CHAPTER      30

Management of Acute and Chronic Complications of Gynecologic Cancer Treatment

ANDREAS OBERMAIR OKECHUKWU A. IBEANU DANIELLE D. JANDIAL DEBORAH K. ARMSTRONG ROBERT E. BRISTOW

GENERAL COMPLICATIONS OF GYNECOLOGIC CANCER SURGERY

Stroke

Stroke is estimated to occur following gynecologic oncology surgery in less than 1% of patients. Risk factors reflect those in the general population: history of previous stroke or transient ischemic attack (TIA), atherosclerosis, hypertension, diabetes, and advanced age (1). The etiology of stroke is attributed to hypoperfusion injury, hemorrhage, or embolism. In contrast to cardiac surgery, the majority of noncardiac stroke is due to cerebrovascular thrombosis, rather than embolic events (2). Hypotension (relative to the patient’s baseline blood pressure) increases the risk of stroke in patients undergoing noncardiac, nonneurological surgery (3, 4). Despite this, no evidence is available that intraoperative monitoring or regulation of blood pressure reduces the incidence of stroke. Avoidance of severe hyperglycemia and hypoglycemia is recommended, though there is a lack of consensus regarding glucose targets (2).

Cardiac events

Major noncardiac surgery is associated with major cardiac events (cardiac arrest, myocardial infarction, heart failure, arrhythmias) in 0.5% to 3.0% (3, 5). Postoperative myocardial infarction is associated with 50% to 70% mortality rate and carries a high risk for future cardiac events. More than half of perioperative myocardial infarctions are unrecognized (asymptomatic non-ST elevation), and the incidence peaks during the first 24 hours postoperatively. Recent myocardial infarction, heart failure, ischemic heart disease, diabetes, renal insufficiency, cerebrovascular disease, obesity, sleep apnea, and poor functional status constitute high-risk factors.

Prevention of perioperative cardiac events should focus on evaluation of risk factors, risk stratification, and maximization of patient function. Good evidence supports the continuation of β-blockers and HMG-CoA reductase inhibitors (“statins”) throughout the perioperative period for patients already treated with β-blockers. Perioperative measures should focus on maintenance of normothermia and postoperative monitoring of serum troponin levels.

Deep Vein Thrombosis and Pulmonary Embolism

Deep vein thrombosis (DVT) and/or pulmonary embolism (PE) comprise the spectrum of complications known as venous thromboembolism (VTE). VTE following surgery is the most common cause of peri- and postoperative death (6). DVT affects 0.1% of patients each year, but the incidence is significantly higher among patients undergoing surgical treatment for gynecological cancer, occurring in up to 20% of cases (7).

Patients with gynecologic cancer are at high risk for VTE because of their underlying malignancy, increased age, and extensive nature of treatment. The underlying mechanism of disease includes increased release of procoagulant factors, cytokine imbalance, and activation of the antifibrinolytic pathways. Clinical risk factors include a history of VTE, obesity, immobility, trauma, prolonged surgical time, radiation therapy, and increasing complexity of surgery. Patients with the highest risk for developing postoperative VTE have 2 or more of the following: age greater than 60 years, malignancy, and history of VTE (8). Early ambulation, heparin, low-molecular-weight heparin, and sequential compression devices (graduated compression stockings or intermittent pneumatic compression) are effective in reducing the incidence of VTE (9). The incidence of VTE in patients undergoing major gynecologic cancer surgery is decreased with dual, prolonged (4-week) prophylaxis without increasing bleeding complications (10). Current guidelines recommend VTE prophylaxis for at least 4 weeks following surgery in the absence of bleeding or other contraindications.

