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Experimental study evaluating EUS-guided RFA using a prototype retractable needle electrode array
Abstracts
other showed no symptoms. The late complications included stent occlusion and stent migration. Stent occlusion occurred in twelve times, and external stent migration occurred once during the follow-up. The average patency of each stent was 167.8 days by using Kaplan- Meier method. Conclusion: EUS-BD is technically feasible for the palliative treatment of obstructive jaundice, offering clinically effective drainage with a comparatively long patency period.
Efficacy and safety of endoscopic ultrasound-guided iodine-125 seed implantation combined with gemcitabine for unresectable pancreatic cancer: a randomized clinical trial Yueping Jiang, Zhendong Jin, Zhaoshen Li, Yan Liu, Yiqi Du, Jie Chen, Xianbao Zhan, Ling Zhang, Zhuan Liao Background and Study Aims: Gemcitabine (GEM) remains the standard of care for advanced pancreatic cancer. A recent preliminary study showed that endoscopic ultrasonography (EUS)-guided iodine-125 (125I) seed implantation was effective for unresectable pancreatic cancer. The aim of the present randomized clinical trial was to evaluate the efficacy and safety of EUS-guided 125I seed implantation combined with GEM for unresectable pancreatic cancer. Patients and methods: Forty-one patients with unresectable pancreatic cancer were randomized to receive either EUS-guided iodine-125 seed implantation combined with GEM (Group A, nZ21), or GEM alone (Group B, nZ20). EUS-guided 125I seed implantation was carried according to the treatment plan system, GEM was administered at the dosage of 1000 mg/m2 in a 30-min intravenous infusion, once a week for 3 consecutive weeks with a one-week interval. All patients were followed up after the first therapy. The primary endpoint was objective tumor response rate and clinical benefit response. Objective tumor response rate, which defined tumor size changed follow-up CT examinations performed after 2 months therapy in both arms, and clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (a 4 weeks) improvement in at least one parameter without worsening in any others. Progression-free survival (PFS) and median overall survival (MOS) were the secondary endpoints. Quality of life was assessed in group A. Results: A mean number of 26 radioactive seeds per patient were implanted into the tumors by EUS-guided needle puncture. The mean total implanted activity was 17.2 mCi, the minimum peripheral dose was 14,000 cGy, and the mean volume of implants was 53 cm3.The median period of follow up was 5.5 (range2-16 months) and 5.2 months (range 2-14 months), respectively, for Group A and Group B. EUSguided 125I seed implantion combined with GEM was superior to GEM alone in clinical benefit response (57.1%v25%, respectively; PZ0.037), objective tumor response rate (28.6% v 5%,respectively; PZ0.016). PFS and MOS were 4 and 3 months (PZ0.16) and 11 and 6 months (PZ0.653), respectively, for
the ideal location of seeds within the tumor to deliver the prescription dose. The number and the activity of seeds are calculated by a computerized treatment planning system according to the therapeutic dose and the size of tumor. The dose distribution was optimized and the dose-volume histogram for the target was generated with modified peripheral loading. The doses at the reference point were adjusted by changing the seeds number, source activity and the distance between the seeds. All dose calculations were hypothetical, and were generated by means of the TPS system. The seed implantation procedure is performed under EUS image guidance; needles are injected and seeds are deposited individually through the needles, according to the pre-plan.
