Subcutaneous Infliximab (CT-P13) as Maintenance Therapy for Inflammatory Bowel Disease: 2 Randomized Phase 3 Trials.

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. We aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. Co-primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Comparison of the Color Doppler Vascularity Index in Patients with Pancreatic Adenocarcinoma and Chronic Pancreatitis from a Single Center in Poland.

BACKGROUND Pancreatic cancer is one of the most common cancers in the world and a major cause of cancer mortality. Therefore, it is extremely important to distinguish between malignant and benign changes quickly and accurately. This single-center study aimed to assess the discriminatory properties of the color Doppler vascularity index (CDVI) in the diagnosis of focal chronic pancreatitis and malignant pancreatic tumors. MATERIAL AND METHODS Seventy-nine patients (42 men, 37 women; age 62.0±13.5 years; 46 adenocarcinomas; 33 pancreatitis) qualified for this study. During endosonographic examination, pancreatic tumors were assessed in the color Doppler option. The dynamic tissue perfusion measurement was used to calculate tissue flow velocity (TFV), tissue perfusion intensity (TPI), and vascularization as the CDVI. RESULTS TFV, TPI, and CDVI were significantly lower in the group with malignant tumors than in the group with pancreatitis (P<0.001). In the receiver operating characteristic analysis, results of TFV=2.181 cm/s, TPI=0.009 cm/s, and CDVI=0.268 allowed for significant prediction of malignant tumors (P<0.001), with sensitivity of 75.8%, 69.7%, and 72.7% and specificity of 91.3%, 93.5%, and 80.4%, respectively, without significant differences between perfusion parameters and CDVI (P=0.07). CONCLUSIONS The findings from this study showed that color Doppler imaging and the use of the CDVI could provide an adjunctive diagnostic approach to distinguish between pancreatic adenocarcinoma and focal chronic pancreatitis. Owing to the possibility of calculating vascularization by non-Doppler methods, the method may be an easier and more accessible diagnostic option for malignant pancreatic tumors than perfusion assessed in external software.

Increased activity of aspartate aminotransferase in an asymptomatic young woman - case report.

Isolated macro-aspartate aminotransferase (macro-AST) in asymptomatic adults and children is a benign condition. In patients, however, macro- AST can be associated with neoplasms and autoimmunologic disorders, particularly with gastrointestinal diseases. CASE REPORT: We described a case of persistently elevated serum aspartate aminotransferase in an asymptomatic young woman who was correctly diagnosed with macro-AST after the elevated serum AST was found four years ago. To establish the diagnosis of macro-AST, we used non-invasive and inexpensive polyethylene glycol (PEG) precipitation assay. We advocate more widespread use of this method for routine laboratory diagnosis.

[Neoadiuvant teleradiotherapy decreases cancer tissue and serum concentration of prostaglandin E2 and cyclooxygenase-2 expression in patients with rectal cancer]. / Teleradioterapia neoadjuwantowa zmniejsza stezenie prostaglandyny E2 w tkance nowotworowej i surowicy oraz ekspresje cyklooksygenazy-2 u chorych na raka odbytnicy.

UNLABELLED: The carcinogenesis of colorectal cancer involves many factors, which modify the functioning of cells and can include prostaglandins. Resection of tumours and/or radiotherapy provide potentially curative therapy for cancer of the rectum. AIM: The aim of the study was to asses the effects of neoadiuvant teleradiotherapy on PGE2 concentrations in the serum and in the resected bowel tissue as well as on COX-2 gene expression in patients with rectal cancer. MATERIALS AND METHODS: Group I (n=20) included patients with resectable tumour (T1-2,No) treated exclusively by surgery, and group II (n=20) - patients with resectable tumours (T3) and nonresectable ones (T4). All the patients out of group II were put to the surgery after the previous teleradiotherapy applied to them. PGE2 concentrations were examined using the RIA method, while COX-2 mRNA expression was analyzed with the use of the PCR method. RESULTS: PGE2 serum concentrations in the group I prior to the resection did not differ from PGE2 concentrations in the group II prior to the resection (p=0,9488). However, radiation had caused reduction of PGE2 serum concentration prior to the resection in patients from the group II in comparison with the group I (p=0,0115). PGE2 serum concentrations after resection in the group I did not differ significantly from PGE2 concentrations in group II after resection (p=0,4511) (two-factor analysis of variation with interaction, p=0,3117). Radiotherapy did not change significantly PGE2 concentrations in the tumour and margin (two-factor analysis of variations with interaction, p=0,3137). The comparison between the number of patients who showed higher COX-2 mRNA expression in tumour than in the margin in the group I and II, did not reveal differences (p=0,6614). CONCLUSIONS: Neoadiuvant teleradiotherapy decreased PGE2 concentration in the serum, thus showed similar effect as tumour resection.

