Insights into treatment of complex Crohn's perianal fistulas.

Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition.

MRI Tumor Regression Grade Combined with T2-Weighted Volumetry May Predict Histopathological Response in Locally Advanced Rectal Cancer following Neoadjuvant Chemoradiotherapy-A New Scoring System Proposal.

Modern studies focus on the discovery of innovative methods to improve the value of post-treatment magnetic resonance imaging (MRI) in the prediction of pathological responses to preoperative neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). The aim of this study was to assess the potential benefits of combining magnetic resonance tumor regression grade (mrTRG) with T2-weighted volumetry in the prediction of pathological responses to nCRT in LARC. This was a cohort study conducted on patients with histopathologically confirmed LARC in a period from 2020 to 2022. After histopathological verification, all patients underwent initial MRI studies, while the follow-up MRI was performed after nCRT. Tumor characteristics, MRI estimated tumor regression grade (mrTRG) and tumor volumetry were evaluated both initially and at follow-up. All patients were classified into responders and non-responders according to pathological tumor regression grade (pTRG) and mrTRG. A total of 71 patients, mostly male (66.2%) were included in the study. The median tumor volume reduction rate was significantly higher in nCRT-responders compared to non-responders (79.9% vs. 63.3%) (p = 0.003). Based on ROC analysis, optimal cut-off value for tumor volume reduction rate was determined with an area under the curve (AUC) value of 0.724 (p = 0.003). Using the tumor volume reduction rate ≥75% with the addition of response to nCRT according to mrTRG, a new scoring system for prediction of pTRG to preoperative nCRT in LARC was developed. Diagnostic performance of prediction score was tested and the sensitivity, PPV, specificity, and NPV were 81.8%, 56.3%, 71.4%, and 89.7%, respectively. The combination of mrTRG and T2-weighted volumetry increases the MRI-based prediction of pTRG to preoperative nCRT in LARC. The proposed scoring system could aid in distinguishing responders to nCRT, as these patients could benefit from organ-preserving treatment and a "watch and wait" strategy.

Analysis of the Prognostic Potential of Schlafen 11, Programmed Death Ligand 1, and Redox Status in Colorectal Cancer Patients.

The Schlafen 11 (SLFN11) protein has recently emerged as pivotal in DNA damage conditions, with predictive potential for tumor response to cytotoxic chemotherapies. Recent discoveries also showed that the programmed death ligand 1 (PD-L1) protein can be found on malignant cells, providing an immune evasion mechanism exploited by different tumors. Additionally, excessive generation of free radicals, redox imbalance, and consequential DNA damage can affect intestinal cell homeostasis and lead to neoplastic transformation. Therefore, our study aimed to investigate the significance of SLFN11 and PD-L1 proteins and redox status parameters as prognostic biomarkers in CRC patients. This study included a total of 155 CRC patients. SLFN11 and PD-L1 serum levels were measured with ELISA and evaluated based on redox status parameters, sociodemographic and clinical characteristics, and survival. The following redox status parameters were investigated: spectrophotometrically measured superoxide dismutase (SOD), sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), and superoxide anion (O2•-). The prooxidative score, antioxidative score, and OXY-SCORE were also calculated. The results showed significantly shorter survival in patients with higher OXY-SCOREs and higher levels of serum SLFN11, while only histopathology-analysis-related factors showed significant prognostic value. OXY-SCORE and SLFN11 levels may harbor prognostic potential in CRC patients.

Application of nanofat for treatment of traumatic faecal incontinence after sphincteroplasty - A pilot study.

AIM: The aim of this study was to investigate whether the application of nanofat containing stem cells improves continence in women who had previously undergone anal sphincteroplasty with unsatisfactory long-term outcomes. METHOD: This prospective pilot study included nine women with various degrees of anal incontinence who had previously undergone anal sphincteroplasty due to obstetric trauma. In all patients, the Wexner Incontinence Score (WS) and Faecal Incontinence Quality of Life Score (FIQLS), as well as anal manometry and endoanal ultrasound measurements, were performed before the procedure and during follow-up. In all patients, liposuction was performed and 50 ml of raw lipoaspirate was obtained and processed using a NanoFat Kit device. Approximately 20 ml of the mechanically emulsified and filtrated fat was obtained and the anal sphincter complex was infiltrated with it. Patient follow-up was conducted in person or via telephone 6 and 12 months after the procedure. RESULTS: The squeeze pressure was significantly increased 6 months after the procedure (p = 0.01). The external anal sphincter measured at the 12 o'clock position was significantly thicker (p = 0.04). A significant decrease in the WS was observed both 6 and 12 months after the procedure compared with baseline values (p < 0.05 for both). CONCLUSION: This study is the first to show that the application of nanofat as an injectable product improves continence in patients with unsatisfactory results after sphincteroplasty, suggesting it to be a promising and effective therapeutic tool. The procedure is safe and can be easily performed as an ambulatory procedure.

