Exercise-Loaded Indocyanine Green Fluorescence Lymphangiography for Diagnosing Lymphedema.

BACKGROUND: Indocyanine green (ICG) fluorescence lymphography (ICGLG) that can visualize the lymphatic vessel and its flow noninvasively and dynamically was developed in 2007. It is frequently used to observe the function and pathway of the lymphatic vessels. ICGLG is simple and easy to perform, and it is useful for understanding the condition of the lymphatic system in real time. However, its protocol is not standardized. In addition, the lymphatic flow is enhanced by an exercise load such as walking. Till now, there is no report of exercise-loaded ICGLG. Therefore, we aimed to shorten the examination time and establish a standard ICGLG protocol. METHODS: We examined 63 patients (126 lower limbs) who visited our clinic for lower extremity edema. We observed detailed images of exercise-loaded ICGLG and examined the changes in findings over time in affected legs classified according to the International Society of Lymphedema. After ICG was injected, the participants exercised for 30 minutes. We observed the farthest proximal point where any ICG could be observed and the appearance of dermal backflow (DB), which is a specific finding of lymphedema, every 5 minutes. RESULTS: The proximal migration speed of ICG tended to slow as the disease stage worsened. For all disease stages, after 20 minutes of exercise, the DB appearance rate did not change further. The rates were 0% for legs with stage 0 lymphedema, 50% for legs with stage 1 lymphedema, and 100% for legs with stages 2a and 2b lymphedema. CONCLUSION: The appropriate exercise duration after ICG injection is 20 minutes. ICGLG is useful for screening for lymphedema.

A Detailed Examination of the Characteristics and Treatment in a Series of 33 Idiopathic Lymphedema Patients.

Background To date, only a few reports have been published on idiopathic lymphedema, and most of these are case reports. In this time, we performed a retrospective review of idiopathic lymphedema patients. Methods Forty patients presented with idiopathic lymphedema that was unrelated to surgery, injury, and medical conditions such as circulatory disease, kidney disease, and thrombotic venous disease. For these patients, we performed a retrospective review for edema-onset age, sex, location and stage of the edema, presence of cellulitis, episode related to edema onset, therapeutic intervention, and follow-up duration in the 33 patients whom we followed up. Results Among the 33 patients with idiopathic lymphedema, there were 11 patients with either congenital or childhood-onset lymphedema, 14 with adult-onset lymphedema, and the remaining 8 patients had an onset age of >60 years. Twenty of the 33 patients had undergone surgical treatment. Of the 19 patients who underwent lymphaticovenular anastomosis (LVA), 2 had good, 4 had fair, and 13 had poor treatment outcomes. Twelve patients successfully received only conservative treatment and follow-up for more than 3 months, without operation. The treatment outcome in these 12 patients was as follows: excellent in 4 patients, good in 6, and fair in 2 patients. Conclusion In this study, the usefulness of LVA for most patients with idiopathic lymphedema was not confirmed. Although this review did not include a conducted case, the indication for new surgical treatments such as vascularized lymph node transfer should be considered in the future.

A Novel Lymphaticovenular Anastomosis Rat Model.

INTRODUCTION: Lymphaticovenular anastomosis (LVA) has become an important procedure for the surgical treatment of lymphedema. In the past, the anatomy of the lymphatic system of animal models has been reported. However, to our knowledge, there have been few reports of animal models of LVA including training model. In this study, we report on a relatively simple and ideal animal LVA model based on peritoneal lymph ducts and veins. PATIENTS AND METHODS: For 10 rats, diameters of lumbar lymphatic ducts and iliolumbar veins in the peritoneal cavity on both sides were measured, and LVA was performed. In addition, we measured the diameters of 28 lymphatic ducts and veins in 8 patients who had previously undergone LVA and compared the results with those obtained in this rat model. RESULTS: The mean diameter of the lymphatic ducts was 0.61 mm, and the iliolumbar veins were 0.81 mm. On the other hand, the mean diameters of the 28 lymphatic ducts and veins of the 8 patients in whom we performed LVA were 0.58 and 0.76 mm, respectively. The differences in the diameters of the lymph vessels and veins between the rats and patients were not statistically significant. CONCLUSIONS: We report on an LVA model involving the use of the lumbar lymphatic duct and iliolumbar veins of rats. The diameter, nature, and placement of the anastomosis using this model are very similar to that noted during real human surgery. We believe that our rat model will be useful as a practical training model for LVA and in studies on postoperative changes in LVA.

