0016-5107/92/3801-0007$03.00
`GASTROINTESTINAL ENDOSCOPY
`Copyright © 1992 by the American Society for Gastrointestinal Endoscopy
`
`Treatment of malignant esophageal
`obstruction with silicone-coated metallic self-
`expanding stents
`
`John Schaer, MD, Ronald M. Katon, MD
`Krassi Ivancev, MD, Barry Uchida, BS, RT
`Josef Rosch, MD, Kenneth Binmoeller, MD
`Portland, Oregon
`
`Six patients with high-grade malignant esophageal obstruction were treated with
`silicone-coated metallic self-expanding esophageal stents (Z stents). Endoscopic
`placement of stents was well tolerated. All patients achieved excellent palliation,
`defined by a decrease of at least two dysphagia grades, which was sustained.
`Complications occurred during follow-up in four patients and included stent
`migration, silicone disruption with tumor ingrowth, food impaction, and perforation
`(discovered at autopsy) at the distal stent site. Three of the four complications
`were promptly treated by endoscopic or radiologic intervention. Recent
`modification in stent design and placement technique will hopefully reduce
`complications. The self-expanding stent has several theoretical advantages over
`the rigid plastic stent and Nd:YAG laser for palliation of obstructing esophageal
`malignancy. (Gastrointest Endosc 1992;38:7-11)
`
`A variety of therapies are employed in the palliative
`treatment of malignant esophageal obstruction. Un-
`fortunately, no single modality provides effective, safe,
`inexpensive relief of dysphagia in all cases. Two of the
`more commonly used modalities are photocoagulation
`with the Nd:YAG laser and the placement of rigid
`plastic endoprostheses. Nd:YAG laser treatment is
`limited by its high cost, the requirement for frequent
`treatment sessions, and tumor recurrence. 1- 3 The use
`of rigid plastic endoprostheses is plagued by high
`complication rates.4- 8 Recently, self-expanding metal-
`lic stents have shown promise in the treatment of
`biliary obstruction.9 It seemed possible that a modified
`version of a self-expanding metallic stent might pro-
`vide benefit in refractory esophageal obstruction. This
`report describes our experience in six consecutive
`patients with malignant esophageal obstruction pal-
`liated with silicone-coated self-expanding metallic Z
`stents.
`
`Received July 10, 1991. For revision August 1, 1991. Accepted August
`26,1991.
`From the Department of Medicine, Division of Gastroenterology, and
`The Charles Dotter Institute for Interventional Therapy, Oregon
`Health Sciences University, Portland, Oregon. Reprint requests: Ron-
`ald M. Katon, MD, Division of Gastroenterology, L-461, Oregon
`Health Sciences University, 3181 S. W. Sam Jackson Park Rd.,
`Portland, Oregon 97201-3098.
`
`VOLUME 38, NO.1, 1992
`
`PATIENTS AND METHODS
`
`Patients
`Six patients with malignant esophageal obstruction were
`studied. All six had severe grade 3 or 4 dysphagia, and none
`were operative candidates. Mean age was 71 years (range,
`57 to 87 years). There were four men and two women. Three
`patients had esophageal squamous cell carcinoma, two pa-
`tients had esophageal adenocarcinoma, and one patient had
`an adenocarcinoma of the lung which was metastatic to the
`mediastinum. Five of the six patients had been refractory to
`prior therapies. All patients had extensive obstructive le-
`sions in the middle or distal esophagus. In three patients,
`the lesion extended to the gastroesophageal junction (Table
`1).
`A total of nine stents were placed in six patients. Informed
`consent was obtained under a compassionate use basis. Five
`of six patients were treated in an outpatient setting, while
`the sixth was hospitalized for 24 hours. Patients were first
`evaluated with a barium esophagram and endoscopy with
`the Olympus GIFXV10 endoscope to determine the location
`and length of esophageal obstruction. Five of the six patients
`underwent initial dilation with American Endoscopy Dila-
`tors (Mentor, Ohio) to 42 to 45 French diameter.
`
`Stents
`The prostheses used were modified self-expanding Z
`stents coated with a silicone membrane and were homemade
`
`7
`
`W.L. Gore & Associates, Inc.
`Exhibit 1019-1
`
`

`
`Table 1.
`Patient demographics
`
`Patient Age Sex
`
`Tumor type
`
`Prior treatment
`
`Location
`(cm)
`67 M ESOPH-SCCAa (27-32) Laser X 8, chemo-
`therapy, radia-
`tion
`(30-40) Pericardial window
`70 F Lung-ADCA
`57 M ESOPH-SCCA (37-47)b Radiation
`87 M ESOPH-SCCA (37-47)b Radiation
`62 M ESOPHADCA (28-36) Chemotherapy
`83 F ESOPHADCA (28-34)b Laser x 2, dilation,
`alcohol inj. x 3
`a SCCA, squamous cell carcinoma; ADCA, adenocarcinoma.
