Evaluation of the clinical efficacy and safety of TST33 mega hemorrhoidectomy fo

lNTRODUCTlON

The patients in the two groups were given routine preoperative preparation, improved preoperative examination, and fasted on the day of operation. All patients were given intraspinal anesthesia, and the left lateral position was used for the operation.

《淮南子·道应训》中的记录和《列子·说符》中的内容大体一致，只是多了老子的一句评价“故老子曰：‘大智若愚，大巧若拙’”。而这段耳熟能详的选千里马的故事要告诉我们的无非是要重视事物内在的本质，也就是原文中说的千里马“其内”(即神韵)，而忽略“其外”。刘勰引用这个故事，就是为了说明在文学创作时也应该注重内在的本质，不能一味注重大文体的创作而忽略了小文体的存在。

MATERlALS AND METHODS

General information

A total of 204 patients with severe prolapsed hemorrhoids that were admitted to the anorectal department of our hospital from April 2018 to June 2020 were selected and randomly divided into Group A and Group B, with 102 cases in each group, by a single-blind, randomized and controlled clinical research scheme. Inclusion criteria: (1) The age range of patients is 19 to 65 years; (2) The diagnostic criteria for patients with severe prolapsed hemorrhoids refer to the criteria in the Chinese Guidelines for the Diagnosis and Treatment of Hemorrhoids (2020)[3]; (3) Non-circular hemorrhoids Suspended for more than half a year, reaching Ⅲ and Ⅳ degree; (4) Conservative treatment for more than 3 mo is not effective; and (5) The research plan obtains the informed consent of patients and their families. The exclusion criteria were as follows: (1) Patients with a rectal tumor; (2) Patients with a perianal abscess, or anal fistula formation; (3) Patients with liver and kidney function diseases; (4)Patients with coagulation diseases; (5) Patients with a history of drug use or addiction; and (6) Patients with mental or psychological diseases.

Surgical methods

The symptoms are more serious and the hemorrhoids generally need to be pushed back with the hand after prolapse, so severe prolapsed hemorrhoids require surgical treatment[1,2]. The procedure for prolapse and hemorrhoids (PPH) can lift and pull the anal cushion by circular resection of the rectal mucosa approximately 2-3 cm above the tooth line and anastomosis. The advantage is that the shortterm therapeutic effect is still acceptable, but the PPH is prone to various complications after surgery,the recurrence rate is high, and the long-term curative effect is poor. The use of tissue-selecting therapy staplers (TSTs) has been reported, but reports are rare. To some extent, this operation reduces the disadvantages of the PPH caused by circular resection, but because of selective resection, the use of TSTs does not change the high recurrence rate after PPH. The TST33 mega stapler has an open window,and the resection tissue boundary is open, so more pathological hemorrhoids are able to be resected.Under the premise of solving PPH complications, the use of TSTs also improves the postoperative recurrence rate to a certain extent[3]. To further summarize and analyze the surgical treatment methods for patients with severe prolapsed hemorrhoids, this study compared the effect of TST33 mega staplers to provide a basis for clinical practice, which is reported as follows.

For patients undergoing TST33 mega stapler hemorrhoid mucosal resection surgery, the appropriate anal mirror was selected (single opening, double opening or three opening anal mirror).The anal mirror was inserted and the inner tube was removed to expose the hemorrhoid tissue to be removed, and sutured with “0” silk sutures at the distance of 2.5-5 cm from the dentate line. Sutures were only placed in the mucosa and submucosa, a needle was placed in each opening suture, and a continuous bag was used. Sutures were only placed in the mucosa and submucosa, a needle was placed in each opening suture, and a continuous bag was used. The tail wing of the stapler was opened counterclockwise. After the head and body of the stapler were completely loosened, the head of the stapler was inserted into the anal expander. The two ends of the purse line were tightened and knotted around the central rod. The suture was exported from the symmetrical side hole of the stapler body through the suture export rod. Moderate traction was performed, the stapler was screwed clockwise,and the traction rectal tissue was pulled into the stapler nail slot. At this time, the feel knob was resistant, and the pointer of the stapler indicator window was displayed in the firing range. For female patients, surgeons paid attention to whether the posterior wall of the vagina was sutured. The stapler was hit, completing the cutting and anastomosis. For a fixed wait time of 30 s, the stapler was spun counterclockwise with a loose 3/4 circle tail, and removed. Observation of anastomotic stoma was performed if there was active bleeding Line 8' sutures were used for hemostasis. The 'cat ear' in the middle of the anastomosis was ligated with “0” silk thread. External hemorrhoid stripping to the teeth near the line parallel low ligation was performed.

