Hong-Cheng Lin

Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer.

BackgroundActivation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues and correlated it with clinicopathologic data.MethodspMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively.ResultspMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues (6 out of 80, 7.5%; P < 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5 in CRC tissues was significantly correlated to the depth of invasion (P = 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and high preoperative CEA level (P < 0.001). Consistently, the pMEK5 level in CRC tissues was increased following stage progression of the disease (P < 0.001). Analysis of the survival curves showed a significantly worse 5-year disease-free (P = 0.002) and 5-year overall survival rate (P < 0.001) for patients whose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic factor for CRC (DFS: P = 0.139; OS: P = 0.071).ConclusionspMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.

The tissue-selecting technique: segmental stapled hemorrhoidopexy.

We describe a technique for the management of prolapsing hemorrhoids, with the aim to minimize the risk of anal stricture and rectovaginal fistula and to reduce the impact of the stapling technique on rectal compliance. This modified procedure was successfully applied in China, and preliminary data showed promising outcomes (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A117).

Reply to invited comment on “Partial stapled hemorrhoidopexy versus circular stapled hemorrhoidopexy for grade III–IV prolapsing hemorrhoids: a two-year prospective controlled study” by I. Khubchandani

We appreciate the opportunity to respond to the letter by Dr. Khubchandani. Based upon the comment from Dr. Khubchandani, we are pleased to find a very thorough colorectal specialist with acute eyesight and cautious support for a novel technique. Circular stapled hemorrhoidopexy (CSH), which has gained wide popularity since 1998 because of its efficacy and the low postoperative pain associated with the technique [1], was adopted by more and more proctologists to treat prolapsing hemorrhoids. According to our estimate, about 20, 000 cases of PPH were treated in China each year. However, potential complications including rectovaginal fistula and anal stenosis cannot be avoided completely, whereas lifethreatening severe complications are increasingly reported [2]. The need to improve the results of this stapled technique led surgeons to develop a modified technique, even a novel technique. The idea of tissue-selecting technique (TST), namely partial stapled hemorrhoidopexy, is aimed at overcoming the weakness and limitations of CSH. Anal stenosis after CSH was often encountered in clinical practice. Some of these cases may be attributed to surgical error such as removal of large areas of anoderm. However, even an experienced surgeon with meticulous technique will also find that a little anal stricture develops in some patients after this circular technique. It will not always be due to surgical error and may be due to the fact that full circumference of the rectal mucosa is affected. TST gets partial circumference anastomosis to avoid anal stenosis and spares the rectal wall adjacent to the vagina to avoid rectovaginal fistula completely by using our specially designed anoscope in female patients. Further clarifications of the ‘‘mucosal bridge’’ in our article are required. Actually, after the stapler in TST is fired and gently withdrawn, a minimal mucosal bridge with some staples connecting the two edges of the mucosectomies (Fig. 1), like in the case of STARR, was found and dissected using electrocautery. Due to the protection by the spatula of the tri-window anoscope, a mucosal bridge, consisting of normal rectal mucosa, was spared (Fig. 2). Because of the preservation of partial of rectal wall between mucosectomies, a better rectal compliance was maintained and this resulted in less damage to anorectal function. CSH has the same safety and efficacy as conventional hemorrhoidectomy, and this could account for the widespread adoption of CSH. Nevertheless, few studies have been performed investigating the potential influence on the anorectal function and the mechanism of postoperative outcomes including pain, fecal urgency, and anal stenosis after CSH. Our preliminary study on TST has demonstrated that this modified technique is associated with good anorectal function including fewer episodes of urgency and no anal incontinence or anal stenosis [3]. Nevertheless, randomized controlled trials that compare the TST and CSH procedures are required to confirm the results of this preliminary trial. Damage to the healthy tissue should be lessened on the condition that therapeutic efficacy is guaranteed. TST is designed to treat prolapsing hemorrhoids with minimal damage to the normal tissue. This is the fundamental idea of TST. Any new approach, first introduced into clinical This reply refers to the comment available at doi:10.1007/s10151-012-0866-x.

