The authors are from the Department of Infectious Diseases, National Cancer Institute, Tlalpan, Mexico.
Objective. To present a 4-year experience of surveillance and management of surgical wound complications in a cohort of patients who underwent breast cancer surgery at a cancer hospital. Methods. A descriptive follow-up study was undertaken at a teaching, referral cancer hospital in Mexico City (National Cancer Institute). Patients (n = 1774) underwent 1888 breast cancer surgeries. The main outcome measures were wound complications (surgical site infections [SSI], flap necrosis, and dehiscence). Results. There were 873 (46.2%) wound complications recorded. The most frequent complications were SSI (n = 387, 20.5%), flap necrosis (n = 274, 14.5%), and dehiscence (n = 212, 11.2%). Most patients with infections were treated with oral antibiotics and local wound management (n = 353, 91.9%) with positive results. Flap necrosis and dehiscence were treated under the wound bed preparation model with debridement plus combined (concomitant or sequential) dressings and ointments that favored wound healing, achieving closure at the last appointment in 189 (48.4%) patients. Average time to closure for necrotized and dehisced wounds was 52.4 ± 45.7 and 45.2 ± 36.1 days, respectively. Conclusion. An average delay of 10 days on the initiation of adjuvant treatment was observed in patients with a wound complication (SSI, flap necrosis, or dehiscence) compared to patients without wound complications (P = 0.002). The frequency of wound complications was high. Active surveillance allowed the authors to diagnose wound complications early in their development. Local wound management under the wound preparation model and use of antibiotics when an infection is suspected were successful therapies in most patients. Breast cancer is a public health problem and represents the most common cancer among women in high-income, and some middle-income, countries.1 In Mexico it is the leading malignant tumor among women and is rapidly increasing.1 In contrast to reports from industrialized countries where screening is widely available, in Mexico most patients have locally advanced breast cancer at the time of diagnosis.2 Surgery is the cornerstone in breast cancer treatment. In patients with locally advanced breast cancer, multimodal treatment with chemotherapy, radiation, and surgery is mandatory, resulting in higher surgical morbidity. In this subset of patients the rate of surgical site infections (SSI), flap necrosis, and dehiscence is higher, especially in those patients who were previously radiated.2–6 These patients frequently develop difficult-to-heal wounds, which can increase the costs of medical care and patient suffering. Chronic wounds can delay the treatment of cancer and compromise disease-free and overall survival. The following report presents a 4-year experience of surveillance and management of surgical wound complications in a cohort of patients who underwent breast cancer surgery at the National Institute of Cancer in Mexico City.
In February 2000, a prospective surveillance program was initiated with the aim to register SSI and identify probable risks factors.6 In 2003, wound dehiscence, flap necrosis, seroma, and hematoma were also included in the surveillance program, and direct observation was further extended upon discharge of the wound clinic if a wound complication developed. On the basis of the observed trends, a therapeutic multidisciplinary approach for difficult-to-heal wounds was established during the same year. All patients who underwent breast cancer surgery between January 2003 and December 2006 who were admitted to the hospital before surgery (the night before for an early morning procedure or the same day) were included. On a regular basis, prophylactic antibiotics (cefalotin or cefuroxime) were prescribed 20–60 minutes before surgery and for patients allergic to penicillin, clindamicyn was usually prescribed. Skin preparation was performed with iodine povacrylex (0.7%) and isopropyl alcohol (74%) (DuraPrep, 3M®, St. Paul, MN). Patients were followed with daily chart review, microbiology reports, and bedside rounds. After hospital discharge, direct observation was conducted at the outpatient clinic for at least 30 days with the surgical team. When infection was suspected, a culture specimen was obtained before treatment initiation. For hospitalized patients, IV antimicrobials were given and/or debridement was performed as needed; any further treatment for wound care was decided along with the surgical team. Dressings and ointments for exudate and infection control were used dynamically depending on wound and patient characteristics. When exudates and bacterial bioburden were controlled, treatments favoring re-epithelialization and contraction were used. Treatment options and costs were discussed with each patient.
Data regarding patient comorbidities, cancer type and treatment, and variables related to the surgical procedure and postoperative care were collected using a standardized questionnaire. Frequency per 100 surgeries was calculated for SSIs, necrosis, wound dehiscence and hematoma. Data obtained were introduced into a database (Paradox 9; Corel, Ottawa, Ontario, Canada). A descriptive analysis was conducted using mean ± standard deviation and/or median and percentiles for continuous variables. For categorical variables, proportions were used. For comparisons, Student’s t test and χ2 for proportions were used as appropriate. To test the association between wound complications with known risk factors, odds ratio (OR), and 95% confidence intervals (CI) were estimated. Adjustment of variables was done by stepwise non-conditional logistic regression analysis. Analysis was conducted using SPSS version 10 (SPSS Inc., Chicago, IL). P < 0.05 was considered statistically significant.
