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Yamamoto 2018
Yamamoto 2018
T
he lymph system is an important homeosta- surgery/radiation therapy, trauma, malforma-
sis system for maintaining fluid balances, the tion, or inflammation results in localized immu-
immune system, and lipid metabolism.1–3 nologic insufficiency, abnormal lipid profiles, and
Lymph flow obstruction, caused by cancer ablative excess lymph in the interstitial space manifested
as lymphedema.2–5 Major trauma or wide resec-
tion for malignant tumor in the extremities often
From the Department of Plastic and Reconstructive Surgery, involves dominant lymph pathways along the
Center Hospital of National Center for Global Health and large subcutaneous veins such as the saphenous
Medicine; the Department of Plastic and Reconstructive Sur-
vein and the cephalic veins, which may cause per-
gery, the University of Tokyo Hospital; the Department of
Plastic Surgery, Tokyo Metropolitan Bokutoh Hospital; and manent lymph flow obstruction and subsequent
the Department of Plastic Surgery, Asahi General Hospital. chronic lymphedema.6–9 Lymphedema affects
Received for publication July 29, 2017; accepted March 8,
2018. Disclosure: The authors have no financial interest
Copyright © 2018 by the American Society of Plastic Surgeons to declare in relation to the content of this article.
DOI: 10.1097/PRS.0000000000004694
796 www.PRSJournal.com
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Volume 142, Number 3 • Lymph Flow Restoration
postoperative rehabilitation and the patient’s linear pattern on a flap skin island and those on
quality of life because of prolonged edematous recipient skin were approximated as close as pos-
conditions and inflammation. sible under intraoperative indocyanine green lym-
Lymphatic channels can usually restore lymph phographic navigation; 3-0 Vicryl (Ethicon, Inc.,
pathways and functions by lymphangiogenesis Somerville, N.J.) subdermal sutures were placed
after anatomical destruction such as surgery or without supermicrosurgical lymphatic anastomo-
trauma, but some cases manifest chronic lymph- sis. Lymph node was not involved in any flaps in
edema.6–12 Although there are a few studies regard- this cohort.
ing lymph flow evaluation using lymph imaging Postoperative indocyanine green lymphogra-
modalities, it is unclear what factors affect lymph phy was performed 3 months after replantation or
flow restoration after trauma or surgery involving free flap surgery. In replantation cases, 0.1 ml of
major lymph pathways.6,11,12 With advancement indocyanine green was injected at the most distal
of near-infrared fluorescent lymphography using site of the replanted tissue. In flap transfer cases,
indocyanine green, precise evaluation of superfi- 0.1 ml of indocyanine green was injected into
cial lymph flow becomes possible.13–22 We aimed the digital tip when a flap was transferred to the
to investigate factors associated with lymph flow hand, digit, or foot. When a flap was transferred
restoration after tissue replantation and transfer to a more proximal region, 0.2 ml of indocya-
by evaluation of superficial lymph flow using indo- nine green was injected 10 to 15 cm distally to the
cyanine green lymphography. recipient site. After indocyanine green injection,
circumferential fluorescent images of lymph flow
were obtained using an infrared camera system.
PATIENTS AND METHODS On postoperative indocyanine green lym-
Medical charts of 38 consecutive patients phography, restoration of lymph flow continu-
who underwent indocyanine green lymphogra- ity between amputee/flap and recipient site was
phy after tissue replantation or free flap trans- evaluated; when the linear pattern was observed
fer from July of 2011 to December of 2016 were in both the amputee/flap and the recipient site
reviewed to evaluate the relationship between continuously, lymph flow restoration was evalu-
postoperative lymph circulation and intraopera- ated as positive; when the linear pattern was not
tive findings. Sixteen patients underwent tissue observed in the amputee/flap because of an
replantation and 22 patients underwent free flap extensive dermal backflow pattern such as splash,
reconstruction. Clinical charts were reviewed to stardust, or diffuse pattern, lymph flow restoration
collect clinical findings and indocyanine green was evaluated as negative (Fig. 1).14 Postoperative
lymphographic findings. indocyanine green lymphographic findings were
In tissue replantation cases, replantation oper- evaluated according to patient characteristics and
ations were performed in a conventional way as intraoperative findings, including age, sex, type
reported previously.23,24 In 15 of the 22 free flap of operation, raw surface in lymph axiality, and
transfer cases, flap surgery was performed in a compatible lymph axiality. When there was a 2-cm-
conventional way without indocyanine green lym- wide or wider raw surface area between lymphatic
phographic guidance. In the remaining seven vessel stumps of an amputee/flap and a recipient
free flap cases, indocyanine green lymphography site, raw surface in lymph axiality was evaluated
was performed preoperatively to map superficial as positive. When lymph flow directions of an
lymph flows in both donor and recipient sites, amputee/flap and a recipient site were matched,
and the linear pattern was marked on the skin as compatible lymph axiality was evaluated as posi-
reported previously; 0.2 ml of indocyanine green tive; when there was a distance shorter than 2 cm
(Diagnogreen 0.25%; Daiichi Pharmaceutical, between lymphatic vessels stumps of an amputee/
Tokyo, Japan) was injected subcutaneously 10 to flap and a recipient site, compatible lymph axial-
15 cm distally to donor and recipient sites.14,15,25 ity was evaluated as positive.
