[The course and clinical manifestations of Peutz-Jeghers syndrome in the Russian population].

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the growth of hamartomatous polyps in the gastrointestinal tract, perioral pigmentation and an increased risk of malignant neoplasms. The syndrome is caused by a pathogenic variant in the STK11 gene. AIM: To assess the clinical picture and treatment of Russian patients with PJS. MATERIALS AND METHODS: A retrospective analysis of 30 patients from 25 families with an established diagnosis of PJS who were in the Ryzikh State Scientific Center for Coloproctology from 2011 to 2021 was carried out. All patients underwent instrumental examination, including esophagogastroduodenoscopy, colonoscopy, X-ray examination of the small intestine/CT-enterography, in the absence of invaginates - video capsule endoscopy, as well as molecular genetic examination for the presence of pathogenic variants in the STK11 gene. All removed polyps were subjected to the histological examination. RESULTS: The analysis of the clinical picture allowed us to establish the following data: the first complaints in patients were noted in childhood and adolescence, while the median age was 11 [7; 19] (0.5-24) years; pathogenic variants in the STK11 gene were identified in 26 (87%) cases, among which 10 were described for the first time; during the initial examination, polyps in the small intestine were detected in all 30 (100%) patients, in the stomach - in 23/30 (77%) patients, and in the colon - in 21/30 (70%); with an age, an increase in the number of polyps in all parts of the gastrointestinal tract was noted; before the diagnosis operations were performed urgently for intestinal obstruction; after the diagnosis of PJS, when polyps were detected in the gastrointestinal tract, endoscopic polypectomies were performed; if endoscopic removal of hamartomatous polyps was impossible, patients were operated as planned; malignant diseases of the predominantly reproductive system were detected in 8/30 (27%) patients. The median age of cancer detection was 52 [31; 52] (17-59) years. CONCLUSION: Russian patients with PJS have population-specific features in the clinical picture of the course of the disease, which dictates the need to develop their own recommendations for monitoring and treatment of such patients.

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.

[Recommendations for the Protocol of functional examination of the anorectal zone and disorders classification: the International Anorectal Physiology Working Group consensus and Russian real-world practice].

This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Aim to provide information about methods of diagnosis and new classification of functional anorectal disorders to a wide range of specialists general practitioners, therapists, gastroenterologists, coloproctologists all who face the manifestations of these diseases in everyday practice and determine the diagnostic and therapeutic algorithm. Current paper provides agreed statements of IAPWG Consensus and comments (in italics) of Russian experts on real-world practice, mainly on methodology of examination. These comments in no way intended to detract from the provisions agreed by the international group of experts. We hope that these comments will help to improve the quality of examination based on the systematization of local experience with the use of the methods discussed and the results obtained. Key recommendations: the International Anorectal Physiology Working Group protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.

Risk factors for postoperative ileus after colorectal cancer surgery.

AIM: To assess the rate and independent risk factors of postoperative ileus (POI) after colorectal cancer surgery. METHODS: Three hundred consecutive patients underwent colorectal surgery for cancer at the State Scientific Centre of coloproctology, Moscow, Russia, between November 2015 and August 2016. POI was diagnosed as an absence of intestinal function for 72 hours or more after operation and confirmed by plain radiography. Uni- and multivariate logistic regression of the tumour-, patient- and treatment-related factors was performed. All patients had epidural catheters with multimodal analgesia. RESULTS: Thirty-nine patients (13%) had postoperative ileus. The variables associated with this condition in univariate analysis were age < 64 y.o. (p = 0.02), male gender (p = 0.02), BMI ≥ 25 kg/m2 (p = 0.02), moderate drinking (p = 0.02), heavier drinking (p < 0.0001), opioids (p = 0.02), history of abdominal operation (p = 0.003), firm, extensive adhesions as a result of previous surgery (p = 0.005), multivisceral resection (p = 0.009), blood loss ≥ 150 mL (p = 0.006), haemotransfusion (p = 0.01) and open approach (p = 0.006). In the multivariate logistic regression, BMI ≥ 26 kg/m2 (p = 0.008), opioids (p = 0.04) history of abdominal operation (p = 0.04) and adhesions (p = 0.03) were identified as independent risk factors. CONCLUSION: Postoperative ileus is a common complication in colorectal surgery. The results of our study suggest at least two surgeon-dependent risk factors, i.e., open approach and opioids in the postoperative period. This article is protected by copyright. All rights reserved.

[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.

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.

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.

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.

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.

Intersphincteric resection with partial removal of external anal sphincter for low rectal cancer.

