Peritoneal regression grading score (PRGS): first evidence for independent predictive and prognostic significance.

Objectives: The peritoneal regression grading score (PRGS) is a four-tied pathologic score measuring tumor regression in biopsies from patients with peritoneal metastasis (PM) receiving chemotherapy. Methods: This retrospective analysis of a prospective registry (NCT03210298) analyses 97 patients with isolated PM under palliative chemotherapy. We examined the predictive value of the initial PRGS for overall survival (OS) and the prognostic value of PRGS in repeated peritoneal biopsies. Results: The 36 (37.1 %) patients with an initial mean PRGS≤2 had a longer median OS (12.1 months, CI 95 % 7.8-16.4) vs. 8.0 months (CI 95 % 5.1-10.8 months) in 61 (62.9 %) patients with PRGS≥3 (p=0.02) After stratification, the initial PRGS was an independent predictor of OS (Cox-regression, p<0.05). Out of 62 patients receiving≥two chemotherapy cycles, 42 (67.7 %) had a histological response (defined as a lower or stable mean PRGS in successive therapy cycles), and 20 (32.3 %) progressed (defined as an increasing mean PRGS). PRGS response was associated with a longer median OS (14.6 months, CI 5-95 % 6.0-23.2) vs. 6.9 (CI 5-95 % 0.0-15.9) months. PRGS response was prognostic in the univariate analysis (p=0.017). Thus, PRGS had both a predictive and prognostic significance in patients with isolated PM receiving palliative chemotherapy in this patient cohort. Conclusions: This is the first evidence for the independent predictive and prognostic significance of PRGS in PM. These encouraging results need validation in an adequately powered, prospective study.

The most influential COVID-19 articles: A systematic review.

Background: Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),causative pathogen of coronavirus disease 2019 (COVID-19), has triggered a pandemic with challenges for health care systems around the world. Researchers have studied and published on the subject of SARS-CoV-2 and the disease extensively. What is the significance of articles published, shared and cited in the early stages of such a pandemic? Materials and methods: A systematic literature search in a time frame of 12 months and analysis rating using Principle Component Analysis (PCA) and Multiple Factor Analysis (MFA) were performed. Results: The 100 most cited COVID-19 articles were identified. The majority of these articles were from China (n = 54), followed by United States of America (USA) (n = 21) and United Kingdom (UK) (n = 8). All articles were published in high-ranked, peer-reviewed journals, with research focusing onthe the diagnosis, transmission and therapy of COVID-19. The level of evidence of the 100 most cited COVID-19 articles on average was low. Conclusion: In the early stages of a pandemic, new and innovative research can emerge and be highly cited, regardless of the level of evidence.

Effects of Lifestyle and Educational Bridging Programs before Bariatric Surgery on Postoperative Weight Loss: A Systematic Review and Meta-Analysis.

OBJECTIVE: To fulfill the requirements for bariatric surgery, patients often need to participate in mandatory preoperative lifestyle interventions. Currently, the efficacy of multi-month preoperative lifestyle intervention programs on body mass index (BMI) reduction from the start of the program (T0) through the immediate preoperative time point (T1) to 1 year post-surgery (T2) and how the amount of preoperative BMI reduction affects postoperative outcome (T1 to T2) is unclear. The aim of this meta-analysis was to analyze the effects of preoperative lifestyle interventions on BMI 1 year post-surgery. METHOD: A systematic literature search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Randomized controlled trials that implemented preoperative lifestyle interventions lasting 1-8 months before bariatric surgery were included. The BMI of the intervention group was compared with that of a control group before participation in the preoperative lifestyle interventions (T0), after completion of the program before surgery (T1), and 1 year post-surgery (T2). Finally, the impact of successful BMI reduction at T1 on BMI at T2 was analyzed. RESULTS: N = 345 patients derived from 4 studies undergoing preoperative lifestyle interventions reduced their BMI at T1 by 1.5 units compared to the control group (95% CI: -2.73, -0.28). One year post-surgery, both groups had lost comparable BMI points. The influence of reduced BMI at T1 on weight status at T2 is unclear due to the lack of available studies. Other endpoints and subgroup analyses were rarely examined. CONCLUSIONS: Preoperative lifestyle interventions reduce BMI before bariatric surgery more effectively than usual care. These differences are not detectable 1 year post-surgery. Although a short-term energy reduction period before surgery is clearly important to minimize surgery risks, it is currently unclear whether, and if so, under what circumstances, participation in a preoperative lifestyle intervention is beneficial.

