for the 30-day (p = 1.0) and hospital mortality (p = 1.0). On univariate analyses, a significant influence on DGE was demonstrated for pre-existing pulmonary comorbidity (p = 0.04), an anastomotic leak (p < 0.01), and postoperative pulmonary complications (pneumonia: p = 0.02, pleural empyema: p < 0.01, and adult respiratory distress syndrome: p = 0.03). Furthermore, there was a non-significant trend toward an increased risk for DGE for the following variable: female gender (p = 0.09) and longer operative time (p = 0.09). On multivariate analysis, only female gender (p = 0.03) and anastomotic leak (p = 0.01) were significantly associated with an increased risk for DGE. CONCLUSIONS: DGE is a frequent complication following esophagectomy that can successfully be managed with conservative or endoscopic measures. DGE did not increase mortality but was associated with increased morbidity and prolonged hospitalization. We identified risk factors that increase the incidence of DGE. However, this has to be confirmed in future studies with standardized definition of DGE.

Perioperative Course, Weight Loss and Resolution of Comorbidities After Primary Sleeve Gastrectomy for Morbid Obesity: Are There Differences Between Adolescents and Adults?

BACKGROUND: Morbid obesity in both adolescents and adults has risen in an alarming rate. Bariatric surgery is playing an increasing role in pediatric surgery. However, current evidence is limited regarding its safety and outcome. METHODS: Since 2005, data from obese patients that undergo bariatric procedures in Germany are prospectively registered. For the current analysis, all adolescent and adult subjects that had undergone laparoscopic sleeve gastrectomy (LSG) from 2005 to 2014 were considered. RESULTS: LSG represents the most common bariatric procedure in Germany with a proportion of 48.1% in adolescent and 48.7% in adult obese in 2014. LSG was performed in 362 adolescent and 15,428 adult subjects. Pre-operative BMI was comparable between the two populations. However, adult obese had more frequently coexisting comorbidities (p < 0.01). Complication rates and mortality (0 vs. 0.2%) did not differ significantly. Adolescents achieved a BMI reduction of 16.8 and 18.0 kg/m2 at 12 and 24 months compared with 15.4 and 16.6 kg/m2 in the adult group. There was a significantly higher BMI reduction in late adolescents (19-21 years) compared with patients ≤18 years at 24 months (19.8 vs. 13.6 kg/m2). Resolution rate of hypertension was significantly higher in adolescents. CONCLUSION: LSG is a safe therapeutic option that can be performed in adolescents without mortality. Late adolescents experienced the highest weight loss; resolution rate of comorbidities was lower in adults. All future efforts should now be focused on the evaluation of the long-term outcomes of LSG in the pediatric population.

Staple Line Leak After Primary Sleeve Gastrectomy-Risk Factors and Mid-term Results: Do Patients Still Benefit from the Weight Loss Procedure?

BACKGROUND: Staple line leak after laparoscopic sleeve gastrectomy (LSG) still represents the most feared complication. The purpose of this study was to investigate whether there are factors that increase the risk for a leakage. Furthermore, we aimed to analyze the impact of a leak on weight change and resolution of comorbidities. METHODS: Since 2005, data from obese patients that undergo bariatric procedures in Germany are prospectively registered. For the current analysis, all adult subjects that had undergone primary LSG from 2005 to 2014 were considered. RESULTS: Overall, 241/15,756 (1.53%) patients experienced a leak. The occurrence of a leakage resulted in a significant increase of the mortality rate (3.7 vs. 0.2%; p < 0.01). Percent excess weight loss did not differ between leak and non-leak patients, both, at 12 (64.2 vs. 60.9%; p = 1.0) and 24 months (68.5 vs. 64.0%, p = 0.86). Similarly, no significant difference was observed for resolution rate of all comorbid conditions. Matched pair analysis confirmed these findings. Multivariable analysis identified operation time, conversion, intraoperative complications, and hypertension and degenerative joint disease as risk factors for a leak. Oversewing the staple line was associated with the lowest risk. CONCLUSION: The postoperative staple line leak after primary LSG significantly increases postoperative morbidity and mortality. We found that there are patient-related factors and operative variables that predispose to leakage after LSG. However, the occurrence of a leakage does not adversely impact the weight loss and resolution of comorbidities in the mid-term.

Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

AIMS: Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. METHOD: Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. RESULTS: Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis. CONCLUSION: In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

miR-221 Mediates Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression.

BACKGROUND: Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies. METHODS: Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples. RESULTS: MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/ß-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT profiler analysis identified a substantial dysregulation of 4 Wnt/ß-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2. CONCLUSION: MiR-221 controls 5-FU resistance of EC partly via modulation of Wnt/ß-catenin-EMT pathways by direct targeting of DKK2 expression. MiR-221 may serve as a prognostic marker and therapeutic target for patients with 5-FU resistant EAC.

Are there risk factors that increase the rate of staple line leakage in patients undergoing primary sleeve gastrectomy for morbid obesity?

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is currently being performed with increasing frequency worldwide. It offers an excellent weight loss and resolution of comorbidities in the short term with a very low incidence of complications. However, the ever present risk of a staple line leak is still a major concern. METHODS: Since 2005, data from obese patients that undergo bariatric procedures in Germany are prospectively registered in an online database and analyzed at the Institute of Quality Assurance in Surgical Medicine. For the current analysis, all patients that had undergone primary sleeve gastrectomy for morbid obesity within a 7-year period were considered. RESULTS: Using the GBSR, data from 5.400 LSGs were considered for analysis. Staple line leak rate decreased during the study period from 6.5 to 1.4 %. Male gender, higher BMI, concomitant sleep apnea, conversion to laparotomy, longer operation time, use of both buttresses and oversewing, and the occurrence of intraoperative complications were associated with a significantly higher leakage rate. On multivariate analysis, operation time and year of procedure only had a significant impact on staple line leak rate. CONCLUSIONS: The results of the current study demonstrated that there are factors that increase the risk of a leakage which would enable surgeons to define risk groups, to more carefully select patients, and to offer a closer follow-up during the postoperative course with early recognition and adequate treatment. All future efforts should be focused on a further reduction of serious complications to make the LSG a widely accepted and safer procedure.

Circular Versus Linear Versus Hand-Sewn Gastrojejunostomy in Roux-en-Y-Gastric Bypass Influence on Weight Loss and Amelioration of Comorbidities: Data Analysis from a Quality Assurance Study of the Surgical Treatment of Obesity in Germany.

BACKGROUND: Since January 1 2005, the outcomes of bariatric surgeries have been recorded in Germany. All data are registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at Otto-von-Guericke University Magdeburg. METHODS: Data are collected in an online data bank. Data collection began in 2005 for the results of Roux-en-Y-Gastric Bypass (RYGB). In addition to primary bariatric operations, data regarding the complications and the amelioration of comorbidities have been analyzed. Participation in the quality assurance study is required for all certified centers in Germany. RESULTS: Roux-en-Y Gastric Bypass is the most popular bariatric operation in Germany. There were 5115 operations performed from 2005 to 2010. A circular anastomosis was performed in 1587 patients, and a linear anastomosis was performed in 2734 patients. In 783 patients, the hand-sewn technique was used. The leakage rate for the linear technique is 1.6%, and the leakage rate is 1.2% for circular anastomosis, and 1.4% for hand-sewn technique. CONCLUSION: Roux-en-Y-Gastric Bypass is a popular procedure in Germany. The complication rate has decreased since 2005. The amelioration of comorbidities is not influenced by the anastomosis technique. Additional data are necessary to evaluate the long-term effect of linear versus hand-sewn and versus circular-stapled gastrojejunal anastomosis regarding pouch dilatation, small bowel dilatation, and consecutive weight loss.

Influence of anatomical subsite on the incidence of microsatellite instability, and KRAS and BRAF mutation rates in patients with colon carcinoma.

