Intra-mammary tumor location does not influence prognosis but influences the prevalence of axillary lymph-node metastases

Background The number of axillary lymph-node metastases is not only a function of disease progression in primary breast cancer, but is also influenced by the intra-mammary location of the tumor. Nevertheless, the prognostic role of the tumor site is discussed controversially. The objective of this study was to analyze the impact of primary-tumor location on axillary lymph-node involvement, relapse, and mortality risk by univariate and multivariate analysis, in patients both with and without systemic and loco-regional treatment.Method Retrospective analysis was conducted on 2,414 patients at the I. Frauenklinik, Ludwig-Maximilians University, Munich and Berlin-Charlottenburg, who underwent R₀ resection of the primary tumor and systematic axillary lymph-node dissection (at least five lymph nodes resected) for UICC I-III-stage breast cancer. Patients with unknown tumor site, multifocal tumor spread, central tumor location, or tumor location within 15° of the border between outer and inner quadrants were excluded from the study. Median observation time was 6.7 years.Results The primary tumor site was within or between the medial quadrants of the breast in 33.6% of the patients (n=810) and in the lateral hemisphere of the breast in 66.4% (n=1,604). Tumor size, histopathological grading, and estrogen receptor status were balanced between patients with lateral and medial tumor location. Metastatic axillary lymph-node involvement was significantly associated with a lateral tumor location (P<0.0001). The mean number of axillary lymph-node metastases was increased by 29% in cases with lateral tumor location (2.2 vs 1.7, P=0.003). In a multivariate logistic regression analysis allowing for tumor location, estrogen receptor status, grading and tumor size, tumor location was confirmed as a significant risk factor (P=0.02) for axillary lymph-node involvement. Tumor location, however, did not correlate with either disease-free survival (DFS) or overall survival (OS), by univariate (DFS: P=0.41; OS: P=0.57) or by multivariate analysis (DFS: P=0.16; OS: P=0.98).Conclusion We conclude that there is no sufficient evidence to support any independent prognostic significance of intra-mammary tumor location in early breast cancer. However, medial tumor location may lead to the underestimation of axillary lymph-node involvement.     

The role of electrical uncoupling in the genesis of atrioventricular conduction disturbance

The contribution of electrical uncoupling between the atrioventricular (A-V) nodal cells to the genesis of A-V nodal conduction disturbance was studied in isolated rabbit hearts. The electrical coupling was estimated by measuring the input resistance through a microelectrode. The A-V nodal conduction time was measured by recording atrial and His bundle electrograms (A-H interval).Treatment with ouabain (6.8 × 10^?7 m) for an hour increased the input resistance of the A-V nodal cells with a concomitant prolongation of the A-H interval. It also decreased the action potential amplitude, the maximal rate of depolarization, and the resting potential of these cells.High calcium perfusate containing 3.6 mm, 5.4 mm and 7.2 mm Ca increased the input resistance of the A-V nodal cells dose-dependently associated with a prolongation of the A-H interval. No significant change in the action potential configurations of the A-V nodal cells was caused by the high calcium perfusate.The increase in the input resistance of the A-V nodal cells under these conditions was considered to reflect an increase in the axial resistance which would cause a reduction in the electrical coupling. It is suggested that the reduction in the electrical coupling between the A-V nodal cells plays an important role in the genesis of the A-V nodal conduction disturbance caused by ouabain or high calcium perfusate.     

