Acupuncture Versus Biofeedback for Treatment of Functional Anorectal Pain.

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.

Ding's herbal enema treats dextran sulfate sodium-induced colitis in mice by regulating the gut microbiota and maintaining the Treg/Th17 cell balance.

Ding's herbal enema (DHEP) is a traditional Chinese medicinal therapy that has been used to treat ulcerative colitis (UC) in China. The present study determined the molecular mechanism of the effect of DHEP in UC treatment. C57BL/6J mice were treated with 3.5% (w/v) dextran sulfate sodium (DSS) for 7 days to establish an animal model of colitis. The mice were divided into five groups (n=5): Control, vehicle, DHEP, mesalazine and ß-sitosterol. After oral administration for 7 days, the body weight, disease activity index, histopathology and inflammatory factors were analyzed. The fractions of CD4+Foxp3+ regulatory T (Treg) cells and CD4+IL-17A+ T helper (Th) cells were determined by flow cytometry. Gut microbiota composition was analyzed by next-generation sequencing. The results revealed that DHEP and ß-sitosterol could significantly alleviate the symptoms of DSS-induced UC. Furthermore, the levels of IL-6, cyclooxygenase-2, TNF-α and p65 were reduced after administration of DHEP. Additionally, the data indicated that DHEP could increase the abundance of seven operational taxonomic units (OTUs) and decrease the abundance of 12 OTUs in the gut microbiota. The content of short-chain fatty acids in the colon remodeled the balance of Treg/Th17 cells in DSS-induced UC in mice. The present study preliminarily defined the mechanism of action of DHEP in UC that may be associated with the regulation of the gut microbiota composition, and maintenance of the balance between Treg and Th17 cells. Furthermore, ß-sitosterol exhibited the same effects with DHEP and it could be a possible substitute for DHEP in UC treatment.

ß-Sitosterol improves experimental colitis in mice with a target against pathogenic bacteria.

In this article, we aim to examine the novel effects of ß-sitosterol on murine experimental colitis. ß-Sitosterol significantly reduces the weight loss, colon length, and alleviated microscopic appearances of colitis induced by dextran sulfate sodium. This compound also decreases the levels of TNF-α, IL-6, and IL-1ß in intestinal tissue of mice with experimental colitis in a concentration-dependent manner. ß-Sitosterol treatment to intestinal epithelial cells significantly increases expression of antimicrobial peptides and reduces survival of intracellular Salmonella typhimurium. These results showed the multiple effects of ß-sitosterol against pathogenic bacteria for a novel approach to the treatment of colonic inflammation.

[Symptom distribution of female pelvic floor dysfunction patients with constipation as chief complaint].

OBJECTIVE: To observe the multiple symptom distribution, severity and quality of life of female pelvic floor dysfunction(FPFD) patients with constipation as chief complaint. METHODS: One hundred FPFD patients with constipation as chief complaint from Speciaty Outpatient Clinic, Pelvic Floor Center of Nanjing Municipal Hospital of Traditional Chinese Medicine between September 2015 and February 2017 were retrospectively enrolled in this study. A comprehensive medical history questionnaire survey and systematical evaluation of severity and quality of life of these patients with constipation was conducted. Constipation scoring system scale (CSS) and patient-assessment of constipation quality of life questionnaire (PAC-QOL) were applied to evaluate the constipation. Other scales included: (1)pain visual analogue scale (VAS) and short form-36 questionnaire (SF-36): if combined with chronic functional anal rectal pain; (2) international consultation on incontinence questionnaire-short form (ICIQ-SF) and urinary incontinence quality of life questionnaires (I-QOL):if combined with urinary incontinence; (3) fecal incontinence severity score scale (Wexner-FIS) and fecal incontinence quality of life questionnaire (FI-QOL):if combined with fecal incontinence. RESULTS: The mean age of 100 FPFD patients was (57.9±13.9) (24-89) years and the mean disease course was (7.0±8.2)(0.5-40.0) years. Seventy-five cases (75%) were complicated with anal pain, 70 with urinary incontinence, 37 with rectocele, 19 with nocturia, 11 with urinary frequency, 10 with defecation incontinence. Complication with only one symptom was observed in 20 cases (20%), and with two or more symptoms was observed in 80 cases (80%). Pelvic floor relaxation syndrome patients were dominant (58 cases, 58%). The severity of constipation (CSS) was 6-22 (13.89±3.79) points and the quality of life (PAC-QOL) was 45-133 (87.13±18.57) points in FPFD patients. VAS and SF-36 of patients combined with chronic functional anal rectal pain were 1-8 (3.0±1.9) points and 14.4-137.0(71.5±31.4) points respectively. ICIQ-SF and I-QOL of patients combined with urinary incontinence were 1-17 (6.1±3.6) points and 52-110 (90.0±15.8) points respectively. Wexner-FIS and FI-QOL of patients combined with fecal incontinence were 1-11 (4.4±3.0) points and 52-116 (83.4±23.3) points respectively. CONCLUSIONS: The symptoms of FPFD patients with constipation as chief complaint are complex. They are mainly complicated with anal diseases, then urinary incontinence, and mostly with more than 2 symptoms. Their quality of life is poor.