`b Tumor extended beyond gastroesophageal junction.
`
`1
`
`2
`3
`4
`5
`6
`
`in our institution. Stents were handmade from O.018-inch
`stainless steel wire. Individual stent bodies had an internal
`diameter of 15 mm and a length of 2 em. Multiple stent·
`bodies were interconnected for a total stent length of 8 to
`12 em. The last four patients treated had a flanged proximal
`end which had a 20-mm internal diameter (Fig. 1). All stents
`had 3-mm long wire hooks on the exterior of the stent that
`"anchored" the stent within the tumor.
`
`Stent placement technique
`Stents were placed under fluoroscopic control using light
`conscious sedation. A 14 French orogastric tube was first
`passed distal to the esophageal obstruction. Two guidewires
`were placed through the orogastric tube, which was then
`removed. Over one guidewire a 5.5 French angiography
`catheter was placed for contrast injection. Over the second
`guidewire, an 18 French Teflon stent delivery catheter was
`placed. The stent was then pushed out of the delivery
`catheter under fluoroscopic guidance and delivered into the
`esophagus.
`Patients underwent a follow-up esophagram and endo-
`scopic examination immediately after stent placement and
`also at 1 week, 4 weeks, 8 weeks, and as needed thereafter.
`Clinical assessment was performed at monthly intervals
`until patient death or the completion of the study period. In
`the three patients whose stent extended beyond the gastro-
`esophageal junction, H2 blockers and anti-reflux measures
`were prescribed prophylactically to minimize gastroesopha-
`geal reflux. Mean duration of follow-up was 4 months. The
`severity of dysphagia was quantified with a 0 to 4 dysphagia
`scale as follows: 0 = no dysphagia; 1 = dysphagia to normal
`solids; 2 = dysphagia to soft solids; 3 = dysphagia to solids
`and liquids; and 4 = inability to swallow saliva.
`
`RESULTS
`Stent placement was successful and well tolerated
`in all six patients. There were no complications noted
`at the time of stent placement. Mean dysphagia grade
`prior to stenting was 3.3. All patients had improve-
`ment of at least
`two dysphagia grades after stent
`placement, and mean dysphagia grade post-stenting
`was 0.67 (Table 2). Endoscopic and radiologic exami-
`nation confirmed the improvement in esophageallu-
`
`8
`
`minal diameter in each patient. In four of six patients,
`the stents expanded to maximal diameter within 24
`hours, while in two patients the stents expanded to
`approximately 75% of their maximal diameter. Relief
`of dysphagia was sustained in all patients with a mean
`follow-up of 4 months. Four patients died during fol-
`low-up with a mean survival of 4 months (Table 2).
`Figures 2 and 3 depict an 83-year-old woman with
`adenocarcinoma of the esophagus (patient 6, Tables 1
`and 2). She had undergone five esophageal dilations,
`four
`treatments with ethanol
`injection, and two
`Nd:YAG laser treatments prior to stenting. She had
`complete dysphagia and was receiving enteral alimen-
`tation through a gastrostomy tube. After stenting she
`was able to ingest a semi-solid diet. Improvement has
`been sustained for 3 months and she no longer requires
`gastrostomy feedings. Figures 4 and 5 represent a 70-
`year-old woman with adenocarcinoma of the lung and
`mediastinal metastases (patient 2, Tables 1 and 2).
`She had an extra-esophageal tumor with esophageal
`compression and complete dysphagia. With placement
`
`Figure 1. Stainless steel self-expanding Z stent with silicone
`membrane.
`
`GASTROINTESTINAL ENDOSCOPY
`
`W.L. Gore & Associates, Inc.
`Exhibit 1019-2
`
`

`
`Table 2.
`Results and complications of self-expandable stent
`Dysphagia grade
`Post-stent
`Pre-stent
`3
`1
`
`Patient
`
`2
`3
`4
`5
`
`6
`
`4
`3
`3
`3
`
`0
`0
`1
`1
`
`_4_
`X= 3.3
`
`1
`X = 0.67
`
`Complications
`
`Foreign body sensation,
`torn membrane with
`tumor ingrowth
`None
`Stent migration
`Meat impaction
`Distal esophageal per-
`foration
`None
`
`Follow-up
`
`Died (8 mol
`
`Died (2 mol
`Died (3.5 mol
`Alive (5 mol
`Died (2 mol
`
`Alive (3 mol
`X=4mo
`
`and no further injury to the silicone membrane oc-
`curred. This problem was treated by placing a second
`stent within the first stent, which provided relief of
`dysphagia and blocked tumor ingrowth. This patient
`was also the only patient with a foreign body sensation
`in the chest after stenting. This sensation persisted,
`but was easily controlled with Tylenol. Patient 3 suf-
`fered migration of his stent into the stomach. The
`stent was retrieved endoscopically by grasping it with
`a polypectomy snare and pulling it into an overtube.
