Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer.

BACKGROUND: Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC. METHODS: We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized. RESULTS: We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4+T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC. CONCLUSIONS: The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients.

Morbidity, Mortality, and Pathologic Outcomes of Transanal Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer Short-term Outcomes From a Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection. BACKGROUND: Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME. METHODS: A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention-to-treat principle; this analysis was preplanned. RESULTS: Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention-to-treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, -1.3%; 95% confidence interval (CI), -4.2% to 1.7%; P =0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, -2.8% to 5.2%; P =0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, -1.9% to 2.2%; P >0.99). CONCLUSIONS: Experienced surgeons can safely perform taTME in selected patients with rectal cancer.

A magnetic resonance imaging-based decision-making tool for predicting complex anal fistulas healing in the early postoperative period.

BACKGROUND: Magnetic resonance imaging (MRI) has excellent accuracy in diagnosing preoperative lesions before anal fistula surgery. However, MRI is not good in identifying early recurrent lesions and effective methods for quantitative assessment of fistula healing are still warranted. This retrospective study aimed to develop and validate a specific MRI-based nomogram model to predict fistula healing during the early postoperative period. METHODS: Patients with complex cryptoglandular anal fistulas who underwent surgery between January 2017 and October 2020 were included in this study. MRI features and clinical parameters were analyzed using univariate and multivariate logistic regression analysis. A nomogram for predicting fistula healing was constructed and validated. RESULTS: In total, 200 patients were included, of whom 186 (93%) were male, with a median age of 36 (18-65) years. Of the fistulas, 58.5% were classified as transsphincteric and 19.5% as suprasphincteric. The data were randomly divided into the training cohort and testing cohort at a ratio of 7:3. Logistic analysis revealed that CNR, ADC, alcohol intake history, and suprasphincteric fistula were significantly correlated with fistula healing. These four predictors were used to construct a predictive nomogram model in the training cohort. AUC was 0.880 and 0.847 for the training and testing cohorts, respectively. Moreover, the decision and calibration curves showed high coherence between the predicted and actual probabilities of fistula healing. CONCLUSIONS: We developed a predictive model and constructed a nomogram to predict fistula healing during the early postoperative period. This model showed good performance and may be clinically utilized for the management of anal fistulas.

Percutaneous versus open posterior stabilization and decompression in AOSpine-type A3 thoracolumbar fractures with neurological deficit.

BACKGROUND: This retrospective cohort study aimed to compare the clinical and radiological outcomes between two treatment strategies focusing on non-osteoporotic AOSpine-type A3 fractures of the thoracolumbar spine with neurological deficits at levels T11 to L2. METHODS: In total, 67 patients between 18 and 60 years of age who were treated operatively with either of the two treatment strategies were included. One treatment strategy included open posterior stabilization and decompression, whereas the other was based on percutaneous posterior stabilization and decompression via a tubular retraction system. Demographic data, surgical variables, and further parameters were assessed. Patient-reported outcomes (PROs), including the Visual Analog Scale (VAS), the Oswestry Disability Index (ODI), and the American Spinal Injury Association (ASIA) impairment score, were measured to assess functional outcomes. The regional Cobb angle (CA), the anterior height ratio of the fractured vertebrae (AHRV), and the degree of canal encroachment (DCE) were assessed. The ASIA score was used to assess neurological function recovery. The follow-up period was at least 12 months. RESULTS: Surgical time and postoperative hospital stay were significantly shorter in the minimally invasive surgery (MIS) group. Intraoperative blood loss was significantly less in the MIS group. Regarding radiological outcome, CA and AHRV at the time of follow-up did not show a significant difference. DCE at the time of follow-up was significantly improved in the MIS group. Lower VAS scores and better ODIs were observed in the MIS group at the 6-month follow-up, but similar outcomes were observed at the 12-month follow-up. The ASIA score was similar between both groups at the 12-month follow-up. CONCLUSIONS: Both treatment strategies are safe and effective; however, MIS could provide earlier pain relief and better functional outcomes compared with OS.

Mucocele: a rare complication following stapled haemorrhoidopexy.

