Abstract
Background
Surgical wound-healing complications after tumor resections in tissue that has been preoperatively radiated are a major clinical problem. Most studies have reported that complications occur in more than 30% of patients undergoing such resections in the lower extremity. There is currently no available method to predict which patients are likely to have a complication. Transcutaneous oximetry has been identified in preliminary studies as potentially useful, but the available evidence on its efficacy for this application thus far is inconclusive.
Questions/purposes
(1) Does transcutaneous oximetry measurement below 25 mmHg at any location in the surgical wound bed predict a wound-healing complication? (2) Does recovery (increase) in transcutaneous oxygen measurement during the rest period between the end of radiation and the time of surgery protect against wound-healing complications?
Methods
A prospective, multi-institution study was coordinated to measure skin oxygenation at three timepoints in patients undergoing surgery for a lower extremity soft tissue sarcoma after preoperative radiation. Between 2016 and 2020, the five participating centers treated 476 patients for lower extremity soft tissue sarcoma. Of those, we considered those with a first-time sarcoma treated with radiation before limb salvage surgery as potentially eligible. Based on that, 21% (98 of 476) were eligible; a further 12% (56 of 476) were excluded because they refused to participate or ultimately, they were treated with a flap, amputation, or skin graft. Another 1% (3 of 476) of patients were lost because of incomplete datasets or follow-up less than 6 months, leaving 8% (39 of 476) for analysis here. The mean patient age was 62 ± 14 years, 62% (24 of 39) of the group were men, and 18% (7 of 39) of patients smoked cigarettes; 87% (34 of 39) of tumors were intermediate/high grade, and the most common histologic subtype was undifferentiated pleomorphic sarcoma. In investigating complications, a cutoff of 25 mmHg was chosen based on a pilot investigation that identified this value. All patients were assessed for surgical wound-healing complications, which were defined as: those resulting in a return to the operating room, initiation of oral or IV antibiotics, intervention for seroma, or prolonged wound packing or dressing changes. To answer the first research question, we compared the proportion of patients who developed a wound-healing complication between those patients who had any reading below 25 mmHg (7 of 39) and those who did not (32 of 39). To answer the second question, we compared the group with stable or decreased skin oxygenation (22 of 37 patient measurements [two patients missed the immediate postoperative measurement]) to the group that had increased skin oxygen measurement (15 of 37 measurements) during the period between the end of radiation and the surgical procedure; again, the endpoint was the development of a wound-healing complication. This study was powered a priori to detect an unadjusted odds ratio for wound-healing complications as small as 0.71 for a five-unit (5 mmHg) increase in TcO2 between the groups, with α set to 0.05, β set to 0.2, and a sample size of 40 patients.
Results
We found no difference in the odds of a wound-healing complication between patients whose transcutaneous oxygen measurements were greater than or equal to 25 mmHg at all timepoints compared with those who had one or more readings below that threshold (odds ratio 0.27 [95% confidence interval (CI) 0.05 to 1.63]; p = 0.15). There was no difference in the odds of a wound-healing complication between patients who had recovery of skin oxygenation between radiation and surgery and those who did not (OR 0.63 [95% CI 0.37 to 5.12]; p = 0.64).
Conclusion
Transcutaneous oximetry cannot be considered a reliable test in isolation to predict wound-healing complications. This may be a function of the fact that transcutaneous oximetry samples a relatively small portion of the landscape in which a wound-healing complication could potentially arise. In the absence of a reliable diagnostic test, clinicians must still use their best judgment regarding surgical timing and work to address modifiable risk factors to avoid complications. The unanswered question that remains is whether there is a skin perfusion or oxygenation issue at the root of these complications, which seems likely. Alternative approaches that can assess the wound more broadly and in real time, such as fluorescent probes, may be deserving of further investigation.
Level of Evidence
Level II, diagnostic study.
Introduction
Soft tissue sarcoma is most often treated with preoperative radiotherapy followed by surgery for local control [1, 8-10, 12]. Radiation is preferred before surgery, as the functional results of the salvaged limb have been demonstrated to be superior when compared with radiation administered after surgery [10, 13]. However, the advantages of preoperative radiation are accompanied by negative effects related to wound healing; an estimated 35% of all patients (and 43% of those who have lower extremity tumors) who receive preoperative radiation develop some form of a wound complication [13]. Most clinicians accept this consequence given that wound-healing complications usually are temporary and salvageable, and so they usually are superior to the permanent ill effects of a less-functional limb, which might be the result of postoperative radiation. There are no clinical criteria that we know of that can aid oncologic surgeons in determining an individual patient’s risk of developing a postoperative wound complication.
