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 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.

Osthole, a Coumadin Analog from Cnidium monnieri (L.) Cusson, Ameliorates Nucleus Pulposus-Induced Radicular Inflammatory Pain by Inhibiting the Activation of Extracellular Signal-Regulated Kinase in Rats.

AIM: This study was aimed at assessing the role of extracellular signal regulated kinase (ERK) in mechanical allodynia resulting from lumbar disc herniation (LDH) and exploring the osthole's anti-nociceptive effect on ERK activation. METHODS: Radicular pain was generated by applying nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). Allodynia was measured using Von Frey filaments to calculate the mechanical pain threshold. Phosphorylated ERK and total ERK protein in the lumbar spinal dorsal horn was detected by using the Western blot technique. Cyclooxygenase 2 (COX-2) mRNA was assessed by real-time reverse-transcription polymerase chain reaction. RESULTS: The application of NP to L5 DRG induced mechanical hypersensitivity which lasted for at least 28 days, and a significant increase of ERK phosphorylation in the ipsilateral spinal dorsal horn from postoperative day (POD) 1 to POD 21. ERK inhibitor attenuated NP-induced hyperalgesia compared to the dimethyl sulfoxide-(vehicle control) administered group (p < 0.05). Epidural treatment with osthole could ameliorate NP-evoked hyperalgesia by suppressing the activation of ERK rather than decreasing the expression of ERK protein. Osthole could also inhibit the increased expression of COX-2 mRNA in spinal dorsal horn, which was a known downstream effect of ERK signaling pathway. CONCLUSIONS: Our results suggest that ERK activation in the spinal dorsal horn plays a vital role in NP-evoked hyperalgesia. Osthole exerts analgesic effect on radicular inflammatory pain in LDH rat model, by down-regulating the mRNA expression of the target gene of COX-2 via inhibiting ERK activation in the spinal dorsal horn.

Astragaloside IV Ameliorates Colonic Adenomatous Polyps Development by Orchestrating Gut Bifidobacterium and Serum Metabolome.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/ß-catenin pathway proteins (Wnt3a, ß-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/ß-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.

Blocking TNF-α with infliximab alleviates ovariectomy induced mechanical and thermal hyperalgesia in rats.

Studies have proved an increased expression of tumor necrosis factor alpha (TNF-α) in estrogen deficiency animals, and TNF-α also plays a role in inflammation and neuropathic pain. This study aimed to explore the relationship between TNF-α and ovariectomy induced hyperalgesia. 36 female Sparague-Dawley were included, estrogen depletion models were established by ovariectomy. Then infliximab (a TNF-α blocker) was administrated to the ovariectomized rats for 8 weeks. Pain behavioral tests were performed once a week. The bone mineral density (BMD), serum estradiol and TNF-α level were determined at the 8th week after ovariectomy. The expression of TNF-α in lumbar 5 dorsal root ganglions (L5 DRGs) was examined by immunofluorescence method. Significant hyperalgesia to mechanical and thermal stimuli in groups Ovx-1 and Ovx-2 was observed 1 week after the operation. After treated with infliximab, the pain threshold of Ovx-2 was partially restored, although still lower than the Sham group. The serum TNF-α level of Ovx-1 was significantly higher than Sham and Ovx-2. TNF-α immunofluorescence indicated a significant increase in the expression of TNF-α at L5 DRGs in group Ovx-1 when compared with groups Sham and Ovx-2. The BMD of group Ovx-2 was significantly higher than group Ovx-1 and lower than group Sham. In conclusion, TNF-α plays an important role in estrogen deficiency induced mechanical and thermal hyperalgesia, and DRG may be one site on which TNF-α acts to cause hyperalgesia. Blocking the effect of TNF-α could partially alleviate the estrogen deficiency induced hyperalgesia in rats. Thus, TNF-α may contribute to chronic pain in postmenopausal women.

Osthole, a herbal compound, alleviates nucleus pulposus-evoked nociceptive responses through the suppression of overexpression of acid-sensing ion channel 3 (ASIC3) in rat dorsal root ganglion.

