Introduction
According to the American Cancer Society (ACS), there will be >900,000 new all-cause cancer cases in American women by 2020, approximately a third of whom will die as a result. The most prevalent gynecologic cancers among women are ovarian cancer, endometrial cancer, cervical cancer, and vulval cancer. Cancer therapies are increasingly complex, and for solid tumors, surgical management remains the cornerstone of treatment. The perioperative period is considered a time of maximum vulnerability in patients with cancer, as outlined in most enhanced recovery protocols.
Ovarian Cancer
An estimated 23,000 new cases of ovarian cancer were diagnosed in the United States in 2020.
Most (90%) were epithelial ovarian cancers, the most common of which is serous carcinoma (52%). Ovarian cancer incidence rates have decreased by approximately 1% per year in the past 50 years among women aged <65 years, but only since the early 1990s in older women. An estimated 14,000 deaths occurred in 2020—accounting for 5% of cancer deaths among women—more than any other gynecologic cancer.
The most important risk factor besides age is a strong family history of breast or ovarian cancer. Women who have tested positive for inherited mutations in cancer susceptibility genes such as BRCA1 or BRCA2 are at increased risk. Modifiable factors associated with increased risk include excess body weight, menopausal hormone therapy (estrogen alone or combined with progesterone), and cigarette smoking. Factors associated with lower risk include pregnancy, fallopian tube ligation or removal (salpingectomy), and use of oral contraceptives.
At first presentation, 75% have metastatic cancer to the peritoneal cavity or liver, corresponding to stage 3 cancer (according to the International Federation of Gynecology and Obstetrics [FIGO]). Surgery aims to achieve maximal reduction of tumor volume. The degree to which this can be achieved correlates with survival ; therefore surgery needs to be extensive. Surgery is often accompanied by 3–6 cycles of prior (neoadjuvant) platinum-based chemotherapy. Second laparotomy (or “interval debulking”) may be required for resection of recurrent disease, or where optimal tumor debulking could not be achieved initially. Survival from ovarian cancer depends on the extent of disease, but currently women with stage 3 disease might only expect 30%–35% survival at 5 years. Women predisposed to ovarian cancer (e.g., carriers of BRCA gene mutations) are increasingly being offered prophylactic salpingo-oophorectomy.
Debulking of ovarian cancer is normally performed via a full mid-line laparotomy. The need for optimal cytoreduction often requires prolonged surgery. Excision of the uterus, ovaries, and adnexa is standard, accompanied by omentectomy and sampling of peritoneal deposits and lymph node chains. Wider spread of disease may necessitate bowel resection and/or splenectomy and can involve difficult dissections.
Cervical Cancer
An estimated 13,500 cases of invasive cervical cancer were diagnosed in the United States in 2020, and there were an estimated 4250 deaths. Almost all cervical cancers are caused by persistent infection with certain types of human papillomavirus (HPV). Several factors are known to increase the risk of both persistent HPV infection and progression to cervical cancer, including a suppressed immune system, a high number of childbirths, and cigarette smoking. Long-term use of oral contraceptives is also associated with increased risk that gradually declines after cessation. Precancerous cervical lesions may be treated with a loop electrosurgical excision procedure (LEEP), which removes abnormal tissue with a wire loop heated by electric current. Precancerous lesions may also be surgically treated by cryotherapy (the destruction of cells by extreme cold), laser ablation (destruction of tissue using a laser beam), or conization (the removal of a cone-shaped piece of tissue containing the abnormal tissue). Invasive cervical cancers are generally treated with surgery or radiation combined with chemotherapy. Chemotherapy alone is often used to treat advanced disease.
Endometrial Carcinoma
An estimated 62,000 cases of cancer of the uterine corpus were diagnosed in the United States in 2020. Cancer of the uterine corpus is often referred to as endometrial cancer because more than 90% occurs in the endometrium. Many of these tumors are associated with excess body weight and insufficient physical activity.
