Potential role of transforming growth factor-beta 1/Smad signaling in secondary lymphedema after cancer surgery.

Secondary lymphedema often develops after cancer surgery, and over 250 million patients suffer from this complication. A major symptom of secondary lymphedema is swelling with fibrosis, which lowers the patient's quality of life, even if cancer does not recur. Nonetheless, the pathophysiology of secondary lymphedema remains unclear, with therapeutic approaches limited to physical or surgical therapy. There is no effective pharmacological therapy for secondary lymphedema. Notably, the lack of animal models that accurately mimic human secondary lymphedema has hindered pathophysiological investigations of the disease. Here, we developed a novel rat hindlimb model of secondary lymphedema and showed that our rat model mimics human secondary lymphedema from early to late stages in terms of cell proliferation, lymphatic fluid accumulation, and skin fibrosis. Using our animal model, we investigated the disease progression and found that transforming growth factor-beta 1 (TGFB1) was produced by macrophages in the acute phase and by fibroblasts in the chronic phase of the disease. TGFB1 promoted the transition of fibroblasts into myofibroblasts and accelerated collagen synthesis, resulting in fibrosis, which further indicates that myofibroblasts and TGFB1/Smad signaling play key roles in fibrotic diseases. Furthermore, the presence of myofibroblasts in skin samples from lymphedema patients after cancer surgery emphasizes the role of these cells in promoting fibrosis. Suppression of myofibroblast-dependent TGFB1 production may therefore represent an effective pharmacological treatment for inhibiting skin fibrosis in human secondary lymphedema after cancer surgery.

Characteristics of Symptomatic Pulmonary Thromboembolism among Postoperative and Hospitalized Patients.

Backgrounds: Pulmonary thromboembolism (PTE) is severe complication which may arise during all medical service. The purpose of this study is to evaluate inpatient symptomatic PTE. Materials and Methods: From 2005 to 2016, we experienced 75 symptomatic PTE patients among 600 venous thromboembolism patients. According to the place of occurrence, patients were divided to inpatient group and outpatient group. We further divided inpatient group to surgical group and non-surgical group. Results: Inpatients group, 38 had PTE (surgical: 23, non-surgical: 15). Outpatients group, 37 had PTE (with medical practice: 22, without medical practice: 15). Severity of PTE were follows; cardiac arrest 2, massive 13, sub-massive 18, non-massive 42. In surgical group, anticoagulation had been used in 3/23 (13.6%), intermittent pneumatic compression had been used in 16/23 (72.9%), compression stockings had been used in 20/23 (90.9%). In non-surgical group, no anticoagulation had not been used, intermittent pneumatic compression had been used in 2/15 (13.3%), compression stockings had been used in 2/15 (13.3%). Conclusion: As PTE prophylaxis, anticoagulation had been scarcely used in surgical group. Delayed anticoagulation may decrease symptomatic PTE in surgical patients. Despite adequate prophylaxis, PTE cannot be prevented completely. Medical staff and patients should recognize the risk of PTE together. (This is a translation of Jpn J Phlebol 2018; 29(1): 33-40.).

Axillo-Axillary Artery Bypass With Coil Embolization of the Innominate Artery for a Traumatic Innominate Artery Aneurysm: A Case Report.

BACKGROUND: Innominate artery aneurysm (IAA) is a rare cervical artery aneurysm. Although atherosclerosis is its most common cause, IAAs due to cervical injury are often reported. Operative indications for IAAs include rupture or symptomatic aneurysm, saccular aneurysm, aneurysm with a diameter of 3 cm or greater, and aneurysmal change of the origin of the innominate artery. Although the ligature of the innominate artery or open surgical repair is well described, the usefulness of endovascular repair has also recently been reported. Herein, we report a case of traumatic IAA with infection in the cervical region after tracheostomy. CASE PRESENTATION: A 40-year-old man with cholecystolithiasis planned to undergo laparoscopic cholecystectomy at another hospital. Urgent tracheostomy was performed because of laryngeal edema at the induction of general anesthesia. Enhanced computed tomography angiography 1 week after the tracheostomy revealed a saccular IAA. The patient was deemed to be at high risk for aneurysm rupture and was referred to our hospital. Preoperative Matas test, Allcock test, and innominate arterial stump pressure measurement were performed to assess the cerebral blood flow and ischemic tolerance of the brain. These examinations showed the patency of the circle of Willis. An axillo-axillary artery bypass with coil embolization of the innominate artery was performed to avoid postoperative vascular graft infection. No postoperative complications such as infection or cerebral infarction occurred. Magnetic resonance imaging angiography performed 6 months after surgical treatment showed that the aneurysm had disappeared, and patency of the bypass graft was present. There were no postoperative complications, such as neurological deficits or graft infection, at more than 5 years after surgery. CONCLUSIONS: We report a successfully treated case of IAA after tracheostomy. Axillo-axillary artery bypass with coil embolization of the innominate artery is an effective treatment of IAA with cervical infection.

