Abstract】With the advancement of laparoscopic equipment and surgeons’ operating techniques and public recognition of minimally invasive laparoscopic surgery, laparoscopic radical hysterectomy (LRH) with pelvic lymphadencetomy has become a new surgical modality for the treatment of early-stage cervical cancer. Nearly 2,000 studies of LRH for cervical cancer have been reported from several centers worldwide with relatively satisfactory results, but the data obtained so far on recurrence and survival are not sufficient to conclude that LRH has a long-term safety profile for cervical cancer. We review the current status and progress of laparoscopic surgery for cervical cancer.
・Review
Since the first laparoscopic radical hysterectomy (LRH) with pelvic lymphadencetomy was reported in the early 1990s, the use of laparoscopy in the treatment of cervical cancer has developed rapidly. Nearly two thousand studies of LRH for cervical cancer have been reported in several centers worldwide, and modified LRH procedures, nerve preservation and robotic surgery have been reported. Preliminary studies have shown that LRH is not only technically safe and feasible, but can achieve clinical outcomes similar to those of open surgery. This procedure may be a new treatment alternative to traditional open surgery due to its advantages of less trauma, lower postoperative morbidity and mortality, shorter hospital stay, and faster recovery. However, due to the lack of results from large prospective clinical randomized controlled studies and long-term follow-up, the data obtained so far on recurrence and survival are not sufficient to conclude that LRH has long-term safety in the treatment of cervical cancer. Several current global LRH research centers are involved, several issues of LRH research and future trends are reviewed. Currently several global LRH research centers due to the difficulty of LRH and the high operational skills required of the operator laparoscopic surgery, clinically limited to be performed by adequately trained oncologic endoscopists, Table 1 shows the distribution of LRH in several larger samples worldwide, it can be seen that China has a pivotal position in LRH research. several issues involved in LRH research.
I. Selection of cases
include indications for surgery, staging, size of the mass and whether radiotherapy was administered preoperatively. Most cases of LRH reported in the literature are early-stage cervical cancer, i.e., stage IA to IB1, with a mass diameter <3 cm and no signs of lymph node metastasis on imaging. Therefore, the survival results achieved in the studies were more satisfactory. However, there are a few study centers that have extended cases to stage IB2, IIA, and even a small number of stage IIB. Since the long-term survival results of these cases have not yet been obtained, it is still controversial whether it is appropriate to use LRH for this group of patients. There are few reports on LRH after post-mounted radiotherapy for cervical cancer.
Pomel et al [2] reported 50 cases of LRH, 31 of which had tumor diameters of 2-4 cm and received preoperative brachytherapy, with one postoperative complication of bladder fistula and one ureteral stricture. Current evidence suggests that preoperative brachytherapy does not affect the feasibility of surgery.In 2009, Colombo et al [13] observed the outcome of 46 patients with locally advanced cervical cancer (ⅠB2, ⅡA, ⅡB) after simultaneous radiotherapy for LRH and 56 patients with open radical hysterectomy (abdominalradical hysterectomy, ARH), 7 patients in the LRH group The mean bleeding volume (200 mL:400 mL, P=0.01), median length of stay (5 d:8 d, P=0.01), local recurrence rate, tumor-free survival and overall survival were similar in the LRH and ARH groups. Although technically simultaneous radiotherapy followed by LRH is feasible, there is still a large controversy about this procedure because of the high potential complication rate.
