[Identification and preservation of arm lymphatics in axillary lymph node dissection to prevent arm lymphedema: a single center randomized controlled trial].

Objective: To evaluate the feasibility of identification and preservation of arm lymphatics (DEPART) in axillary lymph node dissection (ALND) for breast cancer to prevent arm lymphedema. Methods: A randomized controlled study method was used. Two hundred and sixty-five patients who underwent breast cancer surgery at the Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University from November 2017 to June 2018 were included, and the patients were randomly divided into ALND+ DEPART group (132 patients) and standard ALND group (133 patients) by random number table method. In the ALND+ DEPART group, indocyanine green and methylene blue were injected as tracers before surgery, and the arm sentinel nodes was visualized by staged tracing during intraoperative dissection of axillary lymph nodes. Partial frozen sections were made of arm lymph nodes >1 cm in length and hard and suspicious of metastasis, and arm lymph nodes and lymphatic vessels were selectively preserved. Patients in the standard ALND group underwent standard ALND. Objective and subjective indexes of arm lymphedema were evaluated by 5-point circumference measurement and Norman questionnaire. Results: Among 132 breast cancer patients in the ALND+ DEPART group, 121 (91.7%) completed DEPART. There were no statistically significant differences in age, body mass index, pathological type, dissection number of axillary lymph node, N stage, TNM stage, molecular typing, and regional radiotherapy between the ALND+ DEPART and standard ALND groups (P>0.05). At a median follow-up of 24 months, assessment by the 5-point circumference measurement showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.0% (6/121) and 15.8% (21/133), respectively, with statistically significant differences (P=0.005). Assessment by the Norman questionnaire showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.8% (7/121) and 21.8% (29/133), respectively, with a statistically significant difference (P<0.001). No local regional recurrence was observed in either group during the follow-up period. Conclusion: For breast cancer patients with positive axillary lymph nodes, the administration of DEPART during ALND can reduce or avoid the occurrence of arm lymphedema without compromising oncology safety.

[Lesion removal plus whole breast exploration and washing plus micro-plastic procedures in the treatment of granulomatous lobular mastitis: a randomized controlled study].

Objective: To examine the effect of"lesion removal plus whole breast exploration and washing plus micro-plastic surgery"in granulomatous lobular mastitis. Methods: A single-center prospective randomized controlled study method was used to enroll patients diagnosed with granulomatous lobular mastitis for whom surgical procedures were projected from March 2017 to September 2019 at Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University. The sample size is determined by the superiority test. Based on the literatures and the previous work, the two groups require 97 cases. Fifty-two patients underwent"lesion removal+whole breast exploration and washing plus micro-plastic surgery"(observation group). Forty-five cases underwent"empirical breast lesion resection plus fascia tissue flap plasty plus nipple and areola correction"(control group). The primary study endpoint is the recurrence rate, and the secondary study endpoints include surgical complications, incision healing time, and postoperative patient satisfaction. Independent sample t test, Wilcoxon rank-sum test, χ² test and Fisher exact test were used for comparison between groups. Results: All procedures were completed successful, with no severe complications. All patients were followed up for (15.2±1.9) months (range: 12 to 24 months). There were no significant differences in incidence of postoperative complications (7.7% (4/52) vs. 6.7%(3/45), P=1), drainage time ((8.6±0.6) days vs. (8.4±0.8) days, t=1.921, P=0.053) and hospital stay ((7.7±0.6) days vs. (7.6±0.5) days, t=1.633, P=0.102) between the two groups. The recurrence rate of the observation group was lower significantly than that of the control group (3.8% (2/52) vs. 24.4%(11/45), χ²=8.819, P=0.003). The observation group had better cosmetic effects (Z=-2.657, P=0.008) and patient satisfaction than control group (Z=-5.730, P=0.000). Conclusion: The "lesion removal plus whole breast exploration and flushing plus micro-plastic surgery" has a good therapeutic effect and cosmetic value for patients with refractory granulomatous lobular mastitis.

[Factors associated with identification of lymph node detected by axillary reverse mapping for breast cancer].

