TRANSCUTANEOUS OXIMETRY MAY PREDICT WOUND HEALING COMPLICATIONS IN PREOPERATIVELY RADIATED SOFT TISSUE SARCOMA Lukas M. Nystrom, MD, Benjamin J. Miller, MD, MS
ABSTRACT Background: Preoperative radiation is frequently used in management of soft tissue sarcoma. We hypothesize that anoxic tissue from preoperative radiation contributes to surgical wound complications and that transcutaneous oximetr y (TcO2) measurements made preoperatively can predict wounds at risk. Methods: Ten consecutive patients were prospectively enrolled. TcO2 was recorded at five time points. Wound complications (defined as major or minor) and healing outcomes were recorded out to 120 days postoperatively. Means between groups with and without wound complications were compared by use of a Student’s t-test (p < 0.05). Results: There were three major and one minor wound complication. During the time from radiation to surgery, patients with wound complications had a 13.1 mmHg decrease in mean TcO2 while those who healed uneventfully had an increase of 2.3 mm Hg (p=0.09). Patients with complications had a low preoperative TcO2 of 18.7 mmHg compared to those without complications (18.7 vs. 33.4 mmHg; p=0.09). No patient with a TcO2 greater than 25 mmHg immediately preoperatively developed a wound complication. Conclusions: This data suggests an earlier recovery of tissue oxygenation in patients that healed without complication. The TcO2 measurement immediately preceding surger y seems to be the most important in predicting wound complications. Corresponding Author: Lukas M. Nystrom, MD Department of Orthopaedic Surgery and Rehabilitation Loyola University Chicago, Cardinal Bernardin Cancer Center 2160 South First Avenue Maywood, IL 60153 Phone: (708) 216-1274 Fax: (708) 216-5858 Email: [email protected] Investigation Performed at the University of Iowa Conflict of Interest Statement: Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. This study was approved by the Institutional Review Board at the University of Iowa.
Larger scale investigation may determine if TcO2 measurement is a viable clinical tool to aid in risk assessment for potential wound complications. INTRODUCTION Radiation combined with surgical resection is considered the standard of care in the treatment of most soft tissue sarcomas. Preoperative radiation is often preferred as it requires a lower treatment dose, smaller treatment field size, and resultant improved function in the spared limb1. Furthermore, it may potentiate limb salvage by allowing safe marginal resection along vital neurovascular structures and bone2. The benefits of preoperative radiation, compared to postoperative, come at the cost of an increased wound healing complication rate1,3-5. One of the most widely cited studies in sarcoma literature notes a complication rate of 35% in preoperatively radiated surgical wounds in the lower extremity1. What is less well understood is which patients are at risk of developing wound complications and what factors may contribute to those complications. This lack of knowledge is a barrier to progress in improving wound outcomes in patients with soft tissue sarcoma treated with preoperative radiation. We hypothesized that anoxic tissue from preoperative radiation may contribute to surgical wound complications and that TcO2 measurements made preoperatively can predict wounds at risk. To investigate this hypothesis we identified two primary questions: 1) Does radiation negatively affect skin oxygenation and does radiated tissue predictably recover its skin oxygenation during the rest period from the time of radiation completion to surgical resection and 2) Do low transcutaneous oxygen measurements correlate with wound healing complications? METHODS This study was designed as a pilot project to establish a proof of concept for a future larger scale prospective clinical trial. As such, sample size was not based upon a power analysis but rather on the economic and temporal feasibility of patient accrual. The study was conducted at a single academic tertiary referral center over a 12 month time period. This investigation was given full board approval by the institutional review board at the University of Iowa. Volume 36 117
L. M. Nystrom, B. J. Miller Table I. Patient/tumor characteristics treatment variables and wound outcomes for the entire patient cohort. Patient
Age (years)
Size (cm)
Location
Grade
Time to Surg (days)
Rest Period Mean Change (mmHg)
Low Pre-Op (mmHg)