Bladder and Ureteral Injury

Injuries to the lower urinary tract (laceration, transection, crush injury, ligation, thermal injury, injury through devascularization) are uncommonly diagnosed intraoperatively; the outcomes of patients who are diagnosed late (urinomas, peritonitis, sepsis, fistula) are worse (11). The risk of bladder/ureter injury ranges between 1.1% and 5.3% in patients requiring a radical hysterectomy and is approximately 1% for standard hysterectomy for uterine cancer (11 – 14). Bladder injuries recognized at the time of the initial surgical procedure should be repaired immediately using a standard 2-layered closure of delayed absorbable suture. Bladder injuries diagnosed postoperatively (e.g., fistula) may be treated with an indwelling catheter for a period of several weeks. If spontaneous closure does not occur with prolonged drainage, surgical repair is indicated. Ureteral injuries recognized intraoperatively should be repaired by excising the injured segment of ureter, placement of a ureteral stent, and reapproximating the distal urinary tract (ureteroureterostomy, ureteroneocystostomy with psoas hitch, and possibly a Boari flap). Ureteral injuries detected remote from the incident surgical procedure can be managed by attempted placement of a ureteral stent, which can be accomplished either retrograde via cystoscopy or antegrade via a percutaneous nephrostomy tube. If spontaneous closure does not occur after an observation period of 4 to 6 weeks, or if stent placement is not feasible, surgical repair is indicated. Long-term outcomes are generally excellent.

Injury to Small and Large Bowel

Bowel injuries occur in approximately 1% of patients undergoing surgery for gynecologic cancer. Risk factors include previous surgery, adhesions, and previous radiotherapy. Most bowel injuries are recognized at the time of surgery. The general principles of management include that any bowel anastomosis (hand-sewn or stapled) needs to be patent, tension-free, and well-vascularized. If any of these 3 conditions is unmet, the risk of leakage is very high. Small or large bowel injuries require primary bowel resection if the blood supply to the bowel is compromised or if injuries occurred at multiple levels.

Nerve Injury

Poor patient position, improper placement of retractor blades, and radical surgical dissection increase the risk of nerve injury (11). Neurapraxia is caused by compression leading to changes in intraneural microcirculation and is fully reversible. Axonotmesis (crush injury) will sever axons and function will resolve with gradual regeneration of nerve fibers. Transection of nerve fibers causes aberrant regeneration of the axons (misalignment), resulting in permanent functional losses.

The lumbosacral plexus is at risk for injury during gynecologic surgery. The use of short retractor blades or flexible blades with packs placed under the blades instead of self-retainers may reduce the risk of nerve injury intraoperatively (11). Additionally, avoidance of long-term hip extension (femoral nerve) or if flexion (sciatic nerve) in lithotomy position will decrease the risk of nerve injuries.

Hemorrhage

Intraoperative hemorrhage is defined as blood loss greater than 1,000 mL or if there is a requirement for intraoperative blood transfusion. Significant hemorrhage can be expected in 4% to 7.5% of patients undergoing surgery for advanced ovarian cancer (15). Risk factors include anemia prior to surgery, history of prolonged bleeding, blood-thinning medication and herbs/supplements, and intraoperative hypothermia. The principles of management of intraoperative hemorrhage include tamponade (packs) or atraumatic grasping and control of all feeding vessels; identification of sensitive structures (ureters, nerves); dissection of bleeding sources; correction of coagulopathy; the selective use of sutures, clips, diathermy, patches; and the use of topical hemostatic agents. Internal iliac artery ligation and hysterectomy should be considered if other measures fail. Finally, “damage-control” surgery, with placement of pelvic packing, transfer to the intensive care unit for stabilization, and return to the operating room for pack removal after 24 to 48 hours, may be a last resort.

Postoperative Ileus

Postoperative adynamic ileus is delayed gastrointestinal tract recovery; it may impair wound healing and lower the threshold for infections. Gastrointestinal motility is controlled by the enteric autonomous nervous system and influenced by neural reflexes (interfered by regional anesthesia), inflammation/trauma (tissue handling) and neuro-humoral substances (systemic analgesia). Medical illnesses (e.g., diabetes mellitus) or medications may increase the risk of ileus.

Differentiating postoperative ileus from a mechanical small bowel obstruction (SBO) is critical. Rapidly progressive systemic (septicemia) and abdominal symptoms (peritonitis, feculent vomiting) point to the likelihood of SBO. Bowel sounds are an unreliable indicator and are usually quiet or absent with ileus, but may be high-pitched or absent with SBO. Computed tomography (with oral gastrografin) is recommended to help differentiate ileus from SBO. The treatment of ileus is conservative and nonsurgical, and includes restriction of oral intake, nasogastric tube suction, intravenous fluid and electrolyte replacement, and discontinuing systemic opiods if possible. Total parenteral nutrition (TPN) should be considered after 7 to 10 days without satisfactory oral nutrient intake.