Iliolumbar Vein as a Training Model for Microsurgical End-to-Side Anastomosis.

Although a multitude of microsurgical training models have been reported, few experimental animal models are available for end-to-side anastomosis. In this study, the authors developed an end-to-side anastomosis rat training model that utilizes the iliolumbar vein and investigated its characteristics. Ten Wistar male rats were used as microvascular end-to-side anastomosis models. Diameters of the posterior vena cava and the root of the iliolumbar vein were measured on both sides. The mean diameter of the posterior vena cava was 5.40 mm (range, 3.2-3.6 mm). The mean diameter of the root of the iliolumbar vein was 1.12 mm (range, 1.1-1.4 mm). The mean duration of bilateral end-to-side anastomosis was 50.6 minutes (range, 48-55 minutes). The intraoperative patency rate after anastomosis was 100%. The authors described a rat training model for microsurgical end-to-side anastomosis. This model is especially useful because it closely simulates a real operation, and training can be performed relatively quickly.

Analysis of 10-Year Training Results of Medical Students Using the Microvascular Research Center Training Program.

Background In this article, we reviewed the training results of medical students using the Microvascular Research Center Training Program (MRCP), and proposed an ideal microsurgical training program for all individuals by analyzing the training results of medical students who did not have any surgical experience. Methods As of 2015, a total of 29 medical students completed the MRCP. In the most recent 12 medical students, the number of trials performed for each training stage and the number of rats needed to complete the training were recorded. Additionally, we measured the operating time upon finishing stage 5 for the recent six medical students after it became a current program. Results The average operating time upon finishing stage 5 for the recent six medical students was 120 minutes ± 11 minutes (standard deviation [SD]). The average vascular anastomosis time (for the artery and vein) was 52 minutes ± 2 minutes (SD). For the most recent 12 medical students, there was a negative correlation between the number of trials performed in the non-rat stages (stages 1-3) and the number of rats used in the rat stages (stages 4-5). Conclusion Analysis of the training results of medical students suggests that performing microsurgery first on silicon tubes and chicken wings saves animals' lives later during the training program. We believe that any person can learn the technique of microsurgery by performing 7 to 8 hours of training per day over a period of 15 days within this program setting.

[Effects of aprepitant in daily administrations of low-dose cisplatin].

OBJECTIVE: While aprepitant is actually recommended for the prevention of nausea and vomiting induced by a single cisplatin administration, it is still unclear whether it has a clinical benefit when administered along with daily administrations of low- dose cisplatin(20mg/m2 days 1-5). This study was conducted to evaluate the efficacy of aprepitant in patients receiving daily administration of low-dose cisplatin. METHODS: Our study focused on 25 patients who received cancer therapy including cisplatin, with or without aprepitant (days 1-5). We performed a retrospective study to identify any significant positive effect of aprepitant in the prevention of nausea and vomiting for 10 days(days 1-10). Because cisplatin has a long half-life, we assessed the delayed phase nausea and vomiting(days 6-10). RESULTS AND CONCLUSION: Multiple-day dosing of aprepitant was effective for prevention of nausea(Odds ratio: 0. 30, p= 0. 0012)and vomiting(Odds ratio: 0. 04, p=0. 0001)throughout the observation. Furthermore, we observed a significant positive effect of aprepitant in the prevention of delayed nausea(Odds ratio: 0. 19, p=0. 0083)and vomiting(Odds ratio: 0. 07, p=0. 0040). These findings suggest that multiple-day dosing of aprepitant is useful for the inhibition of acute delayed nausea and vomiting caused by chemotherapy including daily administration of low-dose cisplatin.

