Combination of CEACAM5, EpCAM and CK19 gene expressions in mediastinal lymph node micrometastasis is a prognostic factor for non-small cell lung cancer.

BACKGROUND: Lung cancer is known as the most common and highly metastatic form of cancer worldwide. Tumour node metastasis (TNM) staging is the gold standard classification system for the decision-making process for appropriate treatment. Particularly N status has the most important prognostic value in the absence of distant metastasis. Traditional diagnostic methods are capable of detecting metastasis; however, they may fail to detect micrometastasis, which plays a role in disease recurrence and patients' long-term survival. Occult micrometastasis can change the tumour's TNM staging and, consequently, the patient's treatment regimen. METHODS: The median number of three lymph node tissues were collected from 30 patients who underwent surgery for non-small cell lung cancer. Lymph node tissues were collected from different lymph node stations according to the location of the patient's tumour. CK19, EpCAM and CEACAM5 gene expressions were analysed in tissues using quantitative real-time polymerase chain reaction to detect micrometastasis in distant lymph nodes. RESULTS: Triple positivity was seen in 26 out of 30 patients which 19 patients were upstaged from N0 to N2. While survival was not significantly affected between upstaged and non-upstaged patients, patients upstaged with multiple-station N2 had a significantly higher recurrence and lower survival compared to single-station N2. CONCLUSION: A combination of CK19, EpCAM and CEACAM5 gene expressions in lymph nodes can be used to identify micrometastasis which postoperatively may be used as a tool to predict patients' recurrence and survival.

Analysis of bioactive compounds using LC-ESI-MS/MS, cytotoxic, antimicrobial effects, and enzyme activities from Cyclotrichium origanifolium.

Cyclotrichium origanifolium is a medicinal plant belonging to the Lamiaceae family. In this study, phenolic content analysis, antimicrobial effects, and cytotoxic effects of extracts of C. origanifolium were investigated. In the extracts, phenolic compound analysis by the liquid chromatography-electrospray ionization-tandem mass spectrometry method, antimicrobial effect by the minimum inhibition concentration method, and cytotoxic effect on human dermal fibroblasts (HDF), glioblastoma cell (U87), ovarian adenocarcinoma cell (Skov-3), and human colorectal adenocarcinoma cell (CaCo-2) cancer cell lines were investigated. Cytotoxicity analyses were performed by the MTT method. In addition, the GST and AChE enzyme activities of the extracts were also measured. Around 18 compounds were detected in both the methanol and ethanol extract. It was found that the best antimicrobial effect on Gram-negative Pseudomonas aeruginosa was on methanol extract, while the ethanol extract was on Candida albicans fungus (respectively, 2.50 mg/ml, 5.0 µg/ml). A 500 µg/ml of methanol extract has been shown to have cytotoxic activity high effect on HDF cells. GST and AChE activity were found to decrease in a concentration-dependent manner.

Phosphorus and oxygen co-doped carbon particles based on almond shells with hydrothermal and microwave irradiation process for adsorption of lead (II) and cadmium (II).

In this study, the production of activated carbon based on almond shells by microwave heating with KOH activation and then the modification of activated carbon with phosphorus and oxygen as a result of hydrothermal heating with phosphoric acid were carried out to increase the Cd(II) and Pb(II) adsorption efficiency. The resulting materials were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric/differential thermal analyzer (TG-DTA), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and nitrogen adsorption. Adsorption performance, kinetics and thermodynamics of phosphorus, and oxygen-doped activated carbons were evaluated. The results showed that the adsorption of both Cd(II) and Pb(II) on phosphorus and oxygen-doped activated carbons obeyed the Langmuir isotherm and pseudo-second-order kinetics. The adsorption capacity values (Qm) obtained from the Langmuir isotherm for Cd(II) and Pb(II) adsorption were 185.18 mg/g and 54.64 mg/g, respectively. At the same time, the adsorption mechanism of Pb(II) and Cd(II) on the respective adsorbents was evaluated. As a result of phosphorus and oxygen atoms, Lewis base sites on carbon atoms and Lewis acid sites on phosphorus atoms are likely to form on the surface. These Lewis base sites can act as important active sites in adsorption reactions, especially of positively charged Pb(II) and Cd(II) ions.

CoronaVac, BNT162b2 and heterologous COVID-19 vaccine outcomes in patients with ventricular assist device.

