Introduction
Mammary gland tumors are the most common tumor of sexually intact female dogs, comprising 50% to 70% of tumors in this population.1,2,3,4,5 The development of mammary gland tumors in dogs is hormone dependent, and the incidence increases with age.6 Mammary gland tumors in dogs represent a wide spectrum of histologic variants with diverse biological behaviors.5,7,8,9,10,11,12,13 Both new mammary gland tumors and distant metastasis may occur after surgical resection. In general, metastases are associated with a fatal outcome, whereas the consequences of subsequent new mammary gland tumors are more variable, depending on malignancy and whether treatments are pursued. Secondary metastasis (ie, metastasis from subsequent new mammary gland tumors) resulting in death may occur but is relatively rare in dogs that are monitored and treated if such new tumors occur.13
Surgical excision is the treatment of choice for dogs with mammary gland tumors and can be achieved through a lumpectomy, simple mastectomy, regional mastectomy, or chain (or radical) mastectomy. Bilateral chain mastectomy involves removing all of the mammary glands.14
Traditionally, the surgical dose (ie, the aggressiveness of surgical resection) has depended on the extent of the disease and number of tumors present, with a goal of removing all palpable tumors with complete surgical margins. Prophylactic removal of unaffected glands to prevent new mammary gland tumors has generally not been advocated in dogs. A prospective, randomized study15 revealed that, in contrast to cats,16 no benefit was found in prophylactic mastectomy of the other mammary glands in the affected chain. These recommendations are supported by another study17 that found no difference in new tumor development according to surgery type in dogs undergoing surgery for mammary gland tumors. However, another study18 reported a high incidence of new mammary gland tumors in the ipsilateral chain after regional mastectomy in dogs with 1 mammary gland tumor; the authors concluded that complete resection of the ipsilateral chain should be considered in dogs with 1 mammary gland tumor. Notably, the same study18 also reported that 42% of dogs did not develop ipsilateral tumors and thus would undergo unnecessary surgery. Furthermore, although most dogs had their new tumor resected, the impact on survival time was not evaluated and risk factors to identify which dogs were more likely to develop new mammary gland tumors were not identified.18 Importantly, none of the dogs in the study18 were spayed as part of their treatment, which likely contributed to the high incidence of new mammary gland tumors.19,20 Only dogs with a single tumor were included in that particular study,18 and it is unclear how this observation may improve surgical planning of prophylactic mastectomy in dogs with multiple mammary gland tumors, as the occurrence and location of new tumors may not be as predictable in these dogs. In fact, most (70% to 80%) sexually intact female dogs have multiple tumors, and 52.5% have bilateral tumors.7,17 In these dogs, the surgical dose is often large out of necessity even in instances when prophylactic mastectomies are not performed. Performing bilateral chain mastectomies in all dogs with bilateral tumors may add unnecessary cost by staging the surgeries into 2 separate procedures or increase the risk of postoperative complications as well as increase the severity of postoperative pain if surgeries are not staged.21
The duration of anesthesia, surgical time, clipping hair at the surgical site in advance of anesthesia, concurrent endocrinopathies, and hypotension have been associated with an increased risk of postsurgical complications in dogs undergoing different types of surgeries.22,23,24,25,26,27 Conflicting results exist, however, regarding the benefits or risks associated with prophylactic use of antimicrobials after surgery and the development of surgical wound infection.22,27 Comorbidities and long anesthesia durations of dogs with multiple mammary gland tumors requiring extensive mastectomies may place this cohort at an increased risk of developing postsurgical complications.22,23 A prospective study21 evaluating regional and chain mastectomies found a significantly higher complication rate for dogs undergoing a chain mastectomy and an overall high complication rate (77.8%) for both procedures.21 To the authors’ knowledge, no reports exist on the complication rates among dogs undergoing various other mammary gland tumor surgeries (ie, lumpectomy, simple mastectomy, or bilateral mastectomies) and the consequences of such complications when they occur. To optimize treatment decisions for dogs with mammary gland tumors, specifically the surgical approach, we need a comprehensive understanding of the risks and benefits of prophylactic (ie, removal of ipsilateral and bilateral unaffected glands) versus therapeutic (ie, removal of affected glands only) mastectomies in dogs with mammary gland tumors.
The purposes of the study reported here were to determine the complication rate of various mastectomy procedures and the perioperative and postoperative factors associated with an increased risk of such complications in a larger cohort of dogs with mammary gland tumors. Furthermore, we also wanted to evaluate the severity of these complications and their consequences, including the need for rehospitalization and surgical intervention. On the basis of findings in previous reports, we hypothesized that dogs with large surgical doses and long anesthesia times would have increased rates of complications and that dogs with abscesses and wound infections would be more likely to require hospital readmission.