房室结慢径区域消融对迷走神经功能及心房颤动易感性的影响

Objective Atrioventricular node reentrant tachycardia (AVNRT) ablation may effect the vagal response,which is indicated by sinus tachycardia. On the other hand,atrial fibrillation (AF) ,which was found to be associated with vagal irmervation, often coexists with AVNRT. However,little is known about the im-pact of slow pathway ablation on local vagal innervation to atria. Methods In 11 dogs, bilateral cervical sympa-thovagal trunks were decentralized and metoprolol was given to block sympathetic effects. Linear lesion was per-formed from coronary sinus (CS) ostium to the middle area of Koch triangle. Atrial effective refractory period(ERP) ,vulnerability window (VW) of AF, and sinus rhythm cycle length (SCL) were measured at high fight atrium (HRA),low right atrium (LRA), distal (CSd) and proximal CS (CSp) at baseline with and without vagal stimulation before and after ablation. The histological study was also performed. Results (1) SCL during vagal stimulation remained unchanged before and after ablation(107±19)bpm vs (108±8) bpm (P > 0.05). (2) After ablation, ERP during vagal stimulation remained unchanged at HRA (55±34) ms vs (69 ±37) ms (P >0.05),and decreased slightly at CSd (42±32) ms vs (55±30) ms (P =0.08). However,at LRA and CSp,ERP was significantly decreased after ablation (19±21) ms vs (66±24) ms (P <0.001) ; and (7± 18) ms vs (46±24) ms (P < 0.001), respectively. (3) AF was difficult to be induced at baseline before and after ablation in all sites (VW close to 0). While during vagal stimulation, after ablation VW of AF significantly decreased at LRA (1±3) ms vs (49±36) ms (P < 0.005) and CSp (10±12) ms vs (45±34) ms (P < 0.05) ,decreased slightly at CSd after ablation (35±37) ms vs (57±28) ms (P =0.07) ,and remained un-changed at HRA (63±31) ms vs (63±25) ms (P > 0.05). (4) The altered architecture of individual gan-glia was histologically observed. Conclusions The decreased ERP shortening to vagal stimulation in CS and LRA induced by slow pathway ablation indicates that ablation in such area may result in the vagal dennervation in LRA and CS,thereby attenuating the susceptibility to vagal mediated AF. While unchanged SCL,ERP short-ening and VW to vagal stimulation in sinus node area and HRA indicate that slow pathway ablation did not change the vagal innervation to these sites.     

Hepatic resection for colorectal metastases in the caudate lobe of the liver

Although hepatic resections for colorectal metastases have become established procedures, there is still only a small number of reports of hepatic resections for such metastases in the caudate lobe. From 1993 to 2001, seven patients underwent eight hepatic resections for colorectal metastases in the caudate lobe at our department. The patients were five men and two women, and their ages were from 53 to 73 years. The ratio of synchronous to metachronous liver metastases was 2?:?5. Solitary metastasis was observed in one patient. One patient with a metastasis in the Spiegel lobe and three patients with metastasis in the caudate process underwent partial resection of the site. The other patients underwent resection of the Spiegel lobe (two times), resection of the right-sided caudate lobe, and total caudate lobe resection. The mean (±SE) operative time was 315.9 ± 30.6?min. Mean intraoperative blood loss was 1325.9 ± 421.1?ml, and mean postoperative hospital stay was 21 ± 3.7 days. One patient, who underwent sigmoidectomy and hepatectomy as an emergency operation due to ileus, experienced wound infection. No patient died within 12 months after the surgery. Five patients were alive at 24 months, and three at 36 months. The outcome of these patients encourages us to continue performing hepatic resection for colorectal metastases in the caudate lobe, as it is assumed to be a safe and effective procedure.     

Overexpression of the cholesterol-binding protein MLN64 induces liver damage in the mouse

AIM: To examine the in vivo phenotype associated with hepatic metastatic lymph node 64 (MLN64) over-expression. METHODS: Recombinant-adenovirus-mediated MLN64 gene transfer was used to overexpress MLN64 in the livers of C57BL/6 mice. We measured the effects of MLN64 overexpression on hepatic cholesterol content, bile flow, biliary lipid secretion and apoptosis markers. For in vitro studies cultured CHO cells with transient MLN64 overexpression were utilized and apoptosis by TUNEL assay was measured. RESULTS: Livers from Ad.MLN64-infected mice exhibited early onset of liver damage and apoptosis. This response correlated with increases in liver cholesterol content and biliary bile acid concentration, and impaired bile flow. We investigated whether liver MLN64 expression could be modulated in a murine model of hepatic injury. We found increased hepatic MLN64 mRNA and protein levels in mice with chenodeoxycholic acid-induced liver damage. In addition, cultured CHO cells with transient MLN64 overexpression showed increased apoptosis. CONCLUSION: In summary, hepatic MLN64 over- expression induced damage and apoptosis in murinelivers and altered cholesterol metabolism. Further studies are required to elucidate the relevance of these fi ndings under physiologic and disease conditions.     