EUS-guided ethanol lavage with paclitaxel injection for septated cystic tumors of the pancreas Hyoung-Chul Oh, Dong Wan Seo, Sang Soo Lee, Sung Koo Lee, MyungHwan Kim Background and study aims: EUS-guided intervention has been recently tried for treatment of cystic tumors. Factor which might influence the treatment response are presence of septation and mural nodule, and cyst wall thickness. This study aimed to evaluate the effectiveness of EUS-guided ethanol lavage with paclitaxel injection (EUS-EP) for treating septated cystic tumors of the pancreas. Patients and methods: 10 patients with oligolocular cystic tumors who underwent EUS-EP and were followed for more than 6 months after EUS-EP were included. The indications for EUS-EP were oligolocular cystic tumors 1) for which EUS-guided fine needle aspiration (FNA) was required to obtain additional information, and 2) which increased in size during the observation period. Results: The mean age was 38.4 (22-54) and seven patients were female. Cystic tumors were located at the head in 4 patients, body in one, and tail in five. The median diameter was 29.5 mm (20-68 mm) and original volume was 5.07 mL (1.5168.74 mL). The median CEA and amylase concentrations in the cyst fluid were 39.2 ng/mL (1-8,190 ng/mL) and 115.5 U/L (5-75,633 U/L), respectively. The presumed diagnoses were 3 MCNs, 4 SCAs, and 3 indeterminate cysts. The median follow-up period was 8.5 months (6-18 months). The median final volume much decreased to 0.54 mL (0.00-12.42), compared to median original volume of 5.07 mL (1.51-68.74). Complete resolution was achieved in 6 patients, partial resolution in 2 patients, and persistent cyst in 2 patients. Conclusions: Complete resolution was achieved in 6 of 10 patients with septated cystic tumors. Well-defined case selection and tailored intervention planning to maximize the therapeutic efficacy are required for treating septated cystic tumors of the pancreas by EUS-EP.
EUS-guided implatation therapy Zhendong Jin
Experimental study evaluating EUS-guided RFA using a prototype retractable needle electrode array Shyam Varadarajulu, Nirag C. Jhala, Ernesto R. Drelichman
Introduction: The permanent implantation of radioactive seeds in the treatment of tumor is a new technology which develops in recent 20 years. In particular, the successful of the 125 iodine (I) and 103 palladium (Pd) particles with low energy and relative long half-life makes the procedure security and easy protection. The history of brachytherapy: With the concept of presenting the tumor with a higher radiation dose with better sparing of surrounding tissue, Barringer reported permanent interstitial implant for the treatment of this disease using radium needles. Young and Fronz and Young successfully controlled the dosimetry of this procedure. In spite of various other brachytherapy techniques tried subsequently, including colloidal gold, the techniques gradually fell into disfavor because of radiation safety issues associated with handling these isotopes and increased normal tissue complications observed with the crude implantation techniques. In the 1960s, radioisotopes such as gold (Au-198) and iodine (I-125) became clinically available for permanent seed implantation in the prostate. Whitmore et al. reported the use of I-125 seeds for prostatic interstitial irradiation, and this treatment had been commonly performed for a decade. The type of radioactive particles: Radioactive particles are short rodshaped radioactive sources made of titanium shell package radioisotope. The particles are now commonly used 125 I (iodine), 192 Ir (iridium), 103 Pd (Palladium). The titanium shell isolates the radioactive elements, avoiding the loss of radioactive sources and nuclear contamination to the environment, and thus can accurately control the dose of radioactive sources. The following is a brief introduction of the common characteristics of the particles. 125I: half-life 59.6 days, the average energy 30 KeV, length of common particles 4.5 mm, diameter of 0.8 mm. Its lead-reduced thickness is 0.025 mm. 192Ir: half-life 70 days, the average energy 380 KeV. According to clinical requirements, it can be cut into any length and shape. The length of seed 3-6 mm. The shortcoming is the short half-life. 103Pd: half-life 16.79 days, the average energy 21-23 KeV. 103Pd is stability in the body, and its leadreduced thickness is 0.008 mm. Brachytherapy planning and seeds placement: A few days ahead of seed implantation, CT scan is performed to obtain an image and measure the volume of the tumor. In some cases, the largest and smallest diameters are recommended to be measured by EUS, and the plan treatment volume is estimated according the following formula: V Z 1/2 ab2, where a and b are the largest and smallest tumor diameters, respectively, and V is the tumor volume in milliliter. A computerized three-dimensional (3D) structure of the tumor and a plan are made to demonstrate