Topologic distributions of vasa vasorum and lymphatic vasa vasorum in the aortic adventitia--Implications for the prevalence of aortic diseases.

BACKGROUND AND AIMS: Vasa vasorum (VV) and lymphatic vasa vasorum (LVV) form their own networks in the adventitia. VV supply the aorta with nutrition and oxygen; however, the distribution and role of LVV remains to be determined. The purpose of this study was to investigate differences in the distribution of VV and LVV along the aorta. METHODS: Aortic samples were obtained from 22 autopsy cases without medical history of aortic diseases. Aortic segments were classified as arch (Ar), descending thoracic (De), suprarenal abdominal (S-Ab), and infrarenal abdominal (I-Ab). Adventitial VV and LVV were identified immunohistochemically. RESULTS: VV were most dense in the arch aorta, becoming less dense along the aorta in more distal segments, with the lowest density occurring in the infrarenal abdominal aorta. There was a significant correlation between the numbers of VV and medial thickness in the total aortic segments (r = 0.518, p < 0.01). In contrast, there was no significant correlation between the number of LVV and medial thickness in any aortic segments. However, there was a significant correlation between the number of LVV and intimal thickness in I-Ab (r = 0.425, p < 0.05). CONCLUSIONS: The distributions of adventitial VV and LVV were characteristic along the aortic segments. Differences in the distributions may imply the prevalence of aortic diseases such as dissection, abdominal aortic aneurysm, and atherosclerotic occlusive disease in each aortic segment.

Effects of Compression Stockings on Elevation of Leg Lymph Pumping Pressure and Improvement of Quality of Life in Healthy Female Volunteers: A Randomized Controlled Trial.

BACKGROUND: Lymph is pumped through the collecting lymphatic vessels by both intrinsic and extrinsic forces. The intrinsic pump relies on spontaneous lymphatic contraction, which generates the pumping lymph pressure (Plp). Among healthy people with daily leg edema, a considerable number of cases are accompanied with low leg Plp. Herein, a double-blinded controlled trial was conducted in healthy female volunteers with reduced leg Plp to compare the effectiveness of a 15-29 mmHg compression stocking (Stocking A) and a 8-16 mmHg stocking (Stocking B) on elevating Plp. METHOD AND RESULTS: Among 219 healthy female volunteers who underwent measurement of leg Plp, 80 participants (36.5%) had unilateral or bilateral legs with Plp < 20 mmHg (122 legs with Plp < 20 mmHg and 38 legs with Plp ≧ 20 mmHg). These 80 participants were assigned to wear either Stocking A (n = 40) or Stocking B (n = 40) for 16 weeks. Leg Plp was measured using indocyanine green fluorescence lymphography and an occlusion cuff technique while sitting. At 16 weeks, both Stockings A and B resulted in significantly elevated leg Plp, with the effect on elevating Plp being superior for Stocking A. Only Stocking A resulted in decreased prevalence of leg edema and improved Short Form-36 scores. CONCLUSION: Compression stockings may represent a therapeutic option to elevate leg Plp and ameliorate leg edema, thereby leading to improved quality of life in healthy females with low leg Plp.

Low Lymphatic Pumping Pressure in the Legs Is Associated with Leg Edema and Lower Quality of Life in Healthy Volunteers.

BACKGROUND: Lymph is pumped through the collecting lymphatic vessels by both intrinsic and extrinsic forces, propelling it downstream back into circulation. The intrinsic lymph pump relies on the spontaneous contraction of lymphatic muscles to generate the force of pumping lymph (P(lp)). However, the association between leg edema and reduced leg P(lp) in the general population is unknown. Therefore, this study determined the association of leg P(lp) and edema complaints and quality of life in healthy participants. METHODS AND RESULTS: A total of 465 healthy volunteers (78 men and 387 women, age 30-85 years) filled out a questionnaire and medical history to rule out severe systemic diseases and local venous/lymphatic diseases. Quality of life was assessed using the Medical Outcome Study Short Form 36 (SF36). Leg P(lp) was measured using minimally invasive indocyanine green fluorescence lymphography and an occlusion cuff technique while sitting. All participants were divided into three groups according to the P(lp) values, as follows: Participants with P(lp) >40 mmHg in both legs, 20 mmHg-40 mmHg in either leg; and <20 mmHg in both legs were divided into the good (n=100), moderate (n=314), and poor (n=51) P(lp) groups, respectively. The survey revealed the poor leg P(lp) group was associated with more frequently complaints of leg edema, as well as lower quality of life than the moderate and good P(lp) groups. CONCLUSION: Reduced leg P(lp) is significantly associated with leg edema complaints and lower quality of life in the general population.