In a previously published pilot investigation [12], our group proposed using preoperative measurement of transcutaneous oxygen (TcO2) at the proposed incision site to classify patients into high-risk and low-risk categories for the development of wound complications after resection. Measuring preoperative TcO2 is a simple, noninvasive method to assess skin oxygenation. The pilot investigation suggested a correlation between transcutaneous oxygen measurements and wound-healing complications [11].
In that pilot investigation, no patients with a minimum TcO2 measurement above 25 mmHg experienced a wound-healing complication, and we also observed that patients who had any recovery of their skin oxygenation seemed to have better wound-healing outcomes [11]. However, that investigation evaluated only 10 patients, and so it may have been underpowered to detect a true difference. Given the observations in that pilot investigation, we believed that this important clinical problem is well suited for a prospective, multi-institutional investigation.
We asked: (1) Does transcutaneous oximetry measurement below 25 mmHg at any location in the surgical wound bed predict a wound-healing complication? (2) Does recovery (increase) in transcutaneous oxygen measurement during the rest period between the end of radiation and the time of surgery protect against wound-healing complications?
Patients and Methods
Study Design and Setting
The study was designed as a multi-institutional, prospective effort at five tertiary sarcoma referral centers (seven surgeons). Centers varied in the amount of soft tissue sarcoma treated annually, ranging from approximately 20 to 100 procedures annually.
Participants
All patients 18 years and older at the time of sarcoma diagnosis were invited to participate in the study if they met inclusion criteria. Inclusion criteria were a biopsy-proven, soft tissue sarcoma of the lower extremity, which would be treated with preoperative radiation followed by limb-salvage surgical excision with primary closure. Patients were treated with 50 Gy in 25 fractions of preoperative radiotherapy. This recommendation must have been submitted by a multidisciplinary sarcoma team that included a radiation oncologist. Exclusion criteria were patients with an upper extremity sarcoma, recurrent soft tissue sarcoma, previous surgery at the site of the sarcoma (other than a biopsy), previous radiation to the sarcoma site, surgical resections treated with immediate flap or skin graft coverage, tumors not addressed with radiation treatment, or patients who were unwilling to have radiation or surgical treatment. Between 2016 and 2020, the five participating centers treated 476 patients for lower extremity soft tissue sarcoma. Of those, we considered those with a first-time sarcoma treated with radiation before limb salvage surgery as potentially eligible. Based on that, 21% (98 of 476) were eligible; a further 12% (56 of 476) were excluded because they refused to participate or ultimately, they were treated with a flap, amputation, or skin graft. Another 1% (3 of 476) of patients were lost because of incomplete datasets or follow-up less than 6 months, leaving 8% (39 of 476) for analysis here. One of the three patients lost to follow-up was after the conclusion of the study period.
Patients’ Descriptive Data
The mean patient age was 62 ± 14 years, 62% (24 of 39) of patients were men, the mean BMI was 30.1 ± 7.6 kg/m2, and 18% (7 of 39) of the patients smoked cigarettes at the time of the study. A total of 87% (34 of 39) of patients had intermediate-grade or high-grade tumors, and 13% (5 of 39) of tumors were low-grade. Histologic subtypes were 46% (18 of 39) undifferentiated pleomorphic sarcomas, 21% (8 of 39) myxoid liposarcomas, 13% (5 of 39) myxofibrosarcomas, 13% (5 of 39) dedifferentiated liposarcomas, and 8% (3 of 39) other histologic subtypes.
Transcutaneous Oximetry
TcO2 measurements were obtained at three timepoints during the patient’s treatment course: before the start of radiation, immediately after radiation, and within 24 hours before the procedure (either the day before or the morning of the surgical resection). The rest period is defined as the time from the end of radiation to the time of surgery. This is typically in the range of 3 to 6 weeks. TcO2 measurements were performed in the vascular or hyperbaric center of each respective institution and were taken in consultation with the operating surgeon, who planned the incision. Although the specific device was institution-dependent, they were all calibrated devices maintained by the medical engineering department. Five leads were placed based on the line of the planned incision (Fig. 1). A control lead was placed on the contralateral limb in a location corresponding to the center lead on the operative limb.