BACKGROUND: Stapled haemorrhoidopexy (SH) has resulted in a unique collection of procedural complications with postoperative mucocele a particularly rare example. This study is designed to comprehensively describe the characteristics of rectal mucocele and discuss its pathogenesis following SH surgery. METHODS: A database of patients presenting with a rectal mucocele following an SH procedure was established and studied retrospectively. RESULTS: Seven patients (5 males; median age 32 years, range 20-75 years) were identified. All patients complained of variable anal discomfort with 5/7 presenting with inconstant anal pain, 2 with de novo evacuatory difficulty. These cases appeared at a median time of 6 months (range 2-84 months) after SH surgery. CONCLUSION: Rectal Mucocele develops when mucosal fragments become embedded and isolated under the mucosa. It is a preventable complication of SH surgery by ensuring correct purse string placement prior to stapled haemorrhoid excision.

Long-term surgical outcomes after resection of presacral tumours and risk factors associated with recurrence.

AIM: The incidence of presacral tumours is low and pertinent data on the management and outcomes after surgery are sparse. The aim of this study was to identify the risk factors for recurrence in patients with presacral tumours undergoing surgery at our institution. METHOD: Patients undergoing resection of a presacral tumour between 2009 and 2019 were identified from a prospectively maintained database. Demographics, clinicopathological features, preoperative imaging, operative details, morbidity, mortality, recurrence and survival were investigated. RESULTS: A total of 122 patients were identified. There were 95 women (77.9%) and the median age was 34 years. The most common presenting symptoms included pelvic pain (n = 60, 49.2%) and recurrent abscesses or fistulas (n = 40, 32.8%). The accuracy of preoperative magnetic resonance imaging (MRI) in distinguishing malignant from benign tumours was 93.9%. Six patients underwent three-dimensional computed tomography angiography (3D-CTA) and preoperative interventional embolization. Procedures were performed using transabdominal (n = 9), posterior (n = 99) and combined abdominal and posterior (n = 14) approaches. There were 21 (17.2%) malignant and 101 (82.8%) benign tumours. The local recurrence rate was 33.3% for malignant tumours and 9.9% for benign tumours. Multivariate analysis revealed that recurrence of malignant tumours was associated with R1 resection while recurrence of benign tumours was associated with secondary resections and intraoperative lesion rupture. CONCLUSION: Presacral tumours continue to be a diagnostic and therapeutic challenge. A multidisciplinary team, informed by modern imaging modalities, is essential for the management of presacral tumours.

Perianal and perineal rhabdomyosarcomas: a retrospective multicenter study of 35 cases.

BACKGROUND: Perianal/perineal rhabdomyosarcomas (PRMS) are easily misdiagnosed soft tissue tumours with a poor prognosis. This study was designed to analyze the clinical, diagnostic, pathological and prognostic features of PRMS, and to explore currently available therapeutic modalities. METHODS: Clinical data of PRMS patients admitted to the Sixth Affiliated Hospital and the Cancer Center of Sun Yat-sen University and from related Chinese literature published from 1987 to 2018 were collected and analyzed. The Chi-square test was used to evaluate the differences between each group. The Kaplan-Meier methods were applied to estimate and compare survival rates. RESULTS: A total of 35 patients were included in this study; 20 identified within related Chinese literatures and 15 from our center admitted during the period of 1997-2019. Out of these cases, 34 presented with perianal masses and the remaining one manifested as an inguinal mass. Moreover, 20 patients complained of pain and 16 of them were misdiagnosed as perianal abscesses, in which the presence of pain contributed to the misdiagnosis (p < 0.05). The average time interval between symptom onset and pathological diagnosis was 3.1 months. Next, 13 cases were classified into IRS group III/IV and 20 cases into stages 3/4. Additionally, 14 and 9 cases received the pathological diagnoses of embryonal rhabdomyosarcoma and alveolar rhabdomyosarcoma, respectively. Regarding the patients' survival rates, five patients survived for more than 2 years, and three of them survived for more than 5 years. The overall 2 years and 5 years survival rates were 32% and 24%, respectively. The symptom of pain and misdiagnosis both contributed to the poor prognosis in these patients (p < 0.05). MRI showed that the PRMS were closely related to external anal sphincter in 10 cases. CONCLUSION: PRMS are easily misdiagnosed lesions, which often leads to an unfavourable outcome in affected patients. Patients with painful perianal masses should be evaluated to exclude PRMS. MRI revealed that PRMS are closely related to the external anal sphincter. Multidisciplinary management is recommended in the treatment of PRMS.