All study participants, or their legal guardian, provided informed written consent prior to study enrollment.

All authors report no conflict of interest.

Observation indices and evaluation criteria

The operation time, intraoperative blood loss, hospitalization time, cure rate, pain degree, anal edema degree, anal Wexner score and surgical complications were compared between the two groups.

The criteria for healing[5] were postoperative defecation or standing for a long time and no hemorrhoid prolapse when coughing, tired, and loaded was defined as a cure.

Hemorrhoids are common diseases in the anorectal system. On the one hand, the occurrence of hemorrhoids is related to varicose veins. Hemorrhoids are caused by venous congestion of the rectal submucosal and anal skin hemorrhoids[8-10]. Subnuclear prolapse aggravates venous congestion, and venous congestion aggravates the development of hemorrhoids, forming a vicious cycle. Anastomotic hemorrhoid mucosal circumcision is a traditional surgical treatment, but it has been reported that the operation has more postoperative complications and patients are prone to recurrence, mainly because the stapler used in the operation does not have enough space to remove larger amounts of rectal mucosa, resulting in incomplete resection, so the long-term effect is not good. At the same time,prolapsed hemorrhoids will lead to their own rectal elongation, expansion, volume increase, rectal muscle thinning or disappearance of pathological changes, which cannot be effectively removed and easily lead to recurrence[11,12].

The visual analogue scale (VAS) was used to evaluate the degree of pain[5], with 0 indicating no pain,and 10 indicating the most pain. The pain scores at 12 h, 24 h, 48 h, 72 h and 96 h postoperatively were observed.

Observe the edema around the anal margin on the 1

and 7

postoperative day. Degree I: no edema of the anal margin; degree II: mild edema of the anal margin occupies less than 1/4 circle of the perianal;degree III: edema of the anal margin occupies more than 1/4 circle of the perianal, and ≤ 1/2 circle;degree IV: Anal marginal edema occupies more than 1/2 circle perianal.

Tao L and Wei J design the study; Ding XF drafted the manuscript, Ji L and Tao L collected the data; Tao L and Ji L analyzed and interpreted data, Tao L and Wei J revised the manuscript.

Anal Wexner score[7] evaluates the patient’s preoperative and postoperative anal function, mainly from the patient’s stool frequency, defecation difficulty, incomplete defecation feeling, the time required for each defecation, whether defecation requires assistance, and defecation Unsuccessful times/24 h,duration of constipation, a total score of 32 points, the higher the score, the worse the anal defecation function of patients.

Statistical analysis

In this study, measurement indices such as operation time, intraoperative blood loss and hospitalization time were tested by normal distribution, which were in accordance with the approximate normal distribution or normal distribution and are expressed as mean ± SD. The

-test was used for comparisons between the two groups. Non-counting data are represented by percentages, and the

test was used for comparisons. The Mann-Whitney

test was used for comparisons of grade counting data between the groups. Professional SPSS 21.0 software for data processing was used, with the test level α = 0.05.

（2）签证变更需一月一清，及时闭合。工程变更也是问题频发。通常，建设项目预算精准，严格控制材料的供应，项目结构规范，隐蔽设备不多的情况下，工程项目的成本公开透明，施工单位利润可观。工程变更就成为弄虚作假的高发地，虚开工程变更或直接伪造工程变更。

RESULTS

Baseline data comparison of patients in the A and B groups

The baseline data for age, height, weight, course of disease, sex, prolapse of hemorrhoids, constipation,bleeding and pain were compared between Group A and Group B, and the difference was not statistically significant (

＞ 0.05, Table 1).

Comparison of surgery-related indicators between Group A and Group B

The operation time, intraoperative blood loss and hospitalization time in Group A were significantly lower than those in Group B (

＜ 0.05, Table 2).