Treatment of Acute Mesenteric Ischemia: Individual Challenges for Interventional Radiologists and Abdominal Surgeons.

Background: Acute mesenteric ischemia (AMI) is a life-threatening condition resulting from occlusion of the mesenteric arterial vessels. AMI requires immediate treatment with revascularization of the occluded vessels. Purpose: to evaluate the technical success, clinical outcomes and survival of patients receiving endovascular treatment for AMI followed by surgery. Material and Methods: A search of our institution's database for AMI revealed 149 potential patients between 08/2016 and 08/2021, of which 91 were excluded due to incomplete clinical data, insufficient imaging or missing follow-up laparoscopy. The final cohort included 58 consecutive patients [(median age 73.5 years [range: 43−96 years], 55% female), median BMI 26.2 kg/m2 (range:16.0−39.2 kg/m2)]. Periinterventional imaging regarding the cause of AMI (acute-embolic or acute-on-chronic) was evaluated by two radiologists in consensus. The extent of AMI and the degree of technical success was graded according to a modified TICI (Thrombolysis in Cerebral Infarction scale) score (TICI-AMI) classification (0: no perfusion; 1: minimal; 2a < 50% filling; 2b > 50%; 2c: near complete or slow; 3: complete). Lab data and clinical data were collected, including the results of follow-up laparoscopy. Non-parametric statistics were used. Results: All interventions were considered technically successful. The most common causes of AMI were emboli (51.7%) and acute-on-chronic thrombotic occlusions (37.9%). Initial imaging showed a TICI-AMI score of 0, 1 or 2a in 87.9% (n = 51) of patients. Post-therapeutic TICI-AMI scores improved significantly with 87.9% of patients grade 2b and better. Median lactate levels reduced from 2.7 (IQR 2.0−3.7) mg/dL (1−18) to 1.45 (IQR 0.99−1.90). Intestinal ischemia was documented in 79.1% of cases with resection of the infarcted intestinal loops. In total, 22/58 (37.9%) patients died during the first 30 days after intervention and surgery. According to CIRSE criteria, we did not observe any SAE scores of grade 2 or higher. Conclusions: AMI is a serious disease with high lethality within the first 30 days despite optimal treatment. However, interventional revascularization before surgery with resection of the infarcted bowel can save two out of three of critically ill patients.

Role of Rendezvous-Procedure in the Treatment of Complications after Laparoscopic Sleeve Gastrectomy.

INTRODUCTION: Laparoscopic sleeve gastrectomy is one of the most commonly performed bariatric procedures worldwide with good results, high patient acceptance, and low complication rates. The most relevant perioperative complication is the staple line leak. For the treatment of this complication, endoscopic negative pressure therapy has proven particularly effective. The correct time to start endoscopic negative pressure therapy has not been the subject of studies to date. METHODS: Twelve patients were included in this retrospective data analysis over three years. Endoscopic negative pressure therapy was carried out using innovative open pore suction devices. Patients were treated with simultaneous surgery and endoscopy, so called rendezvous-procedure (Group A) or solely endoscopically, or in sequence surgically and endoscopically (Group B). Therapy data of the procedures and outcome measures, including duration of therapy, therapy success, and change of treatment strategy, were collected and analysed. RESULTS: In each group, six patients were treated (mean age 52.96 years, 4 males, 8 females). Poor initial clinical situation, time span of endoscopic negative pressure therapy (Group A 31 days vs. Group B 18 days), and mean length of hospital stay (Group A 39.5 days vs. Group B 20.17 days) were higher in patients with rendezvous procedures. One patient in Group B died during the observation time. DISCUSSION: Rendezvous procedures for patients with staple line leaks after sleeve gastrectomy is indicated for serious ill patients with perigastric abscesses and in need of laparoscopic lavage. The one-stage complication management with the rendezvous procedure seems not to result in an obvious advantage in the further outcome in patients with staple line leaks after laparoscopic sleeve gastrectomy.

