Mesenchymal stem cell therapy for therapy refractory complex Crohn's perianal fistulas: a case series.

BACKGROUND: Mesenchymal stem cell treatment (MST) has emerged as a new therapeutic strategy for Crohn's perianal fistulas. It has been demonstrated that a fibrotic tract on MRI with a MAGNIFI-CD score ≤ 6 is the best predictor for long-term clinical closure. Therefore, the aim of the current study was to analyse the effectiveness of MST for complex Crohn's perianal fistulas based on MRI. METHODS: Consecutive patients with complex Crohn's perianal fistulas, previously failing both anti-TNF treatment and surgical closure, who had surgical closure of the internal opening with MST were included. The primary endpoint was radiological remission of the fistula(s) defined as a MAGNIFI-CD ≤ 6 on MRI, read by an experienced radiologist. RESULTS: Between December 2019 and March 2023, 30 patients (15 males) with 48 fistula tracts were included with a median follow-up of 16.5 months. Radiological remission was achieved in thirteen patients (43.3%) after a median follow-up of 5.0 months (IQR 3.0-6.0). The median MAGNIFI-CD at baseline was 15.0 (IQR 7.0-20.0) which significantly decreased to 8.0 (IQR 3.0-15.0) after treatment (p = 0.001). Clinical closure was achieved in 21 patients (70.0%). Three patients (14.3%) developed a recurrence during long-term FU, all with clinically closed fistula(s), but no radiological remission. The median PDAI decreased significantly from 10.5 (IQR 7.0-14.0) to 4.0 (IQR 0.0-7.3) (p = 0.001). CONCLUSION: MST is a promising treatment strategy for therapy refractory Crohn's perianal fistulas, resulting in > 40% radiological remission, clinical closure in 70% and a significant improvement in quality of life. No recurrences were seen in patients with radiological remission.

Comparison of proactive and conventional treatment of anastomotic leakage in rectal cancer surgery: a multicentre retrospective cohort series.

PURPOSE: Comparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR. METHODS: This retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up. RESULTS: Overall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p < 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008). CONCLUSION: Proactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.

Understanding fluorescence time curves during ileal pouch-anal anastomosis with or without vascular ligation.

BACKGROUND: Intraoperative indocyanine green fluorescence angiography (ICG-FA) may be of added value during pouch surgery, in particular after vascular ligations as lengthening maneuver. The aim was to determine quantitative perfusion parameters within the efferent/afferent loop and explore the impact of vascular ligation. Perfusion parameters were also compared in patients with and without anastomotic leakage (AL). METHODS: All consenting patients that underwent FA-guided ileal pouch-anal anastomosis (IPAA) between July 2020 and December 2021 were included. After intravenous bolus injection of 0.1 mg/kg ICG, the near-infrared camera (Stryker Aim 1688) registered the fluorescence intensity over time. Quantitative analysis of ICG-FA from standardized regions of interests on the pouch was performed using software. Fluorescence parameters were extracted for inflow (T0, Tmax, Fmax, slope, Time-to-peak) and outflow (T90% and T80%). Change of management related to FA findings and AL rates were recorded. RESULTS: Twenty-one patients were included, three patients (14%) required vascular ligation to obtain additional length, by ligating terminal ileal branches in two and the ileocolic artery (ICA) in one patient. In nine patients the ICA was already ligated during subtotal colectomy. ICG-FA triggered a change of management in 19% of patients (n = 4/21), all of them had impaired vascular supply (ligated ileocolic/ terminal ileal branches). Overall, patients with intact vascular supply had similar perfusion patterns for the afferent and efferent loop. Pouches with ICA ligation had longer Tmax in both afferent as efferent loop than pouches with intact ICA (afferent 51 and efferent 53 versus 41 and 43 s respectively). Mean slope of the efferent loop diminished in ICA ligated patients 1.5(IQR 0.8-4.4) versus 2.2 (1.3-3.6) in ICA intact patients. CONCLUSION: Quantitative analysis of ICG-FA perfusion during IPAA is feasible and reflects the ligation of the supplying vessels.

Classification of surgical causes of and approaches to the chronically failing ileoanal pouch.

