Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer.

BACKGROUND: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called "liquid biopsy") is recently developed. AIMS: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. METHODS: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. RESULTS: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36-9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). CONCLUSIONS: In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.

Effectiveness of Menghini-Type Needles for Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Masses.

BACKGROUND: Cutting needles are thought to be effective as biopsy needles. A few types of cutting needles are available for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and the Menghini-type needle is an end-type cutting needle. AIMS: A prospective randomized controlled trial was conducted to compare the results of EUS-FNA using a Menghini-type needle (needle M) versus a conventional needle (needle S). METHODS: The main eligibility criteria were as follows: patients with a pancreatic mass referred for EUS-FNA, ≥ 20 years old, and a performance status < 4. The primary outcome was the sample quality. The secondary outcomes were factors associated with the sample quality, diagnostic accuracy, and adverse events. RESULTS: A total of 97 patients were enrolled in this study. The sample quality for total puncture with needle M (92.8%) was significantly higher than that with needle S (81.4%) (p = 0.0305). The tumor size (p = 0.033) and type of needle (p = 0.031) were significant factors associated with adequate tissue collection in univariate and multivariate analyses (odds ratio [OR] 2.71; 95% confidence interval [CI] 1.12-6.54; p = 0.027 for tumor size, and OR 2.93; 95% CI 1.23-8.21; p = 0.0153 for type of needle). The diagnostic accuracy of each needle was 88.7% (86/97) with needle M and 73.2% (71/97) with needle S. Adverse events occurred in 2 of the 97 patients (0.02%). CONCLUSION: A Menghini-type needle was able to obtain core tissue for histology more effectively than a conventional aspiration needle. TRIAL REGISTRATION NUMBERS: UMIN registration number of 000020668.

A rare case of immunotherapy-induced cholangitis and gastritis.

Immune checkpoint inhibitor-related liver injury usually appears as a hepatitis pattern, with a cholangitis pattern being a rare immune-related adverse event. We report a Japanese man in his fifties with immune checkpoint inhibitor-induced cholangitis and gastritis. The patient had been treated for approximately 7 months with carboplatin, pemetrexed sodium hydrate, and bevacizumab for an undifferentiated cancer of unknown primary, with metastases to the right pleura and nasolacrimal duct. The patient was then treated with immune checkpoint inhibitors, including 2 months of atezolizumab followed by 1 month of ramucirumab and docetaxel. Laboratory examinations showed elevated levels of biliary tract enzymes. He complained of generalized fatigue. Computed tomography revealed thickening of the gallbladder and external hepatic bile duct walls and the periportal collar sign. Endoscopic retrograde cholangiopancreatography was negative for bile duct obstruction but showed diffuse asymmetric irregular findings from the hilar region to the distal bile duct. Upper endoscopy showed diffuse irregular erosions and redness. Histopathological examination of specimens of bile duct and gastric mucosa revealed CD8-predominant inflammatory cell infiltrates. We diagnosed the findings as immunotherapy-induced cholangitis and gastritis. Because there are no published reports on immunotherapyinduced cholangitis combined with gastritis, we here report our patient as a rare case.

Comparison Between Endoscopic Biliary Stenting Combined with Balloon Dilation and Balloon Dilation Alone for the Treatment of Benign Hepaticojejunostomy Anastomotic Stricture.

BACKGROUND: Hepaticojejunostomy anastomotic stricture (HJAS) is an important complication of biliary reconstructive surgery but has no standard treatment. We aimed to evaluate the outcomes of endoscopic treatment for benign HJAS and identify the risk factors for its recurrence. METHODS: This study retrospectively analyzed 176 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for HJAS between April 2008 and March 2016. The outcome of endoscopic biliary stenting combined with balloon dilation (EBS group) and balloon dilation alone (balloon group) was evaluated. RESULTS: The scope was successfully inserted into the HJ site in 93.8% patients (165/176), and 139 patients underwent endoscopic treatment after HJAS was confirmed. Successful biliary drainage was achieved in 137 patients by using ERCP and rendezvous procedures. Among these, 103 patients were included in balloon group and 34 patients were in EBS group. HJAS was resolved in 132 patients; five died from recurrence of primary disease. The 1 (3)-year bile duct patency rates in the balloon and EBS groups were 62.5% (46.6%) and 89.4% (84.7%), respectively (p = 0.015). Univariate analysis showed that balloon dilation (p = 0.009) and early HJAS formation (time from surgery to ERCP < 1 year) (p = 0.02) were risk factors for HJAS recurrence. In the multivariate analysis, balloon dilatation was identified as independent risk factors for HJAS recurrence. CONCLUSIONS: Balloon dilation without stent deployment and early HJAS formation are risk factors for HJAS recurrence after endoscopic treatment. Stent deployment might be recommended for definite resolution of HJAS.

