Метаболизм и микроструктура стенки тонкой кишки у пациентов с колоректальным раком

RELEVANCE In patients with colorectal cancer (CRC), the normal small intestine, located outside the pathological focus, undergoes changes that may be the cause of digestive dysfunction after radical surgery to remove the tumor.The assessment of metabolic and microstructural changes in the ileum mucosa in patients with colorectal cancer is necessary to correct the algorithms of postoperative therapy and enteral nutrition. Modern means of optical bioimaging are potentially capable of solving this complex diagnostic problem.AIM OF STUDY To study the features of metabolism and morphological structure of the wall of a conditionally normal small intestine in the mucosa in patients with stage 1–3 CRC using macro- FLIM and optical coherence tomography (OCT).MATERIAL AND METHODS The object of the study was the wall of the ileum (66 samples) from the mucosal side of patients with histologically confirmed CRC stages 1–3 with tumor location in the right sections of the colon. Eight samples were obtained from patients with stage 1 CRC, 38 samples were obtained from patients with stage 2 and 20 samples were obtained from patients with stage 3 tumor. The volume of surgical intervention is right-sided hemicolectomy with total mesocolonectomy, CME (D2 lymph node dissection). Fresh tissue samples were examined using fluorescent lifetime macroimaging (macro-FLIM ) and OCT, followed by histological analysis of the material.RESULTS According to a histological study in the small intestine of patients with stage 1 CRC, the mucosa is covered with a normal single-layer prismatic border epithelium. In the intestine samples of patients with stage 2 CRC, mucus hypersecretion with areas of fibrosis and vascular congestion was observed. At the 3rd stage of CRC, the mucous membrane of the small intestine was loose, with local thickenings, areas of fibrosis with severe leukostasis, and foci of atrophy. None of the samples showed histological signs of a malignant tumor.According to OCT data, in the mucous membrane of the small intestine in patients with the 1st and 2nd stages of CRC, the contours of the villi and, partially, the crypts were well visualized. The structure of the villi was smooth, not coarse, and the shape was regular. In patients with stage 3 CRC, the contours of the crypts and villi were indistinct. There were no differences in the OCT picture between histologic preparations in the 1st and 2nd stages of CRC: the structure of the villi of the small intestine was clear, the shape was unchanged. According to FLIM data, statistically significant differences were revealed in the mean fluorescence lifetime values of reduced nicotinamide dinucleotide (phosphate) NAD(P)H (τm) between 2nd and 3rd (p=0.031), 1st and 3rd (p=0.018) by CRC stages. At the 1st stage of CRC τm was 1.61 [1.30; 2.02] ns, at the 2nd stage 1.50 [1.36; 1.73] ns, at the 3rd stage 1.37 [1.22; 1.51] ns. The FLIM results suggest an increase in the role of glycolysis in enterocyte energy metabolism along with progression of the CRC stage.CONCLUSION In patients with cancer of the right colon, lesions of the microstructure of the mucous membrane were revealed in the ileum not affected by the malignancy. At the same time, the severity of microstructural disorders in the wall of the small intestine is associated with the stage of tumor development in the colon. Bioimaging technologies, namely, methods of optical coherence tomography and fluorescence lifetime macroimaging, made it possible to objectively display microstructural and metabolic disorders in the ileum wall. The data of optical colorectal tomography demonstrated differences in the structural picture of the intestinal villi in patients with stages 1–2 and 3 of colorectal cancer. Results of fluorescence lifetime macroimaging of the metabolic cofactor nicotinamide dinucleotide (phosphate) confirmed an increase in the role of glycolysis in the energy metabolism of enterocytes along with an increase in the stage of colorectal cancer. The identified disorders in the state of the small intestine develop in patients with colorectal cancer before surgery and are highly likely to be an important pathogenetic link of malabsorption in the postoperative period. If the hypothesis is confirmed, the developed algorithm for the complex diagnosis of microstructural and metabolic disorders in tissues will expand the possibilities for the rehabilitation of patients with cancer of the right colon.