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Lymph Flow Restoration after Tissue Replantation and Transfer: Importance of Lymph Axiality and Possibility of Lymph Flow Reconstruction without Lymph Node Transfer or Lymphatic Anastomosis

Yamamoto, Takumi, M.D., Ph.D.; Iida, Takuya, M.D., Ph.D.; Yoshimatsu, Hidehiko, M.D.; Fuse, Yuma, M.D.; Hayashi, Akitatsu, M.D.; Yamamoto, Nana, M.D.

Plastic and Reconstructive Surgery: September 2018 - Volume 142 - Issue 3 - p 796–804
doi: 10.1097/PRS.0000000000004694
Reconstructive: Lower Extremity: Original Articles
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Background: The lymph system plays important roles in maintaining fluid balances, the immune system, and lipid metabolism. After tissue replantation or transfer, some cases suffer long-lasting edema or lymphedema caused by interruption of main lymph flows; however, this mechanism has yet to be clarified.

Methods: The medical charts of 38 patients who underwent indocyanine green lymphography after tissue replantation or free flap transfer were reviewed to obtain data regarding clinical demographics, intraoperative findings, and postoperative indocyanine green lymphographic findings. Postoperative lymph flow restoration based on indocyanine green lymphographic findings was evaluated according to intraoperative findings, including raw surface in lymph axiality and compatible lymph axiality.

Results: Lymph flow restoration was observed in 24 cases (63 percent). There were significant differences in positive lymph flow restoration with regard to sex (male, 78 percent; female, 40 percent; 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; p = 0.001), and compatible lymph axiality (positive, 96 percent; negative, 0 percent; p < 0.001). Based on lymph axiality, the raw surface in lymph axiality–negative and compatible lymph axiality–positive condition was completely matched with lymph flow restoration positivity; 100 percent accuracy to predict postoperative lymph flow restoration was observed.

Conclusions: Lymph flow can be restored after tissue replantation or free flap transfer without lymph node or supermicrosurgical lymphatic anastomosis. The raw surface in lymph axiality–negative and compatible lymph axiality–positive condition is considered a key for restoring lymph flows after surgery affecting the main lymph pathway.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

This and Related “Classic” Articles Appear on Prsjournal.com for Journal Club Discussions.

Tokyo and Chiba, Japan

From the Department of Plastic and Reconstructive Surgery, Center Hospital of National Center for Global Health and Medicine; the Department of Plastic and Reconstructive Surgery, the University of Tokyo Hospital; the Department of Plastic Surgery, Tokyo Metropolitan Bokutoh Hospital; and the Department of Plastic Surgery, Asahi General Hospital.

Received for publication July 29, 2017; accepted March 8, 2018.

Disclosure: The authors have no financial interest to declare in relation to the content of this article.

Takumi Yamamoto, M.D., Ph.D., Department of Plastic and Reconstructive Surgery, Center Hospital of National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan, tyamamoto-tky@umin.ac.jp

The lymph system is an important homeostasis system for maintaining fluid balances, the immune system, and lipid metabolism.1–3 Lymph flow obstruction, caused by cancer ablative surgery/radiation therapy, trauma, malformation, or inflammation results in localized immunologic insufficiency, abnormal lipid profiles, and excess lymph in the interstitial space manifested as lymphedema.2–5 Major trauma or wide resection for malignant tumor in the extremities often involves dominant lymph pathways along the large subcutaneous veins such as the saphenous vein and the cephalic veins, which may cause permanent lymph flow obstruction and subsequent chronic lymphedema.6–9 Lymphedema affects postoperative rehabilitation and the patient’s quality of life because of prolonged edematous conditions and inflammation.

Lymphatic channels can usually restore lymph pathways and functions by lymphangiogenesis after anatomical destruction such as surgery or trauma, but some cases manifest chronic lymphedema.6–12 Although there are a few studies regarding lymph flow evaluation using lymph imaging modalities, it is unclear what factors affect lymph flow restoration after trauma or surgery involving major lymph pathways.6 , 11 , 12 With advancement of near-infrared fluorescent lymphography using indocyanine green, precise evaluation of superficial lymph flow becomes possible.13–22 We aimed to investigate factors associated with lymph flow restoration after tissue replantation and transfer by evaluation of superficial lymph flow using indocyanine green lymphography.

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PATIENTS AND METHODS

Medical charts of 38 consecutive patients who underwent indocyanine green lymphography after tissue replantation or free flap transfer from July of 2011 to December of 2016 were reviewed to evaluate the relationship between postoperative lymph circulation and intraoperative findings. Sixteen patients underwent tissue replantation and 22 patients underwent free flap reconstruction. Clinical charts were reviewed to collect clinical findings and indocyanine green lymphographic findings.

