Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm—A Pancreas2000/EPC Study

Background: Lesions of the Ampulla of Vater are a rare condition and represent <10% of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA), or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed, recent studies reported considerable efficacy and fewer complications following EP and SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence for a therapeutic standard and post procedure morbidity in ampullary lesions. Methods: International multicenter retrospective study. Adult patients (>18 years of age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions. Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head of the pancreas, and interventions for tumor stages higher than T2. The main objective of this study is to analyze rates of complete resection (R0), recurrence and necessity for complementary interventions following EP, SA, and PD. Treatment-quality for each procedure will be defined by morbidity, mortality and complication rates and will be compared between EP, SA, and PD. Secondary objectives include outcome for patients with incomplete resection or initially understated tumors, lesions of the minor papilla, hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare conditions. Additionally, we will analyze therapy by argon plasma coagulation and radiofrequency ablation. Furthermore, outcome in curative and palliative interventions can be distinguished. Conclusion: The ESAP study will provide evidence for therapeutic algorithms and data for the implementation of guidelines in the treatment of different types of ampullary tumors, including recurrent, or incomplete resected lesions

Systematic Review with Meta-Analysis: Endoscopic and Surgical Resection for Ampullary Lesions

Ampullary lesions (ALs) can be treated by endoscopic (EA) or surgical ampullectomy (SA) or pancreaticoduodenectomy (PD). However, EA carries significant risk of incomplete resection while surgical interventions can lead to substantial morbidity. We performed a systematic review and meta-analysis for R0, adverse-events (AEs) and recurrence between EA, SA and PD. Electronic databases were searched from 1990 to 2018. Outcomes were calculated as pooled means using fixed and random-effects models and the Freeman-Tukey-Double-Arcsine-Proportion-model. We identified 59 independent studies. The pooled R0 rate was 76.6% (71.8–81.4%, I2 = 91.38%) for EA, 96.4% (93.6–99.2%, I2 = 37.8%) for SA and 98.9% (98.0–99.7%, I2 = 0%) for PD. AEs were 24.7% (19.8–29.6%, I2 = 86.4%), 28.3% (19.0–37.7%, I2 = 76.8%) and 44.7% (37.9–51.4%, I2 = 0%), respectively. Recurrences were registered in 13.0% (10.2–15.6%, I2 = 91.3%), 9.4% (4.8–14%, I2 = 57.3%) and 14.2% (9.5–18.9%, I2 = 0%). Differences between proportions were significant in R0 for EA compared to SA (p = 0.007) and PD (p = 0.022). AEs were statistically different only between EA and PD (p = 0.049) and recurrence showed no significance for EA/SA or EA/PD. Our data indicate an increased rate of complete resection in surgical interventions accompanied with a higher risk of complications. However, studies showed various sources of bias, limited quality of data and a significant heterogeneity, particularly in EA studies

Elevated Adipsin and Reduced C5a Levels in the Maternal Serum and Follicular Fluid During Implantation Are Associated With Successful Pregnancy in Obese Women

Introduction: Complement factors mediate the recruitment and activation of immune cells and are associated with metabolic changes during pregnancy. The aim of this study was to determine whether complement factors in the maternal serum and follicular fluid (FF) are associated with in vitro fertilization (IVF) outcomes in overweight/obese women. Methods: Forty overweight/obese (BMI = 30.8 ± 5.2 kg/m2) female patients, 33.6 ± 6.3 years old, undergoing IVF treatment for unexplained infertility were recruited. Baseline demographic information, including biochemical hormonal, metabolic, and inflammatory markers, and pregnancy outcome, was collected. Levels of 14 complement markers (C2, C4b, C5, C5a, C9, adipsin, mannose-binding lectin, C1q, C3, C3b/iC3b, C4, factor B, factor H, and properdin) were assessed in the serum and FF and compared to IVF outcome, inflammatory, and metabolic markers using multivariate and univariate models. Results: Out of 40 IVF cycles, 14 (35%) resulted in pregnancy. Compared to women with failed pregnancies, women with successful pregnancies had higher levels of adipsin in the serum and FF (p = 0.01) but lower C5a levels (p = 0.05). Serum adipsin levels were positively correlated with circulating levels of vitamin D (R = 0.5, p = 0.02), glucagon (R = 0.4, p = 0.03), leptin (R = 0.4, p = 0.01), resistin (R = 0.4, p = 0.02), and visfatin (R = 0.4, p = 0.02), but negatively correlated with total protein (R = −0.5, p = 0.03). Higher numbers of top-quality embryos were associated with increased levels of C3, properdin, C1q, factors H and B, C4, and adipsin, but with reduced C2 and C5a levels (p ≤ 0.01). Conclusions: Higher adipsin and lower C5a levels in the maternal serum during implantation are potential markers of successful outcome in obese women undergoing IVF-assisted pregnancies

Herd Immunity against Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 10 Communities, Qatar.