BACKGROUND: Although there are various surgical causes of and therapeutic approaches to the chronically failing ileoanal pouch (PF), cases are often detailed without distinguishing the exact cause and corresponding treatment. The aim of our study was to classify causes of PF and corresponding surgical treatment options, and to establish efficacy of surgical approach per cause. METHODS: This retrospective study included all consecutive adult patients with chronic PF surgically treated at our tertiary hospital between July 2014 and March 2021. Patients were classified according to a proposed sub-classification for surgical related chronic PF. Results were reported accordingly. RESULTS: A total of 59 procedures were completed in 50 patients (64% male, median age 45 years [IQR 34.5-54.3]) for chronic PF. Most patients had refractory ulcerative colitis as indication for their restorative proctocolectomy (68%). All patients could be categorized according to the sub-classification. Reasons for chronic PF were septic complications (n = 25), pouch body complications (n = 12), outlet problems (n = 11), cuff problems (n = 8), retained rectum (n = 2), and inlet problems (n = 1). For these indications, 17 pouches were excised, 10 pouch reconstructions were performed, and 32 pouch revision procedures were performed. The various procedures had different complication rates. Technical success rates of redo surgery for the different causes varied from 0 to 100%, with a 75% success rate for septic causes. CONCLUSIONS: Our sub-classification for chronic PF and corresponding treatments is suitable for all included patients. Outcomes varied between causes and subsequent management. Chronic PF was predominantly caused by septic complications with redo surgery achieving a 75% technical success rate.

Long-term outcomes after close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: During ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC), rectal dissection can be performed via close rectal dissection (CRD) or in a total mesorectal excision plane (TME). Although CRD should protect autonomic nerve function, this technique may be more challenging than TME. The aim of this study was to compare long-term outcomes of patients undergoing CRD and TME. METHODS: This single-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC between January 2002 and October 2017. Primary outcomes were chronic pouch failure (PF) among patients who underwent CRD and TME and the association between CRD and developing chronic PF. Chronic PF was defined as a pouch-related complication occurring ≥ 3 months after primary IPAA surgery requiring redo pouch surgery, pouch excision or permanent defunctioning ileostomy. Secondary outcomes were risk factors and causes for chronic PF. Pouch function and quality of life were assessed via the Pouch dysfunction score and Cleveland global quality of life score. RESULTS: Out of 289 patients (155 males, median age 37 years [interquartile range 26.5-45.5 years]), 128 underwent CRD. There was a shorter median postoperative follow-up for CRD patients than for TME patients (3.7 vs 10.9 years, p < 0.01). Chronic PF occurred in 6 (4.7%) CRD patients and 20 (12.4%) TME patients. The failure-free pouch survival rate 3 years after IPAA surgery was comparable among CRD and TME patients (96.1% vs. 93.5%, p = 0.5). CRD was a no predictor for developing chronic PF on univariate analyses (HR 0.7 CI-95 0.3-2.0, p = 0.54). A lower proportion of CRD patients developed chronic PF due to a septic cause (1% vs 6%, p = 0.03). CONCLUSIONS: Although differences in chronic PF among CRD and TME patients were not observed, a trend toward TME patients developing chronic pelvic sepsis was detected. Surgeons may consider performing CRD during IPAA surgery for UC.

Dealing with Complications of Colorectal Surgery Using the Transanal Approach-When and How?

The transanal approach is a new and exciting addition to the surgeons' repertoire to deal with complications after colorectal surgery. Improved exposure, accessibility, and visibility greatly facilitate adequate dissection of the affected area with potential increase in effectiveness and reduced morbidity. An essential component in salvaging anastomotic leaks of low colorectal, coloanal, or ileoanal anastomoses is early diagnosis and early treatment, especially when starting with endoscopic vacuum therapy, followed by early surgical closure (endoscopic vacuum-assisted surgical closure). Redo surgery using a transanal minimally invasive surgery platform for chronic leaks after total mesorectal excision surgery or surgical causes of pouch failure successfully mitigates limited visibility and exposure by using a bottom-up approach.

In-hospital Delay of Appendectomy in Acute, Complicated Appendicitis.

