Feasibility and Safety of Hybrid Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Colon Cancer

A Phase II Study to Evaluate the Feasibility and Safety of Hybrid Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Treatment of Patients With Colon Cancer

This study aims to evaluate the safety and efficacy of radical colectomy with hybrid transvaginal natural orifice transluminal endoscopic surgery (hvNOTES). This is a prospective, single-arm, multicenter, uncontrolled, open-label phase II study in 55 eligible subjects with resectable colon cancer. After informed consent, patients will be sent to have hvNOTES radical colectomy by surgeons with good experience in laparoscopic colorectal surgery. Patients' demographic, operative detail and postoperative outcomes including conversion to open surgery, operating time, blood loss, pain score, resumption of gastrointestinal function, postoperative complications, length of hospital stay, sexual function, quality of recovery, recurrence rate, recurrence patterns, relapse-free survival, and overall survival will be recorded prospectively. The results of the patients will be assessed to validate safety, functional outcomes or oncologic outcomes of hvNOTES colectomy.

Study Overview

• Status: Recruiting
• Conditions: Colon Cancer; Natural Orifice Transluminal Endoscopic Surgery
• Intervention / Treatment: Procedure: hvNOTES radical colectomy

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tao Fu, MD; Phone Number: 81333 86-88041911; Email: tfu001@whu.edu.cn
• Study Contact Backup: Name: Jun Ren, MD; Phone Number: 81332 86-88041911; Email: renjun0414@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital of Capital Medical University
      • Contact: Hongwei Yao, MD; Email: yaohongwei@medmail.com.cn
      • Principal Investigator: Hongwei Yao, MD
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Recruiting
      • Daping Hospital of Army Medical University
      • Contact: Weidong Tong, MD; Email: vdtong@163.com
      • Principal Investigator: Weidong Tong, MD
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Recruiting
      • Renmin Hospital of Wuhan University
      • Contact: Jun Ren, MD; Phone Number: 8615902761670; Email: renjun0414@163.com
  • Hunan
    • Changsha, Hunan, China, 410013
      • Not yet recruiting
      • The Third Xiangya Hospital of Central South University
      • Contact: Xiaorong Li, MD; Email: lixiaorong@medmail.com.cn
  • Shandong
    • Qingdao, Shandong, China
      • Recruiting
      • Qingdao Municipal Hospital
      • Contact: Tao Fu, MD; Phone Number: 8613720120190; Email: futao1975@tom.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 313000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University
      • Contact: Lifeng Sun, MD; Phone Number: 8613958103041; Email: sunlifeng@zju.edu.cn
      • Principal Investigator: Lifeng Sun, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female.
2. Age: over 18 and below 80 years old.
3. BMI < 28 kg/m^2.
4. American Society of Anesthesiologists score of class I to III.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Colonic adenocarcinoma by endoscopy with biopsy.
7. Tumor size ≤ 5 cm.

8. Involving a single colon segment:

   1. Right colon from the ileocecal valve up to and including the hepatic flexure.
   2. Left colon from the splenic flexure to the junction of the sigmoid and descending colon.
   3. Sigmoid colon between the descending colon and the rectum (at least 15 cm from the dentate).
9. Clinical stage cT1, T2, or T3, cN0, N1, N2.
10. No advanced local disease that renders laparoscopic resection impossible.
11. No transverse colon cancer (between distal hepatic flexure and proximal splenic flexure).
12. No distant metastasis in preoperative studies.
13. Complete preoperative colonoscopy demonstrating no synchronous colon cancers.

14. Require one of the following elective operations that may be safely performed by current techniques:

    1. Right hemicolectomy
    2. Left hemicolectomy
    3. Subtotal colectomy
    4. Sigmoid colectomy
15. Patients who agree with participating in the clinical study with informed consents. And with willingness and ability to comply with the requirements of the study protocol including follow-up.

