An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

[Diagnosis and treatment of Dunbar syndrome]. / Diagnostik und Therapie des Dunbar-Syndroms.

The rare Dunbar syndrome or medial arcuate ligament syndrome (MALS) is defined as compression of the celiac trunk and/or ganglion by the medial arcuate ligament. It is often diagnosed after patients have suffered for a long time and is characterized by intermittent food-related pain, nausea, and unexplained weight loss. After exclusion of other causes of the above symptoms by gastroscopy, colonoscopy, CT, or MRI, the gold standard for diagnosis is dynamic color-coded duplex sonography, which may be supplemented by CT or MR angiography. The treatment of choice is a laparoscopic division of the arcuate ligament at the celiac trunk, although percutaneous transluminal angioplasty (PTA) with stent implantation may be performed in cases of postoperative persistence of symptoms or recurrent stenosis. Since symptoms persist postoperatively in up to 50% of cases, strict indication and complete diagnosis in designated centers are of great importance for successful treatment.

Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real-world cohort.

In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99). Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P = .001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5-FU/platinum derivate in patients with AEG and non-signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5-FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel.

Surgical site infections are independently associated with the development of postoperative acute-on-chronic liver failure in liver cirrhosis.

Acute-on-chronic liver failure (ACLF) is associated with organ failure and high short-term mortality. Bacterial infections and surgery have been reported as major precipitants for ACLF. However, detailed characterization of postoperative infections after elective surgery in patients with liver cirrhosis and their impact on the development of ACLF have not been investigated yet. A total of 235 patients with cirrhosis without ACLF and proven bacterial infections undergoing elective surgery were included. The primary end point was the development of ACLF within 28 days after surgery, and secondary end points were infection development within 28 days and 3-month ACLF-related mortality. Cox regression analysis was used for identification of risk factors associated with ACLF development, infection development, and mortality. A total of 86 patients (37%) developed ACLF within 28 days after surgery. Patients with new postoperative infections had significantly higher rates of associated ACLF episodes within 28 days (51% vs. 24%, p < 0.001) and higher 3-month mortality ( p < 0.05) than patients without postoperative infections. New infections after surgery [HR: 2.43 (1.59-3.71), p < 0.001] and organ/space surgical site infections [HR: 2.46 (1.26-4.80), p = 0.01] in particular were independent risk factors associated with ACLF development 28 days after surgery. Extensive procedures were associated with the development of new postoperative infection episodes within 28 days. Infections treated with initial appropriate empirical antibiotic strategies showed significantly improved survival. This study characterizes and identifies bacterial infections in general and organ/space surgical site infection in particular as precipitating events for the development of ACLF after elective surgery in patients with cirrhosis. Postoperative ACLF combined with infections leads to higher postoperative short-term mortality than each condition separately, especially in extensive procedures. Interdisciplinary care, early identification of postoperative ACLF and infections, and adequate, broad, and early treatment strategies are needed to improve postoperative outcome.

Surgical treatment for pancreatic cystic lesions-implications from the multi-center and prospective German StuDoQ|Pancreas registry.

