Is robotic-assisted surgery a better choice in vaginectomy of complicated vaginal high-grade squamous intraepithelial lesions than conventional laparoscopic surgery?

doi:10.21203/rs.3.rs-2855122/v1

The aim of this study was to evaluate the operative outcomes of robotic-assisted laparoscopic vaginectomy (RALV) and conventional laparoscopic vaginectomy (CLV) for patients with complicated vaginal high-grade squamous intraepithelial lesions (HSIL). Therefore, an analysis of one hundred and nine patients with complicated vaginal HSIL (32 patients in the RALV group and 77 patients in the CLV group) who underwent minimally invasive vaginectomy was conducted retrospectively. Compared with the CLV group, patients in the RALV group demonstrated less estimated blood loss, a lower rate of intraoperative complications and shorter durations of paralytic ileus time, urinary catheter indwelling time and postoperative hospitalization time (all P < 0.05). However, the RALV group had significantly higher hospital costs than the CLV group (P < 0.05). The total operative time, postoperative complications, positive surgical margins, pathology upgrading or treatment outcomes did not significantly differ between the two groups (all P > 0.05). Our results demonstrated that both RALV and CLV can achieve satisfactory treatment outcomes, while RALV has the advantages of less intraoperative blood loss, fewer intraoperative complications and faster postoperative recovery. RALV has the potential to become a better choice for vaginectomy without regard to the burden of hospital costs.

robotic-assisted laparoscopy

laparoscopy

vaginectomy

vaginal high-grade squamous intraepithelial lesions

operative outcomes

Vaginal squamous intraepithelial lesions (SIL) are a type of diseases characterized by the occurrence of atypical hyperplasia of vaginal squamous cells and carcinoma in situ, excluding invasive carcinoma [1]. They are rare precancerous lesions of the lower genital tract, accounting for approximately 0.4%-1% of epithelial tumors of the lower genital tract, with an incidence 100 times lower than that of cervical squamous intraepithelial lesions [2–5]. Currently, the popularization of cervical cancer screening and improvements in detection technology have increased the detection rate of vaginal SIL [1, 6].

In 2014, the WHO (World Health Organization) classified vaginal intraepithelial lesions into vaginal low-grade squamous intraepithelial lesions (LSIL) and vaginal high-grade squamous intraepithelial lesions (HSIL) in the Classification of Tumors of Female Reproduction Organs [7]. Vaginal LSIL can be treated conservatively due to its high rate of spontaneous regression and low risk of progression to malignancy [8]. Even if vaginal HSIL are benign, active treatment is always recommended, as the risk of malignant transformation in vaginal HSIL can reach 4.6%-12% [1, 9–11]. However, consensus concerning the most effective management of vaginal HSIL is currently lacking. The treatment modalities are diverse and include surgical resection, topical pharmaceuticals, photodynamic therapy, laser ablation, and radiotherapy [3, 12, 13].

In clinical practice, partial or total vaginectomy for complicated vaginal HSIL patients is favored by gynecologists. Anatomically, the vagina is located in the middle of the deep pelvic cavity next to the bladder and rectum, and the space of the vagina is quite small, leading to limited vision in the transvaginal surgery and significantly increasing the difficulty of the procedure. Thus, the application of transvaginal vaginectomy is limited in complex vaginal surgeries that require greater precision because of the restricted space and complex anatomy of the vagina. In recent decades, minimally invasive laparoscopy has developed rapidly, including robotic-assisted laparoscopy, and is widely used in the field of gynecology surgery [14, 15]. Minimally invasive laparoscopy is characterized by magnifying the surgical field, which contributes to identifying blood vessels and separating tissue spaces. In addition, long-arm instruments with small end-effector simplify surgery in narrow spaces compared with the use of human hands and offer a certain degree of flexibility. Unlike conventional laparoscopic surgery, the robotic-assisted laparoscopic process system has a three-dimensional view to better and more precisely visualize the surgical area; it also improves mobility and increases the range of motion of the instrument’s end-effector [14]. The use of robotic-assisted laparoscopic vaginectomy (RALV) has likely increased due to these advantages, despite limited evidence in favor of RALV. Therefore, based on a large cohort of vaginectomy patients, this study was designed to compare the safety and efficiency between RALV and CLV in the treatment of complicated vaginal HSIL.

Study population

All patients with complicated vaginal HSIL who underwent CLV or RALV at the First Affiliated Hospital of Zhengzhou University from December 2013 to May 2022 were retrospectively analyzed. Vaginal HSIL was diagnosed through colposcopically guided biopsy before vaginectomy. Considering a uniform definition for complicated vaginal HSIL is lacking, we defined complicated vaginal HSIL in this study according to the characteristics of disease, history of management and its combination with cervical HSIL. All vaginal HSIL patients fulfilled at least one of the following criteria: 1) the range of lesions beyond the upper third of vagina; 2) multifocal lesions with failure of or recurrence after conservative treatment or with suspicious vaginal carcinoma among patients with a previous hysterectomy or concurrent cervical HSIL; and 3) the range of lesions less than or equal to the upper third of vagina that are multifocal, extensive, and concurrent with cervical HSIL. In addition, all the patients without a previous hysterectomy had concurrent cervical HSIL, and the cervical cancer were excluded by cervical conization before vaginectomy. Patients with vaginitis were cured preoperatively. Patients were excluded if they: 1) were diagnosed with vaginal invasive cancer before vaginectomy; 2) received previous hysterectomy due to a malignant gynecological tumor; 3) had vesical dysfunction (for example, incontinentia urinae or retention of urine); or 4) were unlikely to follow-up.

