Combination of modified FOLFIRINOX with stereotactic body radiotherapy as an induction therapy for locally advanced pancreatic adenocarcinoma - a prospective single-arm study.

Introduction: Radical resection is the only potentially curative treatment for pancreatic adenocarcinoma; however, only a minor fraction of patients are eligible for resection. Induction therapy may be offered to patients, but the response rate in cases with significant vascular involvement is limited. This study aimed to evaluate the efficacy and safety of modified of FOLFIRINOX chemotherapy (mFFX) + stereotactic body radiotherapy (SBRT) in combination as induction therapy for locally advanced pancreatic carcinoma. The primary endpoints were the resection rate and one-year overall survival (OS). The secondary endpoints were progression-free survival (PFS), toxicity, and quality of live (QoL). Material and methods: Thirty patients with locally advanced pancreatic adenocarcinoma were treated with 6 cycles of mFFX, followed by SBRT and additional 3 cycles of mFFX. The response was measured prior to SBRT and after regimen completion. In the absence of disease progression, the patients were referred for surgery. The patients were requested to complete quality of life questionnaires (QLQ)-C30 and QLQ-PAN26 questionnaires biweekly. Results: On the first evaluation, disease control was noted in 26 (86.7%) patients. Stereotactic body radiotherapy was performed in 20 patients. Twelve patients underwent laparotomy, with radical resection possible in 3 cases. The one-year OS rate was 63.3%. Overall, 11 grade ≥ 3 adverse events were noted. No deterioration in the overall QoL was observed. The median PFS was 7.53 months. Conclusions: The expected resection rate of ≥ 30% was not achieved. However, the combination was associated with good local control, low adverse event rate, and good QoL, which advocate its further investigation in this clinical situation.

The Influence of the Sous Vide Cooking Time on Selected Characteristics of Pork Lion.

The aim of this study was to determine the effect of sous vide and pressure-cooker cooking of pork muscles (Longissimus lumborum) on the physicochemical and technological characteristics of pork. The study included an analysis of the basic composition, colour, texture, sensory evaluation, nutritional value (vitamin B1 content), and rheological properties of meat cooked at 60 °C for 6-18 h and, for comparison, in an autoclave at 121.1 °C. The heating conditions affected the weight loss, colour, thiamine content, texture, and rheological properties of the meat. As the heating time increased, the texture determinants of firmness and chewiness decreased, which resulted in softer meat. The differences in the rheological properties of the sous-vide- and autoclave-cooked meat resulted from the different organisation of the spatial matrix of proteins and changes in the structure of muscle fibres caused by the high temperature.

Galectin-9 expression on tumour-associated immune cells is associated with favourable clinicopathological features and better outcomes in oral squamous cell carcinoma.

Introduction: Galectin-9, a ß-galactoside-binding protein, might be a potential target in cancer personalized therapy, but contradicting data exist regarding its prognostic significance in malignancy. Previous studies showed low or absent expression of galectin-9 on tumour cells of oral squamous cell carcinoma (OSCC); thus, we aimed to assess the prognostic impact of its expression on tumour-associated immune cells (TAICs). Material and methods: A retrospective analysis was conducted on 62 patients with OSCC. Tissue microarrays were constructed with chemo- and radiotherapy-naïve tissue samples and stained with anti-galectin-9 antibody. Cytoplasmic reactions in TAICs were counted as positive, and the percentage of galectin-9-positive cells was calculated. Results: The expression of galectin-9 was not associated with any demographic factors, other than diabetes mellitus type 2, for which there were lower levels of expression (p = 0.029). Higher levels of galectin-9 were associated with less locally advanced tumours (p = 0.023) and lack of nodal metastases (p = 0.014). Galectin-9 expression positively correlated with PD-L1 expression on TAICs (p = 0.009). Patients with > 50% galectin-9-positive cells were determined to have a superior 5-year overall survival (p = 0.029). Conclusions: Future studies are necessary to investigate the effects of galectin-9 on the tumour micro-environment, and galectin-9-targeted treatment may be considered, especially with its correlation to PD-L1 in OSCC.

Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.

Tumor-Infiltrating Lymphocytes (TILs) in Breast Cancer: Prognostic and Predictive Significance across Molecular Subtypes.