The study included 1888 surgical procedures among 1774 patients. At the time of surgery, 228 (12.2%) patients had diabetes, 317 (16.8%) were hypertensive, and 194 (10.3%) were smokers. More than half of the patients (1030, 54.6%) had locally advanced breast cancer at time of diagnosis. Four hundred and eighteen (418, 22.3%) were treated with neoadjuvant chemotherapy, and 689 (37.1%) patients had preoperative concomitant chemoradiation (Table 1). Most patients (1200, 63.6%) underwent modified radical mastectomy. Average duration of surgery and bleeding was 133.7 minutes (5–515) and 254.3 mL (0–1600), respectively. Oncological and surgical variables of patients are described in Table 1. In this cohort, 873 (46.2%) wound complications were recorded. The most frequent complications were SSI (n = 387, 20.4%), flap necrosis (n = 274, 14.5%), and wound dehiscence (n = 212, 11.2%; Table 2). Most patients with SSI (n = 387, 20.4%) were treated with oral antibiotics and local wound management on an outpatient basis; 34 (8.8%) required further in-hospital management with IV antibiotics, and 14 (41.2%) patients underwent supplemental surgical debridement. The most frequently isolated bacteria were S aureus (n = 88, 24.5%), E coli (n = 49, 12.7%), and E cloacae (n = 33, 8.5%). The mean diameter of flap necrosis was 4 cm x 1.8 cm (range 1–11 cm x 0.2–11 cm). The majority of patients with flap necrosis and dehiscence were treated with debridement in addition to treatments that favored wound healing. One hundred eighty-three patients (66.7%) with necrosis and 68 patients (57.6%) with wound dehiscence were treated under the wound bed preparation model. Combined treatments were frequent and were adjusted according to wound appearance. Special emphasis on size, depth, exudate, and bacterial burden (only clinically evaluated) was taken under consideration. During the first steps of wound management alginates, silver preparations and honey were the most used treatments (Figure 1 and Table 3). When infection and exudate control was achieved a team discussion was conducted with the aim of determining surgical closure feasibility, particularly in patients waiting for cancer adjuvant treatment. When surgical closure was not achieved, honey and ketanserine were the treatment modalities most used for re-epithelialization, as both had high patient acceptance due to their ease of use and low cost. A description of necrosis and wound dehiscence management is shown in Figure 1 and Table 3. At the final appointment, 189 (48.4%) patients with difficult-to-heal wounds achieved wound closure. Among patients where closure was not achieved and their wound was stable without other complications, they were able to continue their cancer treatment. Average time to wound closure for necrosis and dehiscence was 52.4 ± 45.7 and 45.2 ± 36.1 days, respectively. In Time to healing, initiation of adjuvant cancer treatment, and mean number of visits to the wound care clinic is shown in Table 4. The initiation of adjuvant treatment in patients with a wound complication (SSI, flap necrosis, or dehiscence) was delayed 10 days on average compared to patients without wound complications (P = 0.002; Table 4). The variables independently associated to any major wound complication were: age > 50 years (OR = 1.97, 95% CI = 1.6–2.5; P < 0.0001), bleeding > 250 mL (OR = 1.4; 95% CI = 1.1–1.7; P = 0.006), diabetes mellitus (OR = 1.54; 95% CI = 1.07–2.2; P = 0.02), preoperative radiation (OR = 1.3; 95% CI = 1.1–1.6; P = 0.05), and obesity (OR = 1.63; 95% CI = 1.3–2.06; P < 0.0001). The independently associated variables were duration of surgery (OR = 1.65; 95% CI = 1.16–2.34; P = 0.005) and obesity (OR = 1.8; 95% CI = 1.3–2.5; P = 0.001) when a sub-analysis was conducted for wound dehiscence.