Fig. 1.
A-B This schematic illustration shows the placement of leads along the surgical site for (A) longitudinal and (B) elliptical incisions. A color image accompanies the online version of this article.
Surgical Protocol
After preoperative external beam radiation therapy, limb-sparing surgical resection was performed at a time determined by the surgeon’s preference and a clinical examination of the skin’s condition between 3 and 6 weeks after radiation. The length of the incision and skin excision were determined at the discretion of the treating surgeon, with the goal of a negative-margin resection. Wound closure and management were determined at the discretion of the treating surgeon. Use of a wound vacuum-assisted closure device was at the discretion of the treating surgeon. The duration of the wound vacuum-assisted closure device, drain, and sutures were determined by the surgeon based on the appearance of the wound at routine postoperative visits.
The wound was assessed for healing status and the presence of any complications at 2 weeks, 6 weeks, 3 months, and 6 months postoperatively, as well as at any additional timepoints as needed. We selected wound complications that were severe enough to represent a major detractor to patient quality of life. As such, wound-healing complications were ascertained by the treating surgeon, defined as: any wound-related issue (necrosis, dehiscence, infection, seroma) treated by return to operating room, initiation of oral or intravenous (IV) antibiotics, intervention for seroma including aspiration, or prolonged wound packing or dressing changes greater than 120 days.
Primary and Secondary Study Outcomes
The primary study goal was to assess whether the presence of a wound-healing complication within 6 months of the surgical resection correlated with a transcutaneous oxygen measurement of less than 25 mmHg at any of the five leads at the surgical site. Based on the pilot analysis, we chose 25 mmHg as a dichotomous cutoff for a critical level of skin oxygenation to support wound healing. In that pilot investigation, none of the three patients who had all leads above 25 mmHg experienced a wound-healing complication, whereas four of seven who had a measurement below 25 mmHg experienced a complication. Patients with any lead measuring less than 25 mmHg were compared with the group with all leads greater than or equal 25 mmHg with respect to this outcome. The median (IQR) of the lowest lead TcO2 measurement in all patients was 43 mmHg (30 to 56 mmHg). Among patients with a wound that healed uneventfully, this value was 48 mmHg (IQR 37 to 59 mmHg) compared with 38.9 mmHg (25 to 50 mmHg) among patients who had a wound-healing complication. Eighteen percent (7 of 39) of patients had at least one lead with a preoperative measurement less than 25 mmHg. The wounds in two of those patients healed uneventfully, and five patients had wound-healing complications. By comparison, of the remaining 32 patients with all measurements greater than 25 mmHg, 59% (19) healed uneventfully and 41% (13) had a wound-healing complication.
The second study goal was to assess whether wound-healing complications correlated with recovery of skin oxygenation during the rest period, as defined previously. Patients who had either stable or decreased skin oxygenation were compared with those who had an increase in skin oxygenation. Two patients missed their immediate postoperative radiation measurement, and 37 patients had complete data for this time interval. The median (IQR) change in TcO2 from radiation to the time of surgery was -2.34 (-8.20 to 4.70) among all patients. This represents an average decrease in TcO2 during the rest period. Twenty-two patients had stable or decreased skin oxygenation; these patients formed the first group. They were compared with the 15 patients who had an increase in skin oxygenation.
Additional data collected for comparison included patient demographics; tumor size, grade, histologic subtype, and stage; and associated treatment variables including radiation dose, fractionation, and use of chemotherapy.
Forty-six percent (18 of 39) of patients in our series had a wound-healing complication, with some patients having more than one complication. There were nine infections (eight superficial, one deep), 13 wound dehiscence problems, and six seromas that were treated. Twenty-one percent (8 of 39) returned to the operating room for a wound-healing complication. Seventy-two percent (28 of 39) of wounds were completely healed at the 6-month timepoint, and all wounds healed eventually, with no patients returning to the operating room after 6 months to address a wound-related problem. There was no difference in the proportion of wound healing based on patient age, sex, BMI, tumor size, or smoking status (Table 1).
Table 1.
