Optical Spectral Surveillance of Breast Tissue Landscapes for Detection of Residual Disease in Breast Tumor Margins

We demonstrate a strategy to “sense” the micro-morphology of a breast tumor margin over a wide field of view by creating quantitative hyperspectral maps of the tissue optical properties (absorption and scattering), where each voxel can be deconstructed to provide information on the underlying histology. Information about the underlying tissue histology is encoded in the quantitative spectral information (in the visible wavelength range), and residual carcinoma is detected as a shift in the histological landscape to one with less fat and higher glandular content. To demonstrate this strategy, fully intact, fresh lumpectomy specimens (n = 88) from 70 patients were imaged intra-operatively. The ability of spectral imaging to sense changes in histology over large imaging areas was determined using inter-patient mammographic breast density (MBD) variation in cancer-free tissues as a model system. We discovered that increased MBD was associated with higher baseline β-carotene concentrations (p = 0.066) and higher scattering coefficients (p = 0.007) as measured by spectral imaging, and a trend toward decreased adipocyte size and increased adipocyte density as measured by histological examination in BMI-matched patients. The ability of spectral imaging to detect cancer intra-operatively was demonstrated when MBD-specific breast characteristics were considered. Specifically, the ratio of β-carotene concentration to the light scattering coefficient can report on the relative amount of fat to glandular density at the tissue surface to determine positive margin status, when baseline differences in these parameters between patients with low and high MBD are taken into account by the appropriate selection of threshold values. When MBD was included as a variable a priori, the device was estimated to have a sensitivity of 74% and a specificity of 86% in detecting close or positive margins, regardless of tumor type. Superior performance was demonstrated in high MBD tissue, a population that typically has a higher percentage of involved margins.     

基于B超图像评价HIFU治疗剂量对组织损伤程度的影响

基于B超图像分析HIFU治疗中辐照剂量、组织凝固性坏死区域和图像参数之间的关系。通过对高强度聚焦超声辐照新鲜离体组织前后获得的B超图像做数字减影处理,计算图像灰度平均值,同时切片观察并记录生物组织的凝固性坏死区域大小,在此基础上得到大批量数据的统计特性。结果表明：辐照剂量、组织凝固性坏死区域与B超图像灰度平均值在一定范围内成正相关性;当凝固性坏死区域增大到一定程度时,B超图像灰度平均值不再增大,而是呈无规律分布。B超图像灰度可反映组织损伤程度,为实时监控HIFU治疗效果提供依据。     

Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation

Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs “Synergistic electrolysis and electroporation” (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation.     

A Subcutaneous Octreotide Hydrogel Implant for the Treatment of Acromegaly

ObjectiveTo evaluate the pharmacokinetics, efficacy, and safety of a subcutaneous octreotide hydrogel implant in patients with acromegaly.MethodsIn 2 phase II open-label randomized studies, patients aged ≥ 18 years with confirmed acromegaly and octreotide responsiveness received one or two 52 mg hydrated implants (52 mg study) or a hydrated or nonhy drated 84 mg implant (84 mg study) inserted subcutane ously in the upper arm. Implants were removed after 6 months. The 84 mg study assessed pharmacokinetics in patients with undetectable baseline octreotide concentra tions. Both studies assessed efficacy (serum growth hor mone [GH], insulin-like growth factor 1 [IGF-1]) and safety (adverse events, physical examination, clinical chemistry).ResultsEleven patients received 1 (n = 5) or 2 (n = 6) 52 mg implants; 34 received a hydrated (n = 17 [safety]; n = 16 [efficacy analysis]) or nonhydrated (n = 17) 84 mg implant. With the nonhydrated versus hydrated 84 mg implant, mean maximum serum concen tration (C_max) and mean area under the drug concentration versus time curve from time 0 to 6 months were decreased (P = 0.002 and P = 0.03, respectively) and mean time to C_max was increased (P = 0.002). In both studies, IGF-1 and GH declined in month 1 and were significantly suppressed during the 6-month treatment versus baseline (P < 0.001). With the 52 mg and 84 mg implants, respectively, 3 of 11 patients (27%) and 17 of 33 patients (52%) achieved IGF-1 normalization and 8 of 11 patients (73%) and 13 of 33 patients (39%) exhibited GH < 2.5 ng/mL; 9 of 11 patients (82%) and 11 of 34 patients (32%) experienced treatment related adverse events, which were mainly gastrointestinal.ConclusionOctreotide hydrogel implants were well tolerated and maintained stable octreotide release and sup pression of IGF-1 and GH over 6 months. (Endocr Pract. 2012;18:870-881)     