Background: Radiofrequency ablation (RFA) under CT/USD-guidance permits coagulative necrosis of unresectable malignant lesions. However, not all lesions can be accessed by CT/USD. EUS-guided RFA can be a potential alternative in these patients. Although previously reported in an animal model, the development of EUS-RFA has been impeded due to lack of a retractable needle electrode array which is required for the safe and effective ablation of larger areas. Aim: To evaluate the feasibility and safety of performing EUS-RFA using a 19-gauge FNA needle fitted with an umbrella shaped retractable needle electrode array. Methods: A 19-gauge EUS-FNA needle was modified and fitted with a retractable echogenic umbrella shaped monopolar electrode array at its tip. Ten mm tine spacing was designed between the 6 arrays to help create a spherical thermal lesion. This prototype system was tested on 5 anesthetized pigs. At EUS, following trans-gastric puncture of the central lobe of the liver, RFA was undertaken. The FNA needle was connected to a 200W generator that has an impedence-based feedback system designed to monitor the extent of tissue destruction and permit continued delivery of RF energy until complete ablation is attained. Following RFA, abdomen X-ray was obtained to check for perforation. One pig was euthanized 3 hrs after RFA to assess for immediate complications and subsequent pathologic examination was performed. Four pigs were survived for 7 days during which vital signs and LFT’s were monitored on a periodic basis. Pathologic examination was then performed on the four pigs at day 7. Results: At EUS, in all pigs, the needle electrode was well visualized and could be deployed into the liver without technical difficulty. During ablation a round hyperechoic foci gradually surrounded the electrode tip. Tissue ablation was attained within 7 min and the electrode array could be easily withdrawn into the needle assembly. No GI mucosal bleeding/ulcer was evident at EUS. Abdomen X-ray revealed no perforation in any of the five pigs. The vital signs of all five pigs remained stable throughout the procedure and continually until they were euthanized. LFT’s remained normal following RFA in the four pigs that were survived. Pathology in all pigs revealed a discrete, welldemarcated spherical foci of complete coagulation necrosis measuring 2.6cm in diameter without damage to the surrounding liver parenchyma/vasculature. Conclusions: In this study, EUS-RFA of the liver was performed safely using the retractable umbrella shaped electrode array with effective coagulation necrosis of large areas. Further animal studies evaluating EUS-RFA in other organs must be pursued prior to human trials.
www.giejournal.org
Volume 69, No. 2 : 2009 GASTROINTESTINAL ENDOSCOPY S229
other showed no symptoms. The late complications included stent occlusion and stent migration. Stent occlusion occurred in twelve times, and external stent migration occurred once during the follow-up. The average patency of each stent was 167.8 days by using Kaplan- Meier method. Conclusion: EUS-BD is technically feasible for the palliative treatment of obstructive jaundice, offering clinically effective drainage with a comparatively long patency period.
Efficacy and safety of endoscopic ultrasound-guided iodine-125 seed implantation combined with gemcitabine for unresectable pancreatic cancer: a randomized clinical trial Yueping Jiang, Zhendong Jin, Zhaoshen Li, Yan Liu, Yiqi Du, Jie Chen, Xianbao Zhan, Ling Zhang, Zhuan Liao Background and Study Aims: Gemcitabine (GEM) remains the standard of care for advanced pancreatic cancer. A recent preliminary study showed that endoscopic ultrasonography (EUS)-guided iodine-125 (125I) seed implantation was effective for unresectable pancreatic cancer. The aim of the present randomized clinical trial was to evaluate the efficacy and safety of EUS-guided 125I seed implantation combined with GEM for unresectable pancreatic cancer. Patients and methods: Forty-one patients with unresectable pancreatic cancer were randomized to receive either EUS-guided iodine-125 seed implantation combined with GEM (Group A, nZ21), or GEM alone (Group B, nZ20). EUS-guided 125I seed implantation was carried according to the treatment plan system, GEM was administered at the dosage of 1000 mg/m2 in a 30-min intravenous infusion, once a week for 3 consecutive weeks with a one-week interval. All patients were followed up after the first therapy. The primary endpoint was objective tumor response rate and clinical benefit response. Objective tumor response rate, which defined tumor size changed follow-up CT examinations performed after 2 months therapy in both arms, and clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (a 4 weeks) improvement in at least one parameter without worsening in any others. Progression-free survival (PFS) and median overall survival (MOS) were the secondary endpoints. Quality of life was assessed in group A. Results: A mean number of 26 radioactive seeds per patient were implanted into the tumors by EUS-guided needle puncture. The mean total implanted activity was 17.2 mCi, the minimum peripheral dose was 14,000 cGy, and the mean volume of implants was 53 cm3.The median period of follow up was 5.5 (range2-16 months) and 5.2 months (range 2-14 months), respectively, for Group A and Group B. EUSguided 125I seed implantion combined with GEM was superior to GEM alone in clinical benefit response (57.1%v25%, respectively; PZ0.037), objective tumor response rate (28.6% v 5%,respectively; PZ0.016). PFS and MOS were 4 and 3 months (PZ0.16) and 11 and 6 months (PZ0.653), respectively, for
the ideal location of seeds within the tumor to deliver the prescription dose. The number and the activity of seeds are calculated by a computerized treatment planning system according to the therapeutic dose and the size of tumor. The dose distribution was optimized and the dose-volume histogram for the target was generated with modified peripheral loading. The doses at the reference point were adjusted by changing the seeds number, source activity and the distance between the seeds. All dose calculations were hypothetical, and were generated by means of the TPS system. The seed implantation procedure is performed under EUS image guidance; needles are injected and seeds are deposited individually through the needles, according to the pre-plan.
