Prospective Comparison of Push Enteroscopy and Push-and-Pull Enteroscopy in Patients with Suspected Small-Bowel Bleeding

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1 American Journal of Gastroenterology ISSN C 2006 by Am. Coll. of Gastroenterology doi: /j x Published by Blackwell Publishing Prospective Comparison of Push Enteroscopy and Push-and-Pull Enteroscopy in Patients with Suspected Small-Bowel Bleeding Andrea May, M.D., Ph.D., Lars Nachbar, M.D., Marion Schneider, M.D., and Christian Ell, Ph.D. Department of Internal Medicine II, HSK Wiesbaden, Teaching Hospital of the University of Mainz, Wiesbaden, Germany BACKGROUND AND AIMS: The management of patients with suspected mid-gastrointestinal bleeding has in the past been difficult, as push enteroscopy (PE) only allows limited endoscopic access for diagnosis and treatment. Recently published uncontrolled data on push-and-pull enteroscopy (PPE) using the double-balloon technique suggest that this new method has a high diagnostic yield and therapeutic efficacy. A prospective controlled study was therefore carried out to compare PPE with PE as the common nonsurgical gold standard method. METHODS: The diagnostic yield, complications, and various examination parameters were compared in 52 consecutive patients with suspected mid-gastrointestinal bleeding who were evaluated with both enteroscopy methods. RESULTS: CONCLUSIONS: No relevant complications were observed with either method. Sedoanalgesia, examination times, and X-ray exposure were lower with PE. The insertion depth was significantly greater with PPE than with PE (230 cm vs 80 cm, p < ). The overall diagnostic yield with PPE (38 of 52 patients, 73%) and the results of oral PPE only (33 of 52 patients, 63%) were superior to those with PE (23 of 52 patients, 44%; p < ). PPE identified additional lesions in deeper parts of the small bowel in PE-positive patients in 78% of cases (18 of 23 patients). For endoscopic examination of the small bowel in patients with suspected mid-gastrointestinal bleeding, PPE is superior to PE with regard to the length of small bowel visualized, as well as the diagnostic yield. As the method also allows endoscopic treatment to be carried out, PPE should always be considered before open surgery and intraoperative endoscopy in patients with mid-gastrointestinal bleeding. (Am J Gastroenterol 2006;101: ) INTRODUCTION Since the introduction of wireless capsule endoscopy in 2001, much more effective detection of bleeding sources in the small bowel has become possible in patients with chronic or acute recurrent gastrointestinal bleeding in whom the location of the bleeding source is unclear (1 5). However, the capsule is a purely diagnostic device that does not allow biopsy samples to be taken or treatment to be carried out. Push enteroscopy (PE) became the established endoscopic method of examining the proximal part of the small bowel during the 1980s, and with its facilities for biopsy sampling and treatment it has continued to hold its place. However, the insertion depth is generally limited to the proximal jejunum (6, 7). The new method of push-and-pull enteroscopy (PPE) using a double-balloon technique was first introduced in Japan by Yamamoto and colleagues in 2001 (8) and by May and colleagues in Europe in 2003 (9). PPE allows total enteroscopy in a similar way as capsule endoscopy, while simultaneously providing an ability to take biopsies and carry out endoscopic interventions in the small bowel as in PE and intraoperative enteroscopy, which were the endoscopic methods of choice for examining the small bowel before the introduction of PPE. To date, however, there have been no prospective trials comparing the new push-and-pull method of enteroscopy with PE as the usual nonsurgical gold standard method. The prospective study presented here included 52 consecutive patients with suspected chronic or acute recurrent midgastrointestinal bleeding and compared PE with PPE using the double-balloon technique. The aim of the study was to evaluate the length of small bowel examined, the diagnostic yield, complications, examination time, and other parameters such as the amount of sedoanalgetic medication and X- ray exposure, as well as staffing requirements, with the two methods. 2016