Objective: To investigate the different tracer materials in identifying the axillary reverse mapping(ARM) lymph nodes. Methods: A retrospective analysis of clinical and pathological data of 478 breast cancer female patients(mean age: 50.5±8.0) under axillary lymph node dissection(ALND) with ARM technique was conducted between March 2019 and November 2020 in Wuhan University Zhongnan Hospital. Of the 478 patients, methylene blue was applied in 147 patients, indocyanine green in 119, and indocyanine green plus methylene blue in 212 patients. Wilcoxon rank-sum test, Chi-squire test or Fisher test, and binary logistic regression were carried out to identify the factors associated with identifying ARM lymph nodes. Results: The recognition rates of ARM lymph nodes were 73.5%, 79.0%, and 83.0%(P=0.091), and the recognition rate of ARM lymphatic vessels was 62.6%, 92.4%, 89.6%(P<0.001), respectively. The coincidence rate of ARM lymph node and SLN was 8.1%(12/148), and the metastasis rate was 16.1%(61/378). Supplemental injection of 1 ml of methylene blue or indocyanine green can improve the identification of ARM lymph nodes. The larger BMI and the performance of neoadjuvant therapy were associated with the lower recognition rate of ARM lymph nodes. Neoadjuvant therapy was an independent factor for the identification rate of ARM lymph nodes. Conclusions: Indocyanine green combined with methylene blue can improve the recognition rate of ARM lymph nodes. Obese patients have a lower recognition rate of ARM lymph nodes, and the supplemental injection tracer can be injected to improve the recognition rate. In breast cancer patients whose ARM lymph nodes are not successfully identified during operation, it may be that the ARM lymph nodes are not located in the axilla.

[Application value of intraoperative neuromonitoring plus "classification of EBSLN" to protect the external branch of the superior laryngeal nerve].

Objective: To investigate the application efficacy of the "classification of external branch of superior laryngeal nerve (EBSLN)" combined with intraoperative neuromonitoring (IONM) in the dissection of EBSLN for protecting the nerve from injuery, compared with ligation of branches of the superior thyroid vessels without attempts to visually identify the nerve. Methods: A prospective randomized controled study was performed in our center. Patients subjected to thyroidectomy from January 2017 to June 2019 were randomly divided into 2 groups, patients in experimental group underwent thyroidectomy and "classification of EBSLN" with IONM to dissect EBSLN, and patients in control group received synchronous surgery without attempts to visually identify the nerve. The anatomical subtypes of EBSLN in experimental group were recorded. The voice handicap index 10 (VHI-10) score was evaluated and the movement of bilateral vocal cords was examined by laryngoscope before surgery, 1 month, 3 months, and 6 months after surgery, respectively. SPSS 26.0 statistical software was used for statistical analysis. Results: Among the 1 377 EBSLN from 827 patients (317 males and 510 females, aged 24-58 years old), 691 EBSLNs in experimental group and 686 EBSLNs in control group. Totally 98.3% of EBSLNs in experimental group were identified by IONM including 16.4% (113/691) for type Ⅰ, 21.3% (147/691) for type Ⅱa, 31.4% (217/691) for type Ⅱb, 10.4% (72/691) for type Ⅲa, 3.9% (27/691) for type Ⅲb, 16.6% (115/691) for type Ⅲc. There was no statistical significance difference in baseline data between 2 groups (all P>0.05). All patients were followed up for more than 6 months. The postoperative nerve injury rate of experimental group was significantly lower than that of control group (1.2% vs. 7.5%, χ²=12.659, P<0.001), and the VHI-10 scores and laryngoscope results of experimental group were better than those of control group in three follow-up visits (P<0.001). With postoperative laryngoscope examination, 3 patients in the experimental group and 23 patients in the control group showed vocal cord relaxation, bilateral oblique asymmetry and other phenomena, which were considered as the results of permanent injury. Other patients with symptoms were relieved to varying degrees during the follow-up, and their symptoms were considered as the results of temporary injury. Conclusion: IONM combined with "classification of EBSLN" can reduce significantly the risk of EBSLN injury in thyroidectomy, which is better than direct ligation of branches without attempts to visually identify the nerve.

[Parathyroid hormone assay with eluent of aspirated tissues in parathyroidectomy].

