Author
Premalignant lesion
n
Treatment
Median area of ablation, mm (range)
Outcome
Complications
Gan et al.
Cystic tumors of the pancreas
25
EUS-guided ethanol lavage
19.4 (6–30)
Complete resolution in 35%
None
Oh et al.
Cystic tumors of the pancreas
14
EUS-guided ethanol lavage + paclitaxel
25.5 (17–52)
Complete resolution in 79%
Acute pancreatitis (n = 1)
Hyperamylasemia (n = 6) abdominal pain (n + 1)
Oh et al.
Cystic tumors of the pancreas
10
EUS-guided ethanol lavage + paclitaxel
29.5 (17–52)
Complete resolution in 60%
Mild pancreatitis (n = 1)
DeWitt et al.
Cystic tumors of the pancreas
42
Randomized double-blind study: saline vs ethanol
22.4 (20–68)
Complete resolution in 33%
Abdominal pain at 7 days (n = 5) pancreatitis (n = 1)
Acystic bleeding (n = 1)
Oh et al.
Cystic tumors of the pancreas
52
EUS-guided ethanol lavage + paclitaxel
31.8 (17–68)
Complete resolution in 62%
Fever (1.52)
Mild pancreatitis (1/52)
Splenic vein obliteration (1/52)
Levy et al.
PNET
8
EUS-guided ethanol lavage (5 patients) and intraoperative ultrasound-guided (IOUS) ethanol lavage (3 patients)
16.6 (8–21)
Hypoglycemia symptoms disappeared 5/8 and significantly improved 3/8
EUS guided: no complications
IOUS-guided ethanol injection: minor peritumoral bleeding (1/3), pseudocyst (1/3)
Pai et al.
Cystic tumors of the pancreas + neuroendocrine tumors
8
EUS-guided RFA
Mean size pre-RFA, 38.8 mm vs mean size post-RFA, 20 mm
Complete resolution in 25% (2/8)
2/8 patients had mild abdominal pain that resolved in 3 days
Table 41.2
Endoscopic ultrasound administered non-ablative and antitumor therapies for pancreatic ductal adenocarcinoma
Author | Therapy | Patients | n | Outcome and survival | Complications |
|---|---|---|---|---|---|
Chang et al. | Cytoimplant (mixed lymphocyte culture) | Unresectable PDAC | 8 | Median survival: 13.2 months, 2 partial responders and 1 minor response | 7/8 developed low-grade fever 3/8 required biliary stent placement |
Hecht et al. | ONYX-015 (55-kDa gene-deleted adenovirus) + IV gemcitabine | Unresectable PDAC | 21 | No patient showed tumor regression at day 35. After commencement of gemcitabine, 2/15 had a partial response | Sepsis: 2/15, duodenal perforation: 2/15 |
Hecht et al. Chang et al. | TNFerade (replication-deficient adenovector containing human tumor necrosis factor (TNF)-a gene) | Locally advanced PDAC | 50 | Response: one complete response, 3 partial responses. 7 patients eventually went to surgery, 6 had clear margins, and 3 survived >24 months | Dose-limiting toxicities of pancreatitis and cholangitis were observed in 3/50 |
Herman et al. | Phase III study of standard care plus TNFerade (SOC + TNFerade) vs standard of care alone (SOC) | Locally advanced PDAC | 304 (187 SOC + TNFerade) | Median survival: 10.0 months for patients in both the SOC + TNFerade and SOC arms[hazard ration (HR), 0.90, 95% Cl; 0,66–1.22, P – 0.26] | No major complications, patients in the SOC+ TNFerade arm experienced more grade 1–2 fever than those in the SOC alone arm (P < 0.001) |
Sun et al. | EUS-guided implantation of radioactive seeds (iodine-125) | Unresectable PDAC | 15 | Tumor response: “partial” in 27% and “minimal” in 205. Pain relief: 30% | Local complications (pancreatitis and pseudocyst formation) 3/15. Grade 3 hematologic toxicity in 3/15 |
Jin et al. | EUS-guided implantation of radioactive seeds (iodine-125) | Unresectable PDAC | 22 | Tumor response: “partial” in 3/22 (13.6%) | No complications |
