Lizhi Niu

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

Objective The aim of this study was to retrospectively assess the effect of comprehensive cryosurgery (ablation of intrapancreatic and extrapancreatic tumors) plus immunotherapy in metastatic pancreatic cancer. Methods We divided 106 patients (57 men, 49 women; median age, 65 years) into the cryoimmunotherapy (31 patients), cryotherapy (36 patients), immunotherapy (17 patients), and chemotherapy groups (22 patients). Pretreatment immune function was tested in patients who underwent immunotherapy. Overall survival (OS) after diagnosis of metastatic pancreatic cancer was assessed after a 4-year follow-up. Results Median OS was higher in the cryoimmunotherapy (13 months) and cryotherapy groups (7 months) than in the chemotherapy group (3.5 months; both P < 0.001) and was higher in the cryoimmunotherapy group than in the cryotherapy (P < 0.05) and immunotherapy groups (5 months; P < 0.001). In both the cryoimmunotherapy and cryotherapy groups, median OS was higher after multiple cryoablations than after a single cryoablation (P = 0.0048 and 0.041, respectively). In both groups, the median OS was higher in patients with normal immunologic function than in those with immune dysfunction (P < 0.0001 and P = 0.0004, respectively). Conclusions Cryoimmunotherapy significantly increased OS in metastatic pancreatic cancer. Multiple cryoablations and normal pretreatment immunologic function were associated with better prognosis.

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.

Alleviating visceral cancer pain in patients with pancreatic cancer using cryoablation and celiac plexus block.

Little is known about the effects of pancreas cryoablation (PCA) on abdominalgia in pancreatic cancer patients or its synergism with celiac plexus block (CPB). In patients without abdominalgia, to investigate the effects of PCA; in patients with abdominalgia, to investigate the pain-alleviating effects of PCA+CPB. Sixty-two patients were enrolled in this retrospective review; 12 without abdominalgia refused PCA, 15 without abdominalgia received PCA to reduce their tumor load and 35 with abdominalgia received PCA+CPB to reduce tumor load and alleviate pain. All PCA and PCA+CPB procedures were performed successfully. Some slight adverse effects (e.g. increased serum amylase, abdominal distension and nausea, abdominal bleeding) had disappeared by 3weeks, spontaneously or after symptomatic treatment. In patients without abdominalgia, pain occurred in one-third of cases (all with pancreatic head cancer) after PCA but had stopped 1-12days after treatment; in patients with abdominalgia before treatment, pain stopped immediately after PCA+CPB in 18 cases and 2-24days after treatment in 17 (all with pancreatic head cancer); a significant difference was found between pretreatment and post-treatment pain frequency (P=0.0019), regardless of the presence of advanced (P=0.0096) or metastatic (P=0.0072) cancer. The average time to pain relief was approximately 7days after both PCA and PCA+CPB, and abdominalgia did not recur for more than 8weeks. PCA may cause short-term pain in some pancreatic cancer patients. Combined PCA+CPB can alleviate cancer pain for more than 8weeks, without severe side effects.

Cryosurgery for pancreatic cancer.

The procedure of pancreatic cryosurgery is performed with intraoperative or percutaneous approaches. Based on current data and our initial experience, cryoablation appears to be a feasible, potentially safe and promising option in patients with locally advanced and unresectable pancreatic cancer. It is suggested that there are almost no known contraindications to the use of cryosurgery for pancreatic cancer. For most patients with pancreatic cancer, cryosurgery can substitute conventional surgery.

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.

Percutaneous cryoablation for stage IV lung cancer: A retrospective analysis

The aim of this study was to investigate the therapeutic effect of cryoablation treatment and palliative treatment in stage IV lung cancer. Fifty-four patients were enrolled into the study. Thirty-one patients received cryoablation treatment (including intra- and extrapulmonary tumors), and 23 patients had palliative treatment (no cryoablation). Both the safety of the procedure and overall survival (OS) for stage IV lung cancer were assessed during a 6.5 year follow-up period. The OS of patients in both groups and the effects of treatment timing and frequency were compared. The OS in the cryoablation group was significantly longer than in the palliative group (median OS: 14 months vs. 7 months, P = 0.0009). The OS of those who received delayed cryoablation treatment was longer than that observed for those who received timely treatment (median OS: 18.5 months vs. 10 months, P = 0.0485), but this was not observed in those who received palliative treatment (median OS: 7 months vs. 7.5 months, P = 0.9814). Multiple treatments played an important role in improving the OS of patients who received cryoablation treatment (median OS: 18 months vs. 14 months, P = 0.0376). There was a significant difference between cryoablation and palliative treatment, in terms of OS. In addition, multiple cryoablation treatments may have an advantage over single treatments.

