Pelvic Necrosis with Formation of a Pelvic “Cloaca” and Necrotizing Soft Tissue Infection After Radiation for Anal Squamous Cell Carcinoma

Introduction

Anal squamous cell carcinoma (SCC) is a rare disease that primarily affects patients with human papillomavirus infection (HPV) or those who are chronically immunosuppressed [1]. The annual incidence of anal SCC has however increased by approximately 3.1% yearly between 2001 and 2015, and the mortality rate has increased by 3.7% over the same time period [2].

Treatment of anal SCC is primarily chemoradiation, and the Nigro protocol is the criterion standard regimen. This involves sensitization with 5-fluorouracil and mitomycin C and concurrent radiation [3]. Potential long-term adverse effects include dermatitis, changes in bowel function (increased urgency and rarely incontinence), and sexual dysfunction. Rarer but significant late complications include chronic radiation proctitis, increased risk of hip fracture, and radiation-induced secondary malignancies [4,5].

Radiation necrosis is a rare but highly morbid late complication [1]. Cases of necrosis are well documented after radiation to the brain, bones, and genitourinary system, but few cases exist detailing the presentation, treatment, and outcomes in patients who developed necrosis after radiation for anal cancer. Here, we present a case of a patient who presented with severe necrotizing soft-tissue infection secondary to delayed extensive radiation necrosis after radiation for anal SCC that resulted in near-complete meltdown of her pelvic organs (bladder, vagina, rectum) and formation of a pelvic “cloaca”, a common cavity into which urine, feces, and genital secretions empty. We also present a rapid review of the literature on pelvic radiation necrosis.

Case Report

Our patient was a 66-year-old woman with multiple comorbidities, including hypertension, hyperlipidemia, multiple sclerosis, chronic kidney disease stage IV, and prior history of anal SCC. She provided verbal consent to having her case discussed here.

Her anal SCC was diagnosed in 2005, stage T3N×M0, and treated with the Nigro protocol. Her course was complicated by severe radiation proctitis, necessitating fecal diversion with a loop sigmoid colostomy. In addition, she developed ureteral strictures, requiring frequent ureteral stent exchanges, and formation of a vesicovaginal fistula. Her most recent stent exchange occurred 3.5 weeks prior to her presentation.

She presented to the Emergency Department (ED) with right buttock and leg pain, and was found to have sepsis, with tachycardia, tachypnea, and borderline hypotension. Bloodwork revealed leukocytosis (WBC 31.7 K/µL), acidosis (bicarbonate 9 mmol/L), and acute kidney injury on top of chronic kidney disease (creatinine 5.4 mg/dL from a baseline of 2–3 mg/dL).

On examination, she had a large area of induration in the right ischiorectal fossa/gluteal area, with erythema, tenderness to palpation, and crepitus. She also had a large palpable vesicovaginal fistula with palpable ureteral stents, along with a large rectovaginal fistula with malodorous drainage.

Computed tomography (CT) of the abdomen and pelvis showed a large amount of subcutaneous air in the right ischiorectal fossa and gluteal area. The air tracked from a large pelvic cavity in which the ureteral stents could be seen (Figure 1).

Rapid resuscitation was started in the ED, along with the administration of intravenous antibiotics (clindamycin, piperacillin/tazobactam, vancomycin). She was taken to the operating room expeditiously for an examination under anesthesia and debridement. Intraoperative findings showed complete melt-down of pelvic organs, including the vagina, uterus, bladder, anterior rectum, and surrounding soft tissue, with formation of a large pelvic “cloaca” (Figure 2). She also had bony changes of the right ischial tuberosity suspicious for osteomyelitis. Fluid, bone, and tissue samples were sent for culture and histological analysis and grew B. fragilis and Enterococcus. Pathological analysis confirmed necrosis, without evidence of malignancy. She was taken to the Surgical Intensive Care Unit and intubated for continued resuscitation. A second look in the operating room for further debridement with orthopedic, gynecology, and urology teams was performed on postoperative day 2. Ultimately, all necrotic tissue was debrided down to healthy bleeding tissue (Figure 3). Fecal diversion had already been performed with loop colostomy, and the decision was made to remove the urinary stents and proceed with urinary diversion using nephrostomy tubes. After a prolonged hospital stay, she ultimately recovered and was discharged in stable condition to a long-term care facility, and later discharged home with home wound care.

At follow-up 2 months later, the patient was doing well. Her wound was decreased in size, with good granulation tissue formation, and her anterior labia had completely healed. Orthopedic and plastic surgery teams have been consulted to discuss possible flap reconstruction for coverage of the defect (Figure 4).

