Laparoscopic cryosurgery for hepatic tumors

Background: Hepatic cryosurgery has been shown to be a safe technique that may be well suited to a laparoscopic approach. Methods: The technical feasibility and safety of laparoscopic cryosurgery was explored first in a pig model. Thereafter we performed the first successful case of laparoscopic hepatic cryosurgery at our institution. Results: In the animal model, we found that it is possible to safely identify, target, and cryoablate specific lesions in the liver. Temperature in the peritoneal cavity remained above 35°C, and pathologic examination of the abdominal wall around the cryoprobe site revealed no damage. We also successfully treated a 62-year-old man with a metastatic colorectal carcinoma deep in the right lobe of the liver with laparoscopic cryosurgery using a transpleural approach. Conclusion: We conclude that laparoscopic cryosurgery is feasible for lesions anywhere in the liver. For lesions high on the dome of the liver, a transpleural approach may provide better access.     

经皮穿刺氩氦刀冷冻治疗肝癌56例临床分析

目的　探讨氩氦刀冷冻治疗肝脏恶性肿瘤的临床意义。方法　 2 0 0 1年 7月～ 2 0 0 2年6月 5 6例肝脏恶性肿瘤在B型超声引导下行经皮穿刺氩氦刀冷冻治疗。术后患者定期复查血清肿瘤标记物、B型超声检查及CT或MRI。结果　患者肝功能ChildA级 5 0例 ,ChildB级 5例 ,ChildC级 1例。原发性肝癌 4 6例 ,转移性肝癌 10例。小肝癌 (直径≤ 5cm)甲胎蛋白阳性者治疗后转阴占80 % ,甲胎蛋白阴性者治疗后CT或MRI复查病灶完全坏死达 6 1.5 %。转移性肝癌治疗后瘤标降至正常或CT、MRI提示病灶完全坏死者占 6 0 %。结论　氩氦刀冷冻治疗肝脏恶性肿瘤是一种微创、安全、疗效可靠的新方法。对于不适宜行手术治疗的肝脏恶性肿瘤患者是一种有效的微创外科治疗方法。     

超声引导经皮穿刺冷冻治疗肝癌的实验和临床研究

目的 探讨经皮穿刺冷冻治疗原发性肝癌的应用价值。方法 ①家猪１２只,腹腔镜下显露肝脏,ｒｏｃａｒ针穿刺腹壁,经一非金属鞘将冷冻头插入肝右叶冷冻;②１１例原发性肝癌,超 引导穿刺扩张皮肤直至肝内肿瘤表面,保留一非金属鞘,ＬＣＳ－２０００冷冻机５ｍｍ冻冷头经鞘管插至肿瘤中心冷冻。结果 ①实验动手术后无腹腔内出血,冷冻穿刺部位无严重冻伤;②１１例病人冷冻后恢复均顺利,其中５例肿瘤缩小≥５０％,１例肿瘤完     

Multidisciplinary management of metastatic colorectal cancer

When colorectal cancer metastasizes to distant organs, usually multiple sites are involved and treatment consists primarily of systemic chemotherapy and supportive care. Chemotherapeutic agents effective against metastatic colorectal cancer include 5-fluorouracil, often used in combination with leucovorin or methotrexate, and irinotecan (CPT-11). Median survival with optimal chemotherapy regimens ranges from 10 to 15 months. Less frequently, colorectal cancer metastasizes only to the liver or lung. In a minority of these cases, surgical resection can be performed and results in a median survival of 28-46 months for hepatic resections and 24-25 months for pulmonary resections. Five-year survival rates range from 24 to 38% and 21 to 44% for hepatic and pulmonary resections, respectively. For isolated liver metastases that are not surgically resectable, other regional therapies that can be considered are hepatic cryosurgery, radiofrequency ablation, and hepatic arterial infusion chemotherapy. Median survival following cryosurgery is between 26 and 30 months, while median survival following radiofrequency ablation has not been established in large series. Hepatic arterial infusion chemotherapy, especially with newer combination drug regimens, may increase survival in patients with isolated liver metastases compared to systemic chemotherapy, but this must be confirmed in randomized, prospective trials. Colorectal cancer metastases to the brain can be treated with radiation therapy or surgical resection, but median survival with treatment is less than one year.     

