Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer.

AIM: To retrospectively assess the effect of comprehensive cryosurgery (ablation of intra- and extra-hepatic tumors) plus dendritic cell-cytokine-induced killer cell immunotherapy in metastatic hepatocellular cancer. METHODS: We divided 45 patients into cryo-immunotherapy (21 patients), cryotherapy (n = 12), immunotherapy (n = 5) and untreated (n = 7) groups. Overall survival (OS) after diagnosis of metastatic hepatocellular cancer was assessed after an 8-year follow-up. RESULTS: Median OS was higher following cryo-immunotherapy (32 mo) or cryotherapy (17.5 mo; P < 0.05) than in the untreated group (3 mo) and was higher in the cryo-immunotherapy group than in the cryotherapy group (P < 0.05). In the cryo-immunotherapy group, median OS was higher after multiple treatments (36.5 mo) than after a single treatment (21 mo; P < 0.05). CONCLUSION: Cryotherapy and, especially, cryo-immunotherapy significantly increased OS in metastatic hepatocellular cancer patients. Multiple cryo-immunotherapy was associated with a better prognosis than single cryo-immunotherapy.

Prevention of needle-tract seeding by two-step freezing after lung cancer biopsy.

Fine-needle aspiration biopsy is a method to detect malignancy for undetermined pulmonary nodules, but has the potential to spread malignant cells from the tumor to the pleural cavity or chest wall. We developed a two-step freezing method to avoid needle-tract seeding, by use of percutaneous cryoablation after biopsy but before the biopsy needle was removed. A man aged 72 years was admitted because of a large mass in right upper lobe. After biopsy, the patient underwent surgery. Pathological assessment of the resected tumor showed that tissue around the biopsy probe and cryoprobe had been killed before needle withdrawal.

Radical treatment of stage IV pancreatic cancer by the combination of cryosurgery and iodine-125 seed implantation.

AIM: To investigate the therapeutic effect of radical treatment and palliative treatment in stage IV pancreatic cancer patients. METHODS: 81 patients were enrolled in the study. Radical treatment was performed on 51 patients, while 30 patients were put under palliative treatment. The procedural safety and interval survival for stage IV pancreatic cancer (IS-IV) was assessed by almost 2.5 years of follow-ups. The IS-IV of patients under the two kinds of treatment, and the effects of treatment timing and frequency on IS-IV, were compared. RESULTS: The IS-IV of patients who received radical treatment was significantly longer than those who received palliative treatment (P < 0.001). The IS-IV of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment (P = 0.0034 and 0.0415, respectively). Multiple treatments can play an important role in improving the IS-IV of patients who received radical treatment (P = 0.0389), but not for those who received palliative treatment (P = 0.99). CONCLUSION: The effect of radical treatment was significantly more obvious than that of palliative treatment, and multiple radical treatments may contribute more to patients than a single radical treatment.

[Percutaneous cryoablation and (125)I seed implantation combined with chemotherapy for advanced pancreatic cancer: report of 67 cases].

OBJECTIVE: To assess the efficacy and safety of percutaneous cryoablation (PCC) and (125)I seed implantation combined with chemotherapy for advanced pancreatic cancer. METHODS: Sixty-seven patients with advanced pancreatic cancer (6 in stage III, 61 in stage IV) received PCC and (125)I seed implantation combined with concomitant gemcitabine hydrochloride and DDP chemotherapy. The clinical benefit response (CBR), survival rate and therapy-related complications were assessed. RESULTS: All patients except one were followed up over 1 year. The 6-month and 1-year survival rates were 84.8% and 33.4%, respectively. The median progression free survival were 6.3 months and 5.5 months in the group stage III and group stage IV (P > 0.05), respectively, while the overall survival was 9.1 months in the group stage III and 11.0 months in the group stage IV (P > 0.05). CR,PR and SD were achieved in 5, 8, 54 patients, respectively. Fifty-four and 50 in the 67 patients experienced a ≥ 50% reduction of pain score and analgesic consumption, respectively, 18 patients experienced a ≥ 2 kg weight gaining, and KPS was increasing from 71.2 ± 0.4 to (90.0 ± 0.3, P < 0.05), the overall benefit rate was 80.6%. No serious therapy-related complications except pancreatic fistula accompanied abdominal hemorrhage, bile leakage, acute pancreatitis and needle track seeding in 1, 1, 2 and 1 case, respectively. CONCLUSION: Percutaneous cryoablation and (125)I seed implantation combined with chemotherapy are effective and safe for the treatment of advanced pancreatic cancer.

