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

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

EFFICACY AND SAFETY OF ALBAREL IN PATIENTS WITH MILD, MODERATE AND SEVERE HYPERTENSION

The aim of the study was to evaluate the efficacy and safety (influence on carbohydrate, lipid and mineral metabolism, as well as nitrogen-excreting function of kidneys) of monotherapy with rilmenidine in patients with mild to moderate AH, as well as treatment of patients with severe AH as multiple combined treatment. 43 patients with essential AH I-HI degree, aged 22 to 79, were enrolled in this open label study after signing an informed consent form. Enrolled patients were divided into 2 groups. Group 1 included 20 outpatients. They received monotherapy with rilmenidine 1 mg daily. Duration of treatment was 12 weeks. Group 2 was comprised of 23 subjects admitted to an in-patient clinic. Those subjects received Albarel 1 mg or 2 mg daily as a component of multiple antihypertensive therapy. Albarel was administered 7-10 days following the admission to clinic as a second to fifth hypotensive drug. Albarel's combinations with diuretics, ACE inhibitors, calcium antagonists, beta-blockers. The result is - monotherapy with Albarel 1-2 mg daily allows to achieve target BP in 77, 8 % patients with mild to moderate AH. With Albarel as a component of multiple therapy target BP is achieved in 65, 2 % patients with severe AH. Effectively decreasing BP Albarel does not change its daily profile. It has no influence on renal function, carbohydrate metabolism, and electrolyte content of blood. Albarel is well tolerated. Adverse effects included mouth dryness and drowsiness, was noted in 2, 33 % cases and did not require drug withdrawal

A highly hydrolyzed formula based on whey protein with the prebiotics galactooligosaccharides and fructooligosaccharides effectively abolishes the symptoms of atopic dermatitis: Results of a multicenter open-label trial in Russia

Most cases of atopic dermatitis are caused by allergy to cow’s milk proteins in babies in their first year of life. Dietotherapy with highly hydrolyzed formulas is the basis for timely and adequate medical care to these children. The objective of the open-label multicenter prospective postregistration trial was to evaluate the efficacy of a formula based on the in-depth hydrolysis of whey proteins with the prebiotics GOS/lcFOS 0,8 g/100 ml for infants within their first year of life who received artificial nutrition and suffered from topical dermatitis presumably associated with allergy to cow’s milk proteins. The trial enrolled 51 babies aged 193,64 (SD 73,95) days with mild and moderate atopic dermatitis (SCORAD&lt;40). Results. During a 4-week dietotherapy cycle, there was abolishment of the skin symptoms of atopic dermatitis (SCORAD 26,66 (SD 9,19) and 6,63 (SD 4,36)) at the beginning and end of the trial and a reduction in the needs for topical glucocorticosteroids, zinc-containing topical agents and antihistamines (p&lt;0,01). The individual visual analogue scale efficiency of the dietotherapy was 8,53 (SD 1,51) and 8,72 (SD 1,20) scores as assessed by the parents and physicians, respectively. During the dietotherapy, the physiological rate of defecations was 1,88 (SD 0,94) times/day, the characteristics of stool significantly improved. The average daily formula intake was 786,13 (SD 169,21) ml. Weight-for-height in all the infants was in the normal range. Conclusion. The test formula is well tolerated and effective in more than 90% of the infants with atopic dermatitis presumably associated with allergy to cow’s milk proteins and ensures a child’s growth and development

An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

Aim: The Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units. Method: An online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted. Results: Of hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017. Conclusions: Uptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation

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

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

Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit.

This is the peer reviewed version of the following article: group, T. E. S. o. C. c. (2018). "Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit." Colorectal Disease 20(S6): 47-57., which has been published in final form at https://doi.org/10.1111/codi.1437. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: Some evidence suggests that primary anastomosis following left sided colorectal resection in the emergency setting may be safe in selected patients, and confer favourable outcomes to permanent enterostomy. The aim of this study was to compare the major postoperative complication rate in patients undergoing end stoma vs primary anastomosis following emergency left sided colorectal resection. METHODS: A pre-planned analysis of the European Society of Coloproctology 2017 audit. Adult patients (> 16 years) who underwent emergency (unplanned, within 24 h of hospital admission) left sided colonic or rectal resection were included. The primary endpoint was the 30-day major complication rate (Clavien-Dindo grade 3 to 5). RESULTS: From 591 patients, 455 (77%) received an end stoma, 103 a primary anastomosis (17%) and 33 primary anastomosis with defunctioning stoma (6%). In multivariable models, anastomosis was associated with a similar major complication rate to end stoma (adjusted odds ratio for end stoma 1.52, 95%CI 0.83-2.79, P = 0.173). Although a defunctioning stoma was not associated with reduced anastomotic leak (12% defunctioned [4/33] vs 13% not defunctioned [13/97], adjusted odds ratio 2.19, 95%CI 0.43-11.02, P = 0.343), it was associated with less severe complications (75% [3/4] with defunctioning stoma, 86.7% anastomosis only [13/15]), a lower mortality rate (0% [0/4] vs 20% [3/15]), and fewer reoperations (50% [2/4] vs 73% [11/15]) when a leak did occur. CONCLUSIONS: Primary anastomosis in selected patients appears safe after left sided emergency colorectal resection. A defunctioning stoma might mitigate against risk of subsequent complications

An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

AimThe Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units.MethodAn online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted.ResultsOf hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017.ConclusionsUptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation.AimThe Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units.MethodAn online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted.ResultsOf hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017.ConclusionsUptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation.A

An international multicentre prospective audit of elective rectal cancer surgery; operative approach versus outcome, including transanal total mesorectal excision (TaTME)

IntroductionTransanal total mesorectal excision (TaTME) has rapidly emerged as a novel approach for rectal cancer surgery. Safety profiles are still emerging and more comparative data is urgently needed. This study aimed to compare indications and short-term outcomes of TaTME, open, laparoscopic, and robotic TME internationally.MethodsA pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients undergoing elective total mesorectal excision (TME) for malignancy between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak.ResultsOf 2579 included patients, 76.2% (1966/2579) underwent TME with restorative anastomosis of which 19.9% (312/1966) had a minimally invasive approach (laparoscopic or robotic) which included a transanal component (TaTME). Overall, 9.0% (175/1951, 15 missing outcome data) of patients suffered an anastomotic leak. On univariate analysis both laparoscopic TaTME (OR 1.61, 1.02-2.48, P=0.04) and robotic TaTME (OR 3.05, 1.10-7.34, P=0.02) were associated with a higher risk of anastomotic leak than non-transanal laparoscopic TME. However this association was lost in the mixed-effects model controlling for patient and disease factors (OR 1.23, 0.77-1.97, P=0.39 and OR 2.11, 0.79-5.62, P=0.14 respectively), whilst low rectal anastomosis (OR 2.72, 1.55-4.77, P<0.001) and male gender (OR 2.29, 1.52-3.44, P<0.001) remained strongly associated. The overall positive circumferential margin resection rate was 4.0%, which varied between operative approaches: laparoscopic 3.2%, transanal 3.8%, open 4.7%, robotic 1%.ConclusionThis contemporaneous international snapshot shows that uptake of the TaTME approach is widespread and is associated with surgically and pathologically acceptable results