Evaluation of primary re-excision after recent inadequate resection of soft tissue sarcomas in dogs: 41 cases (1999–2004)

Nicholas J. Bacon Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by Nicholas J. Bacon in
Current site
Google Scholar
PubMed
Close
 MA, VetMB
,
William S. Dernell Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by William S. Dernell in
Current site
Google Scholar
PubMed
Close
 DVM, MS, DACVS
,
Nicole Ehrhart Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by Nicole Ehrhart in
Current site
Google Scholar
PubMed
Close
 VMD, MS, DACVS
,
Barbara E. Powers Veterinary Diagnostic Laboratory, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by Barbara E. Powers in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVP
, and
Stephen J. Withrow Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by Stephen J. Withrow in
Current site
Google Scholar
PubMed
Close
 DVM, DACVS, DACVIM

Click on author name to view affiliation information

Abstract

Objective—To determine the efficacy of primary re-excision alone for treatment of soft tissue sarcomas after recent incomplete resection, the frequency and clinical importance of detecting residual tumor in resected scars, and prognostic factors associated with the procedure.

Design—Retrospective case series.

Animals—41 dogs.

Procedures—Medical records of dogs that had undergone recent incomplete excision of a soft tissue sarcoma at a referring veterinary practice and subsequent re-excision of the scar at the Colorado State University Veterinary Medical Center were reviewed.Owners and referring veterinarians were contacted for follow-up information.Slides from re-excised specimens were reviewed.Dogs that underwent radiation therapy after the re-excision procedure were excluded.

Results—41 dogs met the inclusion criteria, and long-term follow-up information was available for 39 dogs.Median follow-up time was 816 days.Local recurrence of tumor developed in 6 of 39 (15%) dogs, and distant metastasis occurred in 4 of 39 (10%) dogs.Healthy tis sue margins of 0.5 to 3.5 cm were achieved at re-excision. Residual tumor was identified in 9 of 41 (22%) resected scars.No tumor-, patient-, or treatment-related variables were associated with local recurrence except for the presence of liposarcoma or fibrosarcoma or whether fine-needle aspiration had been performed prior to surgery.

Conclusions and Clinical Relevance—After incomplete resection of soft tissue sarcomas, resection of local tissue should be performed, even if excisable tissue margins appear narrow.A long-term favorable prognosis is achievable without radiation therapy or amputation. The presence of residual tumor in resected scar tissue should not be used to predict local recurrence.

Abstract

Objective—To determine the efficacy of primary re-excision alone for treatment of soft tissue sarcomas after recent incomplete resection, the frequency and clinical importance of detecting residual tumor in resected scars, and prognostic factors associated with the procedure.

Design—Retrospective case series.

Animals—41 dogs.

Procedures—Medical records of dogs that had undergone recent incomplete excision of a soft tissue sarcoma at a referring veterinary practice and subsequent re-excision of the scar at the Colorado State University Veterinary Medical Center were reviewed.Owners and referring veterinarians were contacted for follow-up information.Slides from re-excised specimens were reviewed.Dogs that underwent radiation therapy after the re-excision procedure were excluded.

Results—41 dogs met the inclusion criteria, and long-term follow-up information was available for 39 dogs.Median follow-up time was 816 days.Local recurrence of tumor developed in 6 of 39 (15%) dogs, and distant metastasis occurred in 4 of 39 (10%) dogs.Healthy tis sue margins of 0.5 to 3.5 cm were achieved at re-excision. Residual tumor was identified in 9 of 41 (22%) resected scars.No tumor-, patient-, or treatment-related variables were associated with local recurrence except for the presence of liposarcoma or fibrosarcoma or whether fine-needle aspiration had been performed prior to surgery.

Conclusions and Clinical Relevance—After incomplete resection of soft tissue sarcomas, resection of local tissue should be performed, even if excisable tissue margins appear narrow.A long-term favorable prognosis is achievable without radiation therapy or amputation. The presence of residual tumor in resected scar tissue should not be used to predict local recurrence.

Primary re-excision refers to wide resection of a scar at a site at which initial tumor excision left microscopic residual disease or in which insufficient information was available to confirm completeness of the excision.1 The goal of primary re-excision is to remove all remnants of tumor and avoid the necessity for further local treatment, particularly radiation therapy or amputation. However, primary re-excision is not always possible, and the feasibility of the procedure depends on the location of the original tumor and availability of surrounding tissue for reconstruction.