Materials and Methods
Case selection criteria
The medical records and surgical reports for dogs in the Penn Vet Shelter Canine Mammary Tumor Program at the University of Pennsylvania School of Veterinary Medicine from July 2009 to March 2015 were reviewed. The Shelter Canine Mammary Tumor Program was approved by the University of Pennsylvania's Institutional Animal Care and Use Committee, and representatives of the shelters and rescues gave written informed consent for the dogs to participate in the program.
To be eligible for enrollment in the mammary gland tumor program, the dogs were required to have been in foster care for ≥ 2 weeks prior to the screening visit; be up-to-date on vaccination with rabies, distemper, and parvovirus vaccine; have no evidence of upper respiratory or gastrointestinal disease at the time of enrollment; be free of substantial comorbidities that would make them poor surgical or anesthetic candidates; and be free of distant metastatic disease during tumor staging. Dogs with local lymph node metastasis were eligible for enrollment.
Study protocol
All dogs underwent presurgical diagnostics and tumor staging prior to surgery, which included a CBC, serum biochemical analysis, urinalysis, and thoracic radiography. If palpable lymph nodes were not included in the surgical plan, fine-needle aspiration and cytologic examination of the lymph nodes were performed. Abdominal ultrasonography was not routinely performed unless clinically indicated on the basis of serum biochemical analysis results or physical examination findings.
Mammary glands were carefully palpated, all masses were measured with calipers, and the size and location of all tumors were recorded. After anesthetic induction and immediately prior to surgery, mammary glands of dogs were palpated a second time to ensure that all tumors were identified for removal. Dogs that were sexually intact at the time of study enrollment underwent ovariohysterectomy or ovariectomy concurrent with mastectomy. Surgical resection of the tumors was performed according to standard practice (ie, remove all mammary gland tumors with clean surgical margins). The width of the surgical margins was determined by the surgeon and was based on the size of the tumor, but generally varied from 1 to 3 cm. Removal of inguinal lymph nodes was routinely included for dogs that had caudal abdominal and inguinal mammary glands affected. The axillary lymph nodes were resected if they were enlarged or were positive for metastatic disease on the basis of cytologic findings. Dogs with extensive bilateral disease had staged surgeries if deemed necessary by the surgeon. In these instances, dogs were allowed to heal completely (ie, for a minimum of 2 weeks) prior to the second surgery; each surgery was recorded as a separate event. Prophylactic mastectomies of unaffected glands were generally not performed. Dogs developing new tumors or local recurrence at recheck examinations were offered subsequent surgeries to remove the new tumors if they were free of distant metastatic disease on tumor staging. All dogs received antimicrobials IV during anesthesia induction. Antimicrobials were prescribed after surgery for some dogs at the surgeon's discretion. Surgeries were performed by board-certified surgeons or surgical residents under the supervision of a board-certified faculty member. Details regarding tumor staging, treatments, and histopathologic diagnoses from dogs with carcinomas included in the present study are described in a recent publication13 on prognostic bioscoring of dogs with mammary gland carcinomas. In addition, clinical data and postsurgical complications from dogs with benign tumors and mammary sarcomas were also included in the present study.
Data regarding breed, body weight, nutritional status, number of tumors, location and diameter of the largest tumor, histologic findings (ie, benign vs malignant tumor), tumor involvement (ie, unilateral vs bilateral), duration of anesthesia, ovariohysterectomy or ovariectomy status, surgeon's qualification (ie, resident vs faculty), postoperative antimicrobial use (none vs in-hospital administration only vs hospital discharge with antimicrobials), and drain placement (none vs type [ie, open or closed systems]) were recorded. The type of surgery was classified on the basis of the extent of the surgical procedure as follows: lumpectomy (ie, removal of a mass with part of the mammary gland), simple mastectomy (ie, removal of a single mammary gland), regional mastectomy (ie, removal of ≥ 2 adjacent mammary glands), and chain mastectomy (ie, removal of 1 entire chain of mammary glands). Types of complications were classified as seroma, abscess, dehiscence, and infection on the basis of information available in the medical records. The presence of infection or abscess was determined on the basis of cytologic findings and biological culture results in conjunction with physical examination findings and classified as infection versus abscess on the basis of how the attending clinician recorded the complication. A single dog could have multiple complications. Time to complications was recorded from the day of surgery to the first day the complication was noted. The consequences of these complications were also recorded, including hospitalization, surgical debridement and repair, death, and euthanasia.
Statistical analysis
All analysis was conducted by use of a commercial statistical software programa with 2-tailed tests of hypotheses and a value of P < 0.05 as the criterion for statistical significance. Categorical data were expressed as frequencies and percentages. Continuous data (eg, body weight, anesthesia time, number of tumors, size of the largest tumor) were converted to dichotomous categorical data after normality testing by grouping the variable as higher or lower than the median value. The Fisher exact test was used for all categorical variables for the univariate analysis.
