What are the Results of Surgical Treatment of Postoperative Wound Complications in Soft Tissue Sarcoma? A Retrospective, Multi-Center Case Series

Abstract

Background

Non-oncologic wound complications are common following resection of soft tissue sarcomas and factors predisposing to the development of complications have been extensively studied. To our knowledge, the methods and results of surgical treatment of these complications have not been reported. The purposes of this study were to 1) identify time to recognition, treatment employed, and eventual outcome of complications 2) investigate risk factors that may predispose patients to failure in management of complications following resection of soft tissue sarcomas.

Methods

This was a multi-institutional, retrospective case series of patients treated with a primary closure of a limb sparing resection of a soft tissue sarcoma of the pelvis or extremity who developed a non-oncologic wound complication requiring operative intervention. The primary outcomes were a healed wound at the end of treatment and the total number of procedures required to address the complication.

Results

There were 61 patients from 11 institutions included in the analysis. The median time from surgery to the initial recognition of a complication was 22 days (range 0-173 days), with 51 patients (84%) presenting in the first six weeks postoperatively. The definitive procedures included primary closure (44), healing by secondary intention (9), muscle flap (6), and skin graft (2). No patient was treated with an amputation. Six patients (10%) had a wound requiring continued dressing changes. 12 patients (20%) required at least one (range 1-4) additional unplanned procedure. In a bivariate analysis, we found patients with an infection were at increased risk of requiring multiple unplanned procedures (p=0.024).

Conclusion

Limb sparing resection of a soft tissue sarcoma is known to be at high risk of postoperative wound complications. We found that complications uncommonly present greater than six weeks after initial treatment and surgical management predictably results in retention of the affected limb and a healed wound in those requiring operative treatment.

Level of Evidence: 4 – Case Series

Introduction

There is little debate that the optimal treatment of soft tissue sarcoma includes complete surgical resection of the primary tumor. These procedures are associated with a high rate of non-oncologic wound complications such as infection, wound dehiscence, necrosis, hematoma, and seroma, and have been estimated at an incidence of 16-53%.^1-4 The increased risk of wound complications is due to many factors specific to the patient (age, medical comorbidities, obesity, smoking), tumor (size, location), and treatment (adjuvant radiation).^2,5-7 Although the risk factors for postoperative wound complications have been extensively studied and are well known, the methods and results of surgical treatment of these complications, to our knowledge, have not been reported.

A clear understanding of the results of treatment following the development of a postoperative wound complication is important to practitioners and patients alike. For surgeons, guidance regarding the types, expected outcomes, and success rates of interventions can help with decision-making, procedural choices, and patient counseling. For patients, postoperative wound complications come at a time that is physically and emotionally difficult, as they have all recently experienced a cancer diagnosis and are currently recovering from a significant surgical procedure. Accurately defining the goals of treatment of wound complications may help alleviate anxiety and disappointment by providing appropriate expectations of the remaining clinical course and ultimate result.

In order to further define the results of surgical management of wound complications in soft tissue sarcoma, we sought to 1) identify the time to complication, treatment employed, and eventual outcome of wound complications and 2) investigate risk factors that may predispose patients to failure in complication management.

Materials and Methods

This was a multi-institutional, retrospective case series of patient data from December 1, 2009 to November 30, 2014. Thirteen fellowship-trained orthopaedic oncologists at 11 institutions submitted de-identified patient data. The institutions contributed a median of three patients (range 1- 18 patients). Patients were followed until death, clear documentation of a healed wound, or for at least six months after the primary procedure.

We included all patients treated with a primary closure of a limb sparing resection of a soft tissue sarcoma of the pelvis or extremity who developed a non-oncologic wound complication requiring operative intervention. Of note, we were interested only in patients who experienced a wound complication necessitating surgical intervention; we did not collect any patients who did not experience a wound complication, or those who had a wound complication but were treated non-operatively. We excluded patients who were treated with a soft tissue reconstruction (free flap, fasciocutaneous rotational flap, or skin graft) at the time of tumor resection, infections present at time of resection, use of prosthesis or allograft, and atypical lipomatous tumors. Rotational muscle flaps to fill a defect were permitted provided that the wound was closed primarily.

