Endoscopic closure of perforations caused by EMR in the stomach by application of metallic clips

S Tsunacla, S Ogata, T O.hyarna, et al.

Gastric perforation caused by ElVIR: endoscopic s:~tnrewith metallic clips

Additional procedures were required for the first 6 patients in the present series because a period of time was allowed after insertion sufficient for full expansion of the stent. In the other 31 patients, the EMS-. ilthotripsy was conlpleted in a single session. Intravenous administration of isosorbide dinitrate relaxed the papilla and facilitated EMS dilation. Procedure-related pancreatitis occurreci in 1 patient (3%!, a lower rate than thatreported for EPD.7,Wuttire prospective studies are needed to determine whether EMS-lithotripsy has fewer associated complications and preserves sphincter of Oddi function better than EPD.9J@ Because the stents used for EMS-lithotripsy were designed for malignant strictures, their shape is not ideal for stone extraction. This may account in part for the two cases of stent migration. Modification of the stent to make it more suitable for treatment of bile duct stones could reduce the complication rate and simplify the procedure. Furthermore, more data must. be gathered to estimate more accurately the complication rate. Currently, the cost of an EMS is relatively high. However, it is assumed that if EMS-lithotripsy is established as a method of treatment and the shape of the stent is improved, then both the cost of the stent and the risk of migration may gradually decline. Endoscopic papillary dilation continues to play a role in the treatment of bile duct stones in Japan. Endoscopic metallic stent-lithotripsy is not suitable for treatment of most stones. However, once the method is established as safe, it might play a greater role as a safe, easy alternative to EST and EPD for the extraction of bile duct stones.

CASESTLDIES Endoscopic closure of perforations caused by EMR in the stomach by application of metailic clips Receioed S e p t e x b e r 16, 2002. For renisiora December 3, 2002. Accepted January 21, 2003. Current affiliations: Departmefit of' Internal Medicine and Endoscopy, Saga Afedical School, Saga, Japari, Department of Ir~ternalMedicine, Saga Prefectural Hospital, Saga, Japan, Depcirtment of Internal ?/Iedicine, Sagc I~zsaranceHospital, Saga, Japan, Reprint requests: Seiji Tsur:adu, MD, Department o f linternu1 LVfedicir!~, Saga Medical School, 5-1-1LVabeshima,Saga 849-8501, Jaaiian. Copyright 0 2003 by the American SocieLy for Gastrointestinal EfidoscoAv 0016-5107/2U03IS30.00 + 0

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GASTROIATTESTINALELVDOSCOPY

DISCLOSURE

A. Minami is a consultant to Boston Sc:e~tificJ a ~ a nInc. , REFERENCES I . Classen M, Demling E. Endoskopische sp!~inkterotornle der pap11:a Vater: c a d steinestraktlon :*as Gern ductus choledochas [in German wlth Eneiish abstracti. Dtsch M e d Wochenschr ;974;99:496-7. 2. Staritz hl, Ewe K, Meyer zum Busherrfeide KZ-I. Endoscopic papillary dilation (EPD) for the treatrncnt of common bile duct stones and papillary stenosis. Endoscopy 1983;16:19?-8. 3. Riemann JI;Derniing L, Seuberth K. Ciiiiiczl zpplication of a new mechanical lithotripter for smashing common bile duct stones. Endoscopy 1982;14:226-30. 4. Staritz 31, Poralia T, Dorrneyer HH,Meyer zum Bushenfeide ECti. Endoscopic removal of coinnlon bile duct stones through the intact papilla after medical sphincter dilation. Gastroenteroloby 1985;88:180?-11. 5. Ibuki Y, Kudo AtVl? Todo A. Endoscopic retrograde extraction of common bile duct stones with drip inf~eioilof isosorbide dinitrate. Gastrointest Endosc 1992;38:178-80. 6. Bergman JJ, Tytgat GN, Huibregtse I(.Endoscopic dilatation of the biliary sphincter for removal of bile duct stones: an overview of current indications and limitations. Scand J Gastroenterol S u p p l 1998;225:59-65. 7. Bergman JJ, Rauws EA, Fockens P,van Berkel AM, Bossuyt PM.Tijssen JG, et al. Randomized trial of endoscopic balloon dilation versus endoscopic sphincterotoiny for removal of bile duct stones. Lancet 1997;349:1124-9. 8. Mathuna PM, White P, Ciarke E, Lennon J, Crowe J. Endoscopic sphincteroplasty: a novel and safe alternative to papillotomy in the managenlent of bile duct stones. Gut 1994; 35:127-9. 9. Sato H, Kodama T, Takaaki J, Tatsumi Y, Maeda T, Fujita S, et a!. Endoscopic papillary balloon dilation may preseme sphincter of Oddi fanction after common bile duct stone management: evaluation from the viewpoint of endoscopic manometry. Gut 1997;41:541-4. 10. Yasrtda I, Tomita E, Enya M, Kato T, Moriwaki 13. Can endoscopic papillary balloon dilation really preserve sphincter of Oddi function? Gut 2001;49:686-91.