Procedure

The location and range of preoperative lesions were accurately recorded via careful inspection of the total vagina and/or cervix by colposcope. Especially for post-hysterectomy vaginal HSIL, more attention needs to be given to examining the vaginal vault, as some lesions may hide in the vaginal angles, making them difficult to identify.

For each patient, the choice of RALV and CLV was based on the final decision of the patients and their family after being informed by the surgeon about the advantages and disadvantages of the two procedures. RALV was performed using the da Vinci-Si Surgical System (Intuitive Surgical Inc, Sunnyvale CA, USA).

Patients were placed in the lithotomy position. After general anesthesia, the surgical area was routinely disinfected and covered with a sterile surgical towel, a urethral catheter was inserted, and then the trocar was placed by surgeons. In addition, the RALV group needed to connect mechanical arms. Lesion areas were confirmed by applying iodine to the total vagina and/or cervix and marked by a suture or marking pen approximately 0.5 cm (at least 0.3 cm) below the edge of the lesion (Fig. 1). The uterine manipulator was placed in the vagina for patients with a uterus, but a gauze roll or the cup of the uterine manipulator was placed in the vagina for patients who had received a hysterectomy (Fig. 1). For patients with post-hysterectomy vaginal HSIL, the length of the vaginal wall should be resected from the vaginal stump to 0.5 cm (at least 0.3 cm) below the edge of the lesion. For those who had vaginal HSIL combined with cervical HSIL, hysterectomy ± bilateral salpingo-oophorectomy was performed simultaneously in addition to vaginectomy during the operation (Fig. 2 and Fig. 3).

Data collection

Demographic and clinical data, such as age, menopause, body mass index, clinical manifestation, comorbidities, previous hysterectomy, vaginal estrogen medication use and range of vaginal HSIL, were collected. Surgery-related data were recorded, including the total operating time (defined as the time from skin incision to the time of last closure suture of the skin), estimated blood loss, complications, length of resected vagina, paralytic ileus time (calculated in days from the end of the operation to the ability to pass feces or gas), urinary catheter indwelling time (calculated in days from the end of the operation to the removal of urinary catheter smoothly without paruria), postoperative hospitalization time, postoperative pathology and hospital cost. All procedures were performed by gynecologists with several years of experience in conventional laparoscopic or robotic-assisted surgery. Therefore, a learning curve was not included in the operations. Intraoperative complications included hemorrhage (estimated blood loss exceeding 500 mL) and bladder, ureter, and bowl injury. Postoperative complications were defined as any newly unfavorable episodes occurring during the hospital stay or within 30 days after surgery.

All subjects were followed up to assess long-term postoperative outcomes, including the status of homogeneous HPV infection, regression, remission, persistence, recurrence and progression. The status of homogeneous HPV infection was determined by HPV screening at six months after the vaginectomy. Regression was defined as negative colposcopic examination and vaginal biopsy at six months after vaginectomy. Remission was defined as vaginal LSIL diagnosed by vaginal biopsy at six months after vaginectomy. Persistence was defined as vaginal HSIL diagnosed by vaginal biopsy at six months after vaginectomy. Recurrence was defined as vaginal HSIL again after remission or regression. Progression was defined as invasive vaginal carcinoma, a higher grade than previous vaginal HSIL. Disease-free survival was defined as the time from vaginectomy to disease progression or recurrence from vaginal HSIL. All patients were followed-up for the first time at the third month after the operation, then visited every 3 months for half a year, every 6 months for 2.5 years, and then once a year after 3 years. A pelvic examination, human papilloma virus (HPV) test and thinprep cytologic test (TCT) were conducted as the essential items. Patients were referred for colposcopy when meeting the requirements for colposcopy referral, and histopathological examination was performed if necessary. All of the patients were followed up until February 2023.

Statistical analysis

SPSS (version 21.0, Chicago, IL, USA) software was used to analyze the data. Quantitative variables are presented as the mean ± standard deviation or median and interquartile range (IQR), and were compared using Student’s t test or the Mann-Whitney U test, as appropriate. Categorical variables are reported as absolute numbers and percentages and were compared using the Pearson χ² test or the Fisher exact test when appropriate. Survival curves were generated by using the Kaplan–Meier method, and Cox proportional-hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the effect of treatment on disease-free survival. P values < 0.05 (two-tailed) were considered statistically significant.