Astragaloside IV alleviates mouse slow transit constipation by modulating gut microbiota profile and promoting butyric acid generation.

Gut microbiota and short-chain fatty acids (SCFAs) are associated with the development of various human diseases. In this study, we examined the role of astragaloside IV in modulating mouse gut microbiota structure and the generation of SCFAs, as well as in slow transit constipation (STC). An STC model was established by treating mice with loperamide, in which the therapeutic effects of astragaloside IV were evaluated. The microbiota community structure and SCFA content were analysed by 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. The influence of butyrate on STC was assessed using a mouse model and Cajal cells (ICC). Astragaloside IV promoted defecation, improved intestinal mobility, suppressed ICC loss and alleviated colonic lesions in STC mice. Alterations in gut microbiota community structure in STC mice, such as decreased Lactobacillus reuteri diversity, were improved following astragaloside IV treatment. Moreover, astragaloside IV up-regulated butyric acid and valeric acid, but decreased isovaleric acid, in STC mouse stools. Butyrate promoted defecation, improved intestinal mobility, and enhanced ICC proliferation by regulating the AKT-NF-κB signalling pathway. Astragaloside IV promoted intestinal transit in STC mice and inhibited ICC loss by regulating the gut microbiota community structure and generating butyric acid.

Modified Stapled Transanal Rectal Resection Procedure for Limited Rectal Prolapse: A Viable Alternative to the Delorme Operation.

Purpose. The optimal surgical approach for full-thickness rectal prolapse (FTRP) remains controversial. In China, patients with limited FTRP (<5 cm in length) are usually managed by perineal surgery. We retrospectively assessed the outcome of Delorme's procedure and compared it with modified stapled transanal rectal resection (STARR). Methods. The study was conducted in 2 public tertiary referral centers in China with modified STARR or Delorme's procedure performed by experienced surgeons. Outcomes assessed recurrence, operative times, blood loss, complications, length of hospital stay, and continence and constipation scoring. Results. Between December 2012 and May 2019, 65 patients were assessed, including 48 with modified STARR (group 1) and 17 with Delorme's procedure (group 2). The median follow-up was 22 months (range, 3-86 months). The mean operative time for group 1 was 37.4 ± 17.5 minutes vs 74.3 ± 30.6 minutes for group 2 (P < .001). The blood loss for group 1 was significantly lower than that for group 2 (17.4 ± 15.9 mL vs 27.8 ± 16.7 mL, respectively; P = .028). There was no significant difference between groups in recurrence (group 1 18.8% vs group 2 23.5%; P = .944) with no effect of operation type. Both procedures showed improvement in constipation and continence scoring with a similar impact. Conclusions. Modified STARR and the Delorme operation are comparable in managing limited FTRP with superior results in operative time and blood loss for STARR.

ROS/JNK/c-Jun axis is involved in oridonin-induced caspase-dependent apoptosis in human colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common malignant neoplasms with high mortality worldwide. Oridonin, a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens, has been proved to have anticancer effect on various types of cancer cells. However, the detailed mechanisms of oridonin in CRC cells remain unclear and if oridonin can overcome 5-FU resistance have not been investigated yet. In this study, we investigated the anticancer effect of oridonin in both 5-FU sensitive and resistant CRC cells and illuminated the underlying mechanisms. We showed that oridonin induced proliferation inhibition and caspase-dependent apoptosis in both 5-FU sensitive and resistant CRC cells. Oridonin induced reactive oxygen species (ROS) accumulation in both 5-FU sensitive and resistant CRC cells, which resulted in cell apoptosis as oridonin-induced apoptosis was almost abolished when cells were co-treated with the ROS scavenger N-acetyl-L-cysteine (NAC). Moreover, we found that oridonin induced CRC cell apoptosis via the c-Jun N-terminal kinase (JNK)/c-Jun pathway as oridonin activated JNK/c-Jun pathway and the JNK inhibitor SP600125 restored oridonin-induced apoptosis in CRC cells. Interestingly, when CRC cells were co-treated with NAC, the activation of JNK/c-Jun pathway induced by oridonin was nearly reversed, indicating that oridonin induced JNK/c-Jun pathway activation through the accumulation of ROS. Taken together, these data reveal that oridonin induces apoptosis through the ROS/JNK/c-Jun axis in both 5-FU sensitive and resistant CRC cells, suggesting that oridonin could be a potential agent for CRC treatment.