Sequential use of transarterial chemoembolization and percutaneous cryosurgery for hepatocellular carcinoma.

AIM: To evaluate the efficacy of sequential use of transarterial chemoembolization (TACE) and percutaneous cryosurgery for unresectable hepatocellular carcinoma (HCC). METHODS: Four hundred and twenty patients were enrolled in this study. The patients, who were considered to have unresectable tumors due to their location or size or comorbidity, were divided into sequential TACE-cryosurgery (sequential) group (n = 290) and cryosurgery alone (cryo-alone) group (n = 130). Patients in the sequential group tended to have larger tumors and a greater number of tumors than those in the cryo-alone group. Tumors larger than 10 cm in diameter were only seen in the sequential group. TACE was performed with the routine technique and percutaneous cryosurgery was conducted under the guidance of ultrasound 2-4 wk after TACE. RESULTS: During a mean follow-up period of 42 +/- 17 mo (range, 24-70 mo), the local recurrence rate at the ablated area was 17% for all patients, 11% and 23% for patients in sequential group and cryo-alone groups, respectively (P = 0.001). The overall 1-, 2-, 3-, 4- and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1- and 2-year survival rates (71% and 61%) in sequential group were similar to those (73% and 54%) in cryo-alone group (P = 0.69 and 0.147), while the 4- and 5-year survival rates were 49% and 39% in sequential group, higher than those (29% and 23%) in cryo-alone group (P = 0.001). Eighteen patients with large HCC (> 5 cm in diameter) survived for more than 5 years after sequential TACE while no patient with large HCC (> 5 cm in diameter) survived more than 5 years after cryosurgery. The overall complication rate was 24%, and the complication rates were 21% and 26% for the sequential and cryo-alone groups, respectively (P = 0.06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P = 0.02). Liver crack only occurred in two patients of the cryo-alone group. CONCLUSION: Pre-cryosurgical TACE can increase the cryoablation efficacy and decrease its adverse effects, especially bleeding. Sequential TACE and cryosurgery may be the better procedure for unresectable HCC, especially for large HCC.

Percutaneous cryosurgery for the treatment of hepatic colorectal metastases.

AIM: To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases. METHODS: Three hundred and twenty-six patients with non-resectable hepatic colorectal metastases underwent percutaneous cryosurgery under the guidance of ultrasound or CT. Follow-up was 1 mo after cryosurgery and then every 4 mo thereafter by assessment of tumor markers, liver ultrasonography, and abdominal CT. For lesions suspicious of recurrence, a liver biopsy was performed and subsequent repeat cryosurgery was given if histology was positive for cancer. RESULTS: All patients underwent a total of 526 procedures of cryosurgery. There were 151 patients who underwent repeat procedures of cryosurgery for recurrent tumors in the liver and extrahepatic places. At 3 mo after cryosurgery, carcinoembryonic antigen (CEA) levels in 197 (77.5%) patients who had elevated markers before cryosurgery decreased to normal range. Among 280 patients who received CT following-up, cryotreated lesions showed complete response (CR) in 41 patients (14.6%), partial response (PR) in 115 patients (41.1%), stable disease (SD) in 68 patients (24.3%) and progressive disease (PD) in 56 patients (20%). The recurrence rate was 47.2% during a median follow-up of 32 mo (range, 7-61). Sixty one percent of the recurrences were seen in liver only and 13.9% in liver and extrahepatic areas. The recurrence rate at cryotreated site was only 6.4% for all cases. During a median follow-up of 36 mo (7-62 mo), the median survival of all patient was 29 mo (range 3-62 mo). Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4 and 5 years, respectively, after the treatment. Patients with tumor size less than 3 cm, tumor in right lobe of liver, lower CEA levels (<100 ng/dL) and post-cryosurgery TACE had higher survival rate. There was no significant difference in terms of survival based on the number of tumors, pre-cryosurgery chemotherapy and the timing of the development of metastases (synchronous vs metachronous). Patients who underwent 2-3 procedures of cryosurgery had increased survival compared to patients who received cryosurgery once only. There was no intra-cryosurgery mortality. Main adverse effects, such as hepatic bleeding, cryoshock, biliary fistula, liver failure, renal insufficiency and liver abscess were only observed in 0.3%-1.5% of patients. CONCLUSION: Percutaneous cryosurgery was a safe modality for hepatic colorectal metastases. Rather than an alternative to resection, this technique should be regarded as a complement to hepatectomy and as an additional means of achieving tumor eradication when total excision is not possible.

