OBJECTIVE: To summarize the progress of the roles and mechanisms of various types of stem cell-based treatments and their combination therapies in both animal studies and clinical trials of lymphedema. METHODS: The literature on stem cell-based treatments for lymphedema in recent years at home and abroad was extensively reviewed, and the animal studies and clinical trials on different types of stem cells for lymphedema were summarized. RESULTS: Various types of stem cells have shown certain effects in animal studies and clinical trials on the treatment of lymphedema, mainly through local differentiation into lymphoid endothelial cells and paracrine cytokines with different functions. Current research focuses on two cell types, adipose derived stem cells and bone marrow mesenchymal stem cells, both of which have their own advantages and disadvantages, mainly reflected in the therapeutic effect of stem cells, the difficulty of obtaining stem cells and the content in vivo. In addition, stem cells can also play a synergistic role in combination with other treatments, such as conservative treatment, surgical intervention, cytokines, biological scaffolds, and so on. However, it is still limited to the basic research stage, and only a small number of studies have completed clinical trials. CONCLUSION Stem cells have great transformation potential in the treatment of lymphedema, but there is no unified standard in the selection of cell types, the amount of transplanted cells, and the timing of transplantation.
Animals ; Endothelial Cells ; Lymphedema/therapy* ; Stem Cell Transplantation ; Cytokines

OBJECTIVE: To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL). METHODS: This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded. RESULTS: The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group. CONCLUSIONS TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).
Humans ; Female ; Breast Neoplasms/therapy* ; Acupuncture Points ; Retrospective Studies ; Lymphedema/complications* ; Acupuncture Therapy/adverse effects* ; Upper Extremity ; Treatment Outcome

OBJECTIVE: To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise. METHODS: A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated. RESULTS: After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01). CONCLUSION Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.
Humans ; Female ; Breast Neoplasms/surgery* ; Acupuncture Points ; Acupuncture Therapy/methods* ; Upper Extremity ; Treatment Outcome ; Lymphedema/therapy*

PURPOSE: We compared the oncologic outcomes of breast-conserving surgery plus radiation therapy (BCS+RT) and modified radical mastectomy (MRM) under anthracycline plus taxane-based (AT) regimens and investigated the role of adjuvant radiation therapy (RT) in patients with pathologic N1 (pN1) breast cancer treated by mastectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 2,011 patients with pN1 breast cancer who underwent BCS+RT or MRM alone at 12 institutions between January 2006 and December 2010. Two-to-one propensity score matching was performed for balances in variables between the groups. RESULTS: The median follow-up duration for the total cohort was 69 months (range, 1 to 114 months). After propensity score matching, 1,074 patients (676 in the BCS+RT group and 398 in the MRM-alone group) were analyzed finally. The overall survival, disease-free survival, locoregional failure-free survival, and regional failure-free survival (RFFS) curves of the BCS+RT group vs. MRM-alone group were not significantly different. The subgroup analysis revealed that in the group with both lymphovascular invasion (LVI) and histologic grade (HG) III, the BCS+RT showed significantly superior RFFS (p=0.008). Lymphedema (p=0.007) and radiation pneumonitis (p=0.031) occurred more frequently in the BCS+RT group than in the MRM-alone group, significantly. CONCLUSION: There are no differences in oncologic outcomes between BCS+RT and MRM-alone groups under the AT chemotherapy regimens for pN1 breast cancer. However, BCS+RT group showed superior RFFS to MRM-alone group in the patients with LVI and HG III. Adjuvant RT might be considerable for pN1 breast cancer patients with LVI and HG III.
Anthracyclines ; Breast Neoplasms ; Breast ; Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Lymphedema ; Mastectomy ; Mastectomy, Modified Radical ; Mastectomy, Segmental ; Medical Records ; Propensity Score ; Radiation Pneumonitis ; Retrospective Studies

Stewart-Treves syndrome (STS) is a rare cutaneous angiosarcoma that develops in chronic lymphedema. The majority of STS is described in the upper extremity after aggressive locoregional therapy for breast cancer and is rarely reported in lower extremities. A 68-year-old woman presented with a 3-month history of multiple purpuric tumorous plaques and nodules on the right posterior thigh. She had a history of radical hysterectomy with lymph node dissection and postoperative radiotherapy due to uterine cervical cancer 16 years ago. She received right total hip replacement surgery due to hip joint avascular necrosis 14 years ago. She had suffered from chronic leg edema, especially on the right side. Skin biopsy on the right posterior thigh showed irregular vascular channels lined by atypical endothelial cells. Special stains showed positivity for CD31, CD34, factor VIII, and D2~40, which are pan-vascular or lymphatic markers. She showed a pelvic mass and pelvic bone metastasis on radiologic staging work-up. She refused all treatment, including surgery, radiotherapy, and chemotherapy, except for pain control. She died 2 months after diagnosis of this highly malignant tumor. The lymphedema on both lower extremities after uterine cervical cancer treatment was aggravated especially on the right lower extremity after right total hip replacement surgery. Increased weight of the right lower extremity resulted in 4 episodes of recurrent hip dislocation. We contend that these multiple factors (uterine cervical cancer treatment, total hip replacement surgery on the right side, and recurrent hip dislocations) attributed to development of Stewart-Treves syndrome. We herein report a case of Stewart-Treves syndrome of the lower extremity following chronic leg lymphedema after uterine cervical cancer treatment and hip surgery.
Aged ; Arthroplasty, Replacement, Hip* ; Biopsy ; Breast Neoplasms ; Coloring Agents ; Diagnosis ; Drug Therapy ; Edema ; Endothelial Cells ; Factor VIII ; Female ; Hemangiosarcoma ; Hip ; Hip Dislocation ; Hip Joint ; Humans ; Hysterectomy* ; Leg ; Lower Extremity* ; Lymph Node Excision ; Lymphedema ; Necrosis ; Neoplasm Metastasis ; Pelvic Bones ; Radiotherapy ; Skin ; Thigh ; Upper Extremity ; Uterine Cervical Neoplasms