Many subcutaneous soft tissue lesions are benign or inflammatory in character, but 15% of all skin and subcutaneous tumors in dogs are soft tissue sarcomas.2 These develop from various mesenchymal tissues and typically manifest as nonpainful masses on the trunk or extremities. Although they may be firm and attached to deeper tissues, many soft tissue sarcomas are soft and movable and mimic lipomas or other benign masses. Soft tissue sarcomas are typically surrounded by a pseudocapsule, which creates an easy plane of cleavage between tumor and surrounding tissues and enables masses to be shelled out and submitted for histologic evaluation. The pseudocapsule consists of a rim of compressed tumor and reactive tissue with margins that are poorly defined histologically and that contain tumor cells extending into the surrounding tissue. This type of marginal excision, therefore, commonly results in tumor cells extending to the edges of the resected tissue. If the tumor pseudocapsule is entered during surgery and the mass is removed in piecemeal fashion, the excision process is referred to as intralesional. The term excisional biopsy is used when a narrow rim of healthy tissue is excised around a mass, but this technique is still likely to leave tumor cells behind if the tumor in question is a soft tissue sarcoma. In human studies, tumor excision attempts that do not involve wide resection or appropriate preoperative evaluation (including histologic diagnosis from a biopsy specimen or results of imaging studies) are described as unplanned excisions.3–5

Unplanned surgical intervention in humans results in a higher likelihood of local tumor recurrence, even after aggressive revision surgery.6,7 What is less clear in humans, however, is the importance of detecting microscopic tumor in the resected scar: results of earlier studies are conflicting, with various investigators reporting that microscopic detection of tumor is a negative prognostic indicator for recurrence,5,8 is of no clinical significance,1,9 or is unrelated to local relapse but positively associated with distant metastasis.10

Published results of additional treatment after unplanned or incomplete excision of soft tissue sarcomas in dogs are scarce and are confined to reports involving radiation therapy11,12 or chemotherapy.13 At the authors' center and elsewhere, primary re-excision is commonly performed after initial unplanned excisions when feasible. To our knowledge, the success of this primary surgical re-excision has not been reported. The objective of the present study was to assess the effectiveness of primary re-excision with regard to local recurrence and distant metastasis, determine the frequency and clinical importance of residual tumor in resected scars, and assess patient-, disease-, and treatment-related factors for prognosis. We hypothesized that the local recurrence rate after primary re-excision would be at least equivalent to rates after margin resection and adjunctive radiation therapy for soft tissue sarcomas in dogs.

Criteria for Selection of Cases

The medical database at the Colorado State University Veterinary Medical Center was searched for dogs with a diagnosis of soft tissue sarcoma from September 1, 1999, to December 31, 2004. Dogs were included if they had undergone an unplanned and histologically incomplete resection of the sarcoma by the referring veterinarian and were subsequently managed with attempted curative-intent resection of the scar at the medical center.

Exclusion criteria were diagnoses of osteosarcoma, chondrosarcoma, synovial cell sarcoma, hemangiosarcoma, and soft tissue sarcomas affecting the mandible or maxilla; dogs with obvious macroscopic disease at the surgical site arising from rapid local recurrence; dogs that underwent radiation therapy or chemotherapy prior to referral; and dogs that underwent radiation therapy after definitive surgery at the medical center. Dogs with grade 3 sarcomas14 that received adjunctive chemotherapy after primary re-excision were included in the study.

Procedures

Data obtained from the medical records included breed, sex, and age at diagnosis. In reference to the mass and the first unplanned surgery, data collected included anatomic position, size, duration, whether biopsied, tumor type, tumor grade (point scale of 1, 2, or 314), and size of margins. The surgical report from the referring veterinarian was reviewed to determine the intent of the first surgery (intralesional, marginal, or excisional biopsy). For re-excision procedures, data collected included time between surgeries, whether there was metastasis to lymph nodes or lung, width and depth of margin achieved, presence of tumor in the resected scar, and proximity of tumor to tissue edges. All slides of resected tissues from re-excisions were reviewed by a single pathologist (BEP).

At the time of examination at the Veterinary Medical Center, each dog underwent assessment by the surgeon to determine whether primary re-excision and a wider resection and tumor-free margin could be achieved. Alternative options offered to owners included withholding of further treatment and monitoring of the site for recurrence, amputation if the mass was on an extremity, radiation therapy of the scar, and limited re-excision of the scar with assessment of surgical margins for microscopic disease and adjunctive radiation therapy if tumor was detected in the margins (staging re-resection).

During surgery, a margin of healthy tissue as close as possible to 3 cm in all directions was removed, including normal-appearing subcutaneous fat and underlying fascia. The tissue defect was closed with available local skin and simple tension-relieving techniques when indicated. Advanced reconstructive procedures or skin grafting was not used in any dog.