Flap
Complication
1
35
14.3
Deep
High
27
0.2
36.1
No
No
2
44
13.7
Deep
High
28
17.2
56.9
No
No
3
48
5.4
Superficial
High
25
-10.5
15.0
Yes
No
4
64
27.3
Deep
High
34
5
20
22.0
Deep
High
21
6
72
30.6
Deep
High
30
7
56
5.5
Deep
High
24
8
61
11.7
Deep
Low
36
9
70
16.2
Deep
High
29
10
55
12.7
Average
52.5
15.9
Deep
High
29 28.3
All patients with a suspected lower extremity soft tissue sarcoma were staged with appropriate imaging and confirmatory biopsy. The study concept was discussed with eligible patients at the time of diagnosis and enrollment was offered following a multidisciplinary team recommendation for preoperative radiation followed by limb sparing surgical resection. Criteria for inclusion were age 18 or older, treatment with preoperative radiation, and tumor amenable to limb salvage surgery. Exclusion criteria were patients with upper extremity or trunk sarcoma, patients with prior open surgical intervention to the area (excluding incisional biopsy), prior radiation in the area of the surgical site, recurrent soft tissue sarcoma, and patients with a known vascular disorder requiring prior intervention to the affected limb. During the one year period for study enrollment, there were 10 patients eligible for enrollment and all agreed to participate. All 10 patients completed followup at a minimum of 120 days postoperatively and were included in the analysis. All wounds had healed at the time of final follow-up. Due to the pilot study design and limited availability of funds, the study was ended as planned after the enrollment of the tenth patient. The average age of the patient cohort was 52.5 ± 15.4 years. There were seven male and three female patients (Table I). Average tumor size was 15.9 ± 8.0 cm in the maximal dimension. There were nine tumors that were subfascial and a single tumor that was superficial. All but one sarcoma was high grade. Average time from completion of radiation to surgical resection was 28.3 days. Following enrollment, all patients were treated at the senior author’s (BJM) institution with a standard dose of 50 Gray (Gy) of preoperative external beam radiation 118 The Iowa Orthopedic Journal
20.4
No
Minor
23.2
48.9
No
No
-7.4
16.4
No
Major
22.4
No
Major
-17.6
19.8
No
No
1.2
23.8
No
No
-6.1
-26.1
-12.8 -3.9
15.7 27.5
No
Major
Complication Type n/a
n/a n/a
Wound Drainage n/a
Deep Infection Infected Hematoma n/a
n/a
Radiation Necrosis
given in 25 fractions over a five week period. At the conclusion of radiation, surgery was scheduled following a four week “rest period” to allow for tissue recovery. All patients were treated by the same surgeon (BJM) with a standard wound closure protocol which consisted of a layered closure over a deep suction drain and nonabsorbable 2-0 monofilament vertical mattress suture for the skin layer. All patients were treated with 24 hours of perioperative cefazolin, clindamycin or vancomycin depending on their penicillin allergy and screening methicillin resistant Staphylococcus aureus (MRSA) status. Drains were left in place until output was less than 30 milliliters (mL) per 8-hour shift for three consecutive shifts. Sutures were left in place for a minimum of four weeks. One patient was treated with a planned rotational muscle flap and skin graft at the time of sarcoma resection. No other flaps or skin grafts were utilized, and all other wounds were closed primarily. All participants were followed for a minimum of 120 days postoperatively to assess their wound outcome. If a patient experienced a wound complication, it was treated according to the surgeon’s best judgment. Wound complications were defined as major or minor. Major complications included all those requiring unplanned operative wound management (irrigation and debridement, revision wound closure, skin graft, or flap), readmission for intravenous antibiotics, and need for dressing changes or wound packing for beyond 120 days postoperatively. Minor complications were defined as need for aspiration of a seroma, need for oral antibiotics, and need for dressing changes or wound packing for greater than four weeks. Oxygen sensors were placed at five locations on the operative site based on the planned incision drawn
Transcutaneous Oximetry May Predict Wound Healing Complications
Figure 1. A clinical photograph demonstrating the placement of leads around a planned incision for resection of a medial thigh soft tissue sarcoma. The red line demonstrates the planned incision.
