[Stem Cell Therapy for Complex Anal Fistula in Crohn`s Disease: Current Evidence and Future Perspectives]. / Stammzelltherapie bei komplexen perianalen Fisteln bei Morbus Crohn: Aktuelle Evidenz und Ausblick.

Despite progress in multidisciplinary diagnostic and therapeutic strategies, complex anal fistulas associated with Crohn's disease remain a challenge for both medical and surgical management. Conventional surgical techniques such as flap procedures or LIFT are still associated with considerable persistence and recurrence rates. Based on this background, results of stem cell therapy for Crohn's anal fistula have shown promising results and are a sphincter-preserving technique. In particular, adipose-derived, allogeneic stem cell therapy (Darvadstrocel) has shown encouraging healing rates within the randomised controlled ADMIRE-CD trial, which were reproducible in "real world" data of limited clinical studies. The current evidence has led to the integration of allogeneic stem cell therapy into international guidelines. To date, the definitive status of allogeneic stem cells in the multidisciplinary treatment algorithm for complex anal fistulas associated with Crohn's disease cannot be evaluated.

Management of Third and Fourth-Degree Perineal Tears After Vaginal Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/079, December 2020).

Purpose This guideline provides recommendations for the diagnosis, treatment and follow-up care of 3rd and 4th degree perineal tears which occur during vaginal birth. The aim is to improve the management of 3rd and 4th degree perineal tears and reduce the immediate and long-term damage. The guideline is intended for midwives, obstetricians and physicians involved in caring for high-grade perineal tears. Methods A selective search of the literature was carried out. Consensus about the recommendations and statements was achieved as part of a structured process during a consensus conference with neutral moderation. Recommendations After every vaginal birth, a careful inspection and/or palpation by the obstetrician and/or the midwife must be carried out to exclude a 3rd or 4th degree perineal tear. Vaginal and anorectal palpation is essential to assess the extent of birth trauma. The surgical team must also include a specialist physician with the appropriate expertise (preferably an obstetrician or a gynecologist or a specialist for coloproctology) who must be on call. In exceptional cases, treatment may also be delayed for up to 12 hours postpartum to ensure that a specialist is available to treat the individual layers affected by trauma. As neither the end-to-end technique nor the overlapping technique have been found to offer better results for the management of tears of the external anal sphincter, the surgeon must use the method with which he/she is most familiar. Creation of a bowel stoma during primary management of a perineal tear is not indicated. Daily cleaning of the area under running water is recommended, particularly after bowel movements. Cleaning may be carried out either by rinsing or alternate cold and warm water douches. Therapy should also include the postoperative use of laxatives over a period of at least 2 weeks. The patient must be informed about the impact of the injury on subsequent births as well as the possibility of anal incontinence.

Stem cell injection for complex anal fistula in Crohn's disease: A single-center experience.

BACKGROUND: Despite tremendous progress in medical therapy and optimization of surgical strategies, considerable failure rates after surgery for complex anal fistula in Crohn's disease have been reported. Therefore, stem cell therapy for the treatment of complex perianal fistula can be an innovative option with potential long-term healing. AIM: To evaluate the results of local administration of allogenic, adipose-derived mesenchymal stem cells (darvadstrocel) for complex anal Crohn's fistula. METHODS: All patients with complex anal fistulas associated with Crohn's disease who were amenable for definite fistula closure within a defined observation period were potential candidates for stem cell injection (darvadstrocel) if at least one conventional or surgical attempt to close the fistula had failed. Darvadstrocel was only indicated in patients without active Crohn's disease and without presence of anorectal abscess. Local injection of darvadstrocel was performed as a standardized procedure under general anesthesia including single-shot antibiotic prophylaxis, removal of seton drainage, fistula curettage, closure of the internal openings and local stem cell injection. Data collection focusing on healing rates, occurrence of abscess and follow-up was performed on a regular basis of quality control and patient care. Data were retrospectively analyzed. RESULTS: Between July 2018 and January 2021, 12 patients (6 females, 6 males) with a mean age of 42.5 (range: 26-61) years underwent stem cell therapy. All patients had a minimum of one complex fistula, including patients with two complex fistulas in 58.3% (7/12). Two of the 12 patients had horse-shoe fistula and 3 had one complex fistula. According to Parks classification, the majority of fistulas were transsphincteric (76%) or suprasphincteric (14%). All patients underwent removal of seton, fistula curettage, transanal closure of internal opening by suture (11/12) or mucosal flap (1/12) and stem cell injection. At a mean follow-up of 14.3 (range: 3-30) mo, a healing rate was documented in 66.7% (8/12); mean duration to achieve healing was 12 (range: 6-30) wk. Within follow-up, 4 patients required reoperation due to perianal abscess (33.3%). Focusing on patients with a minimum follow-up of 12 mo (6/12) or 24 mo (4/12), long-term healing rates were 66.7% (4/6) and 50.0% (2/4), respectively. CONCLUSION: Data of this single-center experience are promising but limited due to the small number of patients and the retrospective analysis.

