[Medical rehabilitation in patients with anal incompetence after surgery for stage IV hemorrhoids]. / Konservativnaya reabilitatsiya patsientov s nedostatochnost'yu anal'nogo sfinktera posle khirurgicheskogo lecheniya gemorroya IV stadii.

The choice of medical rehabilitation in patients with anal incontinence is impossible without diagnostic data revealing the mechanism of fecal incontinence. The most promising are programs of comprehensive physiotherapeutic rehabilitation based on biofeedback training. The rate of anal incompetence (AI) after hemorrhoidectomy is 1.3-12.5%. However, in addition to the organic cause (surgical trauma), functional disorders of the external sphincter and pelvic floor muscles may contribute to the pathogenesis of anal incontinence, aggravating the incontinence symptoms after surgery. Therefore, these functional disorders should be diagnosed before surgery. However, medical rehabilitation programs for anal incontinence after hemorrhoidectomy are not standardized, and functional outcomes have not been studied. OBJECTIVE: To evaluate the outcomes of comprehensive rehabilitation in patients with AI after hemorrhoidectomy to improve quality of life after surgery. MATERIALS AND METHODS: A retrospective study was carried out on 46 patients (mean age 53.8±15.4 years) after hemorrhoidectomy with fecal incontinence, 13 (28.3%) males and 33 (71.7%) females. The main group included 25 patients who received comprehensive rehabilitation, including biofeedback training and tibial neuromodulation (TNM) for 15 days. The control group consisted of 21 patients who received TNM at home also for 15 days. The severity of fecal incontinence was determined using the Wexner score. The functional state of the sphincter before and after surgery was assessed using the anorectal manometry (sphincterometry) (WPM Solar, the Netherlands). RESULTS: Comprehensive rehabilitation resulted in a statistically significant clinical improvement: a decrease in the Wexner score in both males and females. No significant differences in manometry results were observed: the anal sphincter tone increased by 16.0% in females and 10.6% in males, and contractility increased by 17.7% and 15.1%, respectively. Monotherapy with TNM in control group patients improved tone indices by 8.7% in females and 6.8% in males, and contractility by 6.2 and 5.4%, respectively, which was lower than in the main group. CONCLUSION: Contraindications to physiotherapeutic procedures based on electrical stimulation, extracorporeal magnetic stimulation, and magnetic translumbosacral neuromodulation determine the only possible choice of medical rehabilitation, which is the combination of biofeedback training and TNM (as superior to TNM monotherapy). If out-patient medical rehabilitation is not feasible, patients are recommended to complement the home course with a specially designed set of exercises for anal incontinence treatment.

[Prevention of colorectal anastomotic leakage using its reinforcement (results of the randomized study)]. / Profilaktika nesostoyatel'nosti kolorektal'nogo anastomoza putem ego ukrepleniya (rezul'taty randomizirovannogo issledovaniya).

OBJECTIVE: To reduce the incidence of postoperative complications via reinforcement of colorectal anastomosis. MATERIAL AND METHODS: A randomized prospective study included 115 patients. In the main group (n=60), anterior resections were followed by reinforcement of colorectal anastomosis via suturing the muscular and serous layers at 2, 4, 6, 8, 10, 12 o'clock. In case of low anterior resection, all layers of intestinal wall were transanally sutured at the above-mentioned points. Reinforcement was not performed in the control group (n=55). RESULTS: In the main group, overall incidence of anastomotic leakage was 8.3% (5/60), in the control group - 25.5% (14/55) (p=0.01). We also analyzed the subgroups of anastomoses with high and low risk of leakage. In case of transabdominal reinforcement, incidence of anastomotic leakage was 11% (2/18) in the main group and 0% (0/14) in the control group (p=0.6). Transanal reinforcement was followed by anastomotic leakage in 7% (3/42) of patients in the main group and 34% (14/41) of patients in the control group (p=0.005). CONCLUSION: Reinforcement of colorectal instrumental anastomosis by additional sutures reduces the incidence of postoperative complications associated with anastomotic leakage.