Current trends in clinical genetics of colorectal cancer.

Recent innovations in molecular biology and colorectal cancer (CRC) genetics have facilitated the understanding of the pathogenesis of sporadic and hereditary CRC syndromes. The development of technology has enabled data collection for a number of genetic factors, which lead to understanding of the molecular mechanisms underlying CRC. The incidence and the nature of CRC is a mixture of genetic and environmental factors. The current field of interest is to understand how molecular basis could shape predisposition for developing CRC, disease progression and response to chemotherapy. In this article, we summarize new and developing genetic markers, and assess their clinical value for inherited and sporadic CRC.

Organized colorectal cancer screening in Serbia - the first round within 2013-2014.

Background/Aim: The National Organized Colorectal Cancer Screening Program was conducted in the Republic of Serbia during 2013-2014 covering the population of both genders, aged 50 to 74 years, in 28 municipalities out of 180, with the target population of 651,445 people. This organized colorectal cancer screening aims to reduce mortality from colorectal cancer in the target population. The aim of this study was to show the results of organized screening for colorectal cancer during the first biannual round in Serbia. Methods: General practitioners from the primary health centers, invited target population by letters and by phone to perform immunochemical fecal occult blood test. Persons with a positive test results were referred to the colonoscopy. The database of health insurance and other citizens of the target population was used for invitation for screening in primary health centers. Descriptive statistical analysis of the results in organized colorectal cancer screening in the first round was performed for the key screening indicators. Results: In the first round, a total of 99,592 persons were invited. The participation rate was 62.5%. Colonoscopy was performed in 1,554 persons. Adenomas were found in 586 persons (0.9% of all the tested), e.g. 37.7 % of all colonoscopied. In 129 persons colorectal cancer was diagnosed (0.2% of all the tested), e.g. 8.3% of all the colonoscopied. In the left half of the colon (rectum, sigmoid and descending colon) there were 70.4% diagnosed polyps and 77.3% carcinomas, while 29.6% of polyps and 22.7% carcinomas were found in the proximal parts of the colon. Conclusion: In the first round of the organized colorectal cancer screening in Serbia the participation rate of the targeted population was high and gave encouraging result. It was expected that in the forthcoming rounds even higher coverage of the target population would be accomplished. A positive predictive value of the completed colonoscopies showed that further work on observing the stages of diagnosed adenomas and carcinomas would reach the goals of the expected improvement in early detection of colorectal cancer in Serbia.

The sentinel lymph node (SLN) significance in colorectal cancer: methods and results. General report.

Colorectal cancer appears to be one of the most important malignancies in the world, with a survival rate depending on the TNM stage. The presence of lymph nodes metastasis indicates the necessity of adjuvant chemotherapy but exact classification of the N stage requires at least 12 lymph nodes to be pathologically examined. The sentinel lymph node (SLN) is considered to be the closest lymph node to the tumor, bearing the highest risk of malignant cells colonization. The main advantage of the sentinel lymph node mapping in colorectal cancer is identification and separate pathological examination of the nodes carrying the highest risk of metastasis. There are still open questions regarding the best method for sentinel lymph node mapping (in vivo or ex vivo), the factors influencing it, which substance is better for identification and which are the best histological methods and markers to be used. Numerous studies have discussed the quality and applicability of the method, but the importance of the SLN in colorectal carcinoma remains an open issue.

Comparison of functional outcome of colonic J-pouch and latero-terminal anastomosis in low anterior resection for rectal cancer.

INTRODUCTION: Functional results after low anterior resection for rectal cancer are an issue of increasing attention among colorectal surgeons and others interested in this subject. The consensus on ideal reconstruction type has not been achieved to date, although the number of papers on this subject has been published in recent years. OBJECTIVE: We conducted a prospective, parallel group study comparing latero-terminal with colonic J-pouch anastomosis in terms of defecatory function in patients undergoing stapled low colorectal/ coloanal anastomosis. METHODS: A total of 80 patients were included in this study with either latero-terminal or colonic J-pouch anastomosis. Defecatory function was evaluated using the modified version of MSKCC questionnaire 6, 12 and 24 months after the operation. Fecal continence was evaluated using the Wexner continence score. RESULTS: In both groups, trend towards improvement was registered in all measured variables in all three control intervals. This can apply to bowel frequency, urgency, night soiling, fragmentation and incomplete evacuation. However, the difference was not statistically significant, and when reviewing the trend of results we can note that in the J-pouch group steady state has not been reached even after 24 month control. CONCLUSION: This trial did not reveal any significant differences in defecatory function 6, 12 and 24 months after low anterior resection (LAR) between patients with a latero-terminal anastomosis and those with colonic J-pouch anastomosis. Our results did not confirm superiority of colonic J-pouch over the latero-terminal anastomosis

Adynamic and dynamic muscle transposition techniques for anal incontinence.