Obesity is the main risk factor for uterine cancer, as well as factors that increase estrogen exposure, including the use of postmenopausal estrogen, late menopause, nulliparity, and a history of polycystic ovary syndrome. Tamoxifen, which may be given as treatment for breast cancer, slightly increases risk of endometrial cancer because it has estrogen-like effects on the uterus. Medical conditions that increase risk include Lynch syndrome and type 2 diabetes.
Surgical management ranges from simple hysterectomy with oophorectomy and lymph node sampling to radical hysterectomy. Adjuvant pelvic radiotherapy and brachytherapy are commonly used in women with residual cancer or patients deemed unfit for surgery.
Vulval Cancer
Vulvar cancer comprises approximately 6% of gynecologic cancers and less than 1% of all cancers in women. It is estimated that 1300 deaths from vulvar cancer occur in a given year. The 5-year survival rate for women with vulvar cancer is 71%. Survival rates depend on several factors, including the type of vulvar cancer and the stage of disease at the time it is diagnosed. Incidence peaks in patients aged >65 years and older patients present with later stage disease. Surgical strategies range from laser therapy to wide local excision and radical vulvectomy with groin node dissection.
Perioperative Considerations
Preoperative
Preoperative assessment should include a general approach for underlying pathologies, paying particular interest to general risk factors, including obesity, advanced age, and smoking.
Cancer staging should be assessed, as well as the need for adjuvant therapy that requires specific treatments with a variable impact on the patient’s overall status.
Particular focus on cardiac and pulmonary function is warranted because chemotherapeutic agents may result in toxicity. Commonly observed chemotherapy toxicities are summarized in Table 27.1 .
| Organic System | Chemotherapeutic Agents | Common Concerns |
| Pulmonary toxicity | Vinca alkaloids, antitumor antibiotics, alkylating agents, antimetabolites, biological response modifiers | Pneumonitis, ARDS, interstitial lung disease, pulmonary fibrosis, capillary leak syndrome, pulmonary hypertension |
| Cardiac toxicity | Antitumor antibiotics, vinca alkaloids, metal salts, biological response modifiers | Tachycardia, bradycardia, arrhythmia, hemorrhagic myocarditis, acute pericarditis, myocardial ischemia |
| Hepatic toxicity | Nitrosoureas, antimetabolites, antitumor antibiotics, vinca alkaloids, topoisomerase inhibitors, tyrosine kinase inhibitors, immunotherapy, metal salts | Hepatitis, cholestasis, biliary stricture, steatosis, nodular hyperplasia fibrosis, veno-occlusive disease |
| Renal toxicity | Nitrosoureas, metal salts, antitumor antibiotics, antimetabolites, immunotherapy, biological response modifiers | Capillary leak syndrome, glomerulosclerosis, acute tubular necrosis, Fanconi syndrome, acute interstitial nephritis, crystal nephropathy |
Gynecologic cancers may present paraneoplastic syndromes, such as cerebellar degeneration, nephrotic syndrome, retinopathy, and cauda equina syndrome, and are most likely to appear in ovarian cancer patients. On the other hand, hypercalcemia, retinopathy, peripheral neuropathy, encephalitis, myelitis, and dermatomyositis are more occasionally seen in uterine cancers.
Preoperative investigations should routinely include a full blood count, a clotting screen, urea and electrolyte analyses, liver function tests, group and save or cross-match for blood product transfusion, chest x-ray, and electrocardiogram. However, if specific cardiac, lung, or renal toxicity are suspected, further investigation should be performed in order to accurately establish chemotherapy or radiotherapy-induced organ dysfunction.
Preoperative counseling is important to set expectations regarding surgical and anesthetic procedures, and provide information regarding a care plan in the postoperative period. This can also reduce anxiety and increase patient satisfaction, which may improve fatigue and facilitate early discharge.