Role of three-dimensional endoanal ultrasound in assessing the anal sphincter morphology of female patients with chronic proctalgia.

AIM: To assess the role of three-dimensional endoanal ultrasound (3D-EAUS) for morphological assessment of the anal sphincter of female patients with chronic proctalgia (CP). METHODS: In this unmatched case control study, 30 consecutive female patients with CP and 25 normal women (control group) were enrolled. 3D-EAUS was performed in all subjects. Thickness and length of internal anal sphincter (IAS), thickness of puborectalis muscle (PR), length of the external anal sphincter (EAS) plus PR, and puborectalis angle were measured and compared between the two groups. RESULTS: Patients with CP had significantly shorter IAS length and greater PR thickness, as compared to those in normal individuals (26.28 ± 3.59 mm vs 28.87 ± 4.84 mm, P < 0.05 and 9.67 ± 1.57 mm vs 8.85 ± 0.97 mm, P < 0.05, respectively). No significant between-group differences were observed with respect to IAS thickness and the EAS plus PR length (P > 0.05). Puborectalis angle in the CP group was significantly decreased, both in resting (88.23° ± 1.81° vs 89.94° ± 2.07° in control group, P < 0.05) and straining (88.47° ± 3.32° vs 90.72° ± 1.87° in control group, P < 0.05) phases, which suggest the presence of paradoxical contraction of PR in patients with CP. In the CP group, no significant difference in puborectalis angle was observed between the resting and straining phases (88.23° ± 1.81° vs 88.47° ± 3.32° respectively, P > 0.05). CONCLUSION: The association of greater PR thickness and paradoxical contraction of PR with CP suggest their potential value as markers of CP.

Serum MicroRNA profile in patients with colon adenomas or cancer.

BACKGROUND: Colon cancer, one of the most common causes of cancer-related deaths, arises from adenomatous polyps. In these years, circulating microRNAs (miRNAs) have attracted increasing attention as novel biomarkers for colon cancers. The dysregulated circulating miRNAs in patients with colon adenomas has not been well-understood. METHODS: Here, we aimed to identify miRNA profile in the serum of patients with colon adenomas or colon cancer by using microarray. Then we validated eight differentially expressed miRNAs (DEMs) by qRT-PCR and predicted their targets. RESULTS: We identified 26 DEMs from Adenomas versus Normal comparison (11 up-regulations and 15 down-regulations), 72 DEMs from Cancer versus Normal comparison (19 up-regulations and 53 down-regulations) and 17 DEMs from Cancer versus Adenomas comparison (4 up-regulations and 13 down-regulations). Moreover, three DEMs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Cancer versus Adenomas comparison, and may be specific diagnostic biomarkers for colon cancer. Five down-regulated miRNAs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Adenomas versus Normal comparison, and may be important for the development of colon polyps and cancer. CONCLUSIONS: We discovered 8 circulating miRNAs associated with colon adenomas and colon cancer, and these miRNAs may potentially serve as noninvasive screening biomarkers for colon cancer. Our study is useful for expanding our understanding in the development of colon adenomas and colon cancer, and thus provide novel insights into colon cancer pathogenesis and prevention.

