Low rectal resection for low rectal endometriosis and rectal adenocarcinoma: Are we discussing the same risks?

OBJECTIVE: To evaluate the rate and risk factors for anastomosis leakage in patients undergoing colorectal resection with low anastomosis for rectal endometriosis and rectal adenocarcinoma. METHODS: A retrospective cohort study evaluating prospectively collected data was conducted. Patients undergoing colorectal resection for rectal endometriosis and rectal adenocarcinoma with low anastomosis (<7 cm from the anal verge [AV]) from September 2018 to January 2023 were included in the analysis. The main outcome was the rate of anastomosis leakage. A multivariate logistic regression was conducted to evaluate risk factors for anastomosis leakage in both groups. RESULTS: A total of 159 patients underwent colorectal resection with low anastomosis due to rectal endometriosis (n = 99) and rectal adenocarcinoma (n = 60). Patients with endometriosis were significantly younger than those with adenocarcinoma (35.7 ± 5.1 vs 63.7 ± 12.6; P = 0.001). The leakage rate was similar between the endometriosis (n = 12, 12.1%) and adenocarcinoma (n = 9, 15.0%) patients (P = 0.621). The anastomosis height less than 5 cm from the AV (adjusted odds ratio [aOR] 12.12, 95% confidence interval [CI] 2.24-23.54) was significantly associated with the anastomosis leakage. Protective stoma was associated with the decrease of the leakage risk (aOR 0.12, 95% CI 0.01-0.72). The type of disease (rectal endometriosis or adenocarcinoma) was not associated with the anastomosis leakage (aOR 2.87, 95% CI 0.34-21.23). CONCLUSIONS: Despite the different pathogenesis, the risk of anastomotic leakage was found to be similar between patients with low rectal endometriosis and those with rectal adenocarcinoma. These results must be considered by the gynecologist and colorectal surgeon to deliver proper information before rectal surgery for endometriosis.

Excision of Deep Rectovaginal Endometriosis Nodules with Large Infiltration of Both Rectum and Vagina: What Is a Reasonable Rate of Preventive Stoma? A Comparative Study.

STUDY OBJECTIVE: To compare postoperative complications and rectovaginal fistula rate in women undergoing excision of large rectovaginal endometriosis requiring concomitant excision of rectum and vagina during 2 time periods with differing policies for preventive stoma confection. DESIGN: Retrospective before-and-after comparative cohort study on data prospectively recorded in a database. Patients managed from September 2018 to March 2020 (first period) were compared with those managed from April 2020 to June 2022 (second period). SETTING: Endometriosis Institute. PATIENTS: One hundred sixty-eight patients presenting with deep endometriosis infiltrating the rectum and vagina, with lesions more than 3 cm in diameter during 2 consecutive time periods with differing policies regarding use of preventive stoma. INTERVENTIONS: Rectal disc excision or colorectal resection, concomitantly with large vaginal excision. MEASUREMENTS AND MAIN RESULTS: A total of 87 and 81 women received surgery during the first and the second period, respectively, during which the rate of preventive stoma was, respectively, 32.2% and 8.6%. Deep rectovaginal nodule characteristics were comparable. The mean height (SD) of rectal sutures after disc excision and colorectal resection were, respectively, 6.5 cm (2.3 cm) and 7.2 cm (3.8 cm). Rectovaginal fistula was recorded in 17 patients, corresponding to an overall rate of 10.1%. The rates of rectovaginal fistula in the group of patients with and without preventive stoma, regardless of the period in which surgery was performed, were 11.4% and 9.8%, respectively (p = .76). The rates of fistula recorded during the first and the second period were, respectively, 9.2% and 11.1% (p = .80), and that of overall early main complications were 31% and 29.6% (p = .84). Regression logistic model identified an independent relationship between smoking and rectovaginal fistula (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.1-14) after adjustment for the period (adjusted OR 1.4, 95% CI 0.4-4.9 related to the second period), stoma confection (adjusted OR 1.8, 95% CI 0.5-7.1 related to stoma confection), robotic surgery (adjusted OR 1.7, 95% CI 0.3-10.1 related to robotic assistance), and type of rectal surgery (adjusted OR 0.4, 95% CI 0.1-1.4 related to disc excision when compared with colorectal resection). CONCLUSION: No statistically significant differences were found concerning risk of rectovaginal fistula in women with rectovaginal endometriosis requiring large rectal and vaginal excision after a decision to no longer routinely perform preventive stoma.

Disk Excision Using End-to-End Anastomosis Circular Stapler for Deep Endometriosis of the Rectum: A 492-Patient Continuous Prospective Series.