Postoperative Small Bowel Obstruction

Postoperative SBO results from a mechanical blockage of intestinal motility. Possible causes include herniation of bowel (port sites, internal herniation), early adhesions, intussusceptions, and small bowel tumors. The characteristic presentation of SBO is that patients initially recover well (pass flatus, tolerate oral intake) , but then develop nausea, vomiting, abdominal discomfort, and pain. Computed tomography will show a site of bowel obstruction (transition point), gaseous distension of small bowel, and paucity of air in the rectum. Effective management requires an expedited diagnosis followed by a short (72 to 96 hours) conservative trial of nasogastric suction and fluid resuscitation. If there is no improvement after this period, surgical intervention is warranted. Protracted delays may cause secondary problems, such as bowel ischemia and necrosis.

Surgical Site Infection

Surgical site infections (SSI) lead to delayed wound healing, revision surgery, increased use of antibiotics, and increased length of hospital stay (16). On average, a patient with SSI spends 7 days longer in the hospital, is 60% more likely to spend time in the ICU, is 5 times more likely to be readmitted within 30 days of discharge, and is twice as likely to die (17). The incidence rates vary depending on patient factors and type of surgery, and range from 2% to 10% after laparotomy, while the rate is lower with minimally invasive surgery. Risk factors for SSI include concomitant systemic disease (diabetes, anemia, immunosuppression, immunosuppressive therapy with radiotherapy, chemotherapy, or steroids), obesity, advanced age, preexisting infection, hematoma, damaged tissue, extensive surgery, hypothermia, hemorrhage, and use of drains or catheters (18). Infection control programs reduce the rates of SSI by 35% to 41%, to 35% (19). Prophylactic antibiotics are most effective when administered 30 to 60 minutes preoperatively. A preoperative Chlorhexidine shower is as effective as bar soap or detergents. Trials on antibacterial sutures are ongoing.

DISEASE SITE–SPECIFIC SURGICAL COMPLICATIONS

Surgery for Ovarian Cancer—Cytoreductive Surgery

Acute Complications

Ovarian cancer cytoreductive surgery has evolved to a contemporary approach designed to achieve complete cytoreduction, with an accepted increase in morbidity balanced against the maximal benefit on long-term survival. A comprehensive approach to advanced-stage ovarian cancer must address disease not only in the pelvis, but also frequently involves surgery on the large and small bowel, diaphragm, liver, spleen, and distal pancreas. Recognition and management of associated perioperative complications is critical. The morbidity of extensive surgical debulking is increased with age, poor nutritional status, and poor functional status (20–24).

The en bloc resection of locally advanced ovarian cancer (radical oophorectomy or modified posterior exenteration) carries an operative mortality of 0% to 8%, with more contemporary series reporting rates of 4% or lower (25–27). Wound complications are seen in 6% to 34% of patients, particularly with severe hypoalbuminemia (<3.0 ng/dL) and large-volume ascites (28). The estimated blood loss with radical oophorectomy ranges from 800 to 2900 mL, with as many as 87% of patients receiving blood product transfusion.

