The use of Lactobacillus plantarum 299v (DSM 9843) in cancer patients receiving home enteral nutrition - study protocol for a randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Nutritional treatment is one of the most important components of multidisciplinary anti-cancer therapy. Home enteral nutrition is considered as a safe procedure, however, it may be associated with the risk of side effects, such as nausea, vomiting, abdominal pain, and diarrhoea. It is uncertain whether diarrhoea is the result of the enteral formula administration or gut dysbiosis. One of the methods which may be used to alter the composition of gut microbiota is the administration of a probiotic strain. Lactobacillus plantarum 299v ingestion was found to diminish the adverse events of irritable bowel syndrome and Clostridium difficile infection - entities that share the symptoms with enteral nutrition side effects. Therefore, the primary aim of this study is to determine the effect of Lactobacillus plantarum 299v on prevention of weight loss of cancer patients receiving home enteral nutrition. The secondary aims are to evaluate the role of this probiotic strain in the improvement of nutritional status, enteral nutrition tolerance, and patients' quality of life. METHODS: Forty patients with cancer receiving home enteral nutrition will be enrolled in this clinical trial and randomized to receive one capsule of Lactobacillus plantarum 299v (Sanprobi IBS®) twice a day or placebo for 12 weeks in a double-blind manner. Laboratory tests (the level of albumin, total protein, transferrin, and total lymphocyte count), anthropometric parameters (body mass, the content of fat mass, muscle mass, and total body water), Nutritional Risk Screening (NRS 2002), enteral nutrition tolerance as well as quality of life will be measured. Measurements will be obtained at the baseline and after 4 and 12 weeks of treatment. DISCUSSION: The adverse events observed during administration of enteral nutrition have an negative impact on enteral formula tolerance and as a consequence patients' quality of life. The previous studies have demonstrated that probiotics may reduce the gastrointestinal symptoms related to enteral nutrition. Thus, administration of Lactobacillus plantarum 299v may be effective in improvement of nutritional status, enteral nutrition tolerance, and quality of life of cancer patients receiving home enteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03940768 .

Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases.

The yeast Saccharomyces boulardii CNCM I-745 is a unique, non-bacterial microorganism classified as a probiotic agent. In this review article, at first, we briefly summarized the mechanisms responsible for its probiotic properties, e.g. adhesion to and elimination of enteropathogenic microorganisms and their toxins; extracellular cleavage of pathogens' virulent factors; trophic and anti-inflammatory effects on the intestinal mucosa. The efficacy of S. boulardii administration was tested in variety of human diseases. We discussed the results of S. boulardii CNCM I-745 use in the treatment or prevention of Helicobacter pylori infections, diarrhoea (Clostridium difficile infections, antibiotic-associated diarrhoea, and traveller's diarrhoea), inflammatory bowel diseases, irritable bowel syndrome, candidiasis, dyslipidemia, and small intestine bacterial overgrowth in patients with multiple sclerosis. In case of limited number of studies regarding this strain, we also presented studies demonstrating properties and efficacy of other strains of S. boulardii. Administration of S. boulardii CNCMI I-745 during antibiotic therapy has certain advantage over bacterial probiotics, because-due to its fungal natural properties-it is intrinsically resistant to the antibiotics and cannot promote the spread of antimicrobial resistance. Even though cases of fungemia following S. boulardii CNCM I-745 administration were reported, it should be treated as a widely available and safe probiotic strain.

Immunonutritional support as an important part of multidisciplinary anti-cancer therapy.

Immunonutrition is one of the most important parts of nutritional treatment in patients with cancer. There are studies which confirm positive effects of using immunonutrition (arginine, glutamine, omega-3 fatty acids, nucleotides, pre- and probiotics) among others on the reduction of the pro-inflammatory cytokines concentrations, shortening of the hospital stay and improvement of the nutritional status. Arginine takes part not only in wound healing process, but also it improves body's immunity and reduces the incidence of infections. Glutamine reduces the incidence of acute grade 2 and 3 esophagitis and improves quality of life of gastric cancer patients. Omega 3-fatty acids have the ability to inhibit the activity of NF-κB. They also reduce the symptoms of graft-versus-host disease in patients undergoing hematopoietic cell transplantation. Nucleotides support the regeneration of intestinal villi. Probiotics play many roles, mainly inhibit the process of carcinogenesis, reduce the incidence of diarrhea and modify intestinal microbiome. However, there are studies indicating the lack of advantages of using immunonutrition compared to standard nutrition. Currently, there is no clear evidence for the use of formulae enriched with immunonutrients versus standard oral nutritional supplements exclusively in the preoperative period. This review summarizes the current knowledge about the role of immunonutrition in supporting treatment of cancer diseases.