Summary of patient demographics, tumor volume, and transcutaneous oxygen data
| Parameter | Healed uneventfully (n = 21) | Wound healing complication (n = 18) | p value |
| Age in years | 67 (58 to 71) | 63 (48 to 71) | 0.42 |
| Weight in kg/m2 | 28 (25 to 31) | 30 (25 to 37) | 0.41 |
| Female sex | 38 (8) | 39 (7) | 0.99 |
| Nicotine use | 19 (4) | 17 (3) | 0.99 |
| Tumor volume | 848 (255 to 1364) | 945 (306 to 1698) | 0.59 |
| Preoperative TcO2 < 25 mmHg | 10 (2) | 28 (5) | 0.22 |
| TcO2 recovery (increase) during rest period | -2.34 (-8.00 to 4.37) | -2.36 (-12.44 to 4.33) | 0.99 |
Data presented as median (range) or % (n).
Ethical Approval
We obtained full ethical review board approval for this study at all participating sites.
Statistical Analysis
The wound complication rate in preoperatively radiated lower extremity sarcoma has been reported to be approximately 43% among a similar population [13]. Assuming that TcO2 is normally distributed with a mean of 54 ± 16 mmHg and the overall probability of a wound-healing complication is 43%, 40 patients needed to be evaluated to have an 80% chance of detecting an unadjusted OR as small as 0.71 for a five-unit (5 mmHg) increase in TcO2.
Continuous variables are summarized using medians, IQRs, or minimum and maximum. Categorical variables are summarized using percentages and numbers. First, a univariable logistic regression with TcO2 as a single predictor was built to investigate the relationship between TcO2 and wound healing at 6 months, between TcO2 and complications, and between TcO2 and return to the operating room. Furthermore, to preserve the power of continuous variables, similar models were refit using the continuous version of the TcO2 (minimum before surgery, mean before surgery, and mean change). Additionally, we investigated the univariable relationship with any complications based on age, sex, BMI, nicotine use, Charlson comorbidity index, and tumor volume. Model results are represented using odds ratios and 95% confidence intervals. Data management and analysis were done in R software, version 4.0 (R Foundation). All tests were two-sided, with an alpha level of 0.05.
Results
Does Transcutaneous Oximetry Measurement Below 25 mmHg at Any Point in the Surgical Wound Bed Predict a Wound-healing Complication?
We found no difference in the odds of a wound-healing complication between patients whose transcutaneous oxygen measurements were greater than or equal to 25 mmHg at all timepoints compared with those who had one or more readings below that threshold (OR 0.27 [95% CI 0.05 to 1.63]; p = 0.15) (Table 2). Additionally, evaluating the TcO2 lowest reading as a continuous variable rather than with the 25-mmHg cutoff, we similarly found no difference the odds of having a wound-healing complication with incremental increases in TcO2 (OR 0.97 [95% CI 0.94 to 1.01]; p = 0.13) (Table 3).
Table 2.
Comparison of TcO2 as a dichotomous variable between the low (< 25 mmHg) and high (≥ 25 mmHg) groups and change during the “rest period”a
| Variable | OR (95% CI) | p value |
| Any wound-healing complication | ||
| TcO2 lowest reading before surgery: high vs low | 0.27 (0.05-1.63) | 0.15 |
| TcO2 mean reading preoperatively: high vs low | 0.40 (0.03-4.82) | 0.47 |
| TcO2 mean change: increase vs decrease or stable | 0.63 (0.37-5.12) | 0.64 |
| Return to operating room | ||
| TcO2 lowest reading preoperatively: high vs low | 0.58 (0.09-3.72) | 0.56 |
| TcO2 mean change: increase vs decrease or stable | 0.85 (0.17-4.26) | 0.84 |
| Wound healed by 6 months | ||
| TcO2 low before surgery: ≥ 25 mmHg vs < 25 mmHg | 0.37 (0.04-3.46) | 0.38 |
| TcO2 recovery: increase versus decrease or stable | 0.33 (0.07-1.49) | 0.15 |
The groups are separated by complication types including any wound-healing complication, complications that resulted in return to the operating room, and for patients who achieved full wound healing by 6 months after surgery.
Table 3.