[Obstructed Defecation Syndrome: Aetiology, Diagnostic Assessment and Therapeutic Options]. / Obstruktives Defäkationssyndrom: Ätiologie, Diagnostik und Therapieoptionen.

Obstructed defecation syndrome (ODS) is characterized by disturbed defecation, and morphological disorders can be differentiated from functional pathologies. Differential diagnosis from irritable bowel syndrome and slow transit constipation is frequently difficult. Most patients are female, and rectal intussusception and anterior rectocele are frequent morphological pathologies. In addition to patients' history and basic proctological diagnostic testing, MR defecography plays a central role. As ODS is a benign condition, conservative treatment should be initiated primarily. After failure of conservative treatment and in terms of a morphological disorder, the indication for surgery should be discussed, whereas transabdominal procedures (e.g. resection rectopexy, rectopexy) and transanal procedures (e.g. STARR) are available. Adequate therapy remains a challenge due to multifactorial aetiology and the variety of symptoms - this affects both conservative and surgical treatment options.

[Preliminary Results of Transperineal Ligation of Fistula Tract for Rectovaginal Fistulas]. / Erste Ergebnisse der transperinealen Ligatur des Fisteltrakts bei rektovaginalen Fisteln.

BACKGROUND: Despite a variety of surgical procedures for rectovaginal fistulas, surgical therapy remains a considerable challenge. Therefore, it was the aim of this prospective study to evaluate preliminary results of an innovative technique. METHODS: Surgical transperineal ligation of the fistula tract was performed without any fistulectomy or sphincter reconstruction. Only lower rectovaginal fistulas were selected for this technique. Standardised inclusion and exclusion criteria were defined. RESULTS: Within a 16-month period, 7 female patients with lower rectovaginal fistulas were treated by transperineal ligation of the fistula tract in two centres. Rectovaginal fistulas were associated with iatrogenic obstetric trauma, following Bartholin infection, and with Crohn's disease. In all cases, rectovaginal fistulas could be identified and treated by ligation of the fistula tract. Neither intra- nor postoperative complications were documented. Only one operation was performed under fecal diversion. After a mean follow-up of 9 months, fistula healing was observed in 4 of 7 patients (success rate 57%). CONCLUSION: Preliminary results of transperineal ligation of the fistula tract for rectovaginal fistulas seem to be promising. However, further experience, larger series and long-term follow-up have to be provided to objectively assess this innovative technique.

German S3 guidelines: anal abscess and fistula (second revised version).

BACKGROUND: The incidence of anal abscess and fistula is relatively high, and the condition is most common in young men. METHODS: This is a revised version of the German S3 guidelines first published in 2011. It is based on a systematic review of pertinent literature. RESULTS: Cryptoglandular abscesses and fistulas usually originate in the proctodeal glands of the intersphincteric space. Classification depends on their relation to the anal sphincter. Patient history and clinical examination are diagnostically sufficient in order to establish the indication for surgery. Further examinations (endosonography, MRI) should be considered in complex abscesses or fistulas. The goal of surgery for an abscess is thorough drainage of the focus of infection while preserving the sphincter muscles. The risk of abscess recurrence or secondary fistula formation is low overall. However, they may result from insufficient drainage. Primary fistulotomy should only be performed in case of superficial fistulas. Moreover, it should be done by experienced surgeons. In case of unclear findings or high fistulas, repair should take place in a second procedure. Anal fistulas can be treated only by surgical intervention with one of the following operations: laying open, seton drainage, plastic surgical reconstruction with suturing of the sphincter (flap, sphincter repair, LIFT), and occlusion with biomaterials. Only superficial fistulas should be laid open. The risk of postoperative incontinence is directly related to the thickness of the sphincter muscle that is divided. All high anal fistulas should be treated with a sphincter-saving procedure. The various plastic surgical reconstructive procedures all yield roughly the same results. Occlusion with biomaterial results in lower cure rate. CONCLUSION: In this revision of the German S3 guidelines, instructions for diagnosis and treatment of anal abscess and fistula are described based on a review of current literature.