by the surgeon. One lead was placed centrally on the planned incision and two leads were placed at both the proximal and distal extent of the planned incision and spread approximately 3-5 cm from the incision (Figure 1). Photographs were taken at the time of the initial measurement to ensure consistent lead placement for subsequent measurements. An additional lead was placed on the contralateral limb (corresponding the central lead), serving as a control measurement. TcO2 was measured and recorded in millimeters of mercury (mmHg). The measurements were taken by a hyperbaric oxygen lab technician trained in the use of the transcutaneous oximA Given that there were five leads on the operative eter. extremity, analysis was performed for the average of all five leads, as well as the lowest recording from any of the five leads. TcO2 was measured at five time points across the patient’s treatment course: prior to the start of radiation, during the middle of radiation therapy (day 12 or 13), at the conclusion of radiation therapy, immediately preoperatively, and two weeks following surgical resection. Patients were seen in follow-up at two weeks, six weeks, and three to four months postoperatively, as well as when needed for further wound follow-up. The finalTcO2 measurement was taken at the two week postoperative visit. All patients were also seen routinely for further sarcoma surveillance after the immediate postoperative period, which extended beyond their commitment to the study protocol.
Figure 2. This chart demonstrates the change in the mean TcO2 measurement for each time inter val for the whole patient series (black), as well as divided between cohorts with (diagonal lines) and without (gray) complications. Inter val 1 represents the time from start of radiation to the middle of radiation. Inter val 2 represents the time from middle of radiation to completion of radiation. Inter val 3 (the “rest period”) represents the time from completion of radiation to immediately prior to surgical resection. Lastly, inter val 4 represents the time from immediately preoperative to two weeks postoperative.
A two-tailed Student’s t-test was used to compare the mean TcO2 of for patients with complications and those that healed uneventfully. Statistical significance was defined as a p-value of
ABSTRACT Background: Preoperative radiation is frequently used in management of soft tissue sarcoma. We hypothesize that anoxic tissue from preoperative radiation contributes to surgical wound complications and that transcutaneous oximetr y (TcO2) measurements made preoperatively can predict wounds at risk. Methods: Ten consecutive patients were prospectively enrolled. TcO2 was recorded at five time points. Wound complications (defined as major or minor) and healing outcomes were recorded out to 120 days postoperatively. Means between groups with and without wound complications were compared by use of a Student’s t-test (p < 0.05). Results: There were three major and one minor wound complication. During the time from radiation to surgery, patients with wound complications had a 13.1 mmHg decrease in mean TcO2 while those who healed uneventfully had an increase of 2.3 mm Hg (p=0.09). Patients with complications had a low preoperative TcO2 of 18.7 mmHg compared to those without complications (18.7 vs. 33.4 mmHg; p=0.09). No patient with a TcO2 greater than 25 mmHg immediately preoperatively developed a wound complication. Conclusions: This data suggests an earlier recovery of tissue oxygenation in patients that healed without complication. The TcO2 measurement immediately preceding surger y seems to be the most important in predicting wound complications. Corresponding Author: Lukas M. Nystrom, MD Department of Orthopaedic Surgery and Rehabilitation Loyola University Chicago, Cardinal Bernardin Cancer Center 2160 South First Avenue Maywood, IL 60153 Phone: (708) 216-1274 Fax: (708) 216-5858 Email: [email protected] Investigation Performed at the University of Iowa Conflict of Interest Statement: Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. This study was approved by the Institutional Review Board at the University of Iowa.