STUDY OBJECTIVE: To report a large series including women managed by disk excision using end-to-end anastomosis (EEA) circular transanal stapler to assess the feasibility of the technique, the features of nodules suitable for removal by disk excision, and the rate of major early complications. DESIGN: Retrospective study on data prospectively recorded in 2 databases. SETTING: Two tertiary referral centers. PATIENTS: A total of 492 patients undergoing surgery for rectal endometriosis from May 2011 to June 2022. INTERVENTIONS: Rectal disk excision using the EEA stapler. MEASUREMENT AND MAIN RESULTS: Disk excision using EEA was performed in 492 patients (24.2%) of 2,029 women receiving surgery for deep endometriosis infiltrating the rectum during the 11-year study period. Deep endometriosis involved low rectum in 11% and mid rectum in 55.3%. The diameter of rectal nodules exceeded 3 cm in 65.9%. Mean operative time was 2 hours, mean diameter of rectal patches removed was 41 ± 11 mm, and the mean rectal suture height was 9.2 ± 5.5 cm. The presence of microscopic foci on the edges of rectal patches was identified in 30.2% of cases. Rectal fistula was recorded in 20 patients (4%). The distance from the anal verge was significantly lower in patients with fistula than women with no fistula (5.9 ± 2 cm vs 9.2 ± 5.6 cm, p = .027). Follow-up ranged from 1 to 120 months, with a median value of 36 months. Magnetic resonance imaging in 3 patients during follow-up revealed a recurrent nodule infiltrating the previous stapled line (0.6%) after a postoperative delay of, respectively, 36, 48, and 84 months. CONCLUSION: Disk excision using the EEA stapler is suitable in nodules >3 cm if surgeons ensure deep shaving of the rectum, to allow complete inclusion of the shaved area into the stapler jaws. Postoperative rectal recurrences seem incidental, whereas bowel leakage rate is comparable with that after colorectal resection. This technique is suitable in almost a quarter of patients managed for rectal endometriosis nodules and is therefore a valuable technique that warrants more widespread use.

Natural Orifice Specimen Extraction Colorectal Resection for Deep Endometriosis: A 50 Case Series.

STUDY OBJECTIVE: To describe our experience with the use of natural orifice specimen extraction (NOSE) technique for segmental bowel resection in patients with colorectal endometriosis. DESIGN: A retrospective, observational study. SETTING: A single tertiary referral center. PATIENTS: A total of 50 consecutive patients undergoing NOSE colectomy for colorectal endometriosis in our center, between March 2021 and November 2021. INTERVENTIONS: NOSE colectomy for colorectal endometriosis with removal of the excised colorectal specimen through the vagina or the anus. MEASUREMENT AND MAIN RESULTS: A total of 45 procedures were performed laparoscopically and 5 procedures were performed robotically. All interventions were performed by 3 endometriosis surgeons in a multidisciplinary fashion, with involvement of a colorectal surgeon. There were no cases of conversion to laparotomy. Concomitant surgical procedures were performed in all cases. Eleven patients had concomitant interventions on the digestive tract. Five patients had concomitant interventions on the sacral plexus or sciatic nerve. All anastomoses were lateroterminal. The mean height of colorectal anastomosis was 12 cm (standard deviation [SD] ± 4), and the mean length of the excised colorectal specimen was 9 cm (SD ± 4). In 29 cases, the specimen was extracted through the vagina and in 21 cases through the anus. A total of 5 patients required a reoperation in the early postoperative period: We identified 1 case of anastomotic leak, 1 case of postoperative bowel obstruction, 1 case of hemorrhage and 2 cases of pelvic collection (no macroscopic evidence of pus). No patient received blood transfusion. The mean operative time was 158 minutes (SD ± 70) and mean hospital stay was 4 days (SD ± 1). CONCLUSION: NOSE colectomy is a reproducible surgical technique for the management of colorectal endometriosis. The complication rate appears comparable with the conventional (minilaparotomy) surgical approach. In experienced hands, this technique has a short learning curve, both in laparoscopy and in robotic surgery.

Association between the indole pathway of tryptophan metabolism and subclinical depressive symptoms in obesity: a preliminary study.

Converging data support the role of chronic low-grade inflammation in depressive symptomatology in obesity. One mechanism likely to be involved relies on the effects of inflammation on tryptophan (TRP) metabolism. While recent data document alterations in the indole pathway of TRP metabolism in obesity, the relevance of this mechanism to obesity-related depressive symptoms has not been investigated. The aim of this preliminary study was to assess the association between plasma levels of TRP and indole metabolites and depressive symptoms in 44 subjects with severe or morbid obesity, free of clinically relevant neuropsychiatric disorders. The interaction effect of inflammation, reflected in serum high-sensitive C-reactive protein (hsCRP) levels, and indoles on depressive symptoms was also determined. Higher serum levels of hsCRP and lower concentrations of TRP and indoles, particularly indole-3-carboxaldehyde (IAld), correlated with more severe depressive symptoms. Interestingly, the effect of high hsCRP levels in predicting greater depressive symptoms was potentiated by low IAld levels. These results comfort the link between inflammation, the indole pathway of TRP metabolism, and obesity-related depressive symptoms.

