[Results of total mesorectal excision and transanal endoscopic microsurgery for rectal adenocarcinoma with submucosal invasion]. / Rezul'taty total'noi mezorektumektomii i transanal'noi endomikrokhirurgii pri adenokartsinomakh pryamoi kishki s invaziei v podslizistyi sloi.

OBJECTIVE: To analyze early and long-term outcomes after total mesorectal excision (TME) and transanal endoscopic microsurgery (TEM) in patients with T1 rectal cancer. MATERIAL AND METHODS: A retrospective non-randomized comparative study included 2 groups of patients: group 1 - total mesorectal excision, group 2 - transanal endoscopic microsurgery. In the second group, total mesorectal excision was proposed for patients with tumor invasion depth pT1sm3 and/or lymphovascular invasion and/or low differentiation. If total mesorectal excision was performed as a salvage surgery, the patient was excluded from further analysis. RESULTS: There were 156 patients with rectal adenocarcinoma pT1 between October 2011 and August 2019 (102 cases - TEM, 54 cases - TME). We excluded 10 patients from the TEM group due to salvage surgery. Duration of TEM was 40.0 (34; 50) min, TME - 139 (120; 180) min (p=0.00001). Postoperative hospital-stay was also significantly less in the TEM group (7 (6; 9) vs. 10 (7; 11) days, p=0.00001). Six (6.5%) patients in the TEM group and 1 (1.8%) patient in the TME group developed a local recurrence in pelvic cavity (p=0.1). There were no distant metastases. Disease-free 3-year survival was 92% after TEM and 96% after TME (p=0.058). CONCLUSION: Transanal endoscopic microsurgery is a relatively safe alternative to total mesorectal excision for early rectal cancer.

[One thousand endoscopic submucosal dissections. Experience of the national center]. / Odna tysyacha endoskopicheskikh podslizistykh dissektsii. Opyt natsional'nogo tsentra.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a perspective method of organ-sparing treatment of benign colon tumors. MATERIAL AND METHODS: The study included 1.000 patients with colon neoplasms who underwent ESD between October 2016 and October 2021. All surgeries were performed under intravenous sedation. RESULTS: Mean dimension of tumors was 3.4 cm, median of surgery time - 51 (31; 101) minutes. Conversion of endoscopic approach occurred in 7.6% of cases. The main cause of conversion was unsatisfactory lifting in submucosal injection process. Incidence of en bloc and R0 resections was 84.1% and 68.3%, respectively. Postoperative morbidity was 2.9% that correlates with the world literature data. CONCLUSION: Endoscopic submucosal dissection is an effective and safe method for benign colon neoplasms. Considering high incidence of en bloc resection and low rate of local recurrence in benign neoplasms, further research of efficacy and safety of ESD in early colon cancer is needed.

Lysis of cells of diverse bacteria by l,d-peptidases of Escherichia coli bacteriophages RB43, RB49 and T5.

AIMS: The objective of this work was to study the antibacterial specificity and antibacterial effect of endolysins isolated from colibacteriophages RB43, RB49 and T5-as manifested on the exponential and stationary cell cultures of diverse bacteria depending on the growth stage, structure of peptidoglycan (PG) and antibiotic resistance. METHODS AND RESULTS: Enzyme activity was assayed by the spectrophotometric method. Antimicrobial activity was estimated by the number of colony forming units (CFUs), with the results represented as logarithmic units. Morphological examination of bacterial cells was conducted using phase-contrast and scanning electron microscopy. The enzymes EndoT5, endolysin of bacteriophage T5, EndoRB43, endolysin of bacteriophage RB43 and EndoRB49, endolysin of bacteriophage RB49 turned out to be much less bacteriospecific than the corresponding Escherichia coli phages; they lysed bacteria of the genera Bacillus, Cellulomonas and Sporosarcina, whose PGs had different structures (A1γ, A4α and A4ß) and chemical modifications (amidation). The specific lytic activity of phage enzymes was independent of the antibiotic resistance of bacterial cells and was higher when the cells were in the exponential, rather than stationary, growth phase. The analysis of morphological changes showed that the intermediate stage of the endolysin-induced lysis of bacterial cells was the formation of spheroplasts and protoplasts. CONCLUSIONS: Endolysins of colibacteriophages RB49, RB43 and T5 have a wide spectrum of antibacterial action, which includes a number of diverse micro-organisms with different PG structures. SIGNIFICANCE AND IMPACT OF THE STUDY: This is a study of the bacterial selectivity of enzymes degrading bacterial cell wall in relation to the chemical structure of PG. It is shown that endolysins of bacteriophages RB49 and RB43 efficiently lyse cell wall of Gram-positive bacteria of the genus Bacillus and Gram-negative bacteria of the genus Pseudomonas (including an antibiotic-resistant strain). The number of bacterial cells is reduced by 3-6 orders of magnitude, which indicates good prospects for using these enzymes in biotechnology.