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Seiji Tsunada, MD, Shln~chiOgaia, MD, Takash~Ohyama, MD, H I D I ~Ootan~, I MD, Kayoko Oda, MD, Atsush~K~kkawa, MD, Akrfbrn, Ootan,, MD, HITOYL~I Sakara, Mi), Ryuich~ Iwakiri, MD, Kazuma Fujimofo, MD

Background: The number of cornpllcalions associated with use of EMR for early-stage gastric cancer, including perforation, has increased with the increasing use of this procedure. Endoscopic d i p application was performed in patients who sustained a perforation a s a result of EMR for gastric neoplasm. Patients and methods: Seven patients who underwent endoscopic application of metallic dips to close perforations were studied. The ornental patch method was applied in one case with a large perforation. Observafbrts: tn all patients, endoscopic clip application suecessfufly closed the perforation of the stomach, which occurred aRer EMR. No patient required laparolomy. Conclusions:The technique of endoscopic clip appllcation might be useful for treatment of patients who sustain a perforation caused by EMR. 'JOLCILIE 57, NO. 7,2003

Gastric perforation caused by EMR: endoscopic suture with metallic clips

S Tsur~acla,S Ogata, T Okyama, et al.

EMR for eariy stage gastric cancer is performed in many institutions. Developments in EMR and -~ideoendoscopyhave made endoscopic treatment of early stage cancer possible and have improved the prognosis of' patients with this type of tumor. Methods of endoscopic resection developed to date include endoscopic double-snare polypectomy,l capfitted rnucosectomy,2 endoscopic aspiration mucosectomy,3 use of an esophageal EMR tube,4 use of 33TR with a ligating device,5 and use of EMR with an insulation-tipped knife.6 The most serious complications of EMR are hernorrhage and perforation. Reported rates of perfora",on are 0.8% for endoscopic aspiration mueosectomy and 5.6% for EMR with an insulation-tipped knife.7 Endoscopic metallic clip placement has been used as an emergency measure for GI perforations. A series of patients with eariy stage gastric neo~lasrnswho sustained iatrogenic perforation of the stomach during EMR are described. The perforations were successfi~llytreated by endoscopic clip application. PATIENTS AND METHODS EMR was performed in 789 patients (1997-2001),with a gastric perforation being encountered in 7 patients (6 men, 1 woman; mean age 71 years, range 64-82 years; Table 1).Resections were performed as follows: EMR with a ligating device in 3 patients; EMR by cap-fitted mucosectomy in 3; and EMR with an insulation-tipped knife in one ~ ilesions i were evaiuateci by EUS a t 20 MHZ with a radially scanning echoendoscope before EMR to verify that the neoplasm was confined to the mtlcosa. For EMR, a forward-viewing endoscope (GIF-Q240;Olympus Optical Co., Ltd., Tokyo, Japan) was introduced into the stomach with the patient under local pharyngeal anesthesia. More t h a n 10 n1L of a solution of epinephrine in kyperosmotic saline solution was injected into the submucosa near the lesion to detach the surface layers from the muscularis propria. Perforation was diagnosed endoscopitally just after resection. Informed consent was obtained for closure of the perforation by endoscopic placen~entof ~netallicclips. Once the perforation was recognized, metallic clips (HX-600-135; Olympus) were carefully fitted for closure of the defect with a rotating clip fixing device (fM-5QR-1; Biympus). A nasogastric suction tube was placed, and patients mere permitted nothing by mouth. Treatment also included htravenous alimentation and administration of an W2receptor antagonist and antibiotics. Laboratory tests subsequently obtained included peripheral blood cei! counts and C-reactive protein concentration.