Patient Characteristics

Overall, 109 patients with complicated vaginal HSIL were enrolled in this study, including 77 patients in the CLV group and 32 patients in the RALV group. Among them, 7 patients (5 in the CLV group and 2 in the RALV group) experienced failure of photodynamic therapy, 2 patients in the CLV group experienced recurrence of photodynamic therapy and 3 patients (2 in the CLV group and 1 in the RALV group) experienced failure of laser ablation. The demographic and clinical characteristics of the patients are summarized in Table 1. These baseline characteristics were similar between the two groups except for the range of vaginal HSIL. The mean age of the patients was 55.2 years, and the mean BMI was 24.0 kg/m². Most patients (89.0%) were menopausal. One hundred (91.7%) patients had high-risk HPV infection, among which HPV16 infection (66.0%) was the most common type. Forty-three patients underwent previous hysterectomy (32 patients in the CLV group and 11 patients in the RALV group). Indications included cervical HSIL (27 patients in the CLV group and 8 patients in the RALV group), hysteromyoma (1 patient in the CLV group and 3 patients in the RALV group), adenomyosis (1 patient in the CLV group), abnormal uterine bleeding (2 patients in the CLV group), and benign ovarian tumor (1 patient in the CLV group). There was significant difference between the two groups with respect to the range of vaginal HSIL (P=0.00).

Operative data

In total, 8 patients (25.0%) of robotic-assisted total vaginectomy ± hysterosalpingo-oophorectomy, and 7 (10.0%) patients of conventional laparoscopic total vaginectomy ± hysterosalpingo-oophorectomy were examined, and this difference was not statistically significant (P=0.059). As shown in Table 2, the length of the resected vagina measured after the operation was longer in the RALV group than in the CLV group (5.0 (4.28-5.88) vs 3.5 (3.0-4.5), P=0.000). The operation time in the CLV group (118.2±41.0 minutes) was similar to that in the RV group (129.9±43.8 minutes) (P=0.186). The estimated blood loss was higher in the CLV group than in the RALV group (68.1±56.4 mL vs 41.6±40.3 mL, P=0.017). Intraoperative complications, including hemorrhage (7.8%, 6/77 vs 3.1%, 1/32), bladder injury (13.0%, 10/77 vs 3.1%, 1/32), ureteral injury (2.6%, 2/77 vs 0) and rectal injury (1.3%, 1/77 vs 0), more frequently occurred in the CLV group rather than in the RALV group. The rate of postoperative complications in the CLV group appeared to be higher than in the RALV group, but the difference was not significant (P=0.192). With respect to paralytic ileus time, urinary catheter indwelling time and postoperative hospitalization time, these were all longer in the CLV group when compared with the RALV group (all P<0.05). In this study, only one patient (0.9%) who underwent CLV had a positive surgical margin, and four patients (3.7%) were ultimately diagnosed with occult vaginal invasive carcinoma after vaginectomy. In addition, the RALV group was associated with significantly higher hospital costs in comparison with CLV group (53035.1±9539.0 vs 32706.8±6659.2 yuan, P=0.000).

Long-term follow-up

The median duration of follow-up after vaginectomy was 33.0 months (range 7-109) for all except four patients who were diagnosed with occult vaginal invasive carcinoma after vaginectomy. During the long-term follow-up, similar results of prognosis were found between the two groups (Table 3). Ninety-six patients (88.1%) got negative homogeneous HPV infection at six months postoperatively compared with preoperative HPV infection. A total of 95.2% (100/105) of the patients experienced vaginal HSIL regression to normalization through vaginectomy. Six patients (5 patients in the CLV group and 1 patient in the RALV group) were observed recurrence or progression, but this difference was not significant (HR= 0.507; 95% CI, 0.242-17.499) (Figure 4).

Vaginal squamous intraepithelial lesions are the precancerous lesions of invasive vaginal carcinoma, which lack specific clinical manifestations. The vast majority of patients are asymptomatic, and only a small number of people may experience abnormal vaginal secretions or bleeding after sexual intercourse [16]. Undoubtedly, abnormal vaginal secretions are a characteristic clinical symptom of vaginitis rather than other gynecological diseases. Usyk et al. [17], based on a study of a prospective longitudinal cohort, reported that the cervicovaginal microbiome is related to high-risk HPV progression in cervical squamous intraepithelial lesions. Thus, whether vaginal inflammation is associated with vaginal squamous intraepithelial lesions is intriguing. In this study, only 16.6% (80/109) of patients visited the doctor because of clinical symptoms; the remaining patients were diagnosed from cervical cancer screening. Thus, the timely discovery of vaginal SIL appears to remain difficult.

The mean age of patients in our study was 55.2 years, similar to that in Kim’s report [18]. Many studies had reported that high-risk HPV infection, previous hysterectomy especially due to the indication of cervical HSIL, menopause, smoking, and immunosuppression, are risk factors for vaginal squamous intraepithelial lesions [18–23]. We noted that 91.7% (100/109) of patients had high-risk HPV infection, among which HPV16 infection was more predominant, and these findings are consistent with those of previous related studies [18, 24, 25]. In this study, 43 patients (39.4%) had previously undergone hysterectomy, 35 (81.4%) of whom underwent hysterectomy due to cervical HSIL. Although we did not specifically analyze the relationship between vaginal HSIL and a history of previous hysterectomy, it could obviously show that previous hysterectomy resulting from cervical HSIL was associated with vaginal HSIL. In the current study, 89.0% of patients were postmenopausal, suggesting that vaginal HSIL is more common in postmenopausal women. Li et al. [21], through a case-control study, observed that premenopausal women had a 2.09 times higher increased risk of developing into vaginal SIL than postmenopausal women (P = 0.017; 95% CI = 1.13–3.85), indicating that menopause is a risk factor for vaginal SIL.

