[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].

We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer( invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).

[A Case of Recurrent Breast Cancer with Multiple Bone Metastasis Effectively Treated by CDK4/6 Inhibitor in Addition to Aromatase Inhibitor].

We report a case of recurrent breast cancer with multiple bone metastasis in a 62-year-old woman. Her breast cancer (invasive ductal carcinoma, T2N0M0, Stage ⅡA)was resected in 2001(partial mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(UFT)and irradiation to her left remnant breast. In February 2018, she complained of severe pain in right femoral joint and hip. CT scan showed a left cystic breast tumor(17 cm)and multiple bone metastasis. The core needle biopsy of the costal bone lesion and left mastectomy were performed. These pathological findings were recurrence of the breast cancer(ER+). The endocrine therapy(exemestane, aromatase inhibitor), the administration of denosumab and irradiation to painful bone lesions were performed, but it did not suppress tumor progression. The treatment of letrozole plus palbociclib(CDK4/6 inhibitor)were continued for 3 months from May 2018, and this therapy made her bone lesions smaller, but palbociclib were stopped due to its severe neutropenia. After that, the single administration of letrozole was continued, but the tumor marker did not become normal. In February 2019, abemaciclib was administered in addition to letrozole. One year later, her symptoms improved and her bone metastases have showed partial response.

[A Case of Pyloric Stenosis Due to Gastric Metastasis of Breast Cancer].

We report a case of left advanced breast cancer(T4N1M0, Stage ⅢA)in a 67-year-old woman. In August 2010, her breast cancer(triple-negative invasive ductal carcinoma)was resected(mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(TC)and irradiation to her chest wall. In July 2018, she experienced recurrent vomiting. Gastrointestinal endoscopy(GS)revealed type Ⅳ advanced gastric cancer-like appearance with pyloric stenosis. Pathological findings confirmed hormone-positive gastric metastasis of breast cancer. Systemic chemo-endocrine therapy(EC and anastrozole) was performed, following which her symptoms improved. In May 2019, recurrent vomiting appeared again. Thereafter, systemic chemo-endocrine therapy(paclitaxel plus bevacizumab and fulvestrant)was initiated, and her symptoms showed improvement. In November 2020, she showed obstructive jaundice due to malignant biliary stenosis. She was treated using endoscopic biliary stenting, but died 2 months later. Gastric metastasis is reported rarely in 4% of all breast cancers, and GS should be recommended in cases of recurrent abdominal complaints.

[A Useful Method of Nipple-Side HydroMARK-Marking before Neoadjuvant Chemotherapy in the Breast Preserving Surgery-A Case Report with pCR of the Triple Negative Breast Cancer].

When the primary breast cancer disappears by neoadjuvant chemotherapy, it is often difficult to detect it during the breast preserving surgery. Before neoadjuvant chemotherapy, preoperative nipple-side HydroMARK-marking, which was made of titanium coil and hydrogel, was a very useful and effective method because of its fine detection by ultrasonography. We report a case of 51-year-old female with the triple negative breast cancer(TNBC). At first, the HydroMARK was inserted between the nipple and the tumor. Its distance was about 10 mm toward the nipple. EC therapy followed by docetaxel was performed for 6 months as neoadjuvant chemotherapy. After that, her left TNBC(T1N0M0, Stage Ⅰ, invasive ductal carcinoma, ER[-], PgR[-], HER2[-])was disappeared in all imagings and resected in August 2018. The HydroMARK was clearly detected by intraoperative ultrasonography and her right breast preserving surgery was completely performed. Its pathological finding was pCR(pathological complete response).

[Fluorescence Detection System for Intraoperative Identification of the Parathyroid Glands in a Patient with Thyroid Cancer with a Right Non-Recurrent Inferior Laryngeal Nerve].

Intraoperative identification of the parathyroid gland is very important during thyroid and parathyroid surgery.Recently, intrinsic fluorescence of the parathyroid gland was identified and reported.We report the case of a 45-year-old woman with thyroid papillary cancer.Before surgery, neck and chest CT showed a thyroid tumor(20mm)of the right lobe and an aberrant right subclavian artery.Her thyroid cancer(T1N1M0, Stage Ⅰ)was resected in December 2017(right lobectomy and lymph node dissection).During surgery, her parathyroid glands were visually inspected by the surgeon as well as by a ready-made photodynamic eye(PDE-neo)system.Diagnosis was performed using the intraoperative fast pathological method.Her inferior laryngeal nerve was non-recurrent(Toniato ⅡA).This photodynamic eye(PDE-neo)system is an effective and useful method that decreases the operation time and enables faster detection of the parathyroid gland.