Comparison of oncological and functional outcomes and quality of life after transanal or laparoscopic total mesorectal excision for rectal cancer: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare long-term oncological, functional outcomes and quality of life (QoL) after transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME) for rectal cancer. METHODS: A systematic review and meta-analysis based on Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were conducted on PubMed and Cochrane database. Non-randomized controlled trials (NRCTs) which compared TaTME with LaTME were included. RESULTS: Ten non-randomized studies were identified, including a total of 638 patients (323 TaTME and 315 LaTME). Age, sex, body mass index, neoadjuvant treatment and American Society of Anesthesiologists (ASA) staging of patients in the two groups were comparable in all included studies. The follow-up period was significantly shorter in the TaTME group than in the LaTME group. No significant differences in local (p = 0.71) and distant (p = 0.23) recurrence rate, 2-year disease-free (p = 0.86) and overall (p = 0.25) survival was found. Also, no significant differences in function outcomes and QoL, including the Wexner score (p = 0.48) or the International Prostate Syndrome Score (IPSS) (p = 0.64) were found. However, the low anterior resection syndrome (LARS) score was significantly higher in the TaTME group (p = 0.04). CONCLUSIONS: TaTME and LaTME have similar long-term oncological and functional outcomes as well as QoL. The only exception is higher LARS scores after TaTME. The current data are based mainly on observational studies and further randomized controlled trials are required.

A study investigating the perfusion of colorectal anastomoses using fluorescence angiography: results of the FLAG randomized trial.

AIM: Our aim was to evaluate the efficacy of indocyanine green (ICG) fluorescence angiography (FA) in reducing the incidence of anastomotic leakage (AL) following colorectal anastomosis. METHOD: A single-centre randomized trial was undertaken between 2018 and 2019. Those patients who underwent a stapled colorectal anastomosis were randomized 1:1 for ICG FA versus visual clinical assessment of blood perfusion of the anastomosed colon and rectal stump (non-ICG FA group). The primary end-point was to assess whether ICG FA was associated with a reduction in the incidence of AL. Secondary outcomes were the rate of postoperative complications and change in the level of bowel resection. RESULTS: A total of 380 patients undergoing sigmoid and rectal resection were enrolled. After randomization, three patients were excluded. The results of 377 cases were available for analysis; 187 had ICG FA and 190 were in the non-ICG FA group. ICG FA identified impaired blood perfusion of the colon in 36 (19%) cases. An AL (grade A, B or C) developed in 48 patients: 17 (9.1%) in the ICG FA group and 31 (16.3%) in the non-ICG FA group (P = 0.04). ICG FA did not decrease the rate of AL of high anastomoses (9-15 cm from the anal verge), at 1.3% vs 4.6% in the non-ICG FA group (P = 0.37). In contrast, a decrease in AL rate was found for low (4-8 cm) colorectal anastomoses (14.4% in ICG FA vs 25.7% in the non-ICG FA group; P = 0.04). CONCLUSION: ICG FA is associated with a reduction in AL following low anterior resection.

[Risk factors of regional lymph node metastases in pT1 colorectal cancer]. / Faktory riska porazheniia regionarnykh limfaticheskikh uzlov pri rake priamoi kishki rT1.