Researches have shown that approximately 4.6%-12% of occult vaginal invasive cancers are ultimately discovered in the course of initial management of vaginal HSIL [1, 9–11, 16]. In addition, Hodeib et al. [26] observed that about 12% vaginal HSIL progressed to vaginal invasive carcinoma during close follow-up after active treatment. In this study, 3.7% (4/109) of patients were diagnosed with occult vaginal carcinoma based on postoperative pathology, and three patients progressed to vaginal carcinoma during the follow-up period.

Unfortunately, the managements of vaginal HSIL remain controversial, which include topical pharmaceuticals (such as 5-fluorouracil cream, imiquimod and interferon), laser vaporization, photodynamic therapy, surgery and brachytherapy [3, 12, 18, 27, 28]. In fact, vaginal HSIL is treated individually in the clinic according to the patient’s age, disease characteristics, state of HPV infection and previous therapeutic procedures [27]. Topical pharmaceuticals are prevalent in adjuvant therapy, especially in HPV-induced patients [29]. Young patients with multifocal and exposure-prone vaginal HSIL can be treated with laser vaporization or photodynamic therapy [18]. Surgical treatments, which included local excision, partial vaginectomy and total vaginectomy, were characterized by shortening the time to normalization and had a higher cure rate [10, 18]. However, surgical management could shorten the length of the vagina, which negatively affects the quality of sexual life, and may place patients at risk for stenosis of the vagina [30]. Therefore, surgical treatments should only be considered for selected patients. Unifocal lesions are usually treated by local excision; partial or total vaginectomy is suitable for the complicated vaginal HSIL. In our study, 95.2% (100/105) of patients had a regression of vaginal HSIL to normalization through vaginectomy. Brachytherapy exhibits distinct efficacy on vaginal HSIL, with a cure rate of 77%-96% [31–33]. However, patients face with the vaginal mucosal atrophy, stenosis, ulcers and injury to the rectum and bladder after brachytherapy, leading to a long-term influence on later quality of life [13]. Therefore, brachytherapy is usually recommended to the patient who cannot tolerate surgery but whose disease is resistant to conservative management and have experienced frequent vaginal HSIL recurrence.

This work is the first retrospective study comparing both operative data and patient-centered prognosis between CLV and RALV. We find that RALV was more frequently performed in the complicated vaginal HSIL patients who had more extensive lesions of the vagina. Indeed, based on the anatomy around the vagina, the longer the length of the abnormal vagina needed for resection, the more difficult it is to perform a vaginectomy. However, our study suggested that the total operation time did not significantly differ between the two groups. Compared with the CLV group, the RALV group had less estimated blood loss, which is consistent with the results from most other studies comparing robotic-assisted surgery and conventional laparoscopic surgery [14, 34–36]. In addition, the rate of intraoperative complications was significantly lower in the RALV group than in the CLV group (6.3% vs 24.7%, P = 0.026). Among the reported intraoperative complications, it reveals that 10.1% (11/109) of patients experienced bladder injury, which was the main complication during vaginectomy. Choi et al. [37] reported four patients with vaginal squamous intraepithelial lesions who underwent laparoscopic upper vaginectomy, one of whom developed bladder injury. There are venous plexus, vaginal branch of uterine artery and ureter on both sides of the upper part of vagina. The upper 2/3 of the anterior vaginal wall is adjacent to the bladder through the vesico-vaginal septum, and the venous plexus is densely distributed between them. The lower 1/3 of the anterior vaginal wall is adjacent to the urethra through the urethra-vaginal septum, and the middle part of the posterior vaginal wall is attached to the ampulla of the rectum by a thin layer. Therefore, during vaginectomy, blood vessels, the ureter, the bladder and the rectum are easily damaged, leading to intraoperative complications. The level of estrogen in the body and vaginal elasticity are especially decreased in postmenopausal patients with complicated post-hysterectomy vaginal HSIL. After hysterectomy, the anatomical structures of the vaginal stump are altered and tissue adhesion is formed; consequently, the risks of injury to the ureter, bladder and rectum become higher when the bladder and rectum are pushed down during a vaginectomy, making vaginectomy more difficult. However, these challenges could be overcome by robotic surgery. Well-known that robotic surgery system provide three-dimensional visualization, by which the intraoperative field can be magnified approximately 10–15 times [38]. Thus, surgeons can more distinctly identify the anatomy around the vagina and avoid surgical damage; in addition, robotic instruments have multiple degrees of freedom for movement and mini end-effector, as well as tremor-filtering technology and stable cameras, which provide much flexibility and precision for vaginectomy, leading to fewer intraoperative complications. Feng et al. [35] conducted a multicentre randomised controlled trial of rectal cancer surgery and demonstrated that robotic-assisted surgery is more suitable for operations in the deeply narrow pelvic cavity.