BACKGROUND: A consensus has not yet been reached regarding which COVID-19 vaccine program should be applied in patients with ventricular assist device (VAD). Our aim was to assess the clinical outcome of inactivated, mRNA and heterologous vaccine program in patient with VAD. METHODS: In this retrospective and cross-sectional study; adult patients who underwent VAD implantation between January 2012 and September 2021 and received any vaccine that were used in Republic of Türkiye for COVID-19, were included. The patients were divided into three groups according to the type of vaccine; "inactivated," "mRNA" and "heterologous." Clinical outcomes were analyzed. RESULTS: Eighteen patients were in each group in the "inactivated," "mRNA" and "heterologous" groups. Mean age was 51.6 ± 12 years in "inactivated" group, 42.5 ± 15.5 years in "mRNA" group and 41.1 ± 15.4 years in "heterologous" group. There was no significant difference between the groups in age, gender, body surface area, body mass index and etiology (p > 0.05). After last dose of vaccines, the number of patients had COVID-19 positive test were three (16.7%), one (5.6%), and two (11.1%) in "inactivated," "mRNA" and "heterologous" groups, respectively. Pump thrombosis was seen in two patients in "mRNA" group and one patient in "heterologous" group. No pump thrombosis was seen in "inactivated" group. COVID-19-related death or intubation was not observed. CONCLUSION: All vaccine that used for COVID-19 are safe and effective in patients with VAD. In countries that give priority to inactivated vaccines, mRNA vaccines may then be made as boosters.

Intraductal botulinum toxin injection suppressed the inflammation in experimental acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is inflammation of pancreas in which pancreas enzymatic activity is increased. Parasym-pathetic innervation of pancreas plays an important role in several functions of pancreas. Botulinum toxin (BTx) might be a tool to suppress the pancreas activity in AP. METHODS: In the preliminary experimental study, BTx (15U/kg) was administered directly and intraductal ways. After 10 days, blood amylase, lipase, trypsinogen, insulin, and glucagon levels were compared and no significant difference was seen between groups. Intraductal BTx administration is preferred for experimental AP model in rats; control, AP, intraductal BTx, and AP with Intraductal BTx (AP+BTx). AP was created by intraperitoneal injection of cerulean 20 µg/kg/injection (5 times). After 24 h, serum amylase, lipase, IL-6, IL-1ß, TNF-α, and IL-10 were measured and pancreas tissue was evaluated for inflammation and necrosis. RESULTS: Mean serum amylase, lipase IL-6, IL-1ß, and TNF-α levels of the AP group were significantly higher compared to the other groups (p<0.05). However, there was no significant difference between the amylase and lipase levels of control, BTx, and AP+BTx groups. Serum insulin and glucagon levels in AP group were significantly higher than control and BTx groups (p<0.05). However, there is no significant difference between the insulin and glucagon levels of AP and AP+BTx groups. in pathological evaluation. In AP+ BTx group, there is less amount of centrilobular necrosis and there is mild inflammation and hyperplasia of pancreatic duct epithelium. CONCLUSION: Administration of intraductal BTx suppressed the AP without making significant suppression in endogenous activity of pancreas.

Investigation of Antimicrobial and Cytotoxic Properties and Specification of Silver Nanoparticles (AgNPs) Derived From Cicer arietinum L. Green Leaf Extract.

Using biological materials to synthesize metallic nanoparticles has become a frequently preferred method by researchers. This synthesis method is both fast and inexpensive. In this study, an aqueous extract obtained from chickpea (Cicer arietinum L.) (CA) leaves was used in order to synthesize silver nanoparticles (AgNPs). For specification of the synthesized AgNPs, UV-vis spectrophotometer, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), electron dispersive X-ray (EDX), and zeta potential (ZP) analyses data were used. Biologically synthesized AgNPs demonstrated a maximum surface plasmon resonance of 417.47 nm after 3 h. With the powder XRD model, the mean crystallite dimension of nanoparticles was determined as 12.17 mm with a cubic structure. According to the TEM results, the dimensions of the obtained silver nanoparticles were found to be 6.11-9.66 nm. The ZP of the electric charge on the surface of AgNPs was measured as -19.6 mV. The inhibition effect of AgNPs on food pathogen strains and yeast was determined with the minimum inhibition concentration (MIC) method. AgNPs demonstrated highly effective inhibition at low concentrations especially against the growth of B. subtilis (0.0625) and S. aureus (0.125) strains. The cytotoxic effects of silver nanoparticles on cancerous cell lines (CaCo-2, U118, Sk-ov-3) and healthy cell lines (HDF) were revealed. Despite the increase of AgNPs used against cancerous and healthy cell lines, no significant decrease in the percentage of viability was detected.