A pilot study on combination of cryosurgery and (125)iodine seed implantation for treatment of locally advanced pancreatic cancer.

AIM: To study the therapeutic value of combination of cryosurgery and (125)iodine seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine patients with locally advanced pancreatic cancer (males 36, females 13), with a median age of 59 years, were enrolled in the study. Twelve patients had liver metastases. In all cases the tumors were considered unresectable after a comprehensive evaluation. Patients were treated with cryosurgery, which was performed intraoperatively or percutaneously under guidance of ultrasound and/or computed tomography (CT), and (125)iodine seed implantation, which was performed during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A few patients received regional celiac artery chemotherapy. RESULTS: Thirteen patients received intraoperative cryosurgery and 36 received percutaneous cryosurgery. Some patients underwent repeat cryosurgery. (125)Iodine seed implantation was performed during freezing procedure in 35 patients and 3-9 d after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepatic metastases received regional chemotherapy. At 3 mo after therapy, CT was repeated to estimate tumor response to therapy. Most patients showed varying degrees of tumor necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease (PD), in 10.2%. Adverse effects associated with cryosurgery included upper abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6 patients one of whom developed severe pancreatitis. All adverse effects were controlled by medical management with no poor outcome. There was no therapy-related mortality. During a median follow-up of 18 mo (range of 5-40), the median survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more. Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and 9.5%, respectively. Eight patients had survival of 24 mo or more. The patient with the longest survival (40 mo) is still living without evidence of tumor recurrence. CONCLUSION: Cryosurgery, which is far less invasive than conventional pancreatic resection, and is associated with a low rate of adverse effects, should be the treatment of choice for patients with locally advanced pancreatic cancer. (125)Iodine seed implantation can destroy the residual surviving cancer cells after cryosurgery. Hence, a combination of both modalities has a complementary effect.

Cryosurgery with combination of (125)iodine seed implantation for the treatment of locally advanced pancreatic cancer.

OBJECTIVE: To study the therapeutic value of cryosurgery with combination of (125)iodine seed implantation for locally advanced pancreatic cancer. METHODS: Thirty-eight patients with locally advanced pancreatic cancer were enrolled in this study. The diagnosis was confirmed by pathology in 31 patients. Ten patients had metastases of the peripancreatic lymph node and eight had liver metastases. The therapy included cryosurgery, which was performed intra-operatively or percutaneously under guidance of ultrasound and/or computed tomography (CT), and (125)iodine seed implantation, which was performed during cryosurgery process or post-cryosurgery under the guidance of ultrasound and/or CT. RESULTS: Eleven patients received intra-operative cryosurgery and 27 received percutaneous cryosurgery. Fourteen patients underwent two procedures of cryosurgery and three underwent three procedures of cryosurgery. (125)Iodine seed implantation was performed during the freezing procedure in 29 patients and within 3-7 days after cryosurgery in nine patients under ultrasound and CT guidance. Fifteen patients, of whom 13 had metastases of peripancreatic lymph nodes or liver received regional chemotherapy. At 3 months after therapy, a CT follow-up was performed to estimate the tumor response to therapy. Most of the patients had varying degrees of tumor necrosis. A complete response of the tumor was seen in 23.6% of patients, a partial response in 42.1%, stable disease in 26.3% and progressive disease in 7.9%. The adverse effects associated with cryosurgery mainly included pain of the upper abdomen and increased serum amylase activity. Acute pancreatitis was seen in five patients, one of whom presented a severe type of pancreatitis. During the followed-up of a median of 16 months (range of 5-37) median overall survival was 12 months, 19 patients (50.0%) survived for 12 months or longer and four survived for 24 months or longer. CONCLUSION: As it is far less invasive than conventional pancreas resection and entails a low rate of adverse effects, cryosurgery should be the choice modality for most patients with locally advanced pancreatic cancer. (125)Iodine seed implantation can destroy residue survival cancer cells after cryosurgery. Hence, combination of both modalities has a complementary effect.