AIM: To identify risk factors of lymph node metastases in patients with pT1 rectal cancer. MATERIAL AND METHODS: There were 43 patients aged 62.3±11.3 years with pT1 rectal cancer who underwent mesorectal excision in 2012 - 2018. There were 34 (64%) females and 19 (36%) males. RESULTS: Histological examination revealed SM1-2 in 22/43 (51%) cases, SM3 - in 21/43 (49%) cases. Lymph node metastases were identified in specimens with submucosal invasion: SM3 - in 8/21 (38.1%) cases and SM1-2 - in 3/22 (13.6%) cases (p=0.08). Logistic regression confirmed lymphovascular invasion (p=0.005) and mucosal and/or poorly differentiated carcinoma (p=0.014) as independent predictors of lymph node metastases. CONCLUSION: Lymphovascular invasion and poorly differentiated carcinoma are indications for transabdominal mesorectal excision.

Side-to-end vs. straight stapled colorectal anastomosis after low anterior resection: results of randomized clinical trial.

AIM: The aim of this study is to compare surgical, functional, physiologic outcomes and QOL after low anterior resection (LAR) with andside-to-end or straight colorectal anastomosis. METHOD: Between 2012 and 2015, 86 patients with mid and low rectal tumors were enrolled into randomized trial. Wexner score, number of defecations, use of antidiarrheal medicine or laxatives, enemas, pads, episodes of nocturnal incontinence, and urgency were recorded. The Fecal Incontinence Quality of Life (FIQL) scale was used for assessment of QOL. Anal manometry and volumetric examination were performed. RESULTS: Six patients were excluded from the study. There was no mortality. The morbidity rate was 6 (14.6 %) for side-to-end vs. 8 (20.0 %) for straight anastomosis (p = 0.57). The median Wexner score was 5 vs. 6 (p = 0.033), 4 vs. 5 (p = 0.006), and 2 vs. 3 (p = 0.1) at 1, 3, and 6 months after stoma reversal, respectively. Side-to-end anastomosis resulted in a fewer mean numbers of bowel movements per day at the same check points of follow-up: 5.8 ± 0.14 vs. 6.4 ± 0.15 (p = 0.006), 3.7 ± 0.1 vs. 4.2 ± 0.1 (p = 0.003), and 2.5 ± 0.1 vs. 3.0 ± 0.10 (p = 0.0002), correspondingly. Maximal tolerated volume was higher for side-to-end anastomosis at 3 and 6 months of follow-up: 152.0 vs. 137.8 cm(3) (p = 0.002) and 180.5 vs. 167.0 cm(3) (p = 0.006), respectively. Better FIQL score was found at 1 and 3 months in the side-to-end group. CONCLUSION: Better functional outcomes and QOL were observed in a short period after stoma closure, but at 6 months of follow-up, the only benefit of side-to-end anastomosis was a lower number of bowel movements.

In vitro study of the antibacterial effect of the bacteriophage T5 thermostable endolysin on Escherichia coli cells.

AIMS: This study aimed to evaluate lysis of Escherichia coli stationary cell cultures induced by the combined action of bacteriophage T5 endolysin (l-alanyl-d-glutamate peptidase) and low doses of various cationic agents permeabilizing the outer membrane of Gram-negative bacteria (polymyxin B, gramicidin D, poly-l-lysine, chlorhexidine and miramistin). METHODS AND RESULTS: The enzyme activity was assayed with the turbidimetric method. Antimicrobial activity was assessed through the number of colony-forming units (CFUs); the results of calculation were represented as logarithmic units. The optical microscopy examination of bacterial cells was conducted in the phase-contrast mode. The use of bacteriophage T5 endolysin in combination with polymyxin B (0·4 µg ml-1 ) or chlorhexidine (0·5 µg ml-1 ) made it possible to reduce the number of CFUs by five orders of magnitude; and in combination with poly-l-lysine (80 µg ml-1 ) by four orders, as compared to control. The endolysin was found to be a thermostable protein: it retained ~65% of its initial activity after heating for 30 min at 90°C. Examining the curves of its thermal denaturation revealed the half-transition temperature to be 56·3 ± 1·0°C. Circular dichroism spectra showed that after recooling the protein restored up to 80% of its native structure. CONCLUSIONS: A substantial synergistic effect of the bacteriophage T5 endolysin and membrane-permeabilizing compounds was demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: The study of thermal stability of the bacteriophage T5 endolysin and the quantified assessment of its antimicrobial activity have been done for the first time. The approach examined lays foundations for designing a two-component preparation which would effectively lyse cells of Gram-negative pathogens from outside.