Quality of life and functional results of submucosal injection therapy using dextranomer hyaluronic acid for fecal incontinence.

BACKGROUND AND AIM: The aim of this prospective study was to analyze safety and functional outcome of transanal submucosal injection of dextranomer hyaluronic acid ("bulking agents therapy") in patients with passive fecal incontinence. METHODS: All patients who underwent transanal injection therapy were prospectively enrolled in this study. Inclusion criteria included fecal incontinence (internal anal sphincter dysfunction) after failed conservative treatment. The procedure was performed in a standardized technique, including submucosal injection of 4 × 1 mL dextranomer hyaluronic acid 5 mm above the dentate line. The primary endpoint focused on symptom improvement provided as the change in incontinence status and quality of life using validated scores (Wexner incontinence score, symptom-specific Fecal Incontinence Quality of Life [FIQoL] scale, and generic EQ-5D-Visual Analogue Scale [EQ-5D-VAS]). RESULTS: Within the observation period (July 2007 to May 2009), a total of 21 patients (17 women) with passive fecal incontinence were treated. Neither morbidity nor adverse events were documented. Three months postoperatively, 61.1% (11/18) showed significant improvement of symptoms (reduction of incontinence episodes and soiling), which was sustained after 20 months in 55.6% (10/18). Wexner incontinence score decreased from 16.8 to 12.3 (P > .05). Significant improvement was documented for FIQoL and EQ-5D-VAS (P < .05). CONCLUSION: The current results indicate that injection therapy using hyaluronic acid is an innovative and minimally invasive procedure with no morbidity. Although Wexner incontinence score is not significantly influenced, a significant improvement in quality of life was observed in more than 50% of patients.

Assessing the safety, effectiveness, and quality of life after the STARR procedure for obstructed defecation: results of the German STARR registry.

BACKGROUND: Internal rectal prolapse and rectocele are frequent clinical findings in patients with obstructed defecation syndrome (ODS). However, there is still no evidence whether stapled transanal rectal resection (STARR) provides a safe and effective surgical option. Therefore, the German STARR registry was initiated to assess safety, effectiveness, and quality of life. METHODS: The German STARR registry was designed as an interventional, prospective, multicenter audit. Primary outcomes include safety (morbidity and adverse events), effectiveness (ODS, symptom severity, and incontinence scores), and quality of life (PAC-QoL and EQ-5D) documented at baseline and at 6 and 12 months. Statistical evaluation was performed by an independent research organization of clinical epidemiology. RESULTS: Complete data of 379 patients (78% females, mean age 57.8 years) were entered into the registry database. Mean operative time was 40 min, mean hospitalization was 5.5 days. A total of 103 complications and adverse events were reported in 80 patients (21.1%) including staple line complications (minor bleeding, infection, or partial dehiscence; 7.1%), major bleeding (2.9%), and postsurgical stenosis (2.1%). Comparisons of ODS and symptom severity scores (SSS) demonstrated a significant reduction in ODS score between baseline (mean 11.14) and 6 months (mean 6.43), which was maintained at 12 months (mean 6.45), and SSS at preoperative and at 6- and 12-month follow-up (13.02 vs. 7.34 vs. 6.59; paired t test, p < 0.001). Significant reduction in ODS symptoms was matched by an improvement in quality of life as judged by symptom-specific PAC-QoL and generic ED-5Q (utility and visual analog scale) scores and was not associated with an impairment of incontinence score following STARR (p > 0.05). However, 11 patients (2.9%) showed de novo incontinence, and new-onset symptoms of fecal urgency were observed in 25.3% of patients. CONCLUSION: These data indicate that STARR is a safe and effective procedure. However, conclusions are limited due to the selection and reporting bias of a registry. The problem of fecal urgency needs cautious reassessment.