Multivariable analysis was conducted in several steps. First, a univariable logistic regression exploratory analysis was performed, and then factors that showed an association to outcome (ie, complications as a binary variable) with a value of P < 0.2 were included in the subsequent step. In this analysis, univariable logistic regression was used for the continuous variables to assess association with the outcome of interest. Second, Lasso model selection was used to select a subset of independent variables significantly associated with the outcome of interest.28 Third, on the basis of the factors identified in step 2, a multivariable logistic model of the risk of complications was estimated. The critical values (P values) for the post hoc multiple pairwise comparisons were adjusted by use of the Fisher least significant difference to reduce the probability of false-positive results.
To test the model's ability to identify dogs at risk of developing complications and those that were not (goodness-of-fit), an ROC was created. The ROC provided a more complete description of the classification power of the logistic model. The ROC illustrated the probability of detecting a true signal (ie, sensitivity) and false signal (1-specificity). Points on the ROC were generated by varying the cut-point probability from 0 to 1. The area under the ROC provided a measure (index) of the model's ability to classify samples into positive and negative.29
Subsequently, the optimal cutoff probability was determined for calculation of the sensitivity and specificity. In addition, to further understand the association between variables and specific prophylactic interventions such as drain placements and postoperative administration of antimicrobials, the correlation between surgery type and the use of a surgical drain, use of a surgical drain and the risk of seromas, use of postoperative antimicrobials, surgery type, and risk of postoperative infection or abscess were analyzed with the Fisher exact test.
Results
Dogs included in the study
One hundred forty dogs that underwent 154 surgeries were included in the study; 14 dogs underwent 2 separate surgeries. The 140 dogs included mixed-breed dogs (n = 46 [33%]) and the following breeds: Chihuahua (10 [7%]); Beagle (8 [6%]); Dachshund (7 [5%]); Shih Tzu (7 [5%]); German Shepherd Dog (6 [4%]); Akita (5 [3.6%]); 4 (3%) each of Cocker Spaniel, Maltese, Pomeranian, and Yorkshire Terrier; American bulldog (3 [2%]); English bulldog (3 [2%]); and 21 other breeds representing only 1 or 2 dogs. The 154 surgeries involved 69 malignant tumors (9 sarcomas and 60 various subtypes of carcinomas) and 85 benign tumors. Median diameters of the largest tumor on each dog were as follows: carcinoma, 3.5 cm (range, 0.3 to 26 cm), sarcomas, 6.6 cm (range, 1.5 to 14.7 cm), and benign tumors, 1.6 cm (range, 0.5 to 16 cm). Twenty-seven dogs had 1 tumor and the remaining dogs had > 1 tumor, ranging from 2 to 42 tumors (Table 1).
Distribution of variables and incidence of complications in 140 dogs of the present study that underwent 154 surgical procedures to treat mammary gland tumors.
| Variables | No. of dogs | No (%) of complications | P value* | OR |
|---|---|---|---|---|
| Surgical procedure | 0.002 | NA | ||
| Lumpectomy | 19 | 2 (10.53) | ||
| Simple mastectomy | 33 | 1 (3.03) | ||
| Regional mastectomy | 75 | 12 (16.0) | ||
| Chain mastectomy | 27 | 11 (40.74) | ||
| Sides involved | 0.001 | 5.07 | ||
| Unilateral | 75 | 5 (6.67) | ||
| Bilateral | 79 | 12 (26.58) | ||
| Concurrent ovariohysterectomy | 0.231 | 0.56 | ||
| Yes | 111 | 16 (14.41) | ||
| No | 43 | 10 (23.26) | ||
| AB administered after surgery | < 0.001 | 7.75 | ||
| Yes | 66 | 21 (31.82) | ||
| No | 88 | 5 (5.68) | ||
| AB with hospital discharge | 0.259 | 1.76 | ||
| Yes | 54 | 12 (22.22) | ||
| No | 100 | 14 (14.00) | ||
| Surgical drains | 0.043 | 3.19 | ||
| Yes | 17 | 6 (35.29) | ||
| No | 137 | 20 (14.60) | ||
| Surgeon | 0.463 | 1.62 | ||
| Faculty | 39 | 5 (12.82) | ||
| Resident | 104 | 20 (19.23) | ||
| Not recorded | 11 | 1 (9) | ||
| Tumor type | 0.388 | 1.55 | ||
| Malignant | 69 | 14 (20.29) | ||
| Benign | 85 | 12 (14.12) | ||
| Nutritional status | 0.441 | NA | ||
| Obese | 1 | 0 (00) | ||
| Overweight | 15 | 5 (33.3) | ||
| Good | 93 | 16 (19.35) | ||
| Underweight | 36 | 5 (11.11) | ||
| Cachectic | 0 | 0 (0) | ||
| Not reported | 9 | 0 (0) | ||
| Caudal tumor location | 0.026 | NA | ||
| Yes | 134 | 26 (19.40) | ||
| No | 20 | 0 (0.00) | ||
| Median anesthesia time (3 hours and 2 minutes)† | 0.238 | 1.50 | ||
| < Median | 72 | 10 (13.89) | ||
| ≥ Median | 82 | 16 (19.51) | ||
| Median body weight (9.6 kg [21.12 lb])‡ | 0.051 | 2.63 | ||
| < Median | 77 | 8 (10.39) | ||
| ≥ Median | 77 | 18 (23.38) | ||
| Median No. of tumors (5)§ | 0.005 | 4.02 | ||
| < Median | 76 | 6 (7.89) | ||
| ≥ Median | 78 | 20 (25.64) | ||
| Median largest tumor size (2.9 cm)‖ | 1.00 | 0.97 | ||
| < Median | 76 | 13 (17.11) | ||
| ≥ Median | 78 | 13 (16.67) |
Values of P < 0.05 were considered significant.