Risk of Rectovaginal Fistula in Women with Excision of Deep Endometriosis Requiring Concomitant Vaginal and Rectal Sutures, with or without Preventive Stoma: A Before-and-after Comparative Study.

STUDY OBJECTIVE: To assess whether a liberal policy of preventive stoma (LPS) reduces the rate of rectovaginal fistulas in women with excision of deep endometriosis requiring concomitant vaginal and rectal sutures in comparison with a more restrictive policy of preventive stoma (RPS) and to assess the risk factors for rectovaginal fistula. DESIGN: Retrospective before-and-after comparative study. SETTING: Two referral centers, one with an LPS and the other with an RPS. PATIENTS: A total of 363 patients with deep endometriosis infiltrating the rectum and the vagina. INTERVENTIONS: Rectal disc excision or colorectal resection concomitantly with vaginal excision. MEASUREMENTS AND MAIN RESULTS: Two hundred forty-one and 122 women received surgery at the LPS and RPS centers, respectively. The rate of preventive stomas was 71.4% at the LPS center (n = 172) and 30.3% at the RPS center (N = 37). Rectovaginal fistula was recorded in 31 cases (8.5%): nineteen women were managed at the LPS center, and 12 women underwent surgery at the RPS center. It occurred in, respectively, 9.4%, 10.8%, 10.1%, and 7% of the women managed without and with a stoma at the RPS center and of those managed without and with a stoma at the LPS center (p = .72). The height of the rectal stapled line was significantly lower in the women undergoing a stoma, particularly in those managed at the RPS center (5.4 ± 1.8 cm). Performing rectal sutures within 8 cm from the anal verge increased the risk of rectovaginal fistula more than 3-fold, independently of stoma creation, surgical procedure carried out on the rectum, size of vaginal infiltration, or associated excision of deep endometriosis involving the pelvic nerves (odds ratio 3.4; 95% confidence interval, 1.3-9.1). CONCLUSION: No statistically significant differences were found in terms of the risk of rectovaginal fistula between women with rectovaginal endometriosis managed by either an LPS or an RPS; however, these findings need to be confirmed by a randomized trial.

Live surgery of colorectal endometriosis broadcasted from a surgeon's routine operating theater is not associated with higher complications rate.

INTRODUCTION: Although live surgeries are routinely included in surgical congress programs, they are the subject of an ongoing debate in terms of patient safety and teaching value. The goal of our study was to assess the risk of postoperative complications related to live surgery broadcast from the surgeon's routine theater, in patients managed for deep endometriosis infiltrating the digestive tract. MATERIAL AND METHODS: We report a retrospective comparative study, enrolling women managed for colorectal endometriosis by a gynecologic surgeon, from September 2013 to March 2020 in two referral centers. We compared the rate of postoperative bowel fistula in women managed during live surgery in the routine operating theater, with that observed in women for whom surgery was not broadcast. RESULTS: Among 813 women, 33 (4.1% of cases) underwent surgical procedures transmitted live to various conference rooms located outside the hospital and were compared with 780 patients who underwent non-broadcast surgery. Women's age, body mass index, past surgical and obstetrical history, and major preoperative complaints were comparable. Cases presented with impaired constipation score, more frequent sciatic pain, and infiltration of the vagina, whereas overall revised American Fertility Society classification scores were more severe in controls. The rate of rectal nodules over 3 cm in size was comparable between the two groups (72.7% in cases vs. 72.1% in controls). Operative time was also comparable (153 ± 52 minutes vs. 148 ± 79 minutes). Cases were more frequently managed by disk excision of rectal nodules (63.7% vs. 30.3%), and more frequently involved the sacral plexus (18.2% vs. 7.3%). Postoperative complications were comparable between the two groups, in terms of bowel fistula (3% in the live surgery group vs. 4.1% in controls), pelvic abscess requiring secondary laparoscopy (3% vs. 4.9%), or bladder dysfunction requiring self-catheterization after discharge (6.1% vs. 5.3%). CONCLUSIONS: Performing laparoscopic management of colorectal endometriosis with live transmission of surgery from a surgeon's routine operating theater, is not related to a higher risk of major postoperative complications.

Transcriptomic signaling pathways involved in a naturalistic model of inflammation-related depression and its remission.