Intestinal complications with radical debulking are among the most commonly encountered, with prolonged ileus reported in up to 40% of patients. A large series of 587 patients recently reported an average incidence of postoperative ileus of 30.3% (25.9% without bowel resection, 38.5% with bowel resection) (29). The pattern of spread of ovarian cancer results in the need for bowel resection in 19% to 54% of cases (30,31). Colorectal anastamotic leak occurs in fewer than 4% of cases and can lead to abscess, fistula formation, sepsis, and reoperation; the mean time to diagnosis is 19 days (range, 4 to 32 days) (25,26,31,32–34). Anastamoses below the peritoneal reflection and less than 7 cm from the anal verge are at the highest risk for failure (35). While there are limited data in gynecologic oncology patient populations, randomized studies on the management of colorectal disorders suggest that mechanical bowel preparation does not lower the risk of anastamotic leak. A recent meta-analysis of 18 randomized controlled trials with over 5,800 patients confirmed that administration of mechanical bowel preparation yielded no difference in anastamotic leak rates (4.4% vs. 4.5%; odds ratio [OR], 0.99 [0.74, 1.13]) or wound complications (9.6% vs. 8.5%; OR, 1.16 [0.95, 1.42]) (36). Studies of intraperitoneal pelvic drain placement in the setting of a rectal anastamosis similarly suggest no benefit to lowering the risk of anastamotic leak (37). While the value of pelvic drainage in reducing anastamotic leak has not been demonstrated, drainage may still be useful in the prevention of pelvic fluid collections, abdominal compartment syndrome from re-accumulation of large-volume ascites, infected hematomas, and urinomas following urinary tract resection. Finally, intestinal diversion has historically been utilized for protection of a rectal anastamosis during primary cytoreductive surgery. Older data suggest that up to 59% of patients requiring rectal anastamosis also underwent protective intestinal diversion with colostomy or ileostomy. Based on more contemporary data, intestinal diversion to “protect” a colorectal anastomosis is not routinely required but may be advisable in patients with very low anastamoses, technically suboptimal anastamoses, or severe hypoalbuminemia (21% leak rate with albumin <3.0 g/dL vs. 3.4% leak rate with albumin >3.0 g/dL) (26,33). Initial management of anastamotic leak includes antibiotic therapy and percutaneous drainage under image guidance. If conservative management is unsuccessful, surgical exploration and diversion are required.

Upper abdominal procedures including splenectomy, distal pancreatectomy, partial hepatectomy, and diaphragmatic peritonectomy or full-thickness resection may be required to render a patient completely free of visible disease. Development of pleural effusions following diaphragmatic peritonectomy or resection occurs in 9% to 64% of patients, although these can be managed with thoracentesis alone in the majority of symptomatic patients. When full-thickness resections are required, perioperative morbidity has been reported in as many as 20% of patients (38,39). A small postoperative pneumothorax will frequently resolve spontaneously and can be monitored with daily chest radiographs. Chest tube placement is occasionally required for major resections of the right hemidiaphragm, large pleural effusions, or worsening pneumothorax.

Acute complications associated with splenectomy include hemorrhage, left lower lobe atelectasis, splenic vein thrombosis, arteriovenous fistula between the splenic artery and vein, and infectious morbidity (40,41). Overwhelming postsplenectomy infection, most commonly due to Streptococcus pneumoniae, is a serious complication with a prevalence of 3.2% and a mortality rate as high as 70% (42). Vaccinations for pneumococcus, meningococus, and Haemophilus influenza type B are the cornerstones of prevention.

Distal pancreatectomy is occasionally indicated to achieve complete disease resection and can result in pancreatic fistula (leak) and pancreatic pseudocyst formation (30,43). Intraoperative placement of a closed suction drain in the left upper quadrant can be useful to monitor for signs of early fistula formation as well as prevent pseudocyst formation. Mild enzyme leakage has little clinical impact and can be managed with prolonged drainage and standard oral feeding. Enzyme leakage greater than 3-fold the upper limit of normal or the presence of pain, fever, or leukocytosis requires delay of oral nutrition, administration of antibiotics, somatostatin analogues, and parenteral nutrition.

Chronic Complications

Ovarian cancer patients may experience long-term sequelae related to prior cytoreductive surgery, often exacerbated by the presence of disease recurrence or carcinomatosis. More commonly encountered complications requiring operative intervention are mechanical bowel obstruction or anastamotic stricture. SBO in ovarian cancer patients is best approached with an extended trial of bowel rest and decompression with nutritional supplementation unless bowel dilation is greater than 5 cm, at which point the risk of perforation increases. Carcinomatous ileus can be confused with mechanical bowel obstruction; however, this condition is unlikely to be surgically correctable. If mechanical SBO is refractory to conservative measures, surgical options include resection with reanastamosis, diverting ileostomy, enterocolonic bypass, or palliative percutaneous gastrostomy. Associated complications may include anastamotic failure, blind loop syndrome, or short gut syndrome. Finally, late complications may follow extensive resection of the ileum or a right hemicolectomy; these late complications include chronic diarrhea from impaired absorption of water, fat, and bile salts, and problems related to poor absorption of nutrients, including the fat-soluble vitamins and vitamin B₁₂.