The role of Lactobacillus plantarum 299v in supporting treatment of selected diseases.

Alterations in composition of human gut microbiome can lead to its dysbiosis. It is associated with gastrointestinal side effects during anti-cancer treatment, antibiotics administration, or infectious agents. There are studies confirming positive effect of consuming Lactobacillus plantarum 299v on intestinal microflora. This review summarizes the current knowledge about the role of L. plantarum 299v in supporting treatment of selected diseases, such as cancer, irritable bowel syndrome (IBS), and Clostridium difficile infection. The immunomodulating properties of L. plantarum 299v include an increase in the level of anti-inflammatory cytokines, which reduce the risk of cancer and improve the efficacy of regimens. The intake of L. plantarum 299v provides benefits for IBS patients, mainly due to normalization of stool and relief of abdominal pain, which significantly improves the quality of life of IBS patients. In addition, the intake of L. plantarum 299v prevents C. difficile-associated diarrhea among patients receiving antibiotic treatment. Due to the limited possibilities of treating these diseases and numerous complications of cancer treatment, there is a need for new therapeutic strategies. The administration of L. plantarum 299v seems to be useful in these cases.

Gastrointestinal cancers: the role of microbiota in carcinogenesis and the role of probiotics and microbiota in anti-cancer therapy efficacy.

The gut epithelium is a habitat of a variety of microorganisms, including bacteria, fungi, viruses and Archaea. With the advent of sophisticated molecular techniques and bioinformatics tools, more information on the composition and thus function of gut microbiota was revealed. The gut microbiota as an integral part of the intestinal barrier has been shown to be involved in shaping the mucosal innate and adaptive immune response and to provide protection against pathogens. Consequently, a set of biochemical signals exchanged within microbes and communication between the microbiota and the host have opened a new way of thinking about cancer biology. Probiotics are living organisms which administered in adequate amounts may bring health benefits and have the potential to be an integral part of the prevention/treatment strategies in clinical approaches. Here we provide a comprehensive review of data linking gut microbiota to cancer pathogenesis and its clinical course. We focus on gastrointestinal cancers, such as gastric, colorectal, pancreatic and liver cancer.

Distinct Expression Patterns of Two Tumor Necrosis Factor Superfamily Member 15 Gene Isoforms in Human Colon Cancer.

BACKGROUND: Tumor necrosis factor superfamily member 15 (TNFSF15) gene is involved in development of several cancers. It encodes two proteins: tumor necrosis factor ligand-related molecule 1A (TL1A) and vascular endothelial growth inhibitor 192 (VEGI-192). The main receptor for TL1A is death receptor 3 (DR3). AIMS: We investigated expression of TL1A, VEGI-192, and DR3 transcripts in different stages of colon cancer and compared them with survival of patients. We also aimed to reveal possible effects of microsatellite instability (MSI) and selected TNFSF15 single-nucleotide polymorphisms (SNPs) on expression of this gene. METHODS: Forty-five healthy individuals and 95 colon cancer patients were included in the study. Expression of VEGI-192, TL1A, and DR3 was measured by quantitative PCR. SNP and MSI analyses were performed on DNA isolated from normal or cancer tissue. RESULTS: Expression of VEGI-192 and TL1A was elevated in colon cancer, although the level of VEGI-192 decreased, while the level of TL1A increased with the progression of cancer. Patients with low expression of TL1A and/or high expression of VEGI-192 in tumor-transformed tissue showed longer survival. DR3 expression was decreased in the cancer, but it did not change with the tumor progression. Alleles T of rs6478108 and G of rs6478109 SNPs were associated with elevated expression of the TNFSF15 gene. There was no relation between the MSI status and TNFSF15 expression levels. CONCLUSIONS: Expression of the TNFSF15 gene isoforms was associated with the progression of colon cancer. Levels of TL1A and VEGI-192 transcripts can be considered as independent prognostic factors for colon cancer.

Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation.

Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.

Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium.

Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.

Plasma protein changes reflect colorectal cancer development and associated inflammation.

Introduction: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed. Methods: To identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few µL of plasma sample. Results: Among the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon γ (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC. Discussion: Further study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.

Randomised controlled trial: standard lightweight mesh vs self-gripping mesh in Lichtenstein procedure.

<b> Introduction:</b> Lichtenstein hernioplasty has been a gold standard of hernioplasty for 30 years now. However, the procedure may be followed by an unacceptably high rate of chronic pain, numbness and discomfort. </br></br> <b>Aim:</b> To compare outcomes of Lichtenstein repair using a Parietene ProGrip self-fixing mesh versus the standard lightweight macroporous mesh. </br></br> <b>Material and methods:</b> As many as 141 patients with unilateral primary inguinal hernia participated in this single-centre, randomised, prospective, single-blind (patient-blinded) study. Randomisation yielded two treatment groups: control group of 88 patients treated with Lichtenstein method using lightweight standard mesh (LS) and study group of 53 patients receiving treatment with self-fixing mesh (PG). Patients were followed up for 6 months. Primary outcome was the presence and severity of postoperative pain at discharge, at 30 days and 6 months post-procedure. Other study parameters were: duration of the procedure, duration of hospitalisation, presence of early and late complications, time needed to return to full activity and patient satisfaction. </br></br> <b>Results:</b> No statistically significant differences in pain severity were demonstrated at discharge or at long-term follow-up. In the first 30 days post-procedure the patients in the PG group complained of pain of greater severity on the NRS (2.0 vs 1.4) (P = 0.0466). The duration of the procedure in the PG group was 9.4 minutes shorter than in the LS group (P = 0.0027). No statistically significant differences between the groups were found in other studied parameters. </br></br><b>Conclusions:</b> Self-fixing mesh can be safely used in inguinal canal repair procedures. It significantly shortened the duration of the procedure but at the same time did not reduce the severity of pain, including the rate of chronic postoperative inguinal pain.

Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations.

Gut microbiota plays a significant role in the human body providing many beneficial effects on the host. However, its dysbiotic alterations may affect the tumorigenic pathway and then trigger the development of pancreatic cancer. This dysbiosis can also modulate the aggressiveness of the tumor, influencing the microenvironment. Because pancreatic cancer is still one of the most lethal cancers worldwide with surgery as the only method that influences prognosis and has curative potential, there is a need to search for other strategies which will enhance the efficiency of standard therapy and improve patients' quality of life. The administration of prebiotics, probiotics, next-generation probiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila), synbiotics, postbiotics, and fecal microbiota transplantation through multiple mechanisms affects the composition of the gut microbiota and may restore its balance. Despite limited data, some studies indicate that the aforementioned methods may allow to achieve better effect of pancreatic cancer treatment and improve therapeutic strategies for pancreatic cancer patients.

Influence of malnutrition stage according to GLIM 2019 criteria and SGA on the quality of life of patients with advanced cancer.