2 Push Enteroscopy versus Push-and-Pull Enteroscopy 2017 PATIENTS AND METHODS Patients Between December 2003 and October 2004, 69 patients with chronic or acute recurrent gastrointestinal bleeding and a suspected bleeding source in the small bowel (midgastrointestinal bleeding) presented for PPE at our tertiary referral center. Mid-gastrointestinal bleeding was defined as a bleeding source or sources not accessible either with standard upper gastrointestinal endoscopy (esophagogastroduodenoscopy) or standard colonoscopy. Fifty-two patients, with a mean age of 55 ± 17 yr, were enrolled in the study after providing written consent and underwent both examinations. Data for the patients are listed in Table 1. Seventeen patients declined to undergo the additional PE. The average lowest hemoglobin level was 8.0 ± 6.9 g/dl (median 6.9 g/dl, range g/dl). Thirty-five of the 52 patients (67%) had received blood transfusions, with a median of 10 blood units (range 2 170). The obscure gastrointestinal bleeding had persisted for a median of 21.5 months (range months) (Table 1). All of the patients were suffering from overt or occult bleeding. Overt bleeding is defined as macroscopically visible bleeding i.e., evidence of melena or hematochezia. In occult bleeding, there is no melena or peranal bleeding, but the fecal occult blood test is positive. No bleeding sources had been identified in any of the diagnostic procedures, such as upper and lower gastrointestinal endoscopy (with multiple procedures in the majority of cases), carried out at external institutions before the patients were admitted to our department. Radiological diagnostic procedures (computed tomography, enteroclysis, and/or angiography) and scintigraphic diagnostic procedures had been carried out in 32 of the 52 patients (61.5%) without the bleeding source being identified. Capsule endoscopy had been carried out in 22 of the 52 patients (42%), revealing pathological lesions that were assessed as representing a definite, potential, or uncertain bleeding source in 14 of the 22 patients (64%). In two patients (9%), only blood was seen in the small bowel, without a bleeding source being identified. No relevant pathological findings had been identified in six of the 22 patients (27%). PE examinations were carried out first, followed by oral PPE examinations, by experienced investigators for both enteroscopy techniques (AM, LN). Before the study was started approximately 50 PPE procedures had been done. Anal PPE was carried out if the oral examination did not identify a bleeding source or there was a suspicion that some lesions were also located in the distal part of the small bowel (e.g., angiodysplasias seen with capsule endoscopy). Depending on the individual patient s condition, the anal PPE procedure was conducted on the next day or the day after. A standardized form was completed after each examination to record the following data: all information about the patients, including age, gender, and examination date; and enteroscopy data, including the number of staff required, time required for the examination, amount of sedoanalgetic medication, X-ray exposure time (min and dgy/cm 2 ), insertion depth, pathological findings, and acute complications. Therapeutic procedures such as argon plasma coagulation of angiodysplasias were only carried out in PPE sessions. The endoscopic diagnosis obtained with PE was not blinded for the endoscopist performing PPE, as only two endoscopists conducted all of the investigations in the study. The intention was to ensure that the enteroscopies including parameters that are quite examiner-dependent, such as the assessment of the insertion depth were carried out in a standardized way and that all aspects of interest were documented prospectively. Push Enteroscopy A standard scope (Fujinon EN-410WM, Fujinon Inc., Saitama City, Japan) with a working length of 230 cm and an outer diameter of 10.5 mm was used for PE (Fig. 1). The reusable overtube is 835-mm long, with an outer diameter of 14.6 mm. The enteroscope s working channel has a diameter of 2.8 mm. The overtube was used in all of the PE Table 1. Patient Data and Bleeding Parameters Study Group Parameter (N = 52) Men/women 32/20 Age (yr) Mean ± SD 55 ± 17 Range Lowest hemoglobin value (g/dl) Mean ± SD 8.0 ± 6.9 Median 6.9 Range Period of CGB (months) Median 21.5 Range ( ) Patients requiring blood transfusion, N (%) 35 (67%) Units of packed red cells transfused Median 10 Range (2 170) CGB = chronic gastrointestinal bleeding. Figure 1. A radiological view of push enteroscopy, with an insertion depth of 80 cm.