Patients were identified, and patient data was entered, by the participating institutions into a de-identified Research Electronic Data Capture (REDCap) database managed by the primary research team. The primary research team commonly would clarify discrepancies or incomplete entries with the site investigators to ensure appropriate inclusion criteria and recording of outcomes, but did not have the ability to confirm the exact details of patient or treatment data through examination of medical records.

We recorded patient (age, sex, body mass index, Age-Adjusted Charlson Comorbidity Index Score), tumor (histology, size, grade, location, depth, primary or recurrent), and treatment (chemotherapy, preoperative radiation) factors. The type of complication was defined as an infection (a wound with gross purulence, positive cultures, or labeled as an infection by the treating surgeon), wound dehiscence/ necrosis (a wound that was open, draining, necrotic, or non-healing and thought to be attributed to underlying aseptic tissue compromise), or a hematoma/seroma (a wound with a large fluid collection and/ or drainage not attributable to underlying infection or tissue compromise). Any wound labeled as an infection by the treating surgeon, regardless of the presence of necrosis or hematoma/seroma, was categorized as such; any wound without concern for infection but with a wound dehiscence or necrosis was labeled as “dehiscence/necrosis.” Only wounds without underlying infection or tissue compromise were categorized as “seroma/hematoma.” The primary outcomes were 1) a healed wound at the end of treatment and 2) the total number of additional unplanned procedures required to address the complication. Secondary outcomes included the time from the initial tumor resection to the recognition of the wound complication and the time from recognition of the complication to the surgical intervention to address it.

Contributing centers recorded the type of procedure utilized to address the complication, specifically a repeat primary closure, debridement with healing by secondary intention, skin graft, muscle flap, or amputation. Presence of a healed wound was entrusted to the subjective judgment of the treating surgeon, but was defined as an epithelialized surgical incision or tumor bed not requiring dressing changes. In addition, each center recorded the number of procedures needed to finally address the complication. We queried specifically if the treatment included a planned multiple-stage debridement, which was analyzed as if it were only one procedure. This was to clearly distinguish between an “unplanned” return to the operating room to address the complication. The follow-up regimens were not standardized and were at the discretion of the treating surgeon. We also recorded the use of anticoagulation, antibiotics, and surgical drains in the perioperative and postoperative time periods. However, due to extreme variability in the method and duration of these interventions, and the small apparent effect they had on the success of complication management, we decided not to include them in the final analysis.

We performed a descriptive analysis to report the time to surgical treatment, modalities of surgical treatment, and final wound status. One-tailed bivariate methods (chi-square and Fisher’s exact testing) were used to investigate clinical associations that resulted in failure of wound healing or requirement of multiple unplanned procedures. Calculations were performed with SAS ® software, version 9.4 (SAS Institute, Inc. of Cary, North Carolina).

There were 61 patients from 11 institutions included in the analysis. The median age of the cohort was 67 years old (range 14-96 years old) with a median length of follow-up of 13.3 months (range 0.4-65.8 months) from the time of the final procedure, and 14.7 months (1.3-66.5 months) from the time of tumor removal. 31 patients were male and 30 were female. The mean BMI was 30.9 (standard deviation 8.9) with a mean Age Adjusted Charlson Comorbidity of 5.2 (standard deviation 2.8). Age adjusting was done by adding one point for each decade over 50 years old.⁸ The median tumor size was nine centimeters (range 1.3-32 centimeters). 50 tumors were deep and 11 were superficial. Patients presented with 54 primary and seven recurrent tumors.

Tumors were located in the thigh (41), leg (4), pelvis (4), hip (4), knee (4), foot (1), chest/axilla (1), shoulder (1) and arm (1). Histologic diagnoses included undifferentiated pleomorphic sarcoma (25), liposarcoma (11), leiomyosarcoma (6), myxofibrosarcoma (6), malignant peripheral nerve sheath tumor (3), synovial sarcoma (3), chondrosarcoma (2), angiosarcoma (1), epithelioid sarcoma (1), fibrosarcoma (1), fibromyxoid sarcoma (1), and rhabdomyosarcoma (1). 39 were high-grade, 15 were intermediate-grade, and seven were low-grade. 32 patients were treated with preoperative radiation and 11 were treated with perioperative chemotherapy.

