Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: long-term follow-up in a Western center.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been established as a treatment modality for superficial esophageal squamous cell carcinoma (ESCC). Long-term follow-up data are lacking in Western countries. The aim of this study was to analyze long-term survival in a Western center. METHODS: Patients undergoing ESD for ESCC were included. The analysis was performed retrospectively using a prospectively collected database. RESULTS: R0 resection rate was 96.7% (59/61 lesions in 58 patients). Twenty-seven patients (46.6%) fulfilled the curative resection criteria (M1/M2) (group A), 11 patients (19.0%) had M3 lesions without lymphovascular invasion (LVI) (group B), and 20 patients (34.5%) had lesions with submucosal invasion or LVI (group C). Additional treatment was recommended after non-curative resection. It was not performed in 20/31 patients (64.5%), mainly because of comorbidities (75%). Twenty-nine out of 58 (50.0%) patients died during a mean follow-up of 3.7 years. Death was related to ESCC in 17.2% (5/29) of patients. The disease-specific survival rate after curative resection was 100%. Overall survival rates after 5 years were 61.5%, 63.6% and 28.1% for groups A, B, and C, respectively. The overall survival was significantly worse after non-curative resection (p=0.038). CONCLUSION: Non-curative resection is frequent after ESD for ESCC in Western patients. The long-term prognosis is limited and mainly determined by comorbidity. Early diagnosis and pre-interventional assessments need to be improved.

Intraoperative endoluminal pyloromyotomy for reduction of delayed gastric emptying after pylorus preserving partial pancreaticoduodenectomy (PORRIDGE trial): study protocol for a randomised controlled trial.

BACKGROUND: Pylorus-preserving pancreaticoduodenectomy (ppPD) is a standard surgical procedure for the treatment of resectable neoplasms of the periampullary region. One of the most common postoperative complications after ppPD is delayed gastric emptying (DGE) which reduces quality of life, prevents a timely return to a solid oral diet and prolongs the length of hospital stay. In a retrospective analysis, intraoperative endoluminal pyloromyotomy was associated with a reduced rate of DGE. The aim of this study is to investigate the effect of intraoperative endoluminal pyloromyotomy on postoperative DGE after ppPD in a randomised and controlled setting. METHODS: This randomised trial features parallel group design with a 1:1 allocation ratio and a superiority hypothesis. Patients with a minimum age of 18 years and an indication for ppPD are eligible to participate in this study and will be randomised intraoperatively to receive either endoluminal pyloromyotomy or atraumatic stretching of the pylorus. The sample size calculation (n=64 per study arm) is based on retrospective data. The primary endpoint is the rate of DGE within 30 days. Secondary endpoints are quality of life, operation time, estimated blood loss, length of hospital stay, morbidity and mortality. DISCUSSION: DGE after ppPD is a common complication with an incomplete understood aetiology. Prevention of DGE could improve outcomes and enhance quality of life after one of the most common procedures in pancreatic surgery. This trial will expand the existing evidence on intraoperative pyloromyotomy, and the results will provide additional data on a simple surgical technique that could reduce the incidence of postoperative DGE. TRIAL REGISTRATION: German Clinical Trials Register DRKS00013503 . Registered on 27 December 2017.

Intraoperative endoluminal pyloromyotomy as a novel approach to reduce delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy-a retrospective study.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pylorus-preserving partial pancreaticoduodenectomy (ppPD). The aim of this retrospective study was to assess whether an intraoperative pyloromyotomy during ppPD prior to the creation of duodenojejunostomy reduces DGE. METHODS: Patients who underwent pylorus-preserving pancreaticoduodenectomy between January 2015 and December 2017 were divided into two groups on the basis of whether an intraoperative pyloromyotomy was performed (pyloromyotomy (PM) group) or not (no pyloromyotomy (NP) group). The primary endpoint was DGE according to the ISGPS definition. The confirmatory analysis of the primary endpoint was performed with multivariate analysis. RESULTS: One hundred and ten patients were included in the statistical analysis. Pyloromyotomy was performed in 44 of 110 (40%) cases. DGE of any grade was present in 62 patients (56.4%). The DGE rate was lower in the PM group (40.9%) compared with the NP group (66.7%), and pyloromyotomy was associated with a reduced risk for DGE in univariate (OR 0.35, 95% CI 0.16-0.76; P = 0.008) and multivariate analyses (OR 0.32, 95% CI 0.13-0.77; P = 0.011). The presence of an intra-abdominal complication was an independent risk factor for DGE in the multivariate analysis (OR 5.54, 95% CI 2.00-15.36; P = 0.001). CONCLUSION: Intraoperative endoluminal pyloromyotomy during ppPD was associated with a reduced risk for DGE in this retrospective study. Pyloromyotomy should be considered a simple technique that can potentially reduce DGE rates after ppPD.

