REVIEWS
Aim. To explore the various aspects of colorectal cancer with its correlation with human lifestyles and the inherited genetic makeup and its related metabolism. To understand the various diagnostic patterns, and to explore the nanotechnology-based combined diagnostic and therapeutic methods.
Key points. Colorectal cancer grades as the third most frequently identified malignancy, alongside being the chief cause of cancer related fatalities globally. The modification of normal colonic mucosal lining into a malignant one, as an outcome of collection of many genetic and epigenetic modifications contributes to the colorectal carcinogenesis. However, lifestyle changes have a significant role to play in this. An accumulation of metabolic disorders, the metabolic syndrome, which induces the dysregulation of prime biomolecules are one of the significant factors that induce carcinogenic effects in the normal colonocytes leading to the colorectal carcinogenesis. Non-alcoholic fatty liver disease, also termed as the hepatic expression of metabolic syndrome, is a prime threat for the incidence of colorectal cancer. It induces the malignancy by encouraging secretion of proinflammatory cytokines. As the number of mechanisms leading to colorectal cancer are rising, novel diagnostic tools for the early screening of the cancer are being introduced, and better techniques are still under research. Many studies have indicated the decrease in occurrence and fatalities linked to this disease, which can be attributed to the well-developed screening techniques in cancer management. Nanotechnology, under the area of colorectal cancer management, has improved the screening and delivery of drugs for cancer treatment procedures attributing to its excellent bioimaging and drug encapsulation properties.
Conclusion. This article will review the various genomic and lifestyle interventions affecting the progression of colorectal carcinogenesis. Additionally, we will review the novel and future theranostic techniques available for the management of colorectal cancer.
Aim: to analyse and systematise available literature data on the diagnosis and treatment of patients with locally advanced colon cancer with peritoneal carcinomatosis.
Key points. Even the obvious and rapid progress in the development of surgical and medicinal methods of treating patients with locally advanced colon cancer does not yet guarantee a complete cure. From 4 to 7 % of patients after radical resection report the progression of the disease — peritoneal carcinomatosis. The proportion of patients with isolated peritoneal lesions is about 2 %. This percentage of detection of peritoneal carcinomatosis at an early stage is directly related to the insufficient effectiveness of diagnostic methods, both laboratory and instrumental. To date, surgeons have accumulated quite a wealth of experience in performing diagnostic operations. Laparoscopy is a minimally invasive diagnostic tool and plays an important role in assessing the degree of dissemination, as it allows detailed visualization of the peritoneal surface, performing abdominal biopsies/flushes, and calculating the peritoneal carcinomatosis index (PCI).
The issue of early diagnosis of isolated peritoneal carcinomatosis is still relevant. and one of the most accurate methods of diagnosing small-focal peritoneal carcinomatosis is a repeated diagnostic operation (second look). Given the direct relationship between the severity of peritoneal spread and survival, it can be assumed that early detection of peritoneal carcinomatosis will increase the proportion of patients suitable for radical treatment and improve survival. To date, a sufficient number of studies have been conducted comparing the immediate and long-term results of treating patients with colorectal cancer using various combinations of cytoreductive surgery with/without hyperthermic intraperitoneal chemotherapy and/or systemic chemotherapy.
Conclusion. Evaluation of the current results of the randomized clinical trials in patients with peritoneal carcinomatosis of colon origin, treated with chemotherapy and in combination with targeted therapy, show fairly good results in overall and relapse-free survival.
ORIGINAL ARTICLES
Aim: to analyze risk factors for relapses and complications of peptic ulcer disease in a cohort of patients.
Materials and methods. Retrospective analysis of hospital records of 253 patients (average age — 52.1 ± 8.2 years) with peptic ulcer disease in the acute stage. Patients were stratified by gender, age and anamnestic risk factors, the phenotype of peptic ulcer disease being stratified by etiology, endoscopic characteristics of ulcerative defects of the gastric mucosa and duodenum.