Laparoscopic TME in rectal cancer--electronic supplementary: op-video.

BACKGROUND: Laparoscopic total mesorectal excision (TME) for rectal cancer has been proved in various studies. The minimal invasive procedure is feasible and safe which was demonstrated in many studies. However, the results of prospective, randomized studies providing valuable evidence are still not available. Compared to conventional surgery, the laparoscopic technique has short-term advantages including less pain, shorter duration of postoperative ileus, less fatigue, better pulmonary function, and less blood loss (Leung et al., Lancet 363:1187-1192, 2004; Braga et al., Dis Colon Rectum 48:217-223, 2005; Jayne et al., J Clin Oncol 25:3061-3068, 2007; Agha et al., Surg Endosc 22:2229-2237, 2008). METHODS: The autonomic nerve sparing TME technique is the gold standard in rectal cancer resection even in conventional or laparoscopic procedure. With regard of the oncological dimension, the laparoscopic TME technique is not different compared to the open procedure. However, a standardized laparoscopic step-by-step procedure may simplify the operation and can reduce operation time. RESULTS: There are no studies available which compare different types of TME procedures. Most surgeons start the operation left laterally mobilizing the sigmoid colon first. In the laparoscopic technique, we recommend the medial to lateral approach starting the operation at the right side of the rectum and sigmoid colon. A nerve sparing TME technique can be performed easier, and the identification of the left ureter may be simplified. After multiple workshops and extensive discussion with national and international experts, we developed a standardized laparoscopic "10 step TME procedure." Reviewing the results of laparoscopic TME the studies do not allow firm conclusions as to the questions of whether the safety and efficacy of laparoscopic TME is equal or superior to open TME (Breukink et al. 2006). Actually, we are waiting for large prospective randomized studies comparing laparoscopic TME with the traditional open procedure (Bonjer et al., Dan Med Bull 56:89-91, 2009). CONCLUSION: Laparoscopic TME appears to have clinically measurable short-term advantages in patients with primary resectable rectal cancer based on evidence mainly from nonrandomized studies (Breukink et al. 5). In nearly all published studies, the efficacy and technical feasibility of laparoscopic surgery for rectal cancer could be demonstrated regarding perioperative morbidity and oncological outcome. A standardized laparoscopic TME technique can be strongly recommended.

Preliminary results on efficacy in closure of transsphincteric and rectovaginal fistulas associated with Crohn's disease using new biomaterials.

BACKGROUND AND AIMS: It was the aim of this prospective study to analyze the efficacy of the Surgisis AFP anal fistula plug and the Surgisis mesh for the closure of complex fistulas in Crohn's disease. METHODS: All patients with perianal Crohn's disease suffering from transsphincteric and rectovaginal fistulas who underwent surgery using the Surgisis anal fistula plug or the Surgisis mesh were prospectively enrolled in this study. Inclusion criteria included transsphincteric single-tract fistulas and rectovaginal fistulas. Surgery was performed using a standardized technique, including irrigation of the fistula tract, placement and internal fixation of the Surgisis anal fistula plug, and combined transanal/transvaginal excision of rectovaginal fistula with transvaginal placement of the mesh. Success was defined as closure of both internal and external (perianal or vaginal) openings, absence of drainage without further intervention, and absence of abscess formation. Follow-up information was obtained from clinical examination 3, 6, 9, and 12 months postoperatively. RESULTS: Within the observation period, a total of 16 procedures were performed. After a mean follow-up of 9 months and 1 patient lost to follow-up, the overall success rate was 75%. For transsphincteric fistulas, the success rate was 77%, whereas it was 66% in rectovaginal fistulas associated with Crohn's disease. All 4 patients with failure had reoperation. Rate of stoma reversal in those patients who had fecal diversion was 66%. No deterioration of continence was documented. CONCLUSION: The short-term success rates are promising. Further analysis is needed to explain the definite role of this technique in comparison with traditional surgical techniques.

Decision-making algorithm for the STARR procedure in obstructed defecation syndrome: position statement of the group of STARR Pioneers.