Negative pressure wound therapy with instillation without open-window thoracostomy for empyema.

Treatment of empyema is very challenging. The use of negative pressure wound therapy (NPWT), and NPWT with instillation and dwell time (NPWTi-d) for wound closure have attracted attention. However, they are both limited to use after open-window thoracostomy (OWT) performed to control infection. In some patients with poor general conditions, who cannot undergo surgery, no treatment for empyema is available. Therefore, we devised a new treatment for such patients with NPWTi-d without OWT (non-OWT NPWTi-d). Here we present the cases of two patients with refractory empyema after intrathoracic irrigation and drainage, who underwent non-OWT NPWTi-d using the fistula of the thoracic drain. Both the patients recovered. The first patient was treated for 31 days. As the empyema persisted, he underwent a repeat intrathoracic drainage after which the wound healed. The second patient was treated for 20 days. Non-OWT NPWTi-d may be a new option to treat empyema.

Enhancement of Lymphatic Vessels in the Superficial Layer in a Rat Model of a Lymphedematous Response.

BACKGROUND: The morphologic and histologic behavior of lymphatic vessels in lymphedema has not been well analyzed using laboratory animals. The purpose of the present study was to elucidate the regeneration process of lymphatic vessels after acute lymphedema in a rat model. METHODS: The acute lymphedema was induced by an amputation and a replantation surgery on a rat hind limb. Recovery of lymphatic flow was traced using fluorescent lymphography with dye injection. The morphology and number of lymphatic vessels were immunohistochemically detected and quantified in both superficial and deep layers. RESULTS: The swelling was the most severe, and the number of lymphatic vessels in the superficial layer was significantly and maximally increased on postoperative day 3. Backflows and overflows were also detectable in the superficial layer on postoperative day 3. The number of lymphatic vessels had decreased but remained significantly higher than that in the controls on postoperative day 14, when the swelling decreased to the levels in the controls. In contrast, the number of lymphatic vessels in the deep layer showed a tendency toward increased numbers; however, it was not statistically significant on postoperative day 3, 7, or 14. CONCLUSIONS: We have obtained solid evidence showing the differential potency of lymphatic vessels between the superficial and the deep layers after temporal lymphedematous induction. Further analysis of lymphedematous responses in animal models could provide new insights into the challenges associated with the clinical treatment of lymphedema.

Histologic Evaluation of Lymphaticovenular Anastomosis Outcomes in the Rat Experimental Model: Comparison of Cases with Patency and Obstruction.

BACKGROUND: Lymphaticovenular anastomosis plays an important role in the surgical treatment of lymphedema. The outcomes of lymphaticovenular anastomosis are evaluated based on changes in edema; however, isolated assessment of the anastomosis itself is difficult. The authors used an animal experimental model to conduct a detailed examination of histologic changes associated with lymphaticovenular anastomosis and determined the factors important for success. METHODS: The experimental lymphaticovenular anastomosis model was created using lumbar lymph ducts and iliolumbar veins of Wistar rats. The authors performed anastomosis under a microscope and reviewed postoperative histologic changes using optical and electron microscopy. In addition, electron microscopy and histology were used for detailed examination of the area in the vicinity of the anastomotic region in cases with patency and obstruction. RESULTS: The patency rates immediately after, 1 week after, and 1 month after lymphaticovenular anastomosis were 100 percent (20 of 20), 70 percent (14 of 20), and 65 percent, respectively. A detailed examination of the anastomotic region with electron microscopy revealed that, in cases with patency, there was no notable transformation of the endothelial cells, which formed a smooth layer. In contrast, in obstruction cases, the corresponding region of the endothelium was irregular in structure. CONCLUSIONS: Vessel obstruction after lymphaticovenular anastomosis may be associated with irregular arrangement of the endothelial layer, leading to exposure of subendothelial tissues and platelet formation. One part of the postoperative changes after anastomosis and a cause of obstruction were elucidated in this study. The authors' results may enable improvements in lymphaticovenular anastomosis by translating back to real clinical operations.

