The ideal goal of surgical treatment of cervical cancer is to “reduce early and late complications without compromising oncologic efficacy”. The type of surgery for early-stage cervical cancer depends on the precise assessment of preoperative and intraoperative risk factors. Research on pelvic autonomic anatomy has led to individualized surgical treatment of cervical cancer, and radical hysterectomy with preservation of the pelvic autonomic nerve (NSRH) has become the routine procedure in many women’s cancer centers, significantly improving the quality of life of patients.
Since the 1970s, the Piver surgical classification has been widely used, and in 2007 Okabayashi proposed a new classification principle, and in 2008 a new Q-M staging was introduced, which is divided into types A-D4 (including subtypes) and includes nerve preservation and parametrial lymph node dissection. This article summarizes the knowledge related to the neuroanatomy of the female genitourinary system, discusses the main complications of conventional RH, and describes in detail the individualized surgery for cervical cancer.
I. Neuroanatomy of the female genitourinary system
Before RH is performed, it is necessary to master the characteristics of the surgical area, especially the localization of the pelvic autonomic nerves.
1. Inferior epigastric plexus: It starts from the aortic bifurcation and reaches the pelvis through the anterior sacral region. The inferior epigastric plexus contains sympathetic nerves from the abdominal aortic plexus and the cervical sympathetic ganglion (efferent fibers of the twelfth thoracic vertebra and the first and second lumbar vertebra), as well as visceral nerve fibers from the first and second lumbar vertebrae, and the caudal and lateral continuation of the inferior epigastric plexus is the left and right inferior abdominal nerves. 4-6%.
2. Inferior ventral nerve: It originates from the superior inferior ventral plexus, passes through the lateral aspect of the sacral uterine ligament, travels downward to the dorsal aspect of the paracervical tissue, below the ureter, and fuses into the inferior inferior ventral plexus, and identification of the inferior ventral nerve can prevent injury when removing the dorsal aspect of the paracervical tissue. Part of the SLN is adjacent to the inferior abdominal plexus and injects into the presacral lymph nodes.
3. Inferior subabdominal plexus: It is formed by the confluence of sympathetic nerves from the inferior ventral nerve and parasympathetic nerves from the pelvic visceral plexus, including nerve fibers and ganglia, in which the parasympathetic fibers originate from the second, third and fourth sacral medullary nerve roots, covered by the pelvic fascia for the first 3 cm, and then converge into the inferior subabdominal plexus, which constitutes the most important deep paracervical (including the main ligament, sacral uterine ligament and parametrial tissue) neural network structures.
The efferent fibers of the inferior hypogastric plexus send out branches: rectal, uterine, bladder, and rectovaginal branches, which innervate the corresponding organs and finally reach the deep cervical ligament of the bladder, the most important bladder branch of the inferior hypogastric plexus. The rectovaginal branch is located centrally (at the intersection of the ureter and uterine artery) and is subdivided into the vaginal and rectal branches; the bladder branch is located lateral to the inferior hypogastric plexus and is divided into the lateral and medial triangular branches of the bladder; and the rectal plexus originates from the inferior border of the inferior hypogastric plexus. To identify the inferior infra-abdominal plexus, after pelvic lymph node dissection the lateral bladder space should be separated along the iliac vessels and closed fossa, the lateral rectal space should be pushed open, and the uterine artery should be ligated. The fibers of the infra-abdominal nerve and the fine fibers of the pelvic visceral nerve are below the vascular plexus. The superficial layer of the main ligament is the vascular division, containing blood vessels, fat, lymphatics, small lymph nodes and loose connective tissue. The deep uterine vein is of landmark importance and is the division between the vascular and neural divisions, and in some cases, the middle rectal artery is also important. The bladder branch of the inferior ventral plexus is located deep in the cervical ligament of the bladder and at the end of the ureter. Removal of the tissue below the ureter increases local nerve damage, and preservation of the bladder branch of the inferior ventral plexus minimizes the incidence of postoperative bladder dysfunction.