Identification of large deletions in the APC gene in Russian patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a hereditary syndrome characterized by the presence of multiple adenomatous polyps in the colon. The main cause of the disease is a germline mutation in the APC gene. Here we report 4 unrelated FAP patients with different large deletions in the APC gene detected by Multiplex Ligation-dependent Probe Amplification (MLPA) method: deletion of exons 7-15, deletion of promoters B, A, and 5'-UTR region and deletion of promoter B (in 2 patients). The deletion of promoters B, A, and 5'-UTR was not described in the literature earlier, so we report it for the first time. In 2 families with promoter B deletion, we could identify the tendency for decreasing the age of disease manifestation in each next generation, in contrast to the previous one. The incidence of large deletions in APC among Russian patients with FAP reached 4.8% and our finding suggests the need to study this gene by MLPA in "no mutation patients" after Sanger's sequencing.

MutYH-associated polyposis.

MutYH-associated polyposis is the only polyposis syndrome with an autosomal recessive type of inheritance, often phenotypically similar to a weakened form of familial adenomatous polyposis. For the development of the disease mutations in both alleles of the gene are required, but an increased risk of developing colorectal cancer in carriers of monoallelic mutations is noted. The diagnosis of MutYH-associated polyposis should be suspected in a patient with colorectal cancer over 45 years old on the background of polyps in the colon. The review presents modern algorithms for diagnostic and treatment of the disease.

[Reinforcement of staple line of colorectal anastomosis for leakage prevention: a systematic review and metaanalysis]. / Rol' ukrepleniia kolorektal'nogo anastomoza dlia profilaktiki ego nesostoiatel'nosti: sistematicheskii obzor literatury i metaanaliz.

OBJECTIVE: To evaluate the influence of reinforcement of staple line of colorectal anastomosis on the incidence of leakage. MATERIAL AND METHODS: A systematic review was performed in accordance with the PRISMA recommendations. Statistical analysis was carried out in the Review Manager 5.3 software. RESULTS: This trial included four original articles published in 2011-2018. There were 493 patients. Reinforcement of anastomosis was made in 232 (47%) cases, colorectal anastomosis was not reinforced in 261 (53%) patients. Anastomotic leakage rate was 5.6 and 11.1% in both groups, respectively (OR 0.55, CI 0.13-2.33; p=0.42). Transabdominal reinforcement reduced leakage rate by 10.2% (OR 0.18, CI 0.06-0.55; p=0.002) while transanal reinforcement was ineffective (OR 1.66, CI 0.38-7.19; p=0,5). Incidence of preventive stoma was similar (OR 0.3, CI 0.07-1.22; p=0.09), but it was possible to abandon preventive stoma in 18% of cases after anastomotic reinforcement. CONCLUSION: A small number of studies dedicated to anastomosis reinforcement resulted controversial data.

[Pilot clinical and genetic study of Russian patients with Peutz-Jeghers syndrome].

Peutz-Jeghers syndrome is a rare hereditary syndrome characterized by presence of hamartoma polyps in intestinal tract and usually by mucocutaneous pigmentation. Clinical-genetic characteristics of Russian patients with Peutz-Jeghers syndrome were studied for the first time. Four germline mutations in STK11gene were found in probands from six families and three of them had not been described previously. Clinical pattern of disease in Russian patients included: frequent polyposis of colon and stomach (62,5% and 75%, respectively) along with small bowel; frequent presence of malignant tumors (62,5%). These clinical aspects can help physicians to find out Peutz-Jeghers syndrome. Molecular-genetic testing of individuals should be recommended.

The analysis of microRNAs miR-200C and miR-145 expression in colorectal cancer of different molecular subtypes.

The expression levels of microRNAs miR-200c and miR-145 in two groups of colorectal cancer differing by the presence/absence of epithelial-mesenchymal transition (EMF) were studied. In the EMF-positive cancer, the level of miR-145 is increased, whereas the level of miR-200c is reduced. The reverse situation is observed in the EMI-negative cancer. MiR-145 can serve as a marker of the mesenchymal subtype of cancer. Gene expression profiles and microRNAs allow prognostically unfavorable tumors of the mesenchymal subtype to be distinguished.

Coherent combining of femtosecond pulses parametrically amplified in BBO crystals.

We report on the first experimental realization of coherent combining of parametrically amplified femtosecond pulses. The proposed and implemented two-loop active stabilization system allows us to achieve 110 as relative timing jitter between combined pulses, which is necessary for efficient coherent beam combining. In each channel of the two-channel laser setup, pulses were parametrically amplified in ß-BaB2O4 (BBO) crystals to 50 µJ energy, compressed to 49 fs duration, and then coherently combined with efficiency as high as 97%. Currently, it is the shortest duration of amplified pulses for which coherent combining is demonstrated.

