Risk and Prognosis of Upper Extremity Deep Vein Thrombosis.

Objectives: We aimed to investigate the clinical features of upper extremity deep vein thrombosis (UEDVT). Methods: We retrospectively reviewed the background, thrombus site, treatment, and outcome of 76 UEDVT patients. Results: Of the 76 UEDVT patients, 44 (57.9%) were men, and 51 (67.1%) were complicated by malignancy, 44 (57.9%) had an indwelling central vein (CV) catheter, 8 (10.5%) had concomitant pulmonary embolization (PE), and 33 (43.3%) were symptomatic. Regarding the thrombus site, the right internal jugular vein was the most common, with 30 cases (35.3%). As regards the treatment method, 53 patients (69.7%) received oral anticoagulants. In 2015, when direct oral anticoagulants (DOACs) was covered by insurance, there were 44 UEDVT cases, of which 34 (77.3%) received DOACs. Outcomes at a mean observation period of 37.5±41.5 months included 40 deaths (52.6%) with a mean survival of 16.3±21.3 months. The most common cause of death was malignancy, with 33 cases (82.5%). Conclusion: In the background of UEDVT, the combination of indwelling CV catheter placement and malignancy was frequently observed. While the risk of recurrence or PE complications is low, the prognosis of UEDVT complicated by malignancy is extremely poor.

Real-Time Assessment of Tissue Oxygen Saturation Using a Novel Oximeter During Revascularization for Acute Limb Ischemia: A Case Report.

Emergency surgery was performed to treat acute lower limb ischemia caused by heart thromboembolism and concomitant popliteal artery aneurysm. Using a near-infrared spectroscopy oximeter, regional tissue oxygen saturation (rSO2) was monitored to assess the tissue perfusion pre-, intra-, and postoperatively. rSO2 values did not increase sufficiently following thromboembolectomy of the superficial femoral artery, but they dramatically recovered after additional popliteal-anterior tibial bypass surgery. The affected limb was successfully salvaged. rSO2 monitoring was easily measured intraoperatively, which might be beneficial in evaluating tissue perfusion in patients with acute limb ischemia.

The Usefulness of a Three-Microneedle Device for Indocyanine Green Fluorescence Lymphography.

Background: Indocyanine green (ICG) fluorescence lymphography is widely used to diagnose lymphedema. There is little consensus on the appropriate injection method for ICG fluorescence lymphangiography. We used a three-microneedle device (TMD) for skin injection of ICG solution and investigated its usefulness. Methods and Results: Thirty healthy volunteers were injected with ICG solution using a 27-gauge (27G) needle in one foot and a TMD in the other foot. Injection-related pain was evaluated using the Numerical Rating Scale (NRS) and Face Rating Scale (FRS). The skin depth of the injected ICG solution was evaluated by injecting the solution into the skin of amputated lower limbs using a 27G needle or TMD using ICG fluorescence microscopy. The median and interquartile range of the NRS scores was 3 (3-4) and 2 (2-4) in the 27G needle and TMD groups, respectively; that of the FRS scores was 2 (2-3) and 2 (1-2) in the 27G needle and TMD groups, respectively. Injection-related pain was significantly lower with the TMD than with the 27G needle. The lymphatic vessels were similarly visible using both needles. The depth of the ICG solution varied for each injection with a 27G needle (400-1200 µm) and was consistent at ∼300-700 µm below the skin surface using the TMD. Injection depth was significantly different between the 27G needle and the TMD. Conclusions: Injection-related pain decreased using the TMD, and ICG solution depth was consistent on fluorescence lymphography. A TMD may be useful for ICG fluorescence lymphography. Clinical Trials Registry (UMIN-CTR; ID: UMIN000033425).

Characteristics and Prognostic Factors of Venous Thromboembolism in Cancer Patients.

Background: Improving the prognosis of patients with malignant tumors is increasing the number of patients who develop venous thromboembolism. We examined the characteristics and prognostic factors of VTE patients with cancer. Methods: We diagnosed 725 VTE patients from April 2005 to March 2018. There were 322 cancer associated patients (CAT) and 403 non-cancer associated patients (nonCAT). We examined characteristics and prognostic factors of VTE in CAT patients. Results: There were 156 women and 166 men in CAT, and 132 women and 271 men in nonCAT. There was no significant difference in the location of proximal portion of thrombus. When locations were divided into left leg, right leg, and bilateral legs, bilateral cases were more common in CAT group. Comparing the overall survival after VTE diagnosis in the CAT group, the prognosis was poor in patients with high D-dimer level (≧6 µg/mL) along with cancer metastasis and recurrence. Conclusions: Various VTE factors predict prognosis in CAT patients, and CAT is important in the treatment of cancer patients. (This is secondary publication from Jpn J Phlebol 2020; 31(3): 153-159.).

