ABSTRACT
The bacterium Helicobacter pylori induces gastric inflammation and predisposes to cancer. H. pylori-infected epithelial cells secrete cytokines and chemokines and undergo DNA-damage. We show that the host cell's mitochondrial apoptosis system contributes to cytokine secretion and DNA-damage in the absence of cell death. H. pylori induced secretion of cytokines/chemokines from epithelial cells, dependent on the mitochondrial apoptosis machinery. A signalling step was identified in the release of mitochondrial Smac/DIABLO, which was required for alternative NF-κB-activation and contributed to chemokine secretion. The bacterial cag-pathogenicity island and bacterial muropeptide triggered mitochondrial host cell signals through the pattern recognition receptor NOD1. H. pylori-induced DNA-damage depended on mitochondrial apoptosis signals and the caspase-activated DNAse. In biopsies from H. pylori-positive patients, we observed a correlation of Smac-levels and inflammation. Non-apoptotic cells in these samples showed evidence of caspase-3-activation, correlating with phosphorylation of the DNA-damage response kinase ATM. Thus, H. pylori activates the mitochondrial apoptosis pathway to a sub-lethal level. During infection, Smac has a cytosolic, pro-inflammatory role in the absence of apoptosis. Further, DNA-damage through sub-lethal mitochondrial signals is likely to contribute to mutagenesis and cancer development.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , NF-kappa B/metabolism , Helicobacter Infections/metabolism , Helicobacter Infections/pathology , Mitochondria/metabolism , Epithelial Cells/metabolism , Chemokines/metabolism , DNA/metabolism , Inflammation/metabolism , Gastric Mucosa/metabolism , Gastric Mucosa/microbiology , Gastric Mucosa/pathologyABSTRACT
According to current revised Fukuoka guidelines, there is an indication for resection of BD-IPMN of the pancreas with "worrisome features", as there is a risk of malignant degeneration of up to 30%. This can be performed as a non-anatomical local excision in the absence of clinical, radiological and laboratory signs of malignancy.Robotic enucleation for benign tumours of the pancreas is a very good alternative to resecting procedures, especially those using open techniques. This surgical treatment option is recommended by the "International consensus statement on robotic pancreatic surgery" in a case of a minimum distance to the main pancreatic duct of at least 2 mm.In addition to the known advantages of minimally invasive surgery, this parenchyma-sparing approach results in preservation of endo- and exocrine function (ca. 90%) and 10-year progression-free survival of ca. 75% with slightly increased morbidity (ca. 60%) compared with resecting procedures.The following video article presents the surgical video of a robotic cyst enucleation (for suspected BD-IPMN with "worrisome features") in the pancreatic head and uncinate process in a 62-year-old female patient with special emphasis on the most important vascular landmarks, special features of the approach and advantages of the robotic technique.
Subject(s)
Cysts , Robotic Surgical Procedures , Consensus , Female , Humans , Middle Aged , Pancreas/surgery , Progression-Free SurvivalABSTRACT
BACKGROUND: In recent years, there have been changes in the treatment of ductal pancreatic carcinoma with regard to multimodal therapy and also surgical therapy. These changes have not yet been explored in large nationwide studies in Germany. The present work gives an initial overview from a surgical perspective of the developments in diagnosis, therapy and survival of pancreatic cancer within the last 19 years in Germany. METHODS: In this cohort of 18 clinical cancer registries in Germany, patients with a diagnosis of ductal pancreatic cancer from 2000-2018 were included. The patients were categorised according to the years of diagnosis (2000-2009 vs. 2010-2018) and treatment modalities and compared. RESULTS: In the cohort of approx. 48000 patients with ductal pancreatic cancer, the number of newly diagnosed cases increased from approx. 18000 to 30000 patients in the two ten-year periods. The median overall survival increased slightly but statistically significantly from 7.1 to 7.9 months (p < 0.001). The resection rate increased from 25% to 32%, with the proportion of patients for whom no specific therapy was reported decreased by 11%. The rate of palliative chemotherapy and neoadjuvant chemotherapy also increased from 16% to 20% of the patients and from less than 1% to 2% of the patients, respectively. The median survival in the curatively treated subgroups was up to 24 months. SUMMARY: The cancer registry data appear to confirm the known increase in the incidence of pancreatic cancer in the western world. Resection rates and the rates of treatment with neoadjuvant and palliative intent also increased. The overall survival of all patients with ductal pancreatic cancer only increased marginally. In the subgroups of patients who were treated with curative intent, however, significantly longer survival times were found.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Carcinoma, Pancreatic Ductal/epidemiology , Carcinoma, Pancreatic Ductal/surgery , Humans , Incidence , Pancreatectomy , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/surgery , Pancreatic NeoplasmsABSTRACT
