Identification of the most specific markers to differentiate primary pulmonary carcinoma from metastatic gastrointestinal carcinoma to the lung

Background A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, however, a standardised panel for that purpose does not exist yet. We aimed to identify the smallest panel that is most sensitive and specific at differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract. Methods A total of 170 samples were collected, including 140 primary and 30 non-primary lung tumours and staining for CK7, Napsin-A, TTF1, CK20, CDX2, and SATB2 was performed via tissue microarray. The data was then analysed using univariate regression models and a combination of multivariate regression models and Receiver Operating Characteristic (ROC) curves. Results Univariate regression models confirmed the 6 biomarkers’ ability to independently predict the primary outcome (p < 0.001). Multivariate models of 2-biomarker combinations identified 11 combinations with statistically significant odds ratios (ORs) (p < 0.05), of which TTF1/CDX2 had the highest area under the curve (AUC) (0.983, 0.960–1.000 95% CI). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.7, 100, 100, and 37.5% respectively. Multivariate models of 3-biomarker combinations identified 4 combinations with statistically significant ORs (p < 0.05), of which CK7/CK20/SATB2 had the highest AUC (0.965, 0.930–1.000 95% CI). The sensitivity, specificity, PPV, and NPV were 85.1, 100, 100, and 41.7% respectively. Multivariate models of 4-biomarker combinations did not identify any combinations with statistically significant ORs (p < 0.05). Conclusions The analysis identified the combination of CK7/CK20/SATB2 to be the smallest panel with the highest sensitivity (85.1%) and specificity (100%) for predicting tumour origin with an ROC AUC of 0.965 (p < 0.001; SE: 0.018, 0.930–1.000 95% CI).

Intracellular Reduction-Responsive Molecular Targeted Nanomedicine for Hepatocellular Carcinoma Therapy

The stimuli-responsive polymer-based platform for controlled drug delivery has gained increasing attention in treating hepatocellular carcinoma (HCC) owing to the fascinating biocompatibility and biodegradability, improved antitumor efficacy, and negligible side effects recently. Herein, a disulfide bond-contained polypeptide nanogel, methoxy poly(ethylene glycol)−poly(l-phenylalanine-co-l-cystine) [mPEG−P(LP-co-LC)] nanogel, which could be responsive to the intracellular reduction microenvironments, was developed to deliver lenvatinib (LEN), an inhibitor of multiple receptor tyrosine kinases, for HCC therapy. The lenvatinib-loaded nanogel (NG/LEN) displayed concise drug delivery under the stimulus of glutathione in the cancer cells. Furthermore, the intracellular reduction-responsive nanomedicine NG/LEN showed excellent antitumor effect and almost no side effects toward both subcutaneous and orthotopic HCC tumor-allografted mice in comparison to free drug. The excellent tumor-inhibition efficacy with negligible side effects demonstrated the potential of NG/LEN for clinical molecular targeted therapy of gastrointestinal carcinoma in the future.

Pre-operative immunomodulatory nutrition and post-operative outcomes of surgical treatment of gastrointestinal surgery: a systematic review

Malnutrition is a major health problem in cancer evident in up to 80% of patients. It was associated with high mortality and morbidity, especially with surgical treatment of cancer. That is why many studies are investigating efficient treatment for this problem. One of these treatments is immunomodulatory nutrition. Immunomodulatory nutrition has shown efficacy towards malnutrition, immune status, and other comorbidities. However, there is still a debate about whether it is efficient or not. Five databases were searched using specific search terms. We only included randomized controlled trials that studied the efficacy of preoperative immunomodulatory nutrition before surgical treatment of gastrointestinal carcinoma. The studies were assessed for the quality of evidence. Twenty-three studies were included for the systematic review. Most studies had a low risk of bias. We assessed the efficacy of immunomodulatory nutrition regarding immune markers, infectious complications, non-infectious complications, biological markers, the length of stay, and mortality. Immunomodulatory nutrition has significantly enhanced immune status, biological markers, and post-operative complications. However, it does not have a significant improvement in the mortality rate or hospitalization duration. The immunomodulatory nutrition has promising results in enhancing immune status, and biological markers. However, its effect on post-operative infectious and non-infectious complications is still under debate. Immunomodulatory nutrition had no effect on mortality rates among cancer patients.

DNA methylation detection technology and plasma-based methylation biomarkers in screening of gastrointestinal carcinoma

DNA methylation is of paramount importance for the evolution of human cancers. Its high sensitivity and specificity make it a potential biomarker for early cancer screening in the context of an increasing global burden of gastrointestinal (GI) carcinoma. More DNA methylation biomarkers are emerging with the development of liquid biopsy and sensitive DNA methylation detection technology. This review provides an overview of DNA methylation, focusing on the presentation and comparison of 5-methylcytosine detection technologies, and introduces the promising plasma-based cell-free DNA (cfDNA) methylation biomarkers published in recent years for early screening of GI carcinoma. Finally, we summarize and discuss the future of plasma cfDNA methylation markers detection as a clinical tool for early screening of GI carcinoma.

