Hybrid ablation therapy for multiple hepatocellular carcinomas.
Sub-category: Multidisciplinary Treatment
Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Meeting: 2010 Gastrointestinal Cancers Symposium
Session Type and Session Title:
General Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
A. Chikamoto, T. Beppu, T. Ishiko, H. Okabe, T. Masuda, H. Shigaki, H. Takamori, H. Baba; Kumamoto University, Kumamoto, Japan Abstract: Background: Local ablation therapy (LAT) is one of the effective and less invasive treatment options for hepatocellular carcinoma (HCC). In treatment of multiple HCC with LAT, we have to consider its strategy. Percutaneous ablation (PA) for HCC at the liver surface includes the risk of dissemination of malignant cell or heat injury to adjacent organs. On the other hand, it is difficult to puncture tumors existing in the deep site of the liver precisely under endoscopic ablation (EA). To solve these problems, we have introduced "hybrid ablation therapy (HyA)," which is combination of PA and EA for multiple HCC. Methods: From April 1994 to January 2009, 757 patients treated with LAT were reviewed. Fifty and 81 patients were treated with HyA and only EA for multiple HCC, respectively. Sonazoid, which is ultrasound contrast agent containing perfluorobutane gas, has been used for better visualization since September 2007. PA was applied to tumors at the liver surface, and EA was to those at the deep site of the liver. Including criteria for tumor size were not over 3 cm in diameter for PA and 4 cm for EA. Number of tumor was not over 3, and tumors close to major vessels were excluded. In cases of EA prior to PA, abdominal cavity was filled with saline after completion of EA for better visualization with Sonazoid-enhanced ultrasound. Operation time, amount of bleeding, postoperative hospital stay, and incidence of complication were compared between HyA and EA. Effectiveness of Sonazoid in detection of HCC was analyzed. Results: There was no statistical difference between HyA and EA group in operation time (232 min vs. 213 min, NS), amount of bleeding (14 g vs. 22.2 g, NS), postoperative hospital stay (12.5 days vs. 11.5 days, NS), and in incidence of postoperative complication (10% vs. 11%). After introduction of Sonazoid, 25 nodules of 17 HCC patients existed at the deep site of the liver by preoperative imaging. After EA following filling of abdominal cavity with saline, 10 nodules were detected with conventional ultrasound. Ten nodules were detected with Sonazoid-enhanced ultrasound. Five nodules could not be detected. Conclusions: We recommend that HyA is useful therapeutic option for multiple HCC. Sonazoid could be helpful for detection of HCC at the deep site of the liver.
Ann Surg Oncol. 2009 Dec 22. [Epub ahead of print] Rate of Freeze Alters the Immunologic Response After Cryoablation of Breast Cancer.
Sabel MS, Su G, Griffith KA, Chang AE.
Division of Surgical Oncology, University of Michigan, Ann Arbor, MI, USA, firstname.lastname@example.org.
BACKGROUND: Cryoablation has garnered significant interest as a treatment for solid tumors including breast cancer for both its local effects and potential in stimulating an antitumor immune response. We sought to examine the impact that variances in technique might have on the immune response and examine the mechanism by which cryoablation may stimulate an antitumor immune response. MATERIALS AND METHODS: Balb/c mice with established 4T1 mammary carcinomas were treated by cryoablation at either a high rate of freeze or low rate of freeze, or by surgical excision, after spontaneous metastases occurred. Tumor-draining lymph nodes (TDLN) were excised at 1 week for EliSPOT assay and immunophenotyping. Mice were followed after treatment for enumeration of pulmonary metastases and survival. RESULTS: Compared with surgical excision, cryoablation using a high freeze rate resulted in a significant increase in tumor-specific T cells in the TDLN, a reduction in pulmonary metastases, and improved survival. However, cryoablation using a low freeze rate resulted in an increase in regulatory T cells, a significant increase in pulmonary metastases, and decreased survival. CONCLUSIONS: Cryoablation of breast cancer in mice can generate a tumor-specific immune response that can eradicate systemic micrometastases and improve outcome compared with surgical excision; however, the technique used to freeze the tissue may alter the immune response from stimulatory to suppressive.
