Hisako Hara

Indocyanine Green (ICG) Lymphography Is Superior to Lymphoscintigraphy for Diagnostic Imaging of Early Lymphedema of the Upper Limbs

Background Secondary lymphedema causes swelling in limbs due to lymph retention following lymph node dissection in cancer therapy. Initiation of treatment soon after appearance of edema is very important, but there is no method for early diagnosis of lymphedema. In this study, we compared the utility of four diagnostic imaging methods: magnetic resonance imaging (MRI), computed tomography (CT), lymphoscintigraphy, and Indocyanine Green (ICG) lymphography. Patients and Methods Between April 2010 and November 2011, we examined 21 female patients (42 arms) with unilateral mild upper limb lymphedema using the four methods. The mean age of the patients was 60.4 years old (35–81 years old). Biopsies of skin and collecting lymphatic vessels were performed in 7 patients who underwent lymphaticovenous anastomosis. Results The specificity was 1 for all four methods. The sensitivity was 1 in ICG lymphography and MRI, 0.62 in lymphoscintigraphy, and 0.33 in CT. These results show that MRI and ICG lymphography are superior to lymphoscintigraphy or CT for diagnosis of lymphedema. In some cases, biopsy findings suggested abnormalities in skin and lymphatic vessels for which lymphoscintigraphy showed no abnormal findings. ICG lymphography showed a dermal backflow pattern in these cases. Conclusions Our findings suggest the importance of dual diagnosis by examination of the lymphatic system using ICG lymphography and evaluation of edema in subcutaneous fat tissue using MRI.

Minimally invasive lymphatic supermicrosurgery (MILS): indocyanine green lymphography-guided simultaneous multisite lymphaticovenular anastomoses via millimeter skin incisions.

AbstractAmong various surgical treatments, lymphaticovenular anastomosis (LVA), which bypasses congested lymph into venous circulation, is the least invasive surgical treatment. However, it usually entails skin incisions of around 3 cm, and operation time of around 4 hours. With multiple supermicrosurgeons under guidance of indocyanine green lymphography, LVAs can be simultaneously performed under local anesthesia within approximately 2 hours via small skin incisions with length less than 1 cm, allowing minimally invasive lymphatic supermicrosurgery (MILS). We performed MILS on 11 limbs of compression-refractory peripheral lymphedema cases. Length of skin incision for LVA ranged from 1 to 9 mm. Average operation time was 1.82 hours. Of the11 limbs, 10 showed postoperative volume reduction. Indocyanine green lymphography clearly visualizes superficial lymph flows, which helps us to decide precise skin incision sites and find lymphatic vessels in LVA surgery, shortening skin incision length and operation time. Minimally invasive lymphatic supermicrosurgery can serve as the most reasonable treatment of compression-refractory peripheral lymphedema.

Pathological Steps of Cancer-Related Lymphedema: Histological Changes in the Collecting Lymphatic Vessels after Lymphadenectomy

Introduction To date, an electron microscopy study of the collecting lymphatic vessels has not been conducted to examine the early stages of lymphedema. However, such histological studies could be useful for elucidating the mechanism of lymphedema onset. The aim of this study was to clarify the changes occurring in collecting lymphatic vessels after lymphadenectomy. Methods The study was conducted on 114 specimens from 37 patients who developed lymphedema of the lower limbs after receiving surgical treatment for gynecologic cancers and who consulted the University of Tokyo Hospital and affiliated hospitals from April 2009 to March 2011. Lymphatic vessels that were not needed for lymphatico venous anastomosis surgery were trimmed and subsequently examined using electron microscopy and light microscopy. Results Based on macroscopic findings, the histochemical changes in the collecting lymphatic vessels were defined as follows: normal, ectasis, contraction, and sclerosis type (NECST). In the ectasis type, an increase in endolymphatic pressure was accompanied by a flattening of the lymphatic vessel endothelial cells. In the contraction type, smooth muscle cells were transformed into synthetic cells and promoted the growth of collagen fibers. In the sclerosis type, fibrous elements accounted for the majority of the components, the lymphatic vessels lost their transport and concentrating abilities, and the lumen was either narrowed or completely obstructed. Conclusions The increase in pressure inside the collecting lymphatic vessels after lymphadenectomy was accompanied by histological changes that began before the onset of lymphedema.