3 2018 May et al. procedures, as prospective studies have shown that the insertion depth is significantly greater when an overtube is used (6, 7). The overtube is positioned just in front of the pylorus to avoid damage to the small-bowel tissue and the papilla, as it has been reported that perforation and pancreatitis are possible complications during PE (10, 11). The enteroscope is inserted as far as possible into the small bowel (Fig. 1). As the enteroscope is advanced, the overtube is held in a stable position, avoiding withdrawal and advancement in order to reduce the risk of complications. Under fluoroscopic guidance, the position of the enteroscope is checked and looping within the stomach is avoided. After straightening, the scope is pulled back until the pylorus is reached again. The distance in centimeters between the pylorus and the deepest point after straightening of the scope is documented as the insertion depth. During withdrawal of the enteroscope, hyoscine butylbromide (butylscopolamine) is administered in order to reduce peristalsis in the small bowel and thus optimize visualization. No specific preparation was administered for the oral approach. The examinations were carried out with the patients under conscious sedation, and there was no need for general anesthesia. The examinations were all carried out on an in-patient basis, and the patients were asked about symptoms approximately 4 h after the end of the examination and also the next day. PPE with the Double-Balloon Technique The double-balloon enteroscopy system (Fujinon EN- 450P5/20, Fujinon Inc.) consists of a high-resolution video endoscope with a working length of 200 cm and an outer diameter of 8.5 mm, and a flexible single-use overtube with a length of 145 cm (including the balloon) and an outer diameter of 12 mm (Figs. 2 and 3). The enteroscope s working channel has a diameter of 2.2 mm. Latex balloons are attached at the tip of the enteroscope and the overtube, and are inflated and deflated with air from a pressure-controlled pump system. The small bowel is threaded onto the overtube by alternating the inflation and deflation of the balloons, alternating the insertion of the scope and overtube, and pulling back the enteroscope and overtube (Fig. 2A C). The principle of the double-balloon technique has been described in detail previously (8, 9). During withdrawal, hyoscine butylbromide is administered in order to reduce peristalsis in the small bowel and thus optimize visualization. No specific preparation was administered for the oral approach. For enteroscopy from the anal approach, bowel cleansing was performed in the same way as in colonoscopy. The examinations were carried out with the patients under conscious sedation, in the same way as in colonoscopy and upper gastrointestinal endoscopy. General anesthesia was not required. The examinations were all carried out on an inpatient basis, and the patients were asked about symptoms approximately 4 h after the end of the examination and also the next day. The method used to measure the small-bowel segments visualized has been described in detail elsewhere previously Figure 2. (A) Radiological view of an oral push-and-pull enteroscopy with an insertion depth from the pylorus of approximately 200 cm. (B) Radiological view of an anal push-and-pull enteroscopy with an insertion depth of approximately 350 cm from the ileocecal valve. (C) Radiological view of a complete small-bowel endoscopy from the pylorus to the cecum within one oral PPE session.