The resected scar and tumor bed were inked on all margins and placed in formalin. Tissues were not typically pinned to retain orientation. The tissue underwent routine histologic processing, with sections cut to focus on the region of prior resection. Tumor margins were defined as positive for containing tumor if the pathologist detected microscopically evident disease at the inked margin and were defined as close if microscopically evident disease was detected within 3 mm of the inked margin. In each instance, a follow-up period of at least 12 months after primary re-excision was available for obtaining information from the owner or referring veterinarian.

Statistical analysis—The interval during which dogs remained free of local recurrence was defined as the time between primary re-excision and evidence of local recurrence. Histologic confirmation of recurrence was performed according to owners' wishes, but all new masses developing in the region of the scar were considered to be recurrences for the purposes of the study. Survival time was defined as the interval between primary re-excision and death. Cause of death was classified as tumor related or non−tumor related. When possible, complete necropsy was performed. Survival times were determined by use of the Kaplan-Meier product limit method, and log-rank analysis was used to compare survival times among dogs according to histologic grade, presence of residual tumor in resected specimen, anatomic location, development of recurrence, and development of metastasis.

For the purposes of these analyses, continuous variables were stratified. On the basis of medians, age was classified as < 8.7 or t 8.8 years; mass diameter was < 3 cm or t 3 cm; duration of mass prior to initial surgery was < 42 days or t 42 days; interval between surgeries was < 20 days or t 20 days; and margin achieved was < 1 cm, t 1 cm but < 2 cm, t 2 cm but < 3 cm, or t 3 cm. Between-group differences were considered significant when log-rank values of P were < 0.05.

For survival calculations, dogs that had recurrence or died because of soft tissue sarcoma (recurrence or metastasis) were considered completed events. Dogs that were lost to follow-up, that died of causes other than the soft tissue sarcoma, or that were still alive without evidence of recurrence or metastasis were censored at the time of last contact.

Results

Forty-one dogs with a soft tissue sarcoma and that had previously undergone unplanned resection prior to referral were included in the study. No follow-up information was available for 2 dogs after discharge from the medical center; those dogs were included in the initial analysis but not in the long-term outcome part of the study. Two dogs were lost to follow-up at 420 and 440 days after primary re-excision. Median follow-up time for dogs still alive was 816 days (range, 390 to 1,816 days). Only 1 dog underwent full-course radiation therapy after primary re-excision at the medical center, and that dog was excluded.

Five (12%) dogs were sexually intact males, 18 (44%) were castrated males, and 18 (44%) were spayed females. The most commonly represented breeds were Golden Retriever (n = 8), mixed (8), Labrador (6), Spaniel (4), Miniature Schnauzer (3), and Siberian Husky (3). Other breeds included Jack Russell Terrier, Australian Shepherd, Rottweiler, Standard Schnauzer, Whippet, German Shorthaired Pointer, Doberman, and Pug. Mean age was 8.9 years (range, 2.8 to 15.4 years).

Tumor types included 28 (68%) peripheral nerve sheath tumors, 6 (15%) soft tissue sarcomas of undetermined histiogenesis, 3 (7%) liposarcomas, 2 (5%) neurofibrosarcomas, and 2 (5%) fibrosarcomas. Histopathologic findings in the primary masses revealed that 12 (29%) tumors were grade 1, 24 (59%) tumors were grade 2, and 5 (12%) tumors were grade 3.

Three (7%) tumors were located on the head, 17 (41%) were on the neck or flanks, 11 (27%) were on the proximal portions of limbs, and 10 (24%) were at or distal to the elbow and stifle (femorotibial) joints. Size of the original tumor was recorded in 29 (71%) dogs, and the mean longest diameter was 4.2 cm (range, 0.5 to 20 cm). Duration of the primary tumor prior to initial surgery by the referring veterinarian was known in 27 (66%) dogs, in which the mean was 80 days (range, 4 to 365 days).

Prior to the initial surgery, 24 (59%) dogs did not undergo a biopsy procedure or had no record of a biopsy being performed, and 17 (41%) underwent fine-needle aspiration. Specimens from all 17 of the latter group of dogs had been interpreted in-house by referring veterinarians; 13 of those specimens were nondiagnostic or were interpreted as normal fat or lipoma tissue, 2 were round cell tumors, and in 2, cells were identified as mesenchymal cells but no mention was made of cellular features of malignancy.

A description of the initial surgery was available for 37 (90%) dogs. In 8 (22%) of the surgeries, intralesional procedures were performed (tumor pseudocapsule was entered with the mass often being removed in a piecemeal manner). Twenty-two (59%) surgeries were described as margin resections in which no attempt was made to resect tissue outside the tumor pseudocapsule, and in 11 of those 22 surgery reports, referring veterinarians used the terms peeling or shelling to describe the procedure. Seven (19%) surgeries were excisional biopsies, in which a narrow and insufficient margin of normal-appearing tissue was removed along with the tumor mass. In 39 (95%) first surgeries, tumor cells were detected in 1 or more edges of the resected specimen, and 2 (5%) first surgeries yielded specimens with margins of indeterminate status with regard to presence of tumor (ie, no description of healthy tissue surrounding mass in the original pathology report but not diagnosed as incomplete resection).