Second, operative time and bleeding volume Most studies have shown that the surgical procedure for LRH is relatively long, and the mean operative time reported in different literature varies widely (92-420 min), which reflects the uneven technical level and experience among different investigators, and the learning curve exists in all study groups. The standardization and reproducibility of the procedure largely influences the length of the operative time. spirtos et al [15] in 1996 reported an operative time of 253 min in the LRH group, while in 2002 reported an operative time of 205 min, with the last 52 cases reaching 186 min [1]. Similarly, Pomel et al [2] observed that the mean operative time was reduced from 277 min, first reported in 1997, to 258 min in 2003, with a mean reduction of 19 min, and in the most recent study the operative time was less than 3 h (mean 135 min, range 114-180 min). lee et al [16] found that using a bipolar pulse system (pulsed bipolarsystem (PBS) administration significantly reduced the operative time (172 min:229 min, P<0.001), reduced bleeding (397 mL:564 mL, P=0.03), and lower incidence of postoperative complications compared with conventional bipolar coagulation system administration. In India, Puntambekar et al [5] reported 248 cases of LRH using the "Pune technique" - a six-step approach (anterior U resection, posterior U resection, opening of the rectovaginal space, opening of the pararectal space , opening the ureteral tunnel, and lymph node dissection) resulted in a shorter operative time (65-120 min, mean 92 min) than other reports, and there were no intermediate open cases. The average bleeding volume in most studies was about 200-370 mL (estimated blood loss, EBL). Meticulous intraoperative hemostasis can greatly reduce the need for blood transfusion. The four available studies comparing LRH with ARH have confirmed that EBL is lower in LRH, with statistically significant differences between the two groups in three of these studies [17]. In addition, in published reports on LRH, the rate of intraoperative or postoperative transfusion has been reduced to very low, and in most cases transfusion is required only in case of unexpected vascular injury.
III. Interventional open rate
The literature reports an intermediate open abdomen rate of 0-10.5%, which is associated with serious complications at an early stage of the learning curve. In laparoscopic surgery, conversion to open is not an unfavorable outcome, especially when the decision to convert to open is made after adequate evaluation of the pelvic situation, the feasibility of laparoscopic surgery and whether it will cause serious complications.
IV. Evaluation of the adequacy of tumor resection
Histopathological evaluation of hysterectomy specimens (length of parametrial and vaginal resection) and counting the number of lymph nodes removed are direct methods to evaluate the completeness of LRH surgery. spirtos et al [15] reported an average length of 3.3 cm (1.0-5.0 cm) in 10 cases of LRH parametrial resection and 2.15 cm (1.0-3.5 cm) in vaginal resection. Frumovitz et al [8] compared the length of paraphasectomy in ARH (n=54) and LRH (n=35) (3.6 cm:3.7 cm on the right side; 3.7 cm:3.8 cm on the left side), vaginal stump (1.9 cm:1.7 cm), and negative margin rate (96%:91%), and the differences were not statistically significant. ghezzi et al [18] compared 50 cases of Piver type III or type II The histopathological findings were similar in the two groups: type II (LRH:ARH) had a mean width of 2.4 cm (1.0-3.0):2.3 cm (1.8-4.0 cm) on the right side, respectively, P=0.28; the mean width of 2.3 cm (1.8-4.0 cm):2.2 cm (1.2-3.0 cm) on the left side, P=0.54; type III (LRH:ARH) had a mean width of 3.8 cm (2.2-3.0 cm) on the right side, respectively. 3.8 cm (2.3-6.5 cm):3.4 cm (1.7-7.0 cm), P=0.59; type III (LRH:ARH) was 3.8 cm (2.3-6.5 cm):3.4 cm (1.7-7.0 cm), P=0.59;
The mean width on the left side was 3.6 cm (2.0-6.0 cm):3.5 cm (1.5-6.5 cm), P=0.82, and there was no statistically significant difference in the rate of positive cut edges between the 2 groups. The report shows that Piver III LRH paracentesis of 3.5 cm is a more desirable target, which is comparable to the results of ARH Chongqing, China. In contrast, Xu et al [6] from Chongqing, China, reported even longer parametrial tissue removal [right side (5.0±1.2) cm; left side (5.2±1.1) cm] in their study. Considering the rate of retraction both after uterine dissection and after formalin fixation, in 2008 Querleu et al [19] recommended that whenever radical hysterectomy is performed, the length of uterine specimen resected is examined intraoperatively when the uterus is dissected and postoperatively after fixation, respectively. The gold standard for evaluating adequate lymph node dissection is currently considered to be the clearance of up to 20 pelvic or para-aortic lymph nodes. Li et al [20] in Foshan, China, reported no statistically significant difference in the number of pelvic lymph nodes cleared between 90 LRH and 45 ARH cases [(21.28±8.39) (18.77±9.47); P=0.151]. Zakashansky et al [9] reported that the mean number of lymph nodes cleared in the LRH group was higher than that in the open group (31.0:21.8, respectively; P<0.01). respectively, P<0.01). The adequacy of laparoscopic lymph node dissection is not limited by the procedure itself, but rather by the experience and perseverance of the surgeon. querleu et al [21] reported 1000 patients with gynecologic malignancies undergoing a total of 1192 laparoscopic pelvic and/or para-aortic lymph node dissection. 777 pelvic lymph node dissections (757 transperitoneal and 20 extraperitoneal) and 415 cases underwent abdominal para-aortic lymph node dissection (155 transperitoneal and 260 extraperitoneal), of which 192 patients underwent both pelvic and abdominal para-aortic lymph node dissection. The numbers of transperitoneal pelvic, transperitoneal abdominal aorta and extraperitoneal abdominal aortic lymph node dissection were 18, 17 and 21, respectively. With experience, the number of pelvic and para-aortic lymph node dissections increased to 24 and 22. Kihler et al [22] found that a more constant number of pelvic lymph node dissections (16.9 to 21.9) could be achieved after approximately 20 surgical studies for 650 laparoscopic pelvic and/or para-aortic lymph node dissections.