The Patency of Tibial/Peroneal Arteries Affects the Increment of Regional Tissue Saturation of Oxygen in Each Angiosome after Superficial Femoral Artery Revascularization.

Objective: The angiosome model is a controversial concept in the revascularization of patients with chronic limb-threatening ischemia (CLTI). The aim of this study was to demonstrate the importance of patency of the tibial/peroneal arteries for regional tissue oxygenation in each angiosome during endovascular therapy (EVT) of the superficial femoral artery (SFA). Materials and Methods: We devised a novel near-infrared spectroscopy oximeter, "TOE-20," for real-time monitoring of regional tissue oxygen saturation (rSO2). Using TOE-20, we prospectively assessed rSO2 at each angiosome in 23 CLTI patients who underwent successful revascularization of the SFA. During EVT, three sensor probes were placed at the dorsal foot, plantar foot, and outer ankle for rSO2 monitoring. Results: At the end of EVT, rSO2 at all angiosomes was significantly elevated by SFA revascularization. The change in rSO2 in each angiosome was larger in patients with patent relevant arteries than in those with occluded relevant arteries (i.e., anterior tibial artery patency, posterior tibial artery patency, and peroneal artery patency). Conclusion: The patency of the tibial/peroneal arteries is important for regional tissue oxygenation in EVT. Using TOE-20 and rSO2-based revascularization, it may possible to anticipate whether an ischemic ulcer will heal or not.

Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema.

Background: Secondary lymphedema (LE) occurs due to the disruption of lymphatic circulation. Lymphatic fluid accumulation in subcutaneous tissues induces adipocyte proliferation. Obesity is an important risk factor for the occurrence and deterioration of LE. Although the relationship between LE and subcutaneous adipose tissue increase has been reported clinically, their pathophysiological relationship remains unknown. Thus, we aimed to verify whether subcutaneous adipose tissue increase is involved in the pathophysiology of secondary LE. Methods and Results: The hindlimb model of secondary LE was created using male Sprague-Dawley rats (control and LE groups; n = 5 each). Skin samples were obtained on postoperative day 168. Histological examination and quantitative real-time polymerase chain reaction analysis of inflammatory adipokines, tumor necrosis factor-alpha (Tnf-α), C-C chemokine ligand 2 (Ccl2), and interleukin-6 (Il-6) were performed. Limb volume and subcutaneous adipose tissues significantly increased in the LE group compared with those in the control. Macrophages aggregated in the augmented adipose tissues, around the adipocytes, and formed crown-like structures (CLSs). The number of CLSs significantly increased in the LE group. These macrophages expressed transforming growth factor-beta 1 (TGF-ß1). Inflammatory adipokine secretion was not observed. Although Il-6 expression increased in the LE group, IL-6 was expressed in subcutaneous myofibroblasts but not in subcutaneous adipocytes. Conclusion: As TGF-ß1 derived from subcutaneous myofibroblasts is involved in skin fibrosis during LE, TGF-ß1 derived from adipose tissues may also play a similar role. Drug treatment for subcutaneous adipose tissue reduction may improve the skin condition in secondary LE and may be a new therapeutic strategy.

Differences in Vasa Vasorum Distribution in Human Aortic Aneurysms and Atheromas.

The pathophysiological difference between aortic atheromas and aneurysms is unknown. We focused on the vasa vasorum (VV), which play a critical role in maintaining aortic homeostasis and are also involved in vascular diseases. We investigated the differences in VV between the atheromas and aneurysms. Human abdominal aortic samples were obtained from patients with abdominal aortic aneurysm during surgery or autopsy cases. Autopsy cases were divided into 2 groups according to atheromas. The VV were evaluated using immunohistochemical staining for von Willebrand factor. Intimal VV increased in both the atheroma and aneurysm groups, medial VV increased, and adventitial VV decreased only in the aneurysm group. We also observed that the medial VV were connected to the adventitial VV in the atheroma group and to intimal VV in the aneurysm group. We suggest the outside-in VV or inside-out VV theories. Atheroma induces hypoxia of aortic walls, and angiogenic factors might induce an increase of intimal VV derived from adventitial VV (outside-in VV). However, adventitial VV decrease induces hypoxia of aortic walls, and angiogenic factors might induce an increase of intimal VV derived from aortic lumen (inside-out VV). These differences of VV may contribute in elucidating the pathophysiology of aortic diseases.