肝癌转移相关的骨桥蛋白表达及其糖基化的改变

目的 检测骨桥蛋白(OPN)在不同转移潜能肝癌细胞株及肝癌组织中的蛋白表达水平及其糖基化水平,探讨OPN糖基化改变与肝癌转移的相关性及其意义. 方法 用免疫组织化学和Western blot法检测人肝癌组织(非转移组6例、转移组7例)及不同转移潜能人肝癌细胞株(L02、Hep3B、MHCC97L、MHCC97H、HCCLM3、HCCLM6)中OPN蛋白水平;采用免疫沉淀技术纯化肝癌组织中的OPN蛋白,并采用多重凝集素印迹技术检测转移与非转移肝癌组织中OPN糖基化水平差异.数据统计采用t检验和方差分析.结果 OPN在不同转移潜能肝癌细胞株的表达差异具有统计学意义(F=5.04,P＜0.01).在肝癌组织中,转移组OPN蛋白表达水平明显高于非转移组(t=2.447,P＜0.05),相对吸光度值分别为0.69±0.21和0.45±0.14.免疫沉淀技术成功纯化肝癌组织中的OPN蛋白,后续的凝集素印迹结果显示:与非转移组相比,转移组OPN蛋白对凝集素朝鲜槐、红腰果E型、蔓陀罗、刀豆素A的亲和力较低(P值均＜0.05).结论 OPN蛋白表达水平与肝癌转移潜能增强呈正相关;OPN蛋白的α2,3-唾液酸、平分型GlcNAc、多天线、偏二天线的糖链、高甘露糖型N-糖等糖基化水平改变可能与肝癌转移潜能增高有关.     

Vessel invasion as a predictive factor for recurrence after surgery in stage I lung adenocarcinoma

BackgroundPatients with early-stage lung cancer who underwent R0 resection often encounter disease recurrence, especially during the early phase; thus, it is deemed vital to determine the predictive factors for recurrence after surgery. In this study, we aimed to identify the independent variables associated with recurrence after complete surgical resection of pathological stage I lung adenocarcinoma.MethodsWe retrospectively reviewed the medical records of 169 patients who underwent pulmonary resection for primary lung adenocarcinoma pathological stage I with curative intent lung cancer surgery from 2015 to December 2018 at our institution for information on the recurrence of the disease.ResultsPer the multivariate analysis, the presence of micropapillary pattern and vessel invasion were found to be independent predictors of disease recurrence after surgery (odds ratio [OR]: 9.36, 95% confidence interval [CI]: 2.42–36.2, P = 0.0012; and OR: 4.50, 95% CI: 1.52–13.4, P = 0.0068, respectively). Vessel invasion was also found to be an independent predictor of disease recurrence after surgery within a year (OR 11.4, 95% CI 3.08–42.5, P = 0.0003).ConclusionsThe presence of vessel invasion may help in distinguishing patients with the highest risk of early-phase disease recurrence after surgery. Patients with stage I adenocarcinoma with vessel invasion should undergo intensive surveillance after surgery.     

Accuracy of transrectal ultrasound in predicting pathologic stage of rectal cancer before and after preoperative radiation therapy

Transrectal ultrasound (TRUS) and CT scan staging of rectal cancers before, and TRUS staging after, 45 Gy of irradiation were compared with the pathologic stage of the resected specimen in 19 patients. Accuracy of TRUS before and after irradiation, and of CT scan before irradiation, was 32 percent, 63 percent, and 53 percent, respectively. CT scan before and TRUS after irradiation predicted lymph node involvement in 79 percent and 68 percent of cases, respectively. Positive predictive value for lymph node involvement before irradiation was 60 percent for CT scan and 37.5 percent for TRUS; after irradiation, it was 50 percent for TRUS. Negative predictive value was 100 percent for CT scan and TRUS before radiation and 88 percent for TRUS after irradiation. Preoperative radiation therapy makes TRUS and CT scan less effective as staging techniques. The absence of lymph nodes on TRUS and CT scan before and after irradiation is reliable.Read in part at the Tripartitate Meeting, Birmingham, England, June 19 to 22, 1989.