Lobomycosis: a therapeutic challenge

Lobomycosis or lacaziosis is a chronic granulomatous fungal infection caused by Lacazia loboi. Most cases are restricted to tropical regions. Transmission is believed to occur through traumatic inoculation in the skin, mainly in exposed areas. It is characterized by keloid-like nodules. There are only a few hundred cases reported. The differential diagnoses include many skin conditions, and treatment is difficult. The reported case, initially diagnosed as keloid, proved to be refractory to surgical treatment alone. It was subsequently approached with extensive surgery, cryotherapy every three months and a combination of itraconazole and clofazimine for two years. No signs of clinical and histopathological activity were detected during follow-up.     

The role of cryosurgery in the treatment of hepatic cancer: a report of 113 cases

From November 1973 to June 1992, cryosurgery with liquid nitrogen (–196°C) was performed on 113 patients with hepatic cancer, including 107 patients with primary liver cancer (PLC) and 6 patients with secondary liver cancer (SLC). Of the 107 PLC patients, the subclinical stage constituted 30.8% (33/107), the moderate stage 61.7% (66/107), and the late stage 7.5% (8/107). There were 32 cases with small PLC (up to 5 cm). Liver cirrhosis was observed in 86.0% (92/107). We designed flat cryoprobes for freezing surface tumors, and single and multiple trocar cryoprobes for freezing tumors deep within the hepatic parenchyma. Intraoperative ultrasound was used for monitoring hepatic cryolesions. There were no operative mortalities and complications, such as rupture of a tumor, delayed bleeding, or bile leakage. The 5-year and 10-year survival rates were 22.0% and 8.2%, respectively, for the 107 PLC patients and 48.8% and 17.1%, respectively, for the 32 patients with small PLC. Of the 6 SLC patients, survival ranged from 2 months to 90 months (average, 23.2 months). One SLC patient has been well for 7 years and 6 months after cryosurgery. These results indicate that cryosurgery, the in situ freezing of cancer, is a safe and effective treatment for unresectable hepatic cancer.Abbreviations PLC primary liver cancer - SLC secondary liver cancer - IOUS intraoperative ultrasound - AFP -fetoprotein Presented in part at the 4th World Congress of Hepato-Pancreato-Biliary Surgery, 7–11 June 1992, Hong Kong     

局部治疗联合EGFR-TKIs在晚期耐药肺腺癌中的临床应用研究

目的探讨表皮细胞生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)使用后耐药进展的肺腺癌患者给予局部治疗(冷冻消融、支气管动脉栓塞)联合EGFR-TKIs的临床疗效。方法回顾性分析2012年3月至2018年10月应急总医院经病理证实并完成随访的原发性EGFR敏感突变型晚期肺腺癌患者,进展后再行EGFR基因检测为T790M阴性,继续应用EGFR-TKIs的同时联合局部治疗,分别统计PFS1(从使用EGFR-TKIs到疾病进展时间)、PFS2(从冷冻消融到疾病进展时间)、OS(总生存期)、OS1(冷冻消融后的生存期),及冷冻消融后的并发症情况。分析OS及PFS的统计学相关影响因素。结果32例符合入组标准的晚期肺腺癌患者,PFS1平均时间为(12.4±8.6)个月。其中14例患者冷冻消融前行支气管动脉栓塞治疗,共消融病灶38个。PFS2为(6.7±2.9)个月。OS为(31.5±13.5)个月,其中OS1为(15.5±7.6)个月。统计分析显示PFS1与PFS2与OS存在显著相关性(P<0.05),靶向治疗进展后至氩氦冷冻消融的时间与患者的OS及OS1存在相关性,支气管动脉栓塞联合氩氦消融治疗后并发症主要为气胸及肺内出血,对症处理后均可缓解。结论EGFR-TKIs耐药进展后晚期肺腺癌中,EGFR-TKIs继续使用并联合冷冻消融等局部治疗可延长患者生存,并发症少,取得临床获益。     

Percutaneous Cryoablation for Liver Cancer

Based on the primary tumor site, liver cancer can be divided into two categories: (1) primary liver cancer and (2) metastatic cancer to the liver from a distant primary site. Guided cryoablation via many imaging methods induces iceball formation and tumor necrosisand is an attractive option for treating unresectable hepatocellular carcinoma (HCC) and metastatic liver cancer. There are several advantages to using cryoablation for the treatment of liver cancer: it can be performed percutaneously, intraoperatively, and laparoscopically; iceball formation can be monitored; it has little impact on nearby large blood vessels; and it induces a cryo-immunological response in situ. Clinically, primary research has shown that percutaneous cryoablation of liver cancer is relatively safe and efficient, and it can be combined with other methods, such as radiation therapy, chemotherapy, and immunology, to control disease. Although research is preliminary, cryosurgery is fast becoming an alternative treatment method for HCC or liver tumors. Here, we review the mechanisms of liver tumor cryoablation, cryoablation program selection, clinical efficiency, and complications following treatment.     