4 Push Enteroscopy versus Push-and-Pull Enteroscopy 2019 (12). The endoscopist has to estimate the effective insertion length of the enteroscope by endoscopic checking of the instrument s advancement, and has to estimate the length of small bowel released during insertion of the overtube and pulling back of the enteroscope and overtube. The length of small bowel visualized and threaded on during each pushand-pull maneuver is noted on a standardized form. At the end of the examination, all of the individual lengths advanced are added up. This technique requires some experience, but has been evaluated using an animal model (12). Ethical Aspects A standard information pamphlet (procompliance publishers, Erlangen, Germany) was used for PE, as this examination is already an established investigation method in the small bowel. All of the patients provided written consent to undergo PPE, including endoscopic treatments such as argon plasma coagulation or polypectomy/mucosal resection, after receiving extensive information regarding the experimental nature of the procedure. All of the patients were informed that surgical laparotomy with intraoperative enteroscopy or smallbowel resection is currently the standard approach if conventional PE is unable to find the bleeding source or to reach a lesion requiring treatment that has previously been identified using other methods such as capsule endoscopy. Approval for administering PPE in patients with suspected or proven disease of the small bowel was received from the Ethics Committee of the State of Hesse, Germany. Statistical Analysis Descriptive statistics were calculated for the patients data and clinical parameters and presented as means and medians, as well as standard deviations and ranges (minimummaximum) for continuous data and absolute and relative frequencies for categorical data. For continuous data, comparisons between the two groups were carried out using the Mann-Whitney U test. A p value of 0.05 was considered to be statistically significant. The χ 2 test was used for categorical data. The null hypothesis of the test was that PPE is equivalent to PE. On the basis of previous experience, it was assumed that 40% of the patients would have positive PE findings. It was further assumed that under the aforementioned null hypothesis, a PPE procedure subsequent to a PE procedure would identify 8% more positive cases and would recapture all positive PEs. The null hypothesis therefore implies a 48% rate of positive PPE findings. Because this is a paired-sample design in which double-positive cases do not contribute to the test statistic, only patients with negative PE findings are relevant for the comparison. Hence, P 0 = ( = 0.08/0.60) is the null hypothis to be tested by the binomial test against the alternative of more than 13.3% positive PPEs among negative PEs. The number of cases is calculated for the alternative hypothesis that subsequent PPE provides a 30% rate of additional positive findings among all patients or P 1 = 0.5 ( = 0.3/0.6) among PE-negatives. A test with 5% type I error rate and 90% power needs 19 patients with negative PE findings. To obtain at least 19 negative PE findings with a probability of 90%, 38 patients are needed. With 38 patients, the overall power is at least 81%. RESULTS PE and PPE were carried out successfully in all of the patients without relevant technical problems. No severe enteroscopyassociated complications (in either PE or PPE), such as perforation, bleeding induced by mucosal injury, or pancreatitis, were observed. In one female patient, a mucosal injury was noted in the proximal esophagus just below the upper esophageal sphincter after PE, probably induced by the overtube. The patient suffered from odynophagia for several days, but no severe problems occurred. Six of the 52 patients (11.5%) reported a sore throat after PE. With regard to PPE, minor side effects such as abdominal pain on the day of investigation and the following day (probably mainly caused by air insufflation) and sore throat occurred in 11 of the 52 patients (21%). One patient had a raised temperature (39 C) during the night after the PPE, without further symptoms, and the fever dropped spontaneously without antibiotics by the next day. Details of the conscious sedation and investigation parameters such as X-ray exposure time, investigation time, and the depth of endoscope advancement in centimeters are listed in Tables 2 and 3. Generally, a combination of