Partial Stapled Hemorrhoidopexy Versus Circumferential Stapled Hemorrhoidopexy for Grade III to IV Prolapsing Hemorrhoids: A Randomized, Noninferiority Trial.

BACKGROUND: Long-term outcomes and efficacy of partial stapled hemorrhoidopexy are not known. OBJECTIVE: The purpose of this study was to compare the long-term clinical efficacy and safety of partial stapled hemorrhoidopexy with circumferential stapled hemorrhoidopexy. DESIGN: This was a parallel group, randomized, noninferiority clinical trial. SETTINGS: The study was conducted at a single academic center. PATIENTS: Patients with grade III/IV hemorrhoids between August 2011 and November 2013 were included. INTERVENTIONS: Three hundred patients were randomly assigned to undergo either partial stapled hemorrhoidopexy (group 1, n = 150) or circumferential stapled hemorrhoidopexy (group 2, n = 150). MAIN OUTCOME MEASURES: The primary outcome was the rate of recurrent prolapse at a median follow-up period of 5 years with a predefined noninferiority margin of 3.75%. Secondary outcomes included incidence and severity of postoperative pain, fecal urgency, anal continence, and the frequency of specific complications, including anorectal stenosis and rectovaginal fistula. RESULTS: The visual analog scores in group 1 were less than those in group 2 (p < 0.001). Fewer patients in group 1 experienced postoperative urgency compared with those in group 2 (p = 0.001). Anal continence significantly worsened after both procedures, but the difference between preoperative and postoperative continence scores was higher for group 2 than for group 1. Postoperative rectal stenosis did not develop in patients in group 1, although it occurred in 8 patients (5%) in group 2 (p = 0.004). The 5-year cumulative recurrence rate between group 1 (9% (95% CI, 4%-13%)) and group 2 (12% (95% CI, 7%-17%)) did not differ significantly (p = 0.137), and the difference was within the noninferiority margin (absolute difference, -3.33% (95% CI, -10.00% to 3.55%)). LIMITATIONS: The study was limited because it was a single-center trial. CONCLUSIONS: Partial stapled hemorrhoidopexy is noninferior to circumferential stapled hemorrhoidopexy for patients with grade III to IV hemorrhoids at a median follow-up period of 5 years. However, partial stapled hemorrhoidopexy was associated with reduced postoperative pain and urgency, better postoperative anal continence, and minimal risk of rectal stenosis. See Video Abstract at http://links.lww.com/DCR/A790.Trial registration (chictr.org) identifier is chiCTR-trc-11001506.

A Positive Feedback Loop Between Th17 Cells and Dendritic Cells in Patients with Endplate Inflammation.