In the surgical treatment of gastroesophageal reflux disease and of hiatal hernias, the high rate of recurrence of hiatal hernias is a central problem. Against this background, various, primarily alloplastic, meshes are used to augment suture closure on the esophageal hiatus. Very different results have been reported in the past and the use of meshes in hiatus reconstruction is controversial. In addition to the frequency of recurrences, reports about complications of mesh augmentation are in the foreground. On the basis of several prospective randomised double-blinded comparative studies and meta-analyses (class Ia and Ib evidence), the current data do not show any advantages of mesh-augmented hiatoplasty for the prevention of recurrence of hiatal hernia. At the same time, there exist reports of more long-term postoperative complications, especially dysphagia, after use of meshes for augmentation of hiatus reconstruction. Therefore, routine use of mesh augmentation for hiatus reconstruction is currently not recommended.
Subject(s)
Gastroesophageal Reflux , Hernia, Hiatal , Laparoscopy , Gastroesophageal Reflux/surgery , Hernia, Hiatal/surgery , Humans , Prospective Studies , Recurrence , Surgical MeshABSTRACT
BACKGROUND: Intestinal anastomotic insufficiency (AI) is a common problem in visceral surgery associated with overexpression of matrix metalloproteinases (MMPs). In some patients it occurs more than once. The etiology of recurring anastomotic insufficiency (RAI) is not understood yet and should be addressed as an independent disease entity. MATERIALS AND METHODS: Thirty nine consecutive patients with AI were treated at our university center and were included in this prospective study. Clinical data were evaluated by correlative statistical analysis to identify independent risk factors for RAI. Patients were divided in two groups: 18 patients had a single operative revision until restoration (group SAI), and 21 patients had two or more revisions (group RAI). Anastomotic tissue samples as well as untouched bowel wall were collected during reoperations for analysis of MMPs and tissue inhibitor of metalloproteinases (TIMP2). Clinical data were correlated with pathological observations. RESULTS: Significant differences of clinical and molecular pathological data were found between the two groups. Transfusion of red blood cells until the first reoperation and alcohol abuse led to RAI and were the only independent risk factors for RAI in multivariate analysis. Overexpression of MMP-8, -9, and -13 in anastomotic tissue correlated with the administration of red blood cells during initial operation. Reduced expression of TIMP2 was frequent in nearly all patients without differences throughout the subgroups. CONCLUSIONS: RAI seems to have an independent disease pattern. Transfusion of blood products is not only a known risk factor for AI but seems to significantly disturb the anastomotic healing process leading to RAI.
Subject(s)
Anastomotic Leak/pathology , Blood Component Transfusion/adverse effects , Intestines/surgery , Adult , Aged , Aged, 80 and over , Anastomosis, Surgical/adverse effects , Anastomotic Leak/epidemiology , Anastomotic Leak/surgery , Female , Follow-Up Studies , Humans , Intestines/pathology , Male , Middle Aged , Prospective Studies , Recurrence , Reoperation , Risk Factors , Tissue Inhibitor of Metalloproteinase-2/analysis , Tissue Inhibitor of Metalloproteinase-2/metabolism , Young AdultABSTRACT
BACKGROUND: Advances regarding perioperative mortality rates and oncological outcomes after esophagectomy have been reported extensively by specialized high-volume centers in Europe and the USA over the last decade. However, recent database analyses reveal that the perioperative mortality of esophagectomy remains high in these countries, indicating a discrepancy between surgical quality in baseline hospitals and specialized centers. METHODS: This article provides an overview over the existing literature on the correlation between structural quality, procedural volume, and surgical outcome in e- sophageal surgery. RESULTS: Structural, procedural and outcome measures can be used to assess the quality of surgical treatment and perioperative management. Surgical procedures on the esophagus for both benign and malignant diseases are rare and typically associated with high perioperative morbidity and mortality. Usually, direct outcome measures do not provide enough statistical power to actually identify differences in surgical quality between hospitals, making structural quality measures the only feasible parameter to compare the quality of e- sophageal surgery among different centers. Several analyses from different countries have shown a strong correlation between hospital volume and postoperative mortality. Data from countries in which esophageal surgery has been centralized indicate beneficial effects of a centralized health care system on postoperative mortality after esophagectomy. Additionally, only high-volume centers generally provide optimal preoperative and postoperative management and comprehensive access to modern multimodal treatment. In Germany, esophageal surgery is still decentralized, but hospitals performing complex esophageal procedures have to fulfill minimum caseload requirements of 10 cases per year. In practice, these requirements are not met by the majority of hospitals and a detrimental effect on the achieved surgical outcomes can be noted. CONCLUSION: Therefore, we conclude that structural quality assurance is crucial to further reduce postoperative morbidity after esophageal surgery and to improve long-term results.