Discussion

Radiation necrosis is a rare, late complication of radiation therapy for cancer that can occur at any time after completion of treatment [6], from 24 days to 30 years [7]. Radiation works by directly causing tissue and cellular damage to double-stranded DNA and cell membrane proteins; cells are then eliminated by p53-mediated apoptosis [8,9]. This process causes inflammation, which results in a combination of vascular damage and tissue atrophy that rarely progresses to necrosis [9].

The risk of chronic toxicity, including necrosis, is correlated with the volume of the tissue receiving a total dose of 70 Gy or more [6]. The Nigro protocol is the criterion standard method for treating anal SCC, which includes a chemotherapy regimen of 5-fluorouracil given continuously over days 1 to 4, with a bolus of mitomycin C on day 1. This is concurrent with a total 54 Gy dose (45 Gy+9 Gy boost) of radiation given in fractions [3]. Early publications detailing the treatment of anal SCC reported high rates of radiation necrosis after treatment. In 1974, Papillon reported a 23% rate of radiation necrosis after treatment of anal SCC with 30 Gy external radiation followed by brachytherapy with radium implants [10]. Similarly, in 1996, Gerard et al reported that 5 patients developed rectal necrosis after a total dose of 70 Gy external radiation [11]. However, incidence rates from the early 2000s, when this patient underwent radiation, were much lower, between 3.33% and 6% [12,13]. Thankfully, the incidence of radiation necrosis has continued to decrease and is exceedingly rare nowadays, given the improvements in modern radiation techniques.

Advances in radiation technology, including fractionated dose delivery, proton-based therapy, concomitant chemotherapy, and improved computer-based tumor targeting and volumetric planning (eg, intensity-modulated radiation therapy and volumetric modulated arc therapy) have allowed reduction of both the total radiation dose and the volume of tissue irradiated, therefore decreasing the risk of acute and chronic toxicity [8,14]. With these modern techniques, the most common acute toxicities include dermatitis, gastrointestinal distress, proctitis, and transient hematologic abnormalities, although these are less common and less severe than those of previous radiation technology [4,5]. Severe radiation necrosis, as seen in our case, would be unexpected with modern technology and would prompt a review of the equipment and techniques to assess for possible medical error.

Irradiated tissue is at higher risk of superimposed necrotizing soft-tissue infections (NSTI), due to decreased blood flow and damage to local immune cells, which is compounded by immunosuppression from concomitant chemotherapy [15]. These infections are typically polymicrobial [16]. Common pathogens include those found on the skin (S. aureus, P. aeruginosa, A. baumanni), and in the gut (E. coli, K. pneumoniae, E. faecium) [15]. Presentation ranges from cellulitis and sepsis to necrotizing fasciitis. Expanding erythema and edema, surface skin changes, including cyanosis or bronzing, induration, gangrene, and crepitus, should precipitate concern for NSTI [16]. Resuscitation and broad-spectrum antibiotics should be started rapidly, followed by urgent surgical debridement and intensive care management [16]. Even with aggressive management, mortality rates are as high as 20% and depend on the extent of the infection, delay to surgical debridement, and level of organ system dysfunction at presentation [16].

We hypothesize that our patient likely had subclinical necrosis that was complicated by a NSTI incited by her recent ureteral stent exchange. Due to her pre-existing necrosis, her colon, bladder, and uterus were in communication, allowing the infection to spread and cause catastrophic tissue breakdown. Swift resuscitation, administration of broad-spectrum antibiotics, and urgent surgical debridement down to healthy bleeding tissue, along with fecal and urinary diversion, were instrumental in the recovery of this patient.

Four other cases describe similar pelvic organ meltdown after radiation therapy; 2 for cervical SCC that specifically mention the presence of a pelvic cloaca or large necrotic cavity [17], 1 for vaginal carcinoma resulting in total loss of the anus, distal rectum, and posterior vagina [7], and 1 for rectal cancer resulting in Fournier gangrene involving the scrotum, penis, and perineal/perianal skin [18]. The time between the start of radiation and the development of necrosis ranged from weeks to a year, and the hospital courses after intervention ranged from 14 to 180 days, with a mean stay of 70 days. All patients required extensive, sometimes multiple, debridement; 3 patients had colostomies and 1 patient underwent pelvic exenteration [7]. After the necrotic tissue was sufficiently removed and any superimposed infections controlled, all patients had good outcomes with near complete wound healing.

Conclusions

Rates of radiation necrosis have likely decreased due to better targeting of radiation therapy, which reduces damage to surrounding tissues and structures. As the literature and our case suggest, radiation performed decades prior can result in highly morbid late toxicities requiring extensive surgical and infection management. It is critical that any patient with a history of pelvic radiation prior to modern technological advances is regularly monitored for adverse effects, and that careful treatment planning is done for new patients requiring radiation, to minimize potential complications.