II. Tailored and individualized surgery
Extensive parametrial tissue resection and PLD are the main causes of postoperative complications in RH. Reducing pelvic autonomic nerve injury is the key to surgery, and individualized treatment to reduce treatment-related early and late complications is the trend of cervical cancer.
The scope of individualized surgery needs to refer to multiple tumor-related and patient-related factors. The identification of low-risk groups with paracervical infiltration and pelvic lymph node involvement has been controversial for many years, and MRI, which measures the depth of interstitial infiltration, can help in the selection of the surgical scope. Patients with tumor diameter <2 cm, or interstitial infiltration <1/2, or depth of infiltration <1 cm are at low risk for parametrial infiltration and lymph node involvement. Tumors with interstitial infiltration more than 2/3 or reaching the fascia or infiltrating the uterine body are at higher risk for parametrial infiltration and lymph node metastasis, and radiation therapy should be preferred over surgery. Preoperative SLN localization can reveal high-risk lymph nodes, but the sensitivity of frozen sections is not satisfactory.
Several studies have confirmed the correlation between positive pelvic lymph nodes and parametrial infiltration: parametrial infiltration alone without pelvic or SLN metastasis is rare. strnad et al. reported a prospective study of 158 cases of early-stage invasive carcinoma of the uterine cervix, demonstrating a low risk of parametrial metastasis in SLN-negative individuals. The study confirmed a 27.3% positive parametrial rate in SLN-positive patients with tumor diameter <2 cm and interstitial infiltration <1/2, and another study found a 28.4% positive parametrial rate in SLN-positive patients with tumor diameter of 2-3 cm and infiltration depth <2/3 . Therefore, radical surgery with reduced scope (MRH, NSRH, or surgery to preserve fertility) is feasible for SLN-negative patients, while positive patients need to undergo extensive surgical approaches (i.e., RH and lymph node dissection), or surgery can be abandoned in favor of radiotherapy to avoid the severe side effects of multiple treatments.
In Europe neoadjuvant chemotherapy (NACT) is commonly used for patients with poor prognosis beyond stage IB2. NACT can reduce the number of positive lymph nodes and decrease tumor volume, but its role in cervical cancer is controversial. there is no evidence that NACT improves survival and cannot be recommended as standard treatment.
III. NSRH
Clinical experience and cadaveric anatomical studies have shown that RH can damage the pelvic autonomic nerves, and resection of the sacral uterine ligament is prone to damage the inferior abdominal nerve, and the bladder branch of the inferior abdominal plexus is severely damaged when the tissue below the ureter and the deep cervical ligament of the bladder are removed.
The history of nerve preservation surgery originated in Japan with a review of this technique published by Yuhisa Fujii, and in 1961 Okabayashi first described the NSRH (Okabayashi procedure), describing the concept of improving bladder function and recommending the separation of the vascular part (including the deep uterine veins) from the neural part (including the visceral pelvic nerves) when removing the parametrial tissue. 1983 Fujivara emphasized the protection of the bladder branch of the inferior abdominal plexus. Since then NSRH has been widely disseminated.
In 1998, Höckel9 applied liposuction for NSR in 7 patients and concluded that liposuction facilitated the identification of the pelvic visceral nerves and the inferior abdominal plexus.9 Raspagliesi made it possible to apply this technique to remove fatty tissue and preserve the pelvic autonomic nerves in NSR. and compared type II and III RH with type III NSRH in terms of complications and bladder dysfunction and found no difference in morbidity between type II RH and type III NSRH, which was significantly improved over RH. Höckel then proposed the concept of total mesenteric resection and found, through histoembryological and anatomical studies, that metastases from cervical cancer are usually limited to the uterus where the Mullerian ductogenesis unit, including organs and tissues such as proximal vagina, cervix, uterine body, uterine mesentery (supplying vessels and lymphatic drainage of the uterus) and various supporting ligaments of the uterus, while the pelvic autonomic nerves and the paravaginal tissues where they are located are not part of this disease unit. However, total mesenteric resection is not suitable for bulky tumors, and the shortcomings of the Höckel study were the inappropriate selection of NSRH indications, a lymph node positivity rate of 18.6%, also including patients with stage IB2 and IIB, unadjuvant radiotherapy, and too short follow-up. 2008 Trimbos performed a modified Leiden NSRH, describing a different Sakuragi from 2005 approach to nerve division resection of the inferior abdominal nerve and the main ligament, and developed the NSRH Japanese concept.