Gracilis muscle transposition is well established in general surgery and has been the main muscle transposition technique for anal incontinence. Dynamization, through a schedule of continuous electrical stimulation, converts the fatigue-prone muscle fibres to a tonic fatigue-resistant morphology with acceptable results in those cases where there is limited sphincter muscle mass. The differences between gluteoplasty and graciloplasty, as well as the techniques and complications of both procedures, are outlined in this review. Overall, these techniques are rarely carried out in specialized units with experience, as there is a high revision and explantation rate.

Use of vacuum-assisted closure device in a disastrous form of abdominal sepsis and stoma site infection: systematic review and report of a case.

Use of Vacuum-Assisted Closure (VAC) for treatment of open abdomen has been established predominantly in cases of severe abdominal trauma, resulting with high percentage of primary fascial closure. The role of VAC technique in cases of severe diffuse peritonitis is not definitely incorrigible. However, in cases of severe complicated abdominal sepsis VAC come up as a last resort.

Primary repair of colon injuries: clinical study of nonselective approach.

BACKGROUND: This study was designed to determine the role of primary repair and to investigate the possibility of expanding indications for primary repair of colon injuries using nonselective approach. METHODS: Two groups of patients were analyzed. Retrospective (RS) group included 30 patients managed by primary repair or two stage surgical procedure according to criteria published by Stone (S/F) and Flint (Fl). In this group 18 patients were managed by primary repair. Prospective (PR) group included 33 patients with primary repair as a first choice procedure. In this group, primary repair was performed in 30 cases. RESULTS: Groups were comparable regarding age, sex, and indexes of trauma severity. Time between injury and surgery was shorter in PR group, (1.3 vs. 3.1 hours). Stab wounds were more frequent in PR group (9:2), and iatrogenic lesions in RS group (6:2). Associated injuries were similar, as well as segmental distribution of colon injuries. S/F criteria and Flint grading were similar.In RS group 15 primary repairs were successful, while in two cases relaparotomy and colostomy was performed due to anastomotic leakage. One patient died. In PR group, 25 primary repairs were successful, with 2 immediate and 3 postoperative (7-10 days) deaths, with no evidence of anastomotic leakage. CONCLUSIONS: Results of this study justify more liberal use of primary repair in early management of colon injuries. TRIAL REGISTRATION: Current Controlled Trials ISRCTN94682396.

Endoanal ultrasound evaluation of anorectal diseases and disorders: technique, indications, results and limitations.

Imaging of the rectum, anorectal junction and surrounding tissues is both difficult and technically challenging. CT and conventional barium studies offer limited information in local staging of rectal and perirectal neoplasms, anal carcinomas and extension perianal fistulas in patients with inflamamatory bowel disease, or in evaluating patients with fecal incontinence. During past decade, sonography and MR imaging have resulted in significant improvement in the imaging of rectal and perirectal and anal and perianal disease. The aim of this article is to review possibility of the EAUS in the evaluation both normal anal anatomy and anorectal disease and disorders (anal carcinoma, sphincter defects, anal fistulas, perianal abscesses and other pathological conditions).

Perineal endometriosis in episiotomy scar with anal sphincter involvement: report of two cases and review of the literature.

Perineal endometriosis with anal sphincter involvement is a rare occurrence with only nine cases reported so far. Two such cases are presented, and the literature is reviewed. In presented cases, diagnosis was suspected at clinical exam. Anal manometry was performed in both cases and endoanal ultrasound in one case. Wide surgical excision of endometriotic mass together with part of external anal sphincter was carried out in both cases. The procedure was followed by anal sphincter reconstruction in an "overlapping" fashion in the first and "apposition" technique in the second case. Histopathologic tests confirmed endometriosis. The recovery was uneventful in both cases with excellent functional results. Two years after the operation, patients are asymptomatic and fully continent. According to the literature and our own experience, wide excision of endometrioma with primary sphincteroplasty seems to be the best chance of cure with satisfactory functional results and should be recommended.

Outcome of overlapping anal sphincter repair after 3 months and after a mean of 80 months.