Surgery for Uterine Cancer

Acute Complications

Until recently, total abdominal hysterectomy (TAH) was considered the standard surgical approach to hysterectomy for uterine cancer. However, minimally invasive surgical techniques have become increasingly popular due to their favorable outcomes in treatment. To date, three prospective randomized controlled clinical trials are available to compare outcomes from open and laparoscopic surgery for uterine cancer (12–14). The Gynecologic Oncology Group (GOG) LAP2 Trial (GOG 222) recruited a total of 2,616 women (12). Patients were eligible if they had clinical stage I to IIA uterine cancer; all histological cell types were allowed and all patients had to have pelvic and aortic lymph node dissection. The Australian LACE Trial enrolled 760 patients. Patients were eligible if they had endometrioid cell type, clinical stage I disease. Patients were not eligible if they had a uterine size larger than 10 weeks gestation, had evidence of extrauterine spread (ovarian masses, enlarged lymph nodes), or were unfit for surgery due to medical comorbidities (14). The Dutch TLH Trial aimed to compare outcomes in early-stage endometrial cancer treated by laparoscopy or laparotomy. Patients with early-stage endometrial cancer (endometrioid cell type, FIGO grade 1 or 2, clinically stage I disease, negative endocervical curettage) or complex endometrial hyperplasia with atypia were eligible (13). Intraoperative surgical complications were comparable in all 3 trials.

In the LAP2 trial, postoperative surgical complications were significantly more common in patients who had a laparotomy than in patients who had a laparoscopic procedure (21% vs. 14%). Postoperative ileus (8% vs. 4%) and cardiac arrhythmia (2% vs. 1%) were significantly more common in patients in the open/laparotomy group. In the LACE trial, the open/laparotomy group had a 44% higher incidence of postoperative complications (18.6% in open, 12.9% in laparoscopic) compared to patients in the laparoscopy arm. The incidence of serious adverse events was 74% higher in the open group compared to the laparoscopy group (14.3% for open, 8.2% for laparoscopy). Wound infections or dehiscence were the main contributors to the difference in postoperative complications between laparoscopic (2.0%) and open (8.9%) groups. An open surgical approach (laparotomy), higher Charlson’s medical comorbidities score, moderately or poorly differentiated tumors on curetting, lower performance status prior to surgery, obesity, and anemia were independently associated with an increased risk for surgical adverse events (44). Patient’s age at surgery was not a risk factor for surgical complications. The Dutch TLH trial recorded comparable postoperative surgical complications in the open and the laparoscopic group (10.6% open/laparotomy; 11.9% laparoscopy). Interestingly, the incidence of postoperative complications was similar among all 3 trials for patients randomized to the laparoscopic arm (ranging from 11.9% to 14%). In contrast, the incidence of postoperative complications in the open/laparotomy arm was significantly lower in the Dutch TLH trial (10.6%) compared to LACE (18.6%) or LAP2 (21%). In the Dutch TLH trial, no patient required a retroperitoneal node dissection, whereas in the U.S. LAP2 trial, all patients had to have a pelvic and aortic lymph node dissection. In the Australian LACE trial, approximately half of patients had a retroperitoneal node dissection; however, no differences in the incidence of acute surgical complications were observed between the treatment arms when stratified by nodal dissection status.

Chronic Complications

Lymphedema and lymphocele are the main chronic complications following surgery for uterine cancer, and the incidence varies depending on the type of surgery and extent of lymph node removal. Overall, lymphedema occurs in 20% of patients following hysterectomy with lymphadenectomy (45). Obesity, number of lymph nodes removed, extent of surgery, postoperative infection, radiation therapy, and postoperative DVT increase the risk of developing lymphedema. Lymphoceles are an accumulation of lymphatic fluid in dead space due to postoperative leakage of lymphatic fluid coupled with incomplete lymphatic reabsorption. Most lymphoceles are asymptomatic and found incidentally. Its true incidence is therefore unknown (range, 0% to 58.5%) (46–48).