In this study, we observed that robotic-assisted surgery was associated with better postoperative recovery in terms of shorter paralytic ileus time, urinary catheter indwelling time and postoperative hospitalization time, consistent with other reports [14, 35]. Fourteen patients underwent total vaginectomy in the current study and did not undergo vaginoplasty. Because this study was retrospective, the preoperative communication informed document showed that patients had been informed about the available vaginoplasty options and the impact of total vaginectomy on their sex life, but they all chose not to undergo vaginoplasty. Undeniably, total vaginectomy can have serious influences on the postoperative sex life of patients with complicated vaginal HSIL. Although vaginoplasty which is a challenging procedure has a high requirement on the surgeon’s technique, it can significantly improve the satisfactory of sex life [39, 40]. Consequently, vaginoplasty can be considered for selected patients who will be performed with total vaginectomy.

Although the advantages of robotic-assisted vaginectomy are distinct, the hospital cost of robotic surgery is significantly higher than that of conventional laparoscopic surgery, consistent with the finds of other studies [41–43]. This cost is a continuing limitation to those who choose the surgical approach primarily based on their economic status. However, robotic surgery has the potential to be used in telemedicine, and robot-based telemedicine has become a reality in some hospitals. Through the telemedicine system platform, medical care could be performed without restrictions on time and place, and therefore, more potentialities and advantages of robotic surgery will be found. Jang et al. [44] demonstrated the economic feasibility of a robot-based telemedicine system compared with traditional face-to-face medical services through a cost-benefit analysis. Therefore, the shortcomings of robotic surgery regarding the higher hospital costs can be balanced under the utilizing of robot-based telemedicine systems.

Indeed, this study had several limitations. First, as a single central retrospective study, it might have selection bias of patients and affect the generalizability and transferability of the results. Second, the limited number of patients who underwent robotic-assisted vaginectomy may be considered as a weakness. However, large prospective, randomized controlled clinical trials of robotic-assisted vaginectomy are quite challenging due to the low incidence of complicated vaginal HSIL. Third, the conventional laparoscopy approach used in this study was equipped with two-dimensional cameras. Currently, the latest generation of conventional laparoscopy techniques has been improved with three-dimensional cameras, which has overcome the lack of depth perception in two-dimensional cameras. As this technology evolves, conventional laparoscopic surgery will improve, providing better assistance in vaginectomy.

Our study is the largest retrospective study of patients with complicated vaginal HSIL who underwent vaginectomy via robotic-assisted surgery or conventional laparoscopic surgery. In both groups, patients had similar satisfactory treatment outcomes, but patients more frequently benefited from RALV than from CLV. Except for higher hospital costs, patients who underwent RALV had less estimated blood loss, a lower rate of intraoperative complications and experienced a faster postoperative recovery. Certainly, a multicentric, prospective and randomized trial should be conducted in the future to further verify the demonstrated benefits of RALV.

Ethics approval: The study was approved by the Ethics Committee and Institutional Review Board of the First Affiliated Hospital of Zhengzhou University (No. 2022-KY-0205-002).

Consent to participate: Informed consent from all individual participants has been waived by the Ethics Committee for this is a retrospective study.

Consent to publish: The authors affirm that human research participants provided informed consent for publication of the images in Figure 1A, 2 and 3.

Author Contributions: Conceptualization, Y.L., R.G., Q.W., J.B. and M.C.; methodology, Y.L., M.M., M.Z, and H.F.; formal analysis, Y.L., R.G. and M.Z.; resources, R.G. and C.W.; data curation, R.G., J.B., Q.W. and C.W.; writing—original draft preparation, Y.L.; writing—review and editing, R.G., M.M., M.C., L.S. and H.F.; funding acquisition, R.G. All authors have read and agreed to the published version of the manuscript.

Funding: This research was funded by the young and middle-aged health science and technology innovation leader training project (YXKC2020012).

Institutional Review Board Statement: The study was approved by the Ethics Committee and Institutional Review Board of the First Affiliated Hospital of Zhengzhou University (No. 2022-KY-0205-002).

Informed Consent Statement: Not applicable.

Conflicts of Interest: The authors declare no conflict of interest.