Safety and accuracy of percutaneous core needle biopsy in examining pancreatic neoplasms.

cer, with a median time interval of 0.5 years (range, 0.2Y0.8 years). In the present study, the highest rate of multiple malignancies was recorded in patients with gastric cancer, followed by colorectal and hepatocellular cancers as the second and third highest multiple cancers. The increased incidence of these cancer types in Korea may explain the high proportion of multiple cancers. The gastric cancer incidence rate in Korea (40.4 per 100,000) is the highest in the world, and within Korea, colorectal and hepatocellular cancers are the third and fourth most common cancers. In order of decreasing incidence, gastric, colorectal, hepatocellular, bladder, and gallbladder cancers are common multiple cancers. The primary risk factor for bladder cancer is cigarette smoking. Shen et al showed a significant increase in the standardized incidence ratio of pancreatic cancer among both women and men after pharynx, larynx, stomach, bladder, and cervical cancers. In addition to the common environmental traits with this association, chemicals and occupational exposure, particularly medical conditions of the gallbladder, including gallstones, cholecystectomy, and cholecystitis, may be shared determinants. Improved cancer therapies and resulting enhancement of survival may increase the risk of a therapy-induced second primary malignant neoplasm. In a previous study, the standardized incidence ratio of pancreatic cancer was significantly increased after 10 years of diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix uteri, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin and non-Hodgkin lymphomas. A lengthy latency period is believed to be necessary for the promotion of newmalignant neoplasms by therapeutic factors. In the present study, CT findings suspicious for pancreatic cancer were observed in 7 patients (54%) before pancreatic cancer diagnosis. Typically, pancreatic cancer appears on a contrast-enhanced CT scan as an ill-defined, hypoattenuating focal mass with dilation of the upstream pancreatic duct. Although CT scan as a screening method of early detection for pancreatic cancer is not recommended for the general population or asymptomatic subjects, its use for early detection of pancreatic cancer in other cancer patients has been reported. Computed tomography can be used to detect a significant proportion of asymptomatic incident pancreatic cancers before clinical diagnosis. The presence of focal hypoattenuation and pancreatic duct dilatation are useful findings associated with the diagnosis of pancreatic cancer and are detectable on CT scan with a high degree of reproducibility. In the current study, the proportion of stage III to IV pancreatic cancers was lower in patients subjected to the CT scan than those without the CT scan, but the data did not reach statistical significance. Further studies are thus required to determine the effectiveness of CT use for pancreatic cancer detection in a high-risk population. In conclusion, cancers of the gastrointestinal tract and hepatobiliary system are often associated with pancreatic cancer in patients with multiple primaries in Korea. A significant proportion of incident pancreatic cancers can be detected in prediagnostic CT scans for follow-up evaluation of nonpancreatic cancer.

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.

Two case reports of pilot percutaneous cryosurgery in familial multiple endocrine neoplasia type 1.

We report 2 cases of familial multiple endocrine neoplasia type 1 syndrome (MEN 1) in related Malaysian Chinese individuals: the son had simultaneous primary lesions in the pancreatic tail, parathyroid, adrenal gland, and hypophysis, with metastatic tumors in the left lung, mediastinum and spine; his mother had simultaneous primary lesions in the pancreatic head, parathyroid, and hypophysis, with metastatic tumors in the liver, spine, ilium, chest wall, and rib. Genetic testing of the 2 patients showed the same mutation in exon 9 of MEN1 (c.1288G>T, Glu430, encoding a stop codon). The tumors with the poorest prognosis and clinical sequelae were in the pancreas of both patients, and these were treated by percutaneous cryoablation. The number of hypoglycemic episodes in the son improved for more than 120 days, and the abdominal space occupying lesion resolved in his mother.