Diagnostic Ability of Convex-Arrayed Endoscopic Ultrasonography for Major Vascular Invasion in Pancreatic Cancer.

BACKGROUND/AIMS: This study aimed to examine the diagnostic ability of endoscopic ultrasonography (EUS) for major vascular invasion in pancreatic cancer and to evaluate the relationship between EUS findings and pathological distance. METHODS: In total, 57 consecutive patients who underwent EUS for pancreatic cancer before surgery were retrospectively reviewed. EUS image findings were divided into four types according to the relationship between the tumor and major vessel (types 1 and 2: invasion, types 3 and 4: non-invasion). We also compared the EUS findings and pathologically measured distances between the tumors and evaluated vessels. RESULTS: The sensitivity, specificity, and accuracy of EUS diagnosis for vascular invasion were 89%, 92%, and 91%, respectively, in the veins and 83%, 94%, and 93%, respectively, in the arteries. The pathologically evaluated distances of cases with type 2 EUS findings were significantly shorter than those of cases with type 3 EUS findings in both the major veins (median [interquartile range], 96 [0-742] µm vs. 2,833 [1,076-5,694] µm, p=0.012) and arteries (623 [0-854] µm vs. 3,097 [1,396-6,000] µm, p=0.0061). All cases with a distance of ≥1,000 µm between the tumors and main vessels were correctly diagnosed. CONCLUSION: Tumors at a distance ≥1,000 µm from the main vessels were correctly diagnosed by EUS.

Efficacy and safety of chemotherapy after endoscopic double stenting for malignant duodenal and biliary obstructions in patients with advanced pancreatic cancer: a single-institution retrospective analysis.

BACKGROUND: Advanced pancreatic cancer is accompanied not only by bile duct obstruction, but also occasionally by duodenal obstruction. With new advances in chemotherapy and improvement in the management of stent dysfunction, the life expectancy of patients with pancreatic cancer has increased. This study aimed to evaluate the efficacy and safety of chemotherapy for advanced pancreatic cancer, as well as to analyze the prognostic factors, following endoscopic double stenting. METHODS: This retrospective study was conducted from January 1, 2007 to October 31, 2015 at an academic center. Fifty consecutive patients with pancreatic cancer who had undergone endoscopic double stenting, comprising duodenal and biliary stenting, were analyzed. We reviewed the patients records and analyzed the data of stent dysfunction rates after double stenting, reintervention for stent dysfunction, chemotherapy after double stenting, adverse events associated with chemotherapy after double stenting, survival times following double stenting, and overall survival times. The hospital's institutional review board for human research approved this study. RESULTS: The overall survival time and the survival time following double stenting were 10.9 months (IQR 6.0-18.4 months) and 2.4 months (IQR 1.4-5.2 months), respectively. After double stenting, duodenal stent dysfunction occurred in 6 patients (12%), and biliary stent dysfunction occurred in 12 patients (24%), respectively. All patients who experienced stent dysfunction underwent endoscopic reintervention, and all of the procedures were successful. Twenty-one (42%) patients were treated with chemotherapy post double stenting; 9 patients received chemotherapy as a first-line treatment, 9 as a second-line treatment, and 3 as a third-line treatment. During chemotherapy, 8 (38%) patients had grade 3-4 adverse events, which were manageable. Chemotherapy post double stenting (OR, 0.19; 95% CI, 0.059-0.60; P = .0051), reintervention for biliary stent dysfunction (OR, 0.21; 95% CI, 0.081-0.50; P = .0002), and performance status (< 2) (OR, 0.28; 95% CI, 0.098-0.71; P = .0064) were significant prognostic factors after double stenting. CONCLUSIONS: Systemic chemotherapy was manageable, even in patients with double stenting. Chemotherapy after double stenting and appropriate reintervention for stent obstructions potentially prolonged the survival of patients with advance pancreatic cancer.