PMID: 20033323 [PubMed - as supplied by publisher]
Freezing Breast Tumors Helps Stop Cancer's Spread In Mice
03 Mar 2010
Freezing a cancer kills it in its place, and also appears to generate an immune response that helps stop the cancer's spread, leading to improved survival rates over surgery, according to a new study in mice from researchers at the University of Michigan Comprehensive Cancer Center.
The study showed that the benefit from the rapid freezing is likely due to changes in the immune system that help to kill the tumor. Freezing with the slower technique appeared to make the immune system not as able to kill the tumor.
"Cryoablation has strong potential as a treatment for breast cancer. Not only does it appear effective in treating the primary tumor with little cosmetic concerns, but it also may stimulate an immune response capable of eradicating any cells that have traveled throughout the body, reducing both local and distant recurrence, similar to giving a breast cancer vaccine," says lead study author Michael Sabel, M.D., associate professor of surgery at the U-M Medical School.
Int J Cancer. 2009 Apr 1;124(7):1503-16. Altered gene expression in breast cancer liver metastases.
Erin N, Wang N, Xin P, Bui V, Weisz J, Barkan GA, Zhao W, Shearer D, Clawson GA.
Department of Pathology, Gittlen Cancer Research Foundation, Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA. We previously developed a highly aggressive cell line from heart metastases of 4T1 breast carcinoma (designated 4THM), which produced liver metastases (designated 4TLM). In this study, gene array analysis (GAEA) compared gene expression profiles in 4TLM with profiles in 4T1 and 4THM primary tumors. GAEA demonstrated that 4T1 and 4THM tumors differed in about 250 genes. Over 1,000 genes, however, were expressed differently in 4TLM compared with primary tumors. A cohort of 16 genes showed significantly decreased expression in 4THM tumors, which decreased even further in 4TLM. Many of these genes have been implicated in breast cancer, and many are involved in cell adhesion and junctional complexes. Expression of multiple tight and adherence junction proteins was either downregulated or disappeared in 4TLM; downregulation of claudin 4, claudin 7 and gamma-catenin was confirmed by quantitative polymerase chain reaction, immunoblot, and immunocytochemical (ICC) analyses. At the protein level, intact ZO-1 was also observed in 4T1 tumors, but was not expressed in 4THM or 4TLM tumors. ICC demonstrated expression of gamma-catenin at the plasma membrane with 4T1 tumors, whereas staining appeared to be nuclear/perinuclear in 4THM tumors. Claudin 7 staining was also seen in monocyte/pmacrophage-like cells in liver around metastatic lesions by ICC, and it appeared that larger 4TLM tumors apparently reexpressed claudin 7 RNA and protein. Our results demonstrate that decreased or abnormal expression of a number of cell adhesion/junctional proteins, including claudin 4, 7, ZO-1 and gamma-catenin, correlates with liver metastases, and that cell adhesion molecules in the microenvironment are also altered.
PMID: 19117052 [PubMed - indexed for MEDLINE]
Monday, February 8, 2010 Some doctors tout NanoKnife for tumor removal
MIAMI - A University of Miami doctor recently removed two cancerous tumors from a patient's liver using only three needlelike probes, a computer and a powerful burst of electricity.
His instrument was the NanoKnife not really a knife at all, but yet another new use of nanotechnology, the science of dealing with particles and dimensions down to the atomic level.
The patient, Maria Gomez of Delray Beach, Fla., went home the next day with little pain and no bleeding. She has a good chance of avoiding the liver transplant that was being considered before the operation in early January, says Dr. Govindarajan Narayanan, chief of vascular interventional radiology at the UM Miller School of Medicine.
"I think it's the best procedure," Gomez, 67, said a few days after the procedure. "I studied this. It's my life."
"Rather than using surgery or a transplant, we decided to try this noninvasive technique," said Narayanan. "We did a scan afterwards and it looked very good. In a month, we'll get another scan."
Narayanan is enthusiastic about the NanoKnife. It allows doctors to excise primary tumors that until now were considered inoperable, and can be used on tumors that have spread from cancer in other parts of the body, he said.
The UM center got its NanoKnife late last year, becoming the first facility in Florida and fourth in the United States to use one. Developed by AngioDynamics of Queensbury, N.Y., the device costs about $300,000; each probe costs $2,000.
Narayanan calls the NanoKnife "a major step forward in cancer treatment."
