840584

case-report2019
IJLXXX10.1177/1534734619840584The International Journal of Lower Extremity WoundsZhu et al

Case Report
The International Journal of Lower

Treatment of Diabetic Foot Gangrene

Extremity Wounds
1­–8
© The Author(s) 2019
Using the STAGE Principle: A Case Series Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/1534734619840584
https://doi.org/10.1177/1534734619840584
journals.sagepub.com/home/ijl

Chaojun Zhu, MD1 , Ping Yue, MD2, Jiakang Lü, MD3,

Xianzhou Liu, MD1, Lei Huo, MD1, and Zhaohui Zhang, PhD, MD1

Abstract
Diabetic foot gangrene with lower extremity ischemia can preclude amputation. However, wound treatment principles
based on the Wagner classification system are lacking. We proposed the STAGE principle for the surgical management of
diabetic foot wounds. The STAGE principle guides surgical intervention during the wound treatment of diabetic foot ulcers
and emphasizes that “based on anatomical layers, the management focuses on blood supply and includes layer-by-layer
incision to the infected area, maintenance of effective wound drainage, and step-by-step treatment of the wound.” We
applied the STAGE principle for the treatment of 7 patients with an ankle brachial index <0.5 and Wagner grade 4 diabetic
foot gangrene. The average ankle brachial index was 0.42 (0.32-0.48; SD = 0.06), and male patients smoked an average of
1.28 packs/day (0.4-2; SD = 0.63). The average wound duration was 45.86 days (14-63 days; SD = 18.46). The average
wound healing time was 8.86 months (5-13 months; SD = 2.36). The follow-up time was 37.71 months (3-84 months;
SD = 25.04; median = 36 months). Patient 1 received endovascular interventional therapy twice for the lower extremity
artery, and the wound healed. After 3 months of follow-up, the patient exhibited recurrence. After the third application of
endovascular interventional therapy for the lower extremity artery, the blood supply was improved, and the wound healed
after 1 month. In summary, the treatment of 7 cases of diabetic foot gangrene with severe lower extremity ischemia using
the STAGE principle resulted in remarkable efficacy.

Keywords
diabetic foot, gangrene, severe lower extremity ischemia, STAGE principle