NSRH is increasing year by year, and precise and visualization is very important for nerve fiber identification, which is the biggest advantage of laparoscopic and robotic surgery (earlier studies were able to identify nerves only by magnification), and Possover reported 38 cases of laparoscopic type III NSRH, focusing on the preservation of pelvic visceral nerves and emphasizing the significance of the middle rectal artery. In addition, he pointed out that laparoscopic navigation techniques can assist in determining vascular alignment and facilitate NSRH. katahira has also used electrical stimulation to identify pelvic visceral nerve pathways. butler Manuel used immunohistochemistry to confirm the large number of nerve fibers in the dorsal and lateral aspects of the paracervical tissue of RH specimens, and Mantzaris found that nerve fibers in paracervical tissue specimens of NSRH were significantly were reduced.
IV. Type B RH (MRH)
MRH belongs to the classification originally developed by Piver and has undergone several modifications with significant changes in the extent of paracervical tissue and lymph node dissection, the main differences being the excision of the deep cervical ligament of the bladder below the ureter and the reduction in the extent of paracervical tissue dissection, also including the site of uterine artery ligation and the extent of pelvic lymph node dissection.
In the last 30 years, several studies have demonstrated a significant reduction in complications after MRH. Although there is no consensus on the definition of early cervical cancer (< 3 cm or < 2 cm, infiltrating interstitium < 1/2, with or without LVSI), the feasibility of MRH as early cervical cancer has been accepted.Q-M staging details the extent of its resection , including types B1 and B2. In contrast, radical hysterectomy (Dargent procedure) is a procedure that preserves reproductive function, and the reduction in surgical extent lies in the preservation of the uterine artery. Plante analyzed 600 young patients with cervical cancer <2 cm in diameter who underwent radical hysterectomy, with an overall recurrence rate of less than 5% and a mortality rate of less than 3%.
There is no doubt that MRH reduces the incidence of early and late complications. Raspagliesi compared type II RH, type III NSRH and type III RH for the assessment of bladder dysfunction after 3 months, NSRH was comparable to type II and superior to type III RH with a lesser degree of nerve damage and a reduced incidence of complications.
V. Extra-fascial hysterectomy (type A RH)
Type A RH combined with PLD is an extremely conservative procedure for early-stage cervical cancer. The scope of the procedure is to remove the paracervical tissue within the ureter and outside the cervix, and the location of the ureter is determined by palpation or direct visualization. Previously, this procedure was only indicated for patients with stage IA1 without choroidal infiltration (interstitial infiltration <3 mm with horizontal width <7 mm).
The results of the study confirmed that in stage IA2 and IB1 patients with tumors <2 cm, infiltration depth <1 cm, and negative pelvic lymph nodes, the parametrial positivity rate is less than 1%, and the identification of negative lymph nodes remains a challenge due to the lack of sensitivity of PET-CT for metastases <8 mm, and the detection of SLN is an important complement. RH, followed by 40 patients who underwent this type of laparoscopic procedure with SLN localization and PLD, indications included: tumor diameter <2 cm, maximal interstitial infiltration <1/2, positive LVSI was not an exclusion criterion, median follow-up 47 months (range 18 - 84), only 1 patient with a lesion in the isthmus had a central recurrence, no deaths were recorded so far, 6 patients (15%) of them Type C2 RH due to SLN positivity. a recent study conducted included 60 patients (tumor diameter <2 cm, maximal interstitial infiltration <1/2), 3 stage IA1 (LVSI 100% ), 11 IA2 (LVSI 36.4%), 46 IB1 (LVSI 26.1%) with laparoscopic type A RH and PLD respectively, 5 (8.3%) with positive lymph nodes, 2 of which had frozen sections pseudonegative, with a median follow-up of 47 months (12-92) and no recurrence, and common postoperative complications were lymphoid cysts and lymphedema.