Comparison of preoperative TcO2 as a continuous variablea
| Variable | OR (95% CI) | p value |
| Any wound-healing complication | ||
| TcO2 lowest reading before surgery | 0.97 (0.94-1.01) | 0.13 |
| TcO2 mean reading before surgery | 0.99 (0.95-1.03) | 0.52 |
| Return to operating room | ||
| TcO2 lowest reading before surgery | 1 (0.96-1.04) | 0.92 |
| TcO2 mean reading before surgery | 1.02 (0.97-1.07) | 0.55 |
| Wound healed by 6 months | ||
| TcO2 lowest reading before surgery | 0.99 (0.96-1.03) | 0.78 |
| TcO2 mean reading before surgery | 0.99 (0.95-1.04) | 0.74 |
These ORs reflect a 1-mmHg increase in TcO2; the groups are separated by complication types including any wound-healing complication, complications that resulted in return to the operating room, and patients who achieved full wound healing by 6 months after surgery.
Does Recovery (Increase) in Transcutaneous Oxygen Measurement During the Rest Period Between the End of Radiation and the Time of Surgery Protect Against Wound-healing Complications?
There was no difference in the odds of developing a wound-healing complication between patients whose transcutaneous oxygen levels recovered to greater than 25 mmHg between radiation and surgery than in those whose levels did not recover to greater than 25 mmHg during that rest period (OR 0.63 [95% CI 0.37 to 5.12]; p = 0.64) (Table 2). Among patients with uneventful wound healing, the change was -2.34 [IQR -8.00 to 4.40] and among those with wound-healing complications, the change was -2.36 [IQR -12.44 to 4.33].
Discussion
It is well accepted that operating in a radiated field has undesirable consequences with respect to wound healing [2, 4, 5, 7, 8, 10, 11]. However, the quantitative effects of radiation on local skin perfusion, or whether the increase in wound complications are related to inadequate skin perfusion, are not well described. The current study was based on our pilot investigation of 10 patients [11], which demonstrated that patients with a low TcO2 of greater than 25 mmHg and those with an increase in the mean TcO2 during the rest period were more likely to have uneventful wound healing. Based on these pilot data, we designed the current investigation, which was much larger, to ascertain whether TcO2 correlates with wound-healing complications. Despite the larger group of patients evaluated here, we found that transcutaneous oximetry is unable to predict wound-healing complications. As there remains no clinical tool to be able to predict which patients will experience wound-healing complications, we recommend that surgeons continue to monitor all patients with equivalent vigilance in the postoperative period as all of these patients should be considered high risk.
Limitations
This study has several limitations. First, we used a composite endpoint that considered all wound-related issues as a single outcome. The pooling of small problems with major complications can be misleading; however, this is only problematic if a study finds a difference in the pooled outcome (in this case, that would be all wound complications). Ours was a no-difference study on the composite endpoint (all wound complications), and so unsurprisingly, when we analyzed our data to evaluate only those complications that resulted in a return to the OR, there was still no difference detected. Furthermore, these outcomes were assessed by the treating surgeon who was not blinded; in this context, assessment bias has the potential to make new investigational tools appear to function better than they actually do. Another concern was the use of incisional negative-pressure wound therapy in many of these patients, which might have contributed to a decrease in the overall risk of wound-healing complications. Although there is evidence that the use of an incisional wound vacuum-assisted closure device can substantially decrease complication risk, our reported complication rate appeared similar to that of a prior investigation [6].
An additional limitation was that our study was powered for 40 patients, but ultimately only 39 patients completed the investigation. With the analyses performed it is very unlikely that the additional patient would have impacted the no-difference nature of the investigation. This study was designed to have an 80% power to be able to detect an odds ratio reduction of 29%; the point estimate on our odds reduction was 26%. If indeed the “true” effect size was 26% (and not something larger or smaller, given the spread captured by the 95% CI around that point estimate), then our study might not have detected that difference because of insufficient sample size.
Lastly, transcutaneous oximetry represents a focal test of skin oxygenation at focal points in the surgical wound. Although we attempted to diminish this sampling bias by using multiple leads, ultimately, the data represent a small portion of the entire potential area in which a wound complication could occur. Transcutaneous oximetry also samples the very superficial portion of the surgical wound but does not assess the deeper tissues. Furthermore, although transcutaneous oximetry is standardized to environmental conditions, there is variability across sites that could result in a difference in measurements.