Objective: To explore the values of intraoperative fine-needle aspiration (IFNA) and parathyroid hormone (PTH) detection in the eluate of aspirated tissue during parathyroidectomy. Methods: Fifty-four patients with secondary hyperparathyroidism (SHPT) including 24 males and 30 females, aged 20-83 years, admitted to Zhongnan Hospital of Wuhan University from January 2019 to October 2019, were included. All patients received subtotal parathyroidectomy with autologous transplantation, during surgery, IFNA and PTH detection in the eluate of aspirated tissue were performed, and also routine postoperative pathological examination was performed. The results of PTH detection in the eluate of aspirated tissue and postoperative pathological examinations were compared and analyzed by SPSS and R software for evaluating of the sensitivity, specificity, positive predictive value, negative predictive value, misdiagnosis rate, missed diagnosis and accuracy. Results: Surgery was completed successfully in all patients. After surgery, the symptoms were improved in the patients except two who were asymptomatic. None had any serious postoperative complications such as hypocalcaemia or hoarseness. A total of 231 aspirated tissue samples were tested, of which 216 were identified as parathyroid and 15 non-parathyroid based on intraoperative PTH detection in tissue eluate; while 217 were confirmed as parathyroid tissues and 14 non-parathyroid tissues with postoperative pathological examinations. The specificity and sensitivity of intraoperative IFNA and PTH detection in tissue eluate for identifying parathyroid tissues were 99.5% and 100.0%, respectively. Conclusion: The IFNA and PTH detection in tissue eluate is a rapid, simple, and accurate procedure, which helps the surgeon to identify parathyroid tissue and to ensure the endocrine activity of preserved or autografted parathyroid tissue during parathyroidectomy.

[Functional axillary dissection based on lymphatic drainage for breast cancer: a single center randomized clinical trial].

Objective: To evaluate the effectiveness and safety of functional axillary dissection based on lymphatic drainage (FUND) in decreasing breast cancer-related lymphedema (BCRL) events. Methods: A total of 168 eligible patients in Zhongnan Hospital of Wuhan University from July 2018 to February 2019 were randomly assigned to the FUND group or axillary lymph node dissection (ALND) group using random number table generated by SPSS. In the FUND group, methylene blue (MB) was adopted to reveal the sentinel lymph node (SLN) for all patients; 0.1 ml MB was injected into the SLNs before resection to reveal the efferent lymphatic channels and subsequent-echelon lymph node. The blue-stained lymphatic channels were mapped by bluntly dissecting along the lymphatic drainage channels from the breast to the axilla. Then, the SLNs were removed and pathologically analyzed by immediate frozen sectioning (FS); if the SLNs were positive, the blue-stained bALNs in breast lymphatic level (BLL) Ⅱ were removed and sent for immediate FS; if the blue-stained ALNs in BLL Ⅱ were confirmed negative, the tissues in BLL Ⅱ were removed'en bloc'. Clinicopathologic information for all the patients in the two groups were collected. The fixed-point circumference volume measurement method and the Norman questionnaire scoring method were used to evaluate the arm lymphedema between the two groups. Clinicopathological characteristics, incidences of arm lymphedema, locoregional recurrence, and distant metastasis between the two groups were compared. Results: The mean age were (50.3±8.0) in the FUND group and (51.1±9.0) in the ALND group. Seventy-four cases (88.1%) in the FUND group successfully underwent FUND surgery, and patients whose breast lymphatics failed to be stained blue underwent standard ALND. There was no statistically significant difference in terms of age, BMI, histological types, surgical approaches and adjunct therapy between the FUND group (n=74) and ALND group (n=84) (P>0.05). The average operation time of the FUND group and the stand ALND group were (169±15) and (123±12) min respectively (range: 145-198, 103-146 min) (P<0.001), and the number of lymph nodes removed [M (Q1, Q3)] were 8.3 (6, 15) and 12.9 (7, 18) (P=0.019). The cumulative BCRL rate, within a median follow-up of 24 months and 23 months respectively for FUND and ALND group, were 10.8% (8/74) vs 23.8% (20/84) (P=0.033) measured by fixed-point circumference volume measurement method, and was 12.2% (9/74) vs 27.4% (23/84) by Norman questionnaire (P=0.018). There were no local regional recurrence events during the follow-up period between the two groups. Conclusion: For breast cancer patients with clinically node-positive axilla or positive SLN, FUND based on lymphatic drainage was a less radical axillary surgery, with which eliminating the risk of BCRL might be achieved.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

[Comprehensive benefits of agroforestry snail control forests in Eryuan County, Yunnan Province].