Radiotherapy
Radiotherapy for gynecologic cancers may be associated with short-term toxicity and long-term consequences. Short-term adverse effects occur during therapy or within 3 months afterwards. Short-term or acute toxicity (e.g., mucositis) generally heals within weeks. Later effects, such as fibrosis, are generally considered irreversible and progressive over time. The early and late effects of radiotherapy toxicity are strongly dependent on the tissue targeted and can include acute gastritis, cardiac toxicity, cognitive impairment, reproductive disorders, deformity and impairments to bone growth, hair loss, and secondary malignancy.
Prehabilitation
Prehabilitation aims to optimize patients’ physical and mental well-being in anticipation of an upcoming stress, e.g., tumor resection surgery, rather than being a reactive process to restore wellness. Prehabilitation uses aerobic and resistance exercises to improve physical function, body composition, and cardiorespiratory fitness; dietary interventions to support exercise-induced anabolism and treatment-related malnutrition; and psychological interventions to reduce stress, support behavior change, and encourage overall well-being. Certain patients may benefit with improved postoperative outcomes due to prehabilitation; however, results may vary in different cancer diagnoses and stages.
Preoperative Fasting
Patients should be encouraged to eat a light meal up to 6 h and consume clear fluids, including oral carbohydrate drinks, up to 2 h before initiation of anesthesia. Patients with delayed gastric emptying should fast overnight or for 8 h before surgery. Oral carbohydrate ingestion reduces insulin resistance and improves well-being, and should be used routinely (extrapolated from nongynecologic surgery data). There are insufficient data to make recommendations in diabetic patients. ,
Venous Thromboembolism Prophylaxis
Chemotherapy leads to a 2–6-fold increase in thromboembolic risk, most likely as a result of endothelial damage, reduced concentrations of circulating plasma protein C and S, and release of inflammatory cytokines. Radiotherapy has inflammatory effects on the vasculature with endothelial disruption, cytokine release, and increased platelet aggregation.
Patients at increased risk of venous thromboembolism (VTE) should receive dual mechanical prophylaxis to their lower limbs and chemoprophylaxis with either low-molecular-weight heparin or unfractionated heparin. The use of mechanical prophylaxis, specifically pneumatic compression devices, has been shown to decrease the rate of VTE when compared with no prophylaxis within the first 5 postoperative days. , Prophylaxis should be initiated preoperatively and continued postoperatively. Extended chemoprophylaxis (28 days postoperative) should be prescribed to patients who meet high-risk criteria, including patients with advanced ovarian cancer. Prophylactic anticoagulation has not been shown to increase the risk of intraoperative bleeding, thrombocytopenia, or epidural hematoma; therefore epidural catheter placement and removal should be timed according to the last dose.
Surgical Site Infection Prevention
Surgical site infection (SSI) adversely affects outcomes and is associated with increased morbidity and mortality among cancer patients. The rate for SSI following surgery for gynecologic malignancy has been estimated to be 10%–15%. Many institutions implement a “bundle” of interventions aimed at decreasing the rate of SSI, rather than a single intervention. SSI prevention bundles include antimicrobial prophylaxis, skin preparation, avoiding hypothermia during surgery, avoiding surgical drains, and reducing perioperative hyperglycemia.
Inadequate perioperative glucose control is associated with increased risk of developing SSIs in both diabetic and nondiabetic patients undergoing surgery, and current recommendations suggest that blood glucose levels should be maintained at <10 mmol/L regardless of diabetic status. Hypoglycemia must be avoided, as well as hyperglycemia, as both extremes have been associated with higher mortality risk. ,
Evidence suggests that peritoneal and subcutaneous drains and nasogastric tubes should be removed as soon as possible because their routine use can increase the rate of postoperative complications.
Showering before surgery with a chlorhexidine-based antimicrobial soap and a chlorhexidine-alcohol skin preparation in the operating room before surgery reduces skin SSI.