[Expression of bcl-2 gene in spleen deficiency syndrome in colorectal carcinoma and the regulatory effect of Jianpikangfu decoction].

OBJECTIVE: To investigate the correlation between spleen deficiency syndrome in colorectal carcinoma and bcl-2 gene expression, and observe the regulatory effect of Jianpikangfu decoction. METHODS: Forty-five advanced colorectal carcinoma patients with spleen deficiency were randomized into Jianpikangfu decoction treatment group with also symptomatic treatment with western medicine and control group in which the patients were given expectant treatment with western medicine. The activity of salivary amylase and bcl-2 expression in the tumor tissues were detected before and after the treatment. RESULTS: Jianpikangfu decoction in combination with western medicine treatment produced more obvious inhibition of reduction in salivary amylase activity than exclusive western medicine treatment (t=7.822, P<0.01), and significantly lowered the positivity rate of bcl-2 expression (chi2=4.286, P<0.05) in the tumor tissues, which, however, displayed no obvious changes in response to exclusive western medicine treatment. CONCLUSION: Jianpikangfu decoction can inhibit the decrease in salivary amylase activity and regulate bcl-2 gene expression in colorectal carcinoma patients with spleen deficiency syndrome.

Percutaneous cryoablation in combination with ethanol injection for unresectable hepatocellular carcinoma.

AIM: To evaluate the effectiveness and safety of percutaneous hepatic cryoablation in combination with percutaneous ethanol injection (PEI) in patients with unresectable hepatocellular carcinoma (HCC). METHODS: A total of 105 masses in 65 HCC patients underwent percutaneous hepatic cryoablation. The cryoablation was performed with the Cryocare system (Endocare, Irvine, CA, USA) using argon gas as a cryogen. Two freeze-thaw cycles were performed, each reaching a temperature of -180 degrees C at the tip of the probe. PEI was given in 36 patients with tumor masses larger than 6 cm in diameter 1-2 weeks after cryoablation and then once per week for 4 to 6 sessions. The efficacy was evaluated with survival, change of tumor size and alpha-fetoprotein (AFP) levels. RESULTS: During a follow-up duration of 14 months in average with a range of 5 to 21 months, 33 patients (50.8%) were free of tumors, 22 patients (33.8%) alive with tumor recurrence: two had bone metastases, three were found to have lung metastases, and the remaining 17 recurrences occurred in the liver, of whom only 3 developed a cryosite recurrence. Among the 41 patients who were followed up for more than one year, 32(78%) were alive despite of tumor recurrence. Seven patients (10.8%) died due to disease recurrence. Three patients (4.6%) died due to some noncancer-related causes. Among the 43 patients who had a CT scan available for review, 38 (88.4%) had a shrinkage of tumor mass. Among the 22 patients who received biopsies of cryoablated tumor mass, all biopsies except one, showed only dead or scar tissues. Of the patients who had an increased AFP preablatively, 91.3% had a decrease of AFP to normal or nearly normal levels during postablative 3-6 months. Complications of cryoablation included liver capsular cracking in one patient,transient thrombocytopenia in 4 patients and asymptomatic right-sided pleural effusions in 2 patients. Two patients developed liver abscess at the previous cryoablation site at 2 and 4 months, respectively, following cryoablation, and was recovered after treated with antibiotics and drainage. CONCLUSION: Percutaneous cryoablation offers a safe and possibly curative treatment option for patients with HCC that cannot be surgically removed, and its integration with PEI, may serve as an alternative to partial liver resection in selective patients.