Comparison of cure rate between Group A and Group B

The cure rate of Group A was 98.04%, compared with the cure rate of 95.10% for Group B, and the difference was not statistically significant (

＞ 0.05, Table 3).

Postoperative VAS scores for Group A and Group B

The VAS scores of patients in group A at 12 h and 24 h after operation were lower than those in group B,and the difference was statistically significant (

＜ 0.05). There was no significant difference between group A and group B at 48 h, 72 h, and 96 h after operation (

＞ 0.05), as shown in Table 4.

Comparison of postoperative perianal edema between Group A and Group B

One day postoperatively, the degree of perianal edema in Group A was compared with that in Group B,and the difference was not statistically significant (

＞ 0.05). Seven days postoperatively, the degree of perianal edema in Group A was significantly lower than that in Group B (

＜ 0.05, Table 5).

Comparison of the anal Wexner score between the two groups

Comparisons of preoperative, postoperative, 1 mo, 3 mo, and 6 mo, anal Wexner scores were made between the two groups, and the difference was not statistically significant (

＞ 0.05). The Wexner scores of the two groups at 1 mo, 3 mo and 6 mo postoperatively were significantly lower than the scores preoperatively (

＜ 0.05, Table 6).

本研究所纳入的临床试验普遍质量较低，缺乏高质量、标准化的RCT。由于各研究间针刺所选穴位不同、服用的西药和中成药不同，且各研究间所纳入患者的病情严重程度不一等因素的影响，造成分析过程中各研究间存在较大异质性。在治疗前后NIH-CPSI评分变化量与白细胞降低有效率作为结局指标的分析中，由于纳入的相关分析较少，得出的结果可能可靠性不强。故在今后要多进行相关的临床研究，尤其是与中药汤剂、中药坐浴和微波治疗等方面的对比研究，且要进行高质量、标准化的RCT；尽量多注重治疗后随访的结果，为针刺治疗CP远期疗效提供可靠证据。

Comparison of the complication rate between two groups

The postoperative complication rate of Group A was 2.94% lower than that of Group B (11.76%), which was statistically significant (

＜ 0.05, Table 7).

DlSCUSSlON

我们使用(6)式通过OLS回归估算资本产出弹性α。然后代入(3)式即可得出安徽全要素生产率的增长率。在估算之前，为避免伪回归，需要对数据的平稳性进行检验。

Selective supraclavicular mucosal resection was improved on the basis of traditional surgical suspension and devascularization. The mucosal and submucous tissues above the supraclavicular nucleus were selectively resected, and the normal mucosal tissues between the supraclavicular nuclei were retained, so the trauma to the patients was decreased. This study found that the operation time,intraoperative blood loss and hospitalization time in Group A were lower than those in Group B,suggesting that the use of TST33 mega stapler hemorrhoid mucosal resection in the treatment of severe prolapsed hemorrhoids has reduced trauma and shorter hospitalization times, which is basically consistent with the conclusions of previous studies[13,14]. TST33 mega stapler hemorrhoid mucosal resection surgery has a large window vision, and the operation is smoother. The large window has no resection limitation, and the resection range is greater, which can fully allow for the “pulling” effect but also protect normal tissue. At the same time, the operation height is reduced. The operation height ofthe PPH is 4 cm, and the operation height of the TST33 mega stapler is 2.5-3.5 cm. This height can partially remove hemorrhoid tissue and reduce the recurrence rate to a certain extent. In this study, the postoperative complication rate of Group A was 2.94% lower than that of Group B (11.76%), suggesting that TST33 mega stapler hemorrhoid mucosal resection can reduce the incidence of surgical complications in patients with severe prolapsed hemorrhoids.

This study also showed that the VAS scores at 12 h and 24 h after the operation in Group A were lower than those in Group B, suggesting that TST33 mega stapler mucosal resection for severe prolapsed hemorrhoids could significantly reduce postoperative pain. There are many influencing factors for postoperative pain. TST33 mega stapler hemorrhoid mucosal resection surgery is performedabove the dentate line, where the dominant nerve is mainly the visceral nerve, which is not sensitive to pain. There is less resected rectal mucosa, so the postoperative pain is relatively reduced[15]. This study also found that 7 d after the operation, the degree of perianal edema in Group A was lower than that in Group B, suggesting that TST33 mega stapler hemorrhoid mucosal resection in the treatment of severe prolapsed hemorrhoids for postoperative perianal edema was reduced to some extent, and two surgical methods for the treatment of severe prolapsed hemorrhoids can improve anal function. TST33 mega stapler hemorrhoid mucosal resection reduces the number of anastomotic nails implanted and reduces the anal bulge, thus protecting anal contraction defecation functions[16,17].