BACKGROUND: Present theory is that uncomplicated and complicated appendicitis are different entities. Recent studies suggest it is safe to delay surgery in patients with uncomplicated appendicitis. We hypothesize that patients with complicated appendicitis are at higher risk for postoperative complications when surgery is delayed. METHODS: Data was used from the multicenter, prospective SNAPSHOT appendicitis study of 1975 patients undergoing surgery for suspected appendicitis. Adult patients (≥ 18 years) who underwent appendectomy for appendicitis were included in this study. The primary outcome was the difference in postoperative complications between patients with complicated appendicitis who were operated within and after 8 h after hospital presentation. Secondary outcomes were the incidence of both uncomplicated and complicated appendicitis in relationship to delay of appendectomy. Follow-up was 30 days. A multivariable analysis was performed. RESULTS: Of 1341 adult patients with appendicitis, 34.3% had complicated appendicitis. In patients with complicated appendicitis, 22.8% developed a postoperative complication compared to 8.2% for uncomplicated appendicitis (P < 0.001). Delay in surgery (> 8 h) increased the complication rate in patients with complicated appendicitis (28.1%) compared to surgery within 8 h (18.3%; P = 0.01). Multivariate analysis showed a delay in surgery as an independent predictor for a postoperative complication in patients with complicated appendicitis (OR 1.71; 95%CI 1.01-2.68, P = 0.02). CONCLUSION: In-hospital delay of surgery (> 8 h) in patients with complicated appendicitis is associated with a higher risk of a postoperative complication. It is important that we recognize and treat these patients early.

CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn's disease.

Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn's disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-ß strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn's disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn's disease patients and may play a role in the pathology of the disease.

Impact of a defunctioning ileostomy and time to stoma closure on bowel function after low anterior resection for rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Impaired bowel function after low anterior resection (LAR) for rectal cancer is a frequent problem with a major impact on quality of life. The aim of this study was to assess the impact of a defunctioning ileostomy, and time to ileostomy closure on bowel function after LAR for rectal cancer. METHODS: We performed a systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Comprehensive literature searches were conducted using PubMed, Embase and Cochrane databases for articles published from 1989 up to August 2019. Analysis was performed using Review Manager (version 5.3) using a random-effects model. RESULTS: The search yielded 11 studies (1400 patients) that reported on functional outcome after LAR with at least 1 year follow-up, except for one study. Five scales were used: the Low Anterior Resection Syndrome (LARS) score, the Wexner score, the Memorial Sloan Kettering Cancer Centre Bowel Function Instrument, the Fecal Incontinence Quality of Life scale, and the Hallbook questionnaire. Based on seven studies, major LARS occurred more often in the ileostomy group (OR 2.84, 95% CI, 1.70-4.75, p < 0.0001: I2 = 60%, X2 = 0.02). Based on six studies, a longer time to stoma closure increased the risk of major LARS with a mean difference in time to closure of 2.39 months (95% CI, 1.28-3.51, p < 0.0001: I2 = 21%, X2 = 0.28) in the major vs. no LARS group. Other scoring systems could not be pooled, but presence of an ileostomy predicted poorer bowel function except with the Hallbook questionnaire. CONCLUSIONS: The risk of developing major LARS seems higher with a defunctioning ileostomy. A prolonged time to ileostomy closure seems to reinforce the negative effect on bowel function; therefore, early reversal should be an important part of the patient pathway.

Defining indocyanine green fluorescence to assess anastomotic perfusion during gastrointestinal surgery: systematic review.