The most frequent problems of a mastectomy (infection, skin necrosis, hematoma, and seroma formation) become evident during the first weeks of the postoperative period and should be evaluated and treated at that time. Although these major complications can occur individually, they frequently occur simultaneously,7 which was the case in this series where 244 (12.9%) patients developed SSI + flap necrosis simultaneously, and 63 (3.3%) developed SSI + dehiscence. Incidence of complications after breast cancer surgery has been reported as low,8–11 but in patients with large tumors who were treated with multimodality therapy (radiation and chemotherapy and, at times, preoperatively, as were most of our patients [n = 1107, 59%]), a higher rate of complications is expected2–6,12 In patients who received preoperative chemoradiation, wound healing may be further delayed because radiation has been associated with increased fibrosis and decreased vascularity.3,6,13 This study represents a large series of patients treated for breast cancer. Fifty-five percent had locally advanced breast cancer, and 36.7% were treated preoperatively with concomitant chemoradiation. Overall, 779 (41.2%) patients experienced at least one complication. With regard to these complications, 448 (57.5%) occurred in patients who received preoperative chemoradiation (OR = 1.9; 95% CI = 1.6–2.5; P = 0.0001), consistent with the findings previously reported by our group.2, 6 Radiation injury is inevitable in non-neoplastic tissue as a direct effect of ionizing radiation. The extent of damage depends on factors related to dosage, fraction, energy and particles used, intervals between fractions, volume of normal tissue that receives a high dose and use of concomitant chemotherapy or biological modifier.13,14 Tissue damage can lead to dermatitis, skin necrosis, and ulceration. In patients undergoing surgery, the structural damage caused by radiation may further contribute to delayed healing13 and may have a negative impact on survival and quality of life. Scarce information exists in recent literature on the approach and management of patients with flap necrosis and dehiscence following breast cancer surgery. Although these complications are infrequent in patients with conservative procedures, necrosis of skin flaps or borders are a commonly recognized complication according to Bland, with an average occurrence in 8% of patients.15,16 In the present study this complication occurred in 274 (14.5%) of patients. In those patients treated with concomitant preoperative chemoradiation, the rate of flap necrosis is even higher (151, 21.9%);17 11.3% were associated with infection. Treatment of flap necrosis and dehiscence can be cumbersome for patients and healthcare personnel. Local debridement is usually not necessary for minor areas of necrosis (≤ 2 cm2). Larger areas of partial- or full-thickness skin loss require debridement and even the need for split-thickness skin grafts. In the present review, 4% of patients required the application of a skin graft; however, patients who were treated with preoperative radiation were not always good candidates for surgical treatment due to tissue radiation injury and poorly vascularized tissue. In the latter group, significant postoperative morbidity and the difficulties encountered when dealing with radiated tissue have been recognized. Huang et al4 found that postoperative outcomes in patients with inoperable anthracycline-resistant breast cancer treated preoperatively with radiation are poor with a 5-year rate of significant postoperative morbidity of 53% and 13% requiring additional hospital admission for surgery.4 Surgical treatments were not always feasible despite their good results when well-vascularized flaps are used among these patients.17,18 Surgeons need to reconsider the risks of reconstruction on radiated tissues because the risks may exceed the benefits.13 In patients such as those described in this series, proper wound bed preparation is mandatory and is the most valuable measure to achieve healing (or at least progress) and improve the patient’s quality of life.19 Introduction of the wound bed preparation model along with good surveillance and follow-up is an example of a multidisciplinary approach of patients with difficult-to-treat wounds who have complex healthcare needs. In this cohort, wound complications delayed the initiation of adjuvant treatment (Table 3). The impact of this delay has not been fully studied but may be a cofactor for decreased survival; thus, prevention and early management of complicated wounds is mandatory. In this cohort we used different dressings and ointments for wound management, which have demonstrated various degrees of efficacy. In most patients, as suggested by the wound bed preparation model itself, treatment was dynamic according to the wound appearance and improvement as well as patients’ preferences, which frequently were in accordance with the availability of the product and its cost, because care of patients is almost always paid for by the patients themselves. It is important to mention that 14% of individuals seen at our institution are illiterate and have a family income < $6.00 US dollars/day. The government or insurance companies do not finance their treatment; the cost of wound care tends to be expensive and unaffordable for them. As shown in Figure 1, honey was used in 30 (23.4%) patients with flap necrosis with good clinical results. In the majority of patients, honey was used after alginates or dressings for highly exudative wounds or as an adjuvant for controlling bacterial bioburden and to enhance healing. The type and amount of honey was not standardized because patients were obtaining it locally, but instructions on cleansing and occlusion with gauze were always given. Despite the variability, most patients demonstrated a positive response and high acceptance to honey, similar to other reports.20–23 In some instances, the wound bed preparation model also allowed an appropriate wound environment for surgical closure (13.5% of patients with flap necrosis, 8% of patients with wound dehiscence), rendering better results than the historical controls (data not shown).
Frequency of wound complication in this cohort was higher than that reported elsewhere.8–10 This may be partially explained by the fact that our series included a high proportion of patients with locally advanced breast cancer, more radical surgeries, and the use of preoperative radiation. Prospective surveillance including post-discharge follow-up allowed us to accurately quantify and characterize the type and characteristics of wound complications in patients with breast cancer undergoing surgery. The treatment of these wounds can be cumbersome for patients and healthcare personnel; a multidisciplinary approach and the use of the wound bed preparation model are mandatory to achieve optimal results. Difficult-to-heal wounds in patients undergoing breast cancer surgery may also have a negative impact on patients’ quality of life and increase the cost of healthcare, which has largely been underestimated in regard to these postoperative complications. Any effort to avoid such complications is worthwhile and should be considered as a primary goal in treatment programs designed for patients with breast cancer.