Results

The median time from surgery to the initial recognition of a complication was 22 days (range 0- 173 days), with 51 patients (84%) presenting in the first six weeks. The median time from the recognition of a complication to surgery was five days (range 0-219 days). The complications treated included infection (32), wound dehiscence/ necrosis (23), and seroma/hematoma (6).

The definitive procedures included primary closure (44), debridement with healing by secondary intention (9), muscle flap (6), and skin graft (2). No patient was treated with an amputation to manage the wound complication. Six patients (10%) had a non-healed wound requiring continued dressing changes after the treatment of dehiscence/ necrosis (3) or infection (3). In these patients, the median time of follow-up from the time of the final procedure was 5.8 months (range 0.9-39.5 months). Four of these patients died prior to wound healing, two patients are currently alive 6.4 and 39.5 months after the last procedure. 12 patients (20%) required at least one (median 2 [range 1-4]) additional unplanned procedure to address an infection (10) or hematoma/seroma (2). Eight patients had a planned two-stage procedure (six for infection and two for dehiscence/ necrosis), all but one of whose wounds healed without further complication.

In a bivariate analysis, we found patients with an infection were at increased risk of requiring multiple unplanned procedures (p=0.024). No other factors, including patient age, delays of treatment, type of complication, use of preoperative radiation, tumor location, or tumor size appeared to have any meaningful influence on wound healing or unplanned procedures following the development of a wound complication (Table I).

Table I.

Risk factors for multiple unplanned procedures an non-healed wounds

	Risk factor	One or multiple planned procedures	Multiple unplanned procedures	p value	Healed	Not healed	p value
	Patient age
	≥65	28	5	0.335	28	5	0.205
	<65	21	7		27	1
	BMI
	≥30	23	4	0.522	25	2	0.685
	<30	26	8		30	4
	Location
	Proximal thigh	11	4	0.467	12	3	0.152
	Other	38	8		43	3
	Size
	≥10 cm	24	5	0.649	25	4	0.411
	<10 cm	25	7		30	2
	Depth
	Deep	39	11	0.438	46	4	0.294
	Superficial	10	1		9	2
	Radiation
	Preop	27	6	0.751	29	4	0.678
	Not preop	22	6		26	2
	Delay in treatment
	>2 weeks	11	2	1.000	12	1	1.000
	≤2 weeks	38	10		43	5
	Cause
	Infection	22	10	0.004	29	3	0.836
	Dehiscence	23	0		20	3
	Seroma	4	2		6	0

Discussion

Limb sparing resection of a soft tissue sarcoma is known to be a procedure with a high risk of postoperative wound complications. Although there are several studies illustrating the incidence and risk factors for postoperative wound complications, we are unaware of any investigation that identifies the surgical treatment and eventual outcome of these complications. Our results showed that the majority of complications arise within six weeks of resection and were successfully treated with a single-stage debridement and primary closure. In patients with an infection, there was an increased likelihood of requiring more than one procedure to address the complication.

This study had a number of limitations that warrant further discussion. First, our inclusion criteria limited the investigation to patients that required operative intervention to address a complication. Therefore, we do not have any knowledge of the outcome or successful treatment of complications that were able to be treated non-operatively. There were also no standard criteria to objectively determine which complications required an operation, and this decision was left to each individual surgeon. This resulted in some variability in patient selection and introduced a source of bias that is not easily mitigated. Second, heterogeneity in perioperative and postoperative decision-making by the individual practitioner, including the type of procedure, use of antibiotics, thromboembolic prophylaxis, negative pressure wound therapy, and drains may have led to variation in the incidence of wound complications or the successful treatment of those complications that we were not able to detect. Finally, the research team did not have access to the complete medical records of each patient, and the accuracy of data collection was dependent on the investigators at each site individually. In a retrospective, multi-institutional project dependent on the tendencies of individual practitioners, there is assumed to be some heterogeneity of treatment decisions and follow-up protocols, but it does not detract from the summary of our overall findings.