midazolam and meperidine (pethidine) and/or fat-soluble diazepam was chosen for conscious sedation; propofol was administered alone or in combination with meperidine. For PE, 29 patients received a combination of midazolam, fat-soluble diazepam, and meperidine; midazolam and meperidine were administered in 18 patients; four patients received propofol; and one patient received a combination of propofol and meperidine. For oral PPE, 27 patients received a combination of midazolam, fat-soluble diazepam, and meperidine; two patients received a combination of midazolam and meperidine; and one patient received midazolam alone. Propofol was given alone in 13 patients, and a combination of propofol and meperidine was administered in nine patients. For anal PPE, a combination of midazolam, fat-soluble diazepam, and meperidine was chosen in 16 patients; a combination of midazolam and meperidine was administered in 10 patients; and propofol was given in one patient. Statistically significant differences were seen between the two groups (PE vs oral PPE) with regard to conscious sedation (midazolam p < and propofol p < 0.002) and investigation parameters such as X-ray exposure (duration p < and dgy/cm 2 p < 0.006), insertion depth (p < ), and investigation time (p < ). The insertion depth with oral PPE was nearly three times greater than with PE (230 cm vs 80 cm). Staffing requirements were generally higher with PPE, with three persons (one doctor and two nurses for endoscopic assistance, or two doctors and one

5 2020 May et al. Table 2. Comparison of Push Enteroscopy and Push-and-Pull Enteroscopy with Regard to Sedoanalgetic Medication Push Enteroscopy Oral Push-and-Pull Conscious Sedation (N = 52) Enteroscopy (N = 52) p Value Midazolam (mg) Mean ± SD 8 ± 3 11± 3 < Median Range Meperidine (pethidine) (mg) Mean ± SD 50 ± 0 52± 12 n.s. (p = 0.202) Median Range Diazepam (mg) Mean ± SD 9 ± 3 10 ± 3 n.s. (p = 0.349) Median Range Propofol (mg) Mean ± SD 317 ± ± 287 <0.002 Median Range ,150 Hyoscine butylbromide (mg) Mean ± SD 32 ± ± 20 < Median Range nurse for endoscopic assistance) being needed especially in case of therapeutic interventions or using propofol sedation in comparison with two persons for PE (one doctor and one nurse for endoscopic assistance). With PPE, the examination time is approximately three times longer than with PE (median 21 min vs 68 min). However, it should be taken into account that endoscopic treatment procedures were carried out during the PPE sessions, while PE was only carried out for diagnostic purposes. The detailed results with regard to the diagnostic yield of PE and PPE and the therapeutic implications are listed in Table 3. Comparison of Push Enteroscopy and Push-and-Pull Enteroscopy with Regard to Examination Parameters Push Oral Push-and Enteroscopy Pull Enteroscopy p Value X-ray exposure time (min) Mean ± SD 1.0 ± ± 3.6 < Median Range Dosage (dgy/cm 2 ) Mean ± SD 108 ± ± 239 <0.006 Median Range Insertion depth (cm) Mean ± SD 80 ± ± 100 < Median Range Examination time (min) Mean ± SD 21 ± ± 25 < Median Range PPE was not performed because of the ulcer seen in the stomach. Including therapeutic interventions. Table 4. Altogether, pathological lesions were found with PE in 23 of the 52 patients (44%) and with PPE in 38 of the 52 patients (73%). The bleeding source was found with oral PPE in 32 of the 52 patients (61.5%); the diagnosis was only made with anal PPE in six of the 52 patients (11.5%) including colon cancer (N = 2); ulcerations resulting from nonsteroidal Table 4. Diagnostic Yield of Push Enteroscopy and Push-and-Pull Enteroscopy Push Oral Anal Pathological Enteroscopy PPE PPE Findings (N = 52) (N = 52) (N = 27) Small bowel Angiodysplasias Diverticulosis 2 2 Malignant tumor 3 Benign polyp 1 1 NSAID ulcerations 1 Hypertensive enteropathy 1 1 Behçet s disease 1 1 Dieulafoy ulcer 1 Ulceration of an anastomosis 1 Total Outside of the small bowel Colon cancer 2 NSAID ulceration in 1 the colon Angiodysplasias in 1 the colon Ulceration in the stomach 1 2 NSAID = nonsteroidal antiinflammatory drug; PPE = push-and-pull enteroscopy. Angiodysplasias had already been found on oral PPE in one patient. In this patient, anal PPE revealed one angiodysplasia in the colon, but the diagnosis had been already made with oral PPE, which identified several angiodysplasias in the proximal part of the small bowel. An ulceration not seen during push enteroscopy was found in the gastric fundus in one patient.