PURPOSE: The detection of pancreatic cystic lesions (PCL) causes uncertainty for physicians and patients, and international guidelines are based on low evidence. The extent and perioperative risk of resections of PCL in Germany needs comparison with these guidelines to highlight controversies and derive recommendations. METHODS: Clinical data of 1137 patients who underwent surgery for PCL between 2014 and 2019 were retrieved from the German StuDoQ|Pancreas registry. Relevant features for preoperative evaluation and predictive factors for adverse outcomes were statistically identified. RESULTS: Patients with intraductal papillary mucinous neoplasms (IPMN) represented the largest PCL subgroup (N = 689; 60.6%) while other entities (mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine tumors, pseudocysts) were less frequently resected. Symptoms of pancreatitis were associated with IPMN (OR, 1.8; P = 0.012) and pseudocysts (OR, 4.78; P < 0.001), but likewise lowered the likelihood of MCN (OR, 0.49; P = 0.046) and SCN (OR, 0.15, P = 0.002). A total of 639 (57.2%) patients received endoscopic ultrasound before resection, as recommended by guidelines. Malignancy was histologically confirmed in 137 patients (12.0%), while jaundice (OR, 5.1; P < 0.001) and weight loss (OR, 2.0; P = 0.002) were independent predictors. Most resections were performed by open surgery (N = 847, 74.5%), while distal lesions were in majority treated using minimally invasive approaches (P < 0.001). Severe morbidity was 28.4% (N = 323) and 30d mortality was 2.6% (N = 29). Increased age (P = 0.004), higher BMI (P = 0.002), liver cirrhosis (P < 0.001), and esophageal varices (P = 0.002) were independent risk factors for 30d mortality. CONCLUSION: With respect to unclear findings frequently present in PCL, diagnostic means recommended in guidelines should always be considered in the preoperative phase. The therapy of PCL should be decided upon in the light of patient-specific factors, and the surgical strategy needs to be adapted accordingly.

The Development and Outcome of Acute-on-Chronic Liver Failure After Surgical Interventions.

Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality. Precipitating events, including hemorrhage and infections, contribute to ACLF development, but the role of surgery remains unknown. We investigated the development of ACLF in patients with cirrhosis undergoing surgery. In total, 369 patients with cirrhosis were included in the study. The clinical and laboratory data were collected prior to and on days 1-2, 3-8, and 9-28, and at 3 and 12 months after surgery. Surgery type was classified as limited or extensive, as well as liver and nonliver surgery. A total of 39 patients had baseline ACLF. Surgery was performed during acute decompensation in 35% of the rest of the 330 patients, and 81 (24.5%) developed ACLF within 28 days after surgery. Surrogate markers of systemic inflammation were similar in patients who developed ACLF or not. Age, sex, serum sodium, baseline bacterial infection, and abdominal nonliver surgery were independent predictors for the development of ACLF after surgery. Patients who developed ACLF within 28 days after surgery had a higher mortality at 3, 6, and 12 months. Survival did not differ between patients with ACLF at surgery and those developing ACLF after surgery. Development of ACLF within 28 days after surgery and elevated alkaline phosphatase and international normalized ratio were independent predictors of 90-day mortality. Independent predictors of 1-year all-cause mortality were alkaline phosphatase, Model for End-Stage Liver Disease score, and preoperative hepatic encephalopathy, whereas nonliver surgery was associated with improved survival. ACLF frequently develops in patients with cirrhosis undergoing surgery, especially in those with active bacterial infection, lower serum sodium, and kidney or coagulation dysfunction. Prognoses of ACLF both at and after surgery are similarly poor. Patients with cirrhosis should be carefully managed perioperatively.

Programmed cell death protein 1 (PD-1)-inhibition in hepatocellular carcinoma (HCC): a single center experience.

BACKGROUND: The prognosis for advanced Hepatocellular carcinoma (HCC)is still very poor. Despite initial usefulness of immune checkpoint inhibitor (PD-1), phase 3 trials failed to show significant benefit of PD-1 inhibition with nivolumab or pembrolizumab in the first and second line therapy of HCC. Clinical evidence of PD-1 inhibition in patients with advanced and heavily pretreated HCC outside clinical trials is extremely limited. In this study, we analyzed the clinical experience with PD-1 inhibition in patients with heavily pretreated HCC. METHODS: Between May 2016 and January 2019 14 patients with advanced and heavily pretreated HCC were treated with nivolumab or pembrolizumab at the University Hospital Bonn, Germany. Base line characteristics prior to immunotherapy, immunohistochemistry of different immunological markers, beneficial outcome and safety were recorded and retrospectively analyzed. RESULTS: Immunotherapy with PD-1 inhibition was well tolerated and resulted in significant clinical benefit as last line therapy. Median overall survival (OS) was 6.6 months (95%CI:3.9-11.8), progression-free survival (PFS) was 5.3 months (95%CI:2.4-11.7) and overall response rate (ORR) was 30.8%. One patient reached a complete remission. CONCLUSIONS: Despite numerous pretreatments, PD-1 inhibition was well tolerated and showed clinical benefit in patients with heavily pretreated HCC.