Tumor-infiltrating lymphocytes (TILs) are pivotal in the immune response against breast cancer (BC), with their prognostic and predictive significance varying across BC subtypes. In triple-negative BC (TNBC), higher TIL levels correlate with improved prognosis and treatment response, guiding therapeutic strategies and potentially offering avenues for treatment de-escalation. In metastatic TNBC, TILs identify patients with enhanced immunotherapy response. HER2+ BC, similar to TNBC, exhibits positive correlations between TILs and treatment response, especially in neoadjuvant settings. Luminal BC generally has low TILs, with limited prognostic impact. Single hormone receptor-positive BCs show distinct TIL associations, emphasizing subtype-specific considerations. TILs in ductal carcinoma in situ (DCIS) display ambiguous prognostic significance, necessitating further investigation. Standardizing TIL assessment methods is crucial for unlocking their full potential as biomarkers, guiding treatment decisions, and enhancing patient care in BC.

The influence of the rotational speed of the meat cutter knives and bowl on the microstructure of meat products.

The aim of the study was to determine the structure of meat batter and processed meat products, depending on the chopping time and rotational speed of the cutter knives and bowl, by means of histochemical methods combined with the computer image analysis system. Finely comminuted meat batters and processed meat products were investigated. Four variants of the rotational speed of cutter knives and bowl were applied in the experiment: 1500/10 rpm, 1500/20 rpm , 3000/10 rpm and 3000/20 rpm. The chopping process lasted 10 min. After 5, 6, 8 and 10 min of chopping samples of meat batter and processed meat products were collected for histological analyses. The microstructure of structural elements (fat globules and collagen fibres) was measured using computer image analysis. The following parameters were included in a characteristic of the images: the area, circumference, length and width of fat fields; the number of fat fields analysed; the percentage of fat fields in the field under analysis; the area, circumference, length and width of collagen fibres. The computer image analysis showed that the optimal speed of the cutter knives and bowl was 3000/20 rpm. The chopping time was reduced from 10 to 8 min.

Tumor Budding Is an Independent Prognostic Factor in Pancreatic Adenocarcinoma and It Positively Correlates with PD-L1 Expression on Tumor Cells.

Pancreatic adenocarcinoma is one of the leading causes of cancer-related death in developed countries. Only 15% of patients are candidates for radical surgery, and adequate prognostication may guide proper postsurgical management. We aimed to retrospectively assess the prognostic significance of the immunohistochemical expression of immune checkpoint receptors (PD-L1 and VISTA), markers of systemic inflammation, thrombosis in the tumor area, and the tumor budding in the group of 107 patients diagnosed with pancreatic adenocarcinoma in a single center. The high expression of PD-L1 on tumor cells (TCs) was associated with worse overall survival (OS, p = 0.041, log-rank). On the contrary, high PD-L1 or VISTA on tumor-associated immune cells (TAICs) was correlated with better OS (p = 0.006 and p = 0.008, respectively, log-rank). The joint status of PD-L1 on TCs and TAICs stratified patients into three prognostic groups. The cases with high-grade budding were characterized by higher PD-L1 expression on TCs (p = 0.008) and elevated systemic inflammatory markers. Moreover, budding was identified as the independent prognostic factor in multivariate Cox regression analysis (HR = 2.87; 95% CI = 1.75−4.68; p < 0.001). To conclude, the pattern of PD-L1 and VISTA expression was associated with survival in univariate analysis. Tumor budding accurately predicts outcomes in pancreatic cancer and should be incorporated into routine histopathological practice.

The Process of Pasting and Gelling Modified Potato Starch with LF-NMR.

Currently, society expects convenience food, which is healthy, safe, and easy to prepare and eat in all conditions. On account of the increasing popularity of modified potato starch in food industry and its increasing scope of use, this study focused on improving the physical modification of native starch with temperature changes. As a result, it was found that the suggested method of starch modification with the use of microwave power of 150 W/h had an impact on the change in starch granules. The LF-NMR method determined the whole range of temperatures in which the creation of a starch polymer network occurs. Therefore, the applied LF-NMR technique is a highly promising, noninvasive physical method, which allows obtaining a better-quality structure of potato starch gels.

Surface-Related Kinetic Models for Anaerobic Digestion of Mi-crocrystalline Cellulose: The Role of Particle Size.