Anesthesia time ranged from 1 to 7 hours and 15 minutes.
Body weight ranged from 1.1 to 45 kg (2.42 to 99 lb).
Number of tumors ranged from 1 to 42.
Largest tumor size ranged from 0.3 to 26 cm.
AB = Antimicrobials. NA = Not applicable (odds ratios were not calculated when there were > 2 categories within the variable or there were cells with the value of 0).
Surgical procedures
Of 154 surgeries, 134 (87.0%) involved the caudal abdominal and inguinal mammary glands and 79 (51.3%) involved bilateral tumors. The surgical procedures included lumpectomy (19 [12.3%]), simple mastectomy (33 [21.4%]), regional mastectomy (75 [48.7%]), and chain mastectomy (27 [17.5%]). Of the 154 surgeries, 63 (40.9%) involved 1 surgical procedure, 19 (12.3%) involved multiple small surgeries (ie, lumpectomy and simple mastectomy), and 72 (47%) involved multiple surgical procedures, including a regional or chain mastectomy. For 43 of 154 (27.9%) surgeries, the dogs had been spayed prior to tumor removal, and for 111 (72.1%) surgeries, the dogs were spayed concurrent with tumor removal.
Subcutaneous tissues were closed by use of single interrupted, buried sutures. Cefazolin sodium (22 mg/kg [10 mg/lb], IV) was administered to all dogs perioperatively, according to the standard protocol at our institution. Of 154 surgeries, 66 (42.9%) included postsurgical administration of cefazolin to dogs during recovery in the hospital. Of 154 surgeries, 54 (35.1%) included continuation of oral administration of antimicrobials after hospital discharge as follows: cephalexin (n = 27), cefpodoxime (3), amoxicillin–clavulanic acid (22), doxycycline (1), and clindamycin (1). All doses and treatment intervals were consistent with standard practices. Seventeen (11%) surgeries included the placement of surgical drains; 10 drains were Penrose drains, 5 were closed suction drains, 1 was a wound soaker catheter, and 1 had a vacuum assisted closure.
Variables associated with complications
Of 154 surgeries, 26 (16.9%) resulted in dogs with complications. The reported complications that developed were seroma (n = 15), abscess (3), dehiscence (5), and infection (14). Eight dogs had multiple types of complications. The median time to develop complications was 13.9 days (range, 1 to 60 days).
Of all the variables tested, the type of surgical procedure (P = 0.002), bilateral involvement (P = 0.001), administration of antimicrobials postoperatively (P < 0.001), placement of surgical drains (P = 0.043), caudal location of tumors (ie, involving the caudal abdominal and inguinal mammary glands; P = 0.026), and having more than the median (ie, 5 [range, 1 to 42]) number of tumors (P = 0.005) were all significantly associated with increased odds for developing postoperative complications of any type (Table 1).
The risk of developing infection or abscess in dogs that received antimicrobials postoperatively was analyzed. Of 154 surgeries, 66 included postoperative administration of antimicrobials and 88 did not. Of 14 surgeries that resulted in postoperative infection or abscess, 13 included postoperative administration of antimicrobials. However, of 140 surgeries that did not result in postoperative infection or abscess, 53 (37.9%) included postoperative administration of antimicrobials (P < 0.001).
However, postoperative administration of antimicrobials was significantly (P = 0.001; Fisher exact test) correlated with more extensive surgical procedures. The risk for seroma development was not significantly correlated with drain placement. Specifically, 3 of 15 dogs with seroma had a drain placed, while 12 of these 15 dogs did not involve drain placement. In comparison, 14 of 17 dogs had drain placement but did not develop seromas. The association between seroma and drain placement was not significant (P = 0.22). Drain placement was, however, significantly correlated with larger surgical procedures (P = 0.006).