Gunderson CC, Nugent EK, Elfrink SH, et al. (2013). A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia. Am J Obstet Gynecol 208: 410.e411-416. https://doi.org/10.1016/j.ajog.2013.01.047
Wharton JT, Tortolero-Luna G, Linares AC, et al. (1996). Vaginal intraepithelial neoplasia and vaginal cancer. Obstet Gynecol Clin North Am 23: 325-345.
Gurumurthy M and Cruickshank ME. (2012). Management of vaginal intraepithelial neoplasia. J Low Genit Tract Dis 16: 306-312. https://doi.org/10.1097/LGT.0b013e31823da7fb
Sillman FH, Fruchter RG, Chen YS, et al. (1997). Vaginal intraepithelial neoplasia: risk factors for persistence, recurrence, and invasion and its management. Am J Obstet Gynecol 176: 93-99. https://doi.org/10.1016/s0002-9378(97)80018-x
Murta EF, Neves Junior MA, Sempionato LR, et al. (2005). Vaginal intraepithelial neoplasia: clinical-therapeutic analysis of 33 cases. Arch Gynecol Obstet 272: 261-264. https://doi.org/10.1007/s00404-005-0022-1
Wee WW, Chia YN and Yam PK. (2012). Diagnosis and treatment of vaginal intraepithelial neoplasia. Int J Gynaecol Obstet 117: 15-17. https://doi.org/10.1016/j.ijgo.2011.10.033
Kurman RJ, Carcangiu, M.L., Herrington, C.S., and Yong, R.H. WHO classification of tumours of female reproductive organs. 4th ed. IARC: Lyon, 2014, France: 210-213.
Zeligs KP, Byrd K, Tarney CM, et al. (2013). A clinicopathologic study of vaginal intraepithelial neoplasia. Obstet Gynecol 122: 1223-1230. https://doi.org/10.1097/01.AOG.0000435450.08980.de
Sopracordevole F, De Piero G, Clemente N, et al. (2016). Vaginal Intraepithelial Neoplasia: Histopathological Upgrading of Lesions and Evidence of Occult Vaginal Cancer. J Low Genit Tract Dis 20: 70-74. https://doi.org/10.1097/lgt.0000000000000150
Rome RM and England PG. (2000). Management of vaginal intraepithelial neoplasia: A series of 132 cases with long-term follow-up. Int J Gynecol Cancer 10: 382-390. https://doi.org/10.1046/j.1525-1438.2000.010005382.x
Indermaur MD, Martino MA, Fiorica JV, et al. (2005). Upper vaginectomy for the treatment of vaginal intraepithelial neoplasia. Am J Obstet Gynecol 193: 577-580; discussion 580-571. https://doi.org/10.1016/j.ajog.2005.03.055
Zolciak-Siwinska A, Gruszczynska E, Jonska-Gmyrek J, et al. (2015). Brachytherapy for vaginal intraepithelial neoplasia. Eur J Obstet Gynecol Reprod Biol 194: 73-77. https://doi.org/10.1016/j.ejogrb.2015.08.018
Frega A, Sopracordevole F, Assorgi C, et al. (2013). Vaginal intraepithelial neoplasia: a therapeutical dilemma. Anticancer Res 33: 29-38.
Nobbenhuis MAE, Gul N, Barton-Smith P, et al. (2023). Robotic surgery in gynaecology: Scientific Impact Paper No. 71 (July 2022). Bjog 130: e1-e8. https://doi.org/10.1111/1471-0528.17242
Twijnstra AR, Kolkman W, Trimbos-Kemper GC, et al. (2010). Implementation of advanced laparoscopic surgery in gynecology: national overview of trends. J Minim Invasive Gynecol 17: 487-492. https://doi.org/10.1016/j.jmig.2010.03.010
Zhang J, Chang X, Qi Y, et al. (2016). A retrospective study of 152 women with vaginal intraepithelial neoplasia. Int J Gynaecol Obstet 133: 80-83. https://doi.org/10.1016/j.ijgo.2015.08.014
Usyk M, Zolnik CP, Castle PE, et al. (2020). Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog 16: e1008376. https://doi.org/10.1371/journal.ppat.1008376
Kim MK, Lee IH and Lee KH. (2018). Clinical outcomes and risk of recurrence among patients with vaginal intraepithelial neoplasia: a comprehensive analysis of 576 cases. J Gynecol Oncol 29: e6. https://doi.org/10.3802/jgo.2018.29.e6
Cao D, Wu D and Xu Y. (2021). Vaginal intraepithelial neoplasia in patients after total hysterectomy. Curr Probl Cancer 45: 100687. https://doi.org/10.1016/j.currproblcancer.2020.100687
Schockaert S, Poppe W, Arbyn M, et al. (2008). Incidence of vaginal intraepithelial neoplasia after hysterectomy for cervical intraepithelial neoplasia: a retrospective study. Am J Obstet Gynecol 199: 113.e111-115. https://doi.org/10.1016/j.ajog.2008.02.026
Li H, Guo YL, Zhang JX, et al. (2012). Risk factors for the development of vaginal intraepithelial neoplasia. Chin Med J (Engl) 125: 1219-1223.
Massad LS, Xie X, Greenblatt RM, et al. (2012). Effect of human immunodeficiency virus infection on the prevalence and incidence of vaginal intraepithelial neoplasia. Obstet Gynecol 119: 582-589. https://doi.org/10.1097/AOG.0b013e318244ee3d
Field A, Bhagat N, Clark S, et al. (2020). Vaginal Intraepithelial Neoplasia: A Retrospective Study of Treatment and Outcomes Among a Cohort of UK Women. J Low Genit Tract Dis 24: 43-47. https://doi.org/10.1097/lgt.0000000000000502