[Efficacy analysis of acupuncture with biofeedback in the treatment of patients with functional anorectal pain].

OBJECTIVE: To observe the short- and long-term efficacy of acupuncture combined with biofeedback in the treatment of functional anorectal pain (FARP). METHODS: Clinical data of 142 patients who met the functional gastrointestinal disorders and functional anorectal pain based on criteria of Rome III( undergoing acupuncture with biofeedback therapy from August 2010 to November 2015 in Pelvic Floor Center of The Third Affiliated Hospital of Nanjing University of Chinese Medicine were retrospectively analyzed. Telephone and outpatient clinic recheck were used as standard follow-up. The clinical effect of short-term and long-term data collected from the disease-based database was evaluated with visual analogue pain scale (VAS) (0-10 points), short form health survey questionnaire (SF-36) (0-148 points). The overall satisfaction and effectiveness (VAS was >30%) were evaluated at the end of treatment (short-term) and during follow-up (long-term). RESULTS: The effective follow-up data were obtained from 71.1%(101/142) of patients and the median follow-up time was 28(3-67) months. The VAS of 101 cases was 6.09±1.78, 1.99±1.89 and 3.55±2.60 before treatment, at the end of treatment and during follow-up respectively. Though the VAS during follow-up was higher than that at the end of treatment, but still significantly lower than that before treatment(P<0.05). The SF-36 score of 31 patients was 82.0±16.9, 94.0±15.1 and 88.1±15.3 before treatment, at the end of treatment and during follow-up respectively. Though the SF-36 score during follow-up was lower compared to at the end of treatment, but still significantly higher compared to before treatment (P<0.05). The effective rates were 85.9%(122/142) at the end of treatment and 75.2%(76/101) during follow-up, and the satisfactory rates were 92.3%(131/142) and 84.2%(85/101), respectively. CONCLUSION: Acupuncture with biofeedback has significant short-term and long-term efficacy in treating functional anorectal pain, and its degree of satisfaction is high.

[Variation of Locations of Baliao Acupoints in 290 Volunteer Subjects Analyzed by Using Computed Tomography-aided Three-dimensional Reconstruction Technique].

OBJECTIVE: To observe the variation of sacral vertebrates and foramen involving the bilateral Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34, Baliao acupoints), so as to provide an anatomic basis of acupoint needling in clinical practice. METHODS: A total of 290 patients[161 men and 129 women, mean age and standard devia-tion, (63.6±13.3)years old and (59.5±13.3) years old, respectively] with intact pelvic structure were recruited in the present study. Computed tomography (CT) scans of intact pelves were taken using a SOMATOM Definition AS 128 and the acquired signals were imported into Siemens Syngo Inspace platform for 3 D reconstruction, followed by identification, classification and analysis of the variation of sacral foramen (Baliao acupoint). RESULTS: The total variation rate of posterior sacral foramen (Baliao acupoint) was 20.34%(59/290). The detected three types of variation were sacral vertebrae number variation (4 sacral vertebraes, 6 sacral vertebraes), fusion variant (lumbosacral fusion, sacrococcygeal fusion, lumbosacral & sacrococcygeal fusion, and lumbosacral fusion & S 4 variation) and mixed type. CONCLUSIONS: Variations of sacral vertebrae including the number and fusion exist in the human body, suggesting an increase of the difficulty of acupoint needling. Since posterior iliac spine does not change generally, it is recommended to be used as a reference point for locating the Baliao acupoint.

[Comparison of two-dimensional ultrasound and three-dimensional endoanal ultrasound in the diagnosis of perianal fistula].