`A second stent with a flanged proximal border was
`then placed. All four stents placed subsequently had
`this flanged stent design. No other problems with
`stent migration were encountered. Patient 4 had one
`episode of meat impaction, which was easily cleared
`endoscopically. Patient 6 died 2 months following
`stent placement, and was found at autopsy to have an
`esophageal perforation near the distal margin of the
`stent. The perforation occurred within tissue invaded
`by malignancy and it was not clear whether the per-
`foration occurred from stent trauma or from degen-
`eration of the esophageal tumor. Three other patients
`died at 2 months, 3.5 months, and 8 months following
`stent insertion. No autopsies were obtained in these
`patients.
`
`DISCUSSION
`Self-expanding metallic Z stents were found to be
`efficacious in the palliative therapy of malignant
`esophageal obstruction. Despite the selection of pa-
`tients with challenging strictures, an esophageal lu-
`men adequate to maintain oral alimentation was
`achieved in all six patients. In each patient, dysphagia
`improved by at least two grades, and improvement
`was sustained in all patients.
`The use of self-expanding Z stents has several po-
`tential advantages over Nd:YAG laser or rigid plastic
`stents in the palliation of malignant esophageal
`stenosis. The Nd:YAG laser is expensive, requires
`frequent treatment sessions, and recurrence of ob-
`struction after the initial series of treatments is a
`
`9
`
`AF
`
`igure 2. Barium swallow. A, Approximately 10-cm long
`compression of mid-esophagus with near total obstruction.
`B, Full stent expansion and excellent flow of barium.
`
`oftwo overlapping stents (total length 14 cm), she was
`able to take a regular diet until her death from met-
`astatic disease 2 months later.
`
`Complications
`Two patients experienced no complications. In the
`remaining four patients, five complications were en-
`countered as follows (Table 2). In patient 1, the use
`of an inadequate 14 French diameter delivery catheter
`resulted in tears in the silicone coating of the stent
`which allowed tumor ingrowth. In subsequent pa-
`tients, we employed an 18 French delivery catheter,
`
`VOLUME 38, NO.1, 1992
`
`W.L. Gore & Associates, Inc.
`Exhibit 1019-3
`
`

`
`problem.1- 3 In addition, submucosal lesions are inac-
`cessible to treatment with the Nd:YAG laser. Al-
`though rigid endoprostheses are relatively inexpensive
`and readily available, complication rates are high.
`Perforation rates range between 7 and 18%, and stent
`migration, tumor overgrowth, and bleeding are trou-
`blesome.4- 8
`Endoscopic placement of the Z stent is gentle and
`does not generate the shearing forces necessary for
`right stent insertion. Stent placement is a one-stage
`procedure, obviating the need for multiple sessions as
`in Nd:YAG laser treatment.
`In this investigation there was no morbidity en-
`
`Figure 3. Endoscopic photographs. A, Pin hole size lumen
`prior to stenting. S, Marked improvement in luminal diameter.
`Stent is partially obscured by retained barium.
`
`countered during placement of the stents in any pa-
`tient. Stent placement was performed with light con-
`scious sedation and in five of six patients was accom-
`plished in an outpatient setting. Pre-stenting dilation
`was performed to a modest 42 to 45 French diameter
`in comparison to the 54 to 60 French diameter dila-
`tions usually required for placement of rigid endo-
`prostheses.5,8 Another potential advantage of Z stents
`over rigid stents is in the management of tumor over-
`growth. With Z stents an overlapping stent can be
`placed at either end of the original stent to, in effect,
`extend the stented region. In patient 1, an overlapping
`stent was successfully used to cover a defect in the
`silicone membrane, which had allowed tumor en-
`croachment. This capability is not possible with rigid
`stents. Whether stent migration will be less common
`with the flanged Z stents then with rigid stents re-
`mains to be determined in larger studies.
`The complications encountered with Z stents during
`the follow-up period were easily managed with endo-
`scopic or radiologic interventions in three of four
`patients. Modifications in stent design, such as the
`flanged proximal stent body used to prevent migra-
`tion, should decrease future similar problems.