This study aimed at identifying molecular biomarkers of inflammation-related depression in order to improve diagnosis and treatment. For this, we performed whole-genome expression profiling from peripheral blood in a naturalistic model of inflammation-associated major depressive disorder (MDD) represented by comorbid depression in obese patients. We took advantage of the marked reduction of depressive symptoms and inflammation following bariatric surgery to test the robustness of the identified biomarkers. Depression was assessed during a clinical interview using Mini-International Neuropsychiatric Interview and the 10-item, clinician-administered, Montgomery-Asberg Depression Rating Scale. From a cohort of 100 massively obese patients, we selected 33 of them for transcriptomic analysis. Twenty-four of them were again analyzed 4-12 months after bariatric surgery. We conducted differential gene expression analyses before and after surgery in unmedicated MDD and non-depressed obese subjects. We found that TP53 (Tumor Protein 53), GR (Glucocorticoid Receptor), and NFκB (Nuclear Factor kappa B) pathways were the most discriminating pathways associated with inflammation-related MDD. These signaling pathways were processed in composite z-scores of gene expression that were used as biomarkers in regression analyses. Results showed that these transcriptomic biomarkers highly predicted depressive symptom intensity at baseline and their remission after bariatric surgery. While inflammation was present in all patients, GR signaling over-activation was found only in depressed ones where it may further increase inflammatory and apoptosis pathways. In conclusion, using an original model of inflammation-related depression and its remission without antidepressants, we provide molecular predictors of inflammation-related MDD and new insights in the molecular pathways involved.

Relationship between body mass index and neuropsychiatric symptoms: Evidence and inflammatory correlates.

OBJECTIVE: Neuropsychiatric symptoms are frequent in obese individuals. Mounting evidence suggests that adiposity-related inflammation contributes to this effect. This study assessed the relationship between adiposity, neuropsychiatric symptom dimensions and systemic inflammation in subjects stratified by body-mass-index (BMI). METHODS: The study included 165 subjects, of whom 70 were very severely obese (BMI ≥ 40 kg/m2), 50 severely obese (BMI: 35-39.99 kg/m2), 21 overweight or moderately obese (BMI: 25-34.9 kg/m2), and 24 lean (BMI < 25 kg/m2). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mini-International Neuropsychiatric Interview (MINI). Fatigue and general neurobehavioral symptoms were assessed using the Multidimensional Fatigue Inventory (MFI) and Neurotoxicity Rating Scale (NRS) respectively. Serum levels of the inflammatory markers, high-sensitive (hs) CRP and hsIL-6, were determined by ELISA. RESULTS: Severely obese subjects exhibited higher MADRS, MFI and NRS scores and were more frequently afflicted with current diagnosis of major depression than lean participants. Scores on psychometric scales were also increased in very severely obese subjects, although to a lesser extent. Alterations in neuropsychiatric dimensions were highly inter-related. HsCRP was significantly increased in subjects with severe or very severe obesity, while hsIL-6 was augmented in all obese groups. Overall, increased neuropsychiatric comorbidity was associated with greater systemic inflammation, notably hsCRP. CONCLUSION: Obesity is characterized by an increased prevalence of inter-related neuropsychiatric symptoms together with low-grade systemic inflammation augmenting with adiposity. The association between adiposity, systemic inflammation and neuropsychiatric alterations supports the contribution of adiposity-related inflammatory processes to neuropsychiatric comorbidities in obesity. These data suggest that consideration of adiposity characteristics may help identifying subjects at increased risk for neuropsychiatric comorbidity.

Evaluation of functional outcomes after disc excision of deep endometriosis involving low and mid rectum using standardized questionnaires: a series of 80 patients.

AIM: The aim was to assess the functional outcome and quality of life in patients with low and mid rectal endometriosis who have undergone disc excision using a semicircular transanal staple device, a procedure we have named the Rouen technique. METHODS: This was a retrospective study of patients undergoing the Rouen technique between October 2009 and November 2018. Preoperative and postoperative demographic and operative data were recorded prospectively (mean ± SEM). Postoperative complications were recorded using the Clavien-Dindo classification. Rectal function and quality of life were assessed by the low anterior resection syndrome (LARS) and Bowel Endometriosis Syndrome (BENS) scores respectively at ≥6 months. RESULTS: The Rouen procedure was performed on 80 patients (29.7 ± 4.3). The mean diameter of resected specimens was 57 ± 10 mm, and the height of the rectal suture from the anal verge was 4.6 ± 1.2 cm. The Clavien-Dindo complications were Clavien-Dindo 1 (leg compression), Clavien-Dindo 2 (urinary tract infection, bladder self-catheterization) and Clavien-Dindo 3b (bowel obstruction, rectovaginal fistula, pyelic dilation, colorectal stenosis after resection). A rectovaginal fistula (Clavien-Dindo 3b) developed in nine (11.3%) patients and their stoma could be reversed after 99-162 days. The majority of patients (n = 50, 62.5%) had normal postoperative rectal function with LARS score ≤20. However, minor (LARS ≥ 21-29) and major rectal dysfunction (LARS ≥ 30) was seen in 18 (22.5%) and 12 (15%) patients respectively. Quality of life as measured using the BENS score was normal (BENS score 0-8) in 51 (63.8%) patients, slightly reduced (BENS score 9-16) in 24 (30%) patients and in only five (6.3%) was this a major issue (BENS score > 17). The development of a rectovaginal fistula was independently related to risk of major rectal dysfunction (adjusted OR 6.3, 95% CI 1.3-30.6). CONCLUSIONS: In our series of 80 patients with transmural low and mid rectal endometriosis disc excision using a semicircular staple device can result in good functional outcomes and quality of life and avoid the complexity and potential complications of a low anterior resection.