[Outcomes after Prophylactic Total Gastrectomy for Hereditary Diffuse Gastric Cancer]. / Ergebnisse nach prophylaktischer totaler Gastrektomie bei erblichem diffusem Magenkrebs.

INTRODUCTION: Prophylactic total gastrectomy is the treatment of choice in patients with germline mutation in the CDH1 gene and therefore high risk for hereditary diffuse gastric cancer (HDGC). Minimally invasive techniques have been established in recent years for treatment of gastric cancer. METHODS: We report findings with 12 patients with proven CDH1 mutation who underwent multidisciplinary treatment between 2013 and 3/2018 in our centre for hereditary tumour diseases, followed by prophylactic total gastrectomy in our department. Data were collected in a prospective hereditary tumour database. RESULTS: Open prophylactic total gastrectomy was performed in 5 patients (between 2013 and 2015) and minimally invasive prospective gastrectomy in 7 patients (between 2015 and 2018). The median age of all patients (7 women and 5 men) was 42 (range: 19 - 60) years. The mean operation time was 291 ± 72 minutes (open: 269 ± 70; minimally invasive: 307 ± 75). Perioperative 60-day mortality and anastomotic leakage rate were 0%. In 3 patients, postoperative complications occurred (according to the Clavien-Dindo classification: one each of grades II, IIIa and IVb, respectively), and therefore 25% morbidity. The average postoperative hospital stay was 14.5 ± 6.2 days (open: 16.2 ± 7.9; minimally invasive: 13.3 ± 5.0). In 10 of 12 patients (83%), foci of intramucosal signet ring cell carcinomas were found in the gastric specimen, in 9 patients with multifocal dissemination. There were no cases with advanced carcinomas (≥ pT1b) or lymph node metastases. CONCLUSION: Patients with suspected high risk for hereditary diffuse gastric cancer should be cared for in a multidisciplinary centre for hereditary tumour diseases. Laparoscopic total gastrectomy is a safe and feasible risk-reducing procedure for patients with CDH1 germline mutation. Therefore, in the absence of contraindications and with available surgical expertise, the minimally invasive operation should be the standard procedure for these patients.

Combination of CCl4 with alcoholic and metabolic injuries mimics human liver fibrosis.

Metabolic and alcoholic liver injuries result in nonalcoholic (NAFLD) or alcoholic (ALD) fatty liver disease, respectively. In particular, presence of fibrosis in NAFLD and ALD requires treatment, but development of drugs is hampered by the lack of suitable models with significant fibrosis. The carbon tetrachloride (CCl4) liver fibrosis model does not reflect human NAFLD or ALD, but CCl4 may serve as a fibrosis accelerator in addition to another injury. Ethanol in drinking water (16%) or Western diet (WD) were administered for 7 wk in mice either alone or in combination with CCl4 intoxications. Extent of fibrosis, steatosis, and inflammation was assessed by histology, transcription, and biochemistry. Furthermore, transcription of fibrosis, proliferation, and inflammation-related genes was studied on human liver samples with fibrosis resulting from hepatitis C virus infection (n = 7), NAFLD (n = 8), or ALD (n = 7). WD or ethanol alone induced only mild steatosis and inflammation. Combination of CCl4 and WD induced the most severe steatosis together with significant liver fibrosis and moderate inflammation. Combination of CCl4 and ethanol induced the strongest inflammation, with significant liver fibrosis and moderate steatosis. The relationship pattern between fibrosis, proliferation, and inflammation of human ALD was mostly similar in mice treated with CCl4 and ethanol. The combination of CCl4 intoxication with WD validates previous data suggesting it as an appropriate model for human nonalcoholic steatohepatitis. Especially, CCl4 plus ethanol for 7 wk induces ALD in mice, providing a model suitable for further basic research and drug testing.NEW & NOTEWORTHY Alcoholic fatty liver disease with significant fibrosis is generated within 7 wk using carbon tetrachloride as a fibrosis accelerator and administering gradually ethanol (up to 16%) in mice. The similarity in the pattern of steatosis, inflammation, and fibrosis involved in alcoholic fatty liver disease to those of the human condition renders this mouse model suitable as a preclinical model for drug development.