Ao M, Zheng D, Wang J, et al. (2022). A retrospective study of cytology and HPV genotypes results of 3229 vaginal intraepithelial neoplasia patients. J Med Virol 94: 737-744. https://doi.org/10.1002/jmv.27311
Alemany L, Saunier M, Tinoco L, et al. (2014). Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples. Eur J Cancer 50: 2846-2854. https://doi.org/10.1016/j.ejca.2014.07.018
Hodeib M, Cohen JG, Mehta S, et al. (2016). Recurrence and risk of progression to lower genital tract malignancy in women with high grade VAIN. Gynecol Oncol 141: 507-510. https://doi.org/10.1016/j.ygyno.2016.03.033
Schnürch HG, Ackermann S, Alt-Radtke CD, et al. (2019). Diagnosis, Therapy and Follow-up of Vaginal Cancer and Its Precursors. Guideline of the DGGG and the DKG (S2k-Level, AWMF Registry No. 032/042, October 2018). Geburtshilfe Frauenheilkd 79: 1060-1078. https://doi.org/10.1055/a-0919-4959
Rountis A, Pergialiotis V, Tsetsa P, et al. (2020). Management options for vaginal intraepithelial neoplasia. Int J Clin Pract 74: e13598. https://doi.org/10.1111/ijcp.13598
Ratnavelu N, Patel A, Fisher AD, et al. (2013). High-grade vaginal intraepithelial neoplasia: can we be selective about who we treat? Bjog 120: 887-893. https://doi.org/10.1111/1471-0528.12223
Hoffman MS, DeCesare SL, Roberts WS, et al. (1992). Upper vaginectomy for in situ and occult, superficially invasive carcinoma of the vagina. Am J Obstet Gynecol 166: 30-33. https://doi.org/10.1016/0002-9378(92)91823-s
Graham K, Wright K, Cadwallader B, et al. (2007). 20-year retrospective review of medium dose rate intracavitary brachytherapy in VAIN3. Gynecol Oncol 106: 105-111. https://doi.org/10.1016/j.ygyno.2007.03.005
Song JH, Lee JH, Lee JH, et al. (2014). High-dose-rate brachytherapy for the treatment of vaginal intraepithelial neoplasia. Cancer Res Treat 46: 74-80. https://doi.org/10.4143/crt.2014.46.1.74
Blanchard P, Monnier L, Dumas I, et al. (2011). Low-dose-rate definitive brachytherapy for high-grade vaginal intraepithelial neoplasia. Oncologist 16: 182-188. https://doi.org/10.1634/theoncologist.2010-0326
Ito H, Moritake T and Isaka K. (2022). Does the use of a uterine manipulator in robotic surgery for early-stage endometrial cancer affect oncological outcomes? Int J Med Robot 18: e2443. https://doi.org/10.1002/rcs.2443
Feng Q, Yuan W, Li T, et al. (2022). Robotic versus laparoscopic surgery for middle and low rectal cancer (REAL): short-term outcomes of a multicentre randomised controlled trial. Lancet Gastroenterol Hepatol 7: 991-1004. https://doi.org/10.1016/s2468-1253(22)00248-5
Moon AS, Garofalo J, Koirala P, et al. (2020). Robotic Surgery in Gynecology. Surg Clin North Am 100: 445-460. https://doi.org/10.1016/j.suc.2019.12.007
Choi YJ, Hur SY, Park JS, et al. (2013). Laparoscopic upper vaginectomy for post-hysterectomy high risk vaginal intraepithelial neoplasia and superficially invasive vaginal carcinoma. World J Surg Oncol 11: 126. https://doi.org/10.1186/1477-7819-11-126
Materazzi G and Rossi L. (2021). Robot-assisted adrenalectomy: state of the art. Updates Surg 73: 1131-1146. https://doi.org/10.1007/s13304-020-00915-2
Darai E, Toullalan O, Besse O, et al. (2003). Anatomic and functional results of laparoscopic-perineal neovagina construction by sigmoid colpoplasty in women with Rokitansky's syndrome. Hum Reprod 18: 2454-2459. https://doi.org/10.1093/humrep/deg443
Li JS, Crane CN and Santucci RA. (2021). Vaginoplasty tips and tricks. Int Braz J Urol 47: 263-273. https://doi.org/10.1590/s1677-5538.Ibju.2020.0338
Kristensen SE, Mosgaard BJ, Rosendahl M, et al. (2017). Robot-assisted surgery in gynecological oncology: current status and controversies on patient benefits, cost and surgeon conditions - a systematic review. Acta Obstet Gynecol Scand 96: 274-285. https://doi.org/10.1111/aogs.13084
Specchia ML, Arcuri G, Di Pilla A, et al. (2022). The value of surgical admissions for malignant uterine cancer. A comparative analysis of robotic, laparoscopic, and laparotomy surgery in a university hospital. Front Public Health 10: 920578. https://doi.org/10.3389/fpubh.2022.920578
Stringfield SB, Parry LA, Eisenstein SG, et al. (2022). Experience with 10 years of a robotic surgery program at an Academic Medical Center. Surg Endosc 36: 1950-1960. https://doi.org/10.1007/s00464-021-08478-y
Jang SM, Lee K, Hong YJ, et al. (2020). Economic Evaluation of Robot-Based Telemedicine Consultation Services. Telemed J E Health 26: 1134-1140. https://doi.org/10.1089/tmj.2019.0211