Endoscopic Ultrasound-Guided Hepaticogastrostomy Is Effective for Repeated Recurrent Cholangitis after Surgery: Two Case Reports.

We report the cases of two patients who underwent endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using metallic stents (MS) for recurrent cholangitis due to benign biliary stenosis. The patients had repeatedly undergone double-balloon endoscopy and anastomotic stenosis. Thus, EUS-HGS was performed. The procedures were successful, and placement of a covered metallic stent (C-MS) relieved cholangitis. The occurrence of cholangitis was subsequently considerably reduced. For patients with postoperative recurrent cholangitis, EUS-HGS with MS should be considered because of its efficacy and safety.

Indications for Endoscopic Ultrasound-Guided Pancreatic Drainage: For Benign or Malignant Cases?

Background and Aims: Recurrent pancreatitis associated with pancreatic strictures requires treatment with endoscopic retrograde pancreatography (ERP), but it is sometimes technically unsuccessful. Endoscopic ultrasound-guided pancreatic drainage (EUS-PD) was developed as an alternative to a surgical approach after failed ERP; however, the indications for EUS-PD are unclear. In this study, we evaluated the outcomes of EUS-PD and established the indications for EUS-PD. Methods: A total of 15 patients had indications for EUS-PD for recurrent pancreatitis due to pancreatic strictures. There were eight patients with benign pancreatic strictures and seven with malignant pancreatic strictures. The success rate, adverse events, and long-term outcomes were evaluated. Results: The technical success rates of benign and malignant strictures were 75% (6/8) and 100% (7/7), respectively, and clinical success was achieved in 100% (6/6) and 87.5% of cases (6/7), respectively. Rendezvous procedures were performed in two patients with benign strictures. The adverse event (AE) rate was 26.7% (4/15) and included cases of peritonitis, bleeding, and stent migration. Reinterventions were performed in three patients with benign strictures and two with malignant strictures. Conclusions: EUS-PD was an appropriate treatment for not only benign strictures but also malignant strictures with recurrent pancreatitis after failed ERP. However, the AE rate was high, and reinterventions were required in some cases during long-term follow-up. The indications for EUS-PD should be considered carefully, and careful follow-up is needed.

Efficacy of endoscopic treatment using double-balloon enteroscopy for postoperative bile leakage in patients with hepaticojejunostomy.

Background and study aims Endoscopic treatment for post-operative bile is technically challenging in patients with altered gastrointestinal anatomy. This study evaluated the effectiveness of using a short-type double-balloon enteroscope to treat postoperative bile leakage after hepaticojejunostomy.

Endoscopic balloon dilatation for benign hepaticojejunostomy anastomotic stricture using short double-balloon enteroscopy in patients with a prior Whipple's procedure: a retrospective study.

BACKGROUND: Endoscopic retrograde cholangiography using a short double-balloon endoscope (DB-ERC) is a promising minimally-invasive method for accessing hepaticojejunostomy (HJ) anastomosis in patients with surgically altered anatomy. We aimed to evaluate the immediate and long-term outcomes of balloon dilatation for benign HJ anastomotic stricture (HJAS) in patients who had previously undergone Whipple's procedure using a DB-ERC. METHODS: We conducted a retrospective analysis of 46 patients who underwent balloon dilatation alone with a DB-ERC for benign HJAS between November 2008 and November 2014. The median follow-up duration was 3.5 (interquartile range [IQR], 1.9-5.1) years. RESULTS: The technical and clinical success rates were 100%, and adverse events occurred in 7% (3/46, cholangitis). The median hospitalization period was seven (IQR, 5-10) days. Of 42 patients (91%) followed-up for > 1 year, 24 (51%) had recurrent HJAS at a median of 1.2 (IQR, 0.6-2.9) years after balloon dilatation. The cumulative anastomotic patency rates at 1, 2, and 3 years were 73, 55, and 49%, respectively. In univariate analysis, early stricture formation (< 1 year) was a risk factor for recurrent stenosis, although no statistically significant risk factors were observed in multivariate analysis. CONCLUSIONS: Endoscopic balloon dilatation with DB-ERC for benign HJAS is effective and safe, having good immediate technical success and few adverse events. Further improvements to this procedure are needed to prevent recurrent HJAS.

Comparison of two fluoroscopic images to ensure efficient scope insertion for biliary intervention in patients with Roux-en-Y hepaticojejunostomy.

Background and study aims No standard procedure for endoscopic retrograde cholangiopancreatography is available for patients with Roux-en-Y hepaticojejunostomy (RYHJ) with side-to-end hepaticojejunostomy. We therefore explored methods of efficient scope insertion at a hepaticojejunostomy site. Patients and methods Patients with suspected biliary disease were prospectively enrolled. Based on two fluoroscopic images obtained on scope insertion into each lumen of a two-pronged Roux-en-Y anastomosis, we selected the lumen in which the distal end of the scope progressed toward the patient's liver or head. The accuracy of this method for selecting the correct lumen leading to the hepaticojejunostomy site was investigated. Results Of the 33 included patients, successful insertion to the hepaticojejunostomy site was achieved in 32 (97 %), 26 (81 %) of whom had undergone the imaging method. The accuracy of the method was 88 % (23/26). The time required for insertion between the anastomotic site and the hepaticojejunostomy site was shorter when the lumen selection had been correct (13 minutes [7 - 30] (n = 23) vs. 18 minutes [8 - 28] (n = 9); P = 0.95). Conclusion This method based on two fluoroscopic images was useful for achieving efficient scope insertion in patients with RYHJ.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000014183).

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitrate as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography(ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitrate might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitrate for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitrate can prevent PEP.

A comparative evaluation of treatment methods for bile duct stones after hepaticojejunostomy between percutaneous transhepatic cholangioscopy and peroral, short double-balloon enteroscopy.

BACKGROUND: Bile duct stones after hepaticojejunostomy are considered a troublesome adverse event. Although percutaneous transhepatic procedures using a cholangioscopy is performed to treat these bile duct stones, a peroral endoscopic procedure using a short, double-balloon enteroscope (sDBE) is an alternative. This study aimed to compare the immediate and long-term outcomes of both treatments for bile duct stones in patients who underwent prior hepaticojejunostomy. METHODS: Between October 2001 and May 2013, 40 consecutive patients were treated for bile duct stones after hepaticojejunostomy at a tertiary care hospital. Initial success with biliary access, biliary intervention-related technical success, clinical success, adverse events, hospitalization duration, and stone-free survival were retrospectively evaluated. RESULTS: The initial success rates for biliary access were 100% (8/8) with percutaneous transhepatic cholangioscopy (PTCS) and 91% (29/32) with sDBE. In three patients in whom biliary access during initial sDBE failed, successful access with subsequent PTCS was achieved, and biliary intervention-related technical success and clinical success were eventually achieved in all 40 patients. The rate of adverse events was significantly lower with sDBE than with PTCS (10% versus 45%; p = 0.025). The median hospitalization duration for complete stone clearance was significantly shorter with sDBE than with PTCS (10 versus 35 days; p < 0.001). During the median 7.2 year or 3.1 year follow up, the probabilities of being stone-free at 1, 2, and 3 years were 100%, 73%, and 64% for PTCS and 85%, 65%, and 59% for sDBE, respectively (p = 0.919). CONCLUSIONS: sDBE was useful, with few adverse events and short hospitalization; therefore, experienced endoscopists can consider it as first-line treatment for bile duct stones in patients with prior hepaticojejunostomy.

Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue.

BACKGROUND/OBJECTIVES: The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR). METHODS: DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR. RESULTS: The amount of DNA isolated from the serum was much higher than that from plasma (1.0- to 42.0-fold). At least 1 KRAS mutation was observed in 93% of cancer tissues, whereas we detected the mutations in only 48% of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01). CONCLUSIONS: Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.

Long-term outcomes and risk factors of biliary stent dysfunction after endoscopic double stenting for malignant biliary and duodenal obstructions.

BACKGROUND AND AIM: Few reports describe the endoscopic double-stenting procedure for malignant biliary and duodenal obstructions. We evaluated the clinical outcomes from double stenting, and analyzed the risk factors for biliary stent dysfunction following double stenting. METHODS: Eighty-one patients who underwent endoscopic double stenting for malignant biliary and duodenal obstructions were retrospectively analyzed. We determined the stent dysfunction rate and the biliary stent dysfunction risk factors, and analyzed the endoscopic reintervention results. RESULTS: Overall survival time and survival time following double stenting were 365 (38-1673) days and 73 (20-954) days, respectively. After double stenting, the 3-month and 6-month duodenal stent dysfunction rates were 14% and 41%, respectively. Reintervention technical success rate was 100% (10/10), and mean gastric outlet obstruction scoring system scores improved from 0.7 to 2.4 points (P < 0.001). The 3-month and 6-month biliary stent dysfunction rates were 26% and 41%, respectively. The reintervention technical and clinical success rates were 95% (20/21) and 81% (17/21), respectively. Risk factors for biliary stent dysfunction following double stenting were events associated with duodenal stent dysfunction (odds ratio [OR], 11.1; 95% confidence interval [CI], 2.09-87.4; P = 0.0044) and the biliary stent end's location (OR, 6.93; 95% CI, 1.37-40.2; P = 0.0019). CONCLUSIONS: Some patients had stent dysfunction irrespective of the survival period after double stenting. Endoscopic reintervention was technically feasible and clinically effective even after double stenting. Duodenal stent dysfunction and biliary stent end's location were risk factors for biliary stent dysfunction.

Predictive factors for outcomes of patients undergoing endoscopic therapy for bile leak after hepatobiliary surgery.

BACKGROUND AND AIM: Endoscopic procedures are used as first-line treatment for bile leak after hepatobiliary surgery. Advances have been made in endoscopic techniques and devices, but few reports have described the effectiveness of endoscopic procedures and the management principles based on severity of bile leak. We evaluated the effectiveness of an endoscopic procedure for the treatment of bile leak after hepatobiliary surgery. METHODS: Fifty-eight patients underwent an endoscopic procedure for suspected bile leak after hepatobiliary surgery; the presence of bile leak on endoscopic retrograde cholangiopancreatography (ERCP) was evaluated retrospectively. Two groups were created based on bile leak severity at ERCP. We defined success as follows: technical, successful placement of the plastic stent at the intended bile duct; clinical, improvement in symptoms of bile leak; and eventual, disappearance of bile leak at ERCP. We evaluated several factors that influenced the success of the endoscopic procedure and the differences between bile leak severity. RESULTS: Success rates were as follows: technical, 90%; clinical, 79%; and eventual, 71%. Median interval between first endoscopic procedure and achievement of eventual success was 135 days (IQR, 86-257 days). Bile leak severity was the only independent factor associated with eventual success (P = 0.01). CONCLUSIONS: Endoscopic therapy is safe and effective for postoperative bile leak. Bile leak severity is the most important factor influencing successful endoscopic therapy.

A Prospective Randomized Controlled Study Comparing EUS Sonopsy CY(R) and 22-gauge Biopsy Needles for Endoscopic Ultrasound-guided Fine-Needle Aspiration of Solid Pancreatic Mass Lesions.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a standard procedure for precise histological diagnosis of pancreas tumors, but it is sometimes difficult to obtain adequate specimens. EUS Sonopsy CY® is a newly designed needle with original features. This randomized study will compare the tissue collection rate of EUS Sonopsy CY® to that of a conventional needle in EUS-FNA. The major eligibility criteria are as follows: Patients with a pancreatic mass referred for EUSFNA; age 20 years, and performance status＜4. The primary outcome is the tissue collection rate. This study will elucidate the efficacy of EUS Sonopsy CY®.

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

Time-dependent image changes after ethanol injection into the pancreas: an experimental study using a porcine model.

BACKGROUND: Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma. METHODS: Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven. RESULTS: Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively. CONCLUSIONS: Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes.

Efficacy and Safety of Endoscopic Ultrasound-guided Ethanol Ablation Therapy for Pancreatic Neuroendocrine Tumors.

Recently, endoscopic ultrasonography (EUS)-guided ethanol ablation for small pancreatic neuroendocrine tumors (p-NETs) has been reported. However, the efficacy and safety of the technique remain unclear. We have launched a prospective pilot study of EUS-guided ethanol ablation for p-NETs. The major eligibility criteria are the presence of a pathologically diagnosed grade (G) 1 or G2 p-NET, a tumor size of 2cm, and being a poor candidate for surgery. A total of 5 patients will be treated. The primary endpoint will be the complete ablation rate at 1 month after treatment.