Larger scale investigation may determine if TcO2 measurement is a viable clinical tool to aid in risk assessment for potential wound complications. INTRODUCTION Radiation combined with surgical resection is considered the standard of care in the treatment of most soft tissue sarcomas. Preoperative radiation is often preferred as it requires a lower treatment dose, smaller treatment field size, and resultant improved function in the spared limb1. Furthermore, it may potentiate limb salvage by allowing safe marginal resection along vital neurovascular structures and bone2. The benefits of preoperative radiation, compared to postoperative, come at the cost of an increased wound healing complication rate1,3-5. One of the most widely cited studies in sarcoma literature notes a complication rate of 35% in preoperatively radiated surgical wounds in the lower extremity1. What is less well understood is which patients are at risk of developing wound complications and what factors may contribute to those complications. This lack of knowledge is a barrier to progress in improving wound outcomes in patients with soft tissue sarcoma treated with preoperative radiation. We hypothesized that anoxic tissue from preoperative radiation may contribute to surgical wound complications and that TcO2 measurements made preoperatively can predict wounds at risk. To investigate this hypothesis we identified two primary questions: 1) Does radiation negatively affect skin oxygenation and does radiated tissue predictably recover its skin oxygenation during the rest period from the time of radiation completion to surgical resection and 2) Do low transcutaneous oxygen measurements correlate with wound healing complications? METHODS This study was designed as a pilot project to establish a proof of concept for a future larger scale prospective clinical trial. As such, sample size was not based upon a power analysis but rather on the economic and temporal feasibility of patient accrual. The study was conducted at a single academic tertiary referral center over a 12 month time period. This investigation was given full board approval by the institutional review board at the University of Iowa. Volume 36 117
L. M. Nystrom, B. J. Miller Table I. Patient/tumor characteristics treatment variables and wound outcomes for the entire patient cohort. Patient
Age (years)
Size (cm)
Location
Grade
Time to Surg (days)
Rest Period Mean Change (mmHg)
Low Pre-Op (mmHg)
Flap
Complication
1
35
14.3
Deep
High
27
0.2
36.1
No
No
2
44
13.7
Deep
High
28
17.2
56.9
No
No
3
48
5.4
Superficial
High
25
-10.5
15.0
Yes
No
4
64
27.3
Deep
High
34
5
20
22.0
Deep
High
21
6
72
30.6
Deep
High
30
7
56
5.5
Deep
High
24
8
61
11.7
Deep
Low
36
9
70
16.2
Deep
High
29
10
55
12.7
Average
52.5
15.9
Deep
High
29 28.3
All patients with a suspected lower extremity soft tissue sarcoma were staged with appropriate imaging and confirmatory biopsy. The study concept was discussed with eligible patients at the time of diagnosis and enrollment was offered following a multidisciplinary team recommendation for preoperative radiation followed by limb sparing surgical resection. Criteria for inclusion were age 18 or older, treatment with preoperative radiation, and tumor amenable to limb salvage surgery. Exclusion criteria were patients with upper extremity or trunk sarcoma, patients with prior open surgical intervention to the area (excluding incisional biopsy), prior radiation in the area of the surgical site, recurrent soft tissue sarcoma, and patients with a known vascular disorder requiring prior intervention to the affected limb. During the one year period for study enrollment, there were 10 patients eligible for enrollment and all agreed to participate. All 10 patients completed followup at a minimum of 120 days postoperatively and were included in the analysis. All wounds had healed at the time of final follow-up. Due to the pilot study design and limited availability of funds, the study was ended as planned after the enrollment of the tenth patient. The average age of the patient cohort was 52.5 ± 15.4 years. There were seven male and three female patients (Table I). Average tumor size was 15.9 ± 8.0 cm in the maximal dimension. There were nine tumors that were subfascial and a single tumor that was superficial. All but one sarcoma was high grade. Average time from completion of radiation to surgical resection was 28.3 days. Following enrollment, all patients were treated at the senior author’s (BJM) institution with a standard dose of 50 Gray (Gy) of preoperative external beam radiation 118 The Iowa Orthopedic Journal