In tissue replantation cases, replantation operations were performed in a conventional way as reported previously.23 , 24 In 15 of the 22 free flap transfer cases, flap surgery was performed in a conventional way without indocyanine green lymphographic guidance. In the remaining seven free flap cases, indocyanine green lymphography was performed preoperatively to map superficial lymph flows in both donor and recipient sites, and the linear pattern was marked on the skin as reported previously; 0.2 ml of indocyanine green (Diagnogreen 0.25%; Daiichi Pharmaceutical, Tokyo, Japan) was injected subcutaneously 10 to 15 cm distally to donor and recipient sites.14 , 15 , 25 After indocyanine green injection, circumferential fluorescent images of lymphatic drainage channels were obtained using an infrared camera system (Photodynamic Eye; Hamamatsu Photonics K.K., Hamamatsu, Japan).21 , 22 Indocyanine green lymphographic images were recorded immediately after indocyanine green injection to mark the linear pattern. In flap inset, edges of the linear pattern on a flap skin island and those on recipient skin were approximated as close as possible under intraoperative indocyanine green lymphographic navigation; 3-0 Vicryl (Ethicon, Inc., Somerville, N.J.) subdermal sutures were placed without supermicrosurgical lymphatic anastomosis. Lymph node was not involved in any flaps in this cohort.

Postoperative indocyanine green lymphography was performed 3 months after replantation or free flap surgery. In replantation cases, 0.1 ml of indocyanine green was injected at the most distal site of the replanted tissue. In flap transfer cases, 0.1 ml of indocyanine green was injected into the digital tip when a flap was transferred to the hand, digit, or foot. When a flap was transferred to a more proximal region, 0.2 ml of indocyanine green was injected 10 to 15 cm distally to the recipient site. After indocyanine green injection, circumferential fluorescent images of lymph flow were obtained using an infrared camera system.

On postoperative indocyanine green lymphography, restoration of lymph flow continuity between amputee/flap and recipient site was evaluated; when the linear pattern was observed in both the amputee/flap and the recipient site continuously, lymph flow restoration was evaluated as positive; when the linear pattern was not observed in the amputee/flap because of an extensive dermal backflow pattern such as splash, stardust, or diffuse pattern, lymph flow restoration was evaluated as negative (Fig. 1).14 Postoperative indocyanine green lymphographic findings were evaluated according to patient characteristics and intraoperative findings, including age, sex, type of operation, raw surface in lymph axiality, and compatible lymph axiality. When there was a 2-cm-wide or wider raw surface area between lymphatic vessel stumps of an amputee/flap and a recipient site, raw surface in lymph axiality was evaluated as positive. When lymph flow directions of an amputee/flap and a recipient site were matched, compatible lymph axiality was evaluated as positive; when there was a distance shorter than 2 cm between lymphatic vessels stumps of an amputee/flap and a recipient site, compatible lymph axiality was evaluated as positive.

Fig. 1

Fig. 1

Statistical analyses were performed using the Mann-Whitney U test for continuous variables and the chi-square and Fisher’s exact probability test for categorical variables; Fisher’s exact provability test was used when any of expected values were below 5. Statistical significance was defined as a value of p < 0.05. This retrospective observational study was approved by the institution’s ethical review board, and all patients gave written consent to participate this study.

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RESULTS

Patient age ranged from 22 to 70 years (median, 42 years), and 23 patients were men (60 percent). Cause of defect was acute trauma in 23 cases (60 percent). Twenty-seven patients (71 percent) underwent surgery on the upper extremity, and the remaining 11 (29 percent) underwent surgery on the lower extremity or the penis. In tumor resection cases, no patient underwent lymph node dissection or perioperative adjuvant therapy in this study cohort. Indocyanine green lymphographic guidance was used in seven cases of free flap transfer, among which compatible lymph axiality could be achieved in five cases, with a significantly higher compatible lymph axiality–positive rate than those without indocyanine green lymphographic guidance (indocyanine green lymphography guidance–positive, 71 percent; indocyanine green lymphography guidance–negative, 27 percent; p = 0.047); two of seven indocyanine green lymphography-guided cases could not achieve compatible lymph axiality, because lymphatic vessel stumps could not be approximated when flaps were inset to cover the defects. Raw surface in lymph axiality was seen in two cases (5 percent), and compatible lymph axiality was seen in 25 cases (66 percent). On postoperative indocyanine green lymphography, lymph flow restoration was observed in 24 cases (63 percent) (Tables 1 and 2).