Uterine autotransplantation in cynomolgus macaques: the first case of pregnancy and delivery

BACKGROUND For women with congenital uterine infertility, or for those who have undergone hysterectomy, uterine transplantation is one of the potential treatments to regain fertility. In this study, we utilized a primate model of uterine transplantation, and evaluated the patency of our microsurgical anastomoses, and the perfusion of the transplanted uterus. METHODS Two female cynomolgus monkeys underwent surgery. We anastomosed two arteries and one vein in Case 1 and two arteries and two veins in Case 2. The arteries used were the uterine arteries and the anastomosis was done to the external iliac artery. We used one of the ovarian veins in both animals, but resected the ovary from the Fallopian tube. Uterine arterial blood flow and uterine size were determined by intraoperative indocyanine green (ICG) angiography and ultrasonography. The biopsy of the uterine cervix was performed after surgery. RESULTS ICG angiography showed that the unilateral uterine artery perfused the bilateral uterine bodies and cervix. In Case 1, ICG angiography showed the occlusion of one of the anastomosed arteries during the operation and the uterus appeared atrophied 2 months after operation. In Case 2, the transplanted uterus survived and normal menstruation occurred. The animal achieved a natural pregnancy and was delivered by the Caeserean section due to early separation of the placenta. The newborn suffered fetal distress. CONCLUSIONS These results show the anastomosis of at least the bilateral uterine arteries and the unilateral ovarian vein is required for uterus transplantation. This is the first report of a natural pregnancy in a primate following uterine autotransplantation.

Uterus autotransplantation in cynomolgus macaques: intraoperative evaluation of uterine blood flow using indocyanine green

BACKGROUND Uterus transplantation may be the only theoretical option for some women, for example, those with congenital uterine infertility or who have undergone hysterectomy. In this study, we evaluated the intra- and post-operative blood flow conditions of vascular anastomosed regions and the blood-perfused area of the transplanted uterus in a cynomolgus macaque model of uterus autotransplantation. METHODS Female cynomolgus monkeys (n = 6) underwent surgery: the first two animals were used to study the pelvic vascular anatomy and the remaining four animals were used for uterus autotransplantation. We used indocyanine green (ICG) fluorescent angiography during surgery to assess blood perfusion in the vascular anastomosed region and uterine area. After surgery, the uterine size, presence or absence of the endometrium and blood flow rates in the uterine artery and vein were evaluated using Doppler ultrasonography. RESULTS; Uterine arterial and venous anastomoses succeeded in all four animals that underwent autotransplantation. Intraoperative ICG fluorescence angiography showed favorable blood flow in the vascular anastomosed regions and the entire uterus received a sufficient blood supply from a single uterine artery. Favorable blood flow in the uterine artery and vein immediately after surgery was shown by Doppler ultrasonography. Ultimately, three out of four animals died within 3 months following surgery because of reduced feeding and loss of body strength. CONCLUSIONS ICG fluorescence angiography can be used for simple evaluation of real-time blood flow conditions in the anastomosed uterine artery, vein and uterine area and can facilitate the success rate of uterus transplantation.

Comparison of indocyanine green lymphographic findings with the conditions of collecting lymphatic vessels of limbs in patients with lymphedema.

Background: The authors investigated the relationship between findings from indocyanine green lymphography and the condition of lymphatics according to the Normal, Ectasis, Contraction, Sclerosis Type classifications observed in each area during surgery. Methods: The authors examined 43 limbs of 25 patients who had undergone lymphaticovenous anastomosis from April to July of 2012 at the Department of Plastic and Reconstructive Surgery, University of Tokyo Hospital. After the injection of indocyanine green, linear, splash, stardust, and diffuse patterns were determined. Visual findings of the collecting lymph vessels during the anastomosis at each incision site were evaluated using the Normal, Ectasis, Contraction, Sclerosis Type classifications. Results: Lymphaticovenous anastomosis was conducted on 164 collecting lymph vessels within 43 limbs of 25 people. Normal-type lymph vessels were observed in 36, ectasis type in 43, contraction type in 52, and sclerosis type in 33. Many normal vessels were found in the linear region, but the proportion of this type declined in the more severe stardust and diffuse regions. In contrast, no sclerosis-type vessels were found in the linear region, while the proportion of this type increased with lymphedema severity. Conclusions: Indocyanine green lymphography findings and the Normal, Ectasis, Contraction, Sclerosis Type classification of collecting lymph vessels seem to have a relationship. An increase in the severity of lymphedema according to the indocyanine green lymphography findings indicated an increase in the stage of lymphedema according to the Normal, Ectasis, Contraction, Sclerosis Type classification. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Upper-limb lymphedema treated aesthetically with lymphaticovenous anastomosis using indocyanine green lymphography and noncontact vein visualization.