Current practice and perceptions of safety protocols for the use of intraperitoneal chemotherapy in the operating room: results of the IP-OR international survey.

OBJECTIVES: To assess the risk perception and the uptake of measures preventing environment-related risks in the operating room (OR) during hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: A multicentric, international survey among OR teams in high-volume HIPEC and PIPAC centers: Surgeons (Surg), Scrub nurses (ScrubN), Anesthesiologists (Anest), Anesthesiology nurses (AnesthN), and OR Cleaning staff (CleanS). Scores extended from 0-10 (maximum). RESULTS: Ten centers in six countries participated in the study (response rate 100%). Two hundred and eleven responses from 68 Surg (32%), 49 ScrubN (23%), 45 Anest (21%), 31 AnesthN (15%), and 18 CleanS (9%) were gathered. Individual uptake of protection measures was 51.4%, similar among professions and between HIPEC and PIPAC. Perceived levels of protection were 7.57 vs. 7.17 for PIPAC and HIPEC, respectively (p<0.05), with Anesth scoring the lowest (6.81). Perceived contamination risk was 4.19 for HIPEC vs. 3.5 for PIPAC (p<0.01). Information level was lower for CleanS and Anesth for HIPEC and PIPAC procedures compared to all other responders (6.48 vs. 4.86, and 6.48 vs. 5.67, p<0.01). Willingness to obtain more information was 86%, the highest among CleanS (94%). CONCLUSIONS: Experience with the current practice of safety protocols was similar during HIPEC and PIPAC. The individual uptake of protection measures was rather low. The safety perception was better for PIPAC, but the perceived level of protection remained relatively low. The willingness to obtain more information was high. Intensified, standardized training of all OR team members involved in HIPEC and PIPAC is meaningful.

Endoscopic Negative Pressure Therapy (ENPT) Is Superior to Stent Therapy for Staple Line Leak After Sleeve Gastrectomy: a Single-Center Cohort Study.

PURPOSE: Staple line leak (SLL) is a serious complication after sleeve gastrectomy (SG). Common endoscopic treatment options include self-expandable metallic stent (SEMS), endoscopic internal drainage (EID), and endoscopic closure. The endoscopic negative pressure therapy (ENPT) is a promising treatment option combining temporary sealing of the defect with drainage of the inflammatory bed. In this study, we compare the outcome of ENPT and SEMS for the treatment of SLL following SG. MATERIALS AND METHODS: A retrospective cohort of 27 patients (21 females) treated at a single center for SLL after SG was included. ENPT was primary therapy for 14 patients and compared with 13 patients treated primarily using SEMS. RESULTS: ENPT was associated with a significant reduction of hospital stay (19 ± 15.1 vs. 56.69 ± 47.21 days, p = 0.027), reduced duration of endoscopic treatment (9.8 ± 8.6 vs. 44.92 ± 60.98 days, p = 0.009), and shorter transabdominal drain dwell time (15 (5-96) vs. 45 (12-162) days, p = 0.014) when compared to SEMS. Whereas endoscopic management was successful in 12/14 (85.7%) of patients from the ENPT group, SEMS was successful in only 5/13 (38.5%) of patients (p = 0.015). Furthermore, ENPT was associated with a significant reduction of endoscopic adverse events compared with SEMS (14.3% vs. 76.92% p = 0.001). CONCLUSION: Compared with SEMS, ENPT is effective and safe in treating SLL after SG providing higher success rates, shorter treatment duration, and lower adverse events rates.