[Hygienic hypothesis in immunopathogenesis of inflammatory bowel disease]. / Koncepcja hipotezy higienicznej w immunopatogenezie nieswoistych chorób zapalnych jelit.

Over three last decades, it has been noticed that morbidity of immunology-dependent illnesses, like asthma, inflammatory bowel disease or atopic dermatitis, apparently increased. That is the reason to focus on searching and exploring new ideas which could explain etiopathology of those diseases. In etiopathology the role of environmental factors is particularly emphasized. Research indicated the inverse relationship between the frequency of infectious and/ or parasites and autoimmune diseases. It was a leading subject of many studies what allowed to create a hypothesis which explains the phenomenon. The most original and innovative idea, named hygenic hypothesis, was proposed in the late 80s of the last century. Avoiding or limiting the contact with common bacteria and parasites in well-and very well-developed countries probably caused depletion of immune memory which resulted in the hypersensitive response after exposure to general factors. Nowadays, autoimmunological diseases make really serious problem for medical care in the United States of America and Western European countries, ranking just behind cardiovascular diseases, cancer and metabolic sicknesses.

[Treatment of microscopic colitis - what's new?] / Leczenie mikroskopowego zapalenia jelita grubego ­ co nowego?

Microscopic colitis (MC) is frequent, although still uncommonly diagnosed, cause of chronic diarrhea. The etiopathology of MC is unknown but this disease has strong influence on patient's quality of life (measured by health-related quality of life - HRQoL). MC is characterized by microscopic abnormalities in large bowel's mucosa whereas endoscopic and radiological examination findings are normal. The treatment of MC is an essential social and financial problem due to its frequency in society. Thanks to the results of some controlled research which judged efficiency of some medicines as well as advisory groups recommendations, the MC therapy is nowadays going from empiric to accordance with evidence based medicine.

[Adalimumab as induction therapy for Crohn's disease - one center study]. / Adalimumab w indukcji remisji w chorobie Lesniowskiego- Crohna ­ studium jednoosrodkowe.

Adalimumab is a subcutaneously administered recombinant fully human monoclonal antibody targeting tumor necrosis factor alpha. It has been approved for use in Poland to treat patients with Crohn's disease under the program of Polish National Health Found since 2010. AIM: The aim of this study was to evaluate the efficacy of adalimumab monotherapy for inducing clinical remission in patients with active Crohn's disease . The primary outcome assessment was the reduction in score to 150 or below on the Crohn's Disease Activity Index (CDAI) at 12 weeks and the secondary one was the reduction in ΔCDAI of at least 100 points. MATERIALS AND METHODS: From January 2011 to December 2015 we treated 68 patients with active Crohn's disease (mean CDAI score 359). All the patients came from region of Silesia, an area with the same environment conditions. The patients were given adalimumab (Humira, AbbVie) subcutaneously at a dose of 160 mg at week 0, 80 mg at week 4 and 40 mg every two weeks thereafter. RESULTS: Twenty eight patients (41%) had a clinical remission at week 12 (CDAI ≤150) and 33 patients (49%) had a ΔCDAI response. During the 12-week of induction therapy infection with Clostridium difficile occurred in 4 patients and one patient died of a severe CMV infection. CONCLUSIONS: Adalimumab is effective as induction therapy for patients with moderate-to-severe Crohn's disease, however in individual cases serious infections including CMV infection can occur. A potential predictive factors for response can be female gender, non-smoking status and high CRP level at baseline.

[Microscopic colitis - a frequent cause of chronic diarrhea]. / Mikroskopowe zapalenie jelita grubego ­ czesta przyczyna przewleklej biegunki.