Immunoglobulin G4 (IgG4)-related disease of the stomach - a challenging differential diagnosis in suspected gastric cancer.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) can involve different organs and is diagnosed by a combination of clinicopathological features, including storiform fibrosclerosis infiltrated by numerous IgG4-positive plasma cells that frequently forms tumor-like lesions with or without associated obliterative phlebitis. Involvement of the stomach is rare and can occur as part of a multiorgan involvement of IgG4-RD or as isolated gastric involvement. CASE REPORT: We report 2 female patients with therapy-refractory gastric ulcers associated with gastric wall thickening and lymphadenopathy that were highly suggestive of gastric cancer or lymphoma. Biopsies failed to confirm a diagnosis, and IgG4-RD was diagnosed only after surgical resection in both patients. The previous literature on gastric IgG4-RD is summarized and shows different characteristics in patients with multiorgan IgG4-RD and isolated gastric IgG4-RD. As reported for autoimmune pancreatitis type 1, patients with multiorgan IgG4-RD are mainly elderly men with frequently elevated serum IgG4 concentrations. In contrast, isolated gastric IgG4-RD predominantly affects female patients with normal serum IgG4 levels. Surgical resection is commonly performed due to the clinical suspicion of malignancy and the absence of findings indicative of IgG4-RD on biopsy. Today, diagnosis is confirmed histopathologically only after resection. CONCLUSION: IgG4-RD should be taken into account when gastric malignancy is suspected endoscopically or radiologically and biopsies fail to confirm the presence of a malignancy (especially subepithelial tumors or refractory gastric ulcers). Serum IgG4 concentrations are insufficient to confirm localized gastric IgG4-RD. Diagnostic workups need to be improved to avoid unnecessary surgical resections with the attendant potential morbidity and mortality.

Indications for resection and perioperative outcomes of surgery for pancreatic neuroendocrine neoplasms in Germany: an analysis of the prospective DGAV StuDoQ|Pancreas registry.

PURPOSE: Pancreatic neuroendocrine neoplasms (pNENs) are rare, and their surgical management is complex. This study evaluated the current practice of pNEN surgery across Germany, including its adherence with guidelines and its perioperative outcomes. METHODS: Patients who underwent surgery for pNENs (April 2013-June 2017) were retrieved from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery and retrospectively analyzed. RESULTS: A total of 287 patients (53.7% male) with a mean age of 59.2 ± 14.2 years old underwent pancreatic resection for pNENs. Tumors were localized in the pancreatic head (40.4%), body (23%), or tail (36.6%). A total of 239 (83.3%) patients underwent formal resection with lymphadenectomy, 40 (14%) parenchyma-sparing resection, and 8 (2.8%) only exploration. Fifty (17.4%) patients underwent a minimally invasive approach. Among the 245 patients with complete pathological information, 42 (17.1%) had distant metastases, 78 (31.8%) had stage I tumors, 74 (30.2%) stage II, and 51 (20.8%) stage III. A total of 112 (45.7%) patients had G1 tumors, 101 (41.2%) G2, and 24 (9.8%) G3. Nodal involvement on imaging was an independent predictor of lymph node metastasis according to the multivariable analysis (odds ratio: 0.057; 95% confidence interval: 0.016-0.209; p < 0.01). R0 resection was reported in 240 (83.6%) patients. The 30- and 90-day mortality rates were 2.8% and 4.2%, respectively. CONCLUSION: In Germany the rate of potential curative resection for pNEN is high. However, formal pancreatic resection seems to be overrepresented, while minimally invasive resection is underrepresented.

Implementation of Current ENETS Guidelines for Surgery of Small (≤2 cm) Pancreatic Neuroendocrine Neoplasms in the German Surgical Community: An Analysis of the Prospective DGAV StuDoQ|Pancreas Registry.

BACKGROUND: ENETS guidelines recommend parenchyma-sparing procedures without formal lymphadenectomy, ideally with a minimally invasive laparoscopic approach for sporadic small pNENs (≤2 cm). Non-functioning (NF) small pNENs can also be observed. The aim of the study was to evaluate how these recommendations are implemented in the German surgical community. METHODS: Data from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery were analyzed regarding patient's demographics, tumor characteristics, surgical procedures, histology and perioperative outcomes. RESULTS: Eighty-four (29.2%) of 287 patients had sporadic pNENs ≤2 cm. Forty-three (51.2%) patients were male, and the mean age at diagnosis was 58.8 ± 15.6 years. Twenty-five (29.8%) pNENs were located in the pancreatic head. The diagnosis pNEN was preoperatively established in 53 (65%) of 84 patients. Sixty-two (73.8%) patients had formal pancreatic resections, including partial pancreaticoduodenectomy or total pancreatectomy (21.4%). Only 22 (26.2%) patients underwent parenchyma-sparing resections and 23 (27.4%) patients had minimally invasive procedures. A lymphadenectomy was performed in 63 (75.4%) patients, and lymph node metastases were diagnosed in 6 (7.2%) patients. Eighty-two (97.7%) patients had an R0 resection. Sixty (72%) tumors were classified G1, 24 (28%) tumors G2. Twenty-seven (32.2%) of 84 patients had postoperative relevant Clavien-Dindo grade ≥3 complications. Thirty- and 90-day mortalities were 2.4% and 3.6%. CONCLUSIONS: ENETS guidelines for surgery of small pNENs are yet not well accepted in the German surgical community, since the rate of formal resections with standard lymphadenectomy is high and the minimally invasive approach is underused. The attitude to operate small NF tumors seems to be rather aggressive.