ABSTRACT
INTRODUCTION: Nodal status is a strong prognostic factor after resection of pancreatic cancer. The lymph node ratio (LNR) has been shown to be superior to the pN status in several studies. The role of log odds of the ratio between positive and negative nodes (LODDS) as a suggested new indicator of prognosis, however, has been hardly evaluated in pancreatic cancer. METHODS: Prognostic factors for overall survival after resection for cancer of the pancreatic head were evaluated in 409 patients from two institutions (prospectively maintained databases). The lymph node status, LNR, and LODDS were separately analyzed and independently compared in multivariate survival analysis. RESULTS: The median numbers of examined and positive lymph nodes were 16 and 2, respectively. Actuarial 3- and 5-year survival rates were 29 and 16 %. All three classifications of nodal disease significantly predicted survival in the entire group (n = 409), in patients with free resection margins (n = 297), and in patients with <12 examined nodes. In multivariate analysis, however, both LNR and LODDS were equally superior to the nodal status. In node-negative patients (n = 110), LODDS could not identify subgroups with different prognosis. CONCLUSION: Both LNR and LODDS are superior to the classical nodal status in predicting prognosis in resected pancreatic cancer. However, LODDS has not shown any advantage over LNR in our series, neither in the entire patient group nor in the subgroups with free margins, negative nodes or a low number of examined nodes. Therefore, the use of LODDS to predict the outcome after resection of pancreatic head cancer cannot be recommended.
Subject(s)
Lymph Nodes/pathology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Pancreas/pathology , Pancreas/surgery , Pancreatic Neoplasms/mortality , Prognosis , Survival Analysis , Survival RateABSTRACT
Intramural esophageal dissection (IED) is a rare disease characterized by a partial (PIED) or circumferential (CIED) mucosal rupture. Whereas PIED responds well to nonoperative treatment, complicated courses have been reported necessitating surgery, up to the point of esophagectomy despite complex endoscopic interventions, in CIED. We report the first case of an iatrogenic CIED with perforation in a young patient with underlying eosinophilic esophagitis treated successfully by endoscopy alone, using a partially covered self-expandable metal stent.