Discussion of Key Findings
We found that the cutoff value of 25 mmHg did not predict whether a wound-healing complication would occur. This may be partially related to the low event rate of patients who had a measurement below 25 mmHg. As such, a second analysis was performed to evaluate TcO2 as a continuous variable, which also did not detect a difference. Similarly, recovery (or increase) in transcutaneous oxygen during the rest period from the end of radiation to the start of surgery also did not predict a wound-healing complication. In comparing our results to the available evidence, our finding that 46% (18 of 39) of patients developed wound-healing complications was in line with that of prior investigations, which have found that 15% (8 of 54) to 43% (30 of 70) of patients develop wound complications [2-3, 5-7, 8, 10, 12-14].
Aside from our previously mentioned pilot trial [12], there has been one previous investigation that we are aware of that has evaluated transcutaneous oximetry and wound healing in soft tissue sarcoma [8]. That investigation evaluated TcO2 in 24 patients in the postoperative setting and observed that the postoperative day 1 value of TcO2 was lower in wounds with healing difficulties than in those without. Those investigators observed that those patients with a wound that progressed to normal healing had a mean TcO2 of 28.5 mmHg, whereas those with complications had a mean of 14.3 mmHg. That investigation was heterogeneous in that not all patients were treated with radiation, and those who did were treated with brachytherapy. Thus, although there is a suggested correlation between low TcO2 and wound-healing complications, this relationship is unclear, given the timing and type of radiation used. Most importantly, because the measurements were performed after surgery, transcutaneous oximetry was unable to guide the clinician in changing preoperative and perioperative protocols to reduce the complication rate. Efforts to assess potential wound healing might be the most clinically meaningful if wound healing is assessed immediately preoperatively, and this concept was the primary motivator of our study design to assess TcO2 as patients progressed through radiation and immediately before surgery. The identification of such a tool, whether it be transcutaneous oximetry or some other method, would be beneficial because it may allow the surgeon to alter surgical timing, use more plastic surgical interventions such as flaps and skin grafts, guide immediate postoperative wound surveillance, and potentially use other interventions to improve the likelihood that the surgical wound would heal uneventfully.
Given that the current investigation showed no association between preoperative transcutaneous oximetry and wound-healing complications, the question remains: Is there a tool that clinicians can rely upon? The field of plastic surgery has adopted rather regular use of a fluorescent imaging technique utilizing indocyanine green (ICG) [3, 14, 16, 17]. A recent investigation reported the use of ICG fluorescent imaging of the skin perfusion in sarcoma surgery at the time of resection [15]. That investigation utilized ICG at the time of closure to qualitatively assess whether there was adequate perfusion at the skin edges. This study was limited in that it included flaps and skin grafts, and surgeons also selectively resected areas deemed to have poor perfusion. Therefore, although there is great promise in this technology for wound assessment, it should be evaluated in a more rigorous manner.
Conclusion
In our study, transcutaneous oximetry was not an accurate tool to predict wound-healing complications. As such, transcutaneous oximetry cannot be considered a reliable test in isolation. We theorize that this is because we sampled relatively few points in which a potential wound-healing complication could arise. We believe fluorescent tissue perfusion probes might be useful in this regard, as they can assess the wound more broadly, in real time, at the point of surgical care. Future studies should evaluate that tool, perhaps in a study similar in design to this one.
Acknowledgments
We thank Stephanie Kliethermes PhD for her assistance with the initial statistical planning as well as Heather Keaney MPH and Matt Rerko BS for database management.
Footnotes
The institution of one or more of the authors (LMN, BJM) has received, during the study period, funding from the Orthopaedic Research and Education Foundation (award number 16-054) and funding provided by the Musculoskeletal Tumor Society.
Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members.
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.
Ethical approval for this study was obtained from the Cleveland Clinic, Cleveland, OH, USA (number 17-888).
This work was performed at the Cleveland Clinic, Cleveland, OH, USA.
Contributor Information
Nathan W. Mesko, Email: meskon@ccf.org.
Yuxuan Jin, Email: jiny@ccf.org.
Chirag Shah, Email: shahc4@ccf.org.
Andre Spiguel, Email: spiguar@ortho.ufl.edu.
Jeremy White, Email: jeremy-white@ouhsc.edu.