BACKGROUND: Endplate inflammation remains a difficult disease to treat, in part due to its unclear pathology. Previous experiments showed that patients with idiopathic inflammation presented a systemic upregulation of Th17 cells. Here, we investigated how this change might affect the inflammatory environment in endplate inflammation. METHODS: Peripheral blood was obtained from patients and healthy controls, and Th17 cells were examined. RESULTS: Th17 cells significantly increased the differentiation of CD11c+ and DC-SIGN+ dendritic cells (DCs) from circulating monocytes in the absence of exogenous stimulation as well as in the presence of LPS stimulation. Th17 cells also increased CD80 and CD86 expression by DCs. Importantly, although Th17 cells from both healthy controls and patients with endplate inflammation could induce CD11c, DC-SIGN, CD80, and CD86 expression, Th17 cells from patients with endplate inflammation showed significantly more potent capacity. Both contact-dependent and IL-17-dependent mechanisms were employed by Th17 cells, since blocking cell-to-cell contact significantly inhibited Th17-mediated differentiation of CD11c+ DCs, and neutralization of IL-17 reduced the expression of CD80 and CD86. Strikingly, DCs following incubation with Th17 cells, but not the DCs derived directly from monocytes without Th17 cells, could significantly promote the expression of IL-17 from naive CD4+ T cells. CONCLUSIONS: These results demonstrated that Th17 cells from patients with endplate inflammation could potently induce the differentiation and activation of DCs that preferentially promoted IL-17 response in a positive feedback loop.

Patients with idiopathic endplate inflammation displayed aberrant Th17 responses resulting in proinflammatory monocyte activation.

Endplate inflammation remains a difficult task to diagnose and treat, partly due to the absence of in-depth understanding of the cellular and molecular factors driving this condition. In the current study, we investigated the circulating immune cells in patients with idiopathic endplate inflammation. Compared to healthy controls, the patients with endplate inflammation presented a significant upregulation of Th17 cells, characterized by higher frequencies of circulating IL-17+CD4+ T cells examined directly ex vivo and after PMA and ionomycin (PMA/I) stimulation. The frequency of Th17 cells in patients was not correlated with patient age, sex, or smoking status, but was significantly correlated with patient BMI. The total CD4+ T cells from patients with end plate inflammation also presented significantly higher levels of IL-17 secretion directly ex vivo and after PMA/I stimulation. The IL-17 secretion was primarily mediated by CCR4+CCR6+ CD4+ T cells, followed by CCR4-CCR6+ CD4+ T cells and was nearly absent in CCR4-CCR6- CD4+ T cells. Monocytes incubated with CCR4+CCR6+ CD4+ T cells presented significantly higher MHC class II expression, as well as higher CD80 and CD86 expression. The secretion of IL-6 and TNF was significantly higher in cell cultures containing CCR4+CCR6+ CD4+ T cells than in cell cultures containing CCR4-CCR6- CD4+ T cells. These effects were reduced when the IL-17A cytokine was neutralized. Together, we identified a systemic upregulation of Th17 responses that could contribute to proinflammatory monocyte activation in patients with endplate inflammation.

Stapled Transperineal Fistula Repair of Rectovaginal Fistula: A Preliminary Experience.

PURPOSE: This study is designed to assess the safety, efficacy, and postoperative outcomes of stapled transperineal repair in management of rectovaginal fistula (RVF). METHODS: A prospective database of patients with RVF undergoing stapled transperineal repair between May 2015 and December 2017 was established and studied retrospectively. RESULTS: Seven consecutive RVF patients underwent stapled transperineal repair. The mean operative time was 119 ± 42 minutes. The estimated blood loss during operation was 24 ± 14 mL. Concomitant levatorplasty was performed with 4 patients and sphincteroplasty with 2 patients. Over a median follow-up of 6 months (range 3-33 months), no case was encountered with recurrence. The mean postoperative Wexner score was significantly improved when compared with the preoperative scores (mean preoperative vs postoperative Wexner scores 3 [range 3-4] vs 1 [range 1-2], respectively; P = .01). CONCLUSIONS: Stapled transperineal repair of RVF appears safe and effective. The initial results are encouraging, suggesting the need for a more formal prospective assessment of this technique as part of a randomized trial for the management of low- and mid-vaginal fistulas.

A Modification of the Stapled TransAnal Rectal Resection (STARR) Procedure for Rectal Prolapse.