Internal rectal prolapse (rectal intussusception) and rectocele are frequent clinical findings in patients suffering from refractory constipation that may be best characterized as obstructive defecation syndrome. However, there is still no clear evidence whether the stapled transanal rectal resection (STARR) procedure provides a safe and effective surgical option for symptom resolution in patients with obstructive defecation syndrome, as evidence-based guidelines and functional long-term results are still missing. On the basis of the need for objective evaluation, a European group of experts was founded (Stapled Transanal Rectal Resection Pioneers). Derived from 2 meetings (October 26-28, 2006, Gouvieux, France and November 28-29, 2007, St Gallen, Switzerland) a concept for treatment options in patients suffering from obstructive defecation syndrome was developed, including a clear decision-making algorithm specifically focusing on the role of the stapled transanal rectal resection procedure based on clinical symptoms and dynamic imaging and inclusion and exclusion criteria for the stapled transanal rectal resection procedure.

Gracilis transposition for repair of recurrent anovaginal and rectovaginal fistulas in Crohn's disease.

OBJECTIVE: Local surgical procedures in the presence of Crohn's disease have a markedly reduced success rate, especially in the treatment of recurrent anovaginal and distant rectovaginal fistulas. In these patients, local surgery (e.g., flap closure) has unsatisfactory results if the anal canal is destroyed by ulceration and indurations or in patients with extensive defects of the perineum. MATERIALS AND METHODS: Over a period of 6 years (2000 to 2006), 12 patients with recurrent rectovaginal fistulas were treated with graciloplasty. The age of the female patients ranged from 24 to 47 years, the mean age being 38 years. The presence of Crohn's disease in all patients had a mean duration of 12 years. Corticosteroids, mesalazin, or azathioprin were administered preoperatively. All patients were diverted by a temporary ileostomy before graciloplasty. RESULTS Rectovaginal fistula was closed in 11 of 12 patients after graciloplasty with a mean follow-up of 3.4 years. One rerecurrence of a rectovaginal fistula was documented. One of 12 ileostomies was not closed due to persistence of the fistula tract. One patient had a pouch-anal and, additionally, a pouch-vaginal fistula. In this patient, the first transposition of the gracilis muscle was unsuccessful. After a few months, she underwent renewed graciloplasty. There was no recurrence of a fistula within the follow-up period. Reconstruction of the perineum constituted an additional positive effect of the graciloplasty. In one patient, the preexisting fecal incontinence persisted, even after secondary implantation of a pacemaker. Due to diarrhea and persistent fecal incontinence, the patient opted for a renewed ileostomy. CONCLUSIONS: In our series, gracilis transposition in the treatment of recurrent anovaginal and rectovaginal fistulas in patients with Crohn's disease has excellent short-term results. In addition, graciloplasty can reconstruct the perineal defect.

Radical surgery for early colorectal cancer--anachronism or oncologic necessity?

BACKGROUND AND AIMS: Because of their low morbidity and mortality, limited resection or local excision are accepted therapeutical approaches in early colorectal cancer treatment. Even though, recent publications report recurrence rates after local excision of rectal cancer in up to 30%. This prompted us to evaluate our data for T1N0 colorectal cancer treated by radical surgery regarding recurrence, morbidity, mortality, and survival rates. MATERIALS AND METHODS: Clinical, histopathological, and surveillance data from our prospective "colorectal cancer database" from 1979 to 2005 were analyzed to evaluate outcome and prognosis of T1N0 colorectal cancer treated by radical surgery. Only curative resections were included in this study. All patients were followed in an internal surveillance program, which enabled us to prospectively assess morbidity, mortality, and survival. RESULTS A total of 105 T1N0 colon and 69 rectal carcinomas were included in the study. Overall morbidity was 25% (colon) and 34% (rectum). Thirty-day mortality was 1.9% (colon) and 4.3% (rectum). After a median follow-up of 92 and 87 month, no isolated local recurrence occurred. One patient developed both local recurrence and liver metastases. Distant metastases were seen in 4.9% (colon) and 7.5% (rectum). The 5- and 10-year overall survival was 86 and 71% (colon) and 82 and 68% (rectum), respectively. CONCLUSION: Even if radical surgical approaches are associated with a higher rate of morbidity and mortality, our data show that radical surgery for T1N0 colorectal cancer results in excellent tumor control which is of paramount importance for the patients' prognosis and survival. Combining the data presented with those of the current literature suggests that local approaches to rectal cancer can be recommended for highly selected T1N0 tumors, in palliative situations, or if the patient is unfit for general surgery.