Kecheng Xu

Percutaneous comprehensive cryoablation for metastatic hepatocellular cancer

Percutaneous ablation is the currently preferred locoregional therapy for non-resectable hepatocellular cancer (HCC). Cryoablation is an attractive option because it forms an ice ball viewable by many imaging methods. This study assessed the therapeutic effect of comprehensive cryoablation (of intra- and extrahepatic tumors) in patients with metastatic HCC. Forty-five patients met the inclusion criteria from January, 2004 to October, 2011. Treatment was performed on 33 patients; 12 patients received no treatment. Procedural safety and overall survival (OS) were assessed according to metastatic stage. The OS of patients who received comprehensive treatment was significantly longer than that of those who received no treatment (median: 26 vs. 3.5months, P<0.001). Large (⩾5cm long diameter) hepatic tumors were treated in advance with transarterial chemoembolization, but the OS of patients in the same metastatic stage was similar (P=0.0677). In the comprehensive cryoablation group, timely treatment (within 2months after diagnosis of metastatic HCC) was associated with a longer OS than when treatment was delayed for 3-7months (median: 38.5 vs. 21months, P=0.0167). Multiple treatments improved the survival of patients who received comprehensive treatment (P=0.0489). In terms of increasing the survival time of metastatic HCC patients, the effect of comprehensive cryosurgery was significant. Timely or multiple treatments had greater therapeutic effects than delayed or single treatment.

Cryotherapy protocols for metastatic breast cancer after failure of radical surgery

To retrospectively assess the effect of cryotherapy in patients with metastatic breast cancer (MBC) but without local recurrence after resection of the primary lesion, we divided 120 MBC patients into cryotherapy (91 patients) and chemotherapy (29 patients) groups. In the cryotherapy group, 37 patients with tumor recurrence received multiple cryoablations, while 54 patients received only a single cryoablation. Moreover, 62 cryotherapy-group patients underwent cryoablation immediately after the detection of metastases (timely cryotherapy); 35 patients received simultaneous immunotherapy (cryo-immunotherapy), and 29 patients underwent cryoablation in our hospital 3 months after receiving chemotherapy in other centers (chemo-cryotherapy and delayed cryotherapy). Overall survival (OS) after the diagnosis of MBC was assessed after a 10-year follow-up. The median OS was higher in the cryotherapy group (55 months) than in the chemotherapy group (27 months; P<0.0001). In the cryotherapy group, longer median OS was associated with multiple (76 months) rather than single cryoablations (48 months; P=0.0005) and with timely (67 months) rather than delayed cryoablation (48 months; P=0.0012). The median OS was higher after cryo-immunotherapy (83 months) than after chemo-cryotherapy (48 months) or cryotherapy alone (43 months; P<0.0001 for both). In conclusion, timely and multiple cryoablations, especially when combined with immunotherapy, offer significant advantages over chemotherapy in extending the OS of MBC patients.

Alleviating the pain of unresectable hepatic tumors by percutaneous cryoablation: experience in 73 patients.

Pain caused by liver tumors can be alleviated by cryoablation, but little is known about the analgesic effects and duration of pain alleviation. We retrospectively reviewed the changes in the severity of pain before and after percutaneous cryoablation of hepatic tumors. Each patient enrolled in this study had a single hepatic tumor; patients with large tumors (major diameter, ⩾5 cm) underwent transarterial chemoembolization (TACE) first and then cryoablation. Severe abdominal pain that was not controlled with long-lasting oral analgesics was treated with opioid injections. In all 73 study patients, severe abdominal pain was gradually eased 5 days after cryosurgery, completely disappeared after 15 days and did not recur for more than 8 weeks. There were no differences in analgesic effects between patients with hepatocellular carcinomas and those with liver metastasis (P > 0.05). The patients were divided into four groups depending on their pain outcomes: (i) immediate relief (n = 6), severe abdominalgia was no longer present after cryosurgery; (ii) delayed relief (n = 11), severe abdominalgia disappeared gradually within 15 days after the cryosurgery; (iii) always pain-free (n = 39), severe abdominalgia was not present before or after treatment; and (iv) new pain (n = 17), abdominalgia developed after treatment and disappeared within 15 days. In summary, percutaneous cryoablation of hepatic tumors caused short-term pain in some patients, but this pain disappeared within 15 days. Moreover, the pain-relieving effect of this treatment was sustained for at least 8 weeks, without severe side effects.