Lymphedema is a common complication associated with cancer itself or with cancer treatment. Lymphedema infrequently occurs after drug therapy. Bee venom is one of the materials used in acupuncture, and it has been used in the treatment of a variety of inflammatory diseases including arthritis. We report a 74-year-old male patient with late-onset post-radiation lymphedema provoked by bee venom therapy. He was free of lymphedema for 5 years after the complete remission of prostate cancer which had been treated with transurethral resection and radiation therapy. The patient developed left leg swelling after undergoing bee venom therapy for left hip pain. Computed tomography and lymphoscintigraphy showed lymphedema without tumor recurrence or infection. The lymphatic system was suspected to be injured by bee venom therapy and lymphedema was provoked. Bee venom therapy should be used cautiously in patients prone to lymphedema.
Acupuncture ; Aged ; Arthritis ; Bee Venoms* ; Bees* ; Drug Therapy ; Hip ; Humans ; Leg ; Lymphatic System ; Lymphedema* ; Lymphoscintigraphy ; Male ; Prostatic Neoplasms ; Recurrence

PURPOSE: This study aimed to evaluate the effects of sentinel lymph node biopsy (SLNB) on recurrence and survival after neoadjuvant chemotherapy (NAC) in breast cancer patients with cytology-proven axillary node metastasis. METHODS: We selected patients who were diagnosed with invasive breast cancer and axillary lymph node metastasis and were treated with NAC followed by curative surgery between January 2007 and December 2014. We classified patients into three groups: group A, negative sentinel lymph node (SLN) status and no further dissection; group B, negative SLN status with backup axillary lymph node dissection (ALND); and group C, no residual axillary metastasis on pathology with standard ALND. RESULTS: The median follow-up time was 51 months (range, 3–122 months) and the median number of retrieved SLNs was 5 (range, 2–9). The SLN identification rate was 98.3% (234/238 patients), and the false negative rate of SLNB after NAC was 7.5%. There was no significant difference in axillary recurrence-free survival (p=0.118), disease-free survival (DFS; p=0.578) or overall survival (OS; p=0.149) among groups A, B, and C. In the subgroup analysis of breast pathologic complete response (pCR) status, there was no significant difference in DFS (p=0.271, p=0.892) or OS (p=0.207, p=0.300) in the breast pCR and non-pCR patients. CONCLUSION: These results suggest that SLNB can be feasible and oncologically safe after NAC for cytology-determined axillary node metastasis patients and could help reduce arm morbidity and lymphedema by avoiding ALND in SLN-negative patients.
Arm ; Breast Neoplasms* ; Breast* ; Diagnosis* ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphedema ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Pathology ; Polymerase Chain Reaction ; Recurrence ; Sentinel Lymph Node Biopsy*

We reported on a 60-year-old man presenting lymphedema of both lower extremities and scrotum for 3 years with unknown cause. We took a computed tomography scan of the lower extremities as a follow-up. There were diffuse subcutaneous edema in both lower extremities and multiple enlarged lymph nodes along the para-aortic and bilateral inguinal areas. For further evaluation, biopsy of an enlarged inguinal lymph node was taken, yielding a diagnosis of primary amyloidosis. A treatment of chemotherapy for amyloidosis was recommended for him. To our knowledge, this is the first report of lymphedema presenting with primary amyloidosis in Asia. This case suggests that primary amyloidosis could be one of the differential diagnoses in patients with lymphedema in the lower extremities.
Amyloidosis* ; Asia ; Biopsy ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Edema ; Follow-Up Studies ; Humans ; Lower Extremity ; Lymph Nodes ; Lymphedema* ; Middle Aged ; Scrotum

PURPOSE: This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. MATERIALS AND METHODS: We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. RESULTS: A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. CONCLUSION: We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.
Breast Neoplasms* ; Breast* ; Case-Control Studies* ; Disease-Free Survival ; Drug Therapy* ; Humans ; Lymph Nodes ; Lymphatic Irradiation ; Lymphedema ; Mastectomy, Segmental* ; Neoplasm Metastasis ; Propensity Score ; Radiation Pneumonitis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence

PURPOSE: The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. MATERIALS AND METHODS: A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next follow-up; arm swelling that persisted over two consecutive examinations was considered PLE. RESULTS: At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). CONCLUSION: One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication.
Arm ; Breast Neoplasms* ; Breast* ; Combined Modality Therapy* ; Drug Therapy ; Follow-Up Studies ; Humans ; Incidence ; Lymph Nodes ; Lymphedema* ; Multivariate Analysis ; Risk Factors*