Surgery for Cervical Cancer:Radical Hysterectomy and Pelvic Exenteration

Acute Complications

Radical hysterectomy for early-stage cervical cancer is associated with a major complication rate (excessive blood loss, urinary/gastrointestinal tract injury, nerve injury) of 5% to 10%. Ureterovaginal fistula occurs in 2% to 3% of cases and typically presents within 14 days of surgery with watery leakage per vagina commonly associated with pain or fever (49). A computed tomography urogram is usually diagnostic. Instillation of methylene blue dye intravenously or via retrograde instillation into the bladder can also help to distinguish a vesicovaginal from ureterovaginal fistula by observing for extravasated dye onto a vaginal tampon. Ureterovaginal fistulas can be managed in most cases with ureteral stenting or percutaneous nephrostomy. Vesicovaginal fistulas occur in 1% to 3% of cases, and can often be managed with prolonged catheterization and continuous decompression of the bladder for 4 to 6 weeks. For nonhealing fistulas, larger fistulas (>1 cm), or complex fistulas involving both ureter and bladder, surgical management with closure is indicated. This can be approached vaginally with a Latzko partial colpocleisis if the defect is small, apical, and not in proximity to the ureter. Bulbocavernosus or Martius fat pad grafts can also be used (50). Trigone involvement or larger complex fistulas are best approached abdominally with a layered closure and an omental flap. Urinary retention due to sensory loss and voiding dysfunction are well-recognized complications of radical hysterectomy and result from the denervation of the bladder during the parametrial dissection. Most patients are managed with prolonged bladder decompression for 3 to 7 days with a transurethral or suprapubic catheter. A retrograde voiding trial is recommended to assess for bladder function prior to removal of the catheter, and postvoid residual values of 40 to 50 mL are generally acceptable. Minimally invasive approaches to radical hysterectomy, including both traditional laparoscopic and robotically-assisted techniques, may offer several health-related benefits including less pain, shorter hospital stay, and more rapid return to full activity than the abdominal approach. However, the incidence of vaginal cuff complications/dehiscence (1.6% to 4.1%) may be higher than that observed with laparotomy (<0.5%) (56–60); there is also a potential higher risk for nerve injuries (51,52).

Total pelvic exenteration (TPE) is primarily indicated as salvage therapy for cervical cancer patients who have failed radiation therapy or require combined treatment of recurrence in the central pelvis. Acute perioperative morbidity related to TPE is high, with up to 75% of patients experiencing a major complication; mortality rates of 1% to 5% are typical. Furthermore, reoperation rates to address major complications are high, with rates of 16% to 25.6% reported in the literature (53,54). Morbidity of TPE is attributable to long operative times, compromised healing of the irradiated field, and the complexity of the surgical reconstruction. Significant blood loss, infectious morbidity primarily involving the urinary tract, sepsis, wound complications, fistulas, ileus, and anastomotic leaks of the intestinal or urinary anastomosis are some of the more commonly reported complications. Sepsis, adult respiratory distress syndrome, heart failure, pulmonary embolus, and multiorgan system failure are typical terminal events. The acute complication rate for both urinary continent and incontinent and urinary diversion ranges from 17% to 20%; these complications include urinary leak, fistula, or anastomotic failure (55). Such problems can be managed conservatively in many cases with prolonged conduit drainage and diversion with percutaneous nephrostomy. Refractory leaks may require surgical revision of the reservoir. Despite the high risk of complications, 5-year survival is in the range of 50% (54,56,57).

Chronic Complications

Urinary retention following radical hysterectomy is usually self-limited; however, long-standing bladder dysfunction may require patient intermittent self-catheterization. Long-term rectal dysfunction is similarly encountered and manifests as constipation or urgency. Nerve-sparing radical hysterectomy, which preserves autonomic and splanchnic innervation to the bladder and rectum, has been reported to decrease bladder and rectal morbidity (49,58). Ureteral strictures are encountered in 1% to 3% of patients and may present with fever and pain, but may be asymptomatic and can lead to loss of renal function. Management is with ureteral stent placement, if possible, or percutaneous nephrostomy placement. Occasionally reoperation with ureteral reimplantation can be required. Colonic stomas may be prone to prolapse, hernia, or stricture. However, the most commonly reported intestinal complication is bowel obstruction. Unlike early postoperative bowel obstruction, late obstructions are more likely due to adhesive disease or disease recurrence. Sexual dysfunction is an underreported long-term side effect following radical hysterectomy (59).