In the process of the operation, we believe that attention should be given to the following aspects.First, the appearance of a “cat ear” between anastomotic stomas after TST operation is very common.Ligation with “0” silk thread is a simple, safe and reliable method. Second, surgeons should check whether there is bleeding in the anastomotic stoma carefully before removing the anal mirror, and the bleeding tendency should be removed to stop bleeding by “8” sutures to strengthen the anastomotic stoma. Third, the size of the resected tissue should be evaluated before the operation and the height and mode of the purse suture should be adjusted according to the need to play an individualized treatment role. Fourth, the height of the purse-string should be appropriately lowered. Choose 2.5 cm-3.5 cm on the tooth line, and remove part of the internal hemorrhoid tissue, which has a certain value for improving the postoperative curative effect[18-20].

This study analyzed the advantages of TST33 mega stapler hemorrhoid mucosal resection in the treatment of severe prolapsed hemorrhoids and showed the reduced incidence of postoperative complications, which was in line with the patient-oriented treatment concept of modern surgery and provided a certain basis for the clinical operation in the treatment of severe prolapsed hemorrhoids.However, due to the small number of cases included in this study, the lack of a large sample with a long-term follow-up and survey, the long-term efficacy and recurrence need to be further evaluated by increasing the sample size, improving the corresponding observation index, and carrying out prospective studies with in-depth analysis.

实验方法：将已经收集好的石蜡包埋的组织标本，逐个放置于切片机上，将蜡块与刀刃的位置和角度调好之后，制成5μm，边缘整齐平整的组织切片2张，而且卵巢癌患者蜡块要求每个组织切片中均含有瘤巢。免疫组化的操作步骤按照说明书进行烤片脱水、脱蜡、水化-高温高压抗原热修复-滴加一抗-4°C冰箱中保存过夜-放入PBS缓冲液中清洗后滴加二抗-DBA染色-苏木精复染、分化返蓝——脱水、封片。其中一抗中抗EGR-1抗体稀释浓度为1：100；抗HER-2抗体稀释浓度为 1：150。

CONCLUSlON

In summary, TST33 mega stapler hemorrhoid mucosal resection in the treatment of patients with severe prolapsed hemorrhoids yielded satisfactory results, less postoperative pain, perianal edema recovery block, and fewer complications.

炳发呀！我今年是十九岁了，我难道一点儿不知道吗？每次看到天上的月亮圆了，花园里的花开了，想起我们的青春年少……

ARTlCLE HlGHLlGHTS

FOOTNOTES

1.切实保障中小企业的发展。政府部门需要加强立法，通过相关的法律规定来推动中小企业的有序发展，为中小企业提供良好的环境。从整个中小企业的发展以及社会经济发展的方向，重视中小企业的发展，加强中小企业的规范，对中小企业的管理模式进行科学有效地设计，密切关注中小企业的发展方向，包括中小企业的资金运用以及中小企业的战略决策等，逐步推动中小企业产业结构的升级。

Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou, No.LCZX202022; and Changshu Municipal Science and Technology Bureau Supporting Project, No. CS201925.

This study was approved by the Changshu Hospital Affiliated to Nanjing University of Chinese Medicine.

The PPH was used for the treatment of hemorrhoids, and a PPH stapler was used for the treatment of internal hemorrhoids. External hemorrhoid stripping to the teeth near the line parallel low ligation was performed.

The patients in the two groups could go to the recovery unit after anesthesia recovery, and their diet gradually changed from a half-stream diet to an ordinary diet. The total infusion volume was controlled within 500 mL 6 h after the operation to reduce the incidence of urinary retention. Antibiotics were routinely used for 5 d after the operation, and dressing treatment was performed after sitting in the bath.

No additional data are available.