OBJECTIVE: To compare the accuracy of two-dimensional endoanal ultrasound (2D-EAUS) and three-dimensional endoanal ultrasound (3D-EAUS) in the diagnosis of perianal fistulas. METHODS: Image data of 47 perianal fistula patients undergoing surgery in our department between January 2012 and December 2012 were collected. All the patients underwent 2D-EAUS and 3D-EAUS, and the results were compared to intraoperative findings (gold standard) by kappa concordance test. RESULTS: Both 2D-EAUS and 3D-EAUS showed good concordance with intraoperative findings in internal opening (kappa: 0.776 vs. 0.636). 3D-EAUS had better concordance with intraoperative finding in the diagnosis of intersphincteric, high transsphincteric and suprasphincteric fistulas as compared to 2D-EAUS (kappa: 0.810 vs. 0.592, kappa: 0.863 vs. 0.548, kappa: 1.000 vs. 0.672). 3D-EAUS showed better concordance with intraoperative findings in secondary tract compared to 2D-EAUS(kappa: 0.659 vs. 0.535). Both 2D-EAUS and 3D-EAUS had good concordance with intraoperative findings in complicated abscesses (kappa: 0.881 vs. 0.816). CONCLUSION: 3D-EAUS can show the relationship of fistula with anal sphincter, especially in diagnosing high fistula and fistula with secondary tracts, and has a higher diagnostic accuracy than 2D-EAUS.

[Observation on effect characteristics of electroacupuncture for different types of functional constipation].

OBJECTIVE: To explore the differences of electroacupuncture (EA) on onset time and symptom improvement for treatment of different types of functional constipation. METHODS: Thirty-eight cases of constipation were selected, including 9 cases of constipation-predominant irritable bowel syndrome (IBS-C), 10 cases of slow transit constipation (STC), 10 cases of pelvic floor dyssynergia (PFD) and 9 cases of inadequate defecatory propulsion (IDP). The electroacupuncture was applied at Tianshu (ST 25), Fujie (SP 14), Shenshu (BL 23), Dachangshu (BL 25) and so on in abdominal and lumbosacral area, 5 times per week, 10 times as a treatment course. The onset time, score of clinical symptoms of constipation and improvement of every symptom in each group were compared. RESULTS: (1) The onset time was (1.78 +/- 0.83) days in IBS-C type, (3.11 +/- 1.90) days in IDP type, (4.10 +/- 1.85) days in STC type and (4.30 +/- 2.00) days in PFD type, indicating statistical differences between IBS-C type and STC type, IBS-C type and PFD type (both P < 0.05). (2) Compared before the treatment, the total scores of symptoms on the onset day in each group were all improved (P < 0.05, P < 0.01), and score of IBS-C type was superior to the rest 3 types (P < 0.05, P < 0.01). (3) EA improved desire to defecate or frequency of defecation in each type (P < 0.05, P < 0.01), in which both were improved in STC type and PFD type, and the improvement of defecation frequency was more significant in STC type (P < 0.01). EA relieved unsmooth defecation or pendant-expansion feeling in each type (all P < 0.05), in which both were improved in IBS-C type (both P < 0.05). EA relieved abdominal distension and pain in IBS-C type, STC type and PFD type (all P < 0.05), while its effects were not obvious on defecation difficulty, defecation time and defecation texture (all P > 0.05). CONCLUSION: The electroacupuncture for treatment of 4 types of constipation is characterized by rapid onset; the improved symptoms are not identical in the electroacupuncture treatment plan for each type of defecation; the main improvement of symptoms are lied on desire to defecate and frequency of defecation, unsmooth defecation or pendant-expansion feeling and abdominal distension and pain. Meanwhile the improvements of defecation texture, defecation difficulty and defecation time were not signi-ficant.

[Dynamic three-dimensional ultrasound study on levator ani muscle fissures for female pelvic floor relaxation syndrome].