After referral to the Veterinary Medical Center, all dogs underwent 3-view radiographic examination of the thorax and lymph node aspiration if a node was palpably enlarged; in all instances, the tumor was nonmetastatic. Mean interval between unplanned surgery and primary re-excision was 26 days (range, 5 to 98 days). Margins of healthy tissue around the scar that were achieved at primary re-excision were recorded for 37 (90%) dogs, and mean margin widths were as follows: lesions on the head, 1.2 cm (range, 1 to 1.5 cm); lesions on the neck or flank, 2.3 cm (range, 1 to 3 cm); lesions on the proximal portions of limbs, 2.7 cm (range, 2 to 3.5 cm); and lesions on the distal portions of limbs, 1.4 cm (range, 0.5 to 2 cm). The depth of the deep margin was recorded as being the same as the width of the lateral margin, or beneath 1 fascial plane if the site was on an extremity. No amputations were performed as part of primary re-excision. Histologic evaluation of resected specimens revealed tumor cells among granulation tissue in 9 (22%) dogs. In 7 of those 9 dogs, margins contained no tumor; in 1 dog, tumor was within 1 mm of the edge, and in another dog, the margins contained tumor. In the remaining 32 (78%) dogs, only granulation tissue was identified. Granulation tissue extended to the edge of the resected specimens in 10 (24%) dogs; only 1 of those specimens also contained tumor cells in the center.

No correlations between local tumor recurrence and sex, breed, age, tumor grade, tumor location, tumor size, duration of tumor prior to initial surgery, classification of initial surgery, interval between surgeries, margin achieved at primary re-excision, or presence of tumor in the resected scar were detected, but the number of completed events (n = 6) was low, resulting in low statistical power. It has been suggested15 that a minimum of 10 events/variable are required for analysis of such predictive models, making the results of evaluation for many variables in the present study unreliable.

A correlation between local recurrence and tumor type was identified, with liposarcomas (n = 3; P = 0.003) and fibrosarcomas (2; P = 0.001) being significantly more likely to recur than peripheral nerve sheath tumors (25). A significant correlation between local recurrence and fine-needle aspirate performed prior to initial surgery was identified, with tumors that were aspirated being significantly (P = 0.033) more likely to recur.

Five dogs underwent primary re-excision after unplanned margin resection of grade 3 soft tissue sarcomas. Residual tumor with clean tissue margins was identified in 1 of 5 of the resected scars. None of the dogs with grade 3 tumors had local recurrence after primary re-excision. One dog was euthanized by the referring veterinarian because of pulmonary metastatic disease at 1,176 days, and 1 dog was euthanized because of old age at 1,007 days. Necropsy was not performed in either of those dogs. Three dogs were alive at the time of manuscript preparation at 571, 1,007, and 1,816 days after primary re-excision. Two of the 5 dogs with grade 3 sarcomas underwent postoperative chemotherapy with doxorubicin at a dosage of 30 mg/m2 every 2 weeks for 5 treatments. Those dogs were alive at 571 (tumor identified in resected scar but tissue margins were clean) and 1,816 days after primary re-excision, and neither dog had clinical or radiographic evidence of metastatic disease.

Details for 6 of the 39 (15%) dogs that had local tumor recurrence and long-term follow-up were summarized (Table 1). Median time to recurrence calculated via Kaplan-Meier survival analysis was 142 days.

Table 1—

Summary of details pertaining to tumor characteristics and recurrence in 6 dogs that underwent incomplete excision of a soft tissue sarcoma by the referring veterinarian and subsequent scar re-excision at a referral institution.

SignalmentLocation of massMass diameter (cm)Mass grade and typeWidth of margin at re-excision(cm)Evidence of tumor in resected tissueTime to recurrence (days)Additional treatmentOutcome (No. days from re-excision)
7-year-oldFlank3Grade 2; FSA3No112NoneRecurrence; euthanized (328)
Jack
Russell
Terrier
10-year-oldFlank6Grade 2; PNST2No541ResectionNo recurrence; alive (764)
English
Springer
Spaniel
9-year-oldFemorotibial joint3Grade 2; STS1No142AmputationEuthanized for reasons unrelated to tumor (895)
Miniature
Schnauzer
4-year-oldThigh4Grade 2; PNST2Yes, clean margins185ResectionEuthanized for reasons unrelated to tumor (907)
Labrador
Retriever
13-year-oldThigh5Grade 2; LipoSANot recordedNo137NoneDied for reasons unrelated to tumor (251)
Cocker
Spaniel
9-year-old mixed breedAxillaNot recordedGrade 2; LipoSA3Yes, Incomplete margin120NoneLung metastasis; euthanized (871)

FSA = Fibrosarcoma. PNST = Peripheral nerve sheath tumor. STS = Soft tissue sarcoma. LipoSA = Liposarcoma.

