Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately.Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498).Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies.Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy.

Background/Aims: Functional anorectal pain is one of several types of functional anorectal disorders. In this study, we compared the effectiveness of acupuncture (intervention) and biofeedback (control) as treatment for patients with functional anorectal pain. Materials and Methods: This prospective, single-center, randomized, and comparative study examined 68 patients with functional anorectal pain who were recruited from June 2017 to January 2019 at the Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were randomly assigned to receive acupuncture or biofeedback. Patients in the acupuncture group received acupuncture at Zhongliao (BL33), Xialiao (BL34), Ganshu (BL18), Shenshu (BL23), and Dachangshu (BL25). Patients in the biofeedback group received pelvic floor biofeedback therapy, consisting of Kegel pelvic floor muscle training and electrical stimulation. Patients in both groups received 20 treatments over 4 weeks. The primary outcome was pain score on a visual analog scale, and the secondary outcomes were results from the MOS 36-item short-form health survey (SF-36) quality of life questionnaire, the self-rating depression scale, and the self-rating anxiety scale. Results: Visual analog scale pain scores significantly decreased in both of the groups with treatment (both P < .01). The final visual analog scale score was significantly lower in patients with pelvic floor dyssynergia who were treated with biofeedback (1.40 ± 0.97 vs. 5.30 ± 1.70) (P < .05). The 2 groups had similar decreases in self-rating depression scale and self-rating anxiety scale scores. Intriguingly, the acupuncture group had better mental health outcomes (P < .05). Conclusion: Both acupuncture and biofeedback therapy reduced the pain of patients with functional anorectal pain. Biofeedback provided more relief in patients with pelvic floor dyssynergia, and acupuncture provided greater improvements in mental health status. Cite this article as: Xue Y, Ding S, Zhou H, et al. Acupuncture versus biofeedback for treatment of functional anorectal pain. Turk J Gastroenterol. 2024;35(2):83-91.

Background: As a series of bothersome bowel dysfunction symptoms, low anterior resection syndrome (LARS) has a high incidence after rectal cancer surgery, which grievously impairs health-related quality of life. There have been an increasing number of studies on biofeedback therapy (BFT) to recover intestinal function in patients following anus-preserving surgery. However, few systematic reviews or meta-analyses have been reported.Objective: The purpose of this systematic review with meta-analysis was to identify the short-term and long-term effects of BFT on subjective and objective indicators of LARS.Methods: Randomized controlled trials (RCT) published in PubMed, Cochrane Library, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, China Biology Medicine disc (CBM), and Wei Pu (VIP) database from January 2012 to June 2024 were systematically searched. In accordance with PRISMA guidelines, the pooled findings were examined by Review Manager version 5.4.Results: The review finally included 14 RCT studies, with a total of 1,126 relevant patients. The meta-analysis results showed that following BFT, the mean resting pressure of the anal canal (MD = 5.53; 95% CI: 2.57, 8.49; Z = 3.66; p = 0.0003), the mean initial rectal sensation threshold (MD = 3.04; 95% CI: 1.84, 4.24; Z = 4.96; p < 0.00001), and the incidence rate of LARS (RR = 0.42; 95% CI: 0.31, 0.57; Z = 5.60; p < 0.00001) in the BFT intervention group were significantly better than those in the control group, However, there was no statistically significant differences in the Memorial Sloan-Kettering Cancer Center (MSKCC) intestinal function questionnaire score (MD = 0.79; 95% CI: −0.35, 1.93; Z = 1.37; p = 0.17), the CCIS (Wexner incontinence score) (MD = −0.67; 95% CI: −2.12, 0.78; Z = 0.91; p = 0.36), the LARS score (MD = −2.35; 95% CI: −6.07, 1.37; Z = 1.24; p = 0.22) and Xu ZF et al. “Five points Ten scores” excellent rate (RR = 4.59; 95% CI: 0.37, 56.35; Z = 1.19; p = 0.23) between the two groups.Conclusion: Our systematic review and meta-analysis indicate that BFT may improve the mean resting pressure of the anal canal and the mean initial rectal sensation threshold, reducing the incidence rate of LARS. Still, high-quality studies are necessary to explore the BFT standard for LARS.Systematic review registration: PROSPERO: CRD42024519785, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024519785.