After indocyanine green injection, circumfer- Statistical analyses were performed using the
ential fluorescent images of lymphatic drain- Mann-Whitney U test for continuous variables and
age channels were obtained using an infrared the chi-square and Fisher’s exact probability test
camera system (Photodynamic Eye; Hamamatsu for categorical variables; Fisher’s exact provability
Photonics K.K., Hamamatsu, Japan).21,22 Indocya- test was used when any of expected values were
nine green lymphographic images were recorded below 5. Statistical significance was defined as a
immediately after indocyanine green injection to value of p < 0.05. This retrospective observational
mark the linear pattern. In flap inset, edges of the study was approved by the institution’s ethical
797
Copyright © 2018 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Plastic and Reconstructive Surgery • September 2018
review board, and all patients gave written con- to sex (male, 78 percent; female, 40 percent;
sent to participate this study. p = 0.017), cause of defect (trauma, 83 percent;
others, 33 percent; p = 0.002), type of operation
(replantation, 94 percent; free flap, 41 percent;
RESULTS p = 0.001), and compatible lymph axiality (posi-
Patient age ranged from 22 to 70 years tive, 96 percent; negative, 0 percent; p < 0.001).
(median, 42 years), and 23 patients were men (60 Based on lymph axiality, the “raw surface in lymph
percent). Cause of defect was acute trauma in 23 axiality–negative and compatible lymph axiality–
cases (60 percent). Twenty-seven patients (71 per- positive” condition was completely matched with
cent) underwent surgery on the upper extremity, positivity for lymph flow restoration; 100 percent
and the remaining 11 (29 percent) underwent sur- accuracy to predict postoperative lymph flow res-
gery on the lower extremity or the penis. In tumor toration was achieved (Table 4). Representative
resection cases, no patient underwent lymph node cases are shown in Figures 2 through 6.
dissection or perioperative adjuvant therapy in this
study cohort. Indocyanine green lymphographic
guidance was used in seven cases of free flap DISCUSSION
transfer, among which compatible lymph axiality This study revealed that lymph flows could
could be achieved in five cases, with a significantly be restored after tissue replantation or free flap
higher compatible lymph axiality–positive rate transfer without supermicrosurgical lymphatic
than those without indocyanine green lympho- vessel anastomosis or lymph node transfer.
graphic guidance (indocyanine green lymphog- Lymph flow seemed to be restored by connection
raphy guidance–positive, 71 percent; indocyanine between lymphatic vessels that originally existed
green lymphography guidance–negative, 27 per- in an amputee/flap and a recipient site, not by
cent; p = 0.047); two of seven indocyanine green development of new lymph pathways. In replan-
lymphography-guided cases could not achieve tation cases, lymph flow restoration was observed
compatible lymph axiality, because lymphatic ves- except for one case with raw surface in lymph
sel stumps could not be approximated when flaps axiality. Because lymph axiality between amputee
were inset to cover the defects. Raw surface in and recipient site is usually matched in replanta-
lymph axiality was seen in two cases (5 percent), tion cases, only scar formation attributable to raw
and compatible lymph axiality was seen in 25 surface area seems to interrupt lymph flow resto-
cases (66 percent). On postoperative indocyanine ration by means of lymphangiogenesis.23,24 Among
green lymphography, lymph flow restoration was free flap transfer cases, lymph flow restoration was
observed in 24 cases (63 percent) (Tables 1 and 2). observed only in cases with compatible lymph axi-
Several factors were found to be associ- ality. When there is no compatible lymph axiality,
ated with postoperative lymph flow restoration lymphangiogenesis is considered insufficient to
(Table 3). There were significant differences in connect distant lymphatic vessels between a recip-
positivity for lymph flow restoration with regard ient site and a flap. As shown in Table 4, lymph
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Volume 142, Number 3 • Lymph Flow Restoration
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Plastic and Reconstructive Surgery • September 2018
Table 3. Analysis of Factors Associated with less likely to occur. Because previous studies sug-
Postoperative Lymph Circulation gested that lymphangiogenesis may occur after
LFR- LFR-
wound healing with width of few centimeters, we
Negative* Positive* used 2-cm as a cutoff value of raw surface in lymph
(%) (%) p axiality and compatible lymph axiality.1,8,12,13,15,19 It
No. 14 24 is noteworthy that lymph node is not necessary
Age, yr 0.490 to restore lymph flows when proximal and dis-
Median 37 49 tal ends of lymphatic vessels in a defect can be
Range 22–66 27–70
Sex 0.017† bridged using lymphatic vessels included in a flap.