`In the one case of esophageal perforation found at
`autopsy, a question remains as to whether the pointed
`distal ends of the stent may have contributed to the
`perforation. Accordingly, future stents will have yet
`another design modification, with rounded wires at
`the distal end of the stent and a distal silicone bumper
`
`Figure 4. Barium swallow. A, Long, irregular, near-total obstruction in distal esophagus. S, Expansion of stent is nearly complete,
`except in its mid-portion, which is expanded to 70 to 75%. C, Excellent flow of barium through the stent.
`
`10
`
`GASTROINTESTINAL ENDOSCOPY
`
`W.L. Gore & Associates, Inc.
`Exhibit 1019-4
`
`

`
`Figure 5. Endoscopic photographs. A, Nodular tumor with near-total esophageal obstruction. B, Proximal view of stent with full
`in mid-esophagus. Note visualization of esophageal wall
`through silicone
`expansion. C, View of partially expanded stent
`membrane.
`
`added to prevent trauma to the esophageal mucosa.
`Three other patients died during the course of this
`study, at 2 months, 3.5 months, and 8 months after
`stent insertion. Unfortunately, autopsies could not be
`obtained in these patients, so no further information
`exists regarding possible inflammation and/or injury
`to the esophageal tissue from these metallic stents.
`Long-term placement of metallic stents in the biliary
`tract has not resulted in perforation or necrosis.9 As
`with rigid stents, the only patients unsuitable for the
`Z stent are those with neoplasms completely obstruct-
`ing the esophagus or in close proximity to the crico-
`pharyngeus.
`The mesh stent (Wallstent-Medinvent SA) is an-
`other self-expanding stent design which has been em-
`ployed in a small number of patients for palliation of
`esophageal malignancy.1O, 11 Due to their inherent de-
`sign, mesh stents have openings between the wire
`filaments which cannot be coated, therefore allowing
`tumor ingrowth. This complication occurred in two of
`six patients reported by Knyrim et al.1O The silicone
`coating of the Z stent provides a barrier to tumor
`ingrowth. Also, due to this intact barrier, Z stents may
`have an application ~n the treatment oftracheo-esoph-
`ageal fistula, whereas mesh stents appear unsuitable
`for this purpose.
`Finally,
`the central question is how will self-
`expanding stents fit into the armamentarium available
`for palliation of esophageal malignancy? Future com-
`parative trials between Nd:YAG laser and stents of
`various designs, including both rigid and expandable
`stents, are needed to determine the optimal applica-
`
`tion of these various modalities in the palliative treat-
`ment of malignant esophageal stenosis.
`
`REFERENCES
`1. Fleischer D, Kessler F. Endoscopic Nd:YAG laser therapy for
`carcinoma of the esophagus: a new form of palliative treatment.
`Gastroenterology 1983;85:600-6.
`2. Mellow MH, Pinkas H. Endoscopic therapy for esophageal
`carcinoma with Nd:YAG laser: prospective evaluation of effi-
`cacy,
`complications,
`and survival. Gastrointest Endosc
`1984;30:334-9.
`3. Fleischer D, Sivak M. Endoscopic Nd:YAG laser therapy as
`palliation for oesophagogastric carcinoma. Gastroenterology
`1985;89:827-31.
`4. Ogilivie AL, Dronfield MW, Ferguson R, Atkinson M. Palliative
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`copy. Gut 1984;23:1060-7.
`5. Tytgat GNJ, Huibregste K, Bartlesman JFWM, Den Hartog
`Jaeger FCA. Endoscopic palliative therapy of gastrointestinal
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`1986;15:249-71.
`6. Loizou LA, Grigg D, Atkinson M, Robertson C, Brown SG. A
`prospective comparison of laser therapy and intubation in en-
`doscopic palliation for malignant dysphagia. Gastroenterology
`1991;100:1303-10.
`7. Graham DY, Dobbs SM, Zubler M. What is the role of prosthe-
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`1983;29:1-5.
`8. Buset M, Des Marez B, Cremer M. Endoscopic palliative intu-
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`Endosc 1990;36:357-9.
`9. Huibregtse K, Cheng J, Coene PPLO, Fockens P, Tytgat GNJ.
`Endoscopic placement of expandable metal stents for biliary
`strictures-a preliminary report on experience with 33 patients.
`Endoscopy 1989;21:280-2.
`10. Knyrim K, Wagner HJ, Pausch J, Vakil N, Starck E. Expand-
`able metal stents for the palliative treatment of esophageal
`obstruction [Abstract). Gastrointest Endosc 1990;36:236.
`11. Domschke W, Foerster ECH, Matek W, Rod! W. Self-expand-
`ing mesh stent for esophageal cancer stenosis. Endoscopy
`1990;22:134-6.
`
`VOLUME 38, NO.1, 1992
`
`11
`
`W.L. Gore & Associates, Inc.
`Exhibit 1019-5