Radiological, Clinical, and Histological Findings in the Treatment of Pilonidal Sinus with Phenol Injection.

Objective: Sacrococcygeal pilonidal disease is a chronic discharging wound that causes pain and loss of quality of life. Phenol application is an outpatient procedure with low complications and low recurrence rates. We evaluated the radiological, histological, and clinical results of phenol application. Methods: A total of 44 consecutive patients with sacrococcygeal pilonidal disease underwent phenol application in Kocaeli University Faculty of Medicine, General Surgery Clinic between December 2015 and March 2017. Demographics, complaints, symptom duration, and the number of sinuses were recorded. Patients were examined using ultrasonography (USG) before surgery and two months after surgery. Four patients who wanted rhomboid excision and Limberg flap procedure underwent preoperative local phenol application and were excluded from the study. The excised tissues were used for pathological evaluation. Results: Purulent discharge was the leading symptom. All of the patients had hair in the preoperative USG evaluation, whereas five patients had still hairs in the sinuses in the postoperative USG examination. Four of these cases had recurrences on a 2-month follow-up. After phenol application, a 10% volume decrease was observed. Pathological examination was performed in four cases with phenol application, and in pathological material, the sinuses looked sclerotic and fibrotic. Conclusions: Our study revealed that a single phenol application achieved 90% success. However, no significant difference was observed in the cavity volume after phenol injection.

KRAS signaling in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.

The prediction of spread through air spaces with preoperative 18F-FDG PET/CT in cases with primary lung adenocarcinoma, its effect on the decision for an adjuvant treatment and its prognostic role.

PURPOSE: In lung adenocarcinoma cases, 'spread through air spaces' (STAS) is a new indicator of invasion and directly related to disease survival. The aim of our study is to establish whether a preoperatively performed 18F-Fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging data can predict the presence of STAS in cases with lung adenocarcinoma and thus predict the decision for the type of surgery and adjuvant chemotherapy. MATERIALS AND METHODS: Between 2000 and 2019, we retrospectively analyzed 63 patients with lung adenocarcinoma cases that had undergone lobectomy or pneumonectomy. Semiquantitative parameters were calculated and metabolic tumor volume (MTV)/CT volume (CTV) ratio was recorded from FDG PET/CT data. The pathological samples from these patients were evaluated for STAS. All these values were evaluated for their correlation with the alveolar spread. RESULTS: There was no statistically significant correlation to be found between CTV, MTV, total lesion glycolysis (TLG), standardized uptake value (SUV)max, SUVmean and STAS (P > 0.05). However, MTV/CTV ratio above 1 had statistically more alveolar spread. In the group with an MTV ratio above 1, STAS positivity was 27 (75%), and 9 (25%) did not have STAS, whereas these were 6 (22.2%) patients who had STAS, and 21 (77.8%) did not have STAS in the group with below 1 (P < 0.001). CONCLUSIONS: In the preoperative PET study inoperable lung adenocarcinoma cases, MTV/CTV ratio higher than 1 was found to predict STAS positivity. As a result, it was found that it provided significant clinical additional information regarding the need for a surgical approach (lobar resection instead of sublobar) and adjuvant chemotherapy.

Is elective cancer surgery feasible during the lock-down period of the COVID-19 pandemic? Analysis of a single institutional experience of 404 consecutive patients.

BACKGROUND: We aimed to assess the feasibility and short-term clinical outcomes of surgical procedures for cancer at an institution using a coronavirus disease 2019 (COVID-19)-free surgical pathway during the peak phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. MATERIALS AND METHODS: This was a single-center study, including cancer patients from all surgical departments, who underwent elective surgical procedures during the first peak phase between March 10 and June 30, 2020. The primary outcomes were the rate of postoperative SARS-CoV-2 infection and 30-day pulmonary or non-pulmonary related morbidity and mortality associated with SARS-CoV-2 disease. RESULTS: Four hundred and four cancer patients fulfilling inclusion criteria were analyzed. The rate of patients who underwent open and minimally invasive procedures was 61.9% and 38.1%, respectively. Only one (0.2%) patient died during the study period due to postoperative SARS-CoV2 infection because of acute respiratory distress syndrome. The overall non-SARS-CoV2 related 30-day morbidity and mortality rates were 19.3% and 1.7%, respectively; whereas the overall SARS-CoV2 related 30-day morbidity and mortality rates were 0.2% and 0.2%, respectively. CONCLUSIONS: Under strict institutional policies and measures to establish a COVID-19-free surgical pathway, elective and emergency cancer operations can be performed with acceptable perioperative and postoperative morbidity and mortality.