Effect of transcutaneous vagus nerve stimulation on muscle activity in the gastrointestinal tract (transVaGa): a prospective clinical trial.

PURPOSE: Postoperative ileus (POI) is a common complication after abdominal surgery. Invasive stimulation of the cervical vagus nerve is known to reduce inflammatory response and ameliorated POI after surgery in a mouse model. However, the transcutaneous vagus nerve stimulation (tVNS) is a possible non-invasive approach. In this clinical study, we aimed to investigate the effect of tVNS on the activation of the stomach muscle in humans. METHODS: Patients requiring open laparotomy were screened for this prospective proof of concept clinical study. After open laparotomy, muscle activity of the stomach was measured by a free running electromyography (EMG) before and during tVNS on the ear. Frequency and amplitude of compound gastric action potentials were the electrophysiological parameters we assessed to reveal the changes in electro motor gastric activity. Gastrin levels as a surrogate marker for vagus nerve activation was analyzed before, 1 and 3 h after tVNS. RESULTS: Fourteen patients were included, no severe adverse events and no medical device related adverse events occurred. tVNS led to significant reduction of action potential frequency and significant elevation of action potential amplitude in the stomach compared to control. Gastrin levels were significantly elevated 3 h after tVNS compared to levels before tVNS. CONCLUSION: Application of tVNS is a safe and feasible procedure during surgical intervention. Our results provide evidence that tVNS activates efferent visceral vagal fibers. Therefore, this low risk and easy to perform method could be useful to prevent postoperative ileus. CLINICAL TRIAL REGISTER NUMBER: DRKS00013340.

[Have Multimodal and Perioperative Therapeutic Strategies Changed the Survival after Oncological Oesophageal Surgery in the Last Two Decades? A Retrospective Cohort Analysis over 23 Years]. / Haben multimodale und perioperative Therapiestrategien das Überleben nach onkologischer Ösophaguschirurgie in den letzten 2 Dekaden verändert? Eine retrospektive Kohortenanalyse über 23 Jahre.

BACKGROUND: Esophageal malignoma is among the most frequent causes for cancer-related deaths. The only definite curative therapy is esophagectomy embedded in various multimodal treatment regimens. The aim of this study was to evaluate long-term development after esophageal surgery in the last two decades in order to observe possible trends and their influence on short, medium and long term survival. PATIENTS AND METHODS: Cases of 301 patients who underwent esophagectomy between 1989 and 2012 were analysed retrospectively. To investigate possible changes in perioperative management and their influence on prognosis patients were divided into two cohorts (A: surgery between 1989 and 2000; B: surgery between 2001 and 2012) and further analyzed with regard to demographics, tumor entity, stage, complications and survival. Statistics were conducted to compare both groups while p ≤ 0.05 was regarded as statistically significant. RESULTS: In cohort B patients were significantly older compared to cohort A and underwent surgery in earlier tumor stages with a higher lymphnode yield. Also an increased incidence of adenocarcinoma was observed. While overall morbidity did not change significantly, a decreased rate of anastomotic leakage was observed in cohort B (5.5%) compared to cohort A (12.3%) accompanied by a simultaneous increase in cardiac events (A: 3.6% vs. B: 12.3%). Overall 30-days-mortality was 2.7% and decreased significantly from 5% in cohort A to 0.7% in cohort B (p = 0.05). Median survival was 46 ± 7 month in cohort A, in cohort B an increase could be observed (53 ± 7 months, p = 0.03). By univariate analysis we could demonstrate that stage, affected lymph nodes, lymphnode ratio (LNR) and incidence of postoperative complications were significant predictors for the survival whereas in multivariate analysis T-stage, R-status and LNR were independent predictors for patients outcome. CONCLUSION: Patients undergoing esophageal resection for cancer nowadays are older than in the past decades. Earlier cancer diagnosis, more radical surgical techniques with an extended lymphnode dissection, a decrease in anastomotic leakage and an improved perioperative care seem to compensate for this potential demographic disadvantage. The most important independent predictor of outcome after esophageal resection is the LNR.