Early outcomes of iliac branch grafts in the endovascular repair of abdominal aortic aneurysms with concomitant bilateral common iliac artery aneurysms at a Japanese institution.

PURPOSE: Endovascular aneurysm repair (EVAR) is used to treat abdominal aortic aneurysms (AAAs) with bilateral common iliac artery aneurysms (CIAAs), and an interruption of the bilateral internal iliac arteries (IIAs) is often needed, which may cause postoperative ischemic complications. An iliac branch device (IBD) has thus been introduced as an endovascular technique to preserve the IIA flow. This study aimed to evaluate the technical feasibility and short-term results of using an IBD when treating AAA with bilateral CIAAs in a Japanese institution, where IBD use has still not been approved by the government. METHODS: EVAR was performed using an IBD in six patients at high risk for open repair of an AAA with bilateral CIAAs. RESULTS: Advanta V12 stent grafts were successfully placed in the IIA, bridging between the IIA and the IBD side branch from the contralateral iliac artery. Subsequently, EVAR was performed as usual. The technical success rate was 100 %. At the most recent follow-up (mean follow-up period, 14.2 months), all IBDs were patent. No patients complained of buttock claudication or ischemic colitis. CONCLUSIONS: The implantation of an IBD during EVAR is technically feasible in Japanese AAA patients with bilateral CIAAs, and may be a viable method to avoid pelvic ischemic complications, such as intractable buttock claudication.

Intraoperative lymph mapping with preoperative vein mapping to prevent postoperative lymphorrhea following paramalleolar bypass surgery in patients with critical limb ischemia.

PURPOSE: Paramalleolar bypass surgery requires a long incision to harvest the great saphenous vein (GSV), which is often associated with intractable postoperative lymphorrhea. To prevent this complication, we developed a novel method of intraoperative lymph imaging and preoperative vein mapping for vein harvesting. METHODS: Thirteen consecutive patients with critical limb ischemia (CLI) underwent both preoperative vein mapping and intraoperative lymph mapping (Group A). Duplex vein mapping was performed to mark the GSV. Lymph mapping was performed with indocyanine green fluorescence lymphography. Paramalleolar bypasses were performed using reversed GSV grafts, with careful ligation of the subcutaneous lymph collector vessels above the GSV. The development of intractable postoperative lymphorrhea and the length of the postoperative hospital stay were compared with those in the previous ten consecutive CLI patients without lymph mapping who underwent paramalleolar bypass (Group B). RESULTS: The occurrence of intractable wound lymphorrhea by the 30th postoperative day was 3/10 (30 %) in Group B, while it was 0/13 (0 %) in Group A (p < 0.05). The length of the postoperative hospital stay was 31.7 ± 8.8 and 57.5 ± 39.5 days (Group A and Group B, respectively, p < 0.05). CONCLUSIONS: Intraoperative lymph mapping and preoperative vein mapping are technically feasible and can positively contribute to the prevention of postoperative lymphorrhea after GSV harvesting.

Early experience with fenestrated stent grafts for treatment of juxtarenal aortic aneurysm.

BACKGROUND: Fenestrated endovascular abdominal aneurysm repair (FEVAR) using branched arteries devices for visceral arteries is increasingly being used for the repair of juxtarenal aortic aneurysms (JAAs) in Europe, United States, Australia, New Zealand, and Asia. This study aimed to evaluate the technical feasibility and short-term results of FEVAR in treating JAAs in Japanese patients. METHODS AND RESULTS: FEVAR with Cook fenestrated stent-graft (Cook Medical Inc., Bloomington, Indiana, USA) was performed for 5 patients at high risk for open repair of JAA. Seventeen visceral vessels were successfully accommodated with 12 fenestrations, and five visceral arteries with four scallops with a loss of renal artery. In one case, a type III endoleak occurred at a renal artery fenestration, and this had disappeared in the 1-month postoperative computed tomography (CT). The mean follow-up duration was 8 months. Iliac leg occlusion occurred in 1 case, which was treated with thrombectomy and additional leg device deployment. All patients had survived at the end of the follow-up period and continued their outpatient visits. CONCLUSIONS: Implantation of a Cook fenestrated stent-graft incorporating the visceral arteries is technically feasible in high-risk Japanese patients with JAA and may be a viable alternative to current methods.