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.

Stapled Transperineal Fistula Repair of Rectovaginal Fistula: A Preliminary Experience

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

Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer: HUANG et al.

Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value. Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT‐PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc‐small‐nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set. Furthermore, in the expanded validation set, high expression of lnc‐SNHG15 was significantly associated with lymph‐node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA‐SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003). Multivariate analyses demonstrated that lncRNA‐SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Coxs regression: 2.731). Lnc‐SNHG15 overexpression was significantly associated with CLM and high‐expression of lnc‐SNHG15 in CRC was an independent predictor of poor survival.

Associations between the cyclooxygenase-2 expression in circulating tumor cells and the clinicopathological features of patients with colorectal cancer: CAI et al.

While previous studies have shown that the number of circulating tumor cells (CTCs) alone is not sufficient to reflect tumor progression and that cyclooxygenase‐2 (COX‐2) expression is correlated with colorectal cancer (CRC) metastasis, COX‐2 expression status and its potential functions in CTCs of CRC patients are unknown. Here, epithelial‐mesenchymal transition (EMT) phenotype‐based subsets of CTCs and the COX‐2 expression status in CTCs were identified and their potential clinical values were assessed in 91 CRC patients. CTCs were enumerated in peripheral blood and subsets of CTCs (epithelial [eCTCs], mesenchymal [mCTCs], and biophenotypic [bCTCs]) and the COX‐2 expression status were determined using the RNA in situ hybridization method. CTCs were detected in 80.2% (73 of 91) patients. Neither the total CTC nor eCTC numbers were found to significantly associate with any of the clinicopathological features. However, the number of mCTCs was significantly associated with distance metastasis (P = 0.035) and had a trend of being associated with lymph node metastasis ( P = 0.055). Among the 73 patients enrolled for evaluating COX‐2 expression, 52.5% (38 of 73) were found to express COX‐2 in CTCs, and COX‐2 expression in CTCs was not found to associate with the clinicopathological factors. However, COX‐2 expression in mCTCs tended to have a higher rate in patients with metastasis compared with those without metastasis (72.0% vs 42.8%; P = 0.072). Furthermore, COX‐2 expression and mCTC marker expression correlated positively ( R = 0.287; P = 0.017). Further studies are required to investigate the clinical value of the expression of COX‐2 in mCTCs, especially in CRC patients with the advanced tumor stage and distant metastasis.

Prognostic and predictive value of interstitial cells of Cajal populations following stapled transanal rectal resection (STARR) in patients with obstructed defecation syndrome

Abstract Objective The present study was designed to evaluate the functional outcome of stapled transanal rectal resection (STARR) and to examine the relationship between the population density of the interstitial cells of Cajal (ICC) and the efficacy of the STARR operation in the management of obstructed defecation syndrome (ODS) patients. Methods Full-thickness rectal samples were obtained from 50 ODS patients who underwent STARR. Samples were analysed using ICC immunohistochemistry. Clinical and functional parameters obtained with defecography and anorectal manometry were compared with 20 controls. Results ICCs were significantly decreased in patients in the submucosal (SM), intramuscular (IM) and myenteric (MY) regions when compared with the control group (P < 0.05). The mean pre-operative Cleveland Constipation Score (CCS) was 24.2 ± 4.1, whilst the CCS at 1, 2, 3, 4 and 5 years post-operatively decreased significantly (P < 0.05). At 3 post-operative years, 58.3% (28/48) of the patients reported a favorable outcome (CCS ≤ 10). On univariate analysis, the functional results were worse in those with pre-operative digitation (P = 0.017), a decreased ICC-MY cell population (P = 0.067), a higher resting anal canal pressure (P = 0.039) and a higher rectal sensory threshold (P = 0.073). Multivariate analysis showed the decreased ICC-MY cell population was an independent predictor for low unfavorable functional outcome (odds ratio = 0.097, 95% confidence interval: 0.012–0.766). Conclusions STARR achieved acceptable results at the cost of a slight deterioration over a more prolonged follow-up. Patients with a decreased ICC number in the rectal specimen showed an unfavorable functional outcome where pre-operative histological assessment of a full-thickness rectal sample might predict for the functional outcome following STARR.