There is a growing amount of data supporting the concept that cancers originating from the proximal and distal colon are distinct clinicopathological entities. The incidence of MSI and BRAF mutation is strongly associated with right sided tumor location, whereas there are conflicting results for KRAS mutation rates. However, to date, no data exist whether and to what extent defined colonic subsites influence MSI status, KRAS and BRAF mutation rates. We selected primary colon cancer from 171 patients operated on at our institution between 2007 and 2010. BRAF, KRAS mutation rates and microsatellite instability were determined and correlated with clinicopathological features and tumor location. MSI-h cancers were significantly associated with poor histological grade but a lower rate of distant metastases. KRAS-mutated tumors were linked to lower T-stage and better differentiation. Colon carcinomas with BRAF mutation were significantly associated with distant metastatic spread and poor histological grade. Furthermore, we found that MSI-h status, KRAS and BRAF mutation rates varied remarkably among the colonic subsites irrespective of right- and left-sided origin, respectively. The results of the current study provide further evidence that a simple classification into right- and left-sided colon carcinoma does not represent the complexity of this tumor entity.

Weight loss and changes in salivary ghrelin and adiponectin: comparison between sleeve gastrectomy and Roux-en-Y gastric bypass and gastric banding.

BACKGROUND: Weight loss is associated with increased levels of adiponectin with a greater increase observed following Roux-en-Y gastric bypass (RYGB) compared to restrictive procedures. However, currently there are no data on changes in adiponectin following laparoscopic sleeve gastrectomy (LSG). Ghrelin was reported to be also produced by the salivary glands. There are also no data available regarding its changes following bariatric surgery. METHODS: The present study examined weight loss, and salivary ghrelin and HMW adiponectin levels in 43 morbidly obese subjects undergoing three different types of bariatric surgery. RESULTS: We found that weight loss following LSG is superior to laparoscopic adjustable gastric banding (LAGB) and comparable to RYGB at 12 months after surgery. Although blood glucose decreased similarly following all three procedures, fasting insulin continuously declined only in LSG and RYGB patients. Changes in both fasting and postprandial salivary ghrelin greatly varied between all three procedures with no similarities to changes in serum ghrelin reported in the literature. HMW adiponectin significantly increased following LSG, and this increase was more marked than in LAGB patients and almost identical compared to RYGB. CONCLUSIONS: Weight loss following LSG is comparable to RYGB in the short term. Changes in HMW adiponectin are comparable following LSG and RYGB which may further contribute to the successful results after LSG. Furthermore, the results of the present study support the hypothesis that there is an autonomous production of ghrelin in salivary glands irrespective of nutritional status and weight loss.

Comparison of serum and salivary ghrelin in healthy adults, morbidly obese, and patients with metastatic carcinoma.

BACKGROUND: Ghrelin, a known orexigenic hormone, has been demonstrated to be produced and released by salivary glands. Obtaining saliva for metabolism studies would be preferable for patients since the procedure is non-invasive. METHODS: The present study examined serum and salivary ghrelin levels in 41 morbidly obese subjects, 45 healthy controls, and 17 patients with metastatic carcinoma by using a commercial radioimmunoassay. RESULTS: When comparing serum and salivary levels under fasting conditions, ghrelin levels were significantly higher in saliva for morbidly obese and healthy subjects. A significant correlation between salivary and serum ghrelin could only be demonstrated for healthy subjects. Fasting serum ghrelin concentrations in morbidly obese patients were significantly lower compared with healthy controls and cancer patients, however the levels in whole saliva did not differ significantly between all groups. There was only a highly significant inverse correlation between BMI and serum ghrelin. Serum ghrelin correlated positively with age in morbidly obese. There was no significant difference in serum and saliva ghrelin concentrations between men and women. Following the standardized meal, no significant suppression of serum ghrelin levels in morbidly obese was observed, however salivary ghrelin concentrations were significantly decreased. CONCLUSIONS: The results of the present study support the hypothesis that there is an autonomous production of ghrelin in the salivary glands. Further research should focus on factors involved in the regulation of salivary ghrelin. Until the mechanism of regulation is fully understood, the testing of ghrelin levels in saliva is too limited to recommend a switch from serum testing.