Four of 39 (10%) dogs had radiographic or clinical evidence of metastatic disease at 273, 703, 861, and 1,176 days after primary re-excision. One of those dogs had metastases from a grade 1 peripheral nerve sheath tumor and radiographic evidence of pulmonary metastases, 1 had a grade 1 peripheral nerve sheath tumor and pleural effusion containing neoplastic cells, 1 had a grade 2 liposarcoma and hemoptysis but no radiographic evaluation, and 1 had a grade 3 peripheral nerve sheath tumor and radiographic evidence of pulmonary metastasis. Residual tumor was detected in the resected tissues of the second grade 1 peripheral nerve sheath tumor mentioned and in the liposarcoma (tumor cells were observed in the deep margin of the resected tissue). Local recurrence of the liposarcoma developed at 120 days after primary re-excision. Overall median survival was not reached at median follow-up of 816 days (range, 390 to 1,816 days) because more than half of the dogs were alive at time of last follow-up.

Discussion

Our hypothesis was that the local tumor recurrence rate after primary re-excision would be at least as low as rates associated with margin resection and adjunctive radiation therapy in dogs. Recurrence rates of 17%12 and 31%11 have been reported after incomplete surgical resection and hypofractionated radiation therapy in dogs. The local recurrence rate in dogs in the present study that underwent primary re-excision was 15%. In an earlier report16 in humans, when residual tumor remained after initial primary excision, primary re-excision of the tumor bed resulted in reduced tumor load.

Results of that study and others9,17 indicate that if it is feasible for a second surgery to be performed promptly and it appears that the second procedure would remove the residual tumor, such a surgery should be recommended. Recurrence rates after primary re-excision in humans are hard to compare with rates in the present study because few of the human studies were purely surgical in focus; however, 5-year local control rates of 86% to 89% have been reported7,10 in humans after primary re-excision and radiation.

In humans with soft tissue sarcomas, radiation therapy is often combined with margin surgery to avoid ablative or radical resection, especially amputation, with an aim of attaining better functional and cosmetic outcomes. These concerns are not as acute in veterinary patients, but it was possible to avoid amputation in all primary re-excision procedures in the present study.

The decision of whether to recommend scar re-excision or radiation therapy rests with each surgeon, which may bias the procedure toward being performed more frequently in scars located in the flank region, where there is often more tissue available for wound reconstruction. However, the distribution of lesions in the present study (7% involving the head, 41% involving the neck or flank, and 51% involving the limbs) was similar to the distribution of lesions in earlier studies of dogs undergoing postoperative radiation therapy (head [19%], trunk [31%], and limbs [50%] in 1 study12 and oral cavity [22%], trunk [35%], and limbs [43%] in another study11).

Soft tissue sarcomas are often excised improperly because of failure to diagnose neoplastic disease before surgery, leading to resection of the lesion with no or inadequate margins of healthy tissue. This is a well-recognized problem in human medicine: in 1 study,18 as many as 52% of adults who were evaluated for management of soft tissue sarcomas had previously undergone unplanned excision that resulted in excised masses having margins that contained tumor, and the percentage in children has been reported as 81%.19 Unplanned excision of soft tissue sarcomas by veterinarians is also common; in the present study, 59% of the subcutaneous masses studied had not been biopsied prior to surgery. When an attempt at diagnosis had been made, specimens assessed were all from fine-needle aspirates and were interpreted by the referring veterinarian; a correct diagnosis was made in 12% of those instances, and the specimen was nondiagnostic or an incorrect diagnosis was made in 88% of the instances. In another study20 involving dogs at a university hospital, evaluation of fine-needle aspirates of soft tissue sarcomas yielded a correct diagnosis in 62.5% of cases and an incorrect diagnosis in 15%, and results were nondiagnostic in 22.5%. In the present study, a significant positive correlation was identified between a fine-needle aspirate being performed and tumor recurrence. This finding is difficult to explain but may be associated with hemorrhage at the biopsy site causing seeding or local tumor dissemination through fascial planes, although soft tissue sarcomas typically have low vascularity and this complication has not been reported for this tumor type in dogs (in contrast to urogenital carcinomas).21 It is also possible that some aspect of the tumors' appearance raised concerns about malignancy when first observed by the referring veterinarian (prompting fine-needle aspiration) and that these tumors were accordingly more likely to recur. However, the masses that were aspirated were different in character, being large or small, soft or firm, or fixed or moveable, making this explanation less likely. It should be stressed that the association between aspiration and local recurrence should not be considered as an indication to avoid presurgical biopsy of the mass, because a well-planned curative-intent excision performed with knowledge of biopsy results is still the aim of oncologic surgery.