The authors have read the CONSORT 2010 statement, and the manuscript was checked according to the CONSORT 2010 statement.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

传统数理统计的内容包括哪些呢？虽然不同的教科书在编排上有所不同，但大同小异，主要包括：样本及抽样分布（随机样本、直方图、统计量、抽样分布）、参数估计（参数的点估计、估计量的评选标准、参数的区间估计、正态总体均值与方差的区间估计、置信区间）、假设检验（正态总体均值与方差的假设检验、分布拟合检验）、方差分析和回归分析（单因素试验的方差分析、一元回归分析）．

China

Liu Tao 0000-0002-6962-7122; Jun Wei 0000-0002-7216-0375; Xu-Feng Ding 0000-0002-2858-375X; Li-Jiang Ji 0000-0003-4416-8334.

某深埋隧洞工程全长50 km多，最大埋深超过2 200 m，属于无压洞，隧洞洞径5.3 m。采用TBM与钻爆法相结合的施工方案。隧洞自南向北穿越多个地质构造单元，围岩岩性复杂多变，主要包括志留系、泥盆系、石炭系砂岩、变质砂岩、凝灰岩、凝灰质砂岩以及华力西期花岗岩，少量为奥陶系灰岩和第三系泥岩，除第三系泥岩为软岩外，其余属硬岩类。

Wang JL

A

β2-MG是由淋巴细胞或者其他有核细胞分泌一种内源性低分子量血清蛋白质。血清中的99.9%的β2-MG会被近曲小管细胞重吸收和降解，不再向血液中反流，以此保持β2-MG在体内的恒定。但当近曲小管轻度受损时，尿液中β2-MG会显著增加[7]，可见人体肾脏的损伤程度与β2-MG具有明显的对应关系。

Wang JL

1 Romano G, Cocchiara G, Maniaci S, Buscemi G, Calderone F, Gioè FP, Romano M. [The role of colonoscopy in patient follow-up after surgery for colorectal cancer. A retrospective study and review of the literature].

2007 ; 28 : 399 -402[PMID: 17915057 ]

2 Ruan N, Chen ZH, Lin XB. [Efficacy comparison of tissue selecting therapy stapler and procedure for prolapse and hemorrhoids in the treatment of severe hemorrhoids].

2013 ; 16 : 645 -647 [PMID:23888447 ]

3 Casas-Puig V, Bretschneider CE, Ferrando CA. Perioperative Adverse Events in Women Undergoing Concurrent Hemorrhoidectomy at the Time of Urogynecologic Surgery.

2019 ; 25 : 88 -92 [PMID:30807406 DOI: 10 .1097 /SPV.0000000000000663 ]

4 Zhang G, Liang R, Wang J, Ke M, Chen Z, Huang J, Shi R. Network meta-analysis of randomized controlled trials comparing the procedure for prolapse and hemorrhoids, Milligan-Morgan hemorrhoidectomy and tissue-selecting therapy stapler in the treatment of grade III and IV internal hemorrhoids (Meta-analysis).

2020 ; 74 : 53 -60 [PMID:31887419 DOI: 10 .1016 /j.ijsu.2019 .12 .027 ]

5 Shen K, Wang C, Gao ZD, Jiang KW, Wang YL, Ye YJ. [Procedure for prolapse and hemorrhoids versus stapled transanal rectal resection in the treatment of grade IV hemorrhoids].

2019 ; 22 : 1165 -1169[PMID: 31874533 DOI: 10 .3760 /cma.j.issn.1671 -0274 .2019 .12 .012 ]

6 Ray-Offor E, Amadi S. Hemorrhoidal disease: Predilection sites, pattern of presentation, and treatment. Ann Afr Med 2019 ;18 : 12 -16 [PMID: 30729927 DOI: 10 .4103 /aam.aam_4 _18 ]

7 Forner LB, Beckman EM, Smith MD. Symptoms of pelvic organ prolapse in women who lift heavy weights for exercise: a cross-sectional survey.

2020 ; 31 : 1551 -1558 [PMID: 31813038 DOI: 10 .1007 /s00192 -019 -04163 -w]

8 Percalli L, Passalia L, Pricolo R, Riccò M. Pre-operative assessment of internal mucosal rectal prolapse in internal hemorrhoids: technical details and results from a single institution.