6 Push Enteroscopy versus Push-and-Pull Enteroscopy 2021 antiinflammatory drugs (NSAIDs) in the colon (N = 1); ulceration in the ileum at the anastomosis after a small-bowel resection (N = 1); a polyp (N = 1); and angiodysplasias in the ileum (N = 1). PPE thus provided a significantly higher diagnostic yield than PE, even when only PE and oral PPE were compared (p < ). A significant difference still persists if all the lesions not located in the small bowel are omitted. PE then identified the bleeding source in 21 of 47 patients (46%), oral PPE in 31 of 47 patients (66%), and anal PPE in three of 47 patients (6%). The lesions found with the anal PPE had not been reachable with a colonoscope. In all, PPE provided a diagnostic yield for small-bowel lesions of 72% (34 of 47 patients). Twenty-six patients had negative PE findings, 11 of whom had positive oral PPE findings. The proportion 11/26 = 0.43 is significantly larger than (p <0.0001). The 95% confidence interval for the conditional probability of achieving a positive oral PPE, given a negative PE, is Total enteroscopy with a combination of the oral and anal approaches was carried out in eight of the 52 patients (15%); only a minority of patients required a total enteroscopy. Total enteroscopy was achieved in 8 of the 12 patients in whom it was attempted (67%). All of the lesions found with PE were confirmed on PPE. Additional information (such as more angiodysplasias) was obtained with oral PPE in 18 of the 23 PE positive patients (81%), i.e., who had positive findings on PE. The bleeding source was found outside of the small bowel in five patients. Two patients were suffering from a colon carcinoma located in the cecum that had not been detected during the previous colonoscopy. Passage through the colon had been very difficult in these cases, so that the cecum had probably not been reached before. In a third patient, some, probably NSAID-induced, ulcerations were found in the ascending colon during anal PPE. This patient, who had several concomitant diseases, always had problems with colon cleansing, which may explain why the ulcerations had not been found previously. In addition, he had some angiodysplasias in the stomach and duodenum, so that further angiodysplasias in the small bowel were suspected. The fourth patient was a young man with a history of intensive treatment for scrotal carcinoma; a large ulceration was found in the fundus. The lesion had probably not been identified during a previous esophagogastroduodenoscopy because the patient had been investigated in an external institution on an outpatient basis without any sedation, and he reported having a very strong gag reflex. In the fifth patient, in addition to some tiny angiodysplasias, an ulceration in the stomach was found that had probably been the relevant bleeding source. These findings underline the necessity to always check whether an upper or lower GI endoscopy has to be repeated before a small-bowel diagnostic is done. With regard to the therapeutic implications, the results of the enteroscopy influenced the subsequent treatment in 38 of the 52 patients (73%). Twenty-six of the 52 patients (50%) underwent endoscopic therapy: argon plasma coagulation in 24 of 38 (63%) patients with positive findings, with a combination of injection therapy with diluted epinephrine solution in four patients; polypectomy was carried out in 2 of the 38 patients (5%). All of the endoscopic treatments were administered without complications. Medical therapy was started or changed in 3 of the 52 patients (6%). Surgical treatment was found to be indicated by the PPE findings in 9 of the 52 patients (17%); eight of these patients underwent abdominal surgery, and one received intraoperative enteroscopy with argon plasma coagulation. In the latter patient, total enteroscopy was not possible with PPE because of multiple prior abdominal operations, and the patient was continuing to have bleeding from angiodysplasias. Pathological findings were not identified with either PE or PPE in only 14 of the 52 patients (27%); in these cases, a waitand-see approach without further measures was chosen. DISCUSSION The management of patients with suspected midgastrointestinal bleeding i.e., with a bleeding source suspected in the small bowel after negative upper and lower gastrointestinal endoscopies has been problematic for a considerable period. The results of uncontrolled studies of the new method of PPE, which allows endoscopic examination of the entire small bowel or at least a large part of it, have recently been published and have suggested a high diagnostic and therapeutic yield, as well as a low complication rate (13 16). However, no data have previously been available comparing this new device with the common nonsurgical gold standard method of PE. PE was previously the method of choice for screening the upper part of the jejunum in patients with obscure bleeding, and for treating lesions in the proximal part of the small bowel. It appears that the length of the enteroscope does not significantly affect the insertion depth (17) and that using an overtube can significantly increase the length of small bowel capable of being visualized endoscopically (6, 7). With an overtube, a postpyloric insertion depth