Comparison of mini-gastric bypass with sleeve gastrectomy in a mainly super-obese patient group: first results.

INTRODUCTION: Whereas sleeve gastrectomy (SG) in its beginnings was mainly performed to treat super-obesity, it has become as popular as gastric bypass in the treatment of obesity of any class. In contrast to this, the persisting problems of early staple line leaks and poor long-term results of SG regarding weight loss and new onset of gastroesophageal reflux have become increasingly obvious. The mini-gastric bypass (MGB) with its low complication rates and possibly better long-term results may be a good alternative to SG, especially in super-obesity. METHODS: In this context, two groups of mostly super-obese patients (SG and MGB) of a single bariatric center were retrospectively analyzed and compared for perioperative and early postoperative outcomes. RESULTS: Between August 2007 and March 2015, 169 patients underwent MGB, while 118 patients were operated by SG. Both groups were comparable for BMI at baseline (MGB = 54.1 kg/m2 vs. SG = 54.6 kg/m2, p = 0.657). Mean operation time (81.7 vs. 112.1 min, p < 0.0001) as well as hospital stay was lower in the MGB-group (4.5 vs. 7.2 days, p < 0.0001). Perioperative (30 days) mortality was 0 % in MGB versus 0.8 % in SG (one patient). Perioperative complication rate was also lower in the MGB-group (3.0 vs. 9.3 %, p = 0.449). %EWL was significantly better after 1 year in MGB: 66.2 % (±13.9 %) versus 57.3 % (±19.0 %) in SG (p < 0.0001), as well as BMI which was 34.9 kg/m2 (±4.8 kg/m2) in MGB versus 38.5 kg/m2 (±8.6 kg/m2) in SG (p = 0.001). CONCLUSIONS: MGB achieved superior weight loss at 1 year and had a lower 30-day complication rate in comparison with SG for super-obese patients. Thus, MGB might be superior to SG regarding the treatment of super-obesity.

Advantages of laparoscopic compared to conventional surgery are not related to an innate immune response of peritoneal immune activation: an animal study in rats.

PURPOSE: Laparoscopic surgery (LS) has proved superior compared to conventional surgery (CS) regarding morbidity, length of hospital stay, rate of wound infection and time until recovery. An improved preservation of the postoperative immune function is assumed to contribute to these benefits though the role of the local peritoneal immune response is still poorly understood. Our study investigates the peritoneal immune response subsequent to abdominal surgery and compares it between laparoscopic and conventional surgery to find an immunological explanation for the clinically proven benefits of LS. METHODS: Wistar rats (N = 140) underwent laparoscopic cecum resection (LCR; N = 28), conventional cecum resection (CCR; N = 28), laparoscopic sham operation (LSO; N = 28), conventional sham operation (CSO; N = 28), or no surgical treatment (CTRL; N = 28). Postoperatively, peritoneal lavages were performed, leukocytes isolated and analyzed regarding immune function and phagocytosis activity. RESULTS: Immune function was inhibited postoperatively in animals undergoing LCR or CCR compared to CTRL reflected by a lower TNF-α (CTRL 3956.65 pg/ml, LCR 2018.48 pg/ml (p = 0.023), CCR 2793.78 pg/ml (n.s.)) and IL-6 secretion (CTRL 625.84 pg/ml, LCR 142.84 pg/ml (p = 0.009), CCR 169.53 pg/ml (p = 0.01)). Phagocytosis was not affected in rats undergoing any kind of surgery compared to CTRL. Neither cytokine secretion nor phagocytosis activity differed significantly between laparoscopic and conventional surgery. CONCLUSIONS: According to our findings the benefits associated with LS compared to CS cannot be explained by differences in the postoperative peritoneal innate immune response. Further studies are needed to elucidate the causes for a more favorable postoperative outcome in patients after LS compared to CS.