Postoperative Outcomes after Surgery for Deep Endometriosis of the Sacral Plexus and Sciatic Nerve: A 52-patient Consecutive Series.

STUDY OBJECTIVE: To assess 1-year postoperative outcomes of surgery for deep endometriosis involving the sacral roots and sciatic nerve. DESIGN: Retrospective case series. SETTING: Three referral centers. PATIENTS: Fifty-two women. INTERVENTIONS: Surgery for deep endometriosis involving the sacral roots and sciatic nerve. MEASUREMENTS AND MAIN RESULTS: Deep endometriosis involved the sacral roots in 49 women (94.2%) and the sciatic nerve in 3 cases (5.8%). Sciatic pain (buttock or leg) was recorded in 43 women (82.7%), pudendal neuralgia in 11 women (21.2%), and leg motor weakness in 14 cases (27%). The surgical procedures carried out on the pelvic nerves included complete release and decompression (92.3%), excision of the epineurium by shaving (5.8%), and intraneural excision (1.9%). Additional major surgical procedures involved the digestive tract in 82.7% of the cases and the urinary tract in 46.2%. Rectovaginal fistula occurred in 13.5% of the cases. Self-catheterization was required in 14 cases (27%) at 3 weeks after surgery and in 3 women (5.8%) 12 months later. One-year follow-up showed significant improvement in quality of life measured using the Short-Form 36 questionnaire and standardized gastrointestinal scores. De novo hypoesthesia, hyperesthesia, or allodynia were recorded in 9 women (17.2%). The cumulative pregnancy rate was 77.2%% after natural conception in 47%. CONCLUSION: Laparoscopic management of deep endometriosis involving the sacral roots and sciatic nerve improves patients' symptoms and overall quality of life. Although pain reduction may be rapid after surgery, other sensory or motor complaints, including bladder dysfunction, may be recorded over months or years.

Risk of bowel fistula following surgical management of deep endometriosis of the rectosigmoid: a series of 1102 cases.