[Surgical treatment of patients with severe fecal incontinence].

The objective of the study is improvement of clinical and functional results of surgical treatment of patients with severe fecal incontinence. 79 patients with complete fecal incontinence were included in the study. The technique of surgical intervention was choosed in depending on the localization of structural and functional disorders of the rectum closing apparatus. Complex treatment in pre-operative and post-operative periods was directed on the improvement of functional results. Long-term results (6-24 months) were traced in 63 patients after surgical treatment and complex post-operative rehabilitation. Good and satisfactory results were identified in 57 (90.5%) patients, unsatisfactory results - in 6 (9.5%) patients. Choice of surgical technique in depending on the localization of structural and functional disorders of the rectum closing apparatus and combination of surgical correction with complex functional rehabilitation allow to increase treatment efficiency. Also it improves closing function in the most patients.

[The weakened form of familial adenomatosis: clinical and genetic characteristics and methods of treatment].

Clinical and genetic analysis of 24 Russian patients with attenuated form of family colon adenomatosis was undertaken. On the basis of obtained clinical and genetic data it was defined the algorithm of therapeutic measures in this group of patients--from dynamic monitoring or endoscopic polypectomy to performing extensive resections of the colon in situations associated with cancer development, an increase of the intensity of growth of polyps or an appearance of villous lesions. Some of the patients had molecular-genetics causes of a weakened form of family adenomatosis.

[Molecular genetics study of hereditary predisposition to diffuse gastric cancer in Russian patients].

About 3% of cases of gastric cancer (GC) cases are due to hereditary predisposition. Molecular causes of inherited predisposition to diffuse GC among Russian patients have not been studied. In the present work there was performed the molecular genetics study in 9 probands with signet-ring cell GC. Search of hereditary mutations was conducted in a suppressor gene of diffuse GC - the gene CDH1. We have discovered a new hereditary mutation (c.1005delA) and one rare variant (s.2253C> T). Frequency of hereditary mutations in sample of patients Russian was 1/9 (11,1%).

Transvaginal laparo-endoscopic single-site sigmoidectomy.

We report a case of sigmoid colon resection by single-incision laparoscopic surgery using transvaginal access. The patient was a 54-year-old woman with early stage sigmoid cancer who had no previous surgery and had a body mass index of 23.5 kg/m(2). The operative time was 270 min, and the blood loss was negligible. We used only transvaginal access, since no transabdominal assistance was required. No complications occurred. Minimal postoperative pain and a rapid recovery of gastrointestinal function were observed. As novel equipment is introduced into clinical practice, transvaginal laparoscopic procedures will most likely become increasingly popular in abdominal surgery. In particular, this type of procedure will have a more defined role in colorectal surgery. Indeed, in the future, it may become an alternative for natural orifice transluminal endoscopic surgery.

[The manually assisted laparoscopic surgery of colon cancer].

The experience of 193 manually assisted laparoscopic operations on the reason of colon cancer was analyzed. The mean age of the patients was 63.6±11.3 years. Men were 85 (44%), women - 108 (56%). The majority of patients had tumor of 2nd or 3rd stage. The mean body mass index was 27.6±4.6 kg/m2. The conversion was needed in 8 (4.1%) cases. There were no intraoperative complications. The duration of the manually assisted laparoscopic colon resection was 168±45min. 11 (5.7%) patients had postoperative complications. The thorough analysis of the results allow to recommend the method for the treatment of patients with colon cancer.

[The hand-assisted laparoscopic resections of colon's left parts].

Authors have an experience of 88 hand-assisted laparoscopic procedures. Results of 32 hand-assisted resections of colon's left parts are analyzed. The special original sealing device was used for making of pneumoperitoneum during laparoscopic procedures. The study group consisted of 19 female and 13 male patients. Mean age was 60.0 +/- 9.8 years (42-76 ys). Overweight was seen at 23 (72%) patients, 12 of them had obesity of I-III stage. Previous abdominal operations have been performed at 11 (34.4%) patients. Mean time of surgery was 181 +/- 53 min, operative bleeding--92 +/- 65 ml, no intraoperative complications occurred. Length of minilaparotomy was 7.3 +/- 0.8 cm. Poltoperative complications were seen at 4 (12.5%) cases, there were no lethal outcomes. Mean hospital stay was 9.8 +/- 3.5 bed-days.