BACKGROUND: The aim of this study was to determine the functional results of anal sphincter repair after a long follow-up (mean 80.1 months). METHODS: In the period 1990-2002, 65 sphincter repairs were performed. Obstetric trauma was the cause of incontinence in 72.3% cases, fistulotomy in 13.8%, nonspecific trauma in 9.2%, and war injury in 4.6%. At the time of surgery, 12 patients had undergone an urgent stoma procedure. In all cases, anal manometry, electromyography, and defecography were performed. The severity of incontinence was evaluated preoperatively using the Wexner score system. Anterior sphincteroplasty was performed in 52 cases, lateral in 9 cases, and posterior in 4 cases. RESULTS: The results were determined according to the Wexner score system and the Browning-Parks scale. The Wexner score was calculated 3 months after operation and during every follow-up visit. Preoperative scores and those at the first and last follow-up visits were analyzed. Three months after operation excellent results were achieved in 55.5%, good in 18.5%, fair in 16.9%, and poor in 9.2% patients. After follow-up (mean 80.1 months), 26.8% had excellent results, 21.4% had good results, 12.5% had fair results, and 39.3% of patients had a poor outcome. Results determined by the Wexner score system improved from 17.8 preoperatively to 3.6 three months after operation, but deteriorated over time to 6.3 after longer follow-up (p<0.001). CONCLUSION: Overlapping sphincter repair provides satisfactory results in more than two-thirds of patients initially, but the results tend to worsen over time and are satisfactory in half of patients after longer follow-up.

Adenosquamous carcinoma arising within a retrorectal tailgut cyst: report of a case.

Retrorectal, developmental tail gut cysts, include dermoid cysts, rectal duplication cysts and retrorectal cyst-hamartomas. Retrorectal cyst-hamartomas (RCH) are derived from remnants of the tail gut, the most caudal part of the embryonic hind gut, which normally involutes by the 8(th) wk of embryonic development (3-8 mm stage). They have specific radiological and histopathological features that distinguish them from other similar formations (dermoid cysts, enteric duplication cysts and teratomas). We report a patient with adenosquamous carcinoma arising within RCH, who underwent complete resection of the cyst through anterior laparotomy, and reached complete (recurrence-free for 14 mo, so far) functional recovery. The cyst was incidentally discovered during hysterectomy 12 years ago. Diagnostic, therapeutic and histopathological aspects of this rare case are discussed. The mentioned period between diagnosis and surgical treatment suggests that RCH, given enough time, can develop malignant degeneration, and should be resected at the time of diagnosis.

[Long-term results of treatment of injuries of the sectoral and segmental bile ducts]. / Udaljeni rezultati lecenja povreda sektorskih i segmentalnih zucnih vodova.

INTRODUCTION: Surgically important variations of the sectoral and segmental bile ducts of the right lobe of the liver appear in a significant proportion of patients. Frequency of the injuries to these ducts is not known as the ligature of small ducts may pass without major consequences. MATERIAL AND METHODS: Over a 27 year period (1. Jan 1974-31. Dec 2001) along with 168 patients with benign biliary strictures of type I, II, III and IV according to Bismuth's classification, we treated 13 patients with operative sectoral or segmental bile duct injuries, four patients from our institution and nine patients transferred from elsewhere. The injury was recognized at original surgery in all four patients operated in our institution. Primary repair was performed in three patients, in two patients direct end-to-end repair over T-tube and in one patient with anastomosis between the injured duct and Roux-en-Y jejunal limb, while in one patient the injured duct was ligated. In no one of nine patients transferred from elsewhere the injury was recognized during original surgery. Four patients were sent with biliary peritonitis, another four patients with external biliary fistula and one patient for pain and fever due to liver abscess. RESULTS: All three patients in whom the primary repair was performed had a quick and uneventful recovery and they stayed symptom-free so far. The patient in whom the injured duct was ligated died after series of complications. Four patient sent to us with biliary peritonitis were treated with relaparotomy, lavage and drainage and all developed external biliary fistula. Three of these patients had their fistula ceased spontaneously within few weeks, while in one patient the fistula didn't show signs of ceasing so that injured duct had to be anastomosed with Roux-en-Y jejunal limb. Two out of four patients sent for external biliary fistula had it ceased spontaneously, while in two patients anastomosis between duct and Roux-en-Y jejunal limb was necessary. The last, 13th patient, who had sectoral duct severed and ligated was reoperated, liver abscess drained and duct anastomosed with Roux-en-Y jejunal limb. That patient developed an anastomotic stricture a year later and he was successfully reoperated and stayed symptom-free so far. All 12 patients have been followed up from nine months to 27 years (average 9.2 years) and neither developed biliary symptoms. CONCLUSION: We conclude that the management of these injuries depends upon the time of recognition of the lesion, size of the injured duct and of the type and stage of complications.