АКТУАЛЬНОСТЬ У пациентов с колоректальным раком (КРР) нормальная тонкая кишка, расположенная вне патологического очага, претерпевает изменения, которые могут быть причиной пищеварительной дисфункции после радикальной операции по удалению опухоли.Оценка метаболических и микроструктурных изменений в слизистой оболочке подвздошной кишки у пациентов с КРР необходима для коррекции алгоритмов послеоперационной терапии, энтерального питания. Современные средства оптического биоимиджинга потенциально способны решить эту сложную диагностическую задачу.ЦЕЛЬ Исследовать особенности метаболизма и морфологической структуры стенки условно нормальной тонкой кишки со стороны слизистой оболочки у пациентов с КРР 1–3-й стадий методами макро-FLIM и оптической когерентной томографии (ОКТ).МАТЕРИАЛ И МЕТОДЫ Объектом исследования являлась стенка подвздошной кишки (66 образцов) со стороны слизистой оболочки у пациентов с гистологически подтвержденным КРР 1–3-й стадий с локализацией опухоли в правых отделах ободочной кишки. 8 образцов получены у пациентов с 1-й стадией КРР, 38 образцов — у пациентов со 2-й стадией и 20 образцов — с 3-й стадией развития опухоли. Объем оперативного вмешательства — правосторонняя гемиколэктомия с тотальной мезо­колонэктомией — CME (лимфодиссекцией Д2). Свежие образцы ткани исследовали методами флуоресцентного время-разрешенного макроимиджинга (макро-FLIM) и ОКТ с последующим гистологическим анализом материала.РЕЗУЛЬТАТЫ По данным гистологического исследования в тонкой кишке пациентов с 1-й стадией КРР слизистая оболочка покрыта нормальным однослойным призматическим каемчатым эпителием. В образцах кишки пациентов со 2-й стадией КРР наблюдалась гиперсекреция слизи с участками фиброза и полнокровием сосудов. При 3-й стадии КРР слизистая оболочка тонкой кишки была рыхлой, с локальными утолщениями, участками фиброза с выраженным лейкостазом и очагами атрофии. Ни в одном из образцов не обнаружены гистологические признаки злокачественной опухоли.По данным ОКТ в слизистой оболочке тонкой кишки у пациентов с 1-й и 2-й стадиями КРР хорошо визуализировались контуры ворсинок и, частично, крипты. Структура ворсинок была гладкой, негрубой, а форма регулярной. У пациентов с 3-й стадией КРР контуры крипт и ворсинок были нечеткими. Различий в картине ОКТ между гистологическими препаратами при 1-й и 2-й стадиях КРР получено не было: структура ворсинок тонкой кишки была четкой, форма неизмененной. По данным FLIM выявлены статистически значимые отличия в показателях среднего времени жизни флуоресценции восстановленного никотинамиддинуклеотида (фосфата) НАД(Ф)Н (τm) между 2-й и 3-й (p=0,031), 1-й и 3-й (p=0,018) стадиями КРР. При 1-й стадии КРР τm составило 1,61 [1,30; 2,02] нс, при 2-й стадии — 1,50 [1,36; 1,73] нс, при 3-й стадии — 1,37 [1,22; 1,51] нс. Результаты FLIM предположительно свидетельствуют об увеличении роли гликолиза в энергетическом метаболизме энтероцитов вместе с увеличением стадии КРР.ЗАКЛЮЧЕНИЕ У пациентов с раком правых отделов ободочной кишки в не затронутой злокачественным поражением подвздошной кишке зафиксированы нарушения микроструктуры слизистой оболочки. При этом выраженность нарушений микроструктуры в стенке тонкой кишки связана со стадией развития опухоли в толстой кишке. Технологии биовизуализации, а именно — методы оптической когерентной томографии и флуоресцентного время-разрешенного макроимиджинга, позволили объективно отобразить нарушения микроструктуры и метаболизма в стенке подвздошной кишки. Данные оптической колоректальной томографии продемонстрировали различия в структурной картине ворсинок кишки у пациентов 1–2-й и 3-й стадий колоректального рака. Результаты флуоресцентного время-разрешенного макроимиджинга метаболического кофактора никотинамиддинуклеотида (фосфата) свидетельствовали об увеличении роли гликолиза в энергетическом метаболизме энтероцитов вместе с ростом стадии колоректального рака. Выявленные нарушения в состоянии тонкой кишки развиваются у пациентов с колоректальным раком до операции и с высокой вероятностью являются важным патогенетическим звеном мальабсорбции в послеоперационном периоде. В случае подтверждения гипотезы, разработанный алгоритм комплексной диагностики нарушений микроструктуры и метаболизма в тканях расширит возможности реабилитации пациентов с раком правых отделов толстой кишки

Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection:an international, multi-centre, prospective audit

Introduction: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). Methods: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. Results: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30–0.92, P = 0.02) but MBP was not (OR 0.92, 0.63–1.36, P = 0.69) compared to NBP. Conclusion: This non-randomised study adds ‘real-world’, contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

Aim The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. Methods This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Evaluating the incidence of pathological complete response in current international rectal cancer practice

The mainstay of management for locally advanced rectal cancer is chemoradiotherapy followed by surgical resection. Following chemoradiotherapy, a complete response may be detected clinically and radiologically (cCR) prior to surgery or pathologically after surgery (pCR). We aim to report the overall complete pathological response (pCR) rate and the reliability of detecting a cCR by conventional pre-operative imaging.A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients treated by elective rectal resection were included. A pCR was defined as a ypT0 N0 EMVI negative primary tumour; a partial response represented any regression from baseline staging following chemoradiotherapy. The primary endpoint was the pCR rate. The secondary endpoint was agreement between post-treatment MRI restaging (yMRI) and final pathological staging.Of 2572 patients undergoing rectal cancer surgery in 277 participating centres across 44 countries, 673 (26.2%) underwent chemoradiotherapy and surgery. The pCR rate was 10.3% (67/649), with a partial response in 35.9% (233/649) patients. Comparison of AJCC stage determined by post-treatment yMRI with final pathology showed understaging in 13% (55/429) and overstaging in 34% (148/429). Agreement between yMRI and final pathology for T-stage, N-stage, or AJCC status were each graded as 'fair' only (n = 429, Kappa 0.25, 0.26 and 0.35 respectively).The reported pCR rate of 10% highlights the potential for non-operative management in selected cases. The limited strength of agreement between basic conventional post-chemoradiotherapy imaging assessment techniques and pathology suggest alternative markers of response should be considered, in the context of controlled clinical trials

Assessment of blood loss in total knee arthroplasty depending on the type of the endoprosthesis

Introduction. In the modern conditions arthroplasty of joints has become one of the main methods of treatment that enables to restore joint movements, weight bearing ability and quickly return the patient to an active lifestyle. Total knee arthroplasty (TKA) is accompanied by a significant blood loss resulting in a decrease of hemoglobin level and higher requirements in postoperative blood transfusion. Purpose of the study: to estimate the volume of blood loss in patients after total knee arthroplasty depending on the design of the endoprosthesis. Patients and methods. Retrospective study included 73 patients with stage 3 gonarthrosis by Kosinskaya. All patients were divided into groups: in group 1 (n=50) the standard total cemented knee joint endoprosthesis; in group 2 (n=23) - the associated rotational constructions were used. Hemoglobin and hematocrit tests were performed prior to and in 24 hours after operation. The volume of intra- and postoperative (in 24 hours) blood loss was calculated by the of hemoglobin balance formula. Results. In 24 hours after operation the hemoglobin level was 122.5 ± 9.6 g/l in patients from group 1 and 105.1±8.2 g/l (p=0.001) in patients from group 2. The difference in hemoglobin levels in patients within group 1 was 10.5±6.6 g/l, within group 2 - 28.5±7.5 g/l (p=0.006). The volume of intra- and postoperative (in 24 hours) blood loss for the 1st and 2nd patient groups of made up 420.5±276.7 ml, in group 2 it was 1163.0±302.5 ml (p</jats:p

OLYMP programme-basic clinical immunology programme as a part of continued medicaleducation for pediatritiansOLYMP SCHOOL IN NIZHNIY NOVGOROD REGION

In march 2011 OLIMP school (basics of clinical immunology for pediatricians) as a part of national project for pediatrician's education of basics of clinical immunology was successfully organized in Nizhniy Novgorod with help of Nutricia and Sandoz companies. Program included an actual topics of immune caused diseases in general practice, immune aspects of atopic diseases, nutritional influence to immunity of first - year - old children, evaluation of immune status of sickly children, principals of immune therapy.</jats:p