BACKGROUND: The aim of this systematic review was to identify all methods to quantify intraoperative fluorescence angiography (FA) of the gastrointestinal anastomosis, and to find potential thresholds to predict patient outcomes, including anastomotic leakage and necrosis. METHODS: This systematic review adhered to the PRISMA guidelines. A PubMed and Embase literature search was performed. Articles were included when FA with indocyanine green was performed to assess gastrointestinal perfusion in human or animals, and the fluorescence signal was analysed using quantitative parameters. A parameter was defined as quantitative when a diagnostic numeral threshold for patient outcomes could potentially be produced. RESULTS: Some 1317 articles were identified, of which 23 were included. Fourteen studies were done in patients and nine in animals. Eight studies applied FA during upper and 15 during lower gastrointestinal surgery. The quantitative parameters were divided into four categories: time to fluorescence (20 studies); contrast-to-background ratio (3); pixel intensity (2); and numeric classification score (2). The first category was subdivided into manually assessed time (7 studies) and software-derived fluorescence-time curves (13). Cut-off values were derived for manually assessed time (speed in gastric conduit wall) and derivatives of the fluorescence-time curves (Fmax, T1/2, TR and slope) to predict patient outcomes. CONCLUSION: Time to fluorescence seems the most promising category for quantitation of FA. Future research might focus on fluorescence-time curves, as many different parameters can be derived and the fluorescence intensity can be bypassed. However, consensus on study set-up, calibration of fluorescence imaging systems, and validation of software programs is mandatory to allow future data comparison.

A nationwide database study on colectomy and colorectal cancer in ulcerative colitis: what is the role of appendectomy?

AIM: Although has been suggested that an appendectomy has a positive effect on the disease course in patients with ulcerative colitis (UC), recent studies indicate a potential increase in risk of colectomy and colorectal cancer (CRC). This study aimed to evaluate the rates of colectomy and CRC after appendectomy in UC patients using a nationwide prospective database [the Initiative on Crohn and Colitis Parelsnoer Institute - Inflammatory Bowel Disease (ICC PSI-IBD) database]. METHOD: All UC patients were retrieved from the ICC PSI-IBD database between January 2007 and May 2018. Primary outcomes were colectomy and CRC. Outcomes were compared in patients with and without appendectomy, with a separate analysis for timing of appendectomy (before or after UC diagnosis). RESULTS: A total of 826 UC patients (54.7% female; median age 46 years, range 18-89 years) were included. Sixty-three (7.6%) patients had previously undergone appendectomy: 24 (38.1%) before and 33 (52.4%) after their diagnosis of UC. In multivariate analysis, appendectomy after UC diagnosis was associated with a significantly lower colectomy rate compared with no appendectomy [hazard ratio (HR) 0.16, 95% C: 0.04-0.66, P = 0.011], and the same nonsignificant trend was seen in patients with an appendectomy before UC diagnosis (HR 0.35, 95% CI 0.08-1.41, P = 0.138). Appendectomy was associated with delayed colectomy, particularly when it was performed after diagnosis of UC (P = 0.009). No significant differences were found in the CRC rate between patients with and without appendectomy (1.6% vs 1.2%; P = 0.555). CONCLUSION: Appendectomy in established UC is associated with an 84% decreased risk of colectomy and a delay in surgery. Since the colon is in situ for longer, the risk of developing CRC remains, which underscores the importance of endoscopic surveillance programmes.

IMARI: multi-Interventional program for prevention and early Management of Anastomotic leakage after low anterior resection in Rectal cancer patIents: rationale and study protocol.

BACKGROUND: Anastomotic leakage (AL) is still a common and feared complication after low anterior resection (LAR) for rectal cancer. The multifactorial pathophysiology of AL and lack of standardised treatment options requires a multi-modal approach to improve long-term anastomotic integrity. The objective of the IMARI-trial is to determine whether the one-year anastomotic integrity rate in patients undergoing LAR for rectal cancer can be improved using a multi-interventional program. METHODS: IMARI is a multicentre prospective clinical effectiveness trial, whereby current local practice (control cohort) will be evaluated, and subsequently compared to results after implementation of the multi-interventional program (intervention cohort). Patients undergoing LAR for rectal cancer will be included. The multi-interventional program includes three preventive interventions (mechanical bowel preparation with oral antibiotics, tailored full splenic flexure mobilization and intraoperative fluorescence angiography using indocyanine green) combined with a standardised pathway for early detection and active management of AL. The primary outcome is anastomotic integrity, confirmed by CT-scan at one year postoperatively. Secondary outcomes include incidence of AL, protocol compliance and association with AL, temporary and permanent stoma rate, reintervention rate, quality of life and functional outcome. Microbiome analysis will be conducted to investigate the role of the rectal microbiome in AL. In a Dutch nationwide study, the AL rate was 20%, with anastomotic integrity of 90% after one year. Based on an expected reduction of AL due to the preventive approaches of 50%, and increase of anastomotic integrity by a standardised pathway for early detection and active management of AL, we hypothesised that the anastomotic integrity rate will increase from 90 to 97% at one year. An improvement of 7% in anastomotic integrity at one year was considered clinically relevant. A total number of 488 patients (244 per cohort) are needed to detect this difference, with 80% statistical power. DISCUSSION: The IMARI-trial is designed to evaluate whether a multi-interventional program can improve long-term anastomotic integrity after rectal cancer surgery. The uniqueness of IMARI lies in the multi-modal design that addresses the multifactorial pathophysiology for prevention, and a standardised pathway for early detection and active treatment of AL. TRIAL REGISTRATION: Trialregister.nl ( NL8261 ), January 2020.