OBJECTIVE: To explore the value of dynamic three-dimensional ultrasound in detecting the levator ani muscle fissures morphological changes of female pelvic floor relaxation syndrome after biofeedback and acupuncture treatments. METHODS: Forty female constipation patients with pelvic floor relaxation syndrome were screened from the Constipation Designed Disease Clinic in our hospital between October 2011 and September 2012. Cleveland Constipation Score (CCS) scale was used. Anteroposterior and transverse diameters of the levator ani muscle fissures were measured by dynamic three-dimensional ultrasound in Valsalva maneuver. After a course (10 days) of biofeedback and acupuncture treatments, CCS scale was filled, and dynamic three-dimensional ultrasound was performed in Valsalva maneuver as well. Associated data before and after treatment were compared. RESULTS: Twenty-five patients completed the trial. As compared to pre-treatment, the longitudinal axes of levator ani muscle fissure [(4.89±0.89) cm vs. (5.13±0.82) cm, P<0.01], the horizontal axes of the levator ani muscle fissure [(4.62±0.75) cm vs. (4.86±0.74) cm, P<0.01], and the area of the levator ani muscle fissure [(18.16±6.42) cm(2) vs. (19.92±6.33) cm(2), P<0.01] decreased significantly after treatment, while CCS scale (9.52±2.50 vs. 15.80±3.42, P<0.01) declined significantly as well. CONCLUSIONS: The dynamic three-dimensional ultrasound is an effective, simple and non-invasive method for the determination of levator ani muscle fissure in female patients with pelvic floor relaxation syndrome.

[Study on the measurement and locating of Baliao points (eight sacral foramina)].

OBJECTIVE: To seek the problems of position, measuring and locating methods of Baliao points (posterior sacral foramina) in modern researches. METHODS: Using Baliao (eight sacral foramina), Shangliao(BL 31), Ciliao(BL 32), Zhongliao(BL 33), Xialiao(BL 34), Dihoukong (posterior sacral foramina), Dikong (sacral foramina) and Digu(sacrum) as the key words, literature in the database of the CNKI from 1957 to 2012 were re trieved and analyzed. RESULTS: Problems were found in the past researches including limited numbers of relative literature, disunity of the measurement targets, complicated terms of indices, disunity of the starting and ending point of measurement, unclear weight of indices, deviation of results, lacking of combination with clinical practice and variety of locating methods. CONCLUSION: Position of Baliao points (eight sacral foramina) are clear. However, the locating methods are blurred and vary a lot. Study on living body has more significance for measurement and researches. Factors of gender, body weight, height and childbearing should also be taken into consideration. Therefore, it is necessary to find a more accurate and easier way of locating.

[A multi-center, randomized, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in the treatment of anal fissure].

OBJECTIVE: To evaluate the clinical efficacy and safety of glyceryl trinitrate (GTN) ointment in the treatment of anal fissure. METHODS: In this multi-center, randomized, double-blind and placebo-controlled trial, 240 chronic anal fissure patients from 7 clinical centers were randomized to receive eight-week treatment with GTN ointment (treatment group) or vaseline ointment (control group) respectively. Healing rate, visual analogue score (VAS), maximum anal resting pressure (MARP) and adverse reactions were recorded and compared. RESULTS: A total of 221 patients (92.1%) finished the trial, including 114 patients in treatment group (95.0%, 114/120) and 107 in control group (89.2%, 107/120). At the endpoint of treatment (56 d), 90 patients in treatment group (78.9%, 90/114) healed completely compared to 31 patients in control group (29.0%, 31/107), and decrease rates of VAS in the two groups were (94.8±15.7)% and (61.2±35.7)% respectively, both differences were statistically significant (P<0.01). MARP after first administration was (20.2±18.5) mm Hg in treatment group (n=12) and (7.1±14.7) mm Hg in control group (n=6), which was not significantly different (P=0.152). Adverse reaction incidence was higher in treatment group (42.1% vs. 9.3%, P<0.05), while these adverse reactions were mainly headache and fullness in head, which were self-limiting. CONCLUSION: GTN ointment can effectively promote healing and relieve pain in anal fissure with safety and tolerance.

[Dynamic three-dimensional ultrasound in the diagnosis of pelvic floor dyssynergia].