[A Case Report of Recurrent Bleeding and Massive Malodorous Effusion Due to Skin Invasion of Advanced Breast Cancer Successfully Treated with Mohs' Paste].

We report a case involving a 65-year-old woman with skin invasion and destruction by left large breast cancer(T4cN0M0, Stage ⅢB). She had severe anemia with recurrent bleeding on the cancer surface and needed blood transfusion, and massive malodorous effusion from the skin lesion resulted in hypoalbuminemia and recurrent bacteremia. Metronidazole gel treatment for malodorous effusion and postmenopausal hormonal therapy were administered at first. After using Mohs' paste 4 times with 1- or 2-week intervals, the bleeding and effusion stopped, and the primary cancer tumor almost disappeared. Bacteremia also improved with antibiotics, and amelioration of distress was observed. Following this, systemic chemotherapy was performed. Mohs' paste was a very useful method for symptom management of malignant skin lesions with bleeding and massive effusion.

[A Case Report of Continuous Bleeding due to Severe Skin Metastases of Breast Cancer Successfully Treated Using Mohs Paste].

We report a case of severe skin metastases of advanced right breast cancer in an 84-year-old woman. The tumor (T4bN3cM0, Stage III C)was resected in June 2011(BT+AX)after blood transfusion for severe anemia. Radiotherapy to the right chest wall and supraclavicular lymph nodes was performed, and adjuvant hormonal therapy was administered. Local recurrences in the skin of the right chest wall appeared and were resected in December 2011. Nine months later, continuous bleeding from the progressed, widespread skin metastases needed recurrent blood transfusion. After using Mohs paste twice, the bleeding stopped almost completely. Mohs paste was very useful for stopping bleeding in locally advanced, unresectable skin metastasis.

Therapeutic approach to CLI with tissue loss--a comparative prospective cohort study in Finland and Japan.

BACKGROUND: To compare the demographics, chosen treatment options, and 1-year outcome of patients with severe critical limb ischemia (Fontaine IV) in 2 different patient cohorts. METHODS: A total of 118 consecutive patients with an ischemic tissue lesion in a lower extremity referred for the first time to the vascular surgery outpatient clinic of Helsinki University Hospital and 96 patients referred to the Division of Vascular Surgery of the Tokyo Medical and Dental University Hospital were included in this comparative analysis. Kaplan-Meier estimates were used to assess survival, leg salvage, and amputation-free survival (AFS). Propensity score analysis was used to adjust for differences between the study groups. RESULTS: The median age of the study cohorts was greater in Finland than in Japan (80 vs. 69 years, P < 0.001). The prevalence of coronary artery disease and hypertension were greater in the Finnish cohort (72% vs. 41%, P < 0.001 and 86% vs. 51%, P < 0.001, respectively). The prevalence of male gender (77% vs. 42%, P < 0.001), cerebrovascular disease (35% vs. 20%, P = 0.015), end-stage renal disease (35% vs. 5%, P < 0.001), and current smoking (64% vs. 21%, P < 0.001) was greater in the Japanese cohort. The prevalence of diabetes did not differ between the cohorts (52% vs. 47%, P = 0.286). The proportion of independently ambulant patients at referral was greater in Finland (80% vs. 54%, P < 0.001). In Helsinki and Tokyo, the initial treatment was bypass, an endovascular procedure, conservative treatment, and amputation in 42% vs. 41%, 24% vs. 14%, 24% vs. 41%, and 10% vs. 5% of the cases, respectively. One-year survival, leg salvage, and AFS were 65% vs. 71% (P = 0.326), 82% vs. 74% (P = 0.216), and 59% vs. 55% (P = 0.573) in the Finnish and Japanese cohorts, respectively. AFS was significantly better in ambulant than in nonambulant patients in the combined data (68% vs. 36%, P < 0.001). Adjusted propensity score analysis showed no statistical difference in survival between the study cohorts. CONCLUSIONS: The pattern of comorbid conditions in these 2 patient cohorts is significantly different, but the outcome did not differ significantly between cohorts.