Benjamin J. Miller, Email: benjamin-j-miller@uiowa.edu.
References
- 1.Abarca T, Gao Y, Monga V, et al. Improved survival for extremity soft tissue sarcoma treated in high-volume facilities. J Surg Oncol. 2018;117:1479-1486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Abouarab MH, Salem IL, Degheidy MM, et al. Therapeutic options and postoperative wound complications after extremity soft tissue sarcoma resection and postoperative external beam radiotherapy. Int Wound J. 2018;15:148-158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Moris V, Cristofari S, Stivala A, et al. Fluorescent indocyanine green angiography: preliminary results in microsurgery monitoring. J Stomatol Oral Maxillfac Surg. 2019;120:297-300. [DOI] [PubMed] [Google Scholar]
- 4.Baldini EH, Lapidus MR, Wang Q, et al. Predictors for major wound complications following preoperative radiotherapy and surgery for soft-tissue sarcoma of the extremities and trunk: importance of tumor proximity to skin surface. Ann Surg Oncol. 2013;20:1494-1499. [DOI] [PubMed] [Google Scholar]
- 5.Bedi M, Ethun CG, Charlson J, et al. Is a nomogram able to predict postoperative wound complications in localized soft-tissue sarcomas of the extremity? Clin Orthop Relat Res. 2020;478:550-559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Bedi M, King DM, DeVries J, et al. Does vacuum-assisted closure reduce the risk of wound complications in patients with lower extremity sarcomas treated with preoperative radiation? Clin Orthop Relat Res. 2019;477:768-774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Bell RS, Mahoney J, O’Sullivan B, et al. Wound-healing complications in soft tissue sarcoma management: comparison of three treatment protocols. J Surg Oncol. 1991;46:190-197. [DOI] [PubMed] [Google Scholar]
- 8.Collier CD, Su CA, Reich MS, et al. Six-week interval between preoperative radiation and surgery is associated with fewer major wound complications in soft tissue sarcoma. Am J Clin Oncol. 2020;43:491-495. [DOI] [PubMed] [Google Scholar]
- 9.DeLaney TF. Optimizing radiation therapy and post-treatment function in the management of extremity soft tissue sarcoma. Curr Treat Options Oncol. 2004;5:463-476. [DOI] [PubMed] [Google Scholar]
- 10.Griffin AM, Dickie CI, Catton CN, et al. The influence of time interval between preoperative radiation and surgical resection on the development of wound-healing complications in extremity soft tissue sarcoma. Ann Surg Oncol. 2015;22:2824-2830. [DOI] [PubMed] [Google Scholar]
- 11.Nystrom LM, Miller BJ. Transcutaneous oximetry may predict wound-healing complications in preoperatively radiated soft tissue sarcoma. Iowa Orthop J. 2016;36:117-122. [PMC free article] [PubMed] [Google Scholar]
- 12.Nystrom LM, Reimer NB, Reith JD, et al. Multidisciplinary management of soft tissue sarcoma. ScientificWorldJournal. 2013;2013:852462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet . 2002;359:2235-2241. [DOI] [PubMed] [Google Scholar]
- 14.Pruimboom T, Schols RM, Van Kuijk SM, et al. Indocyanine green angiography for preventing postoperative mastectomy skin flap necrosis in immediate breast reconstruction. Cochrane Database Syst Rev. 2020;4:CD013280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Wilke BK, Schultz DS, Huayllani MT, et al. Intraoperative indocyanine green fluorescence angiography is sensitive for predicting postoperative wound complications in soft-tissue sarcoma surgery. J Am Acad Orthop Surg. 2021;29:433-438. [DOI] [PubMed] [Google Scholar]
- 16.Wormer BA, Huntington CR, Ross SW, et al. A prospective randomized double-blinded controlled trial evaluating indocyanine green fluorescence angiography on reducing wound complications in complex abdominal wall reconstruction. J Surg Res. 2016;202:461-472. [DOI] [PubMed] [Google Scholar]
- 17.Yang C-E, Chung SW, Lee DW, et al. Evaluation of the relationship between flap tension and tissue perfusion in implant-based breast reconstruction using laser-assisted indocyanine green angiography. Ann Surg Oncol. 2018;25:2235-2240. [DOI] [PubMed] [Google Scholar]