Introduction Wagner grade 4 diabetic foot gangrene.2,3 In China, diabetic

There are approximately 92 million diabetes mellitus (DM)
patients and 145 million people with prediabetes in China.1
Diabetic foot disease is a severe complication of DM. It not
only affects the quality of life of patients but also poses a
major challenge to China’s health care system and pension
system. Unfortunately, no specialized foot hospital exists,
there is a shortage of professional podiatrists, and many hos-
pitals have not established a model of multidisciplinary com-
prehensive therapy in China.1 Based on the characteristics and
treatment status of diabetic foot disease in China, we proposed
the STAGE principle for surgical management of diabetic foot
wounds. In this case report, we reported application of the
STAGE principle for the treatment of 7 patients with diabetic
foot gangrene. The longest follow-up time was 7 years.
Materials and Methods
Study Design and Population
The purpose of this study was to show the clinical efficacy
of the surgical STAGE principle for the treatment of high
amputation risk (ankle brachial index [ABI] < 0.5) and
foot disease patients mainly exhibit the neuroischemic type,
followed by the ischemic type.4,5 The disease mainly occurs
in individuals who smoke and have lower educational and
income levels.6,7 We performed a 7-year (October 2010 to
October 2017) single-center retrospective study on the treat-
ment of Wagner grade 4 and severe ischemic diabetic foot
gangrene cases using the STAGE surgical treatment princi-
ple. Because data collection was retrospective, this case
series analysis did not require approval of the institutional
review board. Patients agreed to the use of anonymous med-
ical data, recordings, and photographic materials.
1
Second Affiliated Hospital of Tianjin University of TCM, Tianjin,
China
2
The First Hospital of Lanzhou University, Lanzhou, China
3
Center for Drug Evaluation, National Medical Products Administration,
Beijing, China
Corresponding Author:
Zhaohui Zhang, Surgery of TCM, Second Affiliated Hospital of Tianjin
University of TCM, No. 69, Zengchan Road, Hebei District, Tianjin
300150, China.
Email: zhzh0405@163.com
2 The International Journal of Lower Extremity Wounds 00(0)
Inclusion criteria were the following: meets the diagnos-
tic criteria for diabetic foot; Wagner grade 4 diabetic foot
gangrene patients; ABI < 0.5; application of the STAGE
treatment principle; patients with complete medical infor-
mation; clinical healing of the wound after treatment; a
complete set of foot images during treatment; and more
than 3 months of follow-up.
Exclusion criteria were the following: patients with
severe cardiovascular disease, heart failure, or severe liver
and kidney insufficiency; patients with recurrence of dia-
betic foot disease after healing; patients who met the ampu-
tation (amputation above the ankle) criteria; patients who
had severe pain that was difficult to control using drugs, and
patients who could not achieve remission after endovascu-
lar interventional therapy for the lower extremity artery;
and patients who were lost to follow-up.
The STAGE surgical treatment principle was applied to
treat 56 cases of severe ischemic and Wagner grade 4 dia-
betic foot gangrene in patients. A total of 25 patients exhib-
ited clinical healing, resulting in a rate of 44.64%. Seven
patients were selected according to the inclusion and exclu-
sion criteria. In addition to using the Wagner classification,
the Texas classification system and the ABI for assessment
of the severity of peripheral arterial disease (PAD) and foot
microcirculation was also assessed using a measurement of
the transcutaneous oxygen pressure.6-9
Patient Evaluation and Wound Management
Procedure.  The STAGE principle is formulated for the treat-
ment of diabetic foot wounds and emphasizes that “accord-
ing to the anatomical level, take blood supply as the center,
slice the wound layer by layer to the infected lesion, keep
the wound drainage unobstructed, and treat the wound in
phases.” During the process of treatment, the improvement
in microcirculation and microangiogenesis (A) are the
foundations of wound healing. On this basis, the bone (skel-
eton, S), tendons (tendon, T), and “granulation” (granula-
tion, G) can be gradually realized. So-called wound
granulation (G) is the process of removing necrotic bone
and tendon tissue using drugs to promote capillary growth,
granulation tissue growth, and then granulation tissue to
cover exposed bone and tendon. After granulation of the
wound, the drug is used to promote epithelialization (E);
finally, healing of the wound is achieved. We refer to the
above-mentioned process as the STAGE principle.
Nonsurgical treatment.  According to the “Guidelines for
the Diagnosis and Treatment of Diabetic Foot in China,”
blood glucose, lipids, and platelet aggregation were con-
ventionally controlled, blood pressure was reduced, nerves
were nurtured, infection was controlled, and sensitive anti-
biotics were selected according to the culture results of the
wound secretion.10
Surgical treatment. Based on nonsurgical treatment,
the affected foot was treated using the STAGE principle.
The blood supply was the basis of treatment using the
STAGE principle.11 Improvement of circulation, which
supports wound healing, was crucial for the entire treat-
ment process.
Layered incision and drainage.  This was performed in
layers of soft tissue infection and necrosis that could
not be accurately located by imaging examinations,
including magnetic resonance imaging.12 According to
the STAGE principle, skin, subcutaneous tissues, the
superficial fascia, and the plantar fascia were cut by
layers. The infected metatarsophalangeal joint capsule
was opened to expose the infected tendon. Tissues that
affected drainage were removed to allow unobstructed
drainage. Local dressing or medication was applied for
infection control. Topical traditional Chinese medicine
dressing was applied to inhibit and relieve inflammatory
reactions surrounding the wound.
Staged treatment of the wound.  During treatment, micro-
circulation improvement and microvascular angiogenesis
(A) are essential for granulation tissue formation (drug-
induced capillary growth and granulation [G] after remov-
ing necrotic bone and tendon tissue) in the bone (skeleton,
S) and tendons (T). After the granulation tissue fills in the
wound, a drug is used to promote epithelialization and epi-
thelial coverage (E) in the granulation tissue-filled wound
to finally achieve healing of the wound. We refer to the
above-mentioned process as the STAGE principle. Phase A
is essential for the treatments in Phases S-T and G-E. Phase
A will be introduced first.
Phase A: Improvement in blood circulation was the most
important principle for the entire treatment process: “Time
is tissue.”13 Due to poor blood circulation and foot tissue
gangrene, the edge of the cut skin had gangrene due to isch-