Results of multivariable analysis revealed that increasing body weight was significantly (P = 0.017) associated with increased odds of complications (OR, 1.08 [95% CI, 1.01 to 1.15]). Performing bilateral procedures (OR, 10.99 [95% CI, 2.32 to 51.97]; P = 0.002) and the postoperative administration of antimicrobials (OR, 48.72 [95% CI, 2.32 to 1,022.63]; P = 0.012) were also significantly associated with overall increased odds of complications. However, when considering surgery type for the analysis, it appeared that prophylactic administration of antimicrobials postoperatively in dogs undergoing chain mastectomy was associated with lower odds of complications (OR, 2.96 [95% CI, 0.20 to 44.72]; P = 0.432), compared with dogs not receiving antimicrobials (OR, 14.95 [95% CI, 1.18 to 189.53]; P = 0.037). Interestingly, dogs that underwent concurrent ovariohysterectomy or ovariectomy had significantly (P = 0.028) decreased odds of complications (OR, 0.22 [95% CI, 0.05 to 0.85]). Overall, the model's sensitivity and specificity showed an excellent ability to classify cases according to their risk of complications after surgery with the area under the ROC of 0.89 (Figure 1).
The ROC (connected circles) depicting the sensitivity and specificity of the multivariable logistic model developed for predicting postoperative complications in this study from data on 140 dogs undergoing 154 various types of mastectomies (ie, lumpectomy, simple mastectomy, regional mastectomy, or chain mastectomy). The area under the ROC is 0.89, which indicates that the model has an excellent classification power. The diagonal line in the ROC represents a test with results no different from chance.
Citation: Journal of the American Veterinary Medical Association 258, 3; 10.2460/javma.258.3.295
The ROC (connected circles) depicting the sensitivity and specificity of the multivariable logistic model developed for predicting postoperative complications in this study from data on 140 dogs undergoing 154 various types of mastectomies (ie, lumpectomy, simple mastectomy, regional mastectomy, or chain mastectomy). The area under the ROC is 0.89, which indicates that the model has an excellent classification power. The diagonal line in the ROC represents a test with results no different from chance.
Citation: Journal of the American Veterinary Medical Association 258, 3; 10.2460/javma.258.3.295
The ROC (connected circles) depicting the sensitivity and specificity of the multivariable logistic model developed for predicting postoperative complications in this study from data on 140 dogs undergoing 154 various types of mastectomies (ie, lumpectomy, simple mastectomy, regional mastectomy, or chain mastectomy). The area under the ROC is 0.89, which indicates that the model has an excellent classification power. The diagonal line in the ROC represents a test with results no different from chance.
Citation: Journal of the American Veterinary Medical Association 258, 3; 10.2460/javma.258.3.295
Morbidity and death associated with complications
Of the 26 dogs that developed postoperative complications, 9 (34.6%) were hospitalized, while the remaining 17 (65.4%) were treated on an outpatient basis. Seven of the 9 hospitalized dogs had an infection or abscess as one of their postoperative complications, and 7 dogs required surgical intervention. One dog with incisional dehiscence was euthanized because of a histopathologic diagnosis of carcinosarcoma, which had a poor long-term prognosis.
Discussion
To the authors’ knowledge, our study was the first to evaluate the risks associated with mammary gland tumor removal in dogs undergoing various surgical procedures, including lumpectomy, and simple, regional, and chain mastectomies and the subsequent risks of readmission and revision surgery to treat these complications. Eleven of the 27 (40.7%) dogs undergoing chain mastectomies developed a postoperative complication. Bilateral mammary gland involvement was also an independent risk factor for postoperative complications. This suggested that an increasing surgical dose (ie, the aggressiveness of surgical resection) was associated with an increasing risk of surgical complications. These findings were not surprising; chain and bilateral mastectomies involve exposure of a large area of fascia and subcutaneous tissue, often for a substantial time. Dissection and the use of electrocautery may produce more devitalized tissue than seen in simple lumpectomies. Closure of the incision with buried, simple interrupted, subcutaneous sutures increases surgery time, which is a factor contributing to an increased risk of surgical infection in previous studies14,16 of broader ranges of surgical procedures.
The complication rate in our study, 26 of 154 (16.9%) surgeries, was lower than the 78% rate of postoperative complications found in a prospective study21 evaluating dogs undergoing regional and chain mastectomies. The specific purpose of that study, however, was to record the incidence of postoperative complications; thus, the dogs were monitored specifically for postoperative complications, and all types were noted regardless of severity. It is possible that some postoperative complications were underreported in our study, as some dogs may not have been returned from the rescues for evaluation of minor incisional problems. However, it is unlikely that cases with serious postoperative incisional complications requiring treatment did not return because the costs for all treatment were covered by the mammary gland tumor program funding and these dogs were all cared for by foster families associated with shelters and rescue organizations with limited financial flexibility.
Interestingly, and in contrast to previous studies, anesthesia time was not significantly associated with an increased risk of complication in our study. It seems reasonable to assume that the duration of anesthesia would be directly associated with the size of the surgery and therefore also be associated with increased incidence of complications. However, there were both residents and faculty performing surgery on these dogs, and it is likely that the more inexperienced residents would need more time to perform the same surgery than a more experienced faculty surgeon, consequently eliminating the effect of anesthesia time.