Patients undergoing pelvic exenteration are at risk for a number of long-term complications. Urinary diversions are prone to stomal stricture, chronic urinary tract infection, renal dysfunction, nephrolithiasis, metabolic alterations, and difficulty with accessing the reservoir (56,57). Reestablishing intestinal continuity after exenteration has been advocated to minimize the long-term psychosocial and quality-of-life issues surrounding 2 permanent abdominal stomas but has been associated with a higher risk of reoperation (50% to 60%) and disease recurrence (57). Sexual dysfunction and distorted body image are common problems associated with pelvic exenteration.

Surgery for Vulvar Cancer

Acute Complications

Surgical innovation in vulva cancer evolved as a response to minimize the risk of surgical complications associated with the en bloc radical vulvectomy and bilateral inguinal lymphadenectomy popularized by Stanley Way in the 1950s, rather than from a concern about poor survival outcomes. Vulvar or groin wound breakdown occurs in as many as 50% of patients following radical vulvectomy (60–62). Development of a wound infection is predictive of future wound breakdown and lymphedema (61). Risk factors include increased patient’s age, obesity, diabetes mellitus, smoking, and prior radiation to the groin. The use of myocutaneous flaps can reduce tension on suture lines, prevent wound breakdown, infection, and improve cosmetic and functional outcome. A nonrandomized, prospective study showed a reduction in wound breakdown for patients undergoing radical vulvectomy with lymph node dissection and hyperbaric oxygen therapy (63).

Contemporary management of vulvar cancer is tailored to the size and location of the primary tumor and generally consists of radical partial vulvectomy or wide radical excision combined with ipsilateral or bilateral inguinal lymphadenectomy through separate groin incisions (64). The incidence rates of wound infection, cellulitis, and wound breakdown are 21% to 39%, 21% to 57%, and 17% to 39%, respectively. Optimizing glucose control in patients with diabetes mellitus, using appropriate antibiotic prophylaxis, and sparing the saphenous vein are important prevention strategies (65). Sentinel lymph node biopsy (SLNB) is an emerging technique that has been associated with a reduction in groin wound breakdown (11.7% vs. 34%) and cellulitis (4.5% vs. 21.3%) compared to systematic groin node dissection (66).

Chronic Complications

Chronic complications from vulvar cancer surgery are often a result of groin node dissection. As many as 50% of patients requiring a groin dissection will experience a long-term complication related to the procedure. Lymphedema occurs in 14% to 48% of patients and presents as leg swelling or heaviness of the lower limbs (67). It results in an inability to perform daily activities, impacts on psychological and social well-being, and represents a significant financial burden associated with the treatment (68). Obesity, the number of lymph nodes removed, extent of surgery, postoperative infection, radiation therapy to the groins, and postoperative DVT increase the risk of developing lymphedema after groin dissection (69). SLNB has been associated with a 1.9% incidence rate of lymphedema, compared with 25.2% in patients undergoing systematic groin dissection (66). Lymphocele formation develops in 7% to 19% of patients after inguinal-femoral lymphadenectomy (60).

Over half of women who undergo vulvectomy report sexual dysfunction and psychological issues resulting in dyspareunia, problems with micturition, negative feelings about body image, decreased desire, and inability to orgasm (68). Providing information before and after surgery that details how the treatment may affect sexuality and change anatomy, as well as the provision of methods for how to cope with feelings regarding the illness; may decrease anxiety. The FACT-V questionnaire is a valid and reliable tool that can measure the impact of treatment on QOL and improve standardization or quality of life research efforts.