emia, the skin temperature surrounding the wound was low,
the wound had ischemic necrosis, the tendon had necrosis,
and bone was destroyed. Endovascular interventional ther-
apy for the lower extremity artery was actively performed
(artery, A). Patients without surgical indications received
alprostadil for vasodilation to improve ischemia and cilo-
stazol for vasodilation to improve intermittent claudication;
in addition, these patients also received a combination of an
intravenous drip of traditional Chinese medicine and oral
administration of a traditional Chinese medicine decoction
or traditional Chinese patent drugs to improve microarterial
circulation (angiogenesis, A).14-16
Phases S-T-G-E: When the foot blood circulation was
improved and the timing of debridement was met, necrotic
bone was removed. For patients who required amputation
(foot and toes), the joints were avoided (skeleton, S). The
section plane was approximately 1 cm lower than the skin
Zhu et al 3
edge. If an attached tendon was present during osteotomy,
the attached tendon was resected at the proximal normal
tendon (tendon, T). Dressing or topical traditional Chinese
medicine was applied to promote wrapping of the bone
stump and tendon stump by granulation tissues (granula-
tion, G) to achieve wound granulation and complete the
wound bed preparation. After filling by granulation tis-
sues, the wound was gradually covered by epithelial tis-
sue from outside to inside (epithelialization, E) and
healed. To shorten the wound healing time, autologous
skin grafting could be performed to promote wound heal-
ing. If vascular occlusion or stenosis occur during the
treatment process or restenosis occurs after the endovas-
cular interventional therapy for the lower extremity
artery, the endovascular interventional therapy should be
performed again (A).
After removal of necrotic tissues from a diabetic foot
with dry gangrene, the wound was treated according to the
procedure described in section “Staged Treatment of the
Wound.” A diabetic foot with mixed gangrene or wet gan-
grene with an abscess was first cut open according to the
procedure described in section “Layered Incision and
Drainage,” and then the wound was treated according to
the procedure described in section “Staged Treatment of
the Wound.”
Results
Demographic data and baseline characteristics of patients
are summarized in Table 1. All patients had a Wagner
grade of 4. Patient 7 had gangrene in the back of the foot
and a Texas grade of 3D. All other patients were grade 4C
or 4D. The average ABI was 0.42 (0.32-0.48, SD = 0.06).
Male patients smoked an average of 1.28 packs/day (0.4-
2, SD = 0.63). The average wound duration was 45.86
days (14-63 days, SD = 18.46). Because included patients
had gangrene, it was difficult to objectively measure the
baseline wound area; therefore, these data were not
included. The average wound healing time was 8.86
months (5-13 months, SD = 2.36). The follow-up time
was 37.71 months (3-84 months, SD = 25.04, and median
36 months). Patient 1 had severe low extremity arterial
ischemia and received endovascular interventional ther-
apy twice for the lower extremity artery (superficial fem-
oral artery stent implantation; occlusion occurred again
after 6 months, and intra-stent balloon dilatation was per-
formed). After wound healing, recurrence occurred after
3 months of follow-up. The cause of recurrence was inap-
propriate eating habits. Elevation of triglyceride levels
(14.36 µmol/L), total cholesterol levels (5.51 µmol/L),
and blood glucose levels (random venous blood glucose
= 13.34 µmol/L) and irregular medication caused stent
occlusion and distal blood supply deterioration, and an
inappropriate pedicure caused local ulceration. After the
third application of endovascular interventional therapy
for the lower extremity artery (repeat intra-stent balloon
dilation), the wound healed after 1 month. Because the
use of transcutaneous oxygen pressure for assessment of
microcirculation was initiated in 2015, the data are
incomplete. The results for patients 1 and 5 were 15 mm
Hg and 22 mm Hg, respectively (Table 1).
Selected Cases
Patient 2.  Treatment in the absence of gangrene abscess: A
67-year-old male patient sought treatment due to intermit-
tent claudication. The diagnosis was diabetic foot gangrene
and arteriosclerotic occlusive disease of the lower extrem-
ity. Bilateral lower extremity balloon dilation was per-
formed. At 1 week after balloon dilation, gangrene was
present at the end of the toes in both feet (Figure 1A). The
pain was severe and affected sleep. Basic medical treat-
ment was provided as described in section “Nonsurgical
Treatment,” and foot gangrene was treated using the
STAGE principle as described in section “Staged Treat-
ment of the Wound.” Local circulation was improved using
an intravenous infusion of a traditional Chinese medicine
injection (Sanqi Panax Notoginseng for injection 0.5 g
IVGTT QD was applied for 2 weeks at a time for 8 weeks),
an oral traditional Chinese medicine decoction (Buyang
huanwu decoction and xuefu zhuyu decoction plus or
minus), and a topical traditional Chinese medicine tincture
(saffron tincture). After 1 month, the range of foot gan-
grene was confined and had not spread to the proximal end.
After 4 months, a boundary line gradually developed
between necrotic tissues and normal tissues in the foot
(Figure 1B). Necrotic tissues were removed, and tradi-
tional Chinese medicine was applied (XiangPiShengJiGao).
The distal end of the proximal phalangeal bone of the
fourth toe and the distal phalangeal bone of the fifth toe
were removed from the left foot (Figure 1C). The distal
phalangeal bones of the second and third toes and the distal
end of the proximal phalangeal bone of the fourth toe were
removed from the right foot (Figure 1C). After almost 11
months of treatment, the wound gradually healed (Figure
1C). After wound healing, the daily life of the patient was
not affected. The walking speed was the same as before,
but the patient could not run. After 7 years of follow-up, no
diabetic foot ulcer was present (Figure 1D).
Patient 3.  Treatment in the presence of an abscess with
gangrene: A 70-year-old male patient had poor limb activ-
ity on the left side, gangrene in the second and third toes of
the left foot (Figure 2A), significant reduction of the skin
temperature, and a history of cerebral infarction. Physical
examination results showed no pulsation of the dorsal
artery and posterior tibial artery in the left foot. Portable
Doppler blood flow detector results suggested occlusion of
4
Table 1.  Baseline Patient Demographics, Wound Characteristics, and Mean Study Outcomesa.
The Right
Duration Time for Time to Follow-
of Diabetes TcPO2 TEXAS Cigarettes Wound Debridement Closure up Time Ulcer
Patient (Sex) Age (Years) (Years) ABI (
mm Hg) Classification Revascularization Status (PPD) Duration (Days) Wound Etiology (Months) (Months) (Months) Recurrence