20.4
No
Minor
23.2
48.9
No
No
-7.4
16.4
No
Major
22.4
No
Major
-17.6
19.8
No
No
1.2
23.8
No
No
-6.1
-26.1
-12.8 -3.9
15.7 27.5
No
Major
Complication Type n/a
n/a n/a
Wound Drainage n/a
Deep Infection Infected Hematoma n/a
n/a
Radiation Necrosis
given in 25 fractions over a five week period. At the conclusion of radiation, surgery was scheduled following a four week “rest period” to allow for tissue recovery. All patients were treated by the same surgeon (BJM) with a standard wound closure protocol which consisted of a layered closure over a deep suction drain and nonabsorbable 2-0 monofilament vertical mattress suture for the skin layer. All patients were treated with 24 hours of perioperative cefazolin, clindamycin or vancomycin depending on their penicillin allergy and screening methicillin resistant Staphylococcus aureus (MRSA) status. Drains were left in place until output was less than 30 milliliters (mL) per 8-hour shift for three consecutive shifts. Sutures were left in place for a minimum of four weeks. One patient was treated with a planned rotational muscle flap and skin graft at the time of sarcoma resection. No other flaps or skin grafts were utilized, and all other wounds were closed primarily. All participants were followed for a minimum of 120 days postoperatively to assess their wound outcome. If a patient experienced a wound complication, it was treated according to the surgeon’s best judgment. Wound complications were defined as major or minor. Major complications included all those requiring unplanned operative wound management (irrigation and debridement, revision wound closure, skin graft, or flap), readmission for intravenous antibiotics, and need for dressing changes or wound packing for beyond 120 days postoperatively. Minor complications were defined as need for aspiration of a seroma, need for oral antibiotics, and need for dressing changes or wound packing for greater than four weeks. Oxygen sensors were placed at five locations on the operative site based on the planned incision drawn
Transcutaneous Oximetry May Predict Wound Healing Complications
Figure 1. A clinical photograph demonstrating the placement of leads around a planned incision for resection of a medial thigh soft tissue sarcoma. The red line demonstrates the planned incision.
by the surgeon. One lead was placed centrally on the planned incision and two leads were placed at both the proximal and distal extent of the planned incision and spread approximately 3-5 cm from the incision (Figure 1). Photographs were taken at the time of the initial measurement to ensure consistent lead placement for subsequent measurements. An additional lead was placed on the contralateral limb (corresponding the central lead), serving as a control measurement. TcO2 was measured and recorded in millimeters of mercury (mmHg). The measurements were taken by a hyperbaric oxygen lab technician trained in the use of the transcutaneous oximA Given that there were five leads on the operative eter. extremity, analysis was performed for the average of all five leads, as well as the lowest recording from any of the five leads. TcO2 was measured at five time points across the patient’s treatment course: prior to the start of radiation, during the middle of radiation therapy (day 12 or 13), at the conclusion of radiation therapy, immediately preoperatively, and two weeks following surgical resection. Patients were seen in follow-up at two weeks, six weeks, and three to four months postoperatively, as well as when needed for further wound follow-up. The finalTcO2 measurement was taken at the two week postoperative visit. All patients were also seen routinely for further sarcoma surveillance after the immediate postoperative period, which extended beyond their commitment to the study protocol.
Figure 2. This chart demonstrates the change in the mean TcO2 measurement for each time inter val for the whole patient series (black), as well as divided between cohorts with (diagonal lines) and without (gray) complications. Inter val 1 represents the time from start of radiation to the middle of radiation. Inter val 2 represents the time from middle of radiation to completion of radiation. Inter val 3 (the “rest period”) represents the time from completion of radiation to immediately prior to surgical resection. Lastly, inter val 4 represents the time from immediately preoperative to two weeks postoperative.
A two-tailed Student’s t-test was used to compare the mean TcO2 of for patients with complications and those that healed uneventfully. Statistical significance was defined as a p-value of