Chronic diarrhea is a very common problem in the general population. It requires a physician to differentiate its causes and depending on its etiology referring the patient to a hospital for diagnosis and subsequent treatment. One of the causes of chronic diarrhea may be microscopic colitis, which is characterized by the presence of clinical symptoms without endoscopic or radiological abnormalities. Diagnosis is based on a histopathological examination of the colon and thus clinical suspicion of the disease is so important for further diagnosis and treatment, which is primarily based on the use of topical steroids such as budesonide.

Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin.

Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (µg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.

[Pharmacologists in the camps in the Third Reich--part second]. / Farmakolodzy w obozach III Rzeszy--czesc druga.

SS Hygiene Institute provided adequate funding for research on the treatment of mycobacterial infections, and two scientists who became famous in the subject were Dr. Waldemar Hoven (KL Buchenwald) and Dr. Kurt Heissmeyer (KL Neuengamme). They conducted researches not only on adult prisoners, but also on the Jewish children. Studies of tuberculosis were also conducted under the auspices of the German Medical Association by Dr. Rudolf Brachtel. In turn, Dr. Klaus Schilling dealt with the treatment and immunoprophylaxis of malaria. He tested such substances, as pyramidon, aspirin, quinine and atebrin on more than 1200 prisoners. These sulfonamide-derived drugs, were also studied by prof. Karl Gebhardt and Dr. Fritz Fischer. They assessed the efficacy of these drugs in the treatment of "dirty" wounds incurred by German soldiers. Dr. Heinrich Schutz, Karl Babor and Waldemar Wolter they were enthusiasts in so-called biochemical therapy, based on the use of substances of natural origin, such as salt. After termination of War, during the Nuremberg Trials, many of them evaded responsibility, they were running medical practices, some were publishing. However, despite those facts, trials of Nazi war criminals were not result less, they opened world's eyes for the necessity of clarifying rudiments of human subject research, they gave foundations to define records like The Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine or Good Clinical Practice.

[Pharmacologists in the camps In the Third Reich--part one]. / Farmakolodzy w obozach III Rzeszy--czesc pierwsza.

The outbreak of World War II is considered as the inception of the pharmacology of the III Reich. Hitler's soldiers are decimated on the front lines by malaria, typhoid, gas gangrene, they need efficient and easy accessible medicines. From now on German forces are engaged into pharmacology of war. Only augmentation of Fuehrer's army effectiveness is reckoned with. Research centers in the concentrations camps are being organized, prisoners are used as the human subject. In the investigations many noted and respected personages are involved. Dr. Helmut Vetter and Dr. Ding Erwing Schuler studied chemicals which may had potential use in the prevention and treatment of typhoid. Professor Eugen Haagen carried out experiments concerning the use of vaccines against typhoid. The latter, although sentenced to life imprisonment, he returned to research in 1952 as a result of the amnesty activities in the former West Germany, and then worked as a researcher. His studies were reflected in the book, and scientific publications. Professor. Eugen Haagen died of natural causes in 1972.

Guidelines for the management of ulcerative colitis. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology.

This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2013. It contains 49 recommendations for the diagnosis and treatment, both pharmacological and surgical, of ulcerative colitis in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality of available evidence and the strength of therapeutic recommendations. The degree of expert support for the proposed statements was assessed on a 6-point Likert scale. Voting results, together with comments, are included with each statement.

VEGF and metalloproteinase 2 (MMP 2) expression in gastric cancer tissue.

BACKGROUND: Neoplasms are the second leading cause of death in Poland after vessel diseases, despite the huge progress in medical sciences in the last 20 years. Recently, gastric cancer morbidity has decreased, but mortality is still at a high level. MATERIAL/METHODS: Tissues from 24 patients with a histopathologically diagnosed mucosal and adenomucosal gastric cancer were tested. Patients were divided into 2 equal groups: patients without metastases (G1) and patients with metastases in the liver (G2). In all tested tissues of G1 and G2, the expression of VEGF (vascular endothelial growth factor) and metalloproteinase 2, respectively, were estimated. RESULTS: Results revealed a statistically significant increase in the VEGF expression for G1 and G2 in relation to the margin (p1<0.001; p2<0.001). The increase of gene expression for VEGF did not significantly differ statistically in G1 and G2. The obtained results revealed a statistically significant difference in the increase of gene expression for MMP-2 in G1 in relation to the margin (p<0.05) and a very high one in G2 in relation to the average margin value (p<0.001). A highly statistically significant correlation was obtained for VEGF and MMP-2 in the tissue of patients with metastases (p<0.001; r=0.714). The highly elevated expression of MMP-2 in the tissue of gastric cancer in patients with metastases confirms its participation in the invasiveness of the neoplasmatic process. CONCLUSIONS: The highly significant correlation between VEGF and MMP-2 suggests a connection between both mechanisms in the progression of gastric cancer.