Abdominoperineal resection (APR) remains the standard procedure for rectal cancer located within 0.5 cm from dentate line (DL). In this study, we present a new type of restorative surgery: intersphincteric resection with partial removal of external anal sphincter (EAS) and anorectal reconstruction for-ultra low rectal cancer. Between March 2003 and May 2008 fifty patients (28 males, aged between 39 and 71) were operated on for ultra low rectal cancer uT2-3N0M0 with partial preservation of EAS and total anorectal reconstruction (smooth-muscle neosphincter and colonic pouch). A protective stoma was performed in all cases. Functional outcome and quality of life were recorded at 3, 6, 12, 18, 24 months after stoma closure using Wexner score and FIQL respectively. Anal manometry, vectrum volumetry and myography data were taken as well. Results. Postoperative complications developed in 2 patients, but no secondary surgery was required. Carcinomas were staged as pT2 (n = 14) and pT3 (n = 36). The distal clearance was 2.00.4 (range 1.5-2.8) cm, lateral clearance was 0.80.3 (range 0.2-1.4) cm. After a median follow-up of 24 (range 2-61) months, 2 local recurrences were occurred and salvaged by APR. Contractive activity of saved elements of EAS improved with a course of time and squeezing anal pressure increased as well. Perfect functional outcome was achieved in 25 of 34 patients at 12 months after stoma closure, and all the patients were satisfied with procedure. Good functional results of suggested surgery seems to be an acceptable alternative to APR with permanent stoma in selected patients.

Surgical treatment of benign, myomatous rectal tumors.

Between 1972 and 1990, 36 patients with leiomyoma of the rectum underwent surgery at the Proctology Institute (Moscow). There were 13 male (36.1 percent) and 23 female (63.9 percent) patients. Their median age was 52.1 years. Electroexcision of the tumors measuring below 1 cm was performed through the endoscope in 12 patients. Leiomyomas with a diameter of 2.5 to 5 cm were removed transanally in 10 patients. Six patients underwent excision of the tumor through the pararectal approach, whereas leiomyomas located in the rectovaginal wall were removed through the vagina in one patient. Abdominoperineal extirpation and abdominoanal resection of the rectum was performed in seven patients with tumors measuring from 8 to 20 cm. Recurrences were noted in nine patients after transanal, pararectal, or transvaginal excision of leiomyomas. In seven of them, malignant transformation of the tumor occurred at terms ranging from 9 months to 9.5 years.

Method of creation of a smooth-muscle cuff at the site of the perineal colostomy after extirpation of the rectum.

The authors present a method of creation of a smooth-muscle cuff at the site of the perineal colostomy in 36 patients who have undergone extirpation for malignant neoplasms of the low ampulla recti. Creation of the smooth-muscle sphincter mechanism was performed during the process of removal of the rectum in 29 patients, whereas it was done two to eight years after extirpation of the rectum in seven patients. Inflammatory complications were observed in the perineal colostomy area during the early postoperative period in eight patients. These complications were accounted for by necrosis of the distal colon and transplanted muscle in two patients. There were no deaths. Satisfactory functional results were seen in 22 of 26 patients six months after surgery. Physiologic studies show that there is a functioning sphincter at the site of the perineal colostomy.

Results of radical surgery for advanced rectal cancer.

During the period 1972 to 1987 inclusive, 313 multivisceral resections in advanced rectal cancer were performed, accounting for 10.3 percent of all radical surgical interventions for this disease. Of these resections, 71 were for distant metastases and 242 for tumor infiltration to adherent organs. The postoperative mortality was 5.4 percent, which was not significantly different from that in the total group of patients with rectal cancer (4.9 percent) operated upon during the same period. After multivisceral resections, 49.5 percent of patients developed postoperative complications. In the total group of patients with rectal cancer, the postoperative morbidity was 30.3 percent. Long-term results were assessed in 190 patients who had been operated upon more than five years ago. It has been established that 42.1 percent of patients lived more than five years after multivisceral resections. Hope is inspired by the fact that of 15 patients with hepatic metastases (26 percent) lived over five years following radical surgery. These data allow the conclusion that radical surgery for advanced rectal cancer is justifiable and advisable.

Treatment of patients with rectal cancer.

During a 20-year period (1965 to 1985), 4673 patients with rectal cancer underwent surgical treatment, with 3500 of them being subjected to radical surgery. Postoperative mortality was 6.1 percent. During the last five years, the mortality rate decreased dramatically down to 4.9 percent, despite an increase in the group of elderly patients (35.7 percent) and performance of a considerable percentage of simultaneous, extensive, and combined operations (33.7 percent). The trend of employing sphincter-saving operations (in more than 60 percent of patients, the anterior resection and abdominoanal resection with a pull-through were performed) accounts for the favorable five-year survival rate (62 to 69 percent) and results in a good functional outcome in 80 percent of patients. The use of a combination of conservative and operative methods of rehabilitation contributes to the professional readaptation of 75 to 80 percent of patients after surgery with construction of a stoma. In 223 cases, a Soviet magnetic occlusive device was implanted, while in 67 patients an artificial sphincter mechanism was constructed from the flap of the adductor longus femoris muscle. It should be emphasized that surgical methods of rehabilitation are used both in primary and reconstructive operations. The experience with management of 124 patients with recurrent cancer after resection and extirpation of the rectum shows that local excision or repeated resections of the rectum cure 20 to 29 percent of those operated on.