Treatment strategies for aortic and peripheral prosthetic graft infection.

PURPOSE: The aim of this study was to investigate the outcomes correlated with our treatment strategy for prosthetic graft infection. METHODS: Seventeen patients were treated for prosthetic graft infections between 1997 and 2009. Initially, total graft excision was applied in five cases, partial graft excision was applied in six cases and graft preservation with drainage and irrigation was applied in six cases. Among the graft-preserved cases, four patients were infected with methicillin-resistant Staphylococcus aureus (MRSA) and treated with gentian violet (GV). RESULTS: The overall survival rate was 88% at 30 days and 82% at 1 year in this series. Of the excised cases, nine patients survived; however, two patients died. Among the cases in which MRSA-infected grafts were preserved, three patients survived; however, one patient died under a septicemic state. Infected graft preservation was applied at a high rate of 36%, and the mortality rate remained at 16%, without any signs of graft reinfection. CONCLUSIONS: In the treatment of infected grafts, the patient's condition should be considered in order to select the appropriate treatment in each case. Graft preservation should be considered as an alternative treatment option, especially in high-risk patients, and GV can be effective for conservative treatment of prosthetic graft infections, including MRSA infections.

[A case of cardiac tamponade due to pericarditis carcinomatosa of breast cancer successfully treated via pericardiocentesis and systemic chemo-endocrine therapy].

We report a case of lung and bone metastases of right advanced breast cancer in a 33-year-old woman. Her breast cancer (T4bN1M1, StageIV)was resected in December 2003 (mastectomy [BT] plus axillary lymph node dissection [AX]) after local arterial infusion therapy and subsequent systemic chemo-endocrine therapy was initiated and continued. In June 2007, a computed tomography (CT) scan revealed cardiac tamponade due to pericarditis carcinomatosa. Pericardiocentesis was performed, and the bloody effusion was drained immediately. Subsequently, the sysytemic chemo-endocrine therapy was modified. In 2009, multiple cerebellar metastases were discovered and treated via whole brain irradiation. In 2010, multiple liver metastases appeared, and they were treated by intravenous (IV) administration of nab-paclitaxel. In 2011, superior vena cava syndrome appeared gradually, and it was treated via venous metallic stenting. In 2012, epidural spinal cord compression appeared gradually, and it was treated via irradiation. In November 2012, the patient died because of lymphangitis carcinomatosa; her prognosis was good, as it was approximately 5 years after the pericardiocentesis.

A quantitative method for evaluating local perfusion using indocyanine green fluorescence imaging.

BACKGROUND: The purpose of this study is to introduce a new method, indocyanine green fluorescence imaging (ICG-FI), as an adjunct to distal pressure measurements in patients with peripheral arterial disease and symptomatic lower limb ischemia. METHODS: A total of 34 patients with peripheral arterial disease, including 11 with claudication (Fontaine II), 7 with rest pain (FIII), and 16 with an ulcer or gangrene (FIV), were enrolled. After an intravenous injection of ICG (0.1 mg/kg), foot perfusion was recorded by an infrared light camera. Fluorescence intensity was plotted on a time-intensity curve using recorded images, allowing the calculation of new parameters. Severity of ischemia was assessed as the duration between the rising point and half value of maximum brightness (T½). The difference in the fluorescence intensity between 10 seconds after the rising point and baseline (PDE10) was compared with the transcutaneous oxygen pressure (tcPO2) at the same site (n=51). RESULTS: Median T½ was 23 seconds in FII, 41 seconds in FIII (P<0.05), and 17 seconds in FIV patients. PDE10 correlated moderately with tcpO2 (r2=0.5). A cut-off value (PDE10=28) predicted a critically ischemic limb (FIII and FIV), defined as tcpO2<30 mm Hg with a sensitivity of 100% and specificity of 86.6%. CONCLUSIONS: Local tissue perfusion can be quantitatively evaluated by using ICG fluorescence imaging. It is a safe, fast, noncontact method of imaging, which may be useful even at the ulcer itself and in the circumferential area.