Table 41.3
Studies of cryoablation in pancreatic ductal adenocarcinoma
Study | n | Patients | Study | Outcome | Complications |
|---|---|---|---|---|---|
Patiutko et al. (non-English article) | 30 | Locally advanced PDAC | Combination of cryosurgery and radiation | Pain relief and improvement in performance status 30/30 | Not reported |
Kovach et al. | 9 | Unresectable PDAC | Phase I study of intraoperative cryoablation under US guidance; 4 had concurrent gastrojejunostomy | 7/9 discharged with non-intravenous analgesia and 1/discharged with no analgesia | No complications reported |
Li et al. (non-English article) | 44 | Unresectable PDAC | Intraoperative cryoablation under US guidance | Median overall survival: 14 months | 40.9% (18/44) had delayed gastric emptying. 6.8% (3/44) had a bile and pancreatic leak |
Wu et al. (non-English article) | 15 | Unresectable PDAC | Intraoperative cryoablation under US guidance | Median overall survival: 13.4 months | 1/15 patients developed a bile leak |
Yi et al. (non-English article) | 8 | Unresectable PDAC | Intraoperative cryoablation under US guidance | Not reported | 25% (2/8) developed delayed gastric emptying |
Xu et al. | 38 | Locally advanced PDAC, 8 had liver metastases | Intraoperative or percutaneous cryoablation under US or CT guidance + (125) iodine seed implantation | Median overall survival: 12 months 19/38 (50,9%) survived more than 12 months | Acute pancreatitis: 5/38 (one has severe pancreatitis) |
Xu et al. | 49 | Locally advanced PDAC, 12 had liver metastases | Intraoperative or percutaneous cryoablation under US or CT guidance + (125) iodine seed implantation. Some patients also received regional celiac artery chemotherapy | Median survival: 16.2 months 26 patients (53.1%) survived more than 12 months | Acute pancreatitis: 6/49 (one had severe pancreatitis) |
Li et al. | 68 | Unresectable PDAC requiring palliative bypass | Retrospective case series of intraoperative cryoablation under US guidance, followed by palliative bypass | Median overall survival: 30.4 months (range 6–49 months) | Postoperative morbidity: 42.9% |
Delayed gastric emptying occurred in 35.7% | |||||
Xu et al. | 59 | Unresectable PDAC | Intraoperative or percutaneous cryotherapy | Overall survival at 12 months: 34.5% | Mild abdominal pain: 45/59 (76.3%) |
Major complications (bleeding, pancreatic leak): 3/59 (5%) | |||||
Niu et al. | 36 (CT) | Metastatic PDAC | Intraoperative cryotherapy (CT) or cryo-immunotherapy (CIT) under US guidance | Median overall survival in CIT: 13 months CT: 7 months | Not reported |
31 (CIT) |
Table 41.4
Studies of photodynamic therapy in pancreatic ductal adenocarcinoma
Study | n | Study | Photosensitizer | Number of fibers | Number of ablations | Outcome and survival | Complications |
|---|---|---|---|---|---|---|---|
Brown et al. | 16 | CT-guided percutaneous PDT to locally advanced but inoperable PDAC without metastatic disease | mTHPC | 1 | Single | Tumor necrosis: 16/16 Median survival: 9.5 months 44% (7/16) survived > 1 year | Significant gastrointestinal bleeding: 2/16 (controlled without surgery) |
Huggett et al. | 13 + 2 | CT-guided percutaneous PDT to locally advanced but inoperable PDAC without metastatic disease | Verteporfin | 1 | Single (13) Multiple (2) | Technically feasible: 15/15. Dose-dependent necrosis occurred | Single fiber: no complications. Multiple fibers: CT evidence of inflammatory change anterior to the pancreas, no clinical sequelae |