Systematic Review: Histological Scoring of Strictures in Crohn's Disease.

BACKGROUND AND AIMS: In Crohn's disease, many patients develop a stricture, which can due to inflammation, fibrosis and muscular changes or all at the same time. Determining the predominant component has therapeutic consequences but remains challenging. To develop imaging techniques that assess the nature of a stricture, a gold standard is needed and histopathology is considered as such. This paper provides an overview of published histological scoring systems for strictures in Crohn's disease. METHODS: A systematic literature review according to PRISMA guidelines was performed of histological scoring indices that assessed whether a stricture was inflammation-predominant or fibrosis-predominant. Multiple libraries were searched from inception to December 2018. Two reviewers independently assessed abstracts and full-texts. RESULTS: Sixteen articles were identified as suitable for this systematic review. A large number of parameters were reported. Extent of neutrophil infiltration and extent of fibrosis in the bowel wall were most frequently described to reflect severity of inflammation and fibrosis, respectively. Among the 16 studies, only two described a numerical scoring system for the inflammatory and fibrotic component separately. Smooth muscle changes were scored in a minority of studies. CONCLUSIONS: Multiple scoring systems have been developed. There was large heterogeneity in scoring per parameter and construction of numerical scoring systems. Therefore, we feel that none of the systems is suitable to be used as gold standard. We offer an overview of histological parameters that could be incorporated in a future histological scoring index for strictures.

Safe, selective histopathological examination of gallbladder specimens: a systematic review.

BACKGROUND: Routine histopathological examination after cholecystectomy is costly, but the prevalence of unsuspected gallbladder cancer (incidental GBC) is low. This study determined whether selective histopathological examination is safe. METHODS: A comprehensive search of PubMed, Embase, Web of Science and the Cochrane Library was performed. Pooled incidences of incidental and truly incidental GBC (GBC detected during histopathological examination without preoperative or intraoperative suspicion) were estimated using a random-effects model. The clinical consequences of truly incidental GBC were assessed. RESULTS: Seventy-three studies (232 155 patients) were included. In low-incidence countries, the pooled incidence was 0·32 (95 per cent c.i. 0·25 to 0·42) per cent for incidental GBC and 0·18 (0·10 to 0·35) per cent for truly incidental GBC. Subgroup analysis of studies in which surgeons systematically examined the gallbladder revealed a pooled incidence of 0·04 (0·01 to 0·14) per cent. In high-incidence countries, corresponding pooled incidences were 0·83 (0·58 to 1·18), 0·44 (0·21 to 0·91) and 0·08 (0·02 to 0·39) per cent respectively. Clinical consequences were reported for 176 (39·3 per cent) of 448 patients with truly incidental GBC. Thirty-three patients (18·8 per cent) underwent secondary surgery. Subgroup analysis showed that at least half of GBC not detected during the surgeon's systematic examination of the gallbladder was early stage (T1a status or below) and of no clinical consequence. CONCLUSION: Selective histopathological examination of the gallbladder after initial macroscopic assessment by the surgeon seems safe and could reduce costs.