INTRODUCTION: Introduction: the nutritional status of cancer patients should be screened regularly due to their high risk of malnutrition, which impairs patient quality of life (QoL). Therefore, an assessment of nutritional status is strongly necessary. Recently, the Global Leadership Initiative on Malnutrition (GLIM) criteria for assessing the severity of malnutrition were published (2019). Objectives: the primary aim of this study was the assessment of nutritional status and QoL in advanced cancer patients. A secondary aim was to investigate the impact of malnutrition severity on QoL in these patients. Methods: this study included 33 advanced cancer patients (head/neck, esophageal, gastric) from the Nutritional Counselling Centre Copernicus in Gdansk, and the Department of Surgical Oncology, Medical University of Gdansk, Poland. The assessment of nutritional status was conducted with the 2019 GLIM criteria and the Subjective Global Assessment (SGA) method. QoL was assessed using the World Health Organization Quality of Life-BREF questionnaire (WHOQOL-BREF). Results: according to the SGA method, most of the patients were malnourished (42.42 %) or severely malnourished (42.42 %). Based on the GLIM criteria, 69.7 % of patients (n = 23) were severely malnourished. Among all participants, the highest impairments of QoL were observed in the environmental and psychological domains of the self-assessed satisfaction with own health questionnaire. Severe malnutrition significantly impairs QoL in the psychological (GLIM stage 2, p = 0.0033; SGA C, p = 0.0310) and somatic domains (GLIM stage 2, p = 0.0423). Conclusions: most patients with advanced cancer are malnourished or severely malnourished. Overall, the QoL of these patients is impaired. The severity of malnutrition has an impact on the QoL of cancer patients, which is observed as an impairment of mainly psychological and somatic aspects. This is the first study assessing the impact of malnutrition severity, as based on the new 2019 GLIM criteria, on the QoL of advanced cancer patients.

INTRODUCCIÓN: Introducción: el estado nutricional de los pacientes con cáncer debe examinarse regularmente debido al alto riesgo de desnutrición, lo que perjudica la calidad de vida (QoL) de los pacientes. Por lo tanto, la evaluación del estado nutricional es muy necesaria. Recientemente se han publicado los criterios de la Iniciativa de Liderazgo Global sobre Desnutrición (GLIM) de 2019, que evalúan la gravedad de la desnutrición. Objetivos: los objetivos principales de este estudio fueron la evaluación del estado nutricional y la calidad de vida de los pacientes con cáncer avanzado. El objetivo secundario fue investigar el impacto de la gravedad de la desnutrición en la calidad de vida de estos pacientes. Métodos: este estudio incluyó a 33 pacientes con cáncer avanzado de cabeza/cuello, esófago y gástrico del Centro de Asesoría Nutricional Copernicus de Gdansk y el Departamento de Oncología Quirúrgica de la Universidad de Medicina de Gdansk, Polonia. La evaluación del estado nutricional se realizó con los criterios GLIM 2019 y el método de evaluación subjetiva global (SGA). La calidad de vida se evaluó mediante el cuestionario Quality of Life-BREF de la Organización Mundial de la Salud (WHOQOL-BREF). Resultados: según el método SGA, la mayoría de los pacientes estaban desnutridos (42,42 %) o gravemente desnutridos (42,42 %). Según los criterios GLIM, el 69,7 % de los pacientes (n = 23) estaban gravemente desnutridos. Entre todos los participantes se observó un mayor deterioro de la calidad de vida en la autoevaluación de la satisfacción con la salud, en los dominios ambiental y psicológico. La desnutrición severa afecta significativamente a la calidad de vida en el dominio psicológico (etapa GLIM 2, p = 0,0033; SGA C, p = 0,0310) y somático (etapa GLIM 2, p = 0,0423). Conclusiones: la mayoría de los pacientes con cáncer avanzado están desnutridos o gravemente desnutridos. En general, la calidad de vida de estos pacientes está alterada. La gravedad de la desnutrición repercute sobre la calidad de vida de los pacientes con cáncer, lo que se observa como un deterioro principalmente en los aspectos psicológicos y somáticos. Este es el primer estudio que evalúa el impacto de la gravedad de la desnutrición, según los nuevos criterios GLIM 2019, sobre la calidad de vida de los pacientes con cáncer avanzado.

Fungal Gut Microbiota Dysbiosis and Its Role in Colorectal, Oral, and Pancreatic Carcinogenesis.

The association between bacterial as well as viral gut microbiota imbalance and carcinogenesis has been intensively analysed in many studies; nevertheless, the role of fungal gut microbiota (mycobiota) in colorectal, oral, and pancreatic cancer development is relatively new and undiscovered field due to low abundance of intestinal fungi as well as lack of well-characterized reference genomes. Several specific fungi amounts are increased in colorectal cancer patients; moreover, it was observed that the disease stage is strongly related to the fungal microbiota profile; thus, it may be used as a potential diagnostic biomarker for adenomas. Candida albicans, which is the major microbe contributing to oral cancer development, may promote carcinogenesis via several mechanisms, mainly triggering inflammation. Early detection of pancreatic cancer provides the opportunity to improve survival rate, therefore, there is a need to conduct further studies regarding the role of fungal microbiota as a potential prognostic tool to diagnose this cancer at early stage. Additionally, growing attention towards the characterization of mycobiota may contribute to improve the efficiency of therapeutic methods used to alter the composition and activity of gut microbiota. The administration of Saccharomyces boulardii in oncology, mainly in immunocompromised and/or critically ill patients, is still controversial.

Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study.

Recent evidence suggests that lipid composition in cancer tissues may undergo multiple alterations. However, no comprehensive analysis of various lipid groups in colorectal cancer (CRC) tissue has been conducted thus far. To address the problem in question, we determined the contents of triacylglycerols (TG), an energetic substrate, various lipids necessary for cell membrane formation, among them phospholipids (phosphatidylcholine, phosphatidylethanolamine), sphingolipids (sphingomyelin) and cholesterol (free, esterified and total), and fatty acids included in complex lipids. 1H-nuclear magnetic resonance (1H-NMR) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the lipid composition of colon cancer tissue and normal large intestinal mucosa from 25 patients. Compared with normal tissue, cancer tissues had significantly lower TG content, along with elevated levels of phospholipids, sphingomyelin, and cholesterol. Moreover, the content of oleic acid, the main component of TG, was decreased in cancer tissues, whereas the levels of saturated fatty acids and polyunsaturated fatty acids (PUFAs), which are principal components of polar lipids, were elevated. These lipidome rearrangements were associated with the overexpression of genes associated with fatty acid oxidation, and the synthesis of phospholipids and cholesterol. These findings suggest that reprogramming of lipid metabolism might occur in CRC tissue, with a shift towards increased utilization of TG for energy production and enhanced synthesis of membrane lipids, necessary for the rapid proliferation of cancer cells.

Therapeutic methods of gut microbiota modification in colorectal cancer management - fecal microbiota transplantation, prebiotics, probiotics, and synbiotics.

The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.

Preferential uptake of polyunsaturated fatty acids by colorectal cancer cells.

Although a growing body of evidence suggests that colorectal cancer (CRC) is associated with alterations of fatty acid (FA) profiles in serum and tumor tissues, available data about polyunsaturated fatty acid (PUFA) content in CRC patients are inconclusive. Our study showed that CRC tissues contained more PUFAs than normal large intestinal mucosa. However, serum levels of PUFAs in CRC patients were lower than in healthy controls. To explain the mechanism of PUFA alterations in CRC, we measured FA uptake by the colon cancer cells and normal colon cells. The levels of PUFAs in colon cancer cell culture medium decreased significantly with incubation time, while no changes were observed in the medium in which normal colon cells were incubated. Our findings suggest that the alterations in tumor and serum PUFA profiles result from preferential uptake of these FAs by cancer cells; indeed, PUFAs are essential for formation of cell membrane phospholipids during rapid proliferation of cancer cells. This observation puts into question potential benefits of PUFA supplementation in CRC patients.

In Vivo Effectiveness of Orlistat in the Suppression of Human Colorectal Cancer Cell Proliferation.

BACKGROUND/AIM: Fatty acid synthase (FASN) provides palmitate for cell membrane formation in colorectal cancer (CRC) cells, however, palmitate is also available in the blood of CRC patients. The aim of this study was to examine whether orlistat, a FASN inhibitor, is able to attenuate CRC cell growth despite the availability of extracellular palmitate. MATERIALS AND METHODS: Palmitate concentrations were measured in serum from CRC patients and healthy controls. HT-29 CRC cells were treated with orlistat and palmitate. RESULTS: Treatment of CRC cells with orlistat caused a dose-dependent inhibition of cell proliferation. In turn, delivery of extracellular palmitate at doses lower than those found in the serum of CRC patients reversed inhibition by orlistat concentrations of up to 10 µM. CONCLUSION: Inhibition of CRC cell proliferation by orlistat is reversed by palmitate which is present at high levels in the serum. Therefore, orlistat may be effective in vivo only at high concentrations.

Complicated appendicitis: Risk factors and outcomes of laparoscopic appendectomy - Polish laparoscopic appendectomy results from a multicenter, large-cohort study.