1. Knaul FM, Nigenda G, Lozano R, Arreola-Ornelas H, Langer A, Frenk J. Breast cancer in Mexico: a pressing priority. Reprod Health Matters. 2008;16(32):113–123. 2. Ruvalcaba-Limón E, Robles-Vidal C, Poitevin-Chacón A, Chávez-Macgregor M, Gamboa-Vignolle C, Vilar-Compte D. Complications after breast cancer surgery in patients treated with concomitant preoperative chemoradiation: a case-control analysis. Breast Cancer Res Treat. 2006;95(2):147–152. 3. Badr el Din A, Coibion M, Guenier C, et al. Local postoperative morbidity following pre-operative irradiation in locally advanced breast cancer. Eur J Surg Oncol. 1989;15(6):486–489. 4. Huang E, McNeese MD, Strom EA, et al. Locoregional treatment outcomes for inoperable anthracycline-resistant breast cancer. Int J Radiat Oncol Biol Phys. 2002;53(5):1225–1233. 5. Sauter ER, Eisenberg BL, Hoffman JP, et al. Postmastectomy morbidity after combination preoperative irradiation and chemotherapy for locally advanced breast cancer. World J Surg. 1993;17(2):237–241. 6. Vilar-Compte D, Jacquemin B, Robles-Vidal C, Volkow P. Surgical site infections in breast surgery: case-control study. World J Surg. 2004;28(3):242–246. 7. Aitken DR, Minton JP. Complications associated with mastectomy. Surg Clin North Am. 1983;63(6):1331–1352. 8. Broadwater JR, Edwards MJ, Kuglen C, Hortobagyi GN, Ames FC, Balch CM. Mastectomy following preoperative chemotherapy—strict operative criteria control operative mortality. Ann Surg. 1991;213(2):126–129. 9. Canavese G, Catturich A, Vecchio C, et al. Surgical complications related to peri-operative adjuvant chemotherapy in breast cancer. Results of a prospective, controlled, randomized clinical trial. Eur J Surg Oncol. 1997;23(1):10–12. 10. Furey PC, Macgillivray DC, Castiglione CL, Allen L. Wound complications in patients receiving adjuvant chemotherapy after mastectomy and immediate breast reconstruction for breast cancer. J Surg Oncol. 1994;55(3):194–197. 11. Gaynes RP, Culver DH, Horan TC, Edwards JR, Richards C, Tolson JS. Surgical site infection (SSI) rates in the United States, 1992–1998: the National Nosocomial Infections Surveillance System basic SSI risk index. Clin Infect Dis. 2001;33(Suppl 2):S69–S77. 12. Skinner KA, Silberman H, Florentine B, et al. Preoperative paclitaxel and radiotherapy for locally advanced breast cancer: surgical aspects. Ann Surg Oncol. 2000;7(2):145–149. 13. Olascoaga A, Vilar-Compte D, Poitevin-Chacón A, Contreras-Ruiz J. Wound healing in radiated skin: pathophysiology and treatment options. Int Wound J. 2008;5(2):246–257. 14. Vuilleumier H, Reis ED. Radiation injury. In: Marti GJ, ed. Surgical Management of Anorectal and Colonic Disease. Berlin, Germany: Springer; 1998. 15. Bland KI, Krontiras H. Wound care and complications of mastectomy. In: Bland K, Copeland EM III, eds. The Breast. Comprehensive Management of Benign and Malignant Disorders. St. Louis, MO: Saunders; 2004. 16. Budd DC, Cochran RC, Sturtz DL, Fouty WJ Jr. Surgical morbidity after mastectomy operations. Am J Surg. 1978;135(2):218–220. 17. Miller SH, Rudolph R. Healing in the irradiated wound. Clin Plast Surg. 1990;17(3):503–508. 18. Shack RB. Management of radiation ulcers. South Med J. 1982;75(12):1462–1466. 19. Sibbald RG, Williamson D, Orsted HL, et al. Preparing the wound bed-debridement bacterial balance, and moisture balance. Ostomy Wound Manage. 2000;46(11):14–22, 24–28, 30–35. 20. Jull AB, Rodgers A, Walkers N. Honey as a topical treatment for wounds. Cochrane Database Syst Rev. 2008;8(4):CD005083. 21. Lay-flurrie K. Honey in wound care: effects, clinical application and patient benefit. Br J Nurs. 2008;17(11):S30, S32–36. 22. Mphande AN, Killowe C, Phalira S, Jones HW, Harrison WJ. Effects of honey and sugar dressings on wound healing. J Wound Care. 2007;16(7):317–319. 23. Robson V, Cooper R. Using leptospermum honey to manage wounds impaired by radiotherapy: a case series. Ostomy Wound Manage. 2009;55(1):38–47.