Percutaneous ultrasonography and computed tomography guided pancreatic cryoablation: Feasibility and safety assessment

OBJECTIVE To assess the safety and feasibility of percutaneous cryoablation on pancreatic cancer via ultrasonography (US) and computed tomography (CT) guidance. MATERIALS AND METHODS This retrospective review was approved by the institutional review board and of informed consent. Thirty-two patients (18 men and 14 women; median age 62; age range, 30-77 years) with pancreatic cancer (stage II/III/IV, 3/11/18) treated with percutaneous US and CT guided cryoablations between February 2009 and February 2010 were eligible for this review. Thirteen tumors in pancreatic head and 19 in pancreatic body and/or tail measuring 2-11 cm (mean, 5.2 cm±8 [standard deviation]) were ablated with 49 procedures in total. Feasibility was analyzed by enhanced CT 1-3 months post procedure and safety was assessed by clinical signs, symptoms and laboratory results. RESULTS Neither procedural death nor serious complications occurred. Fifteen tumors (46.9%) smaller than 5 cm were successfully ablated by one session of cryoablation. Twenty-seven patients experienced a ≥50% reduction in pain score, 22 experienced a 50% decrease in analgesic consumption and 16 experienced a ≥20 increase in Karnofsky Performance Status (KPS) Score. Partial response (PR) and stable disease (SD) turned up in 9 and 21 patients, respectively, lesions in whom were identified controlled by none enhancement on enhanced CT. Mean and median survival was 15.9 and 12.6 months, respectively. The 6-, 12- and 24-month survival rates were 82.8%, 54.7% and 27.3%, respectively. CONCLUSION US and CT guided percutaneous cryoablation is a safe and promising local treatment for pancreatic cancer.

Combination percutaneous cryotherapy and iodine-125 seed implantation for unresectable malignant thymoma: Experience in 19 patients☆

Thymomas are the most common tumors of the mediastinum. These tumors often compress vital mediastinal organs and severely impact the quality of life of thymoma patients. To avoid the side effects of chemoradiotherapy, some patients with unresectable malignant thymomas have opted to undergo cryotherapy in our hospital. We reviewed the cryosurgery, nursing and follow-up records of our hospital for the past 8 years, and evaluated the safety and efficiency of cryotherapy in 19 patients with unresectable malignant thymomas. No severe complications involving the vital organs surrounding the tumor occurred during or after cryosurgery. The most common side effect was pleural effusion, which occurred in 11 patients and healed after drainage within 1 week. Cough, mediastinal and pericardial effusions, pneumothorax, mild fever and chest tightness also occurred and resolved 1 week after symptomatic treatment. Since our patients had high KPS scores and mild myasthenia gravis symptoms before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14-29 months (median, 18 months), and did not differ between patients with large tumors and those with small tumors (P = 0.6753). In conclusion, cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma.

Cryotherapy for local recurrent dermatofibrosarcoma protuberans: Experience in 19 patients

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive, cutaneous, malignant tumor characterized by a high propensity for local relapse. Wide and deep local excision with reconstructive surgery is the current standard therapy for DFSP, with a local recurrence rate (LRR) of nearly 40%. In this study, we cured 19 patients with local recurrence of DFSP with 39 sessions of percutaneous cryoablation performed between July 2004 and August 2008. The LRRs after one, two and three cryosurgery sessions per patient were 68%, 54% and 0%, respectively. Moreover, the LRR did not differ with tumor location or size. Furthermore, all patients had a progression-free survival of >5 years. Only minor complications such as fever, local edema, mild nerve injury and local pain occurred, and were resolved within 1 week with symptomatic treatment. In our experience, percutaneous cryoablation is a relatively safe and efficient technique for the treatment of local recurrence of DFSPs.

MiR-187 overexpression inhibits cervical cancer progression by targeting HPV16 E6