Ideally, all subcutaneous masses should be managed with biopsy and marginal or wide excision, depending on whether the neoplasm is benign or malignant. However, our results reveal that many subcutaneous tumors in dogs are treated by marginal excision with referral to an oncology center if subsequent analysis reveals the mass to be malignant. In humans, unplanned surgical excision of subcutaneous sarcomas negatively influences disease-free survival of patients with lesions 4 cm in diameter or larger. However, unplanned excisional biopsy of a lesion 3 cm in diameter or smaller does not seem to compromise outcome when the lesion is unexpectedly a sarcoma,7 presumably because there is more local tissue that can be resected to achieve tumor-free margins. In the present study, no correlation between primary tumor size and local recurrence after primary re-excision was found, although the recurrence rate (completed events, n = 6) was too low for confident statistical analysis.

Despite incomplete resection of soft tissue sarcomas in dogs being common, the frequency of detecting residual tumor in re-resected tissues has not been reported, to our knowledge. In the present study, 22% of resected scars contained tumor cells. In humans, reported percentages range from 24% to 64%.3-5,7-10,15,17

One reason why this percentage is not closer to 100%, given that all primary resections were considered incomplete, is the difficulty in identifying small populations of residual neoplastic mesenchymal cells in beds of active granulation tissue. In veterinary pathology, including the pathologic analyses in the present study, far fewer sections are typically examined in animals than in humans, with most of the dogs in the present study having fewer than 4 sections examined. In 2 prospective studies5,15 in humans, sections were taken at 5- to 10-mm intervals throughout the resected tissue, and residual tumor was detected in 40% to 45% of patients. It is likely that if specimens from dogs were prospectively sectioned into multiple slices, residual tumor would be detected more frequently. The present study also focused on early re-excisions and excluded dogs with macroscopically evident disease, whereas many human re-excision studies include patients with visible local recurrence, increasing the percentage of cases in which tumor is identified.

In the present study, no correlation was found between the presence of tumor in the resected tissue and local recurrence. It is possible that the frequency of residual disease was underestimated, however, for the reasons mentioned previously. This absence of association is in agreement with results of 2 oncologic studies1,9 involving primary re-excision in humans. However, in another study5 in humans, detection of tumor in a reexcision sample following unplanned resection was an important risk factor for local relapse. In that study,5 the tumor recurrence rate when no tumor was identified in a re-excision specimen was 1/62 (2%), whereas in persons in which re-excised tissue specimens had microscopic evidence of tumor, the frequency of recurrence was 7/42 (17%). No correlation was found between granulation tissue at the edge of the resection (incomplete re-excision) and local recurrence.

The higher recurrence rate in humans with tumor in resected tissue could be associated with differences in the amount of tumor left after unplanned resection (ie, volumes of tumor too low to be identified in granulation tissue may be too low to support recurrence) or with rapid regrowth of a more aggressive tumor in the scar tissue that is also more likely to be associated with local resection failure in the future.

In the present study, 78% of dogs had no residual tumor at re-excision. When assessing the feasibility of re-excision surgery for a given dog, it can be difficult to determine the appropriate extent of the excision with regard to resecting skin, subcutaneous tissue, and muscle. At present, there is no accurate testing method that can accurately predict the presence of residual microscopic disease in a wound, so surgical resection should include all potential sites of disease (eg, all previously disturbed tissue). Magnetic resonance imaging is used increasingly frequently in human oncology to plan primary re-excision procedures, but this technique is still associated with a 25% to 33% false-negative rate, with microscopic disease only being detected with subsequent histologic examination.16,22 Predicting tumor presence in a scar may help guide placement of surgical margins, but it apparently does not predict likelihood of local recurrence. It is becoming increasingly clear that tumor biology rather than radical surgery is the primary determinant of patient outcome,23 especially given the fact that local recurrence of sarcoma may occur after clean and wide excision of a scar containing too few neoplastic cells to be identified histologically.