Exclusion Criteria:

1. Patients who have never experienced complete sexual intercourse before the operation.
2. Previous intestinal surgery with any cause.
3. cT4 tumor.
4. Complications of colon cancer (bleeding, obstruction, or perforation).
5. Previous neoadjuvant chemotherapy or radiotherapy for colon cancer.
6. Patients who are diagnosed with other malignancies within 5 years.
7. Vulnerable patients.
8. Vaginal stenosis.
9. Prior reconstructive surgery of the vagina not including hysterectomy.
10. Unstable angina or myocardial infarction within the past 6 months.
11. Cerebrovascular accident within the past 6 months.
12. Continuous systemic steroid therapy within 1 month before the surgery.
13. Patients who participating or participated in other clinical trial within 6 months.
14. Pregnancy or breastfeeding.
15. Any history of pelvic radiation.
16. Anticipated need for an ostomy at the time of operation.
17. Patients requiring urgent or emergent surgery.
18. Patients with prior or suspected diagnosis of inflammatory bowel disease such as Crohn's disease, ulcerative colitis, or familial polyposis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: hvNOTES group; Participants will undergo hvNOTES radical colectomy.

Procedure: hvNOTES radical colectomy; With the patient under general anesthesia, pneumoperitoneum is achieved. Three trocars are inserted, one 12 mm or 5 mm in the umbilicus and two 5 mm in the right and/or left flanks. Mobilization of the splenic flexure or the hepatic flexure is performed with an initial traditional laparoscopic approach. A single-port is inserted into the abdominal cavity transvaginally through the colpotomy. Then most of the procedures are performed transvaginally with conventional rigid laparoscopic instruments. The corresponding arteries and veins are divided. The mesocolon is mobilized. The small intestine/colon/rectum are then divided with stapler. The specimen is removed transvaginally. Intracorporeal anastomosis is performed as per the surgeon's standard of care. For sigmoidectomy, the colon is then exteriorized and the anvil is fixed in the colon. An end-to-end anastomosis is performed using a circular stapler. Drainage tubes may be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative complications	The primary end point is major complication during surgery or within 90 days after surgery. A major intraoperative and postoperative complication is defined as a surgical or medical complication with a CTCAE grade of III or higher. The most severe complication in a patient was considered for the classification of the primary end point.	up to 90 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of c-reactive protein (CRP)	C-Reactive Protein (CRP) values on postoperative day 1and 3.	1 and 3 postoperative days
Concentration of procalcitonine (PCT)	Procalcitonine (PCT) values on postoperative day 1and 3.	1 and 3 postoperative days
Complete pathological assessment of CME specimens	Complete mesocolic excision (CME) is defined as complete resection of the mesocolon with its anatomical envelope. Rate of complete and near-CME achieved with hvNOTES, based on standard pathologic assessment of CME specimens.	up to 1 week after surgery
Postoperative pain assessed by the numeric rating scale (NRS)	Pain score assessments: The investigator's staff will provide a rating scale to the patients to self-rate and record their pain at baseline (prior to surgery), at 24, 48, 72, 96, 120, 144, and 168 hours following the procedure end time (or discharge if earlier) postoperatively using the numeric rating scale (NRS) where 0 is for no pain and 10 is for the worst pain imaginable.	up to 1 week after surgery