高强度聚焦超声消融治疗（HIFU术）联合补肾活血方治疗子宫腺肌病的临床研究

摘要 目的：探讨高强度聚焦超声消融治疗（HIFU术）联合补肾活血方治疗子宫腺肌病的临床疗效。方法：选取我院2020年3月到2023年3月收治的100例子宫腺肌病患者作为研究对象,应用随机数字表法将其分为观察组与对照组,每组50例。对照组患者采取HIFU术治疗,观察组患者采取HIFU术联合补肾活血方治疗,对比两组患者临床疗效,治疗前后中医证候积分,对比手术前、手术后3个月、6个月的糖类抗原CA125及血红蛋白水平变化,并在治疗3个月后和治疗6个月应用子宫体积、痛经评分、经量评分评价患者远期预后情况。结果：两组临床疗效比较无差异（P>0.05）;治疗前两组患者腰膝酸软、经期腰骶痛、经期腹痛相关中医证候积分对比无明显差异（P＞0.05）,治疗后两组患者腰膝酸软、经期腰骶痛、经期腹痛相关中医证候积分均降低,且观察组低于对照组（P＜0.05）;手术两组患者糖类抗原CA125、Hb水平对比无明显差异（P＞0.05）,术后3个月、6个月两组患者糖类抗原CA125水平降低,观察组低于对照组,Hb水平升高,观察组高于对照组（P＜0.05）;观察组治疗后3个月的子宫体积、痛经评分、经量评分明显低于对照组（P＜0.05）,且治疗6个月后两组患者子宫体积、痛经评分、经量评分均降低,观察组低于对照组（P＜0.05）。结论：对子宫腺肌病患者应用高强度聚焦超声消融术联合补肾活血方治疗可提升其临床治疗效果,减轻患者临床症状,改善患者糖类抗原CA125表达水平,减轻贫血情况,且远期疗效较好,能够进一步改善患者子宫体积、疼痛程度和月经量,值得临床应用推广。     

Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins

Purpose

To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features.

Materials and Methods

Tissue excised from a genetically engineered mouse model of sarcoma was imaged using a subcellular resolution microendoscope after topical application of a fluorescent anatomical contrast agent: acriflavine. An algorithm based on sparse component analysis (SCA) and the circle transform (CT) was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma.

Results

Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity). For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach.

Conclusion

The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue.     

射频消融术治疗房颤后并发血栓栓塞形成的机制

心房颤动是临床上常见的心律失常之一,可因心房丧失收缩功能及长期心率增快而导致心房内血栓形成,并脱落至身体各处形成栓塞,严重时甚至可导致心力衰竭,增加患者的死亡率。射频消融术是目前可治愈心房颤动的有效的治疗手段,且在老年患者中具有较高的成功率和安全性。但血栓形成和栓塞仍是其主要并发症之一,发生率甚至可高达7%,一旦栓塞事件发生,将严重影响患者术后生存质量。目前研究结果表明,射频消融术治疗心房颤动后发生血栓及栓塞是一种多因素参与的系统性改变。     

Changes in the Peritubular Tissue of Rat Testis after Cadmium Treatment

The present study demonstrates histological and immunohistochemical changes in the peritubular testicular tissue of rat testis after application of cadmium chloride. After 5-day cadmium exposure, advanced deterioration of the boundary testicular tissue, mainly oedema, disarrangement of collagen fibres and peritubular cells, dilatation and thrombosis of blood vessels were observed. Changes in the boundary tissue were accompanied with desquamation of the germinal epithelium. Immunohistochemically, positive reaction for α-smooth muscle actin and desmin in tunica media of large testicular blood vessels basically was not affected. No reaction for vimentin was seen in endothelial cells of blood capillaries, whereas positive reaction presented only these cells in large blood vessels. The myofibroblasts positively reacting for desmin and α-smooth muscle actin form a single incomplete layer in the lamina propria of seminiferous tubules. Vimentin reactivity in the myofibroblasts and in the supporting Sertoli cells as well as Leydig cells in damaged testicular tissue was not observed. An increase in fibroblasts and free inflammatory cells positive for vimentin in the peritubular space on the peripheric area of the testis was observed.     