STUDY QUESTION: What are the risk factors and prevalence of bowel fistula following surgical management of deep endometriosis infiltrating the rectosigmoid and how can it be managed? SUMMARY ANSWER: In patients managed for deep endometriosis of the rectosigmoid, risk of fistula is increased by bowel opening during both segmental colorectal resection and disc excision and rectovaginal fistula repair is more challenging than for bowel leakage. WHAT IS KNOWN ALREADY: Bowel fistula is known to be a severe complication of colorectal endometriosis surgery; however, there is little available data on its prevalence in large series or on specific management. STUDY DESIGN, SIZE, DURATION: A retrospective study employing data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis (CIRENDO) from June 2009 to May 2019, in three tertiary referral centres. PARTICIPANTS/MATERIALS, SETTING, METHODS: One thousand one hundred and two patients presenting with deep endometriosis infiltrating the rectosigmoid, who were managed by shaving, disc excision or colorectal resection. The prevalence of bowel fistula was assessed, and factors related to the complication and its surgical management. MAIN RESULTS AND THE ROLE OF CHANCE: Of 1102 patients enrolled in the study, 52.5% had a past history of gynaecological surgery and 52.7% had unsuccessfully attempted to conceive for over 12 months. Digestive tract subocclusion/occlusion was recorded in 12.7%, hydronephrosis in 4.5% and baseline severe bladder dysfunction in 1.5%. An exclusive laparoscopic approach was carried out in 96.8% of patients. Rectal shaving was performed in 31.9%, disc excision in 23.1%, colorectal resection in 35.8% and combined disc excision and sigmoid colon resection in 2.9%. For various reasons, the nodule was not completely removed in 6.4%, while in 7.2% of cases complementary procedures on the ileum, caecum and right colon were required. Parametrium excision was performed in 7.8%, dissection and excision of sacral roots in 4%, and surgery for ureteral endometriosis in 11.9%. Diverting stoma was performed in 21.8%. Thirty-seven patients presented with bowel fistulae (3.4%) of whom 23 (62.2%) were found to have rectovaginal fistulae and 14 (37.8%) leakage. Logistic regression model showed rectal lumen opening to increase risk of fistula when compared with shaving, regardless of nodule size: adjusted odds ratio (95% CI) for disc excision, colorectal resection and association of disc excision + segmental resection was 6.8 (1.9-23.8), 4.8 (1.4-16.9) and 11 (2.1-58.6), respectively. Repair of 23 rectovaginal fistulae required 1, 2, 3 or 4 additional surgical procedures in 12 (52.2%), 8 (34.8%), 2 (8.7%) and 1 patient (4.3%), respectively. Repair of leakage in 14 patients required 1 procedure (stoma) in 12 cases (85.7%) and a second procedure (colorectal resection) in 2 cases (14.3%). All patients, excepted five women managed by delayed coloanal anastomosis, underwent a supplementary surgical procedure for stoma repair. The period of time required for diverting stoma following repair of rectovaginal fistulae was significantly longer than for repair of leakages (median values 10 and 5 months, respectively, P = 0.008). LIMITATIONS, REASONS FOR CAUTION: The main limits relate to the heterogeneity of techniques used in removal of rectosigmoid nodules and repairing fistulae, the lack of accurate information about the level of nodules, the small number of centres and that a majority of patients were managed by one surgeon. WIDER IMPLICATIONS OF THE FINDINGS: Deep endometriosis infiltrating the rectosigmoid can be managed laparoscopically with a relatively low risk of bowel fistula. When the type of bowel procedure can be chosen, performance of shaving instead of disc excision or colorectal resection is suggested considering the lower risk of bowel fistula. Rectovaginal fistula repair is more challenging than for bowel leakage and may require up to four additional surgical procedures. STUDY FUNDING/COMPETING INTEREST(S): CIRENDO is financed by the G4 Group (The University Hospitals of Rouen, Lille, Amiens and Caen) and the ROUENDOMETRIOSE Association. No financial support was received for this study. H.R. reports personal fees from ETHICON, Plasma Surgical, Olympus and Nordic Pharma outside the submitted work. The other authors declare no conflict of interests related to this topic.

Tryptophan Metabolic Pathways Are Altered in Obesity and Are Associated With Systemic Inflammation.

Background: Obesity is a condition with a complex pathophysiology characterized by both chronic low-grade inflammation and changes in the gut microbial ecosystem. These alterations can affect the metabolism of tryptophan (TRP), an essential amino acid and precursor of serotonin (5-HT), kynurenine (KYN), and indoles. This study aimed to investigate alterations in KYN and microbiota-mediated indole routes of TRP metabolism in obese subjects relatively to non-obese controls and to determine their relationship with systemic inflammation. Methods: Eighty-five obese adults (avg. BMI = 40.48) and 42 non-obese control individuals (avg. BMI = 24.03) were recruited. Plasma levels of TRP catabolites were assessed using Ultra High Performance Liquid Chromatography-ElectroSpray-Ionization-Tandem Mass Spectrometry. High-sensitive C-reactive protein (hsCRP) and high-sensitive interleukin 6 (hsIL-6) were measured in the serum as markers of systemic inflammation using enzyme-linked immunosorbent assay. Results: Both KYN and microbiota-mediated indole routes of TRP metabolism were altered in obese subjects, as reflected in higher KYN/TRP ratio and lower 5-HT and indoles levels, relatively to non-obese controls. HsIL-6 and hsCRP were increased in obesity and were overall associated with TRP metabolic pathways alterations. Conclusion: These results indicate for the first time that KYN and indole TRP metabolic pathways are concomitantly altered in obese subjects and highlight their respective associations with obesity-related systemic inflammation.

Double Disk Excision of Large Deep Endometriosis Nodules Infiltrating the Low and Mid Rectum: A Pilot Study of 20 Cases.

STUDY OBJECTIVE: To report the technique of double disk excision of deep endometriosis nodules infiltrating the mid or low rectum and surgical outcomes. DESIGN: A retrospective case series using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis database. SETTING: University tertiary referral center. PATIENTS: Twenty women managed for large deep endometriosis nodules infiltrating the mid or low rectum. INTERVENTIONS: Double disk excision using transanal end-to-end anastomosis circular stapler. MEASUREMENTS AND MAIN RESULTS: Twenty women managed by double disk excision from May 2016 to September 2019 were included in the study. The mean time of intervention was 149 ± 74 minutes. The cumulated mean diameter of the excised rectal disks was 53.4 ± 19.1 mm, whereas in 85% of the women, it was ≥50 mm. The mean distance between the lowest margin of the disk and the anal verge was 66 mm. Vaginal infiltration was removed in 15 patients (75%), and in 6 patients (30%) it exceeded 30 mm in diameter. Owing to the presence of sigmoid colon nodules, 2 patients (10%) underwent concomitant segmental sigmoid resection of 4 cm and 6 cm in length, respectively. Transitory stoma was performed in 8 patients (40%) owing to concomitant vaginal excision >3 cm in size. After a follow-up varying from 3 months to 42 months, no digestive fistula was recorded. The rate of Clavien-Dindo 3 complications was 15%. CONCLUSION: Double disk excision is suitable for excising large deep endometriosis nodules infiltrating the mid or low rectum and is associated with a low severe complication rate with good functional outcomes in women. Further studies are required to assess the improvement of functional outcomes in deep endometriosis nodules infiltrating the mid or low rectum in comparison with colorectal resection.