"We're still in the early stages of using it," he says. "It's good for tumors less than five centimeters; for really big tumors it's less good. My guess is it will be very effective in selective patients."
Dr. David Hays, a radiologist in Little Rock, Ark., who also uses the NanoKnife, agrees on its importance.
"It adds to rather than replacing the methods we're using today," he says. "When you take them all together, I believe they can increase cancer survival rates." The NanoKnife is a series of needlelike steel probes with an electrical generator, a computer with monitor and a couple of foot pedals to operate it.
The "nano" aspect of the procedure is that the electrical pulses poke infinitesimal holes in the tumor's cellular walls, causing them to die naturally and be routinely discarded by the body."The liver regenerates in the area where we removed the tumor," Narayanan says.
In his operation on Gomez, Narayanan watched the monitor of a CT scanner to precisely position three probes around the first of her tumors. He then used the NanoKnife's computer and monitor to precisely set the electrical pulse, then triggered it with a foot pedal. In a minute or so, the tumor was destroyed. He then used two probes on the smaller tumor.
Gomez was then brought out of general anesthesia. "She woke up, had some Jell-O, slept through the night, got up, brushed her teeth and went home," he says.
"I feel fine," Gomez said a few days after the procedure.
The new procedure was much less arduous than surgery used in 2006 to remove an earlier tumor in her liver. When the tumors recurred, doctors first recommended a transplant. Then Narayanan suggested the NanoKnife.
"I chose to avoid the transplant if I could," Gomez said.
Doctors hope that, because of its precision, the NanoKnife will be more likely to remove an entire tumor, leaving the patient cancer-free.
They say it's easier on patients than previous methods. A few years ago, Gomez's tumor would have called for major surgery. More modern, less invasive methods such as radio-frequency ablation or cryoablation attack the tumor with extreme heat or cold, which can damage healthy surrounding tissue. The NanoKnife creates no heat or cold, avoiding such damage. And Narayanan says there's a large artery running very close to the liver that could be damaged by the other techniques.
Hays, the Arkansas radiologist, agrees that, since the NanoKnife creates no heat or subfreezing temperatures, it can be used in some patients who can't undergo radio-frequency ablation and cryoablation.
Those methods "do well in killing the cancer," Hays says, "but they cause significant collateral damage to surrounding blood vessels, arteries and bile ducts. So there are some patients we can't treat with those methods."
While Narayanan used the NanoKnife for a liver tumor, doctors in other states and countries also are using it for tumors of the lung, kidney and prostate. In the prostate procedure, they hope the device's precision can spare surrounding nerves and maintain continence and sexual function.
"There's a lot of work going on to see what it can do," Narayanan said
Pol Merkur Lekarski. 2009 May;26(155):545-9. [Microwave ablation of liver tumors as a new instrument for minimally invasive liver surgery]
[Article in Polish] Stańczyk M, Zegadło A, Zwierowicz T, Zak D, Bogusławska R, Maruszyński M.
Military Institute of Health Services, Central Clinical Hospital of the Ministry of National Defense, Warsaw.
Incidence of primary and secondary liver tumors is increasing. Hepatic resection remains the treatment of choice for hepatic tumors. For various reasons the vast majority of patients with liver tumors are not suitable for resection. These patients are candidates for several image-guided focal thermal ablative therapies as alternatives to resection. Currently available ablative techniques include cryotherapy, radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation, high-intensity focused ultrasound ablation (HIFU), and ethanol injection. Presently RFA is most widely heat-based technology used for treatment of liver malignancies due to its availability, efficacy and low complication rates. However, RFA can be time-consuming and associated with higher recurrence rates in larger lesions. MWA is a new thermal ablative technique that uses electromagnetic energy to produce coagulation necrosis. MWA has several advantages over RFA such as an improved convection profile, consistently higher intratumoral temperatures, larger ablation volumes, faster ablation times, and the option of using multiple antennae simultaneously. We report our first experience using MWA and a Coviden Valleyab 915 MHz generator for ablation of liver tumor with respect to our previous experience with RFA. Further this study reviews current literature on the RFA and MWA for the treatment of the liver malignances. In our opinion although experience is limited MWA appears to be a safe and effective technology for hepatic tumor ablation and in some cases may be superior alternative to RFA.