[A case report of liver metastasis of breast cancer successfully treated by hepatic arterial infusion of docetaxel and systemic administration of nab-paclitaxel].

We report the case of an effectively treated 50-year-old woman with liver metastasis of left breast cancer. Her breast cancer (T2N0M0, Stage IIA) was resected in November 1998 (radical mastectomy+axillary lymph nodes dissection). After this operation, tamoxifen(TAM 20 mg daily) was administered. In February 2002, a solitary liver metastasis(S5, 4 cm in diameter) was found by computed tomography(CT) scan. Hepatic arterial infusion of docetaxel(DOC 20 mg weekly)was started. In March 2003, the solitary liver metastasis had become smaller and showed partial remission (PR), but DOC intravenous injection(iv) therapy(40 mg weekly) was started because lung metastases appeared. Therefore, epirubicin+ cyclophosphamide therapy, DOC ia therapy (120 mg triweekly), and anastrozole (1 mg daily) were continued. However, in March 2005, she refused chemotherapy. In January 2011, a CT scan showed progressive disease of multiple liver and lung metastases. Nab-paclitaxel(PTX) iv therapy(400 mg triweekly) and exemestane(25 mg daily) were administered. In March 2012, a CT scan showed PR of the metastatic breast cancer. She has continued to receive nab-PTX iv therapy as an outpatient.

Differential detection rate of periodontopathic bacteria in atherosclerosis.

PURPOSE: Periodontitis has been associated with atherosclerotic cardiovascular lesions. There may be a link between periodontopathic bacterial infection and atherosclerosis. METHODS: In 53 patients with atherosclerosis, periodontal disease was classified according to the probing depth of the periodontal pocket. To compare the detection rate in different arterial lesion, specimens of diseased arteries (10 primary atherosclerotic lesions, 43 anastomotic lesions) and 21 control arteries without atherosclerotic findings macroscopically and microscopically in the arterial wall, obtained during the surgical procedures were examined for the presence of five species of putative periodontal bacteria using polymerase chain reaction (PCR) analysis. RESULTS: Fifty-one of the 53 patients (96%) had periodontitis, and 34 (64%) of those patients had severe periodontitis or were edentulous. In total, PCR analysis detected DNA specific for periodontal bacteria in 28 of the 53 specimens (52%) of atherosclerotic arterial wall. Only 5 of 21 (23%) were detected in control specimens. CONCLUSIONS: A high percentage of periodontopathic bacteria were detected in atherosclerotic arterial wall specimens from patients with atherosclerosis, especially with primary atherosclerotic lesions, and most cases had severe periodontitis.

[Loco-regional chemotherapy at the outpatient clinic for gastric cancer patients with home enteral nutrition].

In over the 10 years from 2000-2010, 21 gastric cancer patients received loco-regional chemotherapy with home enteral nutrition (HEN) at an outpatient clinic because of insufficient oral intake. These loco-regional chemotherapy regimens consisted of 5 intra-aortic chemotherapies, 4 hepato-arterial infusions and 12 intra-peritoneal chemotherapies. Five out of 8 cases that had measurable lesions showed PR, and 3 cases revealed PD. The patients received HEN with peptide central formula, 400-1,200 kcal/day in night time. The average duration of HEN was 12.9 months. The post-operative nutritional management was needed for continuation and securing of outpatient chemotherapy. The author reported an experience of the outpatient loco-regional chemotherapy with HEN for the gastric cancer patients who could not eat a sufficient volume of food.

Supplement of Clinical Practice Guidelines for Endovenous Thermal Ablation for Varicose Veins: Overuse for the Inappropriate Indication.

While endovenous thermal ablation (ETA) become first choice of treatment for varicose veins, overuse of ETA for the inappropriate indication is growing problem. ETA is performed not only on varicose cases without symptom but also non diseased cases with segmental reflux of saphenous veins or no reflux. Indications of ETA was demonstrated in "the Clinical Practice Guidelines for ETA for Varicose Veins 2019" by Japanese Society of Phlebology. Purpose of this supplement is description of basics of correct indication for ETA. We also demonstrate the typical case of overuse of ETA for wrong indication. (This is a translation of Jpn J Phlebol 2020; 31: 39-43.).