We investigated what proportion of the population acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whether the herd immunity threshold has been reached in 10 communities in Qatar. The study included 4,970 participants during June 21-September 9, 2020. Antibodies against SARS-CoV-2 were detected by using an electrochemiluminescence immunoassay. Seropositivity ranged from 54.9% (95% CI 50.2%-59.4%) to 83.8% (95% CI 79.1%-87.7%) across communities and showed a pooled mean of 66.1% (95% CI 61.5%-70.6%). A range of other epidemiologic measures indicated that active infection is rare, with limited if any sustainable infection transmission for clusters to occur. Only 5 infections were ever severe and 1 was critical in these young communities; infection severity rate of 0.2% (95% CI 0.1%-0.4%). Specific communities in Qatar have or nearly reached herd immunity for SARS-CoV-2 infection: 65%-70% of the population has been infected

DATA file for article 10.1371/journal.pone.0209094

All the data file of experiments described in the article: Ultrasonic cavitation induces necrosis and impairs growth in three-dimensional models of pancreatic ductal adenocarcinoma.ABOU ALI E. et a

Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm—A Pancreas2000/EPC Study

Background: Lesions of the Ampulla of Vater are a rare condition and represent <10% of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA), or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed, recent studies reported considerable efficacy and fewer complications following EP and SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence for a therapeutic standard and post procedure morbidity in ampullary lesions. Methods: International multicenter retrospective study. Adult patients (>18 years of age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions. Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head of the pancreas, and interventions for tumor stages higher than T2. The main objective of this study is to analyze rates of complete resection (R0), recurrence and necessity for complementary interventions following EP, SA, and PD. Treatment-quality for each procedure will be defined by morbidity, mortality and complication rates and will be compared between EP, SA, and PD. Secondary objectives include outcome for patients with incomplete resection or initially understated tumors, lesions of the minor papilla, hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare conditions. Additionally, we will analyze therapy by argon plasma coagulation and radiofrequency ablation. Furthermore, outcome in curative and palliative interventions can be distinguished. Conclusion: The ESAP study will provide evidence for therapeutic algorithms and data for the implementation of guidelines in the treatment of different types of ampullary tumors, including recurrent, or incomplete resected lesions

Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm—A Pancreas2000/EPC Study

Background: Lesions of the Ampulla of Vater are a rare condition and represent <10% of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA), or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed, recent studies reported considerable efficacy and fewer complications following EP and SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence for a therapeutic standard and post procedure morbidity in ampullary lesions. Methods: International multicenter retrospective study. Adult patients (>18 years of age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions. Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head of the pancreas, and interventions for tumor stages higher than T2. The main objective of this study is to analyze rates of complete resection (R0), recurrence and necessity for complementary interventions following EP, SA, and PD. Treatment-quality for each procedure will be defined by morbidity, mortality and complication rates and will be compared between EP, SA, and PD. Secondary objectives include outcome for patients with incomplete resection or initially understated tumors, lesions of the minor papilla, hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare conditions. Additionally, we will analyze therapy by argon plasma coagulation and radiofrequency ablation. Furthermore, outcome in curative and palliative interventions can be distinguished. Conclusion: The ESAP study will provide evidence for therapeutic algorithms and data for the implementation of guidelines in the treatment of different types of ampullary tumors, including recurrent, or incomplete resected lesions

Study protocol of the ESAP study: endoscopic papillectomy vs. surgical ampullectomy vs. pancreaticoduodenectomy for ampullary neoplasm - a Pancreas2000/EPC study