The signalment of the dogs in this study was similar to that in previous studies, with older medium- to large-breed dogs predominating. Distribution of tumors, tumor types, and proportion of tumor grades were also similar.11-14,19,24,25 In contrast to findings in previous studies, however, tissues from tumors diagnosed as hemangiopericytomas at the time of initial surgery were retrieved and reviewed, and all were reclassified as peripheral nerve sheath tumors. Because of the low number (6) of recurrences, no reliable correlations were identified for recurrence, although 2 of 3 liposarcomas recurred after primary re-excision, a difference that was significant. Metastasis was only detected in 10% of cases, similar to figures of 8%, 14%, and 17% reported in previous studies.11,12,23 A metastatic rate of 31% was reported in 1 study25 in which many dogs were enrolled in research protocols that included necropsy, and a 44% metastatic rate was reported in another study13 in which high-grade sarcomas alone were evaluated.

A limitation of the present study was its retrospective format. The number of necropsies performed was insufficient to permit confident reporting of the metastatic rate in the dogs because some instances of metastasis may have been missed; however, because local tumor recurrence is typically obvious, the figures for local recurrence rate are likely more accurate. Another criticism is that not all of the original pathology slides from referring veterinarians were reviewed to confirm tumor in tissue margins, grade of tumor, and type of tumor, although 49% of the original slides were read by a single pathologist (BEP) and 76% of the slides were read by 1 of 3 board-certified pathologists. The study does, however, reflect case material evaluated at a referral center during a 5-year period, and 1 aim of the study was to evaluate the success of primary re-excision in this referral population of dogs with incompletely resected soft tissue sarcoma. Decisions to treat were made on the basis of available data, and this study reports the outcome of those decisions. The case number was small (ie, 41 dogs), but the length of the follow-up interval was reasonably long (390 to 1,816 days). Median survival time was not reached, 1 explanation for which may be that recurrence had not yet occurred in some dogs at the time of manuscript preparation. Median time to recurrence, however, was 142 days. Given that the shortest follow-up period was 390 days, which fell outside the 95% confidence interval, that explanation is unlikely.

Another criticism is that dogs that underwent radiation therapy after primary re-excision were excluded. That group included dogs in which tumor, possibly extending to the edge of the tissue, was detected in the resected scar, thus potentially biasing results. This situation only arose in 1 dog, however. In that dog, a grade 2 peripheral nerve sheath tumor was detected in the deep margin of tissue resected in the primary reexcision, and the dog underwent full-course radiation therapy. The dog subsequently died of unrelated disease and was without local tumor recurrence 1,195 days after primary re-excision. All other dogs that underwent primary re-excision from 1999 to 2004 were treated with surgery alone.

Kuntz et al23 reported that dogs in which the margins of tissue removed during a curative-intent first surgery contained tumor had a 28% local recurrence rate. That study, however, involved a referral population of dogs that likely had sarcomas requiring larger and deeper resections than those removed from dogs by general practitioners in the present study. Tumor recurrence rates of 17%12 and 31%11 have been reported after incomplete excision and postoperative radiation therapy, and our findings revealed a rate of 15% with primary re-excision after unplanned resection, arguably with fewer adverse effects and at lower cost. Primary reexcision, however, is not always feasible because of constraints associated with resection and reconstruction or because further surgery may be declined by owners. In that situation, radiation therapy is the recommended alternative. The frequency of detecting microscopic tumor disease in resected tissues reviewed retrospectively in the present study was 22%, a value that is lower than percentages that have been reported in human studies. That percentage, however, is likely an underestimate and should be evaluated prospectively. The presence of tumor cells in resected tissues was not useful in predicting local recurrence in the present study.

References

  • 1

    Cecchetto G, Guglielmi M, Inserra A, et al. Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas. Pediatr Surg Int 2001;17:532534.

    • Search Google Scholar
    • Export Citation
  • 2

    Theilen GH, Madewell BR. Tumours of the skin and subcutaneous tissues. In:Theilen GH, Madewell BR, ed.Veterinary cancer medicine. Philadelphia: Lea & Febiger, 1979;123191.

    • Search Google Scholar
    • Export Citation
  • 3

    Giuliano AE, Eilber FR. The rationale for planned reoperation after unplanned total excision of soft-tissue sarcomas. J Clin Oncol 1985;3:13441348.

    • Search Google Scholar
    • Export Citation
  • 4

    Noria S, Davis A, Kandel R, et al. Residual disease following unplanned excision of soft-tissue sarcoma of an extremity. J Bone Joint Surg Am 1996;78A:650655.

    • Search Google Scholar
    • Export Citation
  • 5

    Davis AM, Kandel RA, Wunder JS, et al. The impact of residual disease on local recurrence in patients treated by initial unplanned resection for soft tissue sarcoma of the extremity. J Surg Oncol 1997;66:8187.