V. Intraoperative and postoperative complications Studies on the feasibility of LRH have reported on complications. The most serious complications include damage to the vessels, bladder, ureter, and bowel. Most bladder injuries can be managed microscopically, whereas vascular injuries are a common cause of intermediate openings. serious postoperative complications of LRH are uncommon, unless an undetected intraoperative injury results in a postoperative urethral fistula. Common intraoperative and postoperative complications of LRH reported in the literature are shown in Table 2.
VI. Bladder dysfunction
Postoperative bladder dysfunction is the most common complication of radical hysterectomy. Early symptoms include decreased bladder capacity, decreased forceps vitality, and loss of bladder sensitivity. Approximately 80% of patients have long-term symptoms such as difficulty emptying the bladder, bladder irritation symptoms and decreased bladder compliance 6 to 12 months after surgery. The occurrence of urinary retention is not only related to the inevitable damage to the sympathetic and parasympathetic nerves innervating the bladder and urethra due to intraoperative radical resection of the parametrial, vaginal and paravaginal tissues, but also to the loss of bladder neck support and posterior bladder tilt due to hysterectomy.Xu et al [6] reported that the median time to recovery of bladder function after LRH was 10.2 (6-50) d. Yan et al [11] from Wenzhou, China reported that The median time to recovery of bladder function after surgery was 8(4-40) d; the incidence of residual urine volume >100 mL after catheter removal at 10 d postoperatively was defined as urinary retention, and its incidence was 32.5%. Ramirez et al [4] defined residual urine volume >100 mL measured after catheter removal at 14 d postoperatively as urinary retention, and the median time to recovery of bladder function after surgery was 16(13-29) d. Since different reports on the definition of urinary retention differ, it is difficult to compare the incidence of urinary retention between studies.
VII. Length of hospital stay
The mean length of stay in some LRH patients in some of the current studies is quite long, which can be explained by the following points: (i) it is related to the length of paraphimosis and vagotomy in different studies. (ii) The intentional prolongation of hospital stay, especially in the early stages of the learning curve, is helpful to observe. (iii) The relatively conservative attitude of some investigators towards the recovery of postoperative bladder function and the longer duration of urinary catheter removal. (iv) It is related to its having a higher rate of postoperative complications.
VIII. Modified procedure for LRH
Theoretically, the indications for laparoscopic modified radical hysterectomy (LMRH, i.e., type II radical hysterectomy) include only patients with FIGO stage IA2 and a small proportion of patients with vascular infiltration stage IA1, while stage IB1 with interstitial infiltration is generally not included in the indications. panici et al [23] reported 83 cases FIGO stage IA2-ⅠB1 cervical cancer underwent open or laparoscopic pelvic lymph node dissection, with lymph node negative patients undergoing modified radicalhysterectomy (MRH) and lymph node positive patients undergoing classical radical hysterectomy (RH) plus pelvic and para-aortic lymph node dissection to the submesenteric level. Sixty-three patients with negative frozen lymph nodes underwent MRH (group A) and 20 with intraoperative lymph node metastases underwent RH (group B), with 5-year survival rates of 95% and 74% in the two groups, respectively, suggesting that the extent of radical hysterectomy can depend on the outcome of intraoperative lymph node freezing.Eisenkop et al [24] reported 50 patients with CIN III or adenocarcinoma in situ of the cervix and/or without follow-up conditions or unable to undergo re LMRH was performed in 35 patients with residual lesions, 26 with precancerous lesions, and 9 with invasive carcinoma. 1 of the 9 cervical invasive carcinomas was stage IA1, 3 were stage IA2, and 5 were stage IB1. The mean operative time was 96(58-185) min, blood loss was 100(50-450) mL, and postoperative hospital stay was 2.5(1-14) d. All patients survived tumor-free (median follow-up 44.2 months). Therefore, LMRH may be a treatment option for patients whose cervical invasive carcinoma cannot yet be completely excluded.