Seromas were the most common postoperative complication recorded in our study. Seromas are more likely to occur during procedures that result in large amounts of dead space, such as mastectomies involving the caudal abdominal and inguinal mammary glands or bilateral mastectomies. Accurate apposition of tissue layers with sutures is an accepted method of incision closure, but in extensive mastectomies, particularly those involving the caudal abdominal and inguinal mammary glands, there may be inadequate tissue to eliminate dead space. The use of tacking sutures, that is, suturing the subcutaneous tissue layer to the rectus abdominus fascia, has been shown to decrease the incidence of incisional seroma in midline celiotomies but has not been evaluated in the closure of mastectomies.30 Drains remove fluid from dead space and also separate the tissue layers on either side of the drain, preventing them from apposing and sealing, thus representing a 2-edged sword for seroma formation. The use of surgical drains did not prevent or increase the incidence of seromas in the present study. They were placed more often in dogs with extensive mastectomies involving the caudal abdominal and inguinal mammary glands because this is the area where dead space and seromas are more likely to develop.
The postoperative administration of antimicrobials was also associated with a significantly increased overall risk of complications according to results of multivariable analysis in the present study. Importantly, however, when introducing the effect of surgery type (ie, lumpectomy, simple mastectomy, regional mastectomy, or chain mastectomy) into the analysis, the OR for developing complications in dogs that underwent chain mastectomy was higher for dogs that did not receive antimicrobials postoperatively than dogs that did. The postoperative administration of antimicrobials is controversial and has been variably associated with an increased risk of complications in other studies.22,27 The decision to prescribe antimicrobials in the present study was made on the basis of the individual surgeon's preference and clinical assessment of the dog; it is therefore not unexpected that dogs that underwent extensive mastectomies (ie, chain mastectomies) were more likely to receive antimicrobials postoperatively. In the present study, 13 of 14 dogs with postoperative infections or abscesses had received antimicrobials postoperatively. These dogs also had inherent increased odds for complications because they underwent more extensive surgical procedures. Because of the relationship between the perceived increased risk and prophylactic intervention (ie, postoperative administration of antimicrobials), it was important to perform multivariable analysis to explore the effect of antimicrobials according to surgery type to fully understand these interactions. However, it may be difficult to determine the actual role of postoperative administration of antimicrobials in a retrospective study such as the present study. Ideally, a prospective randomized trial on the effect of postoperative antimicrobials in dogs stratified according to surgery type should be performed.
In the present study, several factors identified for inclusion in the univariable analysis were not subsequently found to be significant factors in the multivariable analysis. This illustrates the complexities that occur when analyzing multiple variables that are interdependent of and associated with, or are a consequence of, other contributing factors. Therefore, the multivariable analysis in the present study was critical to adjust for these interactions and provided a clearer picture of the most important factors. Additionally, a priori power calculations or estimates were not performed in the present study. However, this was a retrospective exploratory study, and we had relatively limited data to base such calculations; the number of cases in the present study was determined solely by how many dogs with mammary gland tumors had underwent surgery in a particular time frame. The results from the present study may be useful to inform later studies on this topic.
Incision length has been found to be an independent risk factor for surgical site infection following abdominal surgery for colic in horses31 and caesarian section in humans.32 Although not evaluated specifically in the present study, the incision length for chain mastectomies is logically and substantially longer than that for any other mastectomy procedures. This may also partly explain the direct correlation between body weight and risk of postoperative complications. The incision required to perform a chain mastectomy in a 30-kg (66-lb) dog is longer than that required for the same procedure in a 3-kg (6.6-lb) Chihuahua; therefore, the exposure of a larger area of subcutaneous tissues is longer in larger dogs, even when adjusting for surgery type. Furthermore, postoperative activity restrictions are routinely advised when discharging dogs after surgery because it is crucial to promote healing and to prevent seroma formation in residual dead space and subsequent dehiscence and infection. It may be harder for owners to effectively restrict a large dog than a small dog. This may also contribute to more complications in larger dogs. These results highlight the importance of exercise restriction, especially in larger dogs that have undergone chain or bilateral mastectomies.