Reward-related brain activity and behavior are associated with peripheral ghrelin levels in obesity.

BACKGROUND/OBJECTIVES: While excessive food consumption represents a key factor in the development of obesity, the underlying mechanisms are still unclear. Ghrelin, a gut-brain hormone involved in the regulation of appetite, is impaired in obesity. In addition to its role in eating behavior, this hormone was shown to affect brain regions controlling reward, including the striatum and prefrontal cortex, and there is strong evidence of impaired reward processing in obesity. The present study investigated the possibility that disrupted reward-related brain activity in obesity relates to ghrelin deficiency. SUBJECTS/METHODS: Fifteen severely obese subjects (BMI > 35 kg/m2) and fifteen healthy non-obese control subjects (BMI < 30 kg/m2) were recruited. A guessing-task paradigm, previously shown to activate the ventral striatum, was used to assess reward-related brain neural activity by functional magnetic resonance imaging (fMRI). Fasting blood samples were collected for the measurement of circulating ghrelin. RESULTS: Significant activations in the ventral striatum, ventromedial prefrontal cortex and extrastriate visual cortex were elicited by the fMRI task in both obese and control subjects. In addition, greater reward-related activations were present in the dorsolateral prefrontal cortex, and precuneus/posterior cingulate of obese subjects compared to controls. Obese subjects exhibited longer choice times after repeated reward and lower circulating ghrelin levels than lean controls. Reduced ghrelin levels significantly predicted slower post-reward choices and reward-related hyperactivity in dorsolateral prefrontal cortices in obese subjects. CONCLUSION: This study provides evidence of association between circulating ghrelin and reward-related brain activity in obesity and encourages further exploration of the role of ghrelin system in altered eating behavior in obesity.

History of major depression is associated with neuropsychiatric symptoms but not systemic inflammation in a cross-sectional study in obese patients.

Obesity is a major public health burden associated with neuropsychiatric comorbidities leading to social and occupational impairment. Given the growing prevalence of both obesity and mental disorders worldwide, understanding the risk factors of obesity-related neuropsychiatric comorbidities is crucial to develop preventive strategies and individualized treatments. Recent findings suggest that adiposity-driven inflammation contributes to neuropsychiatric comorbidities in obesity. However, not all obese subjects afflicted with chronic inflammation develop neuropsychiatric symptoms, suggesting additional risk factors. The aim of this study was to investigate the impact of personal history of major depressive disorder (MDD) on obesity-related inflammation and neuropsychiatric symptoms, and their relationship. A case-control study was conducted comparing 66 obese patients (body mass index > 35 kg/m2) and 22 healthy non-obese participants, free of any current neuropsychiatric diseases including MDD. Neuropsychiatric symptoms were assessed using the Neurotoxicity Rating Scale (NRS). Sociodemographic and clinical variables were gathered and blood was collected for the measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP). Multiple regression analyses were performed to assess the contribution of obesity and personal history of MDD to clinical outcomes and inflammatory status in study participants. Hs-CRP levels as well as NRS scores were significantly increased in the obese group. Overall, personal history of depression accounted for increased NRS scores but no significant association was found with inflammatory status. In addition, history of depression did not significantly modulate the relationship of obesity-related inflammation with NRS scores. Interestingly, obese individuals with history of recurrent MDD (n = 13) exhibited higher scores in the cognitive and sickness symptoms dimensions of the NRS compared to obese subjects with history of one depressive episode only. Findings indicate that history of depression contributes to neuropsychiatric symptoms, but not to systemic inflammation, in obese subjects free of current depressive episode. These results provide relevant information on the risk factors that may help identify obese subjects with increased risk of neuropsychiatric comorbidity.

Depressive symptoms in obesity: Relative contribution of low-grade inflammation and metabolic health.