1 (Male) 65 27 0.32 15 4D Right superior femoral artery 2– 60 Ischemic infection gangrene 2.67 11+ 4 Yes
stent; stent restenosis was
followed by drug-coated
balloon dilation
2 (Male) 67 5 R: 0.7; L: 0.45 — 4C Balloon dilation of superficial 0.4 40 Ischemic gangrene 5.37 8+ 84 No
femoral artery in both
lower extremities
3 (Male) 70 12 0.37 — 4D No 1 60 Ischemic infection gangrene 2.97 12− 36 No
4 (Male) 68 7 0.38 — 4D No 1 28 Ischemic gangrene infection 3.77 8+ 36 No
5 (Male) 55 10 0.47 22 4D Superficial femoral artery 2 63 Ischemic gangrene 0.8 7+ 8 No
stenting; posterior tibial
balloon angioplasty
6 (Female) 58 20 0.48 — 4C No No 14 Ischemic gangrene 5.3 11− 46 No
7 (Female) 56 13 0.45 — 3D No No 56 Ischemic gangrene infection 2.17 5− 50 No
Mean 62.71 ± 5.75 13.42 ± 7.11 0.42 ± 0.06 45.86 ± 18.46 3.29 ± 1.66 8.86 ± 2.36 37.71 ± 25.04  