Value and risk of laparoscopic surgery in hemophiliacs-experiences from a tertiary referral center for hemorrhagic diatheses.

PURPOSE: Laparoscopic surgery (LS) is gaining popularity worldwide because of benefits like faster recovery, earlier hospital discharge, and better cosmetic results. In hemophiliacs, surgery in general harbors an increased risk for severe complications. Whether LS or conventional surgery (CS) should be recommended in these patients is controversial and therefore the issue of our present study. METHODS: We performed a retrospective matched-pair analysis including laparoscopically operated non-hemophiliacs (LONH), laparoscopically operated hemophiliacs (LOH), and conventionally operated hemophiliacs (COH) concerning duration of surgery, drainages, hospital stay, complications, factor use (VIII, IX, and X), and blood values. Mann-Whitney U test was used (significance level P = 0.05). RESULTS: No significant differences were found in duration of surgery and drains in laparoscopically or conventionally operated hemophiliacs versus matched pairs. Complication rate did not differ among the different groups. Concerning the total duration of hospital stay (t-DHOS) and the postoperative duration of hospital stay (p-DHOS), there was no statistical difference between LOH versus matched LONH. However, in COH versus matched LOH, a longer time was required for preparation and recovery (t-DHOS, P = 0.04; p-DHOS, P < 0.001). Also, the median factor supply perioperatively including the day of surgery did not differ between laparoscopically versus conventionally operated hemophiliacs. CONCLUSIONS: Our study underscores the safety and benefits of laparoscopic procedures in hemophiliacs by showing a significantly shorter hospital stay for these patients resulting in reduced therapeutic costs and a faster mobilization. Still, the surgical and perioperative management of hemophiliacs continues to be a challenge requiring an experienced interdisciplinary team.

Molecular diagnostics of pancreatic cysts.

INTRODUCTION: Due to an extensive use of modern imaging, incidental pancreatic cysts are increasingly diagnosed these days. Fortunately, comprehensive research over the past years has remarkably improved our pathogenetic and clinical understanding of pancreatic cysts that, as we know, are in majority harmless. However, mucinous cysts including intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, as well as solid pseudopapillary neoplasms harbor relevant potential for developing into a lethal invasive cancer and may therefore require immediate surgical resection or at least close surveillance. In order to allow an optimized clinical management, it is crucial to gather reliable information about entity as well as biologic behavior of every cyst detected. Unfortunately, in the absence of reliable biomarkers and by just applying currently available diagnostic means such as clinical and radiologic criteria or cyst fluid cytology, there is still a risk for incorrect preoperative diagnoses. This may be followed by inappropriate treatment possibly resulting in severe morbidity or even mortality. OBJECTIVE: In this review article, we summarize some of the salient recent advances in molecular diagnostics of pancreatic cysts. Herein, we put particular focus on the emerging field of biomarker research in pancreatic cyst fluid based on protein, DNA, and microRNA analyses.

Prognostic factors for the long term outcome after surgical celiac artery decompression in MALS.