射频消融术治疗肝癌的研究新进展

肝癌为我国常见的恶性肿瘤之一。到目前为止,肝癌的治疗方法中,手术治疗仍为肝癌患者能获得较好生存率的首选方法。但由于很多患者发现肝癌时,晚期患者较多,很多肝功能较差剩余肝组织不能代偿,或全身情况较差,已不适合手术治疗。基于此种情况,现很多非手术治疗方法广泛应用于临床。而射频消融术治疗肝癌,作为一种非手术治疗方法,有着微创,疗效好,并发症少,安全,可反复应用等优点,近年来已成为治疗肝癌的一种常用手段。射频消融术治疗肝癌可分为开腹射频,腔镜下射频,影像学引导下经皮射频等。治疗方式可单独射频治疗,也可与介入治疗,酒精注射,静脉全身化疗等联合应用。现从射频消融术治疗肝癌的原理,适应症,方式,并发症,及预后几方面回顾总结该技术。     

Nanodrug-Enhanced Radiofrequency Tumor Ablation: Effect of Micellar or Liposomal Carrier on Drug Delivery and Treatment Efficacy

Purpose

To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs.

Materials/Methods

Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of IV fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4–24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm) or liposomal (100 nm) preparations of doxorubicin (Dox; targeting HIF-1α) or quercetin (Qu; targeting HSP70). Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg IV, 15 min post-RFA), and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg IV). Tumor coagulation and HIF-1α orHSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with IV Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA) compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4–72 hr.

Results

Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm) and liver (100 nm) (p<0.05). Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05). RFA/Mic-Dox had greater early (4 hr) intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24–72 hr post-RFA (p<0.04). No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03).

Conclusion

With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over time and reduced tumor growth. Accordingly, different carriers provide specific advantages, which should be considered when formulating optimal combination therapies.     

肿瘤微波热消融有效毁损区域温度场分布的仿真研究

本研究针对微波热消融肿瘤治疗过程中温度分布实时监测的核心问题,利用计算机模拟生物组织温度场分布,提出了基于有限元的微波消融温度场仿真方法。分别仿真了微波发射功率、作用时间及生物组织热物性参数对温度场分布的影响。研究结果表明:功率增大25%,毁损区温度平均升高20%;功率增大50%,温度升高40%;功率增大75%,温度升高60%。作用时间延长,温度场分布基本不变,但有效毁损体积增大,时间延长2倍可使毁损体积增大150%。导热系数对热疗远场区热能的扩散产生作用。经验证发现仿真结果与实验结果误差较小,证明了仿真方法的准确性。研究结果对于通过微波消融术前模拟来确定合适的发射功率和作用时间,以及制订合理的手术计划有重要的参考价值。     

兔VX2肝癌模型微波消融后磁共振灌注成像的可行性与应用价值

目的通过兔VX2模型探讨肿瘤消融治疗后动态变化过程中,磁共振灌注成像动态量化研究的可行性及其价值。方法16只新西兰大白兔分为实验组12只,对照组4只。实验组在兔肝脏种植VX2肿瘤后,观察肿瘤直径超过2.0 cm时行微波消融治疗。对比术后当天7、d、14 d及28 d实验组与对照组磁共振灌注成像量化指标—最大增强斜率（MSI）的动态变化差异,并与病理结果对照分析。结果对照组兔及实验组兔术后当天肝实质灌注MSI差异无显著性;实验组兔术前肿瘤与术后当天残留肿瘤的平均MSI差异无显著性;实验组兔残留肿瘤与良性强化组织的MSI差异有显著性。残留肿瘤的时间-信号强度曲线表现为快速上升型;良性强化组织的时间-信号强度曲线表现为缓慢上升型。结论磁共振灌注成像的动态量化研究是可行的,量化指标MSI与消融治疗后各种组织的病理结果相吻合,可更为准确地量化表达病变组织的病理状态的改变。     

腹腔镜探查并治疗腹部恶性肿瘤术后肠梗阻的临床研究

目的:探讨腹腔镜辅助探查并治疗腹部恶性肿瘤术后肠梗阻患者的可行性及安全性。方法:应用腹腔镜技术对我院42例腹部恶性肿瘤术后患者行手术治疗,其中包括良性粘连性肠梗阻14例、肿瘤复发16例、原发性结肠癌1例、恶性肠粘连11例。结果:42例患者均在腹腔镜下明确诊断,其中18例患者在完全腹腔镜下手术治疗,13例患者在腹腔镜辅助下行手术治疗,6例患者腹腔严重粘连中转开腹手术治疗,5例患者腹腔广泛转移行保守治疗。腹腔镜手术时间为35~290min,平均住院日9.2±1.7d。患者术后疼痛较轻、下床活动时间及肠道功能恢复时间短、术后并发症少。结论:恶性肿瘤术后肠梗阻患者仍需手术治疗,在严格掌握手术适应症下,应用腹腔镜技术对恶性肿瘤术后肠梗阻病人的治疗是安全、可行的。     

The Roles of Albumin Levels in Head and Neck Cancer Patients with Liver Cirrhosis Undergoing Tumor Ablation and Microsurgical Free Tissue Transfer

Objective

To evaluate the changes of serum albumin levels during the peri-operative period, and correlate these changes to surgical outcomes, postoperative morbidity and mortality in head and neck cancer patients with cirrhosis.