Abbreviations: ABI, ankle brachial index; PPD, packs per day (1 PPD = 20 cigarettes).
a
The right time for debridement: blood supply is the basis of debridement, after evaluation local microcirculation of diabetic foot ulcers was improved, and then debridement is performed. Convert days to months by 30 days per
month. All values are pretreatment values. Three years ago, our department did not purchase transcutaneous oxygen partial pressure equipment.
Zhu et al 5

Figure 1.  Study wound 2. (A) Dry gangrene at the end of the toe of the foot, the color of the foot is the staining of the
traditional Chinese medicine. (B) After 4 months, a boundary line gradually developed between necrotic tissues and normal
tissues in the foot, foot gangrene was treated using the STAGE principle as described in section “Staged Treatment of the
Wound.” (C) The distal end of the proximal phalangeal bone of the fourth toe and the distal phalangeal bone of the fifth toe
were removed from the left foot. The distal phalangeal bones of the second and third toes and the distal end of the proximal
phalangeal bone of the fourth toe were removed from the right foot. Wound healing after Staged treatment. (D) After 7 years
of follow-up, no diabetic foot ulcer was present.

the dorsalis pedis artery, severe posterior tibial artery ste-
nosis, and an audible noise. Computed tomography angi-
ography showed inferior genicular artery occlusion in the
left leg with no outflow tract, and formation of collateral
vessels was observed. This patient did not meet the indica-
tion for endovascular therapy for a lower extremity artery.
Basic medical treatment was provided as described in
section “Nonsurgical Treatment.” Distal blood supply was
improved using an intravenous infusion of a traditional
Chinese medicine injection (Zhusheyong Honghuahuang-
sesu 150 mg IVGTT QD was applied for 2 weeks at a time
for 8 weeks), an oral traditional Chinese medicine decoc-
tion (Buyang huanwu decoction and Yanghe decoction
plus or minus) and a topical traditional Chinese medicine
6 The International Journal of Lower Extremity Wounds 00(0)

Figure 2.  Study wound 3. (A) Mixed gangrene in the second and third toes of the left foot. (B) Based on the STAGE principle,
incision, and drainage were first performed as described in section “Layered Incision and Drainage.” Next, the necrotic toes
and tissues were gradually removed as described in section “Staged Treatment of the Wound.” The second to fourth toes were
amputated from the distal end of the metatarsal bones. (C) Topical traditional Chinese medicine was applied for promotion of wound
granulation. (D) After nearly 12 months of treatment, the wound was healed.