We aimed to evaluate the effectiveness of transperineal ultrasound (TPUS) in diagnosing rectocele, rectal intussusception (RI), enterocele, perineal descent (PD), and cystocele in Chinese women with obstructed defecation syndrome (ODS), and to determine the grading of rectocele via TPUS. Between January 2019 and December 2021, 107 obstructed defecation syndrome patients, with a mean age of 49.76 years, received TPUS and defecation proctography (DEP). Both methods were used to diagnose anorectal angle, rectocele, RI, enterocele, and PD, while cystocele and uterine prolapse were diagnosed only through TPUS. Agreement between DEP and TPUS diagnostic results was compared using Cohen kappa statistics. Seventy-six rectoceles were reported following DEP and 72 after TPUS. DEP detected 7 enteroceles, 6 of which were diagnosed simultaneously by TPUS. 43 patients presented dyssynergic defecation (DD) upon DEP, while 51 upon TPUS. DEP and TPUS detected PD in 13 and 11 patients respectively, and RI in 82 and 73, respectively. Rectocele (kappa = 0.738), RI (kappa = 0.711), DD (kappa = 0.774), enterocele (kappa = 0.847), and PD (kappa = 0.625) were obtained by Cohen kappa statistics, which indicated a good agreement between DEP and TPUS. The cutoff values for the diagnosis of moderate and severe rectocele with TPUS were 12.05 mm (AUC: 0.941) and 18.50 mm (AUC: 0.977), respectively. The DEP-determined and TPUS-determined anorectal angles were significantly correlated in the resting and Valsalva states (P < .01). Compared with DEP, while maintaining good agreement in detecting rectocele, RI, DD, enterocele, and PD, TPUS is a repeatable and noninvasive alternative. Threshold values of 12.05 mm and 18.50 mm on TPUS may diagnose moderate and severe rectocele, respectively.

The utility of transperineal ultrasound (TPUS) in combination with anorectal manometry (ARM) in the evaluation of women with obstructive defecation syndrome (ODS) remains unclear. We investigated the combined performance of TPUS and ARM in the evaluation of female patients with ODS, and determined the clinical utility of both modalities in the evaluation of female patients with ODS. Female patients with ODS were evaluated by TPUS and ARM, and binary logistic regression models were exploited to evaluate the clinical association of abnormal TPUS variables with abnormal ARM variables. Two hundred ninety-six female patients with ODS underwent TPUS, of whom 209 patients underwent both TPUS and ARM. A binary logistic regression model was adopted to evaluate the utility of ARM in predicting abnormalities in TPUS. We found that an abnormal rectoanal gradient in ARM was independently associated with an abnormal ARA during strain maneuvers in TPUS, while reduced rectal defecation pressure was independently associated with rectocele, internal rectal intussusception, and internal rectal prolapse. Reduced anal squeeze pressure was independently associated with various pelvic floor anatomical abnormalities, while reduced anal resting pressure was independently associated with moderate-to-severe rectocele. Additionally, abnormal rectal sensory function was also independently associated with rectocele. In patients with ODS, circumscribed yet specific anatomic-functional correlations exist between select ARM and TPUS parameters. Specifically, reduced anorectal pressure gradient emerged as the strongest ARM predictor of abnormal ARA during defecation. Furthermore, diminished rectal defecation pressure provides independent diagnostic support for pelvic floor laxity conditions, including rectocele, moderate-to-severe rectocele, internal rectal prolapse, and internal rectal intussusception in ODS. We assert that combined imaging and functional testing is essential for comprehensive assessment of pelvic floor structural and functional characteristics in refractory ODS.

Electroacupuncture (EA), as a combination of traditional acupuncture and modern electrotherapy, and has analgesic effects on various acute and chronic pain. It has been proved to ameliorate chronic visceral pain, but its specific role in rectal visceral pain remains underexplored. A capsaicin (CAP)-induced visceral pain rat model was established, and behavioral pain responses were observed and recorded. Measurement of mechanical pain threshold was performed using electronic Von Frey system. Rectal tissues, and the activity of microglia cells were detected by Hematoxylin/eosin staining and immunofluorescence, respectively. Contents of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. Western blot was performed to determine the expressions of P2X4 receptor (P2X4R), p38 mitogen-activated protein kinase (p38), phosphorylated p38 (p-p38), transient receptor potential vanilloid-1 (TRPV1) and ionized calcium binding adapter molecule 1 (Iba-1). Transfection efficiency of TRPV1 overexpression plasmids was examined by quantitative real-time polymerase chain reaction. EA abrogated CAP-induced upregulation of behavioral pain responses and mechanical threshold, damage on rectal tissue, activation of microglia, stimulation of inflammatory response and promotion of P2X4R-p38-TRPV1 pathway expressions in rats, while P2X4R activation reversed the effect of EA. P2X4R antagonist weakened CAP-induced upregulation of P2X4R-p38-TRPV1 pathway expressions, microglia activation as well as increase of IL-1β in HMO6 cells, which was reversed by TRPV1 overexpression. Collectively, EA improves CAP-induced rectal visceral pain via inhibiting TRPV1 expression by blocking the P2X4R-activated p38 pathway in microglia. However, the specificity role of P2X4R needs to be confirmed by more experiment.