In this work, for modelling the anaerobic digestion of microcrystalline cellulose, two surface-related models based on cylindrical and spherical particles were developed and compared with the first-order kinetics model. A unique dataset consisting of particles with different sizes, the same crystallinity and polymerisation degree was used to validate the models. Both newly developed models outperformed the first-order kinetics model. Analysis of the kinetic constant data revealed that particle size is a key factor determining the anaerobic digestion kinetics of crystalline cellulose. Hence, crystalline cellulose particle size should be considered in the development and optimization of lignocellulose pre-treatment methods. Further research is necessary for the assessment of impact of the crystalline cellulose particle size and surface properties on the microbial cellulose hydrolysis rate.

The effects of solid lignin on the anaerobic digestion of microcrystalline cellulose and application of smoothing splines for extended data analysis of its inhibitory effects.

Lignocellulose is an abundant substrate for biogas production; however, for efficient utilization, proper pre-treatment is required to enhance the biomethane yield and hydrolysis rate significantly. Phenolic compounds from dissolved lignin, produced during alkali pre-treatment, have inhibitory effects on the anaerobic digestion; however, the possible inhibitory effects of solid lignin have not gathered enough interest. Especially, the effect of solid lignin on methanogenesis remains a knowledge gap. In this study, kraft lignin was used as a model solid lignin substrate for its co-digestion with microcrystalline cellulose. A new approach of modelling biomethane production curves using smoothing splines was developed to describe the long-term inhibitory effects of solid lignin on hydrolysis and methanogenesis. The method gives possibility to describe long-term inhibitory effects by using batch instead of continuous test data. Results revealed that kraft lignin showed mild inhibitory effects on methanogens. However lignin impact combined with volatile fatty accumulation can prolong hydrolysis and reactor recovery start-up by 47.3% and 75.3%, respectively. For small dosages of solid lignin adaptation of methanogens is possible.

Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes.

In the current study, we aimed to investigate whether expression of immune checkpoint proteins (V-domain Ig suppressor of T cell activation (VISTA) and programmed death-ligand 1 (PD-L1)) and markers of systemic inflammation could predict progression/relapse and death in the cohort of 180 patients with testicular germ-cell tumors (GCTs). Expression of PD-L1 and VISTA was assessed by immunohistochemistry utilizing tissue microarrays. To estimate systemic inflammation neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) were calculated. We found high PD-L1 and VISTA expression on tumor-associated immune cells (TAICs) in 89 (49.44%) and 63 (37.22%) of GCTs, respectively, whereas tumor cells besides trophoblastic elements were almost uniformly negative. High PD-L1 was associated with seminomatous histology and lower stage. Relapses in stage I patients occurred predominantly in cases with low numbers of PD-L1 and VISTA-expressing TAICs. In stage II/III disease, the combination of low VISTA-expressing TAICs and high PLR was identified as predictor of shorter event-free survival (HR 4.10; 1.48-11.36, p = 0.006) and overall survival (HR 15.56, 95% CI 1.78-135.51, p = 0.001) independently of tumor histology and location of metastases. We demonstrated that the assessment of immune checkpoint proteins on TAICs may serve as a valuable prognostic factor in patients with high-risk testicular GCTs. Further study is warranted to explore the predictive utility of these biomarkers in GCTs.

Influence of Fraction Particle Size of Pure Straw and Blends of Straw with Calcium Carbonate or Cassava Starch on Pelletising Process and Pellet.

The aim of this study was to investigate the pressure agglomeration process of wheat straw (WS) and the blends of WS with calcium carbonate (CC) or cassava straw (CS) with a ratio of 6% wt./wt. from seven separate fractions with sizes in the range of 0.21-2.81 mm. The agglomeration was performed at a moisture of 30% wb and a material temperature of 78 °C, with a dose of 0.1 g, in a die of diameter 8 mm and height 80 mm. The effects of the process were evaluated based on the compaction parameters and the pellets' density, tensile strength, and water absorption. The incorporation of additives into the WS improved the pellet process and quality. Refined results were achieved after adding CC, as compared to those achieved after adding CS, and the preferred particle size was in the range of 1.00-1.94 mm. This was because, under the given conditions, the back pressure in the die chamber significantly increased, allowing the achievement of a single pellet density of 800 kg·m-3. The pellets were resistant to compressive loads and cracked only at tensile strength of 6 MPa and a specific compression work of 6.5 mJ·mm-2. The addition of CC to the WS improved the strength of the adhesive and the cohesive bonds between the particles. The water absorption for the uncrushed pellets was considerably less than that for crushed pellets, which results in the safer storage of uncrushed pellets and excellent moisture absorption of crushed pellets. The addition of CC to the WS offers benefits in the form of pellet strength with a high water absorption capability. Notably, a study of crushed pellet litter under broiler rearing conditions and an analysis of the operational costs of using WS additives are required for implementing this study.