EUS-guided ethanol lavage with paclitaxel injection for septated cystic tumors of the pancreas Hyoung-Chul Oh, Dong Wan Seo, Sang Soo Lee, Sung Koo Lee, MyungHwan Kim Background and study aims: EUS-guided intervention has been recently tried for treatment of cystic tumors. Factor which might influence the treatment response are presence of septation and mural nodule, and cyst wall thickness. This study aimed to evaluate the effectiveness of EUS-guided ethanol lavage with paclitaxel injection (EUS-EP) for treating septated cystic tumors of the pancreas. Patients and methods: 10 patients with oligolocular cystic tumors who underwent EUS-EP and were followed for more than 6 months after EUS-EP were included. The indications for EUS-EP were oligolocular cystic tumors 1) for which EUS-guided fine needle aspiration (FNA) was required to obtain additional information, and 2) which increased in size during the observation period. Results: The mean age was 38.4 (22-54) and seven patients were female. Cystic tumors were located at the head in 4 patients, body in one, and tail in five. The median diameter was 29.5 mm (20-68 mm) and original volume was 5.07 mL (1.5168.74 mL). The median CEA and amylase concentrations in the cyst fluid were 39.2 ng/mL (1-8,190 ng/mL) and 115.5 U/L (5-75,633 U/L), respectively. The presumed diagnoses were 3 MCNs, 4 SCAs, and 3 indeterminate cysts. The median follow-up period was 8.5 months (6-18 months). The median final volume much decreased to 0.54 mL (0.00-12.42), compared to median original volume of 5.07 mL (1.51-68.74). Complete resolution was achieved in 6 patients, partial resolution in 2 patients, and persistent cyst in 2 patients. Conclusions: Complete resolution was achieved in 6 of 10 patients with septated cystic tumors. Well-defined case selection and tailored intervention planning to maximize the therapeutic efficacy are required for treating septated cystic tumors of the pancreas by EUS-EP.