Discrimination of types of venous emboli using Doppler ultrasound.

BACKGROUND: Many studies have identified features of the emboli traveling in the arterial system by Doppler ultrasound, and estimated their composition and size for anticipation of cerebral infarct. Another concern is features of the emboli in the venous system for anticipation of pulmonary embolism (PE). The objective is to prove that the emboli in the venous system can be discriminated by Doppler ultrasound in animal study and to assess whether PE can be predicted by using this technique in clinical case. METHODS: Animal study--lard oil, thrombus, or bone marrow was injected to the femoral veins in pigs. High intensity transient signals were transhepatically identified at the inferior vena cava using Doppler ultrasound. Intensity volume (dB) and frequency shift (Hz) of each signal were obtained. The cutoff values at which thrombi, fat emboli, and marrow emboli could be discriminated were calculated by receiver-operating characteristic curves analysis. Human study--Subjects were 47 patients who underwent total knee arthroplasty. On postoperative day 0 and 1, High intensity transient signals were identified at the affected common femoral vein using Doppler ultrasound. Contrast computed tomography was done, and the patients were divided into two groups according to the presence of PE. The two groups were distinguished by intensity volume (dB) and frequency shift (Hz) of each signal and calculated the sensitivity and specificity. The statistics analysis was done as in animal study. RESULTS: Animal study--Thrombus and bone marrow could be discriminated from lard oil well at frequency shift of 208 Hz and 196 Hz (with sensitivity of 86.9, 85.7%, and specificity of 82.3%, 91.8%, respectively). Human study--The sensitivity and specificity were 76.7 and 75.0% to discriminate patients with and without PE at frequency shift of 208 Hz. CONCLUSIONS: Our animal study results indicated that emboli could be identified and discriminated in the venous system. Clinical study informed that the frequency shift (208 Hz) of the Doppler signal was the best parameter to discriminate PE with and without PE in patients with total knee arthroplasty.

Efficacy of the transfer function index using the pulse volume recording as a parameter to assess intermittent claudication.

PURPOSE: The aim of this study was to elucidate whether the ankle brachial pressure index (ABPI) or transfer function index (TFI) was useful as an alternative parameter to the treadmill-walking test using near-infrared spectroscopy (NIRS) in evaluating muscle ischemia for patients with intermittent claudication (IC). METHODS: In 155 claudicants, the treadmill-walking test using NIRS was performed to calculate the recovery ability index (=recovery time/walking time). The ABPI and TFI were measured at the calf (TFI(calf)) and ankle (TFI(ankle)) using pulse volume recording. The area under the curve (AUC) was calculated from the receiver operating characteristic (ROC) curve and cutoff value was determined using crossing point of the ROC curve with a diagonal line. RESULTS: In the nondiabetics, AUCs were 77.3%, 80.0%, and 76.0% in the ABPI, TFI(calf), and TFI(ankle), respectively, which were not different significantly. In the diabetics, the AUC of TFI(calf) was 77.9%, which was different significantly from those of the other indices such as the ABPI or TFI(ankle) showing 66.2% or 68.1%. The cutoff value of ABPI indicating moderate or severe IC was 0.75 in the nondiabetics whereas that of TFI(calf) was 0.85 in the diabetics. CONCLUSION: TFI(calf) was useful to distinguish moderate or severe IC from mild IC in diabetic patients even if the ABPI was sufficient in nondiabetic patients.

Effects of human atrial natriuretic peptide on renal function in patients undergoing abdominal aortic aneurysm repair.