OBSERVATIONS

The largest perforation was estimated to be 25 mm in diameter, and the maximun~number of clips rrsed was 11. Immediately after the resection, the v7GLLT.tfl? 57, NO. 7, 2003

Figure 1. A, Endoscopic view of perforation (arrows) that occurred during EMR (Case 2). B, Closure of perforation by application of 6 clips. resulting defect was observed carefully to determine if a perforation was visible andlor other extra gastric tissue could be seen through the defect. If there was a doubt whether a perforation had occurred, then the resected tissue was examined to determine whether it included the muscular layer andlor serosa of the gastric wall. In Case 2 (Table 11, an attempt was made to resect a neoplasm on the posterior wall of the gastric cardia by EMR,by using a ligating device (Fig. 1A). The perforation was relatively small, and it was not detected with the forward-viewing endoscope because of its location. In this ease, the perforation was closed with clips by using a transparent hood (adapter from an endoscopic variceai ligation kit; Top Go., Tokyo, Japan) fitted to the distal end of the endoscope (Fig. f B 1. This transparent hood mas useful in difficult eases in which the lesion was located tangentially to the endoscope.8 In Case 4 (Table I), an early stage gastric carcinoma in the lesser curvature of the mid body was resected by EMR with an insulation-tipped knife,

S Tsunaclu, S O"gatu, T Oh~yurna,et al.

Gustric per,Goration caused by EMR: endoscopic s ~ t u r ewith metallic clips

Table 1. Clinical features sf 3 patients Case 1 2 3 4 5 6 7

Age

(j.1

73 67 6C

82 ia 64 84 ? , ,

Gender

Method

Wrfora.t~onslze mm)

M NI NI M M NI F

EMR-L EMR-L EMR-L IT-EMF, EMR-C EMR-C EMR-C

4 m

4 26 4

10

"

CLps

Fastriig rci)

WBC+

a 6 3 8 6

19 I1 5 3 4

11 8

4

7300 t(-2200) 7800 (-r2400) 10,300 (-5200, 6400 (-~1000) 7400 (-1600) 7100 (-1600) 5400 (+2503)

4

CRP (:lg/aL) 04

23 42 17 16 28 07

Suturlng methoci S~mpieclosure Simple closure Slrnple c osure 0men:ai patch S1rnp.e closure Slmple closure Slmple ciosare

Clips: Surnber of metallic clips used. CRP, C-reactive protein; EiLfR-L, ERR with a ligating device; EMR-C, EMR with a cap-fitted rnucosectomy; IT-EiLfR, EMR with a n insulated-dip diathermic knife. *'Highest vaiae after EMR. tlncreased value in comparison wi.th the value before EMR.

which resulted in a perforation 25 mm in diameter; omentum was observed through the perforation. Thus, the edges of the muscularis propria were attached with clips to the omentum, which patched the defect. Aspiration of the omentum into the defect with the endoscope facilitated placen~entof clips. The rotating function of the clip-application device, with regard to clip application in this case, was useful for controlling the orientation of the clips. It is important to close the perforation as soon as possible so that the gastric contents do not escape into the peritoneal cavity. In all cases, the perforation was closed within 20 minutes. Eeukocytosis {normal: 3050-90001pLi and elevation of the C-reactive protein level (0.0-0.3 mg!dL) were observed in all cases (Table 1).The mean increase in white blood cell count was 2400iyL compared with the count before EMR. After closure, mild abdonlinal tenderness was recognized in almost all cases, but muscle guarding was not recognized in any case. Abdominal plain radiography andfor CT were obtained after closure of the perforation in ail patients; free air within the intraperitoneal space was demonstrated in all cases. In cases of pneumoperitoneum, the air was removed by needle aspiration. After closure of the perforation, the patients from cases 4 and 2 were not permitted anything by mouth until the white blood cell co~zntand C-reactive protein levels nor~alized,there was no free air detected in the abdomen on imaging studies, and the ulcer defect as a result of the EMR had healed. Based on experience with these Grst two cases, tile investigators' criteria for feeding were as follows: (1) closure of the perforation by endoscopy at 48 hours after clip placement, (21 a decrease in the white blood cell count, (3) no clinical evidence of peritoneal irritation, and (4) a decrease in free air on abdominal imaging. Treatment with an antibiotic (cehetazole sodium) was initiated i~nn~ediately after closure of the perforation and continued until normalization of

the white blood cell coufit and C-reactive protein level. No patient experienced a cornpiication after resuming oral intake. Thus, laparotomy was avoided ill every case. Ail patients were discharged within 2 days of resuming oral intake.