Antimicrobial prophylaxis with the administration of a first-generation cephalosporin and metronidazole reduces SSI if the bowel is inadvertently opened during gynecologic surgery. It should be given 1 h before skin incision in order to obtain the highest drug levels. Intraoperative repeat dosing should be observed depending on surgical duration and blood loss. Preoperative recommendations are summarized in Table 27.2 .
| Preoperative |
| Patient education : anesthetic and surgical procedure related information. |
| Smoking : smoking cessation at least 4 weeks before the procedure. |
| Alcohol : alcohol cessation at least 4 weeks before the procedure. |
| Anemia : diagnose and treat before surgery if possible. |
| Preoperative bowel preparation : no longer recommended. |
| Fasting : light meal up to 6 h before surgery, carbohydrate load up to 2 h before induction. |
| Preanesthetic medication : routine administration of sedatives to reduce anxiety preoperatively should be avoided. |
| Venous thromboembolism prophylaxis : oral contraceptives should be suspended before surgery; use of stockings, pneumatic compression devices, low-molecular-weight heparin. |
| Surgical site infection reduction : antimicrobial prophylaxis (first-generation cephalosporin 1 h before surgery), skin preparation, prevention of hypothermia, avoidance of drains/tubes, control of perioperative hyperglycemia. |
Intraoperative Considerations
The proximity of the gynecologic tumor to other abdominal structures, such as the kidneys or rectum, may require input from other surgical specialties. Neurovascular bundles and lymph nodes often adhere to the pelvic sidewall making dissection difficult.
These procedures usually require general anesthesia in the lithotomy position for extended periods, with attendant risks of common peroneal nerve injury and compartment syndrome in the legs, or pressure injuries in the arms. Careful positioning and padding of all vulnerable points are essential. Head down positioning may also result in facial or airway edema. Supine hypotensive syndrome and abdominal compartment syndrome have also been reported in association with sizeable tumours.
Finally, surgical staging is required for most cancers intraoperatively because microscopic disease cannot always be determined only through radiologic investigations. Maximal surgical debulking may involve radical oophorectomy, bowel resection, splenectomy, diaphragmatic peritonectomy, omentectomy, and partial liver resection.
As a general approach, intraoperative management should consider multimodal analgesia, use of regional anesthesia and nonsteroidal antiinflammatory drugs (NSAIDs), minimization of blood transfusions, and implementation of enhanced recovery protocols.
Minimally Invasive Surgery
The use of laparoscopy and, more recently, robotic surgery has led to substantial improvements in patient outcomes by decreasing intraoperative blood loss, length of stay, analgesic requirements, return of bowel function, length of hospitalization, and return to normal daily activities.
Older age, blood loss, perioperative blood transfusion, and postoperative complications have been associated with prolonged length of stay after laparoscopic gynecologic surgery. Oncologic outcomes have been found to be equivalent in women undergoing minimally invasive surgery and open procedures for endometrial cancer, but not for early-stage cervical cancer.
Given the improvements in surgical recovery in patients undergoing minimally invasive surgery procedures compared with open surgery, minimally invasive surgery is recommended for suitable patients when long-term oncologic outcomes are similar, and where expertise and resources are available. All laparoscopic procedures carry a possible need for conversion to an open procedure, which should be anticipated at 5%–10% risk.
Anesthetic Technique
Multimodal analgesia is recommended. A number of intravenous anesthetic agents may be used in combination with propofol to provide an effective total intravenous anesthesia regimen (TIVA). In addition to its direct sedative-analgesic properties, dexmedetomidine also reduces opioid requirements and minimum alveolar concentration levels for inhalational anesthetics. Ketamine has benefits in reducing chronic postoperative pain, although the optimum treatment duration and dose are yet to be identified.