BACKGROUND: The median arcuate ligament syndrome (MALS) is a rare disease caused by compression of the celiac artery (ORPHA: 293208). Surgical treatment of MALS aims to restore normal celiac blood flow by laparoscopic celiac artery decompression. However, surgical success rates vary widely between patients, therefore adequate selection of patients is essential to improve surgical outcome. Symptoms of MALS might also overlap with other chronic multi-system disorders such as mast cell activation syndrome (MCAS). So far, no clinical or radiological parameter was found to be predictive of the postoperative outcome. We, therefore, aim to study preclinical parameters in one of the largest MALS cohorts with the focus to identify patients that would benefit from surgical MAL release. RESULTS: By analyzing 20 MALS patients that underwent surgical celiac artery decompression, we found 60% of patients (12/20) had a postoperative relief of their symptoms and a simultaneous decrease of analgetic use. No demographic, radiologic or operative parameter was able to predict postoperative symptom relief. However, mast cell activation syndrome correlated significantly (p = 0.04) with persistent symptoms after the operation. CONCLUSIONS: Overall, laparoscopic MAL release can provide immediate symptomatic relief. Despite the missing predictive value of demographic and imaging data, our data show a correlation between persistent symptoms and a co-existing mast cell activation syndrome. This suggests that MCAS symptoms might be interpreted as MALS symptoms in the presence of celiac artery stenosis and therefore surgical treatment should be evaluated carefully. Overall, the selection of patients who are most likely to respond to surgical MAL release may best be accomplished by an interdisciplinary team of gastroenterologists, radiologists and surgeons.

Assessing the Effects of a Perioperative Nutritional Support and Counseling in Gastrointestinal Cancer Patients: A Retrospective Comparative Study with Historical Controls.

The aim of this study was to investigate the effects of perioperative nutritional therapy care in gastrointestinal (esophageal, gastric, gastroesophageal) cancer patients on nutritional status and disease progression (complications, hospitalization, mortality). We considered 62 gastrointestinal cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (August 2017-July 2019). Of these, 42 patients (as intervention group: IG) received pre- and postoperative nutritional support with counseling, while 20 patients (as historical control group CG) received only postoperative nutritional therapy. Several clinical parameters, such as Body Mass Index (BMI), nutritional risk screening (NRS), phase angle, postoperative complications, length of hospital stay, and mortality, were determined. There were significantly fewer patients with gastric cancer/CDH1 gene mutation and more with esophageal cancer in IG (p = 0.001). Significantly more patients received neoadjuvant therapy in IG (p = 0.036). No significant differences were found between the groups regarding BMI, NRS, complications, length of hospital stay, and mortality. However, the comparison of post- and preoperative parameters in IG showed a tendency to lose 1.74 kg of weight (p = 0.046), a decrease in phase angle by 0.59° (p = 0.004), and an increase in NRS of 1.34 points (p < 0.001). Contrary to prior reports, we found no significant effect of perioperative nutritional therapy care in gastrointestinal cancer patients; however, the small cohort size and infrequent standardization in nutritional status may possibly account for the variance. Considering that oncological pathways and metabolic nutritional pathways are interrelated, dividing patients into subgroups to provide a personalized nutritional approach may help in improving their treatment.

A Long-Term Comparative Study Between One Anastomosis Gastric Bypass and Sleeve Gastrectomy.