Background: Lesions of the Ampulla of Vater are a rare condition and represent 18 years of age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions. Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head of the pancreas, and interventions for tumor stages higher than T2. The main objective of this study is to analyze rates of complete resection (R0), recurrence and necessity for complementary interventions following EP, SA, and PD. Treatment-quality for each procedure will be defined by morbidity, mortality and complication rates and will be compared between EP, SA, and PD. Secondary objectives include outcome for patients with incomplete resection or initially understated tumors, lesions of the minor papilla, hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare conditions. Additionally, we will analyze therapy by argon plasma coagulation and radiofrequency ablation. Furthermore, outcome in curative and palliative interventions can be distinguished. Conclusion: The ESAP study will provide evidence for therapeutic algorithms and data for the implementation of guidelines in the treatment of different types of ampullary tumors, including recurrent, or incomplete resected lesions

Systematic Review with Meta-Analysis: Endoscopic and Surgical Resection for Ampullary Lesions

Ampullary lesions (ALs) can be treated by endoscopic (EA) or surgical ampullectomy (SA) or pancreaticoduodenectomy (PD). However, EA carries significant risk of incomplete resection while surgical interventions can lead to substantial morbidity. We performed a systematic review and meta-analysis for R0, adverse-events (AEs) and recurrence between EA, SA and PD. Electronic databases were searched from 1990 to 2018. Outcomes were calculated as pooled means using fixed and random-effects models and the Freeman-Tukey-Double-Arcsine-Proportion-model. We identified 59 independent studies. The pooled R0 rate was 76.6% (71.8–81.4%, I2 = 91.38%) for EA, 96.4% (93.6–99.2%, I2 = 37.8%) for SA and 98.9% (98.0–99.7%, I2 = 0%) for PD. AEs were 24.7% (19.8–29.6%, I2 = 86.4%), 28.3% (19.0–37.7%, I2 = 76.8%) and 44.7% (37.9–51.4%, I2 = 0%), respectively. Recurrences were registered in 13.0% (10.2–15.6%, I2 = 91.3%), 9.4% (4.8–14%, I2 = 57.3%) and 14.2% (9.5–18.9%, I2 = 0%). Differences between proportions were significant in R0 for EA compared to SA (p = 0.007) and PD (p = 0.022). AEs were statistically different only between EA and PD (p = 0.049) and recurrence showed no significance for EA/SA or EA/PD. Our data indicate an increased rate of complete resection in surgical interventions accompanied with a higher risk of complications. However, studies showed various sources of bias, limited quality of data and a significant heterogeneity, particularly in EA studies

Data from: Ultrasonic cavitation induces necrosis and impairs growth in three-dimensional models of pancreatic ductal adenocarcinoma

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a rapidly increasing cause of mortality whose dismal prognosis is mainly due to overwhelming chemoresistance. New therapeutic approaches include physical agents such as ultrasonic cavitation, but clinical applications require further insights in the mechanisms of cytotoxicity. Three dimensional in vitro culture models such as spheroids exploit realistic spatial, biochemical and cellular heterogeneity that may bridge some of the experimental gap between conventional in vitro and in vivo experiments. Purpose: to assess the feasibility and efficiency of inertial cavitation associated or not with chemotherapy, in a spheroid model of PDAC. Methods: we used DT66066 cells ,derived from a genetically-engineered murine PDAC, isolated from KPC-transgenic mice (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1- Cre). Spheroids were obtained by either a standard centrifugation-based method, or by using a magnetic nano-shuttle method allowing the formation of spheroids within 24 hours and facilitating their handling. The spheroids were exposed to ultrasonic inertial cavitation in a specially designed setup. Four conditions were studied: control, gemcitabine alone , US cavitation alone , US cavitation + gemcitabine. Five US inertial cavitation indexes, corresponding to increased US intensities, were evaluated . The effectiveness of treatment was assessed after 24 hours with the following criteria: spheroid size (growth), ratio of phase S cells (proliferation), proportion of cells in apoptosis or necrosis (cellular mortality). These parameters were assessed by quantitative immunofluorescence techniques. Results: The 3D culture model presented excellent reproducibility. Eight or nine spheroids were analyzed for each condition. Cavitation induced a significant decrease in the size of spheroids , an effect significantly correlated to an increasing cavitation index (p < 0.0001). The treatment induced cell death whose predominant mechanism was necrosis (p < 0.0001). There was a tendency to a synergistic effect of US cavitation and gemcitabine at 5μM concentration, however significant in only one of the cavitation indexes used (p = 0. 013). Conclusion: Ultrasonic inertial cavitation induced a significant reduction of tumor growth in a spheroid model of PDAC., with necrosis rather than apoptosis as a Cell dominant mechanism of cell death. More investigations are needed to understand the potential role of inertial cavitation in overcoming chemoresistance