EMR for early stage gastric cancer is superior to surgery in terms of preservation of function. Concomitant with the increase in the number of EMR procedures performed, severe complications of the procedure have been reported. In particular, perforation of the stomach is one of the more serious accidental occurrences and usually requires iaparotomy for treatment, the traditional approach to GI perforations. As noted in the present series, endoscopic closure with metallic clips can be used, with a good clinical outcome, to close perfbrations caused by EMR. One reason for the satisfactory outcome of closure of an EMR-induced perforation is that the degree of peritonitis in the region may be limited. Several factors may account for this, including (1) the antibacterial action of the gastric juice, ( 2 ) the fasting state of patients before EMR. (3) the control of the small degree of bacterial contamination by administration of antibiotics, and (4) the clean, sharp nature of the perforations and their relatively small size. BinmoeSler et al.9 described the first successf~rl endoscopic closure of an iatrogenic perforation by using a clip-application device in 1993. Subsequently, the use of this method in the esophagus,lo,ll duodenum,42 and colon has been described.l3 A? in the present study, the edges of the tissue at the perforation were picked up with several clips for closure when the defect was relatively small, less than the width of the open clip, as previously described. '2 In these reports, failure eo close the perforation was not described. experinental method for endoscopic repair of gastric perforations with an omental paten has been described in a porcine model.i"The omental patch

J Burakat, J Kaufman, K Monnin, et CLI.

Gastric large B-cell Iyn~phornaafter kidne,~transplantation

has been a standard surgical method for treatment of gastroduodenal ulcer perforations. In the present series, an ornentai patch method was applied successfully when the perforation was too large to be closed by simple application of the clips. The omental patch would be suitable for perforations in the anterior wall of the stomach; clip attachment of adjacent soft structures directly to the gastric wall might be recommended as an alternative approach for perforations of the posterior xvall.l"l5 When perforation is caused by EMR, endoscopic closure by using metallic clips without 'laparotomy might be the first choice ibr treatment, although it is essential to monitor the patient closely, with particular attention to signs of a transition from localized to generalized peritonitis. All 5 patients in the present series were successfully treated by clip placement. However, other serious com~lications.such as uncontrolled bleeding and/or any other injury associated with perforation, should be treated surgically. The technique of clip placement is useful in the management of patients who sustain an EMR-induced perforation. Future prospective studies of this technique in larger numbers of patients are warranted. REFERENCES 1. Takekoshi T, Fujii A, Takagi K, Baba Y, Kato H, Yanagisawa A. The indication for endoscopic double snare poiypectorny of gastric lesions. Stomach Intestine 1988;23:387-98. 2. Inoue H, Takeshita K, Hori H, Muraoka Y, Yoneshima H, Endo N.Endoscopic mucosal resection with a cap-fitted panendoscope for esophagus, stomach, and colon mucosal lesions. Gastrointest Endosc 1993;39:68-62. 3. Torii A, Sakai NI;Kajiyanla T, Kishimoto H, Kin 6, Inoue K: et al. Endoscopic aspiration mucoseciomy as curative endoscopic surgery: analysis of 24 cases of early gastric cancer. Gastrointest Endosc 1995;42:475-9.