Immune profiling after minimally invasive lobectomy.

OBJECTIVES: Whether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer. METHODS: Blood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery. RESULTS: Minimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3+CD4+ and CD3+CD8+ CD16+CD56+ cell counts were significantly lower on postoperative day 1. CONCLUSION: There seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy.

Optimization of Erlotinib Plus Sulindac Dosing Regimens for Intestinal Cancer Prevention in an Apc-Mutant Model of Familial Adenomatous Polyposis (FAP).

A clinical trial in patients with familial adenomatous polyposis (FAP) demonstrated that sulindac plus erlotinib (SUL+ERL) had good efficacy in the duodenum and colon, but toxicity issues raised concerns for long-term prevention. We performed a biomarker study in the polyposis in rat colon (Pirc) model, observing phosphorylated Erk inhibition in colon polyps for up to 10 days after discontinuing ERL+SUL administration. In a follow-up study lasting 16 weeks, significant reduction of colon and small intestine (SI) tumor burden was detected, especially in rats given 250 ppm SUL in the diet plus once-a-week intragastric dosing of ERL at 21 or 42 mg/kg body weight (BW). A long-term study further demonstrated antitumor efficacy in the colon and SI at 52 weeks, when 250 ppm SUL was combined with once-a-week intragastric administration of ERL at 10, 21, or 42 mg/kg BW. Tumor-associated matrix metalloproteinase-7 (Mmp7), tumor necrosis factor (Tnf), and early growth response 1 (Egr1) were decreased at 16 weeks by ERL+SUL, and this was sustained in the long-term study for Mmp7 and Tnf. Based on the collective results, the optimal dose combination of ERL 10 mg/kg BW plus 250 ppm SUL lacked toxicity, inhibited molecular biomarkers, and exhibited effective antitumor activity. We conclude that switching from continuous to once-per-week ERL, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care SUL against adenomatous polyps in the colon and SI, with clinical relevance for patients with FAP before or after colectomy. PREVENTION RELEVANCE: This investigation concludes that switching from continuous to once-per-week erlotinib, given at one-quarter of the current therapeutic dose, will exert good efficacy with standard-of-care sulindac against adenomatous polyps in the colon and small intestine, with clinical relevance for patients with FAP before or after colectomy.

Uncertainty of measurement for 14 immunoassay analytes: application to laboratory result interpretation.

Laboratory tests are an integral part of clinical decision making. Therefore, measurement uncertainty comes into prominence in the context of the accuracy of the laboratory result. This study aims to investigate measurement uncertainty of 14 immunoassay analytes, to compare them with different quality goals and to utilize them in the result interpretation. Measurement uncertainties of 14 immunoassay analytes were estimated by using internal and external quality control data by using Nordtest approach. Expanded uncertainties (U) were compared with allowable total error (TEa%), permissible relative deviation in the external quality assessment (PRDEQA%) and permissible expanded uncertainty for external quality assessment (pUEQAS%). Uncertainties were incorporated into the calculation of reference change values (RCV) and uncertainty adjusted reference intervals. RCVs of 14 analytes were calculated by three different methods reported by Harris, Clinical Laboratory Standards Institute (CLSI), and National Pathology Accreditation Advisory Council (NPAAC). Measurement uncertainties of TSH, estradiol, LH, progesterone, prolactin, and vitamin B12 were within defined allowable limits. Uone-sided FT3 and Uone-sided ferritin exceeded defined TEa% but UFT3 and Uferritin were found below the limits of pUEQAS%. Measurement uncertainties of FT4, cortisol, DHEAS, FSH, testosterone, and folate did not meet the specification limits. Recently defined permissible expanded uncertainty promises new targets to compare estimated measurement uncertainty. Measurement uncertainty should be applied to the laboratory result interpretation within the scope of RCV and reference interval to obviate misdiagnosis. Furthermore, we suggest that laboratories should inform clinicians about the tests with high uncertainties to assist them making the right clinical diagnosis. Abbreviations CLSI: Clinical Laboratory Standards Institute; CV: coefficient of variation; CVA: analytic coefficient of variation; CVG: inter-individual coefficient of variation; CVI: intra-individual coefficient of variation; DHEAS: dehydroepiandrosterone sulfate; FSH: follicle-stimulating hormone; FT3: free triiodothyronine; FT4: free thyroxine; k: coverage factor; LH: luteinizing hormone; LRL: lower reference limit; MD: minimal difference; NPAAC: National Pathology Accreditation Advisory Council; PRDEQA%: permissible relative deviation in the external quality assessment; pUEQAS%: permissible expanded uncertainty for external quality assessment; RCV: reference change value; RCV': uncertainty-adjusted reference change value; TSH: thyroid-stimulating hormone; Rw: within-laboratory reproducibility; RMSbias: root mean square of biases; u(Cref): the uncertainty of nominal values; u(bias): uncertainty component for bias; uc: combined standard uncertainty; TEa%: allowable total error; U: expanded uncertainty; Uone-sided%: one sided estimation of expanded measurement uncertainty using coverage factor "1.65"; URL: upper reference limit.