Methods

57 patients with liver cirrhosis out of 3,022 patients who underwent immediate free flap reconstruction after surgical ablation of head and neck cancer performed over a 9-year period were included in the study. Two sets of groups were arranged based on the preoperative albumin (>3.5 g/dL vs. ≤ 3.5 g/dL) and POD1 albumin (>2.7 g/dL vs. ≤ 2.7 g/dL) levels and were compared with respect to patient-related variables, surgical outcomes, medical and surgical complications, and mortalities.

Results

All patients had significant decreases in albumin levels postoperatively. Hypoalbuminemia, both preoperative and postoperative, was associated with the model for end-stage liver disease (MELD) score, the amount of blood loss, the duration of ICU stay and hospital stay, and postoperative medical and surgical complications. In particular, preoperative hypoalbuminemia (serum albumin ≤ 3.5 g/dL) was associated strongly with medical complications and mortality, while postoperative hypoalbuminemia (serum albumin ≤ 2.7 g/dL) with surgical complications.

Conclusion

Our study demonstrated the prognostic values of albumin levels in head and neck cancer patient with liver cirrhosis. The perioperative albumin levels can be utilized for risk stratification to potentially improve surgical and postoperative management of these challenging patients.     

Evidence for the Presence of Bacteria-specific Proteins in Sterile Crown Gall Tumor Tissue

Cross-reacting antigens were found in bacteria-free crown gall tumor tissue tested with serum prepared against Agrobacterium tumefaciens (Smith and Towns.) Conn., but no such antigens were detected in callus tissue. Soluble proteins from tumor tissue, callus tissue, and the crown gall bacteria were fractionated on a DEAE-Sephadex (A-50) column. The diethylaminoethyl-Sephadex elution profile for tumor tissue showed three protein fractions that were not detected in the callus tissue. Two of these protein fractions were shown to be exclusively bacteria specific. Besides these qualitative differences between the two tissues, significant quantitative differences in the amount of protein fractions were also observed. The diethylaminoethyl-Sephadex column fractions from tumorigenic strain of A. tumefaciens corresponding in position to the three additional peaks in the tumor tissue also showed cross-reacting antigens when tested with serum prepared against sterile tumor tissue. It is suggested that tumor formation by A. tumefaciens involves integration of the bacterial genome into the host-cell genome.     

溶瘤痘苗病毒的研究进展

溶瘤病毒可靶向性杀伤肿瘤细胞而不对正常细胞产生杀伤作用。近几年已开发出十余种溶瘤病毒。痘苗病毒曾在全球消灭天花行动中被广泛使用,并且有着复制速度快、免疫原性强、副作用明确等优点。痘苗病毒经过基因改造,可以选择性地在肿瘤细胞中复制并裂解细胞。目前,用于溶瘤痘苗病毒改造的主要有痘苗病毒Western Re verse株、Wyeth株、Lister株和Copenhagen株,我国使用的痘苗病毒天坛株尚未有相关报道。     

20％吡拉西坦在颅内肿瘤术后颅内高压患者中应用效果观察

目的:探讨20％吡拉西坦注射液治疗颅内肿瘤术后高颅内压临床疗效和安全性.方法:选择2009年4月～2012年4月在我院神经外科住院治疗的136例颅内肿瘤术后高颅内压患者为研究对象,随机将其分为对照和实验组,对照组患者给予20％甘露醇快速静脉滴注治疗,而实验组患者则给予20％吡拉西坦快速静脉滴注治疗,比较两组患者临床疗效和不良反应发生情况.结果:实验组患者的治疗总有效率(95.59％)明显高于对照组的(85.29％),差异有显著性(P＜0.05),且对照组和实验组患者在不良反应发生率方面差异无显著性(P＞0.05).结论:20％吡拉西坦注射液治疗颅内肿瘤术后高颅内压临床疗效确切,降颅压疗效好,安全可靠,不良反应少.