Subject(s)
Endoscopy, Digestive System/methods , Eosinophilic Esophagitis/surgery , Esophageal Perforation/surgery , Mucous Membrane/surgery , Stents , Adult , Eosinophilic Esophagitis/complications , Esophageal Diseases/etiology , Esophageal Diseases/surgery , Esophageal Perforation/etiology , Humans , Male , Metals , Rupture, Spontaneous/etiology , Rupture, Spontaneous/surgery , Treatment OutcomeABSTRACT
AIM: The aim of the article is to investigate a new anastomotic technique compared with standardized intestinal anastomotic procedures. MATERIALS AND METHODS: A total of 32 male Wistar rats were randomized to three groups. In the Experimental Group (n = 10), the new double 90 degrees inversely rotated anastomosis was used, in the End Group (n = 10) a single-layer end-to-end anastomosis, and in the Side Group (n = 12) a single-layer side-to-side anastomosis. All anastomoses were done using interrupted sutures. On postoperative day 4, rats were relaparotomized. Bursting pressure, hydroxyproline concentration, a semiquantitative adhesion score and two histological anastomotic healing scores (mucosal healing according to Chiu and overall anastomotic healing according to Verhofstad) were collected. Most data are presented as median (range). p < 0.05 was considered significant. RESULTS: Anastomotic insufficiency occurred only in one rat of the Side Group. Median bursting pressure in the Experimental Group was 105 mm Hg (range = 72-161 mm Hg), significantly higher in the End Group (164 mm Hg; range = 99-210 mm Hg; p = 0.021) and lower in the Side Group by trend (81 mm Hg; range = 59-122 mm Hg; p = 0.093). Hydroxyproline concentration did not differ significantly in between the groups. The adhesion score was 2.5 (range = 1-3) in the Experimental Group, 2 (range = 1-2) in the End Group, but there were significantly more adhesions in the Side Group (range = 3-4); p = 0.020 versus Experimental Group, p < 0.001 versus End Group. The Chiu Score showed the worst mucosal healing in the Experimental Group. The overall Verhofstad Score was significantly worse (mean = 2.032; standard deviation [SD] = 0.842) p = 0.031 and p = 0.002 in the Experimental Group, compared with the Side Group (mean = 1.729; SD = 0.682) and the End Group (mean = 1.571; SD = 0.612). CONCLUSION: The new anastomotic technique is feasible and did not show any relevant complication. Even though it was superior to the side-to-side anastomosis by trend with respect to functional stability, mucosal healing surprisingly showed the worst results. Classical end-to-end anastomosis still seems to be the best choice regarding structural and functional anastomotic stability.
Subject(s)
Anastomosis, Surgical/methods , Intestines/surgery , Animals , Feasibility Studies , Hydroxyproline/metabolism , Intestinal Mucosa/physiology , Intestines/pathology , Intestines/physiology , Male , Random Allocation , Rats, Wistar , Suture Techniques , Tensile Strength , Tissue Adhesions/pathology , Wound HealingSubject(s)
Bronchial Fistula/surgery , Bronchoscopy/methods , Esophagectomy , Gastric Fistula/surgery , Gastroscopy/methods , Postoperative Complications/surgery , Bronchial Fistula/etiology , Bronchial Fistula/pathology , Gastric Fistula/etiology , Gastric Fistula/pathology , Humans , Male , Middle Aged , Postoperative Complications/pathologyABSTRACT
PURPOSE: This investigation focuses on the physiological characteristics of gene transcription of intestinal tissue following anastomosis formation. METHODS: In eight rats, end-to-end ileo-ileal anastomoses were performed (n = 2/group). The healthy intestinal tissue resected for this operation was used as a control. On days 0, 2, 4 and 8, 10-mm perianastomotic segments were resected. Control and perianastomotic segments were examined with an Affymetrix microarray chip to assess changes in gene regulation. Microarray findings were validated using real-time PCR for selected genes. In addition to screening global gene expression, we identified genes intensely regulated during healing and also subjected our data sets to an overrepresentation analysis using the Gene Ontology (GO) and Kyoto Encyclopedia for Genes and Genomes (KEGG). RESULTS: Compared to the control group, we observed that the number of differentially regulated genes peaked on day 2 with a total of 2,238 genes, decreasing by day 4 to 1,687 genes and to 1,407 genes by day 8. PCR validation for matrix metalloproteinases-3 and -13 showed not only identical transcription patterns but also analogous regulation intensity. When setting the cutoff of upregulation at 10-fold to identify genes likely to be relevant, the total gene count was significantly lower with 55, 45 and 37 genes on days 2, 4 and 8, respectively. A total of 947 GO subcategories were significantly overrepresented during anastomotic healing. Furthermore, 23 overrepresented KEGG pathways were identified. CONCLUSION: This study is the first of its kind that focuses explicitly on gene transcription during intestinal anastomotic healing under standardized conditions. Our work sets a foundation for further studies toward a more profound understanding of the physiology of anastomotic healing.