BACKGROUND: Recent reports suggest that the risk of depressive symptoms in obesity is potentiated in subjects presenting a metabolically unhealthy phenotype. Inflammation is often considered a defining criteria of metabolic health. However, this factor may drive the association of metabolic health with depressive symptoms given its well-known role in the pathophysiology of depression. This study aimed at determining the relative contribution of inflammation and metabolic abnormalities to depressive symptoms in obesity. METHODS: One-hundred severely obese adults (BMI ≥ 35-40 kg/m2) and 25 non-obese control individuals (BMI < 30 kg/m2) were recruited. Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and Mini-International Neuropsychiatric Interview (MINI). Serum high-sensitive C-reactive protein (hs-CRP) was measured as a marker of systemic inflammation. Metabolically unhealthy obesity was defined as obesity associated with two or more metabolic alterations, including low high-density lipoprotein cholesterol, hypertriglyceridemia, high fasting glucose and hypertension. RESULTS: Total MADRS scores were significantly higher in obese subjects with significant inflammation (hs-CRP ≥ 5 mg/L) compared to those with low inflammation (hs-CRP < 5 mg/L) and non-obese controls. Interestingly, hs-CRP levels significantly predicted MADRS scores in the whole population under study and in the group of obese subjects. Overall, no association was found between MADRS scores and individual metabolic alterations or the composite measure of metabolically unhealthy obesity. Similarly, the association of hs-CRP with MADRS scores in obese patients was not modulated by metabolic health factors. CONCLUSIONS: These results indicate that systemic inflammation represents a stronger contributor of obesity-related depressive symptoms than metabolic health per se. This supports the notion that inclusion of inflammation in the definition of metabolically unhealthy obesity drives the association found between poor metabolic health and depressive symptoms.

Low-grade inflammation is a major contributor of impaired attentional set shifting in obese subjects.

Impairment in cognitive flexibility and set shifting abilities has been described in obesity. This alteration is critical as it can interfere with obesity management strategies. Recent evidences suggest that chronic low-grade inflammation may be involved in cognitive deficits associated with obesity, but the potential involvement in reduced flexibility remains unknown. The objective of this study was to assess the contribution of low-grade inflammation, determined by circulating levels of high-sensitivity C-reactive protein (hsCRP), in reduced cognitive flexibility and shifting abilities of obese subjects relatively to a group of non-obese participants. Performance in the intra/extra-dimensional set shift (IED) test, extracted from the CANTAB, was assessed in 66 obese subjects and 20 non-obese participants. Obese subjects with concentrations of hsCRP above 5mg/L exhibited reduced performance on the IED test in comparison to obese subjects with lower levels of hsCRP and non-obese participants. This difference was particularly manifest in the number of errors made during the extra-dimensional shift (EDS errors). In contrast, performance before the extra-dimensional shift was spared. Linear regression analyses revealed that the association between obesity and IED alterations was significant only when the condition hsCRP >5mg/L was entered in the model. These findings are important as they indicate that, rather than obesity itself, low-grade inflammation represents a major contributor of IED performance in obese subjects.

[Gastric necrosis following gastroplasty]. / Nécrose gastrique après gastroplastie.

INTRODUCTION: Over the past ten years, laparoscopic surgery in the treatment of morbid obesity has expanded. However, there are few publications describing its side effects, notably the occurrence of gastric necrosis. OBSERVATION: Two years after laparoscopic-banding for morbid obesity, a case of acute gastroenteritis in a 45 Year-old woman proved to be a gastric necrosis. COMMENTS: Relatively unknown, this complication is generally revealed by non-specific clinical signs. Only emergency oeso-gastro-duodenal opacification permits diagnosis. Early diagnosis permits conservative treatment before the onset of necrosis. CONCLUSION: Care must be taken when using this technique, which has not yet proved its innocuousness, and regular follow-up of the patient is crucial.

Methodological index for non-randomized studies (minors): development and validation of a new instrument.

BACKGROUND: Because of specific methodological difficulties in conducting randomized trials, surgical research remains dependent predominantly on observational or non-randomized studies. Few validated instruments are available to determine the methodological quality of such studies either from the reader's perspective or for the purpose of meta-analysis. The aim of the present study was to develop and validate such an instrument. METHODS: After an initial conceptualization phase of a methodological index for non-randomized studies (MINORS), a list of 12 potential items was sent to 100 experts from different surgical specialties for evaluation and was also assessed by 10 clinical methodologists. Subsequent testing involved the assessment of inter-reviewer agreement, test-retest reliability at 2 months, internal consistency reliability and external validity. RESULTS: The final version of MINORS contained 12 items, the first eight being specifically for non-comparative studies. Reliability was established on the basis of good inter-reviewer agreement, high test-retest reliability by the kappa-coefficient and good internal consistency by a high Cronbach's alpha-coefficient. External validity was established in terms of the ability of MINORS to identify excellent trials. CONCLUSIONS: MINORS is a valid instrument designed to assess the methodological quality of non-randomized surgical studies, whether comparative or non-comparative. The next step will be to determine its external validity when used in a large number of studies and to compare it with other existing instruments.