We have described a procedure to minimize surgical wounds, in which lymph vessels and skin venules are identified by indocyanine green (ICG) lymphography and the AV300 noncontact visualization system (AccuVein, Cold Spring Harbor, NY), respectively. This approach allows accurate decisions regarding sites of incision for lymphatic venous anastomosis (LVA). This method was applied in a patient with right upper-limb lymphedema after breast cancer therapy. The low-invasive procedure can be used before and during surgery. The incision size is minimal, and the incision site is at the joint area. Thus, we aim to establish this approach as a standard method for identifying lymph vessels and veins that are suitable for LVA. This innovative vascular-imaging machine makes LVA less invasive and more effective without side effects.

Lymphaticovenular anastomosis to prevent cellulitis associated with lymphoedema

One of the complications of lymphoedema is recurrent cellulitis. The aim was to determine whether lymphaticovenous anastomosis (LVA) was effective at reducing cellulitis in patients with lymphoedema.

Using indocyanine green fluorescent lymphography and lymphatic-venous anastomosis for cancer-related lymphedema.

Advances in cancer therapy have increased the importance of improvement of quality of life after cancer survival. Cancer-related lymphedema or secondary lymphedema that occurs after lymph node dissection in resection of tumors of abdominal visceral organs can impair quality of life. However, standard curative treatment for secondary lymphedema has not been established. This may be due to the lack of a method for early diagnosis of lymphedema, and because of selection of conservative treatment such as compression therapy to delay edema progression in many cases. To develop a curative approach, we have performed definite diagnosis of early-stage lymphedema using magnetic resonance imaging and an indocyanine green fluorescent lymphography, followed by surgical treatment with lymphatic-venous anastomosis using supermicrosurgery. Herein, we report the first case of secondary lymphedema in which we performed early diagnosis and surgery using these techniques and achieved an almost complete cure of lymphedema. We suggest that early diagnostic imaging and early microsurgery is the key of lymphedema treatment.

Scarless lymphatic venous anastomosis for latent and early-stage lymphoedema using indocyanine green lymphography and non-invasive instruments for visualising subcutaneous vein

BACKGROUND Lymphoedema can be treated conservatively or surgically. Early treatment is important, but the surgical indication and the effect of surgery on pain in lymphoedema-affected limbs have not been described. The objective of this study was to examine the effect of low-invasive scarless lymphatic venous anastomosis (LVA) for early or latent lymphoedema. METHODS LVA was performed in six patients (eight legs) with leg lymphoedema between April 2010 and March 2011. Lymphoedema was stage 0 (defined as subclinical) in three patients (five legs) and stage 1 in three patients (three legs). Subjective symptoms, circumference of the affected leg and a lymphoscintigram were evaluated before and 6 months after surgery. Preoperatively, subcutaneous lymph vessels and veins were identified non-invasively using ICG lymphoscintigraphy and non-invasive instruments for visualising subcutaneous vein, AccuVein system, through the skin. These vessels and veins were secured with vessel loops passed underneath and side-to-side anastomosed under a surgical microscope. RESULTS Subjective symptoms improved after surgery in all patients. The leg circumference improved in stage 1 cases, which all had an increased circumference before surgery. Lymph retention was observed on preoperative lymphoscintigraphy in all six patients and was improved after surgery in all cases. CONCLUSIONS Scarless LVA performed through a small incision improves abnormal lymph circulation and subjective symptoms in cases of early lymphoedema, in which the limb circumference has just started to increase, and latent lymphoedema, in which the circumference has not increased, but abnormal findings on lymphoscintigraphy or subjective symptoms are present.