Postoperative wound complications are adverse events common to all surgical procedures. Soft tissue sarcoma resection is known to have a substantially higher risk of wound problems than many routine elective procedures, likely resulting from unique challenges such as large surgical wounds, post-resection tissue voids, thin skin flaps, and use of adjuvant radiation.^9-10 An estimated 16-53% ^1-4 of soft tissue sarcoma resections develop complications that require some form of additional management, but no report of which we are aware has discussed the results of subsequent surgical intervention. In our series, the postoperative complications consisted of infection (52%, 32/61), dehiscence/necrosis (38%, 23/61), and hematoma/seroma (10%, 6/61). We found that 84% of the complications arose within six weeks of surgery. All patients in this cohort retained the affected extremity, and the majority of patients (90%) had a healed wound at the time of death or last follow-up, although 20% required at least one additional unplanned procedure to effectively address the complication. Taken together, this information provides assistance to the treating physician when counseling patients by identifying the common etiologies, timing, and eventual outcome of wound complications.

The risk factors for developing a complication after soft tissue sarcoma resection have been previously described, and include older patient age,³ large tumor size,¹¹ tumors deep to the muscle fascia,¹ location in the lower extremity,¹² and preoperative radiation.¹³ Once a wound complication has developed and the treating physician has deemed it necessary to return to the operating room, we did not find definitive evidence that these same factors influenced the ability to obtain a healed wound in a single procedure. Furthermore, it did not appear that delays in management after the recognition of the complication increased the likelihood of multiple surgical procedures or a non-healed wound, which is consistent with prior research.¹⁴ This finding suggests that an initial attempt at nonsurgical management does not negatively alter the subsequent surgical course or eventual outcome.

We did find an association between infections and multiple unplanned surgical procedures, (10/32 patients with an infection required multiple unplanned procedures compared to 2/29 aseptic complications, p = 0.024). While aseptic complications were often successfully managed in a single intervention, infections pose an additional challenge by requiring eradication of a pathologic organism in addition to obtaining healing in compromised tissue. Infections in sarcoma patients specifically are difficult clinical scenarios, as there is often a substantial amount of necrosis from radiation or ischemia that requires extensive debridement. There were six patients with an infection who were treated with a planned two-stage (5) or three-stage (1) procedure. Although we do not know the details of the presentation, or objective measures used for decision-making, they were cases in which the treating surgeon felt there was extensive necrosis or the infection was significant enough that it was unlikely to be successfully managed in a single operation. Of the six patients with an infection treated with a planned multiple-stage debridement and closure, 5/6 (83%) went on to heal without further incident. Given the high rate of unplanned reoperations in patients with an infection treated with an attempted single-stage debridement (10/26 [38%]), a planned two-stage debridement may be an effective means to expedite healing and minimize that chances for failure in this scenario.

Conclusion

In conclusion, postoperative wound complications in soft tissue sarcoma resections, while common, are always an unfortunate event to patients and practitioners. Our findings detail the types of complications, timing of presentation, surgical modalities employed, and eventual outcome after surgical management. We believe this knowledge will enhance the ability of the treating surgeon to counsel patients both prior to surgery and after a complication develops. Our data demonstrate that a wound complication uncommonly presents greater than six weeks after treatment, and that assertive surgical management predictably results in limb retention and a healed wound in the substantial majority of patients needing operative treatment. Surgeons should be wary of postoperative infections, and may consider a planned multiple-stage approach to surgical management given the high rate of failure with an attempted single-stage debridement. Future research should focus on minimizing the incidence of wound complications. Strategies such as predicting wounds at risk,¹⁵ use of negative-pressure wound therapy,¹⁶ or selective closure with free tissue transfer are all additional avenues that may diminish the incidence of wound complications after resection.

Acknowledgments

The Musculoskeletal Oncology Research Initiative is an association of orthopaedic oncologists unified in the mission of improving patient care through collaborative research. The participating members of the Musculoskeletal Oncology Research Initiative include: Adam Levin, MD (Johns Hopkins University), Tessa Balach, MD (University of Connecticut), Zeke Walton, MD and Lee Leddy, MD (Medical University of South Carolina), Emily Carmody, MD (University of Rochester), David Greenberg, MD (Saint Louis University), Raffi Avedian, MD (Stanford University), Kevin MacDonald, MD (Virginia Mason University), Andre Spiguel, MD (University of Florida), Rajani Rajiv, MD and Amanda Riggs, BS (The University of Texas Health Science Center at San Antonio), Krista Goulding, MD, Robert Turcotte, MD and Montaz Alaqeel, MD (McGill University).