[Early Rectal Cancer: Can Transanal Endoscopic Microsurgery (TEM) Become the Standard Treatment?]

Aim: Transanal endoscopic microsurgery (TEM) is a main treatment technique for rectal adenomas, but can also be used for selected malignant tumors. This study presents TEM experience. Methods: The study enrolled patients with rectal adenomas, and selected adenocarcinomas. Preoperative work-up included: digital rectal examination, rectoscopy with biopsy, colonoscopy, EUS, pelvic MRI. Results: Three hundred and thirty patients [mean age of 61,4±10 (33­88)] underwent TEM. The mean size ± SD of tumors was 3.2±1.2 cm (0.6­10.0). Mean distance from anal verge was 6.7±2.6 cm (2.0­14.0). Preoperative biopsy revealed: adenoma ­ 263/330 (79,7%), adenocarcinoma ­ 67/330 (20,3%). The median operating time was 40 (15­220) min. Tumor-free margins were obtained in all operative specimens. In 5/330 (1.5%) cases tumors were fragmented. The morbidity rate was 19/330 (5.7%). Pathological investigation revealed: adenoma in 192/330 (58.1%) cases, adenocarcinoma stage Tis, T1, T2 and T3 in 138/330 (41.9%). Median follow-up lasted for 24 (1­57) months. Five patients (2.0%) with adenoma and four patients (5.2%) with adenocarcinoma had local recurrence. Conclusion: Transanal endoscopic microsurgery for rectal adenomas and selected malignant tumors is associated with low morbidity and low recurrents rates.

[Possibilities of transanal endoscopic microsurgery: the experience of 202 operations].

Transanal endoscopic microsurgery (TEM/TEO) is a standard treatment for rectal adenomas but can also be used for selected malignant tumors. Rectal adenomas, selected adenocarcinomas and carcinoids were chosen for operations. Preoperative work-up included: digital rectal examination, rectoscopy with biopsy, colonoscopy, EUS, pelvic CT (MRI). Two hundred and two patients [mean age of 62.4 ± 10.3 (33-86)] had TEO. The mean size ± SD of tumors was 3.2 ± 1.4 cm (0.6-8.0). Mean distance from anal verge and dental line was 7.1 ± 2.4 cm (2.5-14.0) and 4.6 ± 2.6 cm (0.5-12.0), respectively. Preoperative biopsy revealed: adenoma--156/202 (77.2%), adenocarcinoma--39/202 (19.3%) and carcinoid--7/202 (3.5%). The median operating time was 40 (20-180) min. Tumor-free margins were obtained in 200/202 (99%) operative specimens, 2/202 (1.0%) cases tumors were fragmented. Morbidity was 7/202 (3.5%). Pathological investigation revealed: adenoma in 109/202 (54.0%) cases, adenocarcinoma stage Tis, T1, T2 and T3 in 86/202 (42.5%), carcinoid in 5/202 (2.5%), neurilemoma in 1/202 (0.5%), neurofibroma in 1/202 (0.5%). One hundred and two patients had follow-up (95%). Median follow-up at 20 (1-41) months; 3/192 patients with adenocarcinoma, 1/192 patient with adenoma and 1/192 patient with carcinoid had local recurrence. Thus, transanal endoscopic microsurgery for rectal adenomas and selected malignant tumors is associated with low morbidity and low recurrents rates.

[Is the localization of the tumor in intra-peritoneal part of the rectum contraindication to transanal endoscopic microsurgery].

Transanal endoscopic microsurgery (TEM) is the method used in cases of benign tumors at the early stages of rectal cancer. The tumor localization in peritonized part of the rectum indicates a limiting level for removal of the neoplasm. TEM was performed on 137 patients. The mean age was 63.8 ± 9.8 years and the number of women consisted of 65.7%. Neoplasms were located in the upper ampullar rectum and a potential possibility of connection with the peritoneal cavity was noted in 12 (8.7%) patients, but during TEM it was only in 5 cases. There wasn't any conversion to a peritoneal surgery. The wound closures were carried out from the side of the rectum lumen and all the operations were finished with the control laparoscopy and formation of sigmostoma. The stomas were closed in 3 patients on fifth- sixth weeks. A connection with the peritoneal cavity during TEM isn't critical event in the case of wound closure through surgical rectoscope and it doesn't lead to the conversion to radical operation.