PMID: 19606722 [PubMed - indexed for MEDLINE]
AJR Am J Roentgenol. 2010 Sep;195(3):W245-52. High-intensity focused ultrasound ablation: effective and safe therapy for solid tumors in difficult locations.
OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound therapeutic ablation of solid tumors in difficult locations.
SUBJECTS AND METHODS: A procedure was performed with a focused ultrasound tumor therapeutic system which provides real-time ultrasound guidance. All patients underwent MDCT or MRI, and some patients underwent PET/CT. From November 2007 through April 2009, 31 patients with 38 lesions of the liver and pancreas in difficult locations were treated. Six patients had hepatocellular carcinoma, 13 patients had hepatic metastasis from colorectal cancer, two had hepatic metastases of breast cancer, two had hepatic metastasis of neuroendocrine tumors, one patient had lymph node metastasis of breast cancer at the hepatic hilum, six patients had pancreatic cancer, and one patient had a neuroendocrine tumor. Difficult location was defined as tumor adjacent to a main blood vessel, the heart, the gallbladder and bile ducts, the bowel, or the stomach.
RESULTS: The mean diameter of tumors was 2.7 +/- 1.4 cm. PET/CT, MDCT, or both on the day after one session of high-intensity focused ultrasound treatment showed complete response in all six patients with hepatocellular carcinoma, the patient with lymph node metastasis, and 22 of 24 patients with hepatic metastasis. The symptoms of all seven patients with pancreatic caner or neuroendocrine tumors were palliated, and PET/CT or MRI showed complete response of six of seven lesions. Portal vein thrombosis occurred after high-intensity focused ultrasound ablation in one patient with pancreatic cancer. No other side effects were detected in a median follow-up period of 12 months.
CONCLUSION: According to our short- and long-term follow-up results, ultrasound-guided high-intensity focused ultrasound ablation can be considered a safe and feasible approach to the management of solid tumors in difficult locations.
PMID: 20729423 [PubMed - in process]
J Cancer Res Clin Oncol. 2010 Sep 22. [Epub ahead of print] Radioembolization and systemic chemotherapy improves response and survival for unresectable colorectal liver metastases. Chua TC, Bester L, Saxena A, Morris DL.
Hepatobiliary and Surgical Oncology Unit, Department of Surgery, University of New South Wales, St. George Hospital, Sydney, NSW, Australia.
PURPOSE: To evaluate the role of radioembolization and systemic chemotherapy as a combined modality therapy for unresectable colorectal liver metastases.
PATIENTS AND METHODS: Prospective database of a major yttrium-90 microsphere radioembolization treatment center in Sydney, Australia, that included 140 patients with unresectable colorectal liver metastases was analyzed. Tumor response, overall survival, treatment-related complications and an evaluation of its role as a combined modality therapy with systemic chemotherapy were performed.
RESULTS: One hundred and thirty-three patients (95%) had a single treatment, and seven patients (5%) had repeated treatments. Response following treatment was complete in two patients (1%), partial in 43 patients (31%), stable in 44 patients (31%), and 51 patients (37%) developed progressive disease. Combining chemotherapy with radioembolization was associated with a favorable treatment response (P = 0.007). The median overall survival was 9 (95% CI 6.4-11.3) months with a 1-, 2-, and 3-year survival rate of 42, 22, and 20%, respectively. Primary tumor site (P = 0.019), presence of extrahepatic disease (P = 0.033), and a favorable treatment response (P < 0.001) were identified as independent predictors for survival.
CONCLUSION: Combined modality therapy appears to improve tumor response rates. Survival is influenced by tumor site, presence of extrahepatic disease, and response to therapy. Yttrium-90 microsphere radioembolization is safe and may best be combined with systemic chemotherapy for patients with unresectable colorectal liver metastases.
PMID: 20859640 [PubMed - as supplied by publisher]
Breakthrough Cancer Treatment Now in Use at UC Davis Medical Center
A Device That Precisely Targets and Isolates Tumors
SAN JOSE, Calif., Nov. 9, 2011 /PRNewswire via COMTEX/ -- Vascular Designs, Inc., a medical device manufacturing company, today announced that its IsoFlow(TM) Infusion Catheter - which received FDA marketing clearance in 2009 - is now in use at UC Davis Medical Center in Sacramento, California in the treatment of liver cancer. The IsoFlow(TM) Infusion Catheter enables targeted sideways perfusion, allowing physicians to precisely target and isolate areas within the body where the infused drugs are delivered. With IsoFlow(TM) Infusion Catheter's unique design, medications can be delivered into areas that could not previously be treated directly, for instance, a cancerous tumor. The device also facilitates the LACE(TM) (lateral arterial chemo embolization) procedure.