K-134, a phosphodiesterase 3 inhibitor, reduces vascular inflammation and hypoxia, and prevents rupture of experimental abdominal aortic aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease, which frequently results in fatal rupture; however, no pharmacologic treatment exists to inhibit AAA growth and prevent rupture. In this study, we investigated whether K-134, a novel phosphodiesterase 3 inhibitor, could limit the progression and rupture of AAA using multiple experimental models. METHODS: A hypoperfusion-induced AAA rat model was developed by inserting of a small catheter and via tight ligation of the infrarenal aorta. Rats were fed with a 0.15% K-134-containing diet (K-134(+) group) or a normal diet (K-134(-) group) from 7 days before the experiment to 28 days after model creation (pretreatment protocol). After the administration period, elastin fragmentation, macrophage infiltration, reactive oxygen species expression, matrix metalloproteinase levels, aneurysmal tissue hypoxia, and adventitial vasa vasorum (VV) stenosis were assessed. In the delayed treatment protocol, rats with AAA >3 mm were randomly divided to K-134(+) or K-134(-) group 7 days after model creation, and the effect of K-134 on suppressing preexisting AAA was examined. Further, elastase-induced rat model and angiotensin II-infused ApoE-/- mouse model were also used to examine the ability of K-134 to prevent rupture. RESULTS: K-134 prevented AAA rupture and significantly improved survival in the pretreatment protocol (P < .01). In the K-134(+) group, elastin degeneration was prevented; macrophage infiltration and reactive oxygen species production were significantly decreased. At 14 days, the enzymatic activity of matrix metalloproteinase-9 was significantly decreased. Further, K-134 inhibited intimal hyperplasia and VV stenosis. Expressions of hypoxic markers, hypoxia-inducible factor-1α, and pimonidazole, in the aneurysmal wall were also attenuated. In the delayed treatment protocol, K-134 also improved survival of rats with preexisting AAA. Similarly, in the elastase-induced rat model and angiotensin II-infused ApoE-/- mouse model, K-134 inhibited rupture and significantly improved survival (P < .01). CONCLUSIONS: K-134 prevented the rupture of AAA and improved survival through suppressing inflammatory reaction. The inhibition of intimal hyperplasia in the adventitial VV may be associated with reduced hypoxia in the aneurysmal tissue. (JVS-Vascular Science 2020;1:219-32.). CLINICAL RELEVANCE: This study shows that K-134, a novel phosphodiesterase 3 inhibitor, suppressed abdominal aortic aneurysm (AAA) rupture. Considering that K-134 had already undergone a phase Ⅱ study in the United States for claudication in peripheral artery occlusive disease patients with good tolerance, K-134 may become a promising new therapeutic option for AAAs and could undergo clinical trials for patients with small AAA.

Development of a Noninvasive Skin Evaluation Method for Lower Limb Lymphedema.

Background: The skin's condition is altered in lymphedema patients, and evaluating this change is important. Some noninvasive methods for evaluating skin condition have been reported, especially in upper limb lymphedema. However, evaluating the skin in lower limb lymphedema remains challenging and is often limited to palpation. We aimed to develop a noninvasive skin evaluation method for lower limb lymphedema patients. Methods and Results: Twenty-five lower limb lymphedema patients were included. Skin induration and elasticity were measured using Indentometer® IDM 400 and Cutometer® MPA580. The relationship between the properties of skin from the healthy forearm and thigh, those of the affected thigh, and age was analyzed. Predicted skin induration age (IA) and elasticity age (EA) were calculated from the forearm, whereas actual values were calculated from the thigh, and the differences (ΔIA and ΔEA) were assessed. Patients were classified according to the International Society of Lymphology clinical staging system, and the differences in ΔIA and ΔEA were analyzed among the three groups (healthy, stage I/IIa, and stage IIb/III). Skin biopsy was performed in five unilateral lower limb lymphedema patients, and the dermal elastic fiber area was determined using microscopy with Elastica van Gieson staining. ΔEA significantly increased with disease progression, but ΔIA did not change significantly. Microscopy revealed elastic fiber filamentous changes, with decreased elastic fiber areas in lymphedema-affected skin. Conclusion: To our knowledge, this is the first report to evaluate lower limb skin elasticity in lymphedema quantitatively and noninvasively. ΔEA is useful for evaluating skin condition progression in lymphedema patients.

[A Case of Advanced Gallbladder Cancer with Paraaortic Lymph Node Metastases Successfully Treated by Chemotherapy and Conversion Surgery].