EUS-guided implatation therapy Zhendong Jin
Experimental study evaluating EUS-guided RFA using a prototype retractable needle electrode array Shyam Varadarajulu, Nirag C. Jhala, Ernesto R. Drelichman
Introduction: The permanent implantation of radioactive seeds in the treatment of tumor is a new technology which develops in recent 20 years. In particular, the successful of the 125 iodine (I) and 103 palladium (Pd) particles with low energy and relative long half-life makes the procedure security and easy protection. The history of brachytherapy: With the concept of presenting the tumor with a higher radiation dose with better sparing of surrounding tissue, Barringer reported permanent interstitial implant for the treatment of this disease using radium needles. Young and Fronz and Young successfully controlled the dosimetry of this procedure. In spite of various other brachytherapy techniques tried subsequently, including colloidal gold, the techniques gradually fell into disfavor because of radiation safety issues associated with handling these isotopes and increased normal tissue complications observed with the crude implantation techniques. In the 1960s, radioisotopes such as gold (Au-198) and iodine (I-125) became clinically available for permanent seed implantation in the prostate. Whitmore et al. reported the use of I-125 seeds for prostatic interstitial irradiation, and this treatment had been commonly performed for a decade. The type of radioactive particles: Radioactive particles are short rodshaped radioactive sources made of titanium shell package radioisotope. The particles are now commonly used 125 I (iodine), 192 Ir (iridium), 103 Pd (Palladium). The titanium shell isolates the radioactive elements, avoiding the loss of radioactive sources and nuclear contamination to the environment, and thus can accurately control the dose of radioactive sources. The following is a brief introduction of the common characteristics of the particles. 125I: half-life 59.6 days, the average energy 30 KeV, length of common particles 4.5 mm, diameter of 0.8 mm. Its lead-reduced thickness is 0.025 mm. 192Ir: half-life 70 days, the average energy 380 KeV. According to clinical requirements, it can be cut into any length and shape. The length of seed 3-6 mm. The shortcoming is the short half-life. 103Pd: half-life 16.79 days, the average energy 21-23 KeV. 103Pd is stability in the body, and its leadreduced thickness is 0.008 mm. Brachytherapy planning and seeds placement: A few days ahead of seed implantation, CT scan is performed to obtain an image and measure the volume of the tumor. In some cases, the largest and smallest diameters are recommended to be measured by EUS, and the plan treatment volume is estimated according the following formula: V Z 1/2 ab2, where a and b are the largest and smallest tumor diameters, respectively, and V is the tumor volume in milliliter. A computerized three-dimensional (3D) structure of the tumor and a plan are made to demonstrate
Background: Radiofrequency ablation (RFA) under CT/USD-guidance permits coagulative necrosis of unresectable malignant lesions. However, not all lesions can be accessed by CT/USD. EUS-guided RFA can be a potential alternative in these patients. Although previously reported in an animal model, the development of EUS-RFA has been impeded due to lack of a retractable needle electrode array which is required for the safe and effective ablation of larger areas. Aim: To evaluate the feasibility and safety of performing EUS-RFA using a 19-gauge FNA needle fitted with an umbrella shaped retractable needle electrode array. Methods: A 19-gauge EUS-FNA needle was modified and fitted with a retractable echogenic umbrella shaped monopolar electrode array at its tip. Ten mm tine spacing was designed between the 6 arrays to help create a spherical thermal lesion. This prototype system was tested on 5 anesthetized pigs. At EUS, following trans-gastric puncture of the central lobe of the liver, RFA was undertaken. The FNA needle was connected to a 200W generator that has an impedence-based feedback system designed to monitor the extent of tissue destruction and permit continued delivery of RF energy until complete ablation is attained. Following RFA, abdomen X-ray was obtained to check for perforation. One pig was euthanized 3 hrs after RFA to assess for immediate complications and subsequent pathologic examination was performed. Four pigs were survived for 7 days during which vital signs and LFT’s were monitored on a periodic basis. Pathologic examination was then performed on the four pigs at day 7. Results: At EUS, in all pigs, the needle electrode was well visualized and could be deployed into the liver without technical difficulty. During ablation a round hyperechoic foci gradually surrounded the electrode tip. Tissue ablation was attained within 7 min and the electrode array could be easily withdrawn into the needle assembly. No GI mucosal bleeding/ulcer was evident at EUS. Abdomen X-ray revealed no perforation in any of the five pigs. The vital signs of all five pigs remained stable throughout the procedure and continually until they were euthanized. LFT’s remained normal following RFA in the four pigs that were survived. Pathology in all pigs revealed a discrete, welldemarcated spherical foci of complete coagulation necrosis measuring 2.6cm in diameter without damage to the surrounding liver parenchyma/vasculature. Conclusions: In this study, EUS-RFA of the liver was performed safely using the retractable umbrella shaped electrode array with effective coagulation necrosis of large areas. Further animal studies evaluating EUS-RFA in other organs must be pursued prior to human trials.
www.giejournal.org
Volume 69, No. 2 : 2009 GASTROINTESTINAL ENDOSCOPY S229