ASSESSMENT OF KNEE JOINT FUNCTION IN PATIENTS AFTER TOTAL KNEE ARTHROPLASTY USING THE KOOS SCALE

The goal was to evaluate the immediate results of treatment and knee function in patients after total knee replacement. Material and methods. The study included: questioning of patients, analyzing the medical records of inpatients, analyzing the features of surgical intervention and treatment during the postoperative period. We examined 81 patients with grade 3 gonarthrosis according to Ahlbäck. The patients underwent an examination of an orthopedic traumatologist with clinical assessment of their state by the KOOS scale (The Knee injury and Osteoarthritis Outcome Score). Results. A significant reduction in the pain syndrome was observed in the period from 30 to 180 days, ranging from 38.07 (11.1-50.0) points to 86.88 (72.2-97.2) points, respectively, which in turn speeded up the rehabilitation time after endoprosthetics (p <0.05). The severity of the pain syndrome in the period of 30-90 days after surgery was significantly lower in patients with rotation-endoprosthesis (50.0 - 66.4 points) than in those with modular endoprosthesis (38.07 - 60.6 points), respectively (p <0.05). The severity of symptoms throughout the period of observation of patients after surgery was significantly lower in patients with rotation-endoprosthesis (50.0 - 65.6 - 88.8 - 92.06 points) than in those with modular endoprosthesis (35.1 - 56.9 – 82.9 - 86.2 points), respectively (p <0.05). Conclusions. The evaluation of the knee joint function restoration after endoprosthetics using the KOOS scale is very detailed, which justifies its wider use in this category of patients

Mizernitskaya Olga Nikolaevna (to the 100^th anniversary of birth)

This article is dedicated to the 100th anniversary of the birth of Olga Nikolaevna Mizernitskaya, it is devoted to her contribution into the Russian pulmonology and allergology of children, it reveals little-known pages in the history of Russian pediatrics. Professional and creative path of Olga Nikolaevna reflects a difficult time. She made a significant contribution to the scientific development of pediatrics, pediatric allergology and pulmonology, for more than 16 years she was the main freelance pediatric allergologist and pulmonologist in Moscow, she brought up a galaxy of students, left an indelible mark in the history of the Scientific Research Clinical Institute of Pediatrics and in the pediatric science in general. The main areas of scientific, practical and organizational activities of Olga Nikolaevna Mizernitskaya were infectious-inflammatory (pneumonia) and allergic (bronchial asthma) lung diseases in young children. She published more than 130 scientific works, including a monograph and chapters in 7 monographs, a variety of methodological letters and recommendations, she prepared 6 candidates of medical sciences. The article presents the most significant aspects of the scientific and organizational activities of O.N. Mizernitskaya, bibliographic data, the paper notes her extraordinary merits of extremely responsive and kind person. Her difficult biography and creative path are consonant with the steps of the country and serve as an example for modern generations of physicians

Immunological disorders and their correction in the complex treatment of gastric and duodenal ulcers

Peptic ulcer of the stomach and duodenum is a disease, the etiology of which has not been precisely established. Taking into account the chronic recurrent course of the disease, seasonality, connection with a violation of the diet, increased sensitivity to parenteral administration of protein preparations, an immunoallergic hypothesis of the pathogenesis of peptic ulcer disease was put forward [46]. In our country, it was supported by S.M. Ryss. In the modern literature, the issue of changes in the general immune status in peptic ulcer disease is widely covered.</jats:p

Role of specialized child pre-school institutions in prophylaxis of allergy in children

Background. To estimate the efficiency of special child pre-school institution (SCPI) in prophylaxis of allergic diseases in children. Methods. 84 children with allergies aged between 10 months and 4 years old were observed. Among them 56 attended the SCPI and 28 (comparative group) attended the basic CPI. All children were passing through clinical, allergological, immunological examination as well as physical and mental development observation. Results. In this research the risks of development of allergies were thoroughly analyzed as well as the results of observation and check-ups of children with allergic diseases who attended to specialized SCPI or basic CPI. In the SCPI dietary conditions were kept, the hypo allergic diet was introduced into practice, the food allowance was balanced in protein, fat, carbohydrates and calorie contents due to physiological needs by substitution of foodstuffs. In the basic CPI these conditions weren't provide. In the SCPIs systematic observation of children is established and the cooperation of parents and doctor in charge of the case allows carrying out continuous pathogenetic therapy. Medical and prophylactic measures decrease the number of allergies' exacerbations and allow parents to proceed their usual activities, also improve the life conditions of children and their parents. Conclusion. The effectiveness of improving of health on the basis of SCPI is approximately 84,5% and the same in basic CPI is 66,75%. The research proposes the method of calculation of needs in SCPI and can be used in the organization of SCPI for children with allergic pathologies.</jats:p