Contrary to what might have been expected, concurrent ovariohysterectomy or ovariectomy was associated with significantly decreased odds for complications according to multivariable analysis. Ovariohysterectomy or ovariectomy is typically performed before the mastectomy, but may not necessarily require longer incisions. But the fact that it decreases the overall risk is puzzling. One possible explanation for this finding may be differences in serum estrogen concentration in spayed versus sexually intact dogs. Estrogen has profound effects on immune functions, regulates inflammation, and plays a crucial role in promoting wound healing through its effect on collagen, all of which may explain the increased risk of complications in dogs that had been spayed prior to tumor removal.33,34,35,36,37 However, the estrous cycle in dogs is infrequent and short, and most dogs in the present study were likely in metestrus or anestrus when they had surgery; thus, serum estrogen concentrations were likely not peaking as a result of proestrus and estrus. However, our most recent research has shown that there is considerable variation in serum estrogen (ie, estradiol) concentrations between dogs during these periods of the estrous cycle, and it is therefore possible that some of the answers regarding postoperative complications may be found here.20
Other factors not included in the analysis of the present study might have contributed to wound complications after surgery. This includes, but may not be limited to, the medication protocols before surgery and the pain medications administered after surgery for individual dogs. The premedication could vary substantially between dogs and was selected by the anesthetist and surgeon on the basis of the dogs’ medical status and the surgical plan. The impact of these variables, if any, would be best evaluated by prospective studies.
Most dogs that developed postoperative complications in the present study could have been treated as outpatients and did not require hospitalization or surgical intervention. However, 9 of 26 (34.6%) required hospitalization, 7 of which also required surgical intervention. Thus, these complications were not negligible and contributed to added discomfort for the dog and financial expense for owners. In light of these findings, it may be reasonable to consider staging the surgeries if both chains are involved and avoid making the surgery dose larger than necessary. Prophylactic mastectomy on unaffected mammary glands should probably not be performed without a compelling reason to do so. For the most part, however, new tumors are easy to detect by regular palpation, and a simple lumpectomy can be performed if they are detected early. Our data indicated that the risk of developing complications with a simple mastectomy is low and new tumors have a low incidence of secondary metastasis.13 It is, however, crucial that dogs are monitored for new tumors and that surgery is offered while these tumors are at an early stage. Lastly, it is important to emphasize the importance of postoperative activity restrictions for large dogs to avoid wound dehiscence and seroma formation.
Acknowledgments
This study was performed at the Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania.
Financial support was provided by multiple donations to the PennVet Shelter Canine Mammary Tumor Program. This work was made possible through this program.
The authors declare that there were no conflicts of interest.
Footnotes
STATA/MP, version 15, StataCorp, College Station, Tex.
AbbreviatioNS
| ROC | Receiver operating characteristic curve |
References
- 1. ↑
Moe L. Population-based incidence of mammary tumours in some dog breeds. J Reprod Fertil Suppl 2001;57:439–443.
- 2. ↑
Merlo DF, Rossi L, Pellegrino C, et al. Cancer incidence in pet dogs: findings of the animal tumor registry of Genoa, Italy. J Vet Intern Med 2008;22:976–984.
- 3. ↑
Vascellari M, Capello K, Carmatio A, et al. Incidence of mammary tumors in the canine population living in the Veneto region (Northeastern Italy): risk factors and similarities to human breast cancer. Prev Vet Med 2016;126:183–189.
- 4. ↑
Salas Y, Marques A, Diaz D, et al. Epidemiological study of mammary tumors in female dogs diagnosed during the period 2002–2012: a growing animal health problem. PLoS One 2015;10:e0127381.
- 5. ↑
Sorenmo KU, Worley DR, Goldschmidt MH. Tumors of the mammary gland. In: Withrow SJ, Vail DM, Page RL, eds. Withrow & MacEwen's small animal clinical oncology. St Louis: Elsevier, 2013;538–556.
- 6. ↑
Schneider R, Dorn CR, Taylor DO. Factors influencing canine mammary cancer development and postsurgical survival. J Natl Cancer Inst 1969;43:1249–1261.
- 7. ↑
Sorenmo KU, Kristiansen VM, Cofone MA, et al. Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence. Vet Comp Oncol 2009;7:162–172.
- 9. ↑
Benjamin SA, Lee AC, Saunders WJ. Classification and behavior of canine mammary epithelial neoplasms based on lifespan observations in beagles. Vet Pathol 1999;36:423–436.
- 10. ↑
Fowler EH, Wilson GP, Koestner A. Biologic behavior of canine mammary neoplasms based on a histogenetic classification. Vet Pathol 1974;11:212–229.
- 11. ↑
Goldschmidt M, Peña L, Rasotto R, et al. Classification and grading of canine mammary tumors. Vet Pathol 2011;48:117–131.
- 12. ↑
Rasotto R, Berlato D, Goldschmidt MH, et al. Prognostic significance of canine mammary tumor histologic subtypes: an observational cohort study of 229 cases. Vet Pathol 2017;54:571–578.
- 13. ↑
Sorenmo KU, Durham AC, Kristiansen V, et al. Developing and testing prognostic bio-scoring systems for canine mammary carcinomas. Vet Comp Oncol 2019;17:10.1111/vco.12509.
- 14. ↑
MacPhail C, Fossum TW. Surgery of the female reproductive tract. In: Fossum TW, ed. Small animal surgery. St Louis: Elsevier, 2018;746–762.