Results. The proportion of complicated forms of peptic ulcer disease varies depending on gender, age and ulcer localization. The total number of complications in the cohort is 38.3 %, men developing complications in every second case (47.9 %). Among complications, bleeding is the most common one and accounts for 52.6 %, 42.9 % and 41.2 % of all complications in duodenal, simultaneous and gastric ulcers correspondingly. Cicatricial and ulcerative deformations are associated with localization in the duodenum and combined location of ulcerative defects, the complication being recorded in men 2 times more often than in women. Perforations of gastric ulcer are associated with the male gender (3 times more often). Stenosis is a rare complication, predominantly in women with duodenal ulcer. Significant predictors of complications of peptic ulcer disease are male gender and smoking. Factors associated with the manifestation of peptic ulcer disease include H. pylori and smoking in men, and H. pylori, nonsteroidal anti-inflammatory drugs or combination of these factors in women.
Conclusions. The factors influencing the incidence of complications and recurrences of peptic ulcer disease in the hospital cohort have been established: male gender, age of 36–59 years, H. pylori infection, tobacco smoking, NSAID use and simultaneous exposure to several factors in one individual.
Gastrointestinal hemorrhage is about 1.3 times more common in HIV-infected patients than in HIV-negative ones. At the same time the structural and etiological causes of hemorrhage in HIV differ in many ways from the main population which is undoubtedly due to the use of modern antiretroviral therapy, opportunistic infections and comorbidities.
Aim: to study the factors which are aggravating the course and influencing the structure of gastrointestinal bleeding in patients with HIV infection on the background of immunosuppressive disorders in comparison with HIV-negative patients.
Material and methods. To achieve this goal a multicenter retrospective cohort study of three groups of patients with gastrointestinal hemorrhage was conducted. Five hundred patients participated in the study: n = 111 — the main group (42 in Group 1 — HIV+, CD4+ > 200; 69 in Group 2 — HIV+, CD4+ < 200); n = 389 — in the control group (Group 3 — HIV-negative status).
Results. It was found that the comparison groups differ in age, the presence of previous hematological pathology (anemia, thrombocytopenia) as well as the sources of gastrointestinal bleeding. It can be noted that in all comparison groups endoscopic hemostasis methods were effective in about half of the cases (50.0 %, 42.0 % and 49.7 %), in the remaining findings hemostatic therapy was effective and sufficient (47.6 %, 33.3 % and 39.7 %). Surgical treatment was much more often required (statistically significant) in the group of patients with low immune status (29.0 %), and the need for it was associated with “rare sources” of bleeding: tuberculous intestinal ulcers, cytomegalovirus intestinal ulcers and decomposing Kaposi’s sarcoma of various parts of the digestive tract. The overall survival rate of HIV-infected patients with low immune status and gastrointestinal bleeding was statistically lower than in HIV-negative patients or patients with satisfactory immune status.
Conclusion. Gastrointestinal bleeding in HIV-positive patients has a number of significant features, that directly affect severity of blood loss, treatment methods and patient survival.
Aim: to investigate the metabolomic profile of patients with alcoholic liver disease and non-alcoholic fatty liver disease.
Materials and methods. The present study included patients diagnosed with non-alcoholic fatty liver disease (NAFLD) (n = 44), patients diagnosed with alcoholic liver disease (ALD) (n = 40) and 14 healthy volunteers. The level of metabolites in the blood serum were determined via high-performance liquid chromatography and tandem mass spectrometry.
Results. In this study, a cross-sectional targeted metabolomic analysis of 96 serum metabolites was performed in patients. Statistical analysis using the principal component method identified six main factors, comprising metabolites from various metabolic pathways. Comparative analysis between patient groups and the control group revealed statistically significant differences in the metabolic activity of individual factors, collectively reflecting alterations in the metabolomic profile. Levels of acylcarnitines, uridine, metanephrine, asymmetric and total dimethylarginine were elevated in patients with NAFLD and ALD compared to the control group. Carnitine, short chain acylcarnitines, valine, leucine, lysine, and alanine were significantly higher in patients with NAFLD compared to those with ALD. In contrast, levels of tyrosine, epinephrine, and methionine were significantly increased in ALD patients compared to both NAFLD patients and healthy volunteers. Among patients with liver cirrhosis (both ALD and NAFLD), there was a noticeable trend toward altered metabolic activity of factors correlating with liver failure indicators and the FIB-4 index. As liver cirrhosis progressed, statistically significant changes in metabolite levels were observed across Child — Pugh classes, taking into account hypocoagulation, hypoalbuminemia, hyperbilirubinemia, the presence of ascites, and hepatic encephalopathy.