Stapled ileostomy closure results in reduction of postoperative morbidity.

BACKGROUND: Loop ileostomy is widely employed as a defunctioning procedure for left-sided colonic anastomoses. Closure of the stoma carries a risk of morbidity and even mortality. The aim of this prospective trial was to evaluate the ability of stapled stoma closure to decrease the rates of perioperative morbidity. METHODS: One hundred and nineteen patients (mean age 56.2 +/- 5.4 years) underwent two-stage operations for rectal carcinoma with protective loop ileostomy between 2005 and 2008. All patients were randomly divided into two groups: 56 patients had conventional ileostomy takedown, while in the other 63, a functional end-to-end anastomosis was created using a linear stapler. Groups were comparable in terms of age, gender, body mass index, and other parameters. RESULTS: Mean time of stoma closure using functional end-to-end anastomosis was 68 +/- 7, when compared to 92 +/- 11 min (P = 0.01) for conventional stoma closure. The overall morbidity rate after ileostomy closure using a stapler was 3.2%: one patient (1.6%) developed a wound infection and self-limited bleeding from the anastomotic line, while another patient (1.6%) had an ileal obstruction caused by adhesions and required additional intervention. Conventional ileostomy closure resulted in a 14.3% morbidity rate: six patients (10.7%) had prolonged ileus, 2 (3.6%) had small bowel obstruction, and 2 (3.6%) had wound infections (P = 0.04). CONCLUSION: Functional end-to-end anastomosis reduces operating time and morbidity compared to conventional ileostomy takedown.

[Hypermethylation of the CDH1, SEPT9, HLTF and ALX4 genes and their diagnostic significance in colorectal cancer].

Sequential treatment of bisulfate-converted DNA was used to study methylation of promoter areas of SEPT9, HLTF, ALX4 and CDH1 genes. Methylation profiles were evaluated by comparing bioptical findings on colorectal cancer (n=55) and morphologically intact areas of the large bowel (n=71). Significant differences between groups were established for SEPT9, HLTF and ALX4 genes (p < or = 10(-9)) in evaluating medium-rate methylation of CpG. Diagnostic sensitivity (Se) peaked for SEPT9 (78 +/- 7%); specificity--(86 +/- 4%) (Sp). On site CpG (position "+14"), similar findings were reported: Se=81 +/- 6%, Sp=77 +/- 5%. Therefore, CpG(14)SEPT9 may be used as a separate marker. As a result of the use of HLTF as marker on all 23 sites, Se was 67 +/- 6% and Sp--87 +/- 3%; ALX4 diagnostic sensitivity--59 +/- 6%. Specificity level was similar to those of the other genes (88 +/- 3%). Despite the role of CDH1 gene in colorectal cancer, the group-to-group differences in methylation rates were minimal. Such values of Se and Sp as 54 +/- 6% and 67 +/- 5%, respectively, could not support methylation of the CDH1 promoter area for diagnostic purposes. Therefore, combined evaluation of SEPT9, HLTF and ALX4 genes offered more advantage as far as diagnosis is concerned. Hypermethylation in two of the three genes was assumed as a criterion for diagnosis. Under such conditions, diagnostic sensitivity was 81 +/- 7% (Sp=93 +/- 3%). With such high values, the criterion has a potential of being instrumental in working out diagnostic tests for colorectal cancer.

Histopathological characteristics and post-operative follow-up of patients with potentially radiogenic papillary thyroid carcinoma depending on oncocytic changes availability in the tumor cells.