Table 1

Table 1

Table 2

Table 2

Several factors were found to be associated with postoperative lymph flow restoration (Table 3). There were significant differences in positivity for lymph flow restoration with regard to sex (male, 78 percent; female, 40 percent; 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; p = 0.001), and compatible lymph axiality (positive, 96 percent; negative, 0 percent; p < 0.001). Based on lymph axiality, the “raw surface in lymph axiality–negative and compatible lymph axiality–positive” condition was completely matched with positivity for lymph flow restoration; 100 percent accuracy to predict postoperative lymph flow restoration was achieved (Table 4). Representative cases are shown in Figures 2 through 6.

Table 3

Table 3

Table 4

Table 4

Fig. 2

Fig. 2

Fig. 3

Fig. 3

Fig. 4

Fig. 4

Fig. 5

Fig. 5

Fig. 6

Fig. 6

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DISCUSSION

This study revealed that lymph flows could be restored after tissue replantation or free flap transfer without supermicrosurgical lymphatic vessel anastomosis or lymph node transfer. Lymph flow seemed to be restored by connection between lymphatic vessels that originally existed in an amputee/flap and a recipient site, not by development of new lymph pathways. In replantation cases, lymph flow restoration was observed except for one case with raw surface in lymph axiality. Because lymph axiality between amputee and recipient site is usually matched in replantation cases, only scar formation attributable to raw surface area seems to interrupt lymph flow restoration by means of lymphangiogenesis.23 , 24 Among free flap transfer cases, lymph flow restoration was observed only in cases with compatible lymph axiality. When there is no compatible lymph axiality, lymphangiogenesis is considered insufficient to connect distant lymphatic vessels between a recipient site and a flap. As shown in Table 4, lymph axiality plays a critical role in lymph flow restoration after tissue replantation or transfer.

If a raw region remains around the lymphatics in an amputee or a flap, formation of scar tissue around the lymphatics inhibits lymph flow restoration.7 , 9 , 10 If the direction of the lymph flow is not in line with the existing flow proximal and/or distal to the defect, lymph flow restoration is less likely to occur. Because previous studies suggested that lymphangiogenesis may occur after wound healing with width of few centimeters, we used 2-cm as a cutoff value of raw surface in lymph axiality and compatible lymph axiality.1 , 8 , 12 , 13 , 15 , 19 It is noteworthy that lymph node is not necessary to restore lymph flows when proximal and distal ends of lymphatic vessels in a defect can be bridged using lymphatic vessels included in a flap.

In replantation cases and toe transfer cases, compatible lymph axiality can be relatively easily achieved, because lymphatic vessels are known to exist in the midlateral aspect of the digits.15 , 26–28 However, as shown in Table 2, compatible lymph axiality is hardly achieved in skin flap transfer cases other than toe flap transfer cases when indocyanine green lymphography is not used for assistance. Indocyanine green lymphography guidance is essential to achieve compatible lymph axiality, but is not possible in all cases. Because the primary objective of skin flap transfer is coverage of a defect, compatible lymph axiality can be achieved only when inset of a flap does not affect defect coverage.

This study revealed other factors associated with postoperative lymph flow restoration. Male sex, defect caused by trauma, and replantation cases were associated with a higher lymph flow restoration rate. In this study cohort, more male and trauma cases were included in the replantation group. This can be explained by the fact that replantation cases were associated with a higher rate of positive compatible lymph axiality and lymph flow restoration, but further studies are required to clarify independent factors associated with lymph flow restoration with a larger sample size, allowing multivariate analysis.

Prolonged edema sometimes affects postoperative rehabilitation, and can even develop as clinically significant lymphedema after replantation surgery or free flap transfer, as shown in Figure 2.5 , 8 , 11 , 12 Once manifested, lymphedema progresses over time and significantly deteriorates a patient’s quality of life.4 , 5 , 8 , 10 , 29–32 Based on the results of this study, a reconstructive surgeon can restore lymph flows without a lymph node flap or supermicrosurgical lymphatic anastomosis; lymph flows can be restored when tissue is replanted/transferred with compatible lymph axiality without raw surface in lymph axiality. Lymph axiality-based tissue transfer has a potential to allow more physiologic reconstruction, facilitates postoperative rehabilitation, and prevents lymphedema even when main lymph pathways are damaged.