Aim: improvement the results of treatment in patients with Grade 2–3 of hemorrhoids.
Materials and methods. A single-center prospective study included 90 patients with Grade 2–3 haemorrhoidal disease who met the inclusion criteria. All patients underwent transdermal laser submucosal destruction of internal hemorrhoids with a water-absorbed laser with a wavelength of 1940 nm according to the method proposed by us. In the course of the procedure the laser effect is applied both to the cavernous tissue of hemorrhoidal nodes and to the terminal branches of the superior rectal artery. The primary endpoints of the study were destruction of the cavernous tissue of internal hemorrhoidal nodes and the frequency of recurrence of the disease. The effectiveness of the technique was assessed using anoscopy, ultrasound examination with a rectal sensor with spectral-wave Dopplerography 1, 3, 6 and 12 months after surgery. At the same time, the quality of life and the severity of hemorrhoidal disease symptoms were assessed using the SF-36 scale and a point assessment of the clinical manifestations of hemorrhoids. In the first 7 days after surgery, the intensity of the pain syndrome was analyzed using the Visual Analog Scale (VAS). In order to determine the safety of the technique with respect to the effect on the locking apparatus of the rectum, sphincterometry was performed in all patients. Intra- and postoperative complications and recurrences of the disease within 1 year were also recorded, the causes of the return of clinical manifestations of hemorrhoidal disease were analyzed.
Results. The level of pain syndrome by day 7 after surgery corresponded to 0 points on the VAS in 52 (58 %) patients. Intraoperatively, bleeding occurred in 3 (3.3 %) patients and submucous hematoma formed in 15 (16.7 %) patients. In the early postoperative period, thrombosis of external hemorrhoids developed in 5 (5.6 %) patients, two of these patients developed acute urinary retention. Internal hemorrhoids determined before surgery were not visualized one month after surgery either by anoscopy or by ultrasound examination with a rectal sensor. According to the results of spectral wave Dopplerography, a persistent decrease in blood flow along the terminal branches of the superior rectal artery is noted for up to 12 months after the intervention. According to sphincterometry, no changes in the parameters of the anal sphincter function were noted compared with the preoperative parameters. 18 and 24 months after the operation, two patients were diagnosed with recurrence of hemorrhoidal disease. The analysis showed that the reason for the return of clinical manifestations of the disease was the supply of insufficient laser energy.
Conclusion. Laser submucosal destruction of internal hemorrhoids using a laser with a wavelength of 1940 nm is a minimally invasive method for treating Grade 2–3 of hemorrhoidal disease, which has demonstrated high efficiency (good results) in the late postoperative period. Thus, according to the results of our study, the return of clinical manifestations of hemorrhoidal disease was revealed only in 2 patients after 18 and 24 months. A repeated laser destruction procedure allowed us to achieve a good result in these patients.
Aim: to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a microbiota-dependent indicator of immune dysfunction and a long-term prognostic factor in patients with cirrhosis.
Materials and methods. A prospective study included 47 patients with cirrhosis. Gut microbiota was analyzed using 16S rRNA gene sequencing. Long-term survival prognosis was assessed over a 4-year follow-up period, and medium-term survival prognosis was assessed over 1 year follow-up period.
Results. During the 4-year follow-up period, 15 patients died, including 6 who died within the first year. Deceased patients had a higher neutrophil-to-lymphocyte ratio compared to survivors. This was significant for both long-term and medium-term prognoses (p = 0.021 and p = 0.048, respectively). Multivariate regression analysis identified a high NLR and low serum albumin levels as independent predictors of mortality for both long- and medium-term outcomes. The NLR was inversely correlated with the abundance of Roseburia, Alistipes, Rikenellaceae, Parabacteroides, Robinsoniella, Paraprevotella, and Odoribacter in the gut microbiota, and positively correlated with the cumulative level of ethanol-producing bacteria. NLR values did not differ significantly between patients who received glucocorticosteroids and those who did not.
Conclusions. The neutrophil-to-lymphocyte ratio correlates with the composition of pro- and anti-inflammatory taxa of the gut microbiota and serves as an independent factor for medium- and long-term prognosis in patients with cirrhosis.