ANTECEDENTES: El examen histopatológico rutinario después de la colecistectomía es caro y la prevalencia de cáncer de vesícula biliar (gallbladder cancer, GBC) no sospechado o incidental es baja. Este estudio determinó si el examen histológico selectivo es seguro. MÉTODOS: Se realizó una búsqueda exhaustiva en PubMed, Embase, Web of Science y en la Biblioteca Cochrane. Se estimaron las incidencias agrupadas de GBC incidental y realmente incidental (GBC detectado durante el examen histopatológico sin sospecha previa o intraoperatoria) utilizando un modelo de efectos aleatorios. Además, se evaluaron las consecuencias clínicas del GBC realmente incidental. RESULTADOS: Se incluyeron 73 estudios (n = 232.155). En los países de baja incidencia, la incidencia agrupada fue de 0,32% para el GBC incidental (i.c. del 95% 0,25 a 0,42) y de 0,18% (0,10 a 0,35) para GBC realmente incidental. El análisis de subgrupos que incluye estudios en los que los cirujanos examinaron sistemáticamente la vesícula biliar reveló una incidencia agrupada de 0,04% (0,01 a 0,14). En los países de alta incidencia, las incidencias agrupadas correspondientes fueron 0,83% (0,58 a 1,18), 0,44% (0.2 a 0.91) y 0,08% (0,02 a 0,39), respectivamente. Se describieron consecuencias clínicas en 176 (39,3%) de 448 pacientes con GBC realmente incidental. Treinta y tres pacientes (18,6%) se sometieron a cirugía secundaria. El análisis por subgrupos mostró que al menos la mitad de los GBC no detectados durante el examen sistemático de la vesícula biliar por parte del cirujano eran tumores de estadio precoz (≤ T1a) y sin consecuencias clínicas. CONCLUSIÓN: El examen histológico selectivo de vesículas biliares después de la evaluación macroscópica inicial realizada por el cirujano parece seguro y podría reducir los costes.

Three-year outcome after transanal versus laparoscopic total mesorectal excision in locally advanced rectal cancer: a multicenter comparative analysis.

BACKGROUND: For patients with mid and distal rectal cancer, robust evidence on long-term outcome and causal treatment effects of transanal total mesorectal excision (TaTME) is lacking. This multicentre retrospective cohort study aimed to assess whether TaTME reduces locoregional recurrence rate compared to laparoscopic total mesorectal excision (LapTME). METHODS: Consecutive patients with rectal cancer within 12 cm from the anal verge and clinical stage II-III were selected from three institutional databases. Outcome after TaTME (Nov 2011 - Feb 2018) was compared to a historical cohort of patients treated with LapTME (Jan 2000 - Feb 2018) using the inverse probability of treatment weights method. The primary endpoint was three-year locoregional recurrence. RESULTS: A total of 710 patients were analysed, 344 in the TaTME group and 366 in the LapTME group. At 3 years, cumulative locoregional recurrence rates were 3.6% (95% CI, 1.1-6.1) in the TaTME group and 9.6% (95% CI, 6.5-12.7) in the LapTME group (HR = 0.4; 95% CI, 0.23-0.69; p = 0.001). Three-year cumulative disease-free survival rates were 74.3% (95% CI, 68.8-79.8) and 68.6% (95% CI, 63.7-73.5) (HR = 0.82; 95% CI, 0.65-1.02; p = 0.078) and three-year overall survival 87.2% (95% CI, 82.7-91.7) and 82.2% (95% CI, 78.0-86.2) (HR = 0.74; 95% CI, 0.53-1.03; p = 0.077), respectively. In patients who underwent sphincter preservation procedures, TaTME was associated with a significantly better disease-free survival (HR = 0.78; 95% CI, 0.62-0.98; p = 0.033). CONCLUSIONS: These findings suggest that TaTME may improve locoregional recurrence and disease-free survival rates among patients with mid and distal locally advanced rectal cancer.

Optimizing omentoplasty for management of chronic pelvic sepsis by intra-operative fluorescence angiography: a comparative cohort study.