Subject(s)
Anastomosis, Surgical , Intestinal Mucosa/metabolism , Intestines/surgery , Wound Healing/physiology , Animals , Gene Expression Profiling , Gene Ontology , Male , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , Random Allocation , Rats, WistarABSTRACT
PURPOSE: Clinical data indicate that laparoscopic surgery has a beneficial effect on intestinal wound healing and is associated with a lower incidence of anastomotic leakage. This observation is based on weak evidence, and little is known about the impact of intraoperative parameters during laparoscopic surgery, e.g., temperature and humidity. METHODS: A small-bowel anastomosis was formed in rats inside an incubator, in an environment of stable humidity and temperature. Three groups of ten Wistar rats were operated: a control group (G1) in an open surgical environment and two groups (G2 and G3) in the incubator at a humidity of 60 % and a temperature of 30 and 37 °C (G2 and G3, respectively). After 4 days, bursting pressure and hydroxyproline concentration of the anastomosis were analyzed. The tissue was histologically examined. Serum levels of C-reactive-protein (CRP) were measured. RESULTS: No significant changes were seen in the evaluation of anastomotic stability. Bursting pressure was very similar among the groups. Hydroxyproline concentration in G3 (36.3 µg/g) was lower by trend (p = 0.072) than in G1 (51.7 µg/g) and G2 (46.4 µg/g). The histological evaluation showed similar results regarding necrosis, inflammatory cells, edema, and epithelization for all groups. G3 (2.56) showed a distinctly worse score for submucosal bridging (p = 0.061) than G1 (1.68). A highly significant increase (p = 0.008) in CRP was detected in G3 (598.96 ng/ml) compared to G1 (439.49 ng/ml) and G2 (460 ng/ml). CONCLUSION: A combination of high temperature and humidity during surgery induces an increased systemic inflammatory response and seems to be attenuating the early regeneration process in the anastomotic tissue.
Subject(s)
Anastomotic Leak/prevention & control , Humidity , Intestines/surgery , Intraoperative Period , Temperature , Wound Healing/physiology , Anastomosis, Surgical/methods , Animals , C-Reactive Protein/metabolism , Hydroxyproline/metabolism , Intestines/pathology , Intestines/physiopathology , Male , Rats, Wistar , Tensile Strength , Tissue Adhesions/pathologyABSTRACT
Pancreatic cancer is a highly aggressive disease with poor survival. The only effective therapy offering long-term survival is complete surgical resection. In the setting of nonmetastatic disease, locally advanced tumors constitute a technical challenge to the surgeon and may result in margin-positive resection margins. Few studies have evaluated the implications of the latter in depth. The aim of this study was to compare the margin-positive situation to palliative bypass procedures and margin-negative resections in terms of perioperative and long-term outcome. By retrospective analysis of prospectively maintained data from 360 patients operated for pancreatic cancer at our institution, we provide evidence that margin-positive resection still yields a significant survival benefit over palliative bypass procedures. At the same time, perioperative severe morbidity and mortality are not significantly increased. Our observations suggest that pancreatic cancer should be resected whenever technically feasible, including, cases of locally advanced disease.
ABSTRACT
BACKGROUND: Postoperative pancreatic fistula (POPF) is regarded as the most serious complication of pancreatic surgery. The preoperative risk stratification of patients by simple means is of interest in perioperative clinical management. METHODS: Based on prospective data, we performed a risk factor analysis for POPF after pancreatoduodenectomy in 62 patients operated between 2006 and 2008 with special focus on clinical parameters that might serve to predict POPF. A predictive score was developed and validated in an independent second dataset of 279 patients operated between 2001 and 2010. RESULTS: Several pre- and intraoperative factors, as well as underlying pathology, showed significant univariate correlation with rate of POPF. Multivariate analysis (binary logistic regression) disclosed soft pancreatic texture (odds ratio [OR] 10.80, 95% confidence interval [CI] 1.80-62.20) and history of weight loss (OR 0.15, 95% CI 0.04-0.66) to be the only independent preoperative clinical factors influencing POPF rate. The subjective assessment of pancreatic hardness by the surgeon correlated highly with objective assessment of pancreatic fibrosis by the pathologist (r = -0.68, P < 0.001, two-tailed Spearman's rank correlation). A simple risk score based on preoperatively available clinical parameters was able to stratify patients correctly into three risk groups and was independently validated. CONCLUSIONS: Preoperative stratification of patients regarding risk for POPF by simple clinical parameters is feasible. Pancreatic texture, as evaluated intraoperatively by the surgeon, is the strongest single predictive factor of POPF. The findings of the study may have important implications for perioperative risk assessment and patient care, as well as for the choice of anastomotic techniques.