Laparoscopic versus open distal pancreatectomy-a propensity score-matched analysis from the German StuDoQ|Pancreas registry.

PURPOSE: The aim of this study was to assess intraoperative, postoperative, and oncologic outcome in patients undergoing laparoscopic distal pancreatectomy (LDP) versus open distal pancreatectomy (ODP) for benign and malignant lesions of the pancreas. METHODS: Data from patients undergoing distal pancreatic resection were extracted from the StuDoQ|Pancreas registry of the German Society for General and Visceral Surgery. After propensity score case matching, groups of LDP and ODP were compared regarding demography, comorbidities, operative details, histopathology, and perioperative outcome. RESULTS: At the time of data extraction, the StuDoQ|Pancreas registry included over 3000 pancreatic resections from over 50 surgical departments in Germany. Data from 353 patients undergoing ODP (n = 254) or LDP (n = 99) from September 2013 to February 2016 at 29 institutions were included in the analysis. Baseline data showed a strong selection bias in LDP patients, which disappeared after 1:1 propensity score matching. A comparison of the matched groups disclosed a significantly longer operation time, higher rate of spleen preservation, more grade A pancreatic fistula, shorter hospital stay, and increased readmissions for LDP. In the small group of patients operated for pancreatic cancer, a lower lymph node yield with a lower lymph node ratio was apparent in LDP. CONCLUSIONS: LDP needed more time but potential advantages include increased spleen preservation and shorter hospital stay, as well as a trend for less transfusion, ventilation, and mortality. LDP for pancreatic cancer was performed rarely and will need critical evaluation in the future. Data from a prospective randomized registry trial is needed to confirm these results.

An evolutionary and structural characterization of mammalian protein complex organization.

BACKGROUND: We have recently released a comprehensive, manually curated database of mammalian protein complexes called CORUM. Combining CORUM with other resources, we assembled a dataset of over 2700 mammalian complexes. The availability of a rich information resource allows us to search for organizational properties concerning these complexes. RESULTS: As the complexity of a protein complex in terms of the number of unique subunits increases, we observed that the number of such complexes and the mean non-synonymous to synonymous substitution ratio of associated genes tend to decrease. Similarly, as the number of different complexes a given protein participates in increases, the number of such proteins and the substitution ratio of the associated gene also tends to decrease. These observations provide evidence relating natural selection and the organization of mammalian complexes. We also observed greater homogeneity in terms of predicted protein isoelectric points, secondary structure and substitution ratio in annotated versus randomly generated complexes. A large proportion of the protein content and interactions in the complexes could be predicted from known binary protein-protein and domain-domain interactions. In particular, we found that large proteins interact preferentially with much smaller proteins. CONCLUSION: We observed similar trends in yeast and other data. Our results support the existence of conserved relations associated with the mammalian protein complexes.

Circulating mediators and organ function in patients undergoing planned relaparotomy vs conventional surgical therapy in severe secondary peritonitis.

HYPOTHESIS: Planned relaparotomy (PRL) has been suggested to have detrimental effects on the systemic activation of inflammation mediators, thereby enhancing organ dysfunctions as assessed by clinical scores in secondary peritonitis. DESIGN: Prospective, nonrandomized control trial. SETTING: Intensive care units of an urban and a university teaching hospital. PATIENTS: Twenty-nine patients with secondary peritonitis. INTERVENTIONS: Of the 29 patients with comparable initial peritonitis conditions, 11 underwent PRL and 18 obtained primary abdominal closure. Blood samples were obtained preoperatively and at 2, 6, 8, 12, 18, 24, 30, 36, 42, and 48 hours after the primary operation, then every 12th hour until day 5 and once daily until day 8. MAIN OUTCOME MEASURES: Quantification of circulating inflammation parameters (coagulation, acute-phase proteins, cytokine system, cell adhesion, opsonization) in correlation with Acute Physiology and Chronic Health Evaluation II, multiple organ failure, and Sepsis-Related Organ Failure Assessment scores. RESULTS: Preoperatively, the patient groups did not differ in mean age, cause of peritonitis, or clinical scores. On average, 5.1 (SEM, +/- 0.7; range, 3-11) lavage treatments were performed in the PRL group, with 90% of the procedures executed during the first 6 days. The PRL treatment resulted in a significantly higher need of blood components and an increased inflammation mediator response, especially concerning coagulation factors, proinflammatory cytokines, adhesion molecules, and opsonic parameters. During PRL, clinical score systems showed higher values and a delayed decline compared with primary abdominal closure treatment. Incidence of multiorgan failure, mortality, and the mean intensive care unit hospitalization period were clearly more pronounced in the PRL group. CONCLUSION: In our pilot study, additional lavage treatment of secondary peritonitis resulted in an enhancement of systemic inflammatory mediator response (in particular interleukin 8), which may contribute to a further impairment of organ function.