BACKGROUND: Preoperative classification of complicated and uncomplicated appendicitis (AA) is challenging. However, the differences in surgical outcomes necessitate the establishment of risk factors in developing, complicated AA. This study was an analysis of the clinical outcomes of laparoscopic appendectomies (LA), as well as preoperative risk factors for the development of complicated AA. METHODS: The data of 618 patients who underwent LA in 18 surgical units across Poland and Germany were collected in an online web-based database created by the Polish Videosurgery Society. The surgical outcomes of patients with complicated and uncomplicated appendicitis were compared. Uni- and multivariate logistic regression models were used to establish risk factors for the development of complicated appendicitis. RESULTS: In all, 1269 (27.5%) patients underwent LA for complicated appendicitis (Group 1) and 3349 (72.5%) for uncomplicated appendicitis (Group 2). The conversion rate, number of intra-operative adverse events, re-intervention rate, postoperative complications, and readmission rate was greater in Group 1. The preoperative risk factors associated with complicated appendicitis were: female sex (Odds ratio [OR]: 1.58), obesity (OR: 1.51), age >50 years (OR: 1.51), symptoms >48 hours (OR: 2.18), high Alvarado score (OR: 1.29 with every point), and C-reactive protein level >100 mg/L (OR: 3.92). CONCLUSION: Several demographic and clinical risk factors for complicated AA were identified. LA for complicated appendicitis was associated with poorer outcomes.

Author Correction: Risk factors for serious morbidity, prolonged length of stay and hospital readmission after laparoscopic appendectomy - results from Pol-LA (Polish Laparoscopic Appendectomy) multicenter large cohort study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Risk factors for serious morbidity, prolonged length of stay and hospital readmission after laparoscopic appendectomy - results from Pol-LA (Polish Laparoscopic Appendectomy) multicenter large cohort study.

Laparoscopic appendectomy (LA) for treatment of acute appendicitis has gained acceptance with its considerable benefits over open appendectomy. LA, however, can involve some adverse outcomes: morbidity, prolonged length of hospital stay (LOS) and hospital readmission. Identification of predictive factors may help to identify and tailor treatment for patients with higher risk of these adverse events. Our aim was to identify risk factors for serious morbidity, prolonged LOS and hospital readmission after LA. A database compiled information of patients admitted for acute appendicitis from eighteen Polish and German surgical centers. It included factors related to the patient characteristics, peri- and postoperative period. Univariate and multivariate logistic regression models were used to identify risk factors for serious perioperative complications, prolonged LOS, and hospital readmissions in acute appendicitis cases. 4618 laparoscopic appendectomy patients were included. First, although several risk factors for serious perioperative complications (C-D III-V) were found in the univariate analysis, in the multivariate model only the presence of intraoperative adverse events (OR 4.09, 95% CI 1.32-12.65, p = 0.014) and complicated appendicitis (OR 3.63, 95% CI 1.74-7.61, p = 0.001) was statistically significant. Second, prolonged LOS was associated with the presence of complicated appendicitis (OR 2.8, 95% CI: 1.53-5.12, p = 0.001), postoperative morbidity (OR 5.01, 95% CI: 2.33-10.75, p < 0.001), conversions (OR 6.48, 95% CI: 3.48-12.08, p < 0.001) and reinterventions after primary procedure (OR 8.79, 95% CI: 3.2-24.14, p < 0.001) in the multivariate model. Third, although several risk factors for hospital readmissions were found in univariate analysis, in the multivariate model only the presence of postoperative complications (OR 10.33, 95% CI: 4.27-25.00), reintervention after primary procedure (OR 5.62, 95% CI: 2.17-14.54), and LA performed by resident (OR 1.96, 95% CI: 1.03-3.70) remained significant. Laparoscopic appendectomy is a safe procedure associated with low rates of complications, prolonged LOS, and readmissions. Risk factors for these adverse events include complicated appendicitis, postoperative morbidity, conversion, and re-intervention after the primary procedure. Any occurrence of these factors during treatment should alert the healthcare team to identify the patients that require more customized treatment to minimize the risk for adverse outcomes.