AIM: Pelviperineal wound complications frequently occur after salvage surgery for chronic pelvic sepsis despite using an omentoplasty. Sufficient perfusion of the omentoplasty following mobilization is essential for proper healing. This study investigated the impact on short-term clinical outcomes of fluorescence angiography (FA) using indocyanine green for assessment of omental perfusion in patients undergoing salvage surgery. METHOD: This was a comparative cohort study including consecutive patients who underwent combined abdominal and transanal minimally invasive salvage surgery with omentoplasty at a national referral centre for chronic pelvic sepsis between December 2014 and August 2019. The historical and interventional cohorts were defined based on the date of introduction of FA in April 2018. The primary outcome was pelviperineal non-healing, defined by the presence of any degree of pelviperineal infection at the final postoperative evaluation. RESULTS: Eighty-eight patients underwent salvage surgery with omentoplasty for chronic pelvic sepsis, of whom 52 did not have FA and 36 did have FA. The underlying primary disease was Crohn's disease (n = 50) or rectal cancer (n = 38), with even distribution among the cohorts (P = 0.811). FA led to a change in management in 28/36 (78%) patients. After a median of 89 days, pelviperineal non-healing was observed in 22/52 (42%) patients in the cohort without FA and in 8/36 (22%) patients in the cohort with FA (P = 0.051). Omental necrosis was found during reoperation in 3/52 and 0/36 patients, respectively (P = 0.266). CONCLUSION: After introduction of FA to assess perfusion of the omentoplasty, halving of the pelviperineal non-healing rate was observed in patients undergoing salvage surgery for chronic pelvic sepsis.

Appendicular neoplasms and consequences in patients undergoing surgery for suspected acute appendicitis.

INTRODUCTION: In patients treated with an appendectomy for acute appendicitis, the specimen is generally sent for histological evaluation. In an era of increasing non-operative treatment for acute appendicitis, it is important to know the incidence, the diagnostic accuracy, and treatment consequences of appendicular neoplasms that are found in acute appendicitis. We hypothesize that pre- and intra-operative parameters might predict an appendicular neoplasm. METHODS: Data was used from our previous prospective observational cohort study. All patients undergoing surgery for suspected acute appendicitis were included. The primary outcome was the incidence of appendicular neoplasms in patients operated for acute appendicitis. Secondary outcomes were pre-operative diagnostics and imaging outcomes, intra-operative surgical judgment, and postoperative management and outcome. Possible predictors of an appendicular neoplasm were identified and used in multivariable logistic regression. Patients with an appendicular neoplasm were followed for 3 years after initial appendectomy. RESULTS: A total of 1975 patients underwent surgery for suspected acute appendicitis and in 98.3% (1941/1975) the appendix was removed. In 1.5% (30/1941) of these patients, an appendicular neoplasm was found. Among the malignant neoplasms, the majority were grade 1 neuroendocrine tumors (NET) in 65% (13/20). On pre-operative imaging, there was no suspicion of malignancy. In three cases, there was an intra-operative suspicion of malignancy. Multivariable analysis showed only age as an independent predictor for appendicular neoplasms. No recurrent or new malignancy was found during follow-up. DISCUSSION: The incidence of appendicular neoplasm in patients undergoing an acute appendectomy is very low and clinical risk factors could not be identified.

Cost-effectiveness of sigmoid resection with primary anastomosis or end colostomy for perforated diverticulitis: an analysis of the randomized Ladies trial.

BACKGROUND: Several studies have been published favouring sigmoidectomy with primary anastomosis over Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis (Hinchey grade III or IV), but cost-related outcomes were rarely reported. The present study aimed to evaluate costs and cost-effectiveness within the DIVA arm of the Ladies trial. METHODS: This was a cost-effectiveness analysis of the DIVA arm of the multicentre randomized Ladies trial, comparing primary anastomosis over Hartmann's procedure for Hinchey grade III or IV diverticulitis. During 12-month follow-up, data on resource use, indirect costs (Short Form Health and Labour Questionnaire) and quality of life (EuroQol Five Dimensions) were collected prospectively, and analysed according to the modified intention-to-treat principle. Main outcomes were incremental cost-effectiveness (ICER) and cost-utility (ICUR) ratios, expressed as the ratio of incremental costs and the incremental probability of being stoma-free or incremental quality-adjusted life-years respectively. RESULTS: Overall, 130 patients were included, of whom 64 were allocated to primary anastomosis (46 and 18 with Hinchey III and IV disease respectively) and 66 to Hartmann's procedure (46 and 20 respectively). Overall mean costs per patient were lower for primary anastomosis (€20 544, 95 per cent c.i. 19 569 to 21 519) than Hartmann's procedure (€28 670, 26 636 to 30 704), with a mean difference of €-8126 (-14 660 to -1592). The ICER was €-39 094 (95 per cent bias-corrected and accelerated (BCa) c.i. -1213 to -116), indicating primary anastomosis to be more cost-effective. The ICUR was €-101 435 (BCa c.i. -1 113 264 to 251 840). CONCLUSION: Primary anastomosis is more cost-effective than Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis.