Amount of narcotic pain medication administered	The amount of narcotic pain medication administered through postoperative day 7 (or discharge if earlier) will be recorded (total dose of morphine equivalent during hospitalization and average dose per day).	up to 1 week after surgery
Time to first flatus after surgery	Time to first flatus is defined as days from a colectomy procedure to first occurrence of flatus during subject's postoperative recovery.	up to 1 week after surgery
Number of harvested lymph nodes	Number of harvested Lymph nodes according to the pathological report.	up to 1 week after surgery
R0 resection	Rate of resection without any affected margins during the surgical procedure according to the pathological report.	up to 1 week after surgery
Length of hospital stay	Days in the hospital after surgery.	up to 4 weeks after surgery
Sexual function assessment	Patient self-reported sexual functions as assessed by the Female Sexual Function Index (FSFI). The FSFI is a 19-item questionnaire to rate sexual function between 2.0 and 36.0, where 2.0 is low sexual function and 36.0 is high sexual function.	baseline, 6 months, and 12 months after surgery
Quality of recovery: Quality of Recovery 40 questionnaire (QoR-40)	Patient's quality of recovery is assessed by using the Quality of Recovery 40 questionnaire (QoR-40, score range: 40-200). Higher values represent better outcomes. The validate questionnaire measure quality of recovery by evaluating patients' comfort, emotions, physical independence, and support using the same scale.	14 days after surgery
Satisfaction with surgical scars: Validated questionnaire Patient Scar Assessment Questionnaire (PSAQ)	Validated questionnaire Patient Scar Assessment Questionnaire (PSAQ, score range: 28-102) will be administered to assess the patient's perception of scarring. Lower values represent better outcomes. The PSAQ consists of 5 subscales: Appearance, symptoms, consciousness, satisfaction with appearance, and satisfaction with symptoms.	3, 6, and 12 months after surgery
Quality of Life Questionnaire (QLQ) of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30	Quality of Life Questionnaire (QLQ) of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Score 3 months and 1 year after the procedure. This scale has functional, global health, and symptoms subscales/items all scored from 0 to 100. Higher scores on these subscales indicate high level of functioning, high quality of life, and high level of symptomatology, respectively.	baseline, 3 and 12 months after surgery
Postoperative recurrence patterns	The recurrence patterns are determined according to the primary recurrence site diagnosed radiologically (CT, US, MRI, or PET-CT), or with histologic proof (ascitic cytology, colonoscopic biopsy, or surgery).	2 years after surgery
Relapse-free survival	Relapse-free survival is defined as the time from random assignment until disease relapse or death from any cause.	2 years after surgery
Overall survival	Overall survival is defined as time from surgery to death.	2 years after surgery
Conversion to laparoscopic or open surgery	One of the secondary outcome measures is the rate of conversion to laparoscopic or open surgery as an indicator of surgical technical difficulty. Conversion is defined as the use of a laparoscopic port for the anastomosis, or a laparotomy wound for any part of the mesocolon dissection or the anastomosis.	during the surgery

Collaborators and Investigators

• Sponsor: Renmin Hospital of Wuhan University
• Investigators: Principal Investigator: Tao Fu, MD, Wuhan University Renmin Hospital

Publications and helpful links

General Publications

• Rattner D, Kalloo A; ASGE/SAGES Working Group. ASGE/SAGES Working Group on Natural Orifice Translumenal Endoscopic Surgery. October 2005. Surg Endosc. 2006 Feb;20(2):329-33. doi: 10.1007/s00464-005-3006-0. No abstract available.
• Rattner DW, Hawes R, Schwaitzberg S, Kochman M, Swanstrom L. The Second SAGES/ASGE White Paper on natural orifice transluminal endoscopic surgery: 5 years of progress. Surg Endosc. 2011 Aug;25(8):2441-8. doi: 10.1007/s00464-011-1605-5. Epub 2011 Feb 27. No abstract available.
• Moloney JM, Gan PS. Hybrid Transvaginal NOTES and Mini-Laparoscopic Colectomy: Benefit Through Synergy. JSLS. 2016 Oct-Dec;20(4):e2016.00062. doi: 10.4293/JSLS.2016.00062.
• Lamm SH, Zerz A, Efeoglou A, Steinemann DC. Transrectal Rigid-Hybrid Natural Orifice Translumenal Endoscopic Sigmoidectomy for Diverticular Disease: A Prospective Cohort Study. J Am Coll Surg. 2015 Oct;221(4):789-97. doi: 10.1016/j.jamcollsurg.2015.07.012. Epub 2015 Jul 21.
• Bulian DR, Runkel N, Burghardt J, Lamade W, Butters M, Utech M, Thon KP, Lefering R, Heiss MM, Buhr HJ, Lehmann KS. Natural Orifice Transluminal Endoscopic Surgery (NOTES) for colon resections--analysis of the first 139 patients of the German NOTES Registry (GNR). Int J Colorectal Dis. 2014 Jul;29(7):853-61. doi: 10.1007/s00384-014-1883-1. Epub 2014 May 7.
• D'Hondt M, Devriendt D, Van Rooy F, Vansteenkiste F, Dozois E. Transvaginal pure NOTES sigmoid resection using a single port device. Tech Coloproctol. 2014 Jan;18(1):77-80. doi: 10.1007/s10151-013-1005-z. Epub 2013 Apr 6.
• Alba Mesa F, Amaya Cortijo A, Romero Fernandez JM, Komorowski AL, Sanchez Hurtado MA, Fernandez Ortega E, Sanchez Margallo FM. Transvaginal sigmoid cancer resection: first case with 12 months of follow-up--technique description. J Laparoendosc Adv Surg Tech A. 2012 Jul-Aug;22(6):587-90. doi: 10.1089/lap.2011.0469. Epub 2012 Jun 12.
• Alba Mesa F, Amaya Cortijo A, Romero Fernandez JM, Komorowski AL, Sanchez Hurtado MA, Sanchez Margallo FM. Totally transvaginal resection of the descending colon in an experimental model. Surg Endosc. 2012 Mar;26(3):877-81. doi: 10.1007/s00464-011-1919-3. Epub 2011 Sep 23.
• Lacy AM, Delgado S, Rojas OA, Almenara R, Blasi A, Llach J. MA-NOS radical sigmoidectomy: report of a transvaginal resection in the human. Surg Endosc. 2008 Jul;22(7):1717-23. doi: 10.1007/s00464-008-9956-2. Epub 2008 May 7.
• Sodergren MH, Clark J, Athanasiou T, Teare J, Yang GZ, Darzi A. Natural orifice translumenal endoscopic surgery: critical appraisal of applications in clinical practice. Surg Endosc. 2009 Apr;23(4):680-7. doi: 10.1007/s00464-008-0278-1. Epub 2009 Jan 1.
• Whiteford MH, Spaun GO. A colorectal surgeons viewpoint on natural orifice translumenal endoscopic surgery. Minerva Chir. 2008 Oct;63(5):385-8.
• Park JS, Choi GS, Lim KH, Jang YS, Kim HJ, Park SY, Jun SH. Clinical outcome of laparoscopic right hemicolectomy with transvaginal resection, anastomosis, and retrieval of specimen. Dis Colon Rectum. 2010 Nov;53(11):1473-9. doi: 10.1007/DCR.0b013e3181f1cc17.
• Alba Mesa F, Sanchez Hurtado MA, Sanchez Margallo FM, Romero Fernandez JM, Amaya Cortijo A, Fernandez Ortega E, Komorowski AL. Laparoscopy-assisted transvaginal resection of sigmoid cancer. Eur J Surg Oncol. 2014 Jun;40(6):713-8. doi: 10.1016/j.ejso.2014.01.008. Epub 2014 Feb 7.
• Noguera JF, Cuadrado A, Dolz C, Olea JM, Garcia JC. Prospective randomized clinical trial comparing laparoscopic cholecystectomy and hybrid natural orifice transluminal endoscopic surgery (NOTES) (NCT00835250). Surg Endosc. 2012 Dec;26(12):3435-41. doi: 10.1007/s00464-012-2359-4. Epub 2012 May 31.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: vNOTESCA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers with academic interest in natural orifice transluminal endoscopic surgery. Data or samples shared will be coded, with no protected health information (PHI) included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact tfu001@whu.edu.cn.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No