2019 ; 90 : 308 -315 [PMID: 31125011 DOI:10 .23750 /abm.v90 i2 .6988 ]

9 Mik M, Rzetecki T, Sygut A, Trzcinski R, Dziki A. Open and closed haemorrhoidectomy for fourth degree haemorrhoids--comparative one center study.

2008 ; 55 : 119 -125 [PMID: 19069704 DOI: 10 .2298 /aci0803119 m]

10 Filingeri V, Gravante G, Cassisa D. Clinical applications of radiofrequency in proctology: a review.

2006 ; 10 : 79 -85 [PMID: 16705953 ]

11 Fan Z, Zhang Y. Treatment of Prolapsing Hemorrhoids in HIV-Infected Patients with Tissue-Selecting Technique.

2017 ; 2017 : 1970985 [PMID: 28356909 DOI: 10 .1155 /2017 /1970985 ]

12 Lin HC, Chen HX, He QL, Huang L, Zhang ZG, Ren DL. A Modification of the Stapled TransAnal Rectal Resection(STARR) Procedure for Rectal Prolapse.

2018 ; 25 : 578 -585 [PMID: 30117358 DOI:10 .1177 /1553350618793415 ]

13 Jeong H, Hwang S, Ryu KO, Lim J, Kim HT, Yu HM, Yoon J, Lee JY, Kim HR, Choi YG. Early Experience With a Partial Stapled Hemorrhoidopexy for Treating Patients With Grades III-IV Prolapsing Hemorrhoids.

2017 ;33 : 28 -34 [PMID: 28289661 DOI: 10 .3393 /ac.2017 .33 .1 .28 ]

14 Palumbo VD, Palumbo VD, Damiano G, Sammartano A, Messina M, Fazzotta S, Curione F, Cudia BM, Lo Monte AI.Colour Doppler-guided Haemorrhoidal Artery Ligation: a possible evolution of Transanal Haemorrhoidal Dearterialisation.

2021 ; 172 : 329 -335 [PMID: 34247216 DOI: 10 .7417 /CT.2021 .2337 ]

15 Kuiper SZ, Dirksen CD, Kimman ML, Van Kuijk SMJ, Van Tol RR, Muris JWM, Watson AJM, Maessen JMC,Melenhorst J, Breukink SO; Napoleon Trial Study Group. Effectiveness and cost-effectiveness of rubber band ligation versus sutured mucopexy versus haemorrhoidectomy in patients with recurrent haemorrhoidal disease (Napoleon trial):Study protocol for a multicentre randomized controlled trial.

2020 ; 99 : 106177 [PMID: 33080380 DOI: 10 .1016 /j.cct.2020 .106177 ]

16 Reese GE, von Roon AC, Tekkis PP. Haemorrhoids. BMJ Clin Evid 2009 ; 2009 [PMID: 19445775 ]

17 Ji L, Li L, Weng L, Hu Y, Huang H, Wei J. Tissue selecting technique mega-window stapler combined with anal canal epithelial preservation operation for the treatment of severe prolapsed hemorrhoids: A study protocol for a randomized controlled trial.

2020 ; 99 : e23122 [PMID: 33157990 DOI: 10 .1097 /MD.0000000000023122 ]

18 Lohsiriwat V, Wilson VG, Scholefield JH, Dashwood MR. Regional Distribution of Nitric Oxide Synthase in Human Anorectal Tissue: A Pilot Study on the Potential Role for Nitric Oxide in Haemorrhoids.

2020 ; 18 :43 -49 [PMID: 30058493 DOI: 10 .2174 /1570161116666180730101532 ]

19 Ng KS, Holzgang M, Young C. Still a Case of "No Pain, No Gain"? Ann Coloproctol 2020 ; 36 : 133 -147 [PMID: 32674545 DOI: 10 .3393 /ac.2020 .05 .04 ]

20 Wang ZG, Zhang Y, Zeng XD, Zhang TH, Zhu QD, Liu DL, Qiao YY, Mu N, Yin ZT. Clinical observations on the treatment of prolapsing hemorrhoids with tissue selecting therapy.

2015 ; 21 : 2490 -2496 [PMID:25741159 DOI: 10 .3748 /wjg.v21 .i8 .2490 ]