OBJECTIVE: To investigate the efficiency of various agroforestry systems for snail control in plateau hilly schistosomiasis-endemic areas of Yunnan Province, so as to provide insights into the construction of agroforestry schistosomiasis control projects in plateau hilly regions. METHODS: The pilot areas of snail control forests with various agroforestry systems were built in snail-breeding farmlands in Eryuan County, Yunnan Province in 2010, and the economic benefits and snail control effect were investigated in 2018. In addition, a fuzzy comprehensive evaluation model was created to screen the agroforestry system with high comprehensive benefits. RESULTS: A total of 14 types of pilot areas of snail control forests with various agroforestry systems were built. Economic benefit analysis showed that the"walnut + garlic"pattern had the best economic benefit, with annual economic benefits of 270 000 Yuan/hm2, followed by the"walnut + chili"pattern (annual economic benefits of 120 000 Yuan/hm2) and the "walnut + vegetables"pattern (annual economic benefits of 105 000 Yuan/hm2). No snails were detected in 8 types of the agroforestry systems, including the"walnut + chili"pattern, the"walnut + tobacco"pattern and the"walnut + garlic"pattern; however, there were snail found with various densities in other types of systems. Fuzzy comprehensive evaluation showed that the"walnut + garlic"pattern had the best comprehensive control effect, followed by the"walnut + chili"pattern and the"walnut + tobacco" pattern, while the pure grassland pattern showed no effect on snail control. CONCLUSIONS: The agroforestry system is a preferential approach of forestry schistosomiasis control in plateau hilly schistosomiasis-endemic areas, which not only achieves snail control effects, but also promotes economic development and ecological construction in poor hilly areas.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

[Prognostic analysis of definitive radiotherapy for early esophageal carcinoma(T1-2N0M0): a multi-center retrospective study of Jing-Jin-ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group].

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

[Effects of chrysin on sphere formation and CK2α expression of ovarian cancer stem-like cells derived from SKOV3 cell line].

OBJECTIVE: To investigate whether inhibitory effect of chrysin on sphere formation of ovarian cancer stem-like cells(spheroids derived from human ovarian cancer SKOV3 cell line ) is involved in the down-regulating of the protein expression of casein kinase CK2α. METHODS: SKOV3-derived ovarian cancer stem-like cells obtained by suspension culture in stem cell-condition medium using ultra-low adhesion plate were treated with various concentrations (5.0, 10.0 and 20.0 µmol/L) of chrysin. Sphere formation assay was used to determine the sphere forming rate of SKOV3-derived ovarian cancer stem-like cells. Western blot was used to analyze the protein expressions of CK2α and cancer stem cell markers CD133 and CD44. Silence of CK2α by siRNA and ectopic expression of CK2α by transfection with pcDNA3.1-CK2α plasmid were used to explore the mechanism underlying the effect of chrysin on sphere formation of SKOV3-derived ovarian cancer stem-like cells. RESULTS: Chrysin (5.0, 10.0 and 20.0 µmol/L) significantly reduced the sphere forming rate of SKOV3-derived ovarian cancer stem-like cells, in a concentration-dependent manner (22.3%±2.5% vs 14.7%±2.1%, 8.6%± 1.7% and 3.8% ± 1.1% respectively; P<0.05). In addition, chrysin (5.0, 10.0 and 20.0 µmol/L) obviously down-regulated the protein expressions of CK2α, CD133 and CD44 in SKOV3-derived ovarian cancer stem-like cells. In combination with CK2α siRNA transfection and chrysin synergistically decreased sphere formation (P<0.05) and the protein expressions of CK2α, CD133 and CD44 in SKOV3-derived ovarian cancer stem-like cells. However, transfection with pcDNA3.1-CK2α plasmid attenuated inhibitory effects of chrysin on sphere formation capability and the expressions of CK2α, CD133 and CD44 of SKOV3-derived ovarian cancer stem-like cells. CONCLUSION: Down-regulation of CK2α protein expression is involved in the inhibition effect of chrysin on the sphere formation capability of SKOV3-derived ovarian cancer stem-like cells.