"I am pleased that UC Davis Medical Center is a part of the IsoFlow(TM) Infusion Catheter family of hospitals," said Robert Goldman, CEO of Vascular Designs, and creator of the IsoFlow(TM) Infusion Catheter. "Directing treatment to specific locations increases the number of treatment options allowing better access to tumors and may reduce the discomfort to patients associated with the systemic application of chemotherapy."
Goldman developed the idea behind Vascular Designs, Inc. and its innovative IsoFlow(TM) Infusion Catheter. His personal experience of watching his sister Amy, suffer from and succumb to cancer, had a profound influence of the creation of IsoFlow(TM) Infusion Catheter.
To view an animation illustrating the IsoFlow infusion catheter in action and other press materials, please visit http://www.vasculardesigns.com/news.htm .
I just can't thank you enough for all the research you perform for us.
When I was considering cryosurgery I spent hours searching the web, only to find articles focused on local treatment to the liver focused on colon cancer. Articles that spoke nominally to breast cancer were not supportive. But...as we know, many of these articles can be old and out of date.
This is the first article I've seen that specifically speaks to the value of local treatments to the liver for breast cancer. And the results are encouraging as well.
Oct - Diagnosed - Stage IV
5 c.m. IDC - Left Side er/pr- Her2+++
Node + 2/14 - Single Liver Met
Nov - Begin T+H
Feb-Complete 6 cycles- T&H- NED
March - Continue - Herceptin Only
April - Rads for 6 weeks 2009
Continue Herceptin - Continue NED
April - Recurrance- 3 cm. Liver Met
May - Cryosurgery
June - November - Abraxane + Herceptin
Aug - PET/CT - CTC = 0 Back to NED 2010
January - Continue NED
July - Recurrance - 3 cm Liver Met CTC=1
August - Cryosurgery #2
August - November Navelbine
November - Back to NED - End Navelbine 2011
Feb - Recur - 4 cm Liver Met - Same Left Lobe
March Surgery it is -Couldn't get a clean margin
July - Confirmed continued liver involvement
August - Begin Herceptin + Tykerb
October - Mixed results from H+T
Add Abraxane + H + T - Nov - April 2012
January PET Scan - It's working!!
April - Back to NED
July - Recurrance
August - Begin TDM-1 Trial (Taxol + TDM-1)
Chris in Scotts Valley June 2002 extensive hi grade DCIS (pre-cancer-stage 0, clean sentinal node) Mastectomy/implant - no chemo, rads. "cured?" 9/2004 Diag: Stage IV extensive liver mets (!) ER/PR- Her2+++
10/04-3/05 Weekly Taxol/Carboplatin/Herceptin , complete response! 04/05 - 4/07 Herception every 3 wks, Continue NED
04/07 - recurrence to liver - 2 spots, starting tykerb/avastin trial
06/07 8/07 10/07 Scans show stable, continue on Tykerb/Avastin
01/08 Progression in liver 02/08 Begin (TDM1) trial
08/08 NED! It's Working! Continue on TDM1 02/09 Continue NED 02/10 Continue NED. 5/10 9/10 Scans NED 10/10 Scans NED
12/10 Scans not clear....4/11 Scans suggest progression 6/11 progression confirmed in liver
07/11 - 11/11 Herceptin/Xeloda -not working:(
12/11 Begin MM302 Phase I trial - bust:(
03/12 3rd times the charm? AKT trial
5/12 Scan shows reduction! 7/12 More reduction!!!!
8/12 Whoops...progression...trying for Perjeta/Herceptin (plus some more nasty chemo!)
9/12 Start Perjeta/Herceptin, chemo on hold due to infection/wound in leg, added on cycle 2 &3
11/12 Poops! progression in liver, Stop Perjeta/Taxo/Herc
11/12 Navelbine/Herce[ptin - try for a 3 cycles, no go.
2/13 Gemzar/Carbo/Herceptin - no go.
3/13 TACE procedure