One of the limitations of the study is that only a relatively small number of Japanese patients were included without long-term follow-up. It is unclear whether this study’s results can be applicable for non-Japanese cases or whether the lymph axiality-based tissue transfer method is clinically useful to prevent lymphedema in long-term follow-up. Most importantly, the lymph axiality-based tissue transfer has yet to be clarified as being useful for the treatment of established lymphedema. Theoretically, lymph axiality-based tissue transfer seems to restore arm lymph flows of patients with upper extremity lymphedema after axillary lymph node dissection, by transferring a skin flap at the axilla with compatible lymph axiality without lymph node inclusion or supermicrosurgical lymphatic anastomosis. Although supermicrosurgical lymphatic vessel anastomosis allows secure restoration of lymph flows, supermicrosurgical technique is required, which can be performed only by experienced microsurgeons; secure anastomosis technique for vessels with diameter of 0.5 mm or smaller is required for supermicrosurgery.13 , 16 , 33 Because lymphedema treatment with vascularized lymph node transfer has a risk of donor-site lymphedema, lymph axiality-based tissue transfer can be a useful therapeutic option for compression-refractory lymphedema, with a minimum risk of donor-site lymphedema.25 , 33–36 Further prospective studies including a larger number of cases with longer clinical follow-up are required to confirm the importance of lymph axiality in lymph flow restoration, to confirm the usefulness of lymph axiality-based tissue transfer in prevention and treatment of lymphedema, and to evaluate which flap is more useful for lymph axiality-based tissue transfer.

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CONCLUSIONS

Lymph flows can be restored after tissue replantation or free flap transfer without lymph node or supermicrosurgical lymphatic anastomosis. Lymph axiality–based tissue transfer, replanting/transferring tissue with compatible lymph axiality without raw surface in lymph axiality, is considered a key for lymph flow restoration.