BACKGROUND: One anastomosis gastric bypass (OAGB) has become increasingly accepted in bariatric surgery and meanwhile represents the third most common procedure worldwide. While it shows promising weight loss results and comorbidity resolution, questions about issues such as reflux or nutritional deficiencies (ND) persist in the long term. On the other hand, the most frequently performed sleeve gastrectomy (SG) has to accept growing criticism regarding long-term results and reflux issues. There is a particular lack of long-term comparative data for both procedures. This study presents our long-term experience. METHODS: We evaluated OAGB and SG patients retrospectively comparing for weight loss and resolution of comorbidities as well as perioperative and long-term complications in a follow-up period of 5 years. RESULTS: Nine hundred eleven OAGB and 241 SG were included in the study. OAGB had a shorter operation time and hospital stay. Overall complication rate did not differ in both groups. Ulcers were more frequent in OAGB (7.7% vs. 1.7%, p = 0.001), whereas insufficient weight loss (IWL)/weight regain (WR) proved to be more prevalent in SG (25.7% vs. 6.4%, p < 0.001). The same held true for reflux (17.8% vs. 8.3%, p < .001). On the other hand, ND were more common in OAGB (20.0% vs. 12.0%, p = 0.005). Revisional surgery was more often indicated after SG. Analysis by linear mixed model showed that OAGB achieved a lower BMI/higher loss of BMI. Improvement of T2DM (94.6% vs. 85.2%, p = 0.008) and sleep apnea (88.8% vs. 78.8%, p = 0.01) was superior in OAGB. CONCLUSIONS: OAGB had a superior effect on weight loss as well as improvement of T2DM and sleep apnea. Furthermore, long-term problems such as IWL/WR and reflux were more related to SG. On the other hand, a malabsorptive procedure such as OAGB showed a higher risk for ND. Our findings support the available data in the literature.

Efficacy and tolerability of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in unselected patients with advanced gastric and gastroesophageal cancer: does age really matter?

PURPOSE: Fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen has shown strong efficacy as perioperative therapy for patients with locally advanced gastric (GC) and gastroesophageal (AEG) carcinoma. In the palliative situation, FLOT is recommended only for young fit patients. Data of efficacy and tolerability of FLOT in elderly patients are scarce and controversial. Thus, this study aimed to provide real-life experience of elderly patients with GC and AEG treated with FLOT as first-line palliative chemotherapy. METHODS: Patients with advanced or metastatic GC or AEG and treated with FLOT as first-line palliative therapy between 2010 and 2021 were analyzed. Patients were grouped into < 65 years old (n = 35) and ≥ 65 years old (n = 22) groups. Overall survival (OS), progression-free survival (PFS), feasibility and toxicity were analyzed. RESULTS: The median OS was 10.4 months with no significant difference between both groups (HR 0.86; 95% CI 0.48, 1.57; p = 0.632). The ECOG performance status showed powerful influence on OS in the subgroup analysis with median OS of 12.3 months for ECOG = 0 compared to 5.0 months for ECOG ≥ 1 (p = 0.015) as well as in multivariate analysis (HR 2.62; 95% CI 1.36, 5.04; p = 0.004). CONCLUSION: In the present study the ECOG performance status showed a stronger prognostic value than patient age in FLOT as first- line therapy in a real-life cohort with advanced and metastatic GC and AEG. The performance status should therefore be considered in the therapeutic decision making of elderly patients with GC and AEG.

GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct.

BACKGROUND: Activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Intraductal papillary neoplasms of the bile ducts (IPNBs) morphologically resemble pancreatic IPMNs. This study sought to assess the mutational status of GNAS at codon 201 in IPNBs. METHODS: Thirty-four patients were included. DNA from microdissected IPNBs was subjected to a polymerase chain reaction and ligation method for the detection of GNAS mutations at codon 201 and of KRAS mutations at codon 12. Mutational status was compared with clinical and pathologic data. RESULTS: The IPNBs had a median diameter of 3.5 cm and were located intrahepatically (n= 6), extrahepatically (n= 13), both intra- and extrahepatically (n= 4) or in the gallbladder (intracystic papillary neoplasms, n= 11). Most exhibited pancreatobiliary differentiation (n= 20), high-grade dysplasia (n= 26) and an associated adenocarcinoma (n= 20). Analysis of GNAS codon 201 identified only one mutant sample in a multifocal intestinal subtype intrahepatic IPNB with high-grade dysplasia. Six lesions harboured a KRAS codon 12 mutation. CONCLUSIONS: GNAS codon 201 mutations are uncommon in IPNBs, by contrast with pancreatic IPMNs. More comprehensive molecular profiling is needed to uncover the pathways involved in IPNB development.