Delay in Diagnosis of Autoimmune Polyendocrine Syndrome Type 2 as a Consequence of Misinterpretation of Gastrointestinal Symptoms.

Background: Type 2 autoimmune polyendocrine syndrome (APS-2) is characterized by the presence of at least two of three endocrinopathies: Addison's disease, autoimmune thyroiditis, and diabetes type 1. The prevalence of APS-2 is estimated to be 1 : 1000 to 1 : 20.000 in the general population. Diagnosis of APS-2 often is delayed due to its rarity and wide spectrum of clinical symptoms. Case Presentation. A 27-year-old presented with a 6-month history of abdominal pain, vomiting, diarrhea, weakness, fatigue, and 15 kg of weight loss. The patient was diagnosed with Crohn's disease in a local hospital and referred to our institution because of treatment failure. Colonoscopy performed in this hospital identified irregular mucosal erosions in terminal ileum, and the microscopy of biopsy specimens demonstrated nonspecific inflammation. On physical examination, the patient appeared cachectic. Blood pressure was 90/60 mmHg. Laboratory results were significant for severe hyponatremia and mild hyperkalemia. Morning cortisol was low, and adrenocorticotropic hormone (ACTH) concentration was high. An ACTH stimulation test did not present any increase in serum cortisol, which confirmed primary adrenal insufficiency. Antithyroid peroxidase antibody (anti-TPO) as well as both anti-21-hydroxylase antibodies and antiglutamic acid decarboxylase antibodies (GAD65) were positive. So, the diagnosis of APS-2 was made, and the replacement doses of hydrocortisone and fludrocortisone has brought a rapid improvement in all clinical symptoms; colonoscopy showed normal. Conclusion: The case presented herein highlights rapidly progressive nature of untreated APS-2 and that the diagnosis of APS-2 may be challenging.

TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases.

JAKs are intracellular protein tyrosine kinases that, through activation of STATs, are responsible for signal transduction pathways that regulate cellular responses to numerous cytokines, growth factors and hormones in many different cells. JAK-STAT signaling plays a key role in regulating immune function, and cytokines - such as IL-23, IL-12 and type I interferons - are central to the pathogenesis of autoimmune diseases, including psoriasis, inflammatory bowel disease and systemic lupus erythematosus. Here the authors review the evidence for targeting TYK2 as a more specific approach to treating these conditions. TYK2 inhibitors are clinically effective in autoimmune and inflammatory diseases and may avoid some of the complications reported with nonselective JAK inhibitors.

Dynamic Doppler Ultrasound Assessment of Tissue Perfusion Is a Better Tool than a Single Vessel Doppler Examination in Differentiating Malignant and Inflammatory Pancreatic Lesions.

Dynamic tissue perfusion measurement (DTPM) and single vessel flow measurement (SVFM) were assessed in differentiating inflammatory and malignant lesions of the pancreas. Sixty-nine patients (age 62.0 ± 14.7; 33 Female and 36 Men; 40 with malignant and 29 with inflammatory lesions) in whom during the endoscopic ultrasound (EUS) of focal pancreatic lesions it was possible to adequately evaluate the flow in the color Doppler, and then perform a biopsy, were qualified for the study. The assessed DTPM parameters flow velocity (TFV), perfusion intensity (TPI), and resistive index (TRI) as well as the following SVFM parameters: flow velocity (FV), volume flow (VolF), and resistive index (RI) differed significantly between the malignant and inflammatory lesions (p < 0.005). TFV and TPI have slightly better discriminatory properties than the corresponding FV and VolF parameters (p < 0.10). Considering the Doppler parameters usually evaluated in a given method, the TPI = 0.009 cm/s (sensitivity 79%, specificity 92%, AUC 0.899, p < 0.001) was significantly better (p = 0.014) in differentiating between inflammatory and malignant pancreatic lesions in comparison to FV = 2.526 cm/s (sensitivity 79%, specificity 70%, AUC 0.731, p < 0.001). Tissue perfusion has better discriminatory properties in the differentiation of solid pancreatic lesions than the Doppler blood flow examination in the single vessel within the tumor.