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REFERENCES

1. Kesler CT, Liao S, Munn LL, Padera TP. Lymphatic vessels in health and disease. Wiley Interdiscip Rev Syst Biol Med. 2013;5:111–124.
2. Kim KW, Song JH. Emerging roles of lymphatic vasculature in immunity. Immune Netw. 2017;17:68–76.
3. Bernier-Latmani J, Petrova TV. Intestinal lymphatic vasculature: Structure, mechanisms, and functions. Nat Rev Gastroenterol Hepatol. 2017;14:510–526.
4. Iwasaki D, Yamamoto Y, Murao N, Oyama A, Funayama E, Furukawa H. Establishment of an acquired lymphedema model in the mouse hindlimb: Technical refinement and molecular characteristics. Plast Reconstr Surg. 2017;139:67e–78e.
5. Ogata F, Fujiu K, Koshima I, Nagai R, Manabe I. Phenotypic modulation of smooth muscle cells in lymphoedema. Br J Dermatol. 2015;172:1286–1293.
6. Kasper DA, Meller MM. Lymphedema of the hand and forearm following fracture of the distal radius. Orthopedics 2008;31:172.
7. Arslan H, Uludağ A, Kapukaya A, Gezici A, Bekler HI, Ketani A. Effect of lymphedema on the recovery of fractures. J Orthop Sci. 2007;12:578–584.
8. van Zanten MC, Mistry RM, Suami H, et al. The lymphatic response to injury with soft-tissue reconstruction in high-energy open tibial fractures of the lower extremity. Plast Reconstr Surg. 2017;139:483–491.
9. Asdourian MS, Skolny MN, Brunelle C, Seward CE, Salama L, Taghian AG. Precautions for breast cancer-related lymphoedema: Risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis. Lancet Oncol. 2016;17:e392–e405.
10. Ito T, Saito T, Ishiura R, Yamamoto T. Diagnosis of trauma-induced lymphedema using indocyanine green lymphography. J Plast Reconstr Aesthet Surg. 2015;68:e177–e178.
11. Cavadas PC, Thione A, Carballeira A, Dominguez PC. Lymphedema after upper limb transplantation: Scintigraphic study in 3 patients. Ann Plast Surg. 2013;71:114–117.
12. Blum KS, Proulx ST, Luciani P, Leroux JC, Detmar M. Dynamics of lymphatic regeneration and flow patterns after lymph node dissection. Breast Cancer Res Treat. 2013;139:81–86.
13. Yamamoto T, Narushima M, Yoshimatsu H, et al. Minimally invasive lymphatic supermicrosurgery (MILS): Indocyanine green lymphography-guided simultaneous multisite lymphaticovenular anastomoses via millimeter skin incisions. Ann Plast Surg. 2014;72:67–70.
14. Yamamoto T, Narushima M, Doi K, et al. Characteristic indocyanine green lymphography findings in lower extremity lymphedema: The generation of a novel lymphedema severity staging system using dermal backflow patterns. Plast Reconstr Surg. 2011;127:1979–1986.
15. Yamamoto T, Yamamoto N, Doi K, et al. Indocyanine green-enhanced lymphography for upper extremity lymphedema: A novel severity staging system using dermal backflow patterns. Plast Reconstr Surg. 2011;128:941–947.
16. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: A prospective study. Plast Reconstr Surg. 2010;126:752–758.
17. Yamamoto T, Iida T, Matsuda N, et al. Indocyanine green (ICG)-enhanced lymphography for evaluation of facial lymphoedema. J Plast Reconstr Aesthet Surg. 2011;64:1541–1544.
18. Yamamoto T, Matsuda N, Doi K, et al. The earliest finding of indocyanine green lymphography in asymptomatic limbs of lower extremity lymphedema patients secondary to cancer treatment: The modified dermal backflow stage and concept of subclinical lymphedema. Plast Reconstr Surg. 2011;128:314e–321e.
19. Yamamoto T, Yoshimatsu H, Narushima M, Yamamoto N, Hayashi A, Koshima I. Indocyanine green lymphography findings in primary leg lymphedema. Eur J Vasc Endovasc Surg. 2015;49:95–102.
20. Yamamoto T, Yamamoto N, Yoshimatsu H, Hayami S, Narushima M, Koshima I. Indocyanine green lymphography for evaluation of genital lymphedema in secondary lower extremity lymphedema patients. J Vasc Surg Venous Lymphat Disord. 2013;1:400–405.e1.
21. Yamamoto T, Narushima M, Yoshimatsu H, et al. Indocyanine green velocity: Lymph transportation capacity deterioration with progression of lymphedema. Ann Plast Surg. 2013;71:591–594.
22. Yamamoto T, Narushima M, Yoshimatsu H, et al. Dynamic indocyanine green (ICG) lymphography for breast cancer-related arm lymphedema. Ann Plast Surg. 2014;73:706–709.
23. Tang JB, Wang ZT, Chen J, Wong J. A global view of digital replantation and revascularization. Clin Plast Surg. 2017;44:189–209.
24. Babaei AR, Safarinejad MR. Penile replantation, science or myth? A systematic review. Urol J. 2007;4:62–65.
25. Yamamoto T, Yoshimatsu H, Yamamoto N. Complete lymph flow reconstruction: A free vascularized lymph node true perforator flap transfer with efferent lymphaticolymphatic anastomosis. J Plast Reconstr Aesthet Surg. 2016;69:1227–1233.
26. O’Brien B, MacLeod AM, Sykes PJ, Browning FS, Threlfall GN. Microvascular second toe transfer for digital reconstruction. J Hand Surg Am. 1978;3:123–133.
27. Yamamoto T, Hayashi A, Tsukuura R, Goto A, Yoshimatsu H, Koshima I. Transversely-inset great toe hemi-pulp flap transfer for the reconstruction of a thumb-tip defect. Microsurgery 2015;35:235–238.
28. Yamamoto T, Yoshimatsu H, Kikuchi K, Taji M, Uchida G, Koshima I. Use of non-enhanced angiography to assist the second toetip flap transfer for reconstruction of the fingertip defect. Microsurgery 2014;34:481–483.
29. Salani R. Survivorship planning in gynecologic cancer patients. Gynecol Oncol. 2013;130:389–397.
30. Herberger K, Blome C, Heyer K, et al. Quality of life in patients with primary and secondary lymphedema in the community. Wound Repair Regen. 2017;25:466–473.
31. Yamamoto T, Yamamoto N, Yoshimatsu H, Narushima M, Koshima I. LEC score: A judgment tool for indication of indocyanine green lymphography. Ann Plast Surg. 2013;70:227–230.
32. Yamamoto T, Yamamoto N, Yoshimatsu H, Narushima M, Koshima I. Factors associated with lower extremity dysmorphia caused by lower extremity lymphedema. Eur J Vasc Endovasc Surg. 2017;54:69–77.
33. Raju A, Chang DW. Vascularized lymph node transfer for treatment of lymphedema: A comprehensive literature review. Ann Surg. 2015;261:1013–1023.
34. Pons G, Masia J, Loschi P, Nardulli ML, Duch J. A case of donor-site lymphoedema after lymph node-superficial circumflex iliac artery perforator flap transfer. J Plast Reconstr Aesthet Surg. 2014;67:119–123.
35. Vignes S, Blanchard M, Yannoutsos A, Arrault M. Complications of autologous lymph-node transplantation for limb lymphoedema. Eur J Vasc Endovasc Surg. 2013;45:516–520.
36. Sulo E, Hartiala P, Viitanen T, Mäki M, Seppänen M, Saarikko A. Risk of donor-site lymphatic vessel dysfunction after microvascular lymph node transfer. J Plast Reconstr Aesthet Surg. 2015;68:551–558.
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