Table 1. Demographic and clinical characteristics.

	CLV group (n=77)	RALV group (n=32)	P value
Age, years	54.9±9.0	56.0±6.5	0.532
BMI, kg/m²	23.9±1.8	24.1±2.0	0.593
ASA grade			0.229
Ⅰ	57 (74.0)	20 (62.5)
Ⅱ	20 (26.0)	12 (37.5)
Menopause			0.492
Yes	67 (87.0)	30 (93.8)
No	10 (13.0)	2 (6.3)
Infection with high-risk HPV			0.969
HPV16	46 (59.7)	20 (62.5)
HPV18	5 (6.5)	2 (6.3)
Other high-risk HPV	19 (24.7)	8 (25.0)
Unknown/none	7 (9.1)	2 (6.3)
Antecedent cytology at diagnosis			0.495
ASC-US	17 (22.1)	10 (31.3)
ASC-H	9 (11.7)	3 (9.4)
LSIL	15 (19.5)	3 (9.4)
HSIL	19 (24.7)	6 (18.8)
Unknown/none	17 (22.1)	10 (31.3)
Vaginal estrogen pretreatment			0.119
Yes	24 (31.2)	15 (46.9)
No	53 (68.8)	17 (53.1)
Clinical symptoms			0.485
Symptom-free	54 (70.1)	26 (33.8)
Abnormal vaginal secretions	16 (20.8)	4 (12.5)
Bleeding after sexual intercourse	7 (9.1)	2 (6.3)
Diabetes			1.000
Yes	9 (11.7)	4 (12.5)
No	67 (88.3)	28 (87.5)
Range of vaginal HSIL			0.000
≤upper third of vagina	43 (55.8)	6 (18.8)
>upper third of vagina	34 (44.2)	26 (81.3)
Previous hysterectomy	32 (41.6)	11 (34.4)	0.485
Indication for hysterectomy (n=43)			0.684
Cervical HSIL	27 (84.4)	8 (72.7)
Benign disease	5 (15.6)	3 (27.3)
Treatment of vaginal HSIL before vaginectomy			0.879
Photodynamic therapy	7 (9.1)	2 (6.3)
Laser ablation	2 (2.6)	1 (3.1)
None detection	68 (88.3)	29 (90.6)

BMI, body mass index; ASA, American Society of Anesthesiologists; HPV: human papillomavirus; ASC-US: Atypical squamous cells of undetermined significance; ASC-H: Atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesions; LSIL: Low-grade squamous intraepithelial lesions; HSIL: High-grade squamous intraepithelial lesions; CLV, conventional laparoscopic vaginectomy; RALV, robotic-assisted laparoscopic vaginectomy.

Table 2. Operative data in the two groups.

	CLV group (n=77)	RALV group (n=32)	P value
Total operation time, min	118.2±41.0	129.9±43.8	0.186
Estimated blood loss, mL	68.1±56.4	41.6±40.3	0.017
Length of resected vagina, cm	3.5(3.0-4.5)	5.0(4.28-5.88)	0.000
Intraoperative complications	19 (24.7)	2 (6.3)	0.026
Hemorrhage	6 (7.8)	1 (3.1)
Bladder injury	10 (13.0)	1 (3.1)
Ureteral injury	2 (2.6)	0
Rectal injury	1 (1.3)	0
Postoperative complications	14 (18.2)	2 (6.3)	0.192
Urinary retention	3 (3.9)	1 (3.1)
Infection	6 (7.8)	0
VTE in the lower limbs	4 (5.2)	1 (3.1)
Split in abdominal incision	1 (1.3)	0
Paralytic ileus time, day	2.0 (2.0-2.0)	2.0 (1.0-2.0)	0.000
Urinary catheter indwelling time, day	4.0 (2.0-6.0)	2.0 (2.0-3.0)	0.001
Postoperative hospitalization time, day	5.0 (4.0-6.0)	4.0(4.0-5.0)	0.020
Positive surgical margin			1.000
Yes	1 (1.3)	0
No	76 (98.7)	32 (100)
Pathology upgrading			0.716
Yes	2 (2.6)	2 (6.2)
No	75 (97.4)	30 (93.8)
Hospital cost, yuan	32706.8±6659.2	53035.1±9539.0	0.000

VTE, venous thromboembolism; CLV, conventional laparoscopic vaginectomy; RALV, robotic-assisted laparoscopic vaginectomy.

Table 3. The difference in prognosis between the two groups.

		CLV group (n=75)	RALV group (n=30)	P value
Status of homogeneous HPV infection				0.741
Negative	69 (92.0)		27 (90.0)
Positive	6 (8.0)		3 (10.0)
Respond to vaginectomy				0.805
Regression	71 (94.7)		29 (96.7)
Remission	3 (4.0)		1 (3.3)
Persistence	1 (1.3)		0
Long-term prognosis				0.533
Normalization	70 (93.3)		29 (96.7)
Recurrence	2 (26.7)		1 (3.3)
Progression	3 (4.0)		0

No competing interests reported.

Is robotic-assisted surgery a better choice in vaginectomy of complicated vaginal high-grade squamous intraepithelial lesions than conventional laparoscopic surgery?

Status:

Version 1

Abstract

Figures

1. Introduction

2. Materials and methods

3. Results

4. Discussion

5. Conclusions

Declarations

References

Tables

Additional Declarations

Status:

Version 1