[Impact of neutron radiation on the viability of tumor cells cultured in the presence of boron-10 isotope].

Objective: To investigate the impact of a neutron beam formed with the accelerator-based epithermal neutron source designed at the G.I. Budker Institute of Nuclear Physics (INP) on the viability of human and animal tumor cells cultured in the presence of boron-10 isotope. Material and Methods: Human U251 and T98G glioma cells and Chinese hamster CHO-K1 and V-79 cells were incubated at various concentrations in the culture medium containing 10B-enriched L-boronophenylalanine. The cells were irradiated with a neuron beam using the accelerator-based epithermal neuron source. A clonogenic assay was used to evaluate the viability of the irradiated cells. The absorbed doses obtained from elastic scattering of fast neutrons by substance nuclei and the doses obtained from boron neutron capture were calculated using the NMS code. The absorbed doses of gamma-radiation were measured with a mixed radiation dosimeter. Results: The viability of boron-containing and intact human U251 and T98G cell lines and Chinese hamster CHO-K1 and V-79 cells was analyzed after neutron beam radiation. Irradiation of all four cell lines were cultured in the presence of 10B was shown to reduce their colony-forming capacity compared with the control. Elevated boron levels in the culture medium resulted in a significant decrease in the proportion of survived cells. Radiation had the most pronounced impact on the proliferative capacity of the human U251 glioma cell lines. Conclusion: The cultures of human tumor cells and mammalian cells demonstrated that the neutron beam formed with the accelerator-based epithermal neutron source designed at the INP, was effective in reducing the viability of tumor cells in the presence of 10B.

Clinical acceptability study of micronized purified flavonoid fraction 1000 mg tablets versus 500 mg tablets in patients suffering acute hemorrhoidal disease.

OBJECTIVE: To compare the clinical acceptability of micronized purified flavonoid fraction (MPFF) 1000 mg with MPFF 500 mg tablets, administered at the same daily dose in patients suffering non-complicated acute hemorrhoids. BACKGROUND: MPFF is an established treatment for hemorrhoidal disease. METHODS: This was a double-blind, multi-center, randomized study. Patients took either MPFF 1000 mg or 500 mg tablets for 7 days (daily dose; 3 g over 4 days followed by 2 g over 3 days). Adverse events were recorded in a patient diary. On day 7, anal pain and bleeding were assessed (visual analog scale [VAS] and Dimitroulopoulos scale, respectively). RESULTS: Patients (162) were randomized to MPFF 1000 mg (79) and MPFF 500 mg (83). No serious adverse events (AEs) occurred; 10 emergent AEs were considered treatment-related (6 for MPFF 1000 mg and 4 for 500 mg). Both regimens were associated with significant reduction in anal pain (VAS); -2.37 cm MPFF 1000 mg (P < 0.001) and -2.17 cm 500 mg (P < 0.001), with a slight trend in favor of MPFF 1000 mg (mean global reduction -2.27 cm, P < 0.001). Bleeding improved significantly in both groups of patients, 56% of patients on MPFF 1000 mg versus 61% on MPFF 500 mg. Bleeding ceased after treatment in 47% patients on MPFF 1000 mg versus 54% on 500 mg. CONCLUSION: After 7 days of treatment with MPFF at the same daily dose, both regimens reduced anal pain and bleeding. MPFF 1000 mg had a comparable safety profile to MPFF 500 mg, with the advantage of fewer tablets. Key limitations: Safety study.

[Long-term results of formation of smooth muscle sphincter in the perineal colostomy area in patients after rectal extirpation]. / Otdalennye rezul'taty formirovaniia gladkomyshechnogo zhoma v oblasti promezhnostnoi kolostomy u bol'nykh posle ékstirpatsii priamoi kishki.