OBJECTIVE: Ischemia-reperfusion injury is an important cause of renal dysfunction after abdominal aortic aneurysm repair. Human atrial natriuretic peptide (hANP) is a potent endogenous natriuretic, diuretic, and vasorelaxant peptide. The objective of the present study was to evaluate the effects of hANP on renal function in patients undergoing abdominal aortic aneurysm repair. DESIGN: A prospective, randomized, placebo-controlled study SETTING: Intensive care unit of a university hospital. PATIENTS: Forty patients undergoing elective abdominal aortic aneurysm repair. INTERVENTIONS: The patients were randomized to receive a continuous infusion of either hANP (0.01-0.05 microg/kg/min) (n = 20) or placebo (n = 20) immediately before aortic cross-clamping. The infusion of hANP or placebo continued for 48 hrs. MEASUREMENTS AND MAIN RESULTS: Blood and urine samples were taken before surgery, at admission to the intensive care unit, and on days 1, 2, and 3 postoperatively, for measurement of serum concentrations of sodium, creatinine, and blood urea nitrogen and plasma concentrations of ANP and brain natriuretic peptide (BNP). Urine volume and urinary concentrations of N-acetyl-beta-D-glucosaminidase (NAG), sodium, and creatinine were also measured. The mean plasma concentration of ANP was significantly higher in the hANP group than in the placebo group. The mean plasma BNP concentration was significantly lower in the hANP group than in the placebo group. The mean serum concentrations of creatinine and blood urea nitrogen were significantly (p < .05) lower in the hANP group than in the placebo group. The mean urine volume and mean creatinine clearance were significantly (p < .05) higher in the hANP group than in the placebo group. The mean urinary NAG/creatinine ratio was significantly (p < .05) lower in the hANP group than in the placebo group. CONCLUSIONS: The intraoperative and postoperative infusion of low-dose hANP preserved renal function in patients undergoing abdominal aortic aneurysm repair. Further studies are needed to assess the efficacy of prophylactic hANP infusion on perioperative renal outcome.

Effects of cilostazol and k-134 on reconstructive surgery using prosthetic grafts in the abdominal aorta of beagle dogs.

Problems associated with prosthetic graft replacement are stenosis at the anastomosis site and thrombus formation on the inner surface. Cilostazol is known to have antiplatelet activity and inhibit vascular smooth muscle cell proliferation and neointima thickening. A cilostazol derivative, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]-propoxy]-2-(1H)-quinolinone (K-134), has more potent anti-platelet activity and anti-neointimal thickening activity than cilostazol in the in-vitro platelet aggregation and in-vivo anti-hyperplastic activity assay. The aim of this study was to investigate effects of cilostazol and K-134 on thrombus formation and neointimal thickening at the site of prosthetic graft replacement. Beagle dogs underwent infrarenal abdominal aortic resection with straight Dacron graft replacement, which were allocated to the control, cilostazol, and K-134 groups. Two dogs were dead without confirming the cause of death. After 6 months, all dogs were necropsied. All prosthetic grafts were patent in each group. Ratios of red thrombus to prosthetic graft area were 0.3+/-6.4%, and 3.3+/-4.5% in the cilostazol and K-134 groups, respectively, which were significant different from that in the control group (24.4+/-16.8%). However, no clear difference was seen among the 3 groups with respect to neointimal thickness (control group, 0.70+/-0.13 mm; cilostazol group, 0.59+/-0.14 mm; K-134 group, 0.67+/-0.14 mm). Cilostazol and K-134 significantly inhibited thrombus formation on the inner surface of the prosthetic graft at 6 months after graft replacement. Neointimal thickening on the inner surface was slight even in control-group animals, and the effects of cilostazol and K-134 on such thickening were unclear.

[Pathophysiology, diagnosis, and laboratoy examination in critical limb ischemia].

The term critical limb ischemia (CLI) is defined as chronic ischemic pain at rest, ulcers, or gangrene lasting more than 2 weeks attributable to objectively confirmed occlusive arterial disease. Patients with ischemic pain at rest generally have ankle pressure (AP) of less than 50 mmHg or toe pressure (TP) of less than 30 mmHg, while patients with ulcers or gangrene usually have AP of less than 70 mmHg or TP of less than 50 mmHg. Healing requires an inflammatory response and additional perfusion above that required for supporting intact skin and underlying tissues. The AP and TP levels needed for healing are, therefore, higher than the pressures found in ischemic pain at rest. A combination of blood-flow reduction due to multisegmental lesions of the proximal artery and blood-flow imbalance in the local tissue lead to CLI. It is important to evaluate not only the macroscopic blood flow but also the microcirculation to understand the pathophysiology of CLI. Transcutaneous oxygen tension measurement (critical level <30 mmHg) and skin perfusion pressure measurement (critical level < 30 mmHg) are useful methods to evaluate the microcirculation.