CASEREPCK;S E~stein-Barr virus-negative gastric large Bcell lymphoma aner kidney transplantation Jehad Barakat, MD, Jemery Kaufman, MD, Kim Monnin, WID, Tahir Qaseern, WID Current affiliations: Department of Internal Medicine a ~ d ~Dathology,Division ofGcstroenterology lHepC1tOIOgY, Uniuersity gf L V eMexico ~ Health Science Center, A13uquer.que, n'ew Mexico. R e p r ~ r ~reque5ts t Tchlr Qoseem AfD, Department of Iri!ernul Medzczne, DZVLSLOE of Gastroer.terologylHepato!o~qi Unzuersrty of Xew ,VIexcco Health Sc~enceCelder, 2211 t o m a s Blvcl ,NE, ACC5, A15;lqL,erque,NIW 87131 5271 Copyr,~ght0 2003 by the Amerscan Soc~etyfor Gastro~ntest~nal 0016-5107/2303/$~0 00 + u Endosco+y do^ 15 10671mge 2003 267

VOLCT.l.IE 57, NO. 7. 2003

4. Makuuchi H. Endoscopic mucosai resection for early esophageai cancer: indication and tecnniqz~es.Dig Endosc 1996;

8:175-9. 5 . Akiyama M, Ota M, Nakajirna PI, Yanlagata K, Munakata A, Endoscopic mucosal resection of gaserfc neoplasm using a ligating device. Gastrointest E~ldosc1997;46:182-6. 6. Ohkuwa M, Rosokawa N, Boku N, Ohestc H, Tajiri S, Yoshida S. S e w endoscopic treatmerit for intramucasa! gastric tumors using a n insulated-tip diathermic hxiie. Endoscopy 2001;33: 221-6. 7. Ida X, Katoh T, Sskajima T, Tsuboi Y, Kojima T,Okuda J. Outcome after using EMR according to standard guideline for endoscopic t r e a h e n t of early gastric cancer. Stomach Intestine 2002;37:1137-43. 8. Noda M, Xobayashi S, Kaneyarna K, Takahashi T, Wakabayashi N, Mitsufuji S, et al. Endoscopic mucosal resectior, usicg a partial transparent hood for !ebions located zangentically to the endoscope. Gastrointest Endosc 2000;51:333-43. 9. Binmoeliar KF, Grimrn N, Suehendrz N. Endoscopic closure of a perforation using metallic clips after snare excision of gastric leiomgoma. Gastrointest Er~dosci993;39:172-4. 10. Wewalka FVJ, Clodi PH, Xaidinger D. Eadoscopic clipping of esophageal perforation after pneumatic dilatation for achalasia. Endoscopy 1995;27:608-11. 11. Shimanloto C, Wiraza I, Cmegaki E, Katsu K. Closure of a n esophageal perforation due to fish bone ingestion by endoscopic clip application. Gastrointeht Endosc 2000;51:736-9. 12. Kaneko T,Akamatsu T, Shirnodaira I(, Ueno T, Gotoh A, Mukawa K, et al. Sonsurgical treatment of duodenal perforation by endoscopic repair using a clipping device. Gastrointest Endosc 1999;50:410-4. 13. Yoshikane H, Widano El, Sakakibara A, Ayakawa T, Mori S, Kawashinla H, et al. Endoscopic repair by clipping of iatrogenic colonic perforation. Gastrointest Endosc 1997;46:464-6. 14. Hashiba K; Can~aihoAM, Diniz G Jr, h i d r a d e SB,Guedes CAF,Filho LS, et al. Experimental endoscopic repair of gastric perforations with a n omentai patch and clips. Gastrointest Endosc 2001;54:500-1. 15. Fry DE, Richardson JD, Flint LM Jr. Closure of a n acute perforated peptic ulcer with fhe falciforni ligament. Arch Surg 1978;113:9209-10.

Patients who have undergone renal transplantstion, along with recipients of o t h r types uf solidorgan transplantations, undergoing long-term immunosuppression are at high risk for the development of lymphomas.' Approximately 1%of renal transplant recipients have post-transplantation lymphoproliferative disorders :PTLD) develop.2 The of PTLD has been obserJed soon afier transplantation followed bv immunosuppression, -especially with cyclosporine.3,"n this setting, the association between Epstein-Barr virus infection and PTLD is well recognized. The pathogenesis of the Epstein Barr virus-negative, iate-occurring PTLD has not been extensively investigated.3 u n u s ~ ~case a l is reporzed here of Epstein Barr i r i r ~ s negative late gastric PTED and Helicobacter p:ylori lnfection in a patient who W ~ being P treated with cyclosporlne 2nd prednisone. GASTROIL~~TESTINAL. E,".;DOSCOPY

951