BACKGROUND: Osthole (Ost), a natural coumarin derivative, has been shown to inhibit many pro-inflammatory mediators and block voltage-gated Na+ channels. During inflammation, acidosis is an important pain inducer which activates nociceptors by gating depolarizing cationic channels, such as acid-sensing ion channel 3 (ASIC3). The aim of this study was to examine the effects of Ost on nucleus pulposus-evoked nociceptive responses and ASIC3 over-expression in the rat dorsal root ganglion, and to investigate the possible mechanism. MATERIAL/METHODS: Radicular pain was generated with application of nucleus pulposus (NP) to nerve root. Mechanical allodynia was evaluated using von Frey filaments with logarithmically incremental rigidity to calculate the 50% probability thresholds for mechanical paw withdrawal. ASIC3 protein expression in dorsal root ganglions (DRGs) was assessed with Western blot and immunohistochemistry. Membrane potential (MP) shift of DRG neurons induced by ASIC3-sensitive acid (pH6.5) was determined by DiBAC(4) (3) fluorescence intensity (F.I.). RESULTS: The NP-evoked mechanical hyperalgesia model showed allodynia for 3 weeks, and ASIC3 expression was up-regulated in DRG neurons, reaching peak on Day 7. Epidural administration of Ost induced a remarkable and prolonged antinociceptive effect, accompanied by an inhibition of over-expressed ASIC3 protein and of abnormal shift of MP. Amiloride (Ami), an antagonist of ASIC3, strengthened the antinociceptive effect of Ost. CONCLUSIONS: Up-regulation of ASIC3 expression may be associated with NP-evoked mechanical hyperalgesia. A single epidural injection of Ost decreased ASIC3 expression in DGR neurons and the pain in the NP-evoked mechanical hyperalgesia model. Osthole may be of great benefit for preventing chronic pain status often seen in lumbar disc herniation (LDH).

Modification of rat model of sciatica induced by lumber disc herniation and the anti-inflammatory effect of osthole given by epidural catheterization.

One of the most treatable causes of lower back pain and associated sciatica is lumbar disc herniation (LDH), which is characterized by rupture of the hard outer wall (annulus fibrosis) in a lumbar intervertebral disc. In the current study, we aimed to: (1) develop and characterize a rat model of sciatica induced by LDH, while introducing a novel method of epidural catheterization; (2) use this model to evaluate the effect of osthole on pain due to LDH, and (3) gain insight into the mechanisms through which osthole affects sciatica induced by LDH. The results indicate that our newly developed rat model maintained mechanical allodynia for 28 days without reduction. Moreover, cyclooxygenase-2 (COX-2) and nitric oxide synthase (NOS) were overexpressed in the associated inflammatory response, which is consistent with clinical manifestations of the disease. We then used this model to study the effect and mechanisms through which osthole affected pain due to LDH. Our study suggests that osthole is capable of reversing hyperalgesia due to LDH, potentially through modulation of activity of COX-2 and NOS, two important proteins for the exacerbation of pain due to LDH. Finally, a molecular modeling simulation showed that osthole has unique binding capabilities to both NOS and COX-2. As the model-induced mechanical hyperalgesia response was consistent, and the position of the catheter tip and the extension/spreading of the drug in the epidural space were reliable, this study developed an improved model to study remedies for sciatic pain. Moreover, our studies demonstrate that osthole may be a feasible treatment for the reduction of pain due to hyperalgesia.

Partial stapled hemorrhoidopexy: a minimally invasive technique for hemorrhoids.

PURPOSE: This study was designed to assess the safety, efficacy, and postoperative outcomes of partial stapled hemorrhoidopexy (PSH). METHODS: A prospective study was conducted between February and March 2010. PSH was performed with single-window anoscopes for single isolated hemorrhoids, bi-window anoscopes for two isolated hemorrhoids, and tri-window anoscopes for three isolated hemorrhoids or circumferential hemorrhoids. The data pertaining to demographics, preoperative characteristics and postoperative outcomes were collected and analyzed. RESULTS: Forty-four eligible patients underwent PSH. Single-window anoscopes were used in 2 patients, and bi- and tri-window anoscopes in 6 and 36 patients. The blood loss in patients with single-window, bi-window, and tri-window anoscopes was 6.0 ml (range 5.0-7.0 ml), 5.0 ml (range 5.0-6.5 ml), and 5.0 ml (4.5-14.5 ml) (P = 0.332). The mean postoperative visual analog scale score for pain was 3 (range, 1-4), 2 (range 1-4), 3 (range 2-6), 1 (range 0-3), 1 (range 0-2) and 2 (range 2-4) at 12 h, days 1, 2, 3, and 7, and at first defecation. The rate of urgency was 9.1%. No patients developed anal incontinence or stenosis. The 1-year recurrence rate of prolapsing hemorrhoids was 2.3%. CONCLUSIONS: Partial stapled hemorrhoidopexy appears to be a safe and effective technique for grade III-IV hemorrhoids. Encouragingly, PSH is associated with mild postoperative pain, few urgency episodes, and no stenosis or anal incontinence.