Patients With Super Obesity Do Not Perceive Themselves as Being at Higher Risk for a More Severe Course of COVID-19 Infection.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to major health-related concerns in the population. Several risk factors for a severe course of COVID-19 disease have been identified, with obesity taking an important role. However, it is unclear whether this association is only known in the expert world or whether individuals also experience themselves as risk patients due to their obesity and whether the desire for weight reduction may also be associated with a hoped-for risk reduction. These questions were addressed in a cross-sectional study of patients who have presented to an obesity center in order to lose body weight. Methods: Patients (n = 155) of the obesity center were asked to complete an ad hoc questionnaire to assess whether the desire to lose weight is also associated with a hoped-for risk reduction with respect to COVID-19 disease during the middle of the pandemic in the period between October 2020 and April 2021. We additionally assessed their perceived general stress using the Perceived Stress Questionnaire (PSQ). Results: In our explorative study, overall worries correlated significantly with worries about contracting COVID-19 (r = 0.483, p < 0.001). There has been an association with concerns about severe COVID-19 progression and psychological distress from the COVID-19 pandemic (r = 0.543, p < 0.001). In addition, a correlation was found between persons who worry about contracting COVID-19 and feeling like an at-risk patient (r = 0.530, p < 0.001). Interestingly, the higher the BMI (>50 kg/m2), the lower were the worries in PSQ (ANOVA p = 0.046). However, COVID-19-related worry was nonetheless present in the higher BMI subgroups. The most intense worries were experienced by individuals with a BMI between 35 and 39 (PSQ worries 50.44), immediately followed by individuals with a BMI between 40 and 49 (PSQ worries 49.36). Discussion and Conclusion: An increased risk for a more severe course of COVID-19 infection is not generally perceived by obese individuals. In particular, individuals with very high BMI (>50)-although being at very high risk for a severe course of the COVID-19 disease-do not display increased worries, which might point toward heightened denial.

Impact of Resection Volume/Stapler Firings-Ratio on Perioperative Complications and Weight Loss After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Major postoperative morbidity after laparoscopic sleeve gastrectomy (LSG) is often related to staple line leaks (SLL). Of note, a recent study suggested a central role of the absolute numbers of stapler firings as a predictive factor for postoperative morbidity due to SLL. In addition, a larger gastric remnant volume could be responsible for lower weight loss after LSG, and nevertheless, the gastric resection volume (GRV) is strictly related to the residual volume. METHODS: Prospectively, collected data of 384 consecutive patients with complete follow-up at 12 months after LSG at our institution were retrospectively analyzed. Patients were stratified according to three different variables (i.e., number of stapler firings, GRV, and GRV/stapler firings-ratio), and respective impact on postoperative complications and weight loss was analyzed. RESULTS: High absolute number of stapler firings was linked to increased intraoperative and postoperative bleeding and prolonged hospitalization, but was not associated with SLL, transfusion rate or revisional procedures. Absolute GRV showed no impact on both complications and outcome after LSG. Interestingly, higher ratio of GRV/stapler firings was not only linked to decreased intraoperative bleeding and shorter hospital stay but also to higher Excess Body Mass Index Loss (EBMIL) at 12 months after LSG. CONCLUSIONS: Here, we introduce GRV/stapler firings-ratio as a simple predictive factor for identifying patients at risk for postoperative complications and impaired weight loss that is superior compared with absolute number of stapler firings or GRV alone.

Pyogenic Liver Abscesses Caused by Acute Appendicitis: Frequency and Diagnostic and Therapeutic Recommendations.

Background: Pyogenic liver abscesses (PLA) are caused by biliary diseases or hematogenous spreading of mostly intra-abdominal infections. Liver abscesses resulted in hematogenous spreading of infections via the portal vein, such as abscesses caused by acute appendicitis. Pyogenic liver abscesses associated with appendicitis have rarely been described in the literature, especially in adults. The standard therapeutic procedures for liver abscesses are broad-spectrum antibiotic therapy and percutaneous drainage. Surgery for liver abscesses is required in cases of unsuccessful processes. Patients and Methods: A retrospective analysis of patients with liver abscesses between January 2005 and June 2013 was performed. Parameters investigated included demographics, etiologies of abscesses, treatment modalities, and germ spectrum including antibiotic profile. Five cases of PLA caused by appendicitis were reviewed in detail. Results: During the study period, 49 patients with PLA and 1,986 patients with acute appendicitis were treated in our hospital. Twenty-one patients with PLA were treated with antibiotic agents and computed tomography (CT)-guided drainage. Liver resections were necessary in 29 of the patients with PLA. In five patients with PLA, abscesses were caused by an acute appendicitis (9.4% of all PLA, 0.25% of all appendicitis operations). Diagnosis of appendicitis as cause of PLA was made during surgery for liver resections in three patients. Previous imaging was not clear in all cases of PLA caused by appendicitis. The most common pre-operative symptoms in patients with PLA caused by appendicitis were fever and right upper quadrant tenderness. Discussion: Pyogenic liver abscesses caused by acute appendicitis are rare. In the study period of eight and one-half years nearly 2,000 cases of acute appendicitis were treated and five of these patients developed liver abscesses (0.25%). Pyogenic liver abscesses should be considered in patients with unusual high infectious parameters, septic symptoms, and detection of unknown liver lesions.