The authors discuss an original method for formation of a smooth-muscle cuff from the wall of a pulled-through colon in the region of a perineal colostoma. It was applied in 89 patients who had undergone extirpation of the rectum for malignant neoplasms. The smooth-muscle sphincter was formed during removal of the rectum in 72 patients and no earlier than 2 years after the extirpation in 17 patients. Inflammatory complications developed in the region of the perineal colostoa in the early postoperative period in 13.5% of cases. They were due to necrosis of the distal part of the pulled-through intestine in 3.4% of cases. There were no fatal outcomes. The late-term results were studied in follow-up periods of up to 7.5 years. Satisfactory functional results were produced in 83% of the patients. Physiological examination showed the presence of a functioning sphincter in the region of the perineal colostoma.

[Laparoscopic rectum repair]. / Laparoskopicheskaia rektopeksiia.

A reliable and simple method of allograft fixation in laparoscopic posterior-loop rectopexy (LPR) was developed. The study was carried out on 40 cadavers, peak effort of separation of the net fixed to the sacrum by various methods was evaluated. Effort of separation in fixation of the net by sutures was 10.1 +/- 2.12 kg, in fixation by hernial stapler--1.13 +/- 0.36 kg, stapler "Pro-Tack"--6.38 +/- 1.85 kg, in fixation of the net by the new device--8.9 +/- 0.75 kg. From 1995 till 1999 LPR was performed with the new device in 15 patients, the open posterior-loop rectopexy (OPR) with fixation of the net by non-absorbable sutures--in 16 patients. In LPR intraoperative blood flow was twice as small (146.0 +/- 79.2 ml) as in OPR (275.6 +/- 76.9 ml). Mean time of LPR was 183.1 +/- 69.8 min, OPR--211.3 +/- 57.9 min. Relief of pain after LPR enabled with reduction of narcotic analgetics requirement (58.3 +/- 1.5 mg). Mean dose of narcotic analgetics after OPR was 93.2 +/- 1.4 mg. The proposed method of allograft fixation and device for it realization are effective and meet all requirements.

[Laparoscopic surgery of rectal cancer (comparative results of laparoscopic and open abdominal resection)]. / Laparoskopicheskie operatsii u bol'nykh rakom priamoi kishki (sravnitel'nye rezul'taty laparoskopicheskikh i otkrytykh perednikh rezektsii).

Attempt to perform surgery with laparoscopic technologies was taken in 80 (50.6%) from 158 patients with cancer of the rectum. Surgery was finished only with laparoscopy in 64 (80.0%) cases, conversion to open operation was necessary in 16 (20.0%). Open anterior surgery was performed in 78 patients. Patients after laparoscopic operations required less narcotic analgesics (63.3 +/- 1.5 and 105.0 +/- 2.2 mg, respectively) and demonstrated earlier restoration of peristalsis (31.7 +/- 1.2 hours and 59.4 +/- 1.7 hours, respectively). Rate of complications after laparoscopic surgeries was 9.4%, after open--25.6%. Three-year survival after laparoscopic anterior resection was 91.7%, after open--84.6%. Survival of patients depends of depth of invasion into intestinal loop and lesion of lymphatic nodes, irrespective of surgical method.

Epithelial-mesenchymal transition and somatic alteration in colorectal cancer with and without peritoneal carcinomatosis.

Colorectal cancer is highly metastatic even when the tumors are small. To disseminate, cells use a complex and multistage process known as the epithelial-mesenchymal transition, in which epithelial phenotype is transformed into mesenchymal phenotype. The objective of this study is to describe the epithelial-mesenchymal transition in terms of gene expression profile and somatic alterations in samples of colorectal cancer with or without peritoneal carcinomatosis. We analyzed samples taken from 38 patients with colorectal cancer (stages II-IV) and samples from 20 patients with colorectal cancer complicated by peritoneal carcinomatosis. The expression of ZEB1, ZEB2, CDH1, VIM, and SNAI1 was analyzed by real-time PCR. KRAS/BRAF mutations were mapped using sequencing. Microsatellite instability was evaluated by fragment analysis. Epithelial-mesenchymal transition was detected in 6 out of 38 samples of colorectal cancer (stages II-IV), 7 out of 20 tumors from patients with peritoneal carcinomatosis, and 19 out of 20 samples taken from carcinomatous nodules. Tumors of the mesenchymal subtype displayed high frequency of somatic mutations, microsatellite stability, and low degree of differentiation. The identification of epithelial-mesenchymal transition may be used as a marker of high metastatic potential, which is particularly relevant at early stages of tumor growth.