ANTECEDENTES: Se han publicado varios estudios en favor de la sigmoidectomía con anastomosis primaria (primary anastomosis, PA) sobre la intervención de Hartmann (Hartmann's procedure, HP) para la diverticulitis perforada con peritonitis purulenta o fecal (Hinchey grado III ó IV), pero apenas existe información de los resultados relacionados con el coste. Por lo tanto, el presente estudio tuvo como objetivo evaluar los costes y el coste efectividad del brazo DIVA en el ensayo clínico Ladies. MÉTODOS: Se realizó un análisis de coste-efectividad del brazo DIVA del ensayo clínico multicéntrico y aleatorizado Ladies, que comparó PA y HP para la diverticulitis Hinchey de grado III ó IV. Durante un seguimiento de 12 meses, se recogieron datos prospectivamente del uso de recursos, costes indirectos (SF-HLQ) y calidad de vida (EQ-5D), y se analizaron de acuerdo con una modificación del principio por intención de tratar. Los resultados principales fueron la relación coste-efectividad incremental (incremental cost-effectiveness ratio, ICER) y la relación coste-utilidad incremental (incremental cost-utility ratio, ICUR), expresados como la razón del incremento de costes y el incremento en la probabilidad de no requerir estoma o años de vida ajustados por calidad, respectivamente. RESULTADOS: En total, se incluyeron 130 pacientes, 64 de los cuales fueron asignados a PA (Hinchey III/IV: 46/20) y 66 a HP (Hinchey III/IV: 46/18). Los costes medios globales por paciente fueron más bajos para la PA (€20.544 (i.c. del 95%: 19.569 a 21.519)) en comparación con HP (€ 28.670 (i.c. del 95%: 26.636 a 30.704)), con una diferencia media de €−8.126 (i.c. del 95% −14.660 a −1.592)). Además, se observó un ICER de € −39.094 (95% bias-corrected and accelerated boodstrap confidence interval, BCaCI −1.213 a −116), lo que indica que PA es más coste efectiva. El ICUR fue € −101.435 (BCaCI del 95%: −1.113.264 a 251.840). CONCLUSIÓN: La anastomosis primaria es más rentable que el procedimiento de Hartmann para la diverticulitis perforada con peritonitis purulenta o fecal.

Curative-intent surgery for isolated locoregional recurrence of colon cancer: Review of the literature and institutional experience.

BACKGROUND: Locoregional recurrence of colon cancer (LRCC) following curative resection is an underreported clinical entity, especially regarding isolated LRCC which is amenable for surgery. The purpose of this study was to review the literature on incidence of LRCC and surgical treatment with corresponding outcome, and to describe an institutional experience with curative-intent surgery, whether or not as part of a multimodality approach. METHODS: The PubMed and Medline literature databases 1978-2017 were searched and retrieved articles were assessed for eligibility. Based on a prospectively maintained database since 2010 at a tertiary referral center, original patient files were retrospectively reviewed. RESULTS: Systematic literature review resulted in 11 studies reporting on incidence of LRCC, which ranged from 3.1% to 19.0% before 2010, and from 4.4% to 6.7% in three most recent studies. Twelve identified studies reported on outcome of surgically treated LRCC, with a median survival of 30 and 33 months in the two largest studies. The institutional database entailed 17 patients who underwent resection of isolated LRCC between 2010 and 2018. Median time to recurrence was 19 months. After a median follow-up after resection of LRCC of 20 months, 7 patients had died, 9 patients were alive without evidence of disease and 1 patient with evidence of disease; Median DFS was 36 months and 3-year OS was 65%. CONCLUSION: Locoregional recurrence of colon cancer occurs in about 5% in most recent series, of whom selected patients are eligible for surgical treatment, with a fair chance of long-term disease control.