VI. RH and postoperative complications
Ureteral injury or bladder fistula is rare, generally not more than 2% ; lymphatic cysts and lymphedema are not uncommon (2-23%), increasing the rate of postoperative disease; lower urinary tract dysfunction, sexual dysfunction, and colorectal dyskinesia are more common, due to pelvic autonomic nerve injury that can occur in all types of RH.
The main cause of bladder dysfunction after RH is injury to the autonomic nerve fibers innervating the bladder, with destruction of supporting structures and peribladderal fibrosis as secondary causes. changes in bladder function after RH surgery occur in two stages: the initial stage is hypertonic, characterized by transient bladder spasm, where trauma and excision of nerves affect parasympathetic function, with bladder smooth muscle hyperexcitability, and surgical injury leading to devolution of nerve stimulation rather than complete loss of innervation. The second stage, namely hypotonic overfilling of the bladder, is the result of mishandling of postoperative overfilling of the bladder, and suprapubic cystostomy or intermittent catheterization is recommended. Abnormal preoperative voiding function and abnormal urodynamic testing are risk factors for postoperative urinary incontinence, and assessment of postoperative lower urinary tract dysfunction should be completed after 6 months, as most patients require a prolonged recovery from abnormal bladder function. Lower urinary tract dysfunction (e.g., loss of sensation, storage and voiding dysfunction, forceps instability, and urinary incontinence) is the most common long-term complication after RH (5-76%). benedetti-Panici reported a 76% incidence of bladder dysfunction after type III and IV RH, while type III NSRH with different pelvic autonomic nerve preservation techniques had a postoperative The incidence of bladder dysfunction was significantly lower in both type III NSRH, and the MRH yield was similar to that of NSRH.
Nerve-preserving prostate cancer and rectal tumor surgery is an effective method to improve postoperative sexual dysfunction.RH and PLD alter the anatomy and function of the vagina, and pelvic autonomic nerve injury is an important cause of postoperative sexual dysfunction in RH because the inferior hypogastric plexus is important for neural modulation of the vascularity of the vaginal wall and is responsible for the neural control of vascular engorgement and lubrication response , Photoplethysmo Graphical vaginal pulse amplitude is a reliable method for detecting vaginal wall vascular congestion and is used to assess sexual function in patients after surgery. Other influencing factors include anatomical changes (e.g., vaginal shortening), large excisions of paravaginal tissue, paravaginal tissue stiffness, and loss of ovarian function.
Postoperative anorectal dysfunction after RH has been studied less frequently and with mixed results. Radical resection of bowel support tissue and paracervical tissue can result in partial damage to the autonomic nerves innervating the rectum. Studies have shown that RH has adverse effects on bowel function (e.g., high-volume rectal dilatation causing anorectal inhibition reflex, slow-transmission constipation, lining, diarrhea, fecal incontinence, and ventilatory incontinence) and that high fiber intake reduces bowel symptoms.
Conclusion
Individualized treatment of cervical cancer is controversial, and the choice of the type of surgery for early-stage cervical cancer should be based on preoperative assessment of high-risk factors (e.g., pathologic prognostic factors and MRI judgment of interstitial infiltration), SLN localization is promising, and the choice of surgical approach is a complex decision-making process. For stage IB1 patients, both NSRH type C1 and MRHB type 2 are available, while type A RH is a useful attempt for IA2 and IB1 cervical cancers, with a better prognosis for SLN-negative patients.