Aberrantly expressed microRNAs contribute to the initiation and progression of human cancer. MiRNA-187 has been reported in nasopharyngeal, renal, pancreatic, prostate, and esophageal cancer, and acts as a tumor suppressor or oncogene. However, the underlying function of miRNA-187 in cervical cancer remains largely unexplored. In the present study, we demonstrated significantly miRNA-187 down-regulation in cervical cancer tissues and cell lines compared to their normal counterparts. Kaplan-Meier analysis revealed that decreased miRNA-187 was closely associated with shorter overall survival and relapse-free survival. Gain- and loss-of-function studies showed that miRNA-187 suppressed cervical cancer cell proliferation, migration, and invasion, and promoted cervical cancer cell apoptosis. Furthermore, luciferase reporter assay determined that human papillomavirus 16 E6 was a direct functional target of miRNA-187. Taken together, our findings indicate the essential role of miRNA-187 in suppressing cervical cancer progression and indicate a novel link between miRNA-187 and human papillomavirus 16 E6 in cervical cancer.Aberrantly expressed microRNAs contribute to the initiation and progression of human cancer. MiRNA-187 has been reported in nasopharyngeal, renal, pancreatic, prostate, and esophageal cancer, and acts as a tumor suppressor or oncogene. However, the underlying function of miRNA-187 in cervical cancer remains largely unexplored. In the present study, we demonstrated significantly miRNA-187 down-regulation in cervical cancer tissues and cell lines compared to their normal counterparts. Kaplan-Meier analysis revealed that decreased miRNA-187 was closely associated with shorter overall survival and relapse-free survival. Gain- and loss-of-function studies showed that miRNA-187 suppressed cervical cancer cell proliferation, migration, and invasion, and promoted cervical cancer cell apoptosis. Furthermore, luciferase reporter assay determined that human papillomavirus 16 E6 was a direct functional target of miRNA-187. Taken together, our findings indicate the essential role of miRNA-187 in suppressing cervical cancer progression and indicate a novel link between miRNA-187 and human papillomavirus 16 E6 in cervical cancer.

Short-term clinical efficacy of percutaneous irreversible electroporation combined with allogeneic natural killer cell for treating metastatic pancreatic cancer

This study was to determine how the short-term clinical efficacy of irreversible electroporation (IRE) combined with allogeneic natural killer (NK) cell therapy for treating metastatic pancreatic cancer. Between March and December 2016, we enrolled 40 patients who met the enrollment criteria and assigned them to two groups: simple IRE (IRE group, n=20) and IRE plus allogeneic NK cell therapy (IRE-NK, n=20). We evaluated immune function changes, quality of life, clinical response, and other related indicators. Combining allogeneic NK cells with IRE had a synergistic effect, not only enhancing the immune function of the patients, but also reducing the expression of carbohydrate antigen 19-9 (CA19-9) and CA242 and significantly exhibiting good short-term outcome and improving the quality of life of the patients. This is the first clinical trial to combine allogeneic NK cells with IRE for treating metastatic pancreatic cancer, and proves the safety and efficacy of the treatment.

Comparison of percutaneous cryoablation with microwave ablation in a porcine liver model

We compared imaging and pathological changes between argon-helium cryosurgical (AH) and microwave (MW) ablation in a porcine liver model. Immediately after ablation, computed tomography (CT) imaging showed that the area affected by MW ablation was considerably greater than that affected by AH ablation; moreover, the surface area of necrotic tissue was considerably greater in the AH group, whereas the depth of the necrotic area was similar. Seven days after ablation, the affected area had not changed much in the AH group, but it had significantly increased in the MW group; similarly, the surface and depth of the necrotic areas had not changed much in the AH group, but they had increased significantly in the MW group. The pathological findings showed similar definitive areas for both groups at both time points. The findings indicated that long time after both therapies, complete tissue necrosis can be achieved, but the extent and depth of necrosis differ: necrosis foci after AH ablation could be predicted by ice ball under CT image, and necrosis foci after MW ablation will increase obviously. MW ablation might therefore be suitable for tumors with a larger volume and simple anatomical structures, and AH ablation might be suitable for tumors with complex anatomical structures or those located near important organs. These two methods could therefore be used in combination in clinical settings, but details of the procedure need to be studied.

Circulating tumor cell as a biomarker for evaluating allogenic NK cell immunotherapy on stage IV non-small cell lung cancer

In this study, we determined the number of peripheral blood circulating tumor cells (CTCs) pre- and post-NK in patients with stage IV non- small cell lung cancer (NSCLC) as a reference for understanding the relevance of any changes to the efficacy of NK cells therapy. The patients were given one to three courses of immunotherapy. CTC numbers and CTC-related gene expression were measured in the peripheral blood of 31 patients with stage IV NSCLC at 1day before and 7 and 30d after NK cells therapy using magnetic activated cell sorting (MACS) and fluorescence activated cell sorting (FACS) combined with real-time quantitative PCR (RT-qPCR). Throughout the research, fever was the most common reaction (34.6%). The number of CTCs was 18.11±5.813, 15.13±5.984 and 10.32±5.623, respectively, and this decreased significantly over time. ΔCt values for the CTC-related genes CEA, MAGE-3 and CK18 increased significantly after NK cells infusion. The expression of CEA, CK18 and MAGE-3 decreased significantly with time after NK. CTC was a useful biomarker for evaluating the efficacy of NK cells therapy on stage IV NSCLC.