Tumor diseases are one of the leading causes of death worldwide. Neoadjuvant and adjuvant chemotherapy can potentially lead to drug-induced liver injury and carcinoma. According to the literature review and meta-analysis, the mean weighted incidence of drug-induced liver injuries for all drugs among patients receiving neoadjuvant chemotherapy for colorectal cancer with liver metastases is 63.2 %. The mean weighted incidence of severe liver injury is 37.2 %. However, we have not found clinical reports of liver carcinoma formation due to chemotherapy. At present, we can say that, despite the theoretical possibility, chemotherapy for colorectal cancer is not accompanied by the development of hepatocellular carcinoma.
NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS
Aim: to provide summarized data on the relationship between menopausal hormone therapy (MHT) and liver health.
Key points. A decrease in estrogen production during the menopausal transition and a deficiency of estrogen and progesterone during postmenopause significantly affect lipid and carbohydrate metabolism and can lead to impaired liver function. With age, the risk of developing metabolic-associated fatty liver disease (MAFLD) in women increases significantly, due to a combination of hormonal changes, a higher incidence of metabolic disorders, and age-related factors. In turn, MAFLD is associated with an increased risk of cardiovascular disease, diabetes mellitus and metabolic disorders. In the absence of well-timed hormonal support, postmenopausal women are at high risk of developing serious complications, therefore, it is extremely important to select MHT with a favorable efficacy and safety profile. The approach to prescribing MHT should take into account the patient’s medical history, individual characteristics, as well as the mode of drug administration, considering the minimum effective dose.
Conclusion. Oral combination MHT provides positive metabolic effects through the first-pass metabolism but is not associated with additional health risks.
CLINICAL CASES
Aim: to present a clinical observation of a patient with Plummer — Vinson syndrome against the background of von Willebrand disease.
Key points. A 40-years-old woman presented to the hematology department of our hospital with fatigue, dizziness, dyspnea on exertion and dysphagia to solid food. Laboratory examination showed microcytic and hypochromic anemia (haemoglobin — 2,0 g/dL; red blood cells — 1.31 × 1012/L), a reduction in serum levels of ferritin to 1.5 ng/mL and a decrease in the von Willebrand factor activity up to 32.4 %. According to esophagogastroduodenoscopy the lumen of the upper esophagus third was circularly narrowed to 8 mm by web formation. Combining these clinical symptoms and examinations, we made the diagnosis of von Willebrand disease and Plummer — Vinson syndrome. Iron supplementation therapy and replacement therapy with von Willebrand factor concentrate were prescribed. At the time of discharge, the patient noted a significant improvement in her general condition, the number of red blood cells was 3.9 × 1012/L, haemoglobin — 8.6 g/L.
Conclusion. Plummer — Vinson syndrome is a rare manifestation of iron deficiency anaemia and therefore can often be overlooked by physicians. The cause of deep tissue iron deficiency in our patient was chronic blood loss against the background of von Willebrand disease. Our literature review did not reveal similar cases of concomitant von Willebrand disease with Plummer — Vinson syndrome.
Aim: to present a clinical case of generalized sarcoidosis that developed after suffering a new coronavirus infection.
Key points. Patient M., 45-years-old female, was hospitalized in the pulmonology department of the Clinic in October 2023 with complaints of shortness of breath that occurs with moderate physical exertion, sweating, increased fatigue. During the examination, the diagnosis was made: Main disease: Generalized sarcoidosis with lesions of the lungs, intrathoracic and peripheral lymph nodes, and spleen. Background disease: New coronavirus infection COVID-19 from January 2022. Prolonged postinfectious (new coronavirus infection) syndrome. Immunohistochemical examination of the biopsy of the supraclavicular lymph node in epithelioid cells, giant multinucleated cells in the cytoplasm revealed nucleocapsid and spike proteins of the SARS-CoV-2 virus. According to the treatment algorithms for sarcoidosis, 1st line therapy with systemic glucocorticosteroids was prescribed, followed by dose reduction and case monitoring.
Conclusion. A clinical case of generalized sarcoidosis with verified virus persistence in sarcoid granuloma cells 1.5 years after an acute episode of COVID-19 is presented.
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