PURPOSE: This study was designed to assess the safety, efficacy, and postoperative outcomes of the modified Stapled TransAnal Rectal Resection (modified STARR) in patients presenting with cases of limited external rectal prolapse. METHODS: A prospective cohort of patients with mild rectal prolapse undergoing rectal resection with the Tissue-Selecting Technique Stapled TransAnal Rectal Resection Plus (TSTStarr Plus) stapler between February 2014 and September 2016 was reviewed retrospectively. RESULTS: Twenty-five eligible patients underwent rectal resection with the TSTStarr Plus stapler. The median vertical height of the resected specimen was 5.0 cm (range = 3.1-10 cm) with all cases being confirmed histologically as full-thickness resections. Over a follow-up of 33.6 ± 9.4 months, only 1 case (4%) was encountered with recurrence. The mean postoperative Wexner score was significantly improved when compared with the preoperative scores (preoperative: median = 3, range = 0-20, vs postoperative: median = 2, range = 0-20, respectively; P = .010). The median preoperative Symptom Severity Score and Obstructed Defecation Score were both decreased compared with the postoperative scores ( P = .001). CONCLUSIONS: Modified STARR in management of mild rectal prolapse appear to be a safe and effective technique. The initial results would encourage a more formal prospective assessment of this technique as part of a randomized trial for the management of mild rectal prolapse.

Clinical Significance of 2 Deep Posterior Perianal Spaces to Complex Cryptoglandular Fistulas.

BACKGROUND: Confusion exists regarding the clinical significance of the deep posterior intersphincteric space and deep postanal space to complex perianal fistulas. OBJECTIVE: The purpose of this study was to assess the clinical significance of the 2 deep posterior perianal spaces and to describe in detail the courses of posterior complex cryptoglandular fistula extensions. DESIGN: This was a retrospective study. MRI-based characteristics of selected perianal fistulas were independently evaluated by examiners who focused on lesions in these 2 spaces and were blinded to each other's findings. SETTINGS: This study was conducted in the colorectal surgery and radiology departments of a large university teaching hospital in China. PATIENTS: Included in the study were patients who underwent pelvic MRI for posterior perianal fistula between October 2012 and December 2014. MAIN OUTCOME MEASURES: The occurrence rates of these 2 deep perianal space lesions in posterior cryptoglandular fistulas were determined. RESULTS: A total of 513 primary posterior cryptoglandular fistulas were identified in 508 patients, including 167 deep posterior intersphincteric space lesions (32.6%) and 23 deep postanal space lesions (4.5%). Of those, 173 fistulas (33.7%) were evaluated as complex. The former and latter spaces were involved in 79.2% (137/173) and 13.3% (23/173) of posterior complex fistulas. Compared with deep postanal space lesions, deep posterior intersphincteric space lesions were more common in cases with high transsphincteric or suprasphincteric fistulas (80.1% vs 15.8%), synchronous multiple transsphincteric fistulas (82.4% vs 20.6%), horseshoe-like fistulas (85.5% vs 14.5%), and supralevator fistulas (93.5% vs 16.1%). Similar incidences were also seen in cases with ischioanal-involved horseshoe-like fistulas (75.0% vs 25.0%). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: The deep posterior intersphincteric space is more likely than the deep postanal space to be involved in complex cryptoglandular fistulas and is likely to play a more important role in the management of complex cryptoglandular fistulas.

Tailored prolapse surgery for the treatment of haemorrhoids and obstructed defecation syndrome with a new dedicated device: TST STARR Plus.

OBJECTIVE: The aim of the study was to assess the safety, efficacy and feasibility of stapled transanal procedures performed by a new dedicated device, TST STARR Plus, for tailored transanal stapled surgery. METHODS: All the consecutive patients admitted to eight referral centres affected by prolapses with III-IV degrees haemorrhoids or obstructed defecation syndrome (ODS) with rectocele and/or rectal intussusception that underwent stapled transanal resection with TST STARR plus were included in the present study. Haemostatic stitches for bleeding of the suture line, specimen volume, operative time, hospital stay and perioperative complications were recorded. RESULTS: From 1 November 2012 to 31 March 2013, 160 consecutive patients (96 females) were enrolled in the study. In 94 patients, the prolapse was over the half of the circular anal dilator (CAD). The mean duration of the procedure was 25 min. The mean resected volume of the specimen was 13.3 cm(3), the mean hospital stay was 2.2 days. In 88 patients (55%), additional stitches on the suture line were needed (mean 2.1). Suture line dehiscence was reported in four cases, with intraoperative reinforcement. Bleeding was reported in seven patients (5%). Urgency after 30 days was reported in one patient. No major complication occurred. CONCLUSIONS: The new device seems to be safe and effective for a tailored approach to anorectal prolapse due to haemorrhoids or obstructed defecation.