Table 41.5
Studies of radiofrequency ablation in pancreatic ductal adenocarcinoma
Study | Patients | n | Route of administration | Device | RFA temp | RFA duration (min) | Outcome | Complication |
|---|---|---|---|---|---|---|---|---|
Matsui et al. | Unresectable PDAC | 20 LA:9 M:11 | At laparotomy 4 RFA probes were inserted into the tumor 2 cm apart | A 13.56-MHz RFA pulse was produced by the heating apparatus | 50 | 15 | Survival: 3 months | Mortality: 10% (septic shock and gastrointestinal bleeding) |
Hadjicostas et al. | Locally advanced and unresectable PDAC | 4 | Intraoperative – followed by palliative bypass surgery | Cool-tip™ RF Ablation system | NR | 2–8 | All patients were alive 1 year post-RFA | No complications encountered |
Wu et al. | Unresectable PDAC | 16 LA:11 M:5 | Intraoperative | Cool-tip™ RF Ablation system | 30–90 | 12 at 30 °C then 1 at 90 °C | Pain relief: back pain improved (6/12) | Mortality: 25% (4/16 pancreatic fistula: 18.8% (3/16) |
Spiliotis et al. | Stage III and IV PDAC receiving palliative therapy | 12 LA: 8 M:4 | Intraoperative – followed by palliative bypass surgery | Cool-tip™ RF Ablation system | 90 | 5–7 | Mean survival: 33 months | Morbidity: 16% (biliary leak) Mortality: 0 % |
Girelli et al. | Unresectable locally advanced PDAC | 50 | Intraoperative – followed by palliative bypass surgery | Cool-tip™ RF Ablation system | 105 (25 pts) 90 (25 pts) | Not reported | Not reported | Morbidity 40% in the first 25 patients. Probe temperature decreased from 105 to 90 °C. Morbidity 8% in second cohort of 25 patients 30-day mortality: 2% |
Girelli et al. | Unresectable locally advanced PDAC | 100 | Intraoperative – followed by palliative bypass surgery | Cool-tip™ RF Ablation system | 90 | 56–10 | Median overall survival: 20 months | Morbidity: 15%. Mortality: 3% |
Giardino et al. | Unresectable PDAC, 47 RFA alone, 60 had RFA + RCT and/or IASC | 107 | Intraoperative – followed by palliative bypass surgery | Cool-tip™ RF Ablation system | 90 | 5–10 | Median overall survival: 14.7 months in RFA alone but 25.6 months in those receiving RFA + RCT and/or IADC (P = 0.004) | Mortality 1,8% (liver failure and duodenal perforation) morbidity: 28% |
Arcidiacono et al. | Locally advanced PDAC | 22 | EUS-guided | Cryotherm probe; bipolar RFA + cryogenic cooling | NR | 2–15 | Feasible in 16/22 (72.8%) | Pain (3/22) |
Steel et al. | Unresectable malignant bile duct obstruction (16/22 due to PDAC) | 22 | RFA + SEMS placement at ERCP | Habib EndoHPB wire-guided catheter | NR | Sequential 2-min treatments – median 2 (range 1–4) | Success ful biliary decompression (21/22) | Minor bleeding (1/22) asymptomatic biochemical pancreatitis (1/22), percutaneous gallbladder drainage (2/22). At 90 days, 2/22 had died, one with a patent SEMS |
Figueroa-Barojas et al. | Unresectable malignant bile duct obstruction (7/20 due to PDAC | 20 | RFA + SEMS placement at ERCP | Habib EndoHPB wire-guided catheter | NR | Sequential 2-min treatments | SEMS occlusion at 90 days (3/22), bile duct diameter increased by 3.5 mm post-RFA (P = 0.0001) | Abdominal pain (5/20), mild post-ERCP pancreatitis and cholecystitis (1/20) |
Pai et al. | Locally advanced PDAC | 7 | EUS guided | Habib EUS-RFA catheter | NR | Sequential 90-s treatments – median 3 (range 2–4) | 2/7 tumors decreased in size | Mild pancreatitis: (1/7) |
Table 41.6
Studies of high-intensity focused ultrasound in pancreatic ductal adenocarcinoma