OBJECTIVE: To explore the feasibility of dynamic three-dimensional ultrasound measurement in the diagnosis of pelvic floor dyssynergia(PFD). METHODS: Thirty female patients with PFD received dynamic three-dimensional ultrasound. The differences in angle α measured by transperineal three-dimensional ultrasound, and angle ß, angle γ, and H line as measured by transanorectal three-dimensional ultrasound were compared between resting state and Valsalva maneuver. In addition, the detective rate of PFD by different parameters was analyzed. RESULTS: In 30 patients, rectocele was found in 13 cases(43.3%), rectal internal mucous intussusception in 14 cases(46.7%), uterine prolapse in 11 cases(36.7%), and bladder prolapse in 1 case(3.3%). Compared with the resting state, α, ß and H decreased obviously, but γ increased apparently in Valsalva maneuver, and differences of these parameters were statistically significant(all P<0.01). Detective rates of PFD for parameters of α, ß, γ and H were 93.3%(28/30), 96.7%(29/30), 96.7%(29/30) and 86.7%(26/30), respectively. CONCLUSION: Measurements of α, ß, γ and H can provide feasible indicators for clinical diagnosis of PFD.

Tumor-infiltrating immune cells: triggers for tumor capsule disruption and tumor progression?

BACKGROUND: Our previous studies of human breast and prostate cancer have shown that aberrant immune cell infiltration is associated with focal tumor capsule disruption and tumor cell budding that facilitate invasion and metastasis. Our current study attempted to determine whether aberrant immune cell infiltration would have similar impact on colorectal cancer (CRC). MATERIALS AND METHODS: Tissue sections from 100 patients with primary CRC were assessed for the frequencies of focal basement membrane (BM) disruption, muscularis mucosa (MM) fragmentation, and tumor cell dissemination in epithelial structures adjacent and distal to infiltrating lymphoid aggregates using a panel of biomarkers and quantitative digital imaging. RESULTS: Our study revealed: (1) epithelial structures adjacent to lymphoid follicles or aggregates had a significantly higher (p<0.001) frequency of focally disrupted BM, dissociated epithelial cells in the stroma, disseminated epithelial cells within lymphatic ducts or blood vessels, and fragmented MM than their distal counterparts, (2) a majority of dissociated epithelial cells within the stroma or vascular structures were immediately subjacent to or physically associated with infiltrating immune cells, (3) the junctions of pre-invasive and invasive lesions were almost exclusively located at sites adjacent to lymphoid follicles or aggregates, (4) infiltrating immune cells were preferentially associated with epithelial capsules that show distinct degenerative alterations, and (5) infiltrating immune cells appeared to facilitate tumor stem cell proliferation, budding, and dissemination. CONCLUSIONS: Aberrant immune cell infiltration may have the same destructive impact on the capsule of all epithelium-derived tumors. This, in turn, may selectively favor the proliferation of tumor stem or progenitor cells overlying these focal disruptions. These proliferating epithelial tumor cells subsequently disseminate from the focal disruption leading to tumor invasion and metastasis.

Cell budding from normal appearing epithelia: a predictor of colorectal cancer metastasis?

BACKGROUND: Colorectal carcinogenesis is believed to be a multi-stage process that originates with a localized adenoma, which linearly progresses to an intra-mucosal carcinoma, to an invasive lesion, and finally to metastatic cancer. This progression model is supported by tissue culture and animal model studies, but it is difficult to reconcile with several well-established observations, principally among these are that up to 25% of early stage (Stage I/II), node-negative colorectal cancer (CRC) develop distant metastasis, and that circulating CRC cells are undetectable in peripheral blood samples of up to 50% of patients with confirmed metastasis, but more than 30% of patients with no detectable metastasis exhibit such cells. The mechanism responsible for this diverse behavior is unknown, and there are no effective means to identify patients with pending, or who are at high risk for, developing metastatic CRC. NOVEL FINDINGS: Our previous studies of human breast and prostate cancer have shown that cancer invasion arises from the convergence of a tissue injury, the innate immune response to that injury, and the presence of tumor stem cells within tumor capsules at the site of the injury. Focal degeneration of a capsule due to age or disease attracts lymphocyte infiltration that degrades the degenerating capsules resulting in the formation of a focal disruption in the capsule, which selectively favors proliferating or "budding" of the underlying tumor stem cells. Our recent studies suggest that lymphocyte infiltration also triggers metastasis by disrupting the intercellular junctions and surface adhesion molecules within the proliferating cell buds causing their dissociation. Then, lymphocytes and tumor cells are conjoined through membrane fusion to form tumor-lymphocyte chimeras (TLCs) that allows the tumor stem cell to avail itself of the lymphocyte's natural ability to migrate and breach cell barriers in order to intravasate and to travel to distant organs. Our most recent studies of human CRC have detected nearly identical focal capsule disruptions, lymphocyte infiltration, budding cells, and the formation of TLCs. Our studies have further shown that age- and type-matched node-positive and -negative CRC have a significantly different morphological and immunohistochemical profile and that the majority of lymphatic ducts with disseminated cells are located within the mucosa adjacent to morphologically normal appearing epithelial structures that express a stem cell-related marker. NEW HYPOTHESIS: Based on these findings and the growth patterns of budding cells revealed by double immunohistochemistry, we further hypothesize that metastatic spread is an early event of carcinogenesis and that budding cells overlying focal capsule disruptions represent invasion- and metastasis-initiating cells that follow one of four pathways to progress: (1) to undergo extensive in situ proliferation leading to the formation of tumor nests that subsequently invade the submucosa, (2) to migrate with associated lymphocytes functioning as "seeds" to grow in new sites, (3) to migrate and intravasate into pre-existing vascular structures by forming TLCs, or (4) to intravasate into vascular structures that are generated by the budding cells themselves. We also propose that only node-positive cases harbor stem cells with the potential for multi-lineage differentiation and unique surface markers that permit intravasation.