Guidelines for the management of patients with Crohn's disease. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology.

This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2012. It contains 46 recommendations for the diagnosis and treatment, both pharmacological and surgical, of Crohn's disease in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality and strength of the available recommendations. The degree of expert support for the proposed statement, assessment of the quality of evidence and the strength of the recommendation was assessed on a 6-point Likert scale. Voting results, quality and strength ratings with comments are included with each statement.

Gastric myoelectrical activity in patients with primary biliary cirrhosis.

OBJECTIVE: To examine gastric myoelectrical activity in patients with primary biliary cirrhosis (PBC). MATERIALS AND METHODS: The study comprised 11 female PBC patients (average age 53.4 years, range 43-70) and two aged-matched control groups: 11 (53.4 years, range 37-78) healthy women, and 10 female patients with chronic hepatitis C, CHC (53.9 years, range 35-66), who were examined prior to administration of an antiviral therapy. Every subject underwent an electrogastrographic recording comprising a 30-min interdigestive and a 120-min postprandial period. RESULTS: Abnormal electrogastrograms, containing prolonged epochs of tachygastria in the postprandial phase were found in 2 out of 11 (18.2%) patients having both stage IV of the Scheuer's PBC classification, as well as in 1 patient out of 10 (10%) with CHC at stage F2 according to the METAVIR fibrosis score. CONCLUSION: Electrogastrographic abnormalities do not seem to be pathognomonic for the PBC as a disease, but rather would be considered an unspecific sequel of a morbid liver affection.

Biosimilar biological drugs in the treatment of inflammatory bowel diseases.

Within the last 20 years, tumour necrosis factor inhibitors have been proven to be effective in achieving and maintaining clinical and endoscopic remission in patients with Crohn's disease and ulcerative colitis. Since 2013, when infliximab originator lost its patent protection, patients with inflammatory bowel diseases (IBDs) in Poland have also been treated with biosimilar drugs. Biosimilars are drugs with high similarity to their reference products in terms of physicochemical properties, including structure, safety, and efficacy. Biosimilars are approved for use on the basis of the same rigorous quality standards as their reference products. In 2018, also biosimilars of adalimumab have become available. Studies published to date have shown that biosimilars do not differ from reference drugs in terms of the efficacy and safety. There are numerous data to confirm that a single switch of biological drugs (mainly from reference to biosimilar drugs) has no effect on therapy efficacy and safety. However, a significantly lower cost of therapy with biosimilars not only allows us to treat a much larger number of patients but may also necessitate multiple switches from reference drugs to biosimilars (including biosimilars produced by different manufacturers). Recently, the first results have been published concerning multiple switches in patients with psoriasis and rheumatoid arthritis. However, no such data are currently available for patients with IBDs.

Potential biomarkers for the early diagnosis of colorectal adenocarcinoma - transcriptomic analysis of four clinical stages.

BACKGROUNDS: Colorectal cancer is the third most common cancer in economically developed countries. Molecular studies and, in particular, gene expression have contributed to advances in the diagnosis and treatment of many cancers. Genes can be molecular and therapeutic markers, but because of the large molecular diversity in colorectal cancer the knowledge is not yet fully established. Probably one of the most crucial processes during early cancer development is inflammation. The inflammatory response in the tumor is an important indicator of molecular etiology and later of cancer progression. OBJECTIVE: The aim of this work is to identify potential biomarkers for early stage of colorectal adenocarcinoma in patients' bowel tissues using transcriptomic analysis. METHODS: Expression of the inflammatory response genes of colorectal cancer at all clinical stages (I-IV) and control of the bowel were evaluated by oligonucleotide microarrays. RESULTS: Based on statistical analysis many differentially expressed genes were selected. LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase), GNLY (granulysin), SLC6A6 (Solute-Carrier Family 6 Member 6) and LAMP2 (Lysosomal Associated Membrane Protein 2) were specific for the early stage of the disease. These genes had the properties of the good biomarkers. CONCLUSIONS: The expression of LCK, GNLY, SLC6A6 and LAMP2 genes could be valuable potential diagnostic biomarkers of the early stage of colorectal adenocarcinoma.