IX. Prognostic gold standard – tumor recurrence and survival
Due to the different environment between laparoscopic and open surgery (e.g., carbon dioxide, high pressure and low pH), patients with perforator incisional implantation after laparoscopy have been reported in recent years.Ramirez et al [25] reviewed all gynecologic malignancies undergoing laparoscopic operation from 1978-2004 that resulted in perforator metastasis (port
site metastasis, PSM) in 58 patients in 31 studies, including 12 cases of cervical cancer, with a median time between presentation of PSM and diagnosis of cervical cancer of 5 (1.5-19) months.Belval et al [26] reported a patient with FIGO stage IB1 cervical adenocarcinoma treated with post-mounted radiotherapy followed by LRH, in which peritoneal metastases were found 16 months after surgery.Park et al [ 27] recently reported a patient with stage IIB cervical cancer who underwent laparoscopic pelvic and para-arterial lymph node dissection with postoperative perforation site implantation and liver metastases; this case had a single pelvic lymph node metastasis on one side of the scope only. The cause of perforation hole implantation is still unknown, and most scholars now advocate appropriate intraoperative reduction of pneumoperitoneal pressure (<12 mmhg, 1 mmhg=0.133 kpa); avoiding excessive manipulation of the cervical tumor; placing the lymph nodes in the specimen bag for removal, and careful and slow deflation. Survival outcomes of LRH in cervical cancer are poorly reported. spirtos et al [1] reported 78 cases of FIGO stage IA2 to IB (14 cases of IB2) with a mean follow-up of 68.3 months, a recurrence rate of 10.3% and a 5-year survival rate of 93.6%. Risk factors for recurrence included tumor size, depth of interstitial infiltration, vascular infiltration, lymph node metastasis, and proximity of surgical margins to the tumor.Pomel et al [2] reported that 45 of 50 patients with stage IA2 to IB1 had 5-year tumor-free and overall survival rates of 90.5% and 96.8%, respectively, with a mean follow-up of 44 months (3-100 months) and a recurrence rate of 6%.Obermair et al [3] reported a recurrence rate of 7.9% in 39 cases during a median follow-up period of 36.5 months (8.9-54.1 months), including some advanced cases.Puntambekar et al [5] reported 7 (2.8%) recurrences in 248 cases of FIGO stages IA2 to IB1, with no deaths during a mean follow-up period of 36 months.Malzoni et al [12] reported that stages I Li et al [20] compared ARH and LRH with a follow-up of 26 months, except for 5 and 10 lost cases in the two groups, and the morbidity and mortality rates were 8% and 10%, respectively, which may be related to the proportion of patients with large tumors (tumors up to 4-5 cm) and advanced stages (lymph node metastases).Chong et al [14] reported that 100 cases of ⅠA2 to ⅡB were followed up for 66.5 months, with a recurrence rate of 10% and 5-year survival rates of 96% and 90% in the first 50 and last 50 cases, respectively. pellegrino et al [10] followed up 107 ⅠB1 patients with tumor diameter <3 cm for 30 months, with a recurrence rate of 10% and a survival rate of 95%.