Gut Microbiota, Probiotics and Psychological States and Behaviors after Bariatric Surgery-A Systematic Review of Their Interrelation.

The gastrointestinal (GI) microbiota plays an important role in health and disease, including brain function and behavior. Bariatric surgery (BS) has been reported to result in various changes in the GI microbiota, therefore demanding the investigation of the impact of GI microbiota on treatment success. The goal of this systematic review was to assess the effects of BS on the microbiota composition in humans and other vertebrates, whether probiotics influence postoperative health, and whether microbiota and psychological and behavioral factors interact. A search was conducted using PubMed and Web of Science to find relevant studies with respect to the GI microbiota and probiotics after BS, and later screened for psychological and behavioral parameters. Studies were classified into groups and subgroups to provide a clear overview of the outcomes. Microbiota changes were further assessed for whether they were specific to BS in humans through the comparison to sham operated controls in other vertebrate studies. Changes in alpha diversity appear not to be specific, whereas dissimilarity in overall microbial community structure, and increases in the abundance of the phylum Proteobacteria and Akkermansia spp. within the phylum Verrucomicrobia after surgery were observed in both human and other vertebrates studies and may be specific to BS in humans. Human probiotic studies differed regarding probiotic strains and dosages, however it appeared that probiotic interventions were not superior to a placebo for quality of life scores or weight loss after BS. The relationship between GI microbiota and psychological diseases in this context is unclear due to insufficient available data.

The correlation between vitamin D levels and demographics in patients with gastrointestinal disorders; a cross-sectional study.

AIM: The aim of the present study was to evaluate vitamin D levels, in correlation with age, body mass index (BMI), gender and ethnicity, in patients with gastrointestinal disorders (GID). BACKGROUND: Vitamin D deficiency (VDD) is a global health issue, affecting over 1 billion people. A great body of evidence has shown that it can lead to increased morbidity and mortality. Furthermore, latitude, sedentary lifestyle, limited sunlight exposure, ageing and the presence of comorbidities and chronic illnesses, places patients at an increased risk of VDD. METHODS: 305 consecutive patients, with GID, were assessed for vitamin D levels, using a two-step competitive binding immunoenzymatic assay. Patients were then classified as adequate (50-150nmol/l), insufficient (25-50nmol/l) and deficient (<25nmol/l). RESULTS: 62% of the investigated subjects had low vitamin D levels. From this group, 132 patients (43.3%) had insufficient vitamin D levels, 57 (18.7%) had deficient levels and 116 (38%) had adequate levels. Age was not significantly different in the 3 groups (p=0.29). Interestingly, vitamin D levels were significantly lower in men (39.23±23.62) compared to women (50.68±24.46) (p=0.0001). The BMI was significantly higher in patients with insufficient vitamin D levels. Being of Asian ethnicity had a positive influence on vitamin D levels (B=0.076) (p<0.0001). 71.4% of patients, with IBD, and 60% of patients, with abnormal liver function, had low vitamin D levels. CONCLUSION: VDD has a high prevalence in patients with GID in particular IBD and liver disease in the United Kingdom. Routine vitamin D testing and supplementations in the case of deficiency and suboptimal level of vitamin D for patients with hepatobiliary, pancreatic, kidney, malabsorptive and restrictive diseases/surgeries is recommended.

Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-ß1 Inhibition.