- 15. ↑
MacEwen EG, Harvey HJ, Patnaik AK, et al. Evaluations of effects of levamisole and surgery on canine mammary cancer. J Biol Response Mod 1985;4:418–426.
- 16. ↑
MacEwen EG, Hayes AA, Harvey HJ, et al. Prognostic factors for feline mammary tumors. J Am Vet Med Assoc 1984;185:201–204.
- 17. ↑
Horta RS, Lavalle GE, de Castro Cunha RM, et al. Influence of surgical technique on overall survival, disease free interval and new lesion development interval in dogs with mammary tumors. Adv Breast Cancer Res 2014;3:38–46.
- 18. ↑
Stratmann N, Failing K, Wehrend A. Mammary tumor recurrence in bitches after regional mastectomy. Vet Surg 2008;37:82–86.
- 19. ↑
Kristiansen VM, Nodtvedt A, Breen AM, et al. Effect of ovariohysterectomy at the time of tumor removal in dogs with benign mammary tumors and hyperplastic lesions: a randomized controlled clinical trial. J Vet Intern Med 2013;27:935–942.
- 20. ↑
Sorenmo KU, Durham AC, Radaelli E, et al. The estrogen effect; clinical and histopathological evidence of dichotomous influences in dogs with spontaneous mammary carcinomas. PLoS One 2019;14:e0224504.
- 21. ↑
Horta RS, Figueiredo MS, Lavalle GE, et al. Surgical stress and postoperative complications related to regional and radical mastectomy in dogs. Acta Vet Scand 2015;57:34.
- 22. ↑
Beal MW, Brown DC, Shofer FS. The effects of perioperative hypothermia and the duration of anesthesia on postoperative wound infection rate in clean wounds: a retrospective study. Vet Surg 2000;29:123–127.
- 23. ↑
Brown DC, Conzemius MG, Shofer F, et al. Epidemiologic evaluation of postoperative wound infections in dogs and cats. J Am Vet Med Assoc 1997;210:1302–1306.
- 24. ↑
Turk R, Singh A, Weese JS. Prospective surgical site infection surveillance in dogs. Vet Surg 2015;44:2–8.
- 25. ↑
Nazarali A, Singh A, Weese JS. Perioperative administration of antimicrobials during tibial plateau leveling osteotomy. Vet Surg 2014;43:966–971.
- 26. ↑
Yap FW, Calvo I, Smith KD, et al. Perioperative risk factors for surgical site infection in tibial tuberosity advancement: 224 stifles. Vet Comp Orthop Traumatol 2015;28:199–206.
- 27. ↑
Nicholson M, Beal M, Shofer F, et al. Epidemiologic evaluation of postoperative wound infection in clean-contaminated wounds: a retrospective study of 239 dogs and cats. Vet Surg 2002;31:577–581.
- 28. ↑
Hastie T, Tibshirani R, Wainwright M. In: Hastie T, Tibshirani R, Wainwright M, eds. Statistical learning with sparsity: the lasso and generalizations. Boca Raton, Fla: CRC Press, 2015.
- 29. ↑
Hosmer DW, Lemeshow S. Assessing the fit of the model. In: Hosmer DW, Lemeshow S, eds. Applied logistic regression. 2nd ed. New York: John Wiley & Sons Inc, 2000;143–203.
- 30. ↑
Travis BM, Hayes GM, Vissio K, et al. A quilting subcutaneous suture pattern to reduce seroma formation and pain 24 hours after midline celiotomy in dogs: a randomized controlled trial. Vet Surg 2018;47:204–211.
- 31. ↑
Darnaud SJM, Southwood LL, Aceto HW, et al. Are horse age and incision length associated with surgical site infection following equine colic surgery? Vet J 2016;217:3–7.
- 32. ↑
Nagaria T, Kujur A, Thakur N. Incision length: an emerging risk factor for surgical-site infection following caesarian section. Int J Reprod Contracept Obstet Gynecol 2017;6:1829–1833.
- 33. ↑
Horng HC, Chang WH, Yeh CC, et al. Estrogen effect on wound healing. Int J Mol Sci 2017;18:https://doi.org/10.3390/ijms18112325.
- 34. ↑
Hardman MJ, Waite A, Zeef L, et al. Macrophage migration inhibitory factor: a central regulator of wound healing. Am J Pathol 2005;167:1561–1574.
- 35. ↑
Margolis DJ, Knauss J, Bilker W. Hormone replacement therapy and prevention of pressure ulcers and venous leg ulcers. Lancet 2002;359:675–677.
- 36. ↑
Hesketh M, Sahin KB, West ZE, et al. Macrophage phenotypes regulate scar formation and chronic wound healing. Int J Mol Sci 2017;18:E1545.
- 37. ↑
Wilkinson HN, Hardman MJ. The role of estrogen in cutaneous ageing and repair. Maturitas 2017;103:60–64.