Trends in development
I. Nerve-preserving surgery
In recent years, based on the development of pelvic neuroanatomy, some domestic and foreign medical centers actively carry out extensive hysterectomy with preservation of pelvic autonomic nerve, aiming to ensure radical surgery while preserving pelvic autonomic nerve structures and improving patients’ quality of life, and this surgery is one of the hot spots of research at home and abroad today. Using the NSRH procedure systematic never-sparing radical hysterec-tomy (SNSRH), which dissects the pelvic autonomic nerve structures, the pelvic splanchnic nervers (PSN), the hypogastric nerve (HN), and the paravaginal tissues are treated during the operation while the main ligament, the uterosacral ligament, the deep bladder-cervical ligament, and the paravaginal tissues are treated, respectively. In 2005, Possover et al [28] reported that different sacral nerve functions were identified by laparoscopic neuro-guidance technique laparoscopic neuro- navigation (LANN) was performed to identify the function of the pelvic autonomic nervous system in each patient by microscopic electrical stimulation of the nerve with monopolar or bipolar forceps and microprobes placed into the rectum and urethra for kinetic testing. Finally, the visceral pelvic nerves of the bladder and rectum were selectively dissected as a nerve preservation technique.
In 2010, Park et al [29] reported the technical points of laparoscopic SNSRH: (i) identification of IHP sacral nerve afferent fibers during dissection of the main ligament. (ii) Identify the HN and proximal IHP when dissecting the sacral ligament and rectovaginal ligament. ③Identify the vesicovaginal vein when dissecting the posterior lobe of the cystocervical ligament of the bladder. ④Identify the efferent branches of the IHP when dissecting the posterior lobe of the cystocervical ligament of the bladder. ⑤ Preserve the bladder branch of the IHP when dissecting the paravaginal area and remove the vaginal branch of the uterus. The time to recovery of bladder function after conventional surgery (e.g., based on residual urine <50 mL) is approximately 3-6 weeks postoperatively, whereas bladder function after SNSRH is usually recovered 10-14
d after SNSRH recovery. Both radical hysterectomy with preservation of the nerve without reducing the radical outcome can improve the quality of patient survival to varying degrees, and its superiority is attracting more and more investigators to try this technique.
Second, robotic assisted laparoscopic radical hysterectomy (RALRH) In 2006, Sert et al [30] reported the first case of stage IB1 cervical cancer in which Piver III laparoscopic radical hysterectomy was performed with the assistance of da Vinci robotic system (Intuitive Surgical Inc, Sunnyvale, CA). Sert et al [31] subsequently reported the results of a study of 15 cases of early stage cervical cancer with RALRH or LRH (type II or III).The pathological findings such as number of lymph nodes, parametrial tissue and length of vaginal dissection were similar in the 2 groups, with less bleeding and shorter hospital stay in the robotic group.Boggess et al [32] compared 51 cases of RALRH with 49 cases of ARH. the robotic group had less bleeding, shorter operative time, and higher number of lymph nodes removed than the open group. kim et al [33] reported 10 cases of RALRH for FIGO stage IA2-ⅠB1 cervical cancer with a mean operative time (including assembly time) of 207 (120-240) min. of which the mean assembly time was 26 (10-45) min and the mean EBL was 355
mL, and there were no intraoperative complications or intermediate open cases. The mean number of pelvic lymph nodes removed was 27.6 (12 to 52) and the mean length of stay was 7.9 (5 to 17) d. There were no recurrent cases during a mean follow-up period of 9 months.Magrina et al [34] did a prospective study of 3 groups, RALRH, LRH and ARH, including patients with cervical cancer (18 cases/27, 18 cases/31, 21 cases/35, respectively) and uterine There were no recurrent cases of cervical cancer in the 3 groups at a mean follow-up of 31.1 months after the procedure. Overall, although the machine assembly time may still be longer, the total time for robotic surgery is significantly less, with less bleeding and fewer complications compared to LRH. Thus, robotic surgery is safe and reliable. Evidence suggests that robotic-assisted laparoscopic surgery for cervical cancer is feasible, but results from randomized controlled studies with conventional laparoscopic and open surgery are lacking, and Mayo Clinic Arizona is conducting a prospective randomized study comparing the outcomes of robotic versus conventional laparoscopic surgery. The American Board of Gynecologic Oncology Gynecologic Lumpectomy Group recently planned a 740-case randomized controlled study comparing robotic, laparoscopic, and open groups for radical hysterectomy. Although robotic surgery is promising for the radical surgical treatment of cervical cancer, the traditional laparoscopic technique remains necessary for now because robotic equipment is expensive and difficult to scale up in some developing countries.