Use of X-ray Tomography to Map Crystalline and Amorphous Phases in Frozen Biomaterials

The outcome of both cryopreservation and cryosurgical freezing applications is influenced by the concentration and type of the cryoprotective agent (CPA) or the cryodestructive agent (i.e., the chemical adjuvants referred to here as CDA) added prior to freezing. It also depends on the amount and type of crystalline, amorphous and/or eutectic phases formed during freezing which can differentially affect viability. This work describes the use of X-ray computer tomography (CT) for non-invasive, indirect determination of the phase, solute concentration and temperature within biomaterials (CPA, CDA loaded solutions and tissues) by X-ray attenuation before and after freezing. Specifically, this work focuses on establishing the feasibility of CT (100–420 kV acceleration voltage) to accurately measure the concentration of glycerol or salt as model CPA and CDAs in unfrozen solutions and tissues at 20°C, or the phase in frozen solutions and tissue systems at −78.5 and −196°C. The solutions are composed of water with physiological concentrations of NaCl (0.88% wt/wt) and DMEM (Dulbecco’s Modified Eagle’s Medium) with added glycerol (0–8 M). The tissue system is chosen as 3 mm thick porcine liver slices as well as 2 cm diameter cores which were either imaged fresh (3–4 h cold ischemia) or after loading with DMEM based glycerol solutions (0–8 M) for times ranging from hours to 7 days at 4°C. The X-ray attenuation is reported in Hounsfield units (HU), a clinical measurement which normalizes X-ray attenuation values by the difference between those of water and air. NaCl solutions from 0 to 23.3% wt/wt (i.e. water to eutectic concentration) were found to linearly correspond to HU in a range from 0 to 155. At −196°C the variation was from −80 to 95 HU while at −78.5°C all readings were roughly 10 HU lower. At 20°C NaCl and DMEM solutions with 0–8 M glycerol loading show a linear variation from 0 to 145 HU. After freezing to −78.5°C the variation of the NaCl and DMEM solutions is more than twice as large between −90 and +190 HU and was distinctly non-linear above 6 M. After freezing to −196°C the variation of the NaCl and DMEM solutions increased even further to −80 to +225 HU and was distinctly non-linear above 4 M, which after modeling the phase change and crystallization process is shown to correlate with an amorphous phase. In all tissue systems the HU readings were similar to solutions but higher by roughly 30 HU, as well as showing some deviations at 0 M after storage, probably due to tissue swelling. The standard deviations in all measurements were roughly 5 HU or below in all samples. In addition, two practical examples for CT use were demonstrated including: (1) glycerol loading and freezing of tissue cores and, (2) a mock cryosurgical procedure. In the loading experiment CT was able to measure the permeation of the glycerol into the sample at 20°C, as well as the evolution of distinct amorphous vs. crystalline phases after freezing to −196°C. In the mock cryosurgery example, the iceball edge was clearly visualized, and attempts to determine the temperature within the iceball are discussed. An added benefit of this work is that the density of these frozen samples, an essential property in measurement and modeling of thermal processes, was obtained in comparison to ice.     

超声引导下深度冷冻治疗原发性肝癌

应用超声引导对３２例原发性肝癌进行了插入式深低温冷冻治疗。全部病例术后恢复均顺利，无手术死亡及严重并发症。其中２５例冷冻后肿瘤均有不同程度缩小，１３例肿瘤缩小≥５０％。认为深度低温冷冻治疗肝癌不仅能有效地杀灭冷冻区所有的肿瘤细胞，还能最大限度地保存正常肝组织；而且在术中Ｂ超的监测下能对冷冻的范围进行准确的控制，避免损伤肝内重要的管道系统。因此深度低温冷冻治疗对某些无法手术切除的肝癌是一种安全有效的治疗方法。