In chronic peritoneal diseases, mesothelial-mesenchymal transition is determined by cues from the extracellular environment rather than just the cellular genome. The transformation of peritoneal mesothelial cells and other host cells into myofibroblasts is mediated by cell membrane receptors, Transforming Growth Factor ß1 (TGF-ß1), Src and Hypoxia-inducible factor (HIF). This article provides a narrative review of the reprogramming of mesothelial mesenchymal transition in chronic peritoneal diseases, drawing on the similarities in pathophysiology between encapsulating peritoneal sclerosis and peritoneal metastasis, with a particular focus on TGF-ß1 signaling and estrogen receptor modulators. Estrogen receptors act at the cell membrane/cytosol as tyrosine kinases that can phosphorylate Src, in a similar way to other receptor tyrosine kinases; or can activate the estrogen response element via nuclear translocation. Tamoxifen can modulate estrogen membrane receptors, and has been shown to be a potent inhibitor of mesothelial-mesenchymal transition (MMT), peritoneal mesothelial cell migration, stromal fibrosis, and neoangiogenesis in the treatment of encapsulating peritoneal sclerosis, with a known side effect and safety profile. The ability of tamoxifen to inhibit the transduction pathways of TGF-ß1 and HIF and achieve a quiescent peritoneal stroma makes it a potential candidate for use in cancer treatments. This is relevant to tumors that spread to the peritoneum, particularly those with mesenchymal phenotypes, such as colorectal CMS4 and MSS/EMT gastric cancers, and pancreatic cancer with its desmoplastic stroma. Morphological changes observed during mesothelial mesenchymal transition can be treated with estrogen receptor modulation and TGF-ß1 inhibition, which may enable the regression of encapsulating peritoneal sclerosis and peritoneal metastasis.

MRI-guided percutaneous thermoablation in combination with hepatic resection as parenchyma-sparing approach in patients with primary and secondary hepatic malignancies: single center long-term experience.

BACKGROUND: Combination therapy using hepatic resection (HR) and intra-operative thermal ablation is a treatment approach for patients with technically unresectable liver malignancies. The aim of this study was to investigate safety, survival and local recurrence rates for patients with technically unresectable liver tumors undergoing HR and separate percutaneous MR-guided thermoablation procedure as an alternative approach. METHODS: Data from all patients with primary or secondary hepatic malignancies treated at a single institution between 2004 and 2018 with combined HR and MR-guided percutaneous thermoablation was collected and retrospectively analyzed. Complications, procedure related information and patient characteristics were collected from institutional records. Overall survival and disease-free survival were estimated using the Kaplan-Meier method. RESULTS: A total of 31 patients (age: 62.8 ± 9.1 years; 10 female) with hepatocellular carcinoma (HCC; n = 7) or hepatic metastases (n = 24) were treated for 98 hepatic tumors. Fifty-six tumors (mean diameter 28.7 ± 23.0 mm) were resected. Forty-two tumors (15.1 ± 7.6 mm) were treated with MR-guided percutaneous ablation with a technical success rate of 100%. Local recurrence at the ablation site occurred in 7 cases (22.6%); none of these was an isolated local recurrence. Six of 17 patients (35.3%) treated for colorectal liver metastases developed local recurrence. Five patients developed recurrence at the resection site (16.1%). Non-local hepatic recurrence was observed in 18 cases (58.1%) and extrahepatic recurrence in 11 cases (35.5%) during follow-up (43.1 ± 26.4 months). Ten patients (32.3%) developed complications after HR requiring pharmacological or interventional treatment. No complication requiring therapy was observed after ablation. Median survival time was 44.0 ± 7.5 months with 1-,3-, 5-year overall survival rates of 93.5, 68.7 and 31.9%, respectively. The 1-, 3- and 5-year disease-free survival rates were 38.7, 19.4 and 9.7%, respectively. CONCLUSION: The combination of HR and MR-guided thermoablation is a safe and effective approach in the treatment of technically unresectable hepatic tumors and can achieve long-term survival.

Citation classics in general medical journals: assessing the quality of evidence; a systematic review.