of up to 120 cm was found to be possible in two prospective studies (6, 7). A single-center retrospective analysis even reported average insertion depths of 120 cm (18) lengths that have otherwise only been reported with the new type of variable-stiffness enteroscope (19, 20). The examiners level of experience is one possible explanation for these divergences, and the use of different measurement methods may also play a role. However, the average insertion depth of about 70 cm reported in the two prospective trials (6, 7) appears to reflect the general situation better and is confirmed by the prospective data obtained in the present study, with an average insertion depth of 80 cm. As the use of an overtube is important for effective PE, a system with an overtube was used in the present study. Complications such as mucosal stripping, perforation, and pancreatitis that have been reported with PE were caused by the overtube and mainly located in the duodenum (10, 11, 21). To minimize the risk of complications, it was decided in the present study to position the overtube in front of the pylorus and not to pass the pylorus. This is probably the reason why there was only

7 2022 May et al. one minor complication in the proximal part of the esophagus in this trial, with no problems being encountered in the small bowel and no cases of pancreatitis. Even when a combination of the oral and anal route is used with PE, it is not possible to achieve total enteroscopy of the entire small bowel partly explaining the low diagnostic yield of 26% with PE in this study (18). In previously published data, the reported diagnostic yield with PE in patients with obscure gastrointestinal bleeding has ranged from 26% to 75% (7, 11, 21 25). Three points are very important in interpreting these data: the selection of patients and number of patients, on the one hand, and the number of lesions in the proximal upper gastrointestinal tract, on the other. Particularly in papers reporting a high diagnostic yield, about 50% of the findings have been located in the upper gastrointestinal tract, accessible with a standard gastroscope; this means that the percentage of pathological findings in the distal duodenum and proximal jejunum in which PE is needed to obtain the diagnosis is much lower. In a prospective study including a large number of patients, Taylor et al. (25) reported a diagnostic yield of 40%, a rate that is quite similar to the present results at about 45%. One of the reasons for the diagnostic yield of PE being higher in the present study than in trials comparing the results of PE and capsule endoscopy (1, 2, 26 28) is the large numbers of angiodysplasias, often scattered all over the small bowel. The diagnostic yield of PE in these comparative studies varied from 28% to 38% in comparison with the results of capsule endoscopy, which had figures about two times higher. The explanation for this is clear capsule endoscopy allows the examination of the entire small bowel, whereas the insertion depth of PE is limited. Intraoperative enteroscopy was therefore for a long period the gold standard for the detection and treatment of lesions in the small bowel, with a diagnostic yield of 70 80% (29 33). Even after the introduction of wireless capsule endoscopy, intraoperative enteroscopy continued to be the method of choice for the treatment of lesions in the deep small bowel that were not accessible using PE. However, intraoperative enteroscopy requires considerable time, staff, and costs, and is associated with a substantial risk of complications and mortality (5, 29 33). The new method of PPE with the double-balloon technique (double-balloon enteroscopy) (9, 8, 13, 14) for the first time allows total enteroscopy and visualization of a large part of the small bowel with a conventional endoscope without the need for surgical laparotomy. In rare cases, total enteroscopy can be achieved via the oral route alone, but generally a combination of the oral and anal routes is necessary. Because the whole small bowel, or at least a large part of it, can be seen approximately 250 cm with the oral approach, on average a high diagnostic yield can be expected with PPE. This assumption has been confirmed by several prospective and retrospective single-center and multicenter trials of PPE, reporting diagnostic yields of approximately 70 80% (13 16). These data correspond to the results of the present trial, with an overall diagnostic yield of approximately 70%. However, even in cases in which PE did provide a diagnosis, PPE was able to identify additional lesions in the deeper part of the small bowel in nearly 80%, as well as providing the option of treating them. This advantage comes at the cost of a significantly longer investigation time, as well as increased requirements for sedoanalgetic medication, longer X-ray exposure, and higher staffing requirements in comparison with PE. However, it can be assumed that time, staffing, and costs are much lower in comparison with intraoperative enteroscopy, although there have not yet been any prospective trials or cost analyses on these issues. In addition, the complication rate of PPE, at about 1% (13 16), appears to be lower than that in intraoperative enteroscopy, for which complication rates up