Male 5 (22) 18 (78) In replantation cases and toe transfer cases,
Female 9 (60) 6 (40) compatible lymph axiality can be relatively eas-
Cause 0.002†
Trauma‡ 4 (17) 19 (83) ily achieved, because lymphatic vessels are known
Others§ 10 (67) 5 (33) to exist in the midlateral aspect of the digits.15,26–28
Site 0.482 However, as shown in Table 2, compatible lymph
Upper extremity 9 (33) 18 (67)
Lower extremity 5 (45) 6 (55) axiality is hardly achieved in skin flap transfer
Operation 0.001† cases other than toe flap transfer cases when indo-
Replantation 1 (6) 15 (94) cyanine green lymphography is not used for assis-
Free flap 13 (59) 9 (41)
RLA║ 0.057 tance. Indocyanine green lymphography guidance
Positive 2 (100) 0 (0) is essential to achieve compatible lymph axiality,
Negative 12 (33) 24 (167) but is not possible in all cases. Because the primary
CLA¶ <0.001†
Positive 1 (4) 24 (96) objective of skin flap transfer is coverage of a defect,
Negative 13 (100) 0 (0) compatible lymph axiality can be achieved only
LFR, lymph flow restoration; RLA, raw surface in lymph axiality; when inset of a flap does not affect defect coverage.
CLA, compatible lymph axiality; ICG, indocyanine green. This study revealed other factors associated with
*Postoperative LFR between an amputee and a recipient site on ICG
lymphography. postoperative lymph flow restoration. Male sex,
†Statistically significant. defect caused by trauma, and replantation cases were
‡Skin defect caused by acute trauma.
§Skin defect caused by contracture release, tumor resection, or ulcer.
associated with a higher lymph flow restoration rate.
║Existence of raw surface area in main lymph flows. In this study cohort, more male and trauma cases
¶Compatible lymph axiality between amputee/flap and recipient site. were included in the replantation group. This can
be explained by the fact that replantation cases were
Table 4. Association between Lymph Axiality and
associated with a higher rate of positive compat-
Postoperative Lymph Circulation ible lymph axiality and lymph flow restoration, but
further studies are required to clarify independent
LFR- LFR- factors associated with lymph flow restoration with
Negative Positive
(%)* (%)* p a larger sample size, allowing multivariate analysis.
No. 14 24
Prolonged edema sometimes affects postop-
RLA-negative†/ erative rehabilitation, and can even develop as
CLA-positive‡ 0 (0) 24 (100) <0.001§ clinically significant lymphedema after replan-
Others║ 14 (100) 0 (0) tation surgery or free flap transfer, as shown in
LFR, lymph flow restoration; RLA, raw-surface in lymph axiality;
CLA, compatible lymph axiality; ICG, indocyanine green.
Figure 2.5,8,11,12 Once manifested, lymphedema
*Postoperative LFR between an amputee and a recipient site on ICG progresses over time and significantly deteriorates
lymphography. a patient’s quality of life.4,5,8,10,29–32 Based on the
†Existence of raw surface area in main lymph flows.
‡Compatible lymph axiality between amputee/flap and recipient site.
results of this study, a reconstructive surgeon can
§Statistically significant. restore lymph flows without a lymph node flap or
║Others include RLA-negative/CLA-negative, RLA-positive/CLA- supermicrosurgical lymphatic anastomosis; lymph
negative, and RLA-positive/CLA- positive.
flows can be restored when tissue is replanted/
transferred with compatible lymph axiality with-
axiality plays a critical role in lymph flow restora- out raw surface in lymph axiality. Lymph axiality-
tion after tissue replantation or transfer. based tissue transfer has a potential to allow more
If a raw region remains around the lymphat- physiologic reconstruction, facilitates postop-
ics in an amputee or a flap, formation of scar tis- erative rehabilitation, and prevents lymphedema
sue around the lymphatics inhibits lymph flow even when main lymph pathways are damaged.
restoration.7,9,10 If the direction of the lymph flow One of the limitations of the study is that only
is not in line with the existing flow proximal and/ a relatively small number of Japanese patients were
or distal to the defect, lymph flow restoration is included without long-term follow-up. It is unclear
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Volume 142, Number 3 • Lymph Flow Restoration
Fig. 2. Case 3 in Table 1. A 28-year-old man suffering from crush amputation of the right middle finger under-
went replantation. Postoperative indocyanine green lymphography showed the linear pattern through the
replanted site; lymph flowed continuously beyond the replanted site (dotted line). Arrows indicate indocyanine
green injection site.