Vascularized peripheral nerve grafting promotes myelination of regrowing optic nerve.

We investigated whether the use of vascularized peripheral nerve grafts on the optic nerve stump enhances axonal regeneration of retinal ganglion cells compared with isolated nonvascularized grafts. The rat median nerve was microsurgically sutured with its supplying artery and vein to the optic nerve stump. The number of retinal ganglion cells with regenerating axons was evaluated by retrograde labeling into the grafted peripheral nerve, and the myelination of the regenerating axon fibers was examined by electron microscopy. The number of retinal ganglion cells with regenerating axons was significantly higher in the vascularized graft than in the nonvascularized graft. The ratio of myelinated axon fibers was also increased in vascularized grafts. Thus, grafting with their supplying arteries and veins to an injured nerve stump represents a promising strategy to accelerate axonal regeneration from neurons of the central nervous system.

Evaluation of the microvascular research center training program for assessing microsurgical skills in trainee surgeons.

BACKGROUND: We established the Microvascular Research Center Training Program (MRCP) to help trainee surgeons acquire and develop microsurgical skills. Medical students were recruited to undergo the MRCP to assess the effectiveness of the MRCP for trainee surgeons. METHODS: Twenty-two medical students with no prior microsurgical experience, who completed the course from 2005 to 2012, were included. The MRCP comprises 5 stages of training, each with specific passing requirements. Stages 1 and 2 involve anastomosing silicone tubes and blood vessels of chicken carcasses, respectively, within 20 minutes. Stage 3 involves anastomosing the femoral artery and vein of live rats with a 1-day patency rate of >80%. Stage 4 requires replantation of free superficial inferior epigastric artery flaps in rats with a 7-day success rate of >80%. Stage 5 involves successful completion of one case of rat replantation/transplantation. We calculated the passing rate for each stage and recorded the number of anastomoses required to pass stages 3 and 4. RESULTS: The passing rates were 100% (22/22) for stages 1 and 2, 86.4% (19/22) for stage 3, 59.1% (13/22) for stage 4, and 55.0% (11/20) for stage 5. The number of anastomoses performed was 17.2±12.2 in stage 3 and 11.3±8.1 in stage 4. CONCLUSIONS: Majority of the medical students who undertook the MRCP acquired basic microsurgical skills. Thus, we conclude that the MRCP is an effective microsurgery training program for trainee surgeons.

Demonstrating the lymphatic system in rats with microinjection.

The lymphatic system plays an important role in human health and disease. In addition to a role in the immune response, the lymphatics can serve as a pathway for cancer metastasis. Visualizing the lymphatic system has been a difficult part of anatomic dissection studies. Anatomists have attempted to map the lymphatic system using various methods and materials; vivisection of dogs, injection of mercury into the skin and lymphatic vessel in cadavers, and injection of dye indirectly into the skin of dead and living specimens. In this study, we introduce a method of using a mixture of acrylic blue dye and hydrogen peroxide to visualize the lymphatic system in rats. The lymphatic vessels were cannulated with micropipettes, and radio-opaque orange lead oxide was selectively injected. The lymphatic system became visible from the dorsal side of the hand and foot, and distal region of the tail to their termination at the left and right subclavicular veins via lymph nodes. Cisterna chyli in the abdominal cavity and thoracic duct ran along with the aorta. The advantage of this technique is that lymph nodes as well as lymphatic channels could be recorded not only photographically but also radiographically. This microinjection technique is useful for demonstrating the lymphatic system in rats and may provide further information that will help in cancer metastasis research.