tincture (saffron tincture). For wound treatment, based
on the STAGE principle, incision, and drainage were
first performed as described in section “Layered Incision
and Drainage.” Next, the necrotic toes and tissues were
gradually removed as described in section “Staged Treat-
ment of the Wound.” The second to fourth toes were
amputated from the distal end of the metatarsal bones
(Figure 2B), and topical traditional Chinese medicine
(ShengJi YuHong Gao and XiangPiShengJiGao) was
applied for promotion of wound granulation (Figure 2C).
At 12 months after treatment, the wound was healed
(Figure 2D). After wound healing, no recurrence was
observed after 3 years of follow-up. The patient was lost
to follow-up after 4 years.
Discussion
In China, diabetic foot diseases mainly include neuroisch-
emic ulcers.4,5 In tertiary hospitals in China, 27.3% of
amputations are performed due to diabetic foot diseases,
accounting for 56.5% of nontraumatic amputations.1
Approximately 40% of DM patients who undergo amputa-
tion (including minor and major amputations) die within 5
years of the procedure. Diabetic foot gangrene with isch-
emia combined with tendon degeneration, necrosis, and
bone destruction is difficult to treat clinically.
The Wagner and Texas classifications are internationally
recognized diabetic foot disease classification and staging
methods.6,7 Currently, Wagner classification is widely used
to assess the severity of diabetic foot wounds. Compared
with the Wagner classification, the TEXAS classification
system is better at assessing the severity of the wound and
predicting the prognosis of the limb. However, its applica-
tion in clinical and scientific research is not as extensive as
the former. We developed the STAGE wound treatment
principle based on Wagner grading in clinical practice.
The STAGE principle emphases infection and ischemia
factors and focuses on the anatomical levels involved in
diabetic foot ulcers. In the treatment process of diabetic foot
ulcers, tissues were cut open in layers until the focus of
infection was reached. The blood supply is an important
factor for wound healing.11 Wound treatment after incision
is the A-focused portion of the ST and GE stages. Ulcers or
gangrene that involve the skeletal and tendon layers should
be treated according to the STAGE principle, whereas
ulcers or gangrene that involve the tendon layer should be
treated according to the TAGE principle. Treatment of all
stages is not absolutely separated and can be performed
simultaneously.
Diabetic foot treatment involves the endocrinology,
orthopedics, vascular surgery, general surgery, and reha-
bilitation departments. Therefore, the multidisciplinary
Zhu et al 7
collaboration model is mainly recommended for diabetic
foot treatment. However, multidisciplinary comprehen-
sive treatment for diabetic foot disease in China is diffi-
cult to achieve within a short time period. We suggest that
collaboration of doctors and nurses in a one-stop treat-
ment program is suitable for diabetic foot treatment in
China. All types of issues in the process of diabetic foot
treatment are managed by collaboration between doctors
and nurses in a department or hospital.17 This one-stop
treatment is currently implemented in our hospital.
The STAGE principle is conducive to the realization of
one-stop treatment of diabetic foot. The STAGE principle
emphasizes blood supply as the center and anatomy as the
basis and guides intervention during key points in the treat-
ment of diabetic foot ulcers, such as determining the level of
the incision, improving the blood supply, providing the tim-
ing of debruising, and guiding the management of bone and
tendons. The advantage of this principle is that after the
application of Wagner grading assessment of the wound, the
wound anatomy level after surgical intervention is clear, the
treatment stage and target are clear, and it compensates for
the deficiency of Wagner grading in the blood supply assess-
ment. It should be noted that the wound surface should be
evaluated in a timely manner at each stage, and potential
problems affecting wound repair should be addressed in a
timely manner. For example, granulation edema on the
wound surface at stage G indicates that degeneration,
necrotic tissue, or dead bone still exists under the granula-
tion tissue. Granulation dullness and wound repair stasis
suggest poor local circulation, and the blood supply should
be reevaluated. The STAGE principle applies to the treat-
ment of all diabetic foot wounds. However, for life-threaten-
ing diabetic foot, the pros and cons should be assessed. If the
patient outcome will be good general health, amputation
should be considered. Of course, the STAGE principle is
also applicable to patients who refuse amputation and who
cannot tolerate amputation due to a poor general health con-
dition. Major amputation in patients with infection and gan-
grene diabetes foot can sometimes be avoided by correct
managing appropriately with STAGE principle.18
In China, Chinese medicine is widely used for the treat-
ment of diabetic foot. As shown in Table 1, compared with
the application of arterial endovascular interventional
therapy for blood circulation improvement, the applica-
tion of traditional Chinese medicine for blood circulation
improvement requires a longer time frame. In addition, we
observed that the major function of traditional Chinese
medicine was the establishment of collateral circulation,
while arterial endovascular interventional therapy
improved the microcirculation through improvement of
the blood supply in large and medium arteries. The appli-
cation of endovascular therapy to improve the arterial
blood supply was prone to restenosis; however, the appli-
cation of traditional Chinese medicine for improvement
and establishment of microcirculation was more sustained,
and foot microcirculation was still improved after 3 to 7
years of follow-up. Unfortunately, the majority of injec-
tions, oral drugs, and topical drugs in traditional Chinese
medicine have not been evaluated in randomized, multi-
center, and/or double-blind clinical trials for diabetic foot
diseases, and evidence of their efficacy is lacking. The
STAGE principle is summarized from our clinical experi-
ence in the treatment of diabetic foot wounds. However,
this principle still requires prospective multicenter ran-
domized clinical trials for further assessment of its effec-
tiveness and superiority.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
study was financially supported by the project grant from the
Traditional Chinese Medicine Key Specialized Disease of Tianjin.
ORCID iD
Chaojun Zhu https://orcid.org/0000-0001-5469-4202
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