The patient was a 76-year-old man who was admitted to our hospital with a diagnosis of ileus. A gallbladder tumor was found incidentally on CT, and it was diagnosed as gallbladder cancer. Enlargement of multiple lymph nodes, including the paraaortic lymph nodes, was observed, and PET-CT further showed FDG uptake in the lymph nodes. Based on these findings, the patient was diagnosed with Stage ⅣB gallbladder cancer with paraaortic lymph node metastases. Since surgical resection was not possible, chemotherapy with gemcitabine and cisplatin(GEM plus CDDP)was started. After completion of 4 courses of GEM plus CDDP, the enlarged lymph nodes were decreased in size on CT, and there was no FDG uptake on PET-CT. These findings indicated downstaging to Stage Ⅱ; thus, conversion surgery with extended cholecystectomy and lymph node dissection was performed. The pathological diagnosis confirmed that the patient had Stage Ⅱ cancer(pT2N0M0). A case of unresectable gallbladder cancer that was treated with GEM plus CDDP and subsequent conversion surgery is reported, along with a literature review.

[Four Cases of Ileocolic Intussusception Associated with Malignant Lymphoma of the Ileum].

We report the cases we encountered in our department involving 4 patients with malignant ilial lymphoma that caused ileocolic intussusception. The patients were 2 male and 2 female, aged 65-76 years. All patients' chief complaint was abdominal pain. Computed tomography revealed target signs characteristic of intussusception. Colonoscopy showed a tumor that escaped into the colon, leading to the diagnosis of ileocolic intussusception due to an ileal tumor. However, definitive diagnosis could not be achieved from biopsy. Thus, ileocecal resection or right hemicolectomy was performed. Macroscopically, all tumors were polypoid type and were present within 25 cm from the valve of Bauhin. Histological diagnoses were diffuse large B-cell lymphoma(DLBCL)in 2 patients, T-cell lymphoma in one, and follicular lymphoma in one. Postoperative chemotherapy was performed in patients with DLBCL and T-cell lymphoma. Tumors are commonly the cause of intussusception in adults; therefore, emergent surgery is imperative. When malignant lymphoma is diagnosed, a multidisciplinary approach that includes postoperative chemotherapy is necessary.

[A Case of Retroperitoneal Liposarcoma That Required Three Times Surgical Resections during Four Years].

The patient was a 64-year-old man, who had undergone surgical resection for a right retroperitoneal giant tumor. The histopathological diagnosis was a well-differentiated liposarcoma. Two years and 4 months after the initial surgery, 3 recurrent lesions were found on the dorsal side of the colon hepatic flexure, and resection was performed. One year and 1 month after the secondary surgery, the tumor recurred again, and invaded the right abdominal wall and right transverse colon. Tumor was completely resected macroscopically. All resected tumors were well-differentiated liposarcoma. There have not been any signs of recurrence until 1 year and 6 months after the last operation. For retroperitoneal liposarcoma, complete surgical resection is the only established treatment, but the tumor often recurs. Aggressive resection against recurrent cases is known to contribute to life prognosis, but there is a possibility of the degeneration to a highly malignant dedifferentiated tumor while recurrence is repeated. Therefore, sufficient follow-up observation is needed.

[Results of Preoperative Colon Stent Placement for Obstructive Colorectal Cancer].

We examined short-term outcomes in 34 patients who had stenting as a bridge to surgery(BTS)for obstructive colorectal cancer during the 5-year period between April 2012 and March 2017.T he patients were 22 men and 12 women with a mean age of 72.6 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.5 days.No serious complications related to stenting occurred.Elective surgery could be performed in all patients after stenting.The mean number of days to surgery was 24.7 days.Laparoscopic surgery was performed in 14 patients.Postoperative complications included minor leakage in 1 patient, an abdominal wall abscess due to tumor invasion of the abdominal wall in 1 patient, and heart failure and pneumonia, as serious complications, in 1 patient each.Colorectal stenting in patients with obstructive colorectal cancer is a safe and relatively simple procedure.This is an effective treatment strategy in which preoperative colorectal decompression enables a one-stage resection.

[Findings from Total Colonoscopy in Obstructive Colorectal Cancer Patients Who Underwent Stent Placement as a Bridge to Surgery(BTS)].

We clinically investigated 34 patients with obstructive colorectal cancer who underwent placement of a colonic stent as a bridge to surgery(BTS), focusing on endoscopic findings after stent placement.Twenty -nine patients(85.3%)underwent colonoscopy after stent placement, and the entire large intestine could be observed in 28(96.6%).Coexisting lesions were observed in 22(78.6%)of these 28 patients.The lesions comprised adenomatous polyps in 17 patients(60.7%), synchronous colon cancers in 5 patients(17.9%), and obstructive colitis in 3 patients(10.7%), with some overlapping cases.All patients with multiple cancers underwent one-stage surgery, and all lesions were excised at the same time.Colonoscopy after colonic stent placement is important for preoperative diagnosis of coexisting lesions and planning the extent of resection. These considerations support the utility of colonic stenting for BTS.