Fig. 3. Case 4 in Table 1. A 38-year-old man suffering from clean amputation of the penis underwent replanta-
tion. Postoperative indocyanine green lymphography showed a linear pattern through the replanted site; lymph
flowed continuously beyond the replanted site (dotted line). Arrows indicate indocyanine green injection site.
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Plastic and Reconstructive Surgery • September 2018
Fig. 4. Case 5 in Table 1. A 42-year-old woman suffering from crush amputation of the left little finger under-
went replantation. Artificial dermis was used to cover a raw surface. Postoperative indocyanine green lym-
phography showed the stardust pattern in the replanted finger; lymph did not flow beyond the replanted site
(dotted line). Arrows indicate indocyanine green injection site.
Fig. 5. Case 9 in Table 2. A 70-year-old woman suffering from sarcoma in the right upper extremity underwent
wide resection and superficial circumflex iliac artery perforator flap transfer without indocyanine green lym-
phographic guidance. Postoperative indocyanine green lymphography showed the stardust pattern in the flap
and the recipient site, but the linear pattern was not seen in the flap; a diagnosis of secondary lymphedema
was made. Arrows indicate indocyanine green injection site; dotted circle indicates the flap margin; and dotted
arrows indicate expected lymph pathways in the flap.
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Volume 142, Number 3 • Lymph Flow Restoration
Fig. 6. Case 18 in Table 2. A 54-year-old woman suffering from sarcoma in the right lower leg underwent wide
resection and transverse rectus abdominis myocutaneous flap transfer with indocyanine green lymphographic
guidance. The linear pattern was marked with a red pen based on preoperative indocyanine green lympho-
graphic findings. Postoperative indocyanine green lymphography showed the linear pattern in both the flap
and the recipient site, although the stardust pattern was seen in the distal edge of the flap; lymph flowed con-
tinuously beyond the edges of the flap. Arrows indicate indocyanine green injection site; dotted circle indicates
the flap margin; and dotted arrows indicate lymph pathways in the flap.
whether this study’s results can be applicable for risk of donor-site lymphedema.25,33–36 Further pro-
non-Japanese cases or whether the lymph axiality- spective studies including a larger number of cases
based tissue transfer method is clinically useful to with longer clinical follow-up are required to con-
prevent lymphedema in long-term follow-up. Most firm the importance of lymph axiality in lymph flow
importantly, the lymph axiality-based tissue transfer restoration, to confirm the usefulness of lymph axi-
has yet to be clarified as being useful for the treat- ality-based tissue transfer in prevention and treat-
ment of established lymphedema. Theoretically, ment of lymphedema, and to evaluate which flap is
lymph axiality-based tissue transfer seems to restore more useful for lymph axiality-based tissue transfer.
arm lymph flows of patients with upper extremity
lymphedema after axillary lymph node dissection, CONCLUSIONS
by transferring a skin flap at the axilla with com-
patible lymph axiality without lymph node inclu- Lymph flows can be restored after tissue
replantation or free flap transfer without lymph
sion or supermicrosurgical lymphatic anastomosis.
node or supermicrosurgical lymphatic anastomo-
Although supermicrosurgical lymphatic vessel anas-
sis. Lymph axiality–based tissue transfer, replant-
tomosis allows secure restoration of lymph flows,
ing/transferring tissue with compatible lymph
supermicrosurgical technique is required, which
axiality without raw surface in lymph axiality, is
can be performed only by experienced microsur-
considered a key for lymph flow restoration.
geons; secure anastomosis technique for vessels with
diameter of 0.5 mm or smaller is required for super- Takumi Yamamoto, M.D., Ph.D.
microsurgery.13,16,33 Because lymphedema treatment Department of Plastic and Reconstructive Surgery
with vascularized lymph node transfer has a risk of Center Hospital of National Center for Global Health and
Medicine
donor-site lymphedema, lymph axiality-based tissue 1-21-1 Toyama, Shinjuku-ku
transfer can be a useful therapeutic option for com- Tokyo 162-8655, Japan
pression-refractory lymphedema, with a minimum tyamamoto-tky@umin.ac.jp
803
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Plastic and Reconstructive Surgery • September 2018
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