Gastrointestinal dysfunction is associated with mortality in severe burn patients: a 10-year retrospective observational study from South China.

BACKGROUND: Data on severe and extensive burns in China are limited, as is data on the prevalence of a range of related gastrointestinal (GI) disorders [such as stress ulcers, delayed defecation, opioid-related bowel immotility, and abdominal compartment syndrome (ACS)]. We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality. METHODS: This retrospective analysis was conducted on patients with severe [≥ 20% total burn surface area (TBSA)] and extensive (> 50% TBSA or > 25% full-thickness TBSA) burns admitted to three university teaching institutions in China between January 1, 2011 and December 31, 2020. Both 30- and 90-day mortality were assessed by collating demographic data, burn causes, admission TBSA, % full-thickness TBSA, Baux score, Abbreviated Burn Severity Index (ABSI) score, and Sequential Organ Failure Assessment (SOFA) score, shock at admission and the presence of an inhalation injury. GI dysfunction included abdominal distension, nausea/vomiting, diarrhoea/constipation, GI ulcer/haemorrhage, paralytic ileus, feeding intolerance and ACS. Surgeries, length of intensive care unit (ICU) stay, pain control [in morphine milligram equivalents (MME)] and overall length of hospital stay (LOHS) were recorded. RESULTS: We analyzed 328 patients [75.6% male, mean age: (41.6 ± 13.6) years] with a median TBSA of 62.0% (41.0-80.0%); 256 (78.0%) patients presented with extensive burns. The 90-day mortality was 23.2% (76/328), with 64 (84.2%) of these deaths occurring within 30 d and 25 (32.9%) occurring within 7 d. GI dysfunction was experienced by 45.4% of patients and had a significant effect on 90-day mortality [odds ratio (OR) = 14.070, 95% confidence interval (CI) 5.886-38.290, P < 0.001]. Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and % full-thickness TBSA. Overall, 88.2% (67/76) of deceased patients had GI dysfunction [hazard ratio (HR) for death of GI dysfunction = 5.951], with a survival advantage for functional disorders (diarrhoea, constipation, or nausea/vomiting) over GI ulcer/haemorrhage (P < 0.001). CONCLUSION: Patients with severe burns have an unfavourable prognosis, as nearly one-fifth died within 90 d. Half of our patients had comorbidities related to GI dysfunction, among which GI ulcers and haemorrhages were independently correlated with 90-day mortality. More attention should be given to severe burn patients with GI dysfunction.

[Effects and mechanisms of osthole on sciatica induced by lumber disc herniation].