Tissue-Selecting Technique for Haemorrhoid Prolapse

We describe a technique for the management of prolapsing haemorrhoids, with the aim to minimize the risk of anal stricture and rectovaginal fistula and to reduce the impact of the stapling technique on rectal compliance. Tissue-selecting technique (TST) is associated with mild post- operative pain, few urgency episodes and no stenosis or anal incontinence.

The 16th National Congress of the Coloproctology Society of the Chinese Association of Integrative Medicine (CSCAIM)

The sixteenth National Congress of the Coloproctology Society of the Chinese Association of Integrative Medicine (CSCAIM) took place in Guangzhou on 24th–26th of August. Many colorectal surgeons from all over the world, the majority from China, took part in this important meeting. Special invited overseas speakers included Neal Ellis from the United States, Darren Gold from Australia, Arun Rojanasakul and Chucheep Sahakitrungruang from Thailand, Hyeon Keun Shin from South Korea, Takano Masahiro from Japan and Andrew Zbar from Israel. Dr. Ellis spoke on the use of bioprosthetics in colorectal surgery, with Dr. Gold outlining the indications and techniques of stapled haemorrhoidopexy and stapled repair of rectal prolapse. Professor Rojanasakul gave an insightful talk on the latest outcomes of his LIFT procedure. Professor Shin gave a masterful presentation on the history and the modern practical use of setons in complicated perirectal sepsis. Prof. Andrew Zbar discussed new developments in postprocessing of the 3D enodosonographic images of complex fistula-in-ano and perianal Crohn’s disease as well as one on the rudiments of how to write and successfully publish a colorectal paper. The full gamut of benign and malignant anorectal and colorectal disease was covered and highlighted the use of the tissue selecting technique (TST) in haemorrhoid surgery in a session headed by Professor Dong-Lin Ren from the sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou) ably supported by Prof. Dong Wang (Shenzhen). This was supplemented by a technical presentation on the stapler’s mechanics and limitations given by Les Hill (Australia) and one on post-PPH complications given by Prof. Zhan-Bin Luo (Guangzhou). Colorectal cancer screening and treatment were discussed (Prof. Dong-Wang Ma from Tianjin, Prof. Chuan-Gang Fu from Shanghai) as was the Chinese perspective on the management of anal cancer (Prof. Jian-Ping Wang from Guangzhou). Laparoscopic and single-port colorectal resection along with intersphincteric proctectomy and the endorectal TAMIS procedure were presented by a range of speakers (Prof. Zi-Qiang Wang from Chengdu, Prof. Li-Ming Pang from Nanning, Prof. Kai Pan from Shenzhen, Prof. ShangKuiXie, Prof. Liang Kang, Prof. Chu-Jun Li and Prof. Hai-Jun Deng from Guangzhou as well as by Dr. Sahakitrungruang from Thailand). Functional bowel disorders were addressed by various speakers; Prof. Xiao-Hua Hou from Wuhan, Prof. Guan-Gen Yang from Huangzhou and Prof. XiangDong Yang from Chengdu with the role of acupuncture treatment, which is making a scientific comeback, for the treatment of slow-transit constipation being presented from Prof. Guo-Dong Li (Beijing) of the Faculty of Traditional Chinese Medicine. Fistula management was presented in a talk given by Prof. Yong-Qing Cao from Shanghai, along with recommendations for its imaging and for the management of perianal Crohn’s disease (Prof. Zhi-Yang Zhou and Prof. Xiao-Jian Wu from Guangzhou). This was supported by an update on the Chinese view of VAAFT from Prof. Xiang-Dong Zeng’s group in Shenyang. Finally, the modern management of faecal incontinence was discussed in a talk given by Dr. Takano (Japan) and the Chinese viewpoint on sacral neuromodulation was reported by Dr. Xue-Zhi Xin (Jinan). H.-C. Lin (&) J. Li Guangzhou, China e-mail: linhongcheng@hotmail.com