Preoperative assessment of fistula-in-ano using SonoVue enhancement during three-dimensional transperineal ultrasound.

Background: Accurate preoperative evaluation of fistula-in-ano can guide the choice of surgical procedure and may improve healing rates. This prospective study aimed to evaluate the accuracy of conventional 3D transperineal ultrasound (3D-TPUS) compared with SonoVue (SVE)-enhanced 3D-TPUS for the detection and classification of anal fistula. Methods: In this prospective study, 3D-TPUS reconstructions were performed before and after SVE enhancement in 60 patients with fistula-in-ano who intended to undergo surgery at the Department of Anorectal Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University (P. R. China) between January 2021 and October 2021. Accuracies of anal fistula classification, complexity classification, detection of anal fistula branches, and detection of internal opening between 3D-TPUS and SVE 3D-TPUS were compared based on a reference standard-intraoperative findings. Results: This study enrolled 60 patients (mean age, 37.1 ± 11.4 years; mean follow-up, 9 ± 3 months). Intraoperative findings showed that the fistula type was intersphincteric in 23 patients (38.3%), trans-sphincteric in 35 (58.3%; 12 high and 23 low), and suprasphincteric in 2 (3.3%). Moreover, 68 internal openings were found. Compared with the accuracy of 3D-TPUS, that of SVE 3D-TPUS was similar in fistula classification [95.0% (57/60) vs 96.7% (58/60), P = 0.392], but significantly higher in internal opening evaluation [80.9% (55/68) vs 97.1% (66/68), P = 0.001], complexity classification [85.0% (51/60) vs 98.3% (59/60), P = 0.018], and detection of fistula branches [70.4% (19/27) vs 92.6% (25/27), P = 0.031]. Conclusions: SVE 3D-TPUS may be a useful examination for patients with perianal fistulae because of its high accuracy and consistency with intraoperative findings, especially in complex fistula-in-ano and difficult cases.

Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation.

The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and dysfunctions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.

Stapled transperineal rectovaginal fistula repair for low- and mid-level rectovaginal fistulas: A comparison study with rectal mucosal advancement flap repair.

BACKGROUND: As an innovative treatment, stapled transperineal rectovaginal fistula repair (STR) for rectovaginal fistula (RVF) has demonstrated effectiveness in preliminary reports. This study aims to compare STR with rectal mucosal advancement flap repair (RAF), a widely utilized surgical procedure, for the surgical outcome of the low- and mid-level RVF. METHODS: In this retrospective cohort study, patients with low- and mid-level RVF who underwent STR or RAF were included from both the Sixth Affiliated Hospital of Sun Yat-sen University and Xi'an Daxing Hospital. Among the 99 total patients, 77 underwent STR and 22 underwent RAF. Patient demographics, operative data, and outcomes were collected and analyzed. Recurrence rate and associated risk factors were evaluated. RESULTS: There were no statistically significant differences among patients in terms of clinical characteristics like age, BMI, aetiology, and fistula features. During the follow-up period of 20 months (interquartile range 3.0-41.8 months), a total of 28 patients relapsed, with a significantly lower recurrence rate in the STR group (20.8 %) than in the RAF group (54.6 %) (P = 0.005). In the multivariate Cox analysis, STR was an independent protective factor against recurrence (HR: 0.37, 95%CI: 0.17-0.79, P = 0.01). Logistic regression indicated that there was no statistically significant difference between these two procedures in terms of surgical complications (OR: 0.53, 95%CI: 0.19-1.48, P = 0.23). CONCLUSION: For low- and mid-level RVF, STR may be an alternative option for treatment modality that offers a lower recurrence rate, without observed disadvantage in terms of surgical complication rates.