[Expression of JAG1 and DLL1 genes in colorectal cancer and its clinical significance].

OBJECTIVE: To study the expression of JAG1 and DLL1 in colorectal cancer and its clinical significance. METHODS: Patients with colorectal cancer were treated in the Center of Colorectal Surgery of the Third Affiliated Hospital of Nanjing University of TCM were collected prospectively and followed up. A tissue microarray was made and expressions of JAG1 and DLL1 were detected by immunohistochemical staining. RESULTS: A total of 146 cases with colorectal cancer were included. The differences in JAG1 expression were significant among different tumor differentiation types and the differences in DLL1 expression were significant among different tumor locations(all P<0.05). There were no significant differences in the expression of the two genes and microsatellite instability(MSI)(P>0.05). One hundred and thirty-four (91.8%) cases were followed up and the mean follow-up time was (42.3±13.3) months. Tumor-free survival was noticed in 86 patients. The overall survival was 93% at 1 year, 74% in 3 years, and 67% in 5 years. Multivariate analysis showed that long-term survival rate was related to TMN stage, pathology types, MSI status and expression of JAG1. The prognosis of patients with high expression of JAG1 was better than those with low and negative expression(P<0.05). CONCLUSIONS: The expressions of JAG1 and DLL1 are related to tumor differentiation and tumor location. The expression of JAG1 gene is associated with long-term survival.

[Strategies on perianal abscess and fistula-in-ano: interpretation of the guidelines from USA and German].

The Practice Parameters for the Management of Perianal Abscess and Fistula-in-ano from USA(2011) and German guidelines for anal abscess (2012) are based on the evidence and specialists consensus from colorectal field. Standardization of the anal abscess management may simplify the anal fistula treatment. This review is to concepts from other countries and guide the treatment in China.

[Analysis on human papillomavirus 16 and 18 types infection among 805 patients with common anorectal lesions].

OBJECTIVE: To analyze the infection condition of human papillomavirus (HPV) type 16 and 18 in the squamous cells and columnar cells of patients with common anorecatal lesions. METHODS: Infections of HPV type 16 and 18 were determined with real-time fluorescent quantitative PCR in the wax-embedded surgical specimen of 805 patients with common anorectal diseases. RESULTS: The overall infection rate among 805 patients with anorecatal lesions was 66.1% (532/805). The infection rate was 82.6% (95/115) in patients with mixed hemorrhoids, 76.5% (88/115) in anal papillary fibromas, 74.8% (86/115) in internal hemorrhoids, 72.2% (83/115) in fistulas, 69.6% (80/115) in external hemorrhoids, 47.8% (55/115) in anal perianal abscesses, and 39.1% (45/115) in anal fissures. CONCLUSION: Infection rate of HPV type 16, 18 in common anorectal lesions is high.