OBJECTIVE: To study the effects of osthole on sciatica induced by lumber disc herniation and its mechanisms. METHODS: 54 male SD rats were randomly divided into 6 groups. Model (M) group (n = 12): Autologous nucleus pulposus was harvested from the tail and applied to the L5 dorsal root ganglion (DRG) and epidural space. Epidural catheterization was performed. Control(C) group (n = 12): On the basis of nucleus pulposus group, 50 microL tween-80 was administered epidurally on the day 6th after surgery. T2 (n = 6), T6 (n = 12), T13 (n = 6) and T20 (n = 6) group: 50 microL 2% osthole was administered epidurally on the 2th, 6th, 13th day and 20th after surgery respectively. General behaviors were observed and 50% paw withdrawal threshold (50% PWT) was measured 1 day before surgery, on the 1st, 3th, 7th,14th, 21th, 28th day after surgery, immediately before and 1 hour after osthole or tween-80 administration in each group. On the 7th day after surgery, the left L5 DRGs were obtained for detecting the expression of NOS and COX-2 in M, C and T6 group with 6 rats. RESULTS: No lameness or autophagy was oberserved. 50% PWT decreased after surgery (P < 0.05). In T2 and T6 group, 50% PWT after osthole administration were significantly higher than those of M group and C group (P < 0.05), which recovered to the same level as 1 day before surgery (P > 0.05). In T13 and T20 group, 50% PWT 1 hour after osthole administration were significantly higher than those of M group and C group (P < 0.05), which recovered to the same level as 1 day before surgery (P > 0.05), but on days after 1 hour after administration, there was no significant difference when 50% PWT compared with M group or nucleus C group (P > 0.05). NOS positive cells and COX-2 positive cells were no significant difference when M group compared with C group (P > 0.05). But these positive cells in T6 group were significantly lower than those of M group and C group (P < 0.05). CONCLUSION: 50 microL 2% osthole could completely inhibit the mechanical allodynia in the rat model of sciatica induced by lumbar disc herniation when it was administered epidurally on 2 or 6 day after surgery. But when administered on 13 or 20 day after surgery, its analgesic effect was transient. The effect of 50 microL 2% osthole epidural administration on day 6 after surgery on the rat model of sciatica induced by lumbar disc herniation may relate to inhibition of the expression of COX-2 and NOS in DRG.

Outcomes in patients with Fournier's gangrene originating from the anorectal region with a particular focus on those without perineal involvement.

BACKGROUND AND AIM: Fournier's gangrene (FG) is a fulminant infection in the external genital region and perineum. The present study explored the clinical features of FG originating from the anorectal region, from primary conditions such as anal fistulas and abscesses. METHODS: A retrospective analysis was performed in order to identify the factors associated with clinical outcomes in FG patients derived from two hospitals-the Sixth Affiliated Hospital of Sun Yat-sen University and People's Hospital Affiliated to Fujian University of Traditional Chinese-over the period from May 2013 to April 2017. RESULTS: Sixty FG patients were included in this study. The common causative microorganisms cultured were Escherichia coli species. Genital and perirectal regional involvement was evident in 52 and 59 cases, respectively, although the perineum was unaffected in 7 cases (12%), as confirmed by imaging examination and surgical exploration. Management with early radical debridement and broad-spectrum antibiotic therapy is effective with an acceptably sepsis mortality (1.7%). Ten patients underwent protective colostomy. No patient underwent an orchidectomy and required urinary diversion. CONCLUSIONS: FG originating from the anorectal region can be rapidly progressive and life-threatening. Infection can spread superiorly to the genital region without the involvement in perineal tissue. An aggressive surgical debridement of non-viable tissue is essential for satisfactory outcomes and a protective colostomy is not mandatory.

Does intraoperative ulinastatin improve postoperative clinical outcomes in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

INTRODUCTION: The systematic meta-analysis of randomized controlled trials (RCTs) evaluated the effects of intraoperative ulinastatin on early-postoperative recovery in patients undergoing cardiac surgery. METHODS: RCTs comparing intraoperative ulinastatin with placebo in cardiac surgery were searched through PubMed, Cochrane databases, Medline, SinoMed, and the China National Knowledge Infrastructure (1966 to May 20th, 2013). The primary endpoints included hospital mortality, postoperative complication rate, length of stay in intensive care unit, and extubation time. The physiological and biochemical parameters illustrating postoperative cardiac and pulmonary function as well as inflammation response were considered as secondary endpoints. RESULTS: Fifteen RCTs (509 patients) met the inclusion criteria. Ulinastatin did not affect hospital mortality, postoperative complication rate, or ICU length of stay but reduced extubation time. Ulinastatin also increased the oxygenation index on postoperative day 1 and reduced the plasma level of cardiac troponin-I. Additionally, ulinastatin inhibited the increased level of tumor necrosis factor-alpha, polymorphonuclear neutrophil elastase, interleukin-6, and interleukin-8 associated with cardiac surgery. CONCLUSION: Ulinastatin may be of value for the inhibition of postoperative increased inflammatory agents and most likely provided pulmonary protective effects in cardiac surgery. However, larger adequately powered RCTs are required to define the clinical effect of ulinastatin on postoperative outcomes in cardiac surgery.