AIM: To compare the frequency of main histopathological characteristics, 131І thyroid radiation doses, invasive properties and post-operative follow-up of patients of different age groups with potentially radiogenic papillary thyroid carcinoma (PTC) with the presence and absence of oncocytic changes in tumor cells. MATERIALS AND METHODS: PTC removed in 483 patients from high risk age-group for radiogenic thyroid cancer development (children and adolescents at the time of Chornobyl accident who lived in the northern regions of Ukraine: Kyiv, Zhytomyr, and Chernihiv regions) have been studied microscopically. RESULTS: The frequency of PTC with the presence of oncocytic changes (OCh) in tumor cells increased significantly with increasing of patients' age at the time of surgery: from 8.3% in children 4-14 years old to 54.3% in adults 39-48 years old (ptrend < 0.0001). The presence of such changes is associated with papillary and solid-trabecular dominant tumor growth pattern in more than 90% of cases in each age group. The mean 131І thyroid dose in the whole series of PTC patients with OCh was significantly lower compared to the same index in PTC patients without OCh (493.7 mGy and 765.8 mGy, respectively, p < 0.0001). In addition, regional metastases recurrences were revealed more frequently in patients with OCh in primary PTC compared with patients without OCh in primary tumor (7.2% vs 1.5%, p = 0.0022). CONCLUSIONS: Significantly increasing age-trend of OCh in PTC of patients affected by the Chornobyl fallout and operated at age from 4 to 48 years, as well as opposite decreasing linear age-trend of 131І thyroid dose may reflect a gradual increase of sporadic PTCs frequency in the potentially radiogenic series with time elapsed since accident. The frequency of oncocytic insensitive to radioiodine therapy of lymph node metastases recurrences also increased with patients age and OCh availability in primary PTC.

[Photoluminescence band and anti-Stokes emission of native collagen in the visible range of the spectrum]. / Polosa fotoliuminestsentsii i antistoksovo izluchenie nativnogo kollagena v vidimoi oblasti spectra.

Photoluminescence (PL) of collagen, phenylalanine and tyrosine has been experimentally studied in the range of 400-700 nm. Anti-Stokes emission was observed when PL was excited by visible light. Possible participation of an excimer in generation of PL was shown. It has been pointed out that phenylalanine chromophore plays a dominant role in fluorescence generation of collagen in the spectrum visible range.

[Outbreak of tularemia in the Republic of Dagestan]. / Vspyshka tuliaremii v Respublike Dagestan.

In Daghestan in the focus of the flood-plain swamp type 64 persons fell ill with tularemia in 1999. During the epizootological survey 8 Francisella tularensis strains were isolated from vectors and carriers and in 7 samples taken from open water reservoirs, as well as in 1 sample obtained from Ixodes ticks, tularemia antigen was detected. Humans were infected mainly by the transmissive route, as found in 71.8% of patients. 28% of patients were infected through contacts. The disease took mainly a mild course, registered in 95.6% of patients. The disease affected those persons who had not been immunized against tularemia.

[Extrapyramidal dyskinesias and their neurosurgical treatment]. / Ekstrapiramidnye diskinezii i ikh neirokhirurgicheskoe lechenie.

The clinico-pathophysiological analysis of the main forms of extrapyramidal dyskinesias is discussed. The authors distinguish 2 main forms of hyperkinesias and dystonias which are designated conditionally phasic and tonic. Stereotaxic interventions on deeply located brain structures (ventrolateral complex of thalamic nuclei, subthalamic region, putamen, dentate nuclei of cerebellum) are substantiated anatomicofunctionally. On the basis of the results of 569 stereotaxic operations the indications and contraindications for various types of operative interventions were elaborated. The result was good in 26.7% of patients, considerable improvement occurred in 32%, mild improvement in 32.6%, no changes occurred in the condition of 5.2% of patients.

Cytotoxic activity of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide is underlain by DNA interchain cross-linking.

Currently, chemical bifunctional cross-linkers are regarded as promising therapeutic agents capable of affecting cell metabolism. Depending on the nature of the active groups and on the length of their mediating spacer, these cross-linkers have been shown to influence mitochondrial functions, the cell cycle and cell death. The current study was aimed to assay cellular effects of a cross-linker with 'zero'-length spacer, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). When added to cultures of transformed cells, EDC induced a G2/M blockade followed by cell death. Analysis of the molecular targets revealed that alteration of the cell cycle was caused by EDC-induced interchain cross-linking within double-stranded DNA. Administration of EDC to animals with experimental tumors increased their life span. The analysis of tumor cells from EDC-treated mice showed up-regulation of p21/WAF1, disturbance of tumor cell cytokinesis and, hence, cell death. Thus, both in vitro and in vivo, EDC exhibits cytotoxic activity, which may be of potential therapeutic use.