Intravenous lidocaine infusion in the perioperative period decreases intraoperative anesthetic requirements, lowers pain scores, reduces postoperative analgesic requirements, and improves return of bowel function with decreased length of hospital stay. There is also evidence that ketamine, lidocaine, propofol, and avoidance of inhalational anesthetic agents may lead to a reduction in cancer recurrence.
Regional anesthetic techniques can be a major component of reducing the stress response and diminishing opioid consumption. Some studies have proposed that regional anesthesia could impact on clinical outcomes such as overall survival and recurrence-free survival; however, recent evidence has demonstrated that use of regional anesthesia or analgesia did not reduce breast cancer recurrence after potentially curative surgery compared with volatile anesthesia and opioids. The frequency and severity of persistent incisional breast pain were unaffected by anesthetic technique. Multimodal nonopioid analgesia use decreases postoperative nausea and vomiting (PONV) and allows more rapid recovery.
Fluid Management
Maintaining proper fluid management in the postoperative period and avoiding fluid overload are just as important as in the preoperative period. The aim of intravenous fluid therapy is to maintain normovolemia and reduce flux across the extracellular space. Enhanced recovery protocols and modern surgical techniques reduce the need for both total volume and duration of intravenous fluid therapy. While salt and fluid overload in the postoperative period is a major cause of morbidity, very restrictive fluid regimes also lead to increased morbidity and mortality.
Most important is the prevention of unwanted complications related to fluid overload and excessive intravenous hydration, ranging from improved pulmonary function, tissue oxygenation, gastrointestinal motility, and wound healing.
Postoperative hydration provides an improved method of fluid delivery, and it is recommended that patients receive 25–35 mL/kg water per day in the recovery period. Early transition to oral hydration postoperatively improves conditions for healing and recovery from surgery, allowing for an improved patient experience and earlier discharge without an increase in morbidity. ,
Goal-Directed Fluid Therapy
Goal-directed fluid therapy (GDT) has been associated with improvements in short- and long-term outcomes. GDT extrapolates a patient’s fluid responsiveness from measurable hemodynamic changes. Fluid responders will demonstrate an increase in stroke volume (SV) by ≥10%–15% after a fluid challenge. However, larger clinical studies have not demonstrated a benefit of GDT over zero balance or moderately positive fluid balance.
Nausea and Vomiting Prevention
A multimodal approach to Postoperative Nausea and Vomiting (PONV) prevention is quickly becoming standard of care. Antiemetics are classified into the following categories: 5HT3 antagonists, NK-1 antagonists, corticosteroids, butyrophenones, antihistamines, anticholinergics, and phenothiazines. Combinations of two or more classes of antiemetics may enhance potency (e.g., aprepitant, ondansetron, midazolam, or haloperidol combined with dexamethasone). ,
Drains and Tubes
It has been suggested that nasogastric intubation increases the risk of postoperative pneumonia (6% vs. 3%) after elective abdominal surgery, while nasogastric decompression does not reduce the risk of wound dehiscence. Only 10% of the early feeding arm required nasogastric tube insertion because of subocclusive symptoms. Conversely, 88% of patients who had a nasogastric tube experienced moderate-to-severe discomfort. One exception where gastric decompression may be of benefit is during laparoscopic or robotic surgery, whereby decompression may be used to reduce the risk of gastric perforation by trochar or Veress needle insertion.
Hypothermia Prevention
Inadvertent perioperative hypothermia during prolonged surgery has been shown to impair drug metabolism, adversely affect coagulation, and increase bleeding, cardiac morbidity, and wound infection. Temperature monitoring should always be used. Forced convective air warming devices are the most effective intervention to prevent this. Underbody warming mattresses are also effective particularly in robotic surgery. Intravenous fluids should be warmed. Patients who have prolonged surgery with a likelihood of a systemic inflammatory response (SIRS), such as open debulking procedures, could possibly extend to hyperpyrexia as surgery progresses if warming is not monitored. Intraoperative recommendations are summarized in Table 27.3 .
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