Primarily resectable pancreatic adenocarcinoma - to operate or to refer the patient to an oncologist?

The aim of this work is to investigate the optimal therapeutic sequence of resectable pancreatic cancer - primary surgery with adjuvant therapy or neoadjuvant followed by resection. Application of the neoadjuvant approach in routine treatment of pancreatic cancer is rapidly growing every year, despite the lack of final results from randomized trials. Recent advancements in the adjuvant therapy, due to the more effective chemotherapy regimens, favor the upfront surgery strategy. On the other hand, theoretical background and metaanalyses favor the neoadjuvant strategy. Currently, primary resection with adjuvant chemotherapy remains the standard approach in resectable pancreatic cancer, but the first recommendations considering the neoadjuvant approach as an option seem to arise among the scientific societies with a global impact. Preliminary results of Prodige 24 study and PREOPANC-1 trial demonstrates that both options are worth further evaluation in clinical trials. Their results should soon provide more answers to this important clinical questions.

Application of titration methods for measuring the contents of ammonium nitrogen and volatile fatty acids in agricultural biogas plants.

The aim of our research was to assess a relatively new method of estimating ammonium nitrogen concentration in anaerobic digestion of plant substrates. We analysed our own data, received from the anaerobic digestion of maize silage (PM), as well as data published by Purser et al. (2014) who measured energy crops and slurry (ECS), and food waste (FW). In our study, the process was monitored for VFA content that was determined by gas chromatography, and for the content of ammonium nitrogen determined using the HACH LANGE LCK 303 cuvette test. We created polynomial regression models that bind the content of ammonium nitrogen with the volume of H2SO4 used to titrate the sample from initial pH to pH 5. To estimate parameters of model, the PM dataset was used. The obtained models were positively validated using ECS and FW datasets. Our results confirmed the effectiveness of the Purser et al. method with an average absolute error of less than 223mgl-1 of the VFA concentration, which was approximately 20-times less than the level that caused inhibition. In conclusion, we can affirm the suitability of using titration methods to assess the ammonium nitrogen content of bioreactors with a stable composition.

The dynamics of an anaerobic digestion of crop substrates with an unfavourable carbon to nitrogen ratio.

The purpose of this study was to investigate the effects of the characteristics of basic crop substrates, such as the carbon, nitrogen, ash and volatile fatty acids contents, on the dynamics of the anaerobic digestion process. For this purpose, the stepwise anaerobic digestion of silage from six different plant species was carried out. Scaled probability distributions (log-normal, log-logistic, logistic, Weibull and Gompertz) were used to approximate the cumulative methane production curves obtained. The results indicated that the Gompertz distribution best fit the process. The hazard function of the Gompertz distribution was used to describe the process change dynamics. Ridge regression models were made and tested to clarify the impact of the crop properties on the distribution parameters. The analysis results indicated that the initial rate of the process depended on the reactor acidity and that the nitrogen content of the substrate was a key factor that affected the process dynamics.

A comparative quality appraisal of finely comminuted batters produced using three types of knives.

The aim of this study was to compare the work efficiency of three types of knives mounted successively on a knife roll of a cutter by evaluating the quality and structure of produced finely comminuted batters as well as power consumption and electric energy consumption during chopping. Experimental material comprised finely comminuted meat batters produced under commercial scale production conditions using smooth knives, knives with riffles and knives with holes. Parameters measured in batter included temperature, water, fat, free water, apparent viscosity, thermal drip and batter structure using computer image analysis. Computer image analysis showed that the best comminution and dispersion of fat globules in the protein matrix together with very good comminution of collagen fibres were observed at the application of knives with holes. Among the three types of knives used in the production of finely comminuted meat batters the best batter in terms of its quality and structure was produced using knives with holes.

Assessment of the safety and efficiency of sunitinib malate in metastatic neuroendocrine tumours of the pancreas (NEN G1/G2) depending on the number and type of earlier therapeutic lines - initial report.

INTRODUCTION: The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy. MATERIAL AND METHODS: Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-67 < 20%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0. RESULTS: Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) - including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) - occurred in one patient after three lines and in one patient after two lines; anaemia (25%) - in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2-3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months. CONCLUSIONS: Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied.