Official reprint from UpToDate ©2014 UpToDate · from the stomach, duodenum, or rectum. The most abundant experience has been with drainage of pancreatic ... followed by transmural

10/7/14, 4:26 PMTherapeutic endoscopic ultrasound

Page 1 of 22http://www.uptodate.com/contents/therapeutic-endoscopic-ultrasou…+ultrasound&selectedTitle=1%7E150&view=print&displayedView=full#

Official reprint from UpToDate www.uptodate.com ©2014 UpToDate

AuthorsKenneth E Fasanella, MDMichael K Sanders, MD

Section EditorDouglas A Howell, MD, FASGE, FACG

Deputy EditorAnne C Travis, MD, MSc, FACG, AGAF

Therapeutic endoscopic ultrasound

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Sep 2014. | This topic last updated: Oct 02, 2013.

INTRODUCTION — Endoscopic ultrasound (EUS) was developed as a diagnostic modality but rapidly gained a role fora variety of therapeutic applications. EUS has been used increasingly for drainage of pancreatic pseudocysts, treatmentof cystic lesions of the pancreas, EUS-guided cholangiopancreatography, localized therapy for pancreatic tumors, andtreatment of subepithelial lesions and gastric varices.

DRAINAGE PROCEDURES — EUS is well-suited to safely drain fluid collections of various types in areas accessiblefrom the stomach, duodenum, or rectum. The most abundant experience has been with drainage of pancreaticpseudocysts, but case reports have described a variety of drainage procedures, including a hepatic abscess [1],subphrenic abscesses [2], pelvic abscesses [3-5], bilomas [6-8], and infected gallbladders [9-11].

Pseudocysts — The traditional endoscopic approach to transmural drainage of pseudocysts relies on the presence ofan intraluminal bulge and/or accurate cross-sectional imaging techniques to detect the location of the pseudocyst anddetermine the distance between the pseudocyst and gastric wall. Despite this information, avoidance of interposedvasculature can be challenging.

The technique of EUS-guided drainage starts with localization of the pseudocyst with EUS. A 19-gauge needle is thendirected into the pseudocyst, with care being taken to avoid interposed vasculature. A guidewire is then introduced intothe cavity under fluoroscopy (image 1), followed by transmural balloon dilation of the tract into the pseudocyst (image 2).It is often difficult to place a dilating balloon catheter across the stomach wall. When this occurs, creating a fistulous tractwith a push dilating catheter, a needle-knife, or a cystenterostome may aid with balloon placement. Once the tract isdilated, one or more plastic stents are placed into the pseudocyst cavity (picture 1 and picture 2) for drainage.

EUS-guided drainage from the duodenum can be technically challenging because the oblique view from a linearechoendoscope makes endoscopic visualization more difficult than a standard side-viewing duodenoscope. Ongoingdevelopment of forward-viewing and side-viewing echoendoscopes may improve these technical limitations and improveendoscopic visualization.

The endoscopic management of pancreatic pseudocysts is discussed in detail elsewhere. (See "Endoscopicmanagement of walled-off pancreatic fluid collections: Efficacy and complications" and "Endoscopic management ofwalled-off pancreatic fluid collections: Techniques".)

Subphrenic abscesses — Case series have described drainage of subphrenic abscesses in two patients under EUSguidance [2]. In an illustrative report, the abscess was perisplenic, measuring 4 x 5.5 cm, in a patient with portalhypertension and multiple venous collaterals in the region, which were thought to be too high risk for a percutaneousapproach. The second case was a 5 x 2.5 cm left subphrenic abscess complicating a Nissen fundoplication. In bothcases, the cysts were punctured using a linear array echoendoscope, followed by placement of a 0.035 inch guidewire,looping it inside the cyst. Over the wire, a 7 Fr naso-abscess drainage catheter was placed along with an adjacent 10 Fr

®®

http://www.uptodate.com/

http://www.uptodate.com/contents/therapeutic-endoscopic-ultrasound/contributors







http://www.uptodate.com/home/editorial-policy

http://www.uptodate.com/contents/therapeutic-endoscopic-ultrasound/abstract/1


http://www.uptodate.com/contents/therapeutic-endoscopic-ultrasound/abstract/3-5



http://www.uptodate.com/contents/image?imageKey=GAST%2F56108&topicKey=GAST%2F2653&rank=1%7E150&source=see_link




http://www.uptodate.com/contents/endoscopic-management-of-walled-off-pancreatic-fluid-collections-efficacy-and-complications?source=see_link

http://www.uptodate.com/contents/endoscopic-management-of-walled-off-pancreatic-fluid-collections-techniques?source=see_link




double pigtail catheter. The catheters were flushed with 500 cc sterile saline three times per day and removed after eightdays. The patients were both treated with imipenem for the first five days. The stents were removed after repeat EUS atfour weeks later demonstrated complete resolution.

Hepatic abscess — One report described a patient with a 7 x 11 cm left lobe hepatic abscess that was drained using asimilar technique as described above [2] under EUS guidance [1]. The abscess was flushed three times daily through anasobiliary catheter for seven days. A stent was not placed. The patient did well without recurrence.

Bilomas — Case reports have described successful drainage of a biloma with EUS [6-8]. The largest report describedfour patients with bile leaks and gallbladder fossa bilomas who were drained via EUS-guided double pigtail stentplacement [6]. ERCP was performed initially with placement of a biliary endoprosthesis. Subsequently, a 19-gaugeneedle was used to access the biloma from the stomach or proximal duodenum, a 0.035 inch guidewire was used tosecure access, and 6 to 8 mm balloon dilators were used to dilate the fistula. In one case, a single pigtail stent wasplaced, and in the other three, one to two double pigtail stents were left in place to drain the bilomas. The size of the fluidcollections ranged from 4 x 2 cm up to 8 x 6 cm. Antibiotic coverage was given the day of the procedure and for 10 to 14days afterward. The duration of drainage was 11 days in one case, and one to three months in the others. Nocomplications were reported.

Gallbladder — Cholecystectomy is generally preferred for management of acute cholecystitis but is not always anoption due to comorbidities. For patients with severe sepsis who do not respond to medical therapy, transcutaneouscholecystostomy or transpapillary drainage of the cystic duct has been performed as a temporary measure to clear theinfection until surgery is feasible.

Case series have also demonstrated the feasibility of EUS-guided gallbladder drainage in such patients [9-11].

The largest series included nine patients with acute cholecystitis who were deemed poor surgical candidates [9]. Thegallbladder was punctured from the duodenal bulb or the stomach and dilation was performed with 7 Fr bougie dilationcatheters, followed by placement of a 5 Fr nasocholecystic tube. Seven of the nine patients subsequently underwentsurgical cholecystectomy (six laparoscopic, one open) without complication, and the other two had the drainage tuberemoved without complication once the cholecystitis had clinically resolved.

Pelvic abscesses — Case series have described drainage of pelvic and perirectal abscesses by EUS [3-5].

One series involved 25 patients with abscesses that were predominantly postsurgical or posttraumatic [5]. Patients withabscesses less than 8 cm in size were treated with two 7 Fr transrectal stents. If the abscess was 8 cm or more in size,a 10 Fr drainage catheter was also placed. The drainage catheter was removed once the abscess had decreased in sizeby at least 50 percent, and the stents were removed after two weeks. The abscesses were successfully drained in all ofthe patients at the time of EUS and there were no procedure-related complications. In 24 patients, there was completeresolution of the abscesses on follow-up CT at two weeks.

Another case series included 12 patients with abscesses mostly from pelvic surgery [4]. Stents were insertedsuccessfully in nine patients, resulting in complete resolution of the abscesses in eight, and incomplete resolution in onewith a large cyst (>8 cm) that required subsequent surgical management. Stents were removed after three to sixmonths. In the three patients who were not amenable to stent placement, two had recurrence of the abscess followingaspiration. No major complications were encountered. The only significant difference in technique to the drainageprocedures described above was the use of a needle-knife for puncture of the abscess wall prior to guidewire insertionand balloon dilation.

These data suggest EUS-guidance can be a safe, effective technique for drainage of pelvic abscesses. Placement ofdrainage catheters or stents appears to be crucial for successful resolution, since recurrence rates are high withaspiration alone.

http://www.uptodate.com/contents/imipenem-and-cilastatin-drug-information?source=see_link












FINE-NEEDLE INJECTION — EUS permits precise targeting for the delivery of various substances directly intopancreas, liver, or subepithelial lesions. EUS-guided injection of ethanol for celiac plexus neurolysis has been performedfor over a decade [12,13]. More recently, EUS-guided fine-needle injection (FNI) of various substances has beenreported for treatment of gastrointestinal stromal tumors [14], insulinomas [15], hepatic metastases [16], esophagealcancer [17,18], cystic neoplasms of the pancreas [19,20], and pancreatic adenocarcinoma [21,22]. (See "Endoscopicultrasound-guided celiac plexus and ganglia interventions".)

Cystic neoplasms of the pancreas — The role of ablative therapies administered by EUS for the treatment ofpancreatic cystic neoplasms is discussed elsewhere. (See "Pancreatic cystic neoplasms", section on 'Experimentalmethods'.)

Gastrointestinal stromal tumors (GISTs) — Injection of concentrated ethanol for ablation of subepithelial lesions of thestomach was reported more than 30 years ago in 54 patients who were poor surgical candidates [23]. More recently,EUS-FNI (1.5 mL of 95 percent ethanol directly into the tumor in a single session) was used to treat a 4 cm symptomaticGIST in the stomach of a poor surgical candidate [14]. Treatment was associated with complete resolution of the tumor.The patient developed abdominal pain one week after the injection, and ulcer formation documented on endoscopyseven weeks after the injection, which had healed by the follow-up EUS at six months.

Insulinoma — A case report described EUS-FNI of a symptomatic 13 mm insulinoma [15]. The tumor was ablated afterinjecting 8 cc of 95 percent ethanol in four 2 mL aliquots. No tumor recurrence was observed based upon surveillanceEUS or development of recurrent symptoms after 34 months of follow-up.

Hepatic metastases — Several studies have described percutaneous ablation of hepatic metastases with ethanolinjection. Ablation with EUS-FNI has been described only in a case report [16]. The patient had a solitary livermetastasis from rectal cancer, measuring 1.6 cm that was not amenable to percutaneous approach due to vascularinterposition. Ethanol, at a concentration of 95 percent and a volume averaging 6 mL, was used during multiple EUS-FNIsessions several weeks apart.

The patient had a good response, with disappearance of the lesion and a decrease in CEA level. He eventually had anadditional lesion that was treated similarly with four sessions with a good response. The only complication was asubcapsular hematoma after one procedure. At the time of the report, the patient was still alive and in relatively goodhealth 5.5 years after the initial diagnosis of metastatic cancer.

Pancreatic adenocarcinoma — Various biologic anti-tumor agents have been introduced into pancreatic cancers underEUS-guided FNI for control of locally advanced disease. Although long-term results are not well studied, preliminaryresults suggest these approaches are generally safe and may prove to be an adjunct or alternative to traditionalchemoradiation therapies.

Cytoimplant — EUS-guided intratumoral injection for the treatment of advanced pancreatic cancer was first reportedin 2000 [21]. The study evaluated the safety and feasibility of injecting a mixed lymphocyte culture of donor and hostmononuclear cells (cytoimplant) into the tumor with EUS-guided FNI. It was hypothesized that the mixed lymphocytereaction would result in activation of immune effector cells and release of cytokines with tumor suppressive properties.

Of eight patients, two had partial responses and one a minor response with a median survival of 13.2 months. Therewere no procedure-related complications. Although no additional studies of cytoimplant have been reported, this was thefirst study to demonstrate the safety and feasibility of EUS-guided FNI for the treatment of locally advanced tumors.

TNFerade(TM) — TNFerade is a replication-deficient adenoviral vector that contains the human TNF-alpha generegulated by Egr-1, a chemoradiation inducible promoter. When combined with subsequent chemoradiation, TNF-alphalevels in the tumor increase, potentially leading to tumor suppression [24].

A multicenter study (presented as an abstract) described transfer of TNFerade into locally advanced pancreatic

TM

TM

http://www.uptodate.com/contents/therapeutic-endoscopic-ultrasound/abstract/12,13







http://www.uptodate.com/contents/endoscopic-ultrasound-guided-celiac-plexus-and-ganglia-interventions?source=see_link

http://www.uptodate.com/contents/pancreatic-cystic-neoplasms?source=see_link&anchor=H24#H24









cancer via endoscopic ultrasound or percutaneous (PTA) guidance [25]. Of the 37 patients treated, stabilization of tumorwas observed in 83 percent at one month and 74 percent at three months. Tumor area reduction of greater than 25percent at one month and 50 percent at three months occurred in 31 and 11 percent of cases, respectively. Survivalwithout overall progression was 63 percent at one month and 47 percent at three months. The therapy was generallywell tolerated and considered safe and effective.

A phase I/II study found less promising results [26]. TNFerade was injected into locally advanced pancreatic carcinomasin 50 patients. Only 20 patients (40 percent) were free from local progression at three months.

In March 2010, a phase III trial using TNFerade™ injections into locally advanced pancreatic adenocarcinoma wasterminated early when interim analysis showed only an 8 percent lower risk of death with projected inability to reach astatistically significant improvement in outcome.

Brachytherapy — Interstitial brachytherapy is used for treatment of various cancers including head, neck, breast, lung,prostate, and gastrointestinal tract. After radioactive seed placement, the target tissue is exposed to gamma radiation,producing localized tissue injury and tumor ablation. A potential advantage of brachytherapy over traditional externalbeam radiotherapy is limited radiation toxicity to surrounding normal tissue. (See appropriate topic reviews).

The radioactive seeds are usually implanted under CT-guidance or during laparotomy. However, EUS-guidedbrachytherapy has been reported for head and neck tumors [27], recurrent esophageal cancer with perigastricadenopathy [17], and pancreatic adenocarcinoma [28].

An illustrative series included 15 patients with unresectable pancreatic cancer who underwent EUS-guided implantationof an average of 22 radioactive seeds [22]. During a median follow-up of 11 months, 27 percent of patientsdemonstrated a "partial" tumor response, 20 percent showed a "minimal" response, and 33 percent demonstrated"stable disease." Clinical benefit was shown in up to 30 percent of patients, mostly due to a reduction in pain.

Pancreatitis occurred in three patients with formation of a pseudocyst in two of the three patients. However, theseadverse events were considered mild and treated conservatively without additional therapy. This study demonstratedthat EUS-guided brachytherapy was technically feasible and generally well tolerated, but more studies are needed.

Oncogel — OncoGel (MacroMed Inc, West Valley, Utah) is a chemotherapeutic formulation for intralesional injection ofpaclitaxel for local treatment of unresectable solid tumors [29]. This product uses a thermosensitive, biodegradablecopolymer, ReGel, to deliver paclitaxel to solid tumors, providing continuous controlled-release into the surroundingtissue for up to six weeks. OncoGel is undergoing clinical studies within the United States for the treatment of incurablelung and breast cancers [30].

Esophageal cancer — As noted above, TNFerade(TM), an adenoviral vector that carries the transgene encodinghuman TNF-alpha, has been used for treatment of locally advanced esophageal cancer and pancreatic adenocarcinoma[18,25]. (See 'TNFerade(TM)' above.)

A multicenter Phase I clinical trial (published in abstract form) reported experience with 24 patients who had stage II andIII esophageal cancer, using escalating doses [18]. The vector was injected directly into the tumors, 18 patients withtraditional endoscopy and six with EUS-FNI. Results were promising with minimal morbidity, and a 40 percent pathologiccomplete response in the top three dose cohorts. At the time of the final report, median follow up was 42.9 months, andthree- and five-year disease free survival rates were 57 and 52 percent, respectively. Further studies have not beenpublished. There was a non-significant trend toward increased efficacy but prolonged procedure times using EUScompared with traditional endoscopy.

A case report described the use of EUS-FNI to place specially adapted brachytherapy beads for nodal spread ofesophageal squamous cell carcinoma [17]. A 66 year old woman with T3 N1 M0 disease had disease recurrencemanifested by celiac lymph node recurrence after neoadjuvant chemotherapy and external beam radiation, and surgical







http://www.uptodate.com/contents/paclitaxel-drug-information?source=see_link




http://www.uptodate.com/contents/therapeutic-endoscopic-ultrasound?topicKey=GAST%2F2653&elapsedTimeMs=8&source=search_result&searchTerm=endoscopic+ultrasound&selectedTitle=1%7E150&view=print&displayedView=full#H196737562





resection with gastric pull-through. The celiac lymph node was treated with CT-guided brachytherapy bead placement.Subsequent recurrence manifested by two lymph nodes at the diaphragmatic crus was not amenable to percutaneousplacement; as a result, EUS-FNI was used. Two I(125) beads were placed that had been designed to fit within a 19-gauge needle, which was sealed with sterile bone wax to prevent a bead from prematurely dislodging from the needle.No recurrence was detected at eight months follow-up.

GI bleeding — The utility of EUS in the setting of gastrointestinal bleeding has been evaluated in a few small series forspecific situations, including refractory bleeding lesions [31] and esophageal [32] and gastric varices [33,34].

Refractory bleeding lesions — EUS guidance was used for treatment by FNI into lesions with at least two failuresof hemostasis by conventional endoscopy [31]. The series included one Dieulafoy's lesion and one pancreaticpseudoaneurysm successfully treated with 99 percent ethanol, and one duodenal ulcer and two GISTs treated withcyanoacrylate. No rebleeding was observed.

Esophageal varices — A controlled trial included 48 patients who were randomly assigned to sclerotherapy ofesophageal varices using EUS guidance or using standard endoscopy with ethanolamine as the sclerosant [32]. Therewas no significant difference in the number of sessions required for obliteration (4.1 versus 4.3) or time to successfulobliteration (59 versus 63 days). No difference was observed in variceal recurrence rates.

Gastric varices — At least two series evaluated EUS-guided injection for treatment of actively bleeding gastricvarices [33,34].

One series used 0.5 mL cyanoacrylate (CYA) and 0.7 mL lipiodol, comparing "on demand" injection after theindex procedure (reserved for recurrent bleeding) in 47 patients with scheduled biweekly procedures in 54patients [34]. Successful obliteration of varices was observed in 80 percent of patients in an average of just overtwo sessions, spanning approximately five weeks. A median of three doses of cyanoacrylate was required forobliteration. Repeated procedures on a scheduled basis significantly reduced the frequency of late rebleeding.

A prospective series of five patients with bleeding gastric varices described experience with EUS-guided injectionof 1 mL of 1:1 CYA-lipiodol or Glubran2-lipiodol, focusing on localization of the perforating veins as the target forinjection [33]. Hemostasis was achieved in all five patients. Eradication of the varices was successful in twopatients after one session, and in three patients after two sessions (mean 1.6). There were no cases of recurrentbleeding over a 10-month follow-up period, and no complications were encountered. The authors noted that EUS-FNI may have an advantage over traditional endoscopy due to a lack of need for good endoscopic visualization totarget the injection.

Botulinum toxin for achalasia — At least two case series reported the use of EUS-FNI of botulinum toxin directly intothe lower esophageal sphincter to ensure proper localization of the injection [35,36]. The first included four patients withachalasia who were deemed poor operative candidates [35]. All four had durable responses after 5 to 13 months follow-up.

The second included three patients, with reportedly good results and objective improvement on manometry and bariumswallow, but with follow-up limited to one month [36].

Botulinum toxin for the treatment of obesity — EUS-guided botulinum toxin injection into antrum has been studiedfor the treatment of obesity in a pilot study. In the study, 10 patients received an EUS-guided injection of 100 or 300 unitsof botulinum toxin into the muscularis propria of the antrum and were then followed for 16 weeks [37]. The maximumtolerated volume during a nutrient drink test (a measure of satiety) decreased significantly from 1380 mL at baseline to620 mL two weeks after injection, though the decrease was only statistically significant in those who received 300 unitsof botulinum toxin. Gastric emptying was not significantly prolonged in patients who received the higher dose. The mean











http://www.uptodate.com/contents/barium-drug-information?source=see_link





weight loss was 5 kg after 16 weeks.

EUS-GUIDED TISSUE ABLATION — A common clinical dilemma is the management of cystic and neuroendocrinetumors. Given the variability in clinical behavior and morbidity of surgical resection, local therapy would be an attractiveoption if adequate safety and efficacy data were available. While prospective human trials documenting safety andefficacy of treating pancreatic cystic lesions already exist [19,20], solid tissue ablation in the pancreas has beendescribed only in case reports [15]. As a result, use of these techniques outside of desperate situations and researchprotocols awaits human trials.

EUS-GUIDED CELIAC PLEXUS BLOCK (CPB) AND CELIAC PLEXUS NEUROLYSIS (CPN) — The role of EUS-guided celiac plexus block and neurolysis are discussed separately. (See "Endoscopic ultrasound-guided celiac plexusand ganglia interventions".)

EUS-GUIDED CHOLANGIOPANCREATOGRAPHY — EUS-guided cholangiopancreatography has evolved as atechnique for gaining access to the bile ducts and/or the pancreatic duct in patients where conventional ERCP has failedor was not possible due to altered surgical anatomy [38-42]. Due to the close proximity to the gastrointestinal tract, theleft intrahepatic ducts, common bile duct, and main pancreatic duct are well visualized with EUS and can be accessedwith either a transgastric or transduodenal approach.

As a general rule, three EUS-guided approaches have been used to decompress the biliary system:

Creation of a choledochoduodenal fistula with stent placementCreation of a cholangiogastric fistula with stent placementEUS-guided rendezvous through accessing either the left intrahepatic ducts or common bile duct with conversionto conventional endoscopic retrograde cholangiopancreatography (ERCP) (image 3)

In an illustrative report, 23 patients underwent EUS-guided cholangiography for biliary drainage after failed ERCP [43].Thirteen underwent intrahepatic intervention with EUS-guided access from the stomach into the left intrahepatic ductsusing either a 19- or 22-gauge needle. In 11 patients, a transpapillary stent was placed with one patient requiring thecreation of a cholangiogastric fistula and placement of a double pigtail stent for biliary decompression. The obstructionresolved in 12 of 13 patients for a success rate of 92 percent. The one patient in whom intervention was unsuccessfulhad primary sclerosing cholangitis with multiple strictures precluding passage of a guidewire.

Extrahepatic intervention was attempted in 10 patients with successful placement of a biliary stent in nine. Two patientsunderwent creation of a choledochoduodenal fistula and one required a choledochogastric fistula. The single failureoccurred in a patient with an impacted stone that required percutaneous transhepatic drainage with subsequent stentinternalization. Complications included bile leak, minor bleeding, and self-limited pneumoperitoneum. Overall, thesuccess rate was 91 percent with a complication rate of 17 percent and only one major complication (bile leak, 4percent).

The same group also published their experience with EUS-guided drainage of the main pancreatic duct [44]. Thirteenpatients with failed ERCP underwent EUS-guided pancreaticogastrostomy for endoprosthesis placement anddecompression of the main pancreatic duct. Successful drainage was established in 10 of 13 patients (77 percent).Complications included one case of bleeding treated with endoclip placement and one case of a contained perforation.No major complications were encountered.

EUS-guided cholangiopancreatography is technically feasible and relatively safe in the hands of experiencedinterventional endoscopists skilled in both ERCP and EUS. This technique offers a potential alternative to surgery inpatients in whom conventional ERCP is unsuccessful or not possible. However, the risk of complications including biliaryperitonitis, pancreatitis, bleeding, perforation, and stent migration needs to be evaluated in larger numbers of patientswith longer follow-up to determine the true potential for this approach. Currently, this procedure should be reserved for



http://www.uptodate.com/contents/endoscopic-ultrasound-guided-celiac-plexus-and-ganglia-interventions?source=see_link







tertiary centers with highly skilled endoscopists using a multidisciplinary approach (ie, pancreatic surgeons,interventional radiologists) to these challenging cases.

EUS-GUIDED FIDUCIAL PLACEMENT FOR CYBERKNIFE THERAPY — CyberKnife stereotactic radiotherapy(Accuray, Sunnyvale, CA) delivers multiple beams of precisely directed radiation to a tumor using real-time imageguidance. Radiographic markers (fiducials) are implanted at the tumor site as reference points to assist in targeting theradiation beams.

Fiducials have traditionally been placed surgically or percutaneously under ultrasound or computed tomographyguidance [45-47]. More recently, case series have demonstrated the feasibility of placing them with EUS. In one series,for example, EUS was used to place fiducials in patients with tumors located in the mediastinum, retrocardiac region,retrocrural region, esophagogastric junction, porta hepatis, and pancreas [48]. Placement was successful in 11 of 13patients (85 percent) with one failure secondary to gastric outlet obstruction precluding endosonographic visualization ofthe tumor, and the second failure due to intervening vasculature with increased risk for bleeding with needle puncture. Of13 patients, seven were treated for pancreatic cancer with successful fiducial placement in 100 percent.

The technique for fiducial placement was similar to the previously mentioned approach for EUS-guided brachytherapy.After loading the fiducial into a 19-gauge needle and partially withdrawing the stylet to allow room, the fiducial is placedunder EUS guidance near the treatment field (image 4 and image 5) to assist monitoring of respiratory variation underfluoroscopy (image 6).

A single complication occurred after fiducial placement in a patient with porta hepatis lymph node metastasis fromcolorectal cancer. The patient was admitted 25 days after the procedure for cholangitis and treated with antibiotics andpercutaneous biliary drainage. Following this case, all patients were treated with prophylactic antibiotics followed by athree-day course after the procedure.

Another series (reported in abstract form) described experience with EUS-guided fiducial placement in patients withunresectable gastrointestinal malignancies (ie, pancreatic cancer, cholangiocarcinoma, recurrent gastric and coloncancer) [49]. Fiducials were successfully placed in 15 of 16 (94 percent) patients with no adverse clinical outcomes.

In our own published experience, 51 patients underwent EUS-guided fiducial placement for locally advanced (n = 36) orrecurrent (n = 15) pancreatic cancer. Successful placement was achieved in 90 percent, with spontaneous migration in 7percent and technical failure in 8 percent (all in patients with recurrent cancer after pancreaticoduodenectomy). Only onecomplication of mild pancreatitis occurred in a patient who underwent simultaneous celiac plexus neurolysis [50].

EUS-guided fiducial placement for stereotactic radiosurgery appears to be safe and feasible. However, additional studiesare needed to determine the efficacy of this approach with CyberKnife radiotherapy. Infectious complications may bereduced by using sterile precautions and prophylactic antibiotic therapy.

EUS-GUIDED FINE-NEEDLE TATTOO FOR PREOPERATIVE LOCALIZATION OF SMALL PANCREATICTUMORS — Small pancreatic tumors may be difficult to locate during minimally invasive surgeries such as laparoscopicenucleation and laparoscopic distal pancreatectomy (LDP). EUS-guided fine-needle tattoo (EUS-FNT) was firstdescribed for the preoperative localization of a pancreatic insulinoma [51]. Since then, several case reports and caseseries have demonstrated the efficacy and safety of this technique for both pancreatic endocrine tumors (PET) andpancreatic adenocarcinoma [52-54]. Once the tumor is localized with EUS, fine-needle injection is performed withvarious dyes (eg, india ink, purified carbon particles [SPOT], methylene blue, or indocyanine green) to tattoo the tumor(picture 3). EUS-FNT may provide better localization of small tumors, thereby limiting the amount of resected pancreaticparenchyma, an important goal for a minimally invasive surgery.

EUS-GUIDED ANGIOGRAPHY — EUS-guided angiography is a potential alternative to the traditional percutaneousroute for accessing the vascular system. Studies in animals have demonstrated feasibility in accessing the portal vein,










http://www.uptodate.com/contents/methylene-blue-drug-information?source=see_link

http://www.uptodate.com/contents/indocyanine-green-drug-information?source=see_link




thoracic and abdominal aorta, celiac axis, superior mesenteric artery, splenic artery, splenic vein, and hepatic vein [55-57]. EUS-guided creation of an intrahepatic portosystemic shunt (IPSS) was technically feasible in a live porcine modeland may become an alternative to transjugular intrahepatic portosystemic shunt (TIPS) placement [58]. However, therisks, benefits, and complications need to be carefully investigated before its role in humans becomes clear.

FORWARD-VIEWING CURVILINEAR ARRAY ECHOENDOSCOPE — Traditionally, oblique-viewing curvilinear arrayechoendoscopes have been used for therapeutic EUS procedures. However, these instruments are limited by impairedendoscopic visualization, difficult orientation for EUS-guided drainage procedures, and difficulty passing accessoryinstruments through the endoscope channel. A prototype forward-viewing therapeutic curvilinear array echoendoscope(GIF-UCT 160J-AL5; Olympus America Inc., Center Valley, PA) was developed in an effort to overcome some of theselimitations. Initial reports have demonstrated success with this instrument in both diagnostic and therapeutic EUSprocedures [59-61]. Additional studies are needed to determine whether this prototype instrument offers advantagesover current technology.

SUMMARY AND RECOMMENDATIONS

The efficacy and safety of therapeutic endoscopic ultrasound (EUS) is evolving. It has been used for drainage ofpancreatic pseudocysts, treatment of cystic and neuroendocrine neoplasms of the pancreas, EUS-guidedcholangiopancreatography, localized therapy for pancreatic tumors, and treatment of subepithelial lesions andgastric varices.

At present, therapeutic EUS should be limited to tertiary centers with experienced endoscopists, interventionalradiologists, and surgeons.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Seewald S, Imazu H, Omar S, et al. EUS-guided drainage of hepatic abscess. Gastrointest Endosc 2005; 61:495.2. Seewald S, Brand B, Omar S, et al. EUS-guided drainage of subphrenic abscess. Gastrointest Endosc 2004;

59:578.3. Varadarajulu S, Drelichman ER. EUS-guided drainage of pelvic abscess (with video). Gastrointest Endosc 2007;

66:372.4. Giovannini M, Bories E, Moutardier V, et al. Drainage of deep pelvic abscesses using therapeutic echo endoscopy.

Endoscopy 2003; 35:511.5. Varadarajulu S, Drelichman ER. Effectiveness of EUS in drainage of pelvic abscesses in 25 consecutive patients

(with video). Gastrointest Endosc 2009; 70:1121.6. Shami VM, Talreja JP, Mahajan A, et al. EUS-guided drainage of bilomas: a new alternative? Gastrointest Endosc

2008; 67:136.7. Ponnudurai R, George A, Sachithanandan S, et al. Endoscopic ultrasound-guided drainage of a biloma: a novel

approach. Endoscopy 2006; 38:199.8. Kahaleh M, Wang P, Shami VM, et al. Drainage of gallbladder fossa fluid collections with endoprosthesis

placement under endoscopic ultrasound guidance: a preliminary report of two cases. Endoscopy 2005; 37:393.9. Lee SS, Park do H, Hwang CY, et al. EUS-guided transmural cholecystostomy as rescue management for acute

cholecystitis in elderly or high-risk patients: a prospective feasibility study. Gastrointest Endosc 2007; 66:1008.10. Kwan V, Eisendrath P, Antaki F, et al. EUS-guided cholecystenterostomy: a new technique (with videos).

Gastrointest Endosc 2007; 66:582.11. Baron TH, Topazian MD. Endoscopic transduodenal drainage of the gallbladder: implications for endoluminal




http://www.uptodate.com/contents/license














treatment of gallbladder disease. Gastrointest Endosc 2007; 65:735.12. Wiersema MJ, Wiersema LM. Endosonography-guided celiac plexus neurolysis. Gastrointest Endosc 1996;

44:656.13. Wiersema M, Sandusky D, Carr R, et al. Endosonography Guided Celiac Plexus Neurolysis (Eus Cpn) in Patients

with Pain Due to Intraabdominal (Ia) Malignancy. Gastrointest Endosc 1995; 41:315.14. Günter E, Lingenfelser T, Eitelbach F, et al. EUS-guided ethanol injection for treatment of a GI stromal tumor.

Gastrointest Endosc 2003; 57:113.15. Jürgensen C, Schuppan D, Neser F, et al. EUS-guided alcohol ablation of an insulinoma. Gastrointest Endosc

2006; 63:1059.16. Barclay RL, Perez-Miranda M, Giovannini M. EUS-guided treatment of a solid hepatic metastasis. Gastrointest

Endosc 2002; 55:266.17. Lah JJ, Kuo JV, Chang KJ, Nguyen PT. EUS-guided brachytherapy. Gastrointest Endosc 2005; 62:805.18. Pinto H, Chang KJ, Reid TR, et al. Final report of a phase I evaluation of TNFerade biologic plus

chemoradiotherapy prior to esophagectomy for locally advanced resectable esophageal cancer. J Clin Oncol 2011;29:AB e13610.

19. Gan SI, Thompson CC, Lauwers GY, et al. Ethanol lavage of pancreatic cystic lesions: initial pilot study.Gastrointest Endosc 2005; 61:746.

20. Oh HC, Seo DW, Lee TY, et al. New treatment for cystic tumors of the pancreas: EUS-guided ethanol lavage withpaclitaxel injection. Gastrointest Endosc 2008; 67:636.

21. Chang KJ, Nguyen PT, Thompson JA, et al. Phase I clinical trial of allogeneic mixed lymphocyte culture(cytoimplant) delivered by endoscopic ultrasound-guided fine-needle injection in patients with advanced pancreaticcarcinoma. Cancer 2000; 88:1325.

22. Sun S, Xu H, Xin J, et al. Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreaticcancer: results of a pilot trial. Endoscopy 2006; 38:399.

23. Otani T, Tatsuka T, Kanamaru K, Okuda S. Intramural injection of ethanol under direct vision for the treatment ofprotuberant lesions of the stomach. Gastroenterology 1975; 69:123.

24. Senzer N, Mani S, Rosemurgy A, et al. TNFerade biologic, an adenovector with a radiation-inducible promoter,carrying the human tumor necrosis factor alpha gene: a phase I study in patients with solid tumors. J Clin Oncol2004; 22:592.

25. Chang KJ, Senzer N, Chung T, et al. A novel gene transfer therapy against pancreatic cancer (TNFerade)delivered by endoscopic ultrasound (EUS) and percutaneous guided fine needle injection (FNI). GastrointestEndosc 2004; 59:Ab92.

26. Hecht JR, Farrell JJ, Senzer N, et al. EUS or percutaneously guided intratumoral TNFerade biologic with 5-fluorouracil and radiotherapy for first-line treatment of locally advanced pancreatic cancer: a phase I/II study.Gastrointest Endosc 2012; 75:332.

27. Maier W, Henne K, Krebs A, Schipper J. Endoscopic ultrasound-guided brachytherapy of head and neck tumours.A new procedure for controlled application. J Laryngol Otol 1999; 113:41.

28. Jin Z, Du Y, Li Z, et al. Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combinedwith chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study. Endoscopy2008; 40:314.

29. Zentner GM, Rathi R, Shih C, et al. Biodegradable block copolymers for delivery of proteins and water-insolubledrugs. J Control Release 2001; 72:203.

30. Vukelja SJ, Anthony SP, Arseneau JC, et al. Phase 1 study of escalating-dose OncoGel (ReGel/paclitaxel) depotinjection, a controlled-release formulation of paclitaxel, for local management of superficial solid tumor lesions.Anticancer Drugs 2007; 18:283.

31. Levy MJ, Wong Kee Song LM, Farnell MB, et al. Endoscopic ultrasound (EUS)-guided angiotherapy of refractorygastrointestinal bleeding. Am J Gastroenterol 2008; 103:352.

32. de Paulo GA, Ardengh JC, Nakao FS, Ferrari AP. Treatment of esophageal varices: a randomized controlled trial
























Page 10 of 22http://www.uptodate.com/contents/therapeutic-endoscopic-ultrasou…ultrasound&selectedTitle=1%7E150&view=print&displayedView=full#

comparing endoscopic sclerotherapy and EUS-guided sclerotherapy of esophageal collateral veins. GastrointestEndosc 2006; 63:396.

33. Romero-Castro R, Pellicer-Bautista FJ, Jimenez-Saenz M, et al. EUS-guided injection of cyanoacrylate inperforating feeding veins in gastric varices: results in 5 cases. Gastrointest Endosc 2007; 66:402.

34. Lee YT, Chan FK, Ng EK, et al. EUS-guided injection of cyanoacrylate for bleeding gastric varices. GastrointestEndosc 2000; 52:168.

35. Hoffman BJ, Knapple WL, Bhutani MS, et al. Treatment of achalasia by injection of botulinum toxin underendoscopic ultrasound guidance. Gastrointest Endosc 1997; 45:77.

36. Maiorana A, Fiorentino E, Genova EG, et al. Echo-guided injection of botulinum toxin in patients with achalasia:initial experience. Endoscopy 1999; 31:S3.

37. Topazian M, Camilleri M, De La Mora-Levy J, et al. Endoscopic ultrasound-guided gastric botulinum toxininjections in obese subjects: a pilot study. Obes Surg 2008; 18:401.

38. Wiersema MJ, Sandusky D, Carr R, et al. Endosonography-guided cholangiopancreatography. GastrointestEndosc 1996; 43:102.

39. Giovannini M, Moutardier V, Pesenti C, et al. Endoscopic ultrasound-guided bilioduodenal anastomosis: a newtechnique for biliary drainage. Endoscopy 2001; 33:898.

40. Burmester E, Niehaus J, Leineweber T, Huetteroth T. EUS-cholangio-drainage of the bile duct: report of 4 cases.Gastrointest Endosc 2003; 57:246.

41. Bories E, Pesenti C, Caillol F, et al. Transgastric endoscopic ultrasonography-guided biliary drainage: results of apilot study. Endoscopy 2007; 39:287.

42. Mallery S, Matlock J, Freeman ML. EUS-guided rendezvous drainage of obstructed biliary and pancreatic ducts:Report of 6 cases. Gastrointest Endosc 2004; 59:100.

43. Kahaleh M, Hernandez AJ, Tokar J, et al. Interventional EUS-guided cholangiography: evaluation of a technique inevolution. Gastrointest Endosc 2006; 64:52.

44. Kahaleh M, Hernandez AJ, Tokar J, et al. EUS-guided pancreaticogastrostomy: analysis of its efficacy to draininaccessible pancreatic ducts. Gastrointest Endosc 2007; 65:224.

45. King CR, Lehmann J, Adler JR, Hai J. CyberKnife radiotherapy for localized prostate cancer: rationale andtechnical feasibility. Technol Cancer Res Treat 2003; 2:25.

46. Gerszten PC, Ozhasoglu C, Burton SA, et al. CyberKnife frameless single-fraction stereotactic radiosurgery fortumors of the sacrum. Neurosurg Focus 2003; 15:E7.

47. Whyte RI, Crownover R, Murphy MJ, et al. Stereotactic radiosurgery for lung tumors: preliminary report of a phaseI trial. Ann Thorac Surg 2003; 75:1097.

48. Pishvaian AC, Collins B, Gagnon G, et al. EUS-guided fiducial placement for CyberKnife radiotherapy ofmediastinal and abdominal malignancies. Gastrointest Endosc 2006; 64:412.

49. Ellsmere JC, Mahadevan A, Kelleher T, et al. EUS-Guided radiotherapy fiducials for upper gastrointestinalmalignancies. Gastrointest Endosc 2007; 65:Ab208.

50. Sanders MK, Moser AJ, Khalid A, et al. EUS-guided fiducial placement for stereotactic body radiotherapy in locallyadvanced and recurrent pancreatic cancer. Gastrointest Endosc 2010; 71:1178.

51. Gress FG, Barawi M, Kim D, Grendell JH. Preoperative localization of a neuroendocrine tumor of the pancreaswith EUS-guided fine needle tattooing. Gastrointest Endosc 2002; 55:594.

52. Ashida R, Yamao K, Okubo K, et al. Indocyanine green is an ideal dye for endoscopic ultrasound-guided fine-needle tattooing of pancreatic tumors. Endoscopy 2006; 38:190.

53. Farrell JJ, Sherrod A, Parekh D. EUS-guided fine-needle tattooing for preoperative localization of early pancreaticadenocarcinoma. Gastrointest Endosc 2009; 69:176.

54. Lennon AM, Newman N, Makary MA, et al. EUS-guided tattooing before laparoscopic distal pancreatic resection(with video). Gastrointest Endosc 2010; 72:1089.

55. Lai L, Poneros J, Santilli J, Brugge W. EUS-guided portal vein catheterization and pressure measurement in an



























animal model: a pilot study of feasibility. Gastrointest Endosc 2004; 59:280.56. Giday SA, Clarke JO, Buscaglia JM, et al. EUS-guided portal vein catheterization: a promising novel approach for

portal angiography and portal vein pressure measurements. Gastrointest Endosc 2008; 67:338.57. Magno P, Ko CW, Buscaglia JM, et al. EUS-guided angiography: a novel approach to diagnostic and therapeutic

interventions in the vascular system. Gastrointest Endosc 2007; 66:587.58. Buscaglia JM, Dray X, Shin EJ, et al. A new alternative for a transjugular intrahepatic portosystemic shunt: EUS-

guided creation of an intrahepatic portosystemic shunt (with video). Gastrointest Endosc 2009; 69:941.59. Voermans RP, Eisendrath P, Bruno MJ, et al. Initial evaluation of a novel prototype forward-viewing US endoscope

in transmural drainage of pancreatic pseudocysts (with videos). Gastrointest Endosc 2007; 66:1013.60. Trevino JM, Varadarajulu S. Initial experience with the prototype forward-viewing echoendoscope for therapeutic

interventions other than pancreatic pseudocyst drainage (with videos). Gastrointest Endosc 2009; 69:361.61. Larghi A, Lecca PG, Ardito F, et al. Evaluation of hilar biliary strictures by using a newly developed forward-

viewing therapeutic echoendoscope: preliminary results of an ongoing experience. Gastrointest Endosc 2009;69:356.

Topic 2653 Version 8.0










GRAPHICS

EUS-guided pancreatic pseudocyst drainage

Fluoroscopic image demonstrating looping of a guidewire in apseudocyst under EUS-guidance.

Courtesy of Kenneth E Fasanella, MD, and Michael K Sanders, MD.

Graphic 56108 Version 2.0




Fluoroscopic image demonstrating balloon dilatation of fistulous tractbetween gastric wall and the adjacent pseudocyst.






Fluoroscopic image demonstrating insertion of a stent introductioncatheter into the pseudocyst over the previously placed guidewirefollowing balloon dilatation.





Pancreatic pseudocyst drainage

Endoscopic view of double pigtail stents protruding from fistulous tractinto the pseudocyst.





EUS-guided cholangiography

(A) EUS-guided cholangiography for antegrade access to the bile duct following unsuccessfulretrograde access with ERCP. Two large filling defects consistent with choledocholithiasis areseen on the cholangiogram.(B) A guidewire is passed through the FNA needle into the bile duct and across the majorduodenal papilla into the second portion of the duodenum in preparation for a "rendezvous"procedure.(C) The guidewire is then snared and withdrawn through a side-viewing duodenoscope,allowing access to the bile duct for completion of the "rendezvous" procedure. Stoneextraction is then performed using conventional ERCP techniques.






EUS-guided fiducial placement for pancreatictumor localization

Endoscopic ultrasound image showing needle insertion into pancreatictumor in preparation for fiducial placement.





EUS-guided fiducial placement for pancreatictumor localization

Endoscopic ultrasound image of fiducial within the pancreatic tumor.





Pancreatic tumor localization with fiducials

Radiographic image of fiducials (radiographic markers) in the region ofthe pancreatic tumor, which is marked by the metal stent within thecommon bile duct.





Tattooed pancreatic endocrine tumor followingpreoperative endoscopic ultrasound-guided fine-needle tattooing

(A) Intraoperative photo demonstrating tattooed pancreatic endocrinetumor (PET) following preoperative endoscopic ultrasound-guided fine-needle tattooing. The PET was excised with laparoscopic enucleation.Arrow denotes tattoo.(B) Laparoscopic enucleation successfully removed the tumor withnegative margins, while preserving the normal pancreatic parenchyma.Arrow denotes site of laparoscopic enucleation of PET.




Disclosures: Kenneth E Fasanella, MD Nothing to disclose. Michael K Sanders, MD Speaker’s Bureau: Forest Laboratories (ChronicIdiopathic Constipation and IBS [linaclotide]). Consultant/Advisory Boards: Boston Scientific Corporation (Biliary endoscopy, EUS[duodenoscope visualization system]). Douglas A Howell, MD, FASGE, FACG Grant/Research/Clinical Trial Support: Cook Endoscopy[Endoscopic Scopes/Imaging (Endoscopic wires, stents)]; Olympus America [Endoscopic devices]; Boston Scientific [Endoscopic stents,wires, introducers]; Advanced Endoscopic Devices [Scopes, Magnetic imaging, endoscopic clips]. Speaker’s Bureau: Olympus America[Endoscopic Scopes/Imaging (Scopes, Magnetic imaging)]. Patent Holder: Cook Endoscopy [Stent introducer system]; Advanced EndoscopicDevices [wire guide access]. Anne C Travis, MD, MSc, FACG, AGAF Employee of UpToDate, Inc. Equity Ownership/Stock Options: Proctor& Gamble.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through amulti-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content isrequired of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures

http://www.uptodate.com/home/conflict-interest-policy

Documents

Official reprint from UpToDate ©2014 UpToDate · from the stomach, duodenum, or rectum. The most abundant experience has been with drainage of pancreatic ... followed by transmural