Comparison of conventional fluid management with PVI-based goal-directed fluid management in elective colorectal surgery.

Intraoperative fluid management is quite important in terms of postoperative organ perfusion and complications. Different fluid management protocols are in use for this purpose. Our primary goal was to compare the effects of conventional fluid management (CFM) with the Pleth Variability Index (PVI) guided goal-directed fluid management (GDFM) protocols on the amount of crystalloids administered, blood lactate, and serum creatinine levels during the intraoperative period. The length of hospital stay was our secondary goal. Seventy ASA I-II elective colorectal surgery patients were randomly assigned to CFM or GDFM for fluid management. The hemodynamic data and the data obtained from ABG were recorded at the end of induction and during the follow-up period at 1 h intervals. In the preoperative period and at 24 h postoperatively, blood samples were taken for the measurement of hemoglobin, Na, K, Cl, serum creatinine, albumin and blood lactate. In the first 24 h after surgery, oliguria and the time of first bowel movement were recorded. Length of hospital stay was also recorded. Intraoperative crystalloid administration and urine output were statistically significantly higher in CFM group (p < 0.001, p: 0.018). The end-surgery fluid balance was significantly lower in Group GDFM. Preoperative and postoperative Na, K, Cl, serum albumin, serum creatinine, lactate and hemoglobin values were similar between the groups. The time to passage of stool was significantly short in Group-GDFM compared to Group-CFM (p = 0.016). The length of hospital stay was found to be similar in both group. PVI-guided GDFM might be an alternative to CFM in ASA I-II patients undergoing elective colorectal surgery. However, further studies need to be carried out to search the efficiency and safety of PVI.

Level of heavy metals in some edible and poisonous macrofungi from Batman of South East Anatolia, Turkey.

The macrofungi specimens were collected and identified from locations around Batman province of Turkey. A group of 21 macrofungi were collected from 29 different locations and analysed for the heavy metal contents. The highest Pb and Cu levels were found in Russula rubroalba while the highest Cd level was determined for the species Agaricus xanthodermus. Fe level was maximum for the species Funalia trogii; Mn for Mycena personsii; Zn level was for Morchella esculenta and Co level was for the species Agaricus xanthodermus. The lowest Cd, Cu, Mn and Zn contents were found in Inotus hispidus.

Removal of copper, nickel, cobalt and manganese from aqueous solution by kaolinite.

The removal of some heavy metals such as Mn(II), Co(II), Ni(II), and Cu(II) from aqueous solution is studied using a raw kaolinite. The sorption of these metals on kaolinite conformed to linear form of Langmuir adsorption equation. Langmuir C(m) constants for each metal were found as 0.446 mg/g (Mn), 0.919 mg/g (Co), 1.669 mg/g (Ni), 10787 mg/g (Cu) at 25 degrees C, respectively. Also, kinetic and thermodynamic parameters such as enthalpy (deltaH), free energy (deltaG) and entropy (deltaS) were calculated and these values show that adsorption of heavy metal on kaolinite was an endothermic process and the process of adsorption was favoured at high temperatures.