Surgery in the Irradiated Field

Radiation induces a complex series of tissue changes including vascular sclerosis and tissue ischemia, the end result of which is fibrosis. Tissue planes are obliterated and healing is compromised. It is estimated that approximately 5% to 7% of patients who undergo radiation therapy for cervical cancer will experience major treatment complications that require surgery (70). The most common sites of intestinal injury in patients who undergo pelvic irradiation are areas that typically lie in the pelvic field. The ileum is the most frequent site of injury, because of the greater radiosensitivity of the small intestine compared with the colon. The most common indications for reoperative surgery in patients irradiated for cervical or endometrial cancer are intestinal obstruction (44%) and intestinal fistula or perforation (32%). Radiation damage frequently leads to matted loops of distal ileum densely fixed in the pelvis associated with obstruction or fistula. In the setting of intestinal necrosis, perforation, or abscess formation, resection should be attempted if it can be done without undue risk of damage to adjacent structures. Alternative more conservative approaches such as intestinal bypass procedures are less morbid but may lead to the development of blind-loop syndrome or result in subsequent spontaneous perforation or fistula formation. In a series of 77 patients who underwent surgery for radiation injury to the small intestine, no difference in short-term complications was noted whether patients underwent resection or bypass (71).

Urinary tract complications that may lead to surgery in a previously radiated patient include radiation-induced nonhealing or complex ureterovaginal or vesicovaginal fistulas and ureteral strictures, which compromise renal function. Asymptomatic stricture is likely more common and underreported in the literature and may lead to a silent loss of renal function. Many cases of radiation injury to the lower urinary tract can be managed conservatively with ureteral stent placement, percutaneous nephrostomy, or attempts at endoureteral dilation. Recurrent cancer must always be considered and the appropriate diagnostic biopsies and imaging obtained prior to consideration for surgical correction or urinary diversion (72).

ACUTE AND CHRONIC COMPLICATIONS OF RADIATION THERAPY FOR GYNECOLOGIC CANCERS

Radiation therapy plays a major role as a primary, adjuvant, and palliative treatment of cancers of the cervix, vulva, vagina, and endometrium. Notable progress has been made in the treatment of locally advanced cervical cancers, with the addition of radio-sensitizing chemotherapy based on demonstrated improved patient outcomes in multiple studies (73–75). Vaginal brachytherapy is also increasingly being delivered using high-dose-rate (HDR) application. Unfortunately, external beam pelvic radiation therapy and brachytherapy are associated with effects on normal tissues, with subsequent acute and chronic manifestations that may adversely affect patients’ quality of life, and pose limitations to treatment.

Acute effects usually develop beyond a radiation dose of 2000 Gy, and symptoms present within 4 weeks of starting treatment, while chronic effects are usually diagnosed after 1 month of completion of therapy. Normal tissue tolerance, volume of tissue irradiated, total dose received, dose fractions, as well as the arrangement of radiation treatment fields; are treatment-related factors that determine the severity of radiation effects in normal tissues. In addition, age, tobacco use, and chronic diseases such as diabetes, hypertension, peripheral vascular disease, and prior inflammation can influence the onset and severity of postradiation symptoms. The most common acute and chronic complications of radiation therapy in gynecologic cancers occur in the gastrointestinal tract, lower urinary tract, and reproductive tract (76). The GOG and Radiation Therapy Oncology Group (RTOG) use the National Cancer Institute Common Terminology Criteria for Adverse Events and the Common Toxicity Criteria for reporting the tissue effects and complications of radiation therapy. Table 30.1 shows the RTOG Morbidity Grading System. Normal tissue tolerance to therapeutic radiation varies by organ site (Table 30.2).

GASTROINTESTINAL TRACT AND URINARY BLADDER

Gastrointestinal symptoms and side effects are among the most common complications of radiation therapy. Intestinal cells have a fast doubling time of approximately 12 to 15 hours. Radiation induces acute gastrointestinal injury by causing acute mucosal inflammation and death of superficial intestinal cells with accompanying cytokine activation and release in the intestinal submucosa. These changes manifest as deepithelialization and ulceration, edema, erythema, and mucosal hemorrhage. Subsequently, there is mucosal ischemia with fibrosis and tissue hypoxia. In the chronic state, the intestinal mucosa appears pale and flat with multiple telangiectasias, and the bowel demonstrates decreased compliance and luminal capacity (77).

Stay updated, free articles. Join our Telegram channel

Join