AIM: This review provides a comprehensive overview of more than 100 of the most cited studies in general medical journals and evaluates whether citations predict the quality of a scientific article. BACKGROUND: The number of citations is commonly used as a measure of the quality and impact of a scientific article. However, it is often criticised that the number of citations is in fact a poor indicator of the true quality, as it can be influenced by different factors such as current trends. METHODS: This review was conducted in line with the PRISMA guidelines. The Journal Citation Report (JCR) within Incites allowed the evaluation and comparison of articles, published in general medical journals, using far-reaching citation data drawn from scholarly and technical journals and conference proceedings. All steps of the review were performed in duplicate and conflicts were resolved through consensus. RESULTS: The 100 most cited articles published from 1963 until the end of 2018 were identified. The number of citations ranged from 4012 to 31853. Most of the articles were published in the 2000's, followed by the 1990's, 1980's, 1970's and 1960's, respectively. All of the articles were published in five journals. There were 50 studies at level II, 28 at level V, 10 at level IV, 7 at level III, and 5 at Level I. CONCLUSION: This systematic review provides an overview of the most cited articles, published in general medical journals. The number of citations provides an indication of the quality of evidence. However, researchers and clinicians should use standardized assessment tools rather than solely rely on the number of citations in order to judge the quality of published articles.

Endoscopic negative pressure therapy with open-pore film drainage and open-pore polyurethane sponge drainage for iatrogenic perforation of the esophagus.

BACKGROUND: Management of iatrogenic esophageal perforation (IEP) is challenging. Endoscopic negative pressure therapy (ENPT) is an emerging and effective tool for the treatment of gastrointestinal and anastomotic leaks. We have used ENPT as first-line therapy for IEP since 2017. The aim of this study was to present our results with this strategy in patients with IEP. METHODS: Nine patients were treated with ENPT for IEP between August 2017 and August 2019. Their treatment characteristics, including duration of therapy, strategy used, and outcomes, were analyzed. Treatment included ENPT with open-pore film drainage (OFD) and open-pore polyurethane foam drainage (OPD). RESULTS: Early diagnosis (< 24 hours) of IEP occurred in four patients. After a mean (standard deviation) of 19.0 (13.5) days of ENPT, 6.4 (3.4) endoscopies, and 38.1 (40.3) days of hospitalization, endoscopic treatment was effective and successful in all of the patients. Additional video-assisted thoracic surgery (VATS) was done in four patients. CONCLUSIONS: ENPT is an effective new method for the management of IEP. ENPT with OFD and OPD can be combined with minimally invasive operative methods for sepsis control in IEP.

shRNA-mediated inhibition of PhosphoGlycerate Kinase 1 (PGK1) enhances cytotoxicity of intraperitoneal chemotherapy in peritoneal metastasis of gastric origin.

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) plays metabolic, kinase and translational roles in Peritoneal metastasis (PM) of gastric origin and is associated with chemoresistance. Silencing PGK1 might potentiate the effect of chemotherapy. METHODS: In an orthoptic xenograft nude mice model, human gastric cancer cells (MKN45) were grown in 22 donor animals. Solid tumors were then grafted into the gastric subserosa of 102 recipient animals and allowed to grow for 10 days. Animals were randomized into 7 groups: Five test groups: 1) Mitomycin C (MMC), 2) MMC and small hairpin RNA silencing of PGK1 with an adenoviral vector (Adv-shPGK1), 3) 5-fluorouracil (5-FU), 4) 5-FU and Adv-shPGK1, 5) Adv-shPGK1 alone; two control groups: 1) Sham (NaCl 0.9%), 2) empty viral vector. Intraperitoneal therapy was administered on postoperative day (POD) 11 and 18. Animals were sacrificed at POD 21, analysis was blinded to therapy. RESULTS: Adding Adv-shPGK1 to 5-FU reduced the number (0.23 ± 0.43 vs. 1.36 ± 1.00, p = 0.005) and weight (0,005 ± 0.012 mg vs. 0.05 ± 0.08 mg, p = 0.002) of PM as compared to 5-FU alone. The effect of adding Adv-shPGK1 to MMC did not reach statistical significance. Mortality was not increased by adding Adv-shPGK1 to chemotherapy but was increased by Adv-shPGK1 alone as compared to sham. CONCLUSION: In this experimental model, combined therapy with chemotherapy and Adv-shPGK1 improves control of PM of gastric origin as compared to chemotherapy alone and might counteract chemoresistance of PM. A systemic toxicity of Adv-shPGK1 cannot be excluded.