The Influence of Lactobacillus Acidophilus on MUC1, GAL-3, IL-1β and IL-17 Gene Expression in BALB/c Mice Stomach

Background and Objective: Lactobacillus acidophilus has been widely used for the management of gastrointestinal carcinoma owing to its immunomodulation effect; however, the role of L. acidophilus and its specific mechanism of action in the stomach is not fully comprehended. The present study evaluated the expression profile of MUC-1, GAL-3, IL -1β, and IL-17 in the L. acidophilus treated mice stomach. Methods: The study was conducted utilizing three groups of mice, 6 mice for each group, administered with different doses of L. acidophilus and a control group treated with normal saline. The results were analyzed with the Mann-Whitney Test. Results: The results demonstrated that L. acidophilus elevated IL-1β insignificantly and inhibited the expression of IL-17. The MUC-1 expression is influenced by L. acidophilus and inversely proportional to GAL-3 expression. Conclusion: Lactobacillus acidophilus plays a prominent role against inflammatory responses and has a potential in the treatment of gastrointestinal cancer.

“Black Ovaries”: An Uncommon Case of First Systemic Recurrence of Melanoma

Here we describe a rare case of a 48-year-old woman with a previous history of malignant melanoma (pT2a pathological stage, IB clinical stage) occurring about five years previously. She complained of abdominal pain and pelvic discomfort, diagnosed as a consequence of a bilateral ovarian solid masses completely occupying the recto-uterine space. She underwent laparotomy surgery with total hysterectomy and bilateral salpingo-oophorectomy. Gross examination of the excised material revealed an unusual grey-black bilateral ovarian tumor; a histopathological diagnosis of ovarian bilateral metastatic melanoma was made. Imaging study (CT/MRI) did not reveal metastasis in other zones of the body. Melanoma metastasis usually affects the skin, liver, brain and lungs, and rarely gynecological localizations. On the other hand, most bilateral ovarian tumors are comprised of serous carcinoma, mature teratoma and gastrointestinal carcinoma metastasis. Exceptionally, primary ovarian melanoma may arise in mature ovarian cystic teratomas.

MO288NEPHROTIC SYNDROME AS A PARANEOPLASTIC ENTITY: ARE WE KEEPING IT IN MIND?

Background and Aims Association between nephrotic syndrome (NS) and cancer is well known. However, it has been barely studied and scarcely sustained. Membranous nephropathy (MN) has been identified often as a glomerular paraneoplastic disease. Reported incidence of cancer at the time of biopsy or one year follow-up of MN is 10-20%. Incidence rates in other glomerulopathies are limited. Concomitant malignancy is associated with poor renal outcome in NS. Therapy for cancer is priority and immunosuppressives therapies should be restricted. Furthermore, there is no consensus for cancer screening in patients with NS with or without known risk factors for cancer, as smoking or alcohol consumption. The aim of our study is to stablish the incidence of neoplasia in a cohort of patients of a tertiary hospital of Spain who develop NS. We analyze clinical characteristics, glomerular disease, type of malignancies, screening procedures and risk factors for cancer in this population. Method All patients with NS at our center between January 2013 and December 2019 were included. Demographical and clinical data, and laboratory results were collected, as well as all tests performed for cancer screening. Patients who presented cancer the year before or 24 months after the diagnosis of NS were identified. We performed a logistic regression model to identify independent risk factors for cancer in this population. Results During the study period, 47 patients presented with NS at our center. 38.3% were women and mean age was 57.28±17.3 years. 46.8% patients presented high blood pressure and 23.4% type 2 DM. 5 patients presented HIV infection, and 4 hepatitis C. 51% reported smoking, and 19% of alcohol consumption. Mean creatinine at NS diagnosis was 2.48±2.30 mg/dL, and proteinuria 10.9±6.7 g per day. Histologic diagnosis were: MN (n=7), membranoproliferative glomerulonephritis (n=5), diabetic nephropathy (n=5), and focal and segmental glomerulosclerosis (n=4). 9 out 47 patients presented cancer: 6 patients had a malignancy diagnosed the year before the NS onset (prostate carcinoma n=2, gastrointestinal carcinoma n=2, lung carcinoma n=1, and Hodgkin lymphoma n=1), and 3 patients one the year after the NS onset (thyroid carcinoma n=1, melanoma n=1, and multiple myeloma n=1). In the univariate analysis, patients with cancer were older (69.3±12.1 vs 54.4±17.2 years old, p=0.018) and had more frequently alcohol consumption (33.3% vs 15.8%, p=0.0187). There were no differences in terms of smoking, viral infections, renal function, proteinuria or type of glomerulopathy. In multivariate analysis including these two variables and gender, neither age nor alcohol intake were a risk factors for the presence of cancer in patients with NS. Conclusion: 19.1% patients with NS presented also concomitant cancer in our cohort, without association to the type of glomerulopathy, age or known risk factors for neoplasia such as alcohol, tobacco or viral infection. As our data showed, the presence of cancer in patients with NS is considerable, so the development of screening strategies to find occult malignancies in this group of patients is necessary since this condition compromises renal outcome and life expectancy