    • Search Google Scholar
    • Export Citation
  • 6

    Gustafson P, Dreinhofer KE, Rydholm A. Soft tissue sarcoma should be treated at a tumor centre. A comparison of quality of surgery in 375 patients. Acta Orthop Scand 1994;65:4750.

    • Search Google Scholar
    • Export Citation
  • 7

    Rougraff BT, Davis K, Cudahy T. The impact of previous surgical manipulation of subcutaneous sarcoma on oncological outcome. Clin Orthop 2005;438:8591.

    • Search Google Scholar
    • Export Citation
  • 8

    Peiper M, Knoefel WT, Izbicki JR. The influence of residual tumor on local recurrence after unplanned resection of soft tissue sarcoma. Dtsch Med Wochenschr 2004;129:183187.

    • Search Google Scholar
    • Export Citation
  • 9

    Gibbs CP, Peabody TD, Mundt AJ, et al. Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities. J Bone Joint Surg Am 1997;79:888897.

    • Search Google Scholar
    • Export Citation
  • 10

    Fiore M, Casali PG, Miceli R, et al. Prognostic effect of re-excision in adult soft tissue sarcoma of the extremity. Ann Surg Oncol 2006;13:110117.

    • Search Google Scholar
    • Export Citation
  • 11

    Forrest LJ, Chun R, Adams WM, et al. Postoperative radiotherapy for canine soft tissue sarcoma. J Vet Intern Med 2000;14:578582.

  • 12

    McKnight JA, Mauldin GN, McEntee MC, et al. Radiation treatment for incompletely resected soft-tissue sarcomas in dogs. J Am Vet Med Assoc 2000;217:205210.

    • Search Google Scholar
    • Export Citation
  • 13

    Selting KA, Powers BE, Thompson LJ, et al. Outcome of dogs with high-grade soft tissue sarcomas treated with or without adjuvant doxorubicin chemotherapy: 39 cases (1996–2004). J Am Vet Med Assoc 2005;227:14421448.

    • Search Google Scholar
    • Export Citation
  • 14

    Kuntz CA, Dernell WS, Powers BE, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc 1997;211:11471151.

    • Search Google Scholar
    • Export Citation
  • 15

    Concato J, Feinstein A, Holford TR. The risk of determining risk with multivariable models. Ann Intern Med 1993;118:201210.

  • 16

    Raney RB, Ragab AH, Ruymann FB, et al. Soft-tissue sarcoma of the trunk in childhood. Results of the Intergroup Rhabdomyosarcoma Study. Cancer 1982;49:26122616.

    • Search Google Scholar
    • Export Citation
  • 17

    Zornig C, Peiper M, Schroder S. Re-excision of soft tissue sarcoma after inadequate initial operation. Br J Surg 1995;82:278279.

  • 18

    Manoso MW, Frassica DA, Deune EG, et al. Outcomes of re-excision after unplanned excisions of soft-tissue sarcomas. J Surg Oncol 2005;91:153158.

    • Search Google Scholar
    • Export Citation
  • 19

    Chui CH, Spunt SL, Liu T, et al. Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection? J Pediatr Surg 2002;37:14241429.

    • Search Google Scholar
    • Export Citation
  • 20

    Baker-Gabb M, Hunt GB, France MP. Soft tissue sarcomas and mast cell tumours in dogs; clinical behaviour and response to surgery. Aust Vet J 2003;81:732738.

    • Search Google Scholar
    • Export Citation
  • 21

    Nyland TG, Wallack ST, Wisner ER. Needle-tract implantation following US-guided fine-needle aspiration of transitional cell carcinoma of the bladder, urethra, and prostate. Vet Radiol Ultrasound 2002;43:5053.

    • Search Google Scholar
    • Export Citation
  • 22

    Davies AM, Mehr A, Parsonage S, et al. MR imaging in the assessment of residual tumour following inadequate primary excision of soft tissue sarcomas. Eur Radiol 2004;14:506513.

    • Search Google Scholar
    • Export Citation
  • 23

    Weitz J, Antonescu CR, Brennan MF. Localized extremity soft tissue sarcoma: improved knowledge with unchanged survival over time. J Clin Oncol 2003;21:27192725.

    • Search Google Scholar
    • Export Citation
  • 24

    Banks T, Straw R, Thomson M, et al. Soft tissue sarcomas in dogs: a study assessing surgical margin, tumour grade and clinical outcome. Aust Vet Pract 2004;34:158163.

    • Search Google Scholar
    • Export Citation
  • 25

    Heller DA, Stebbins ME, Reynolds TL, et al. A retrospective study of 87 cases of canine soft tissue sarcomas, 1986–2001. Int J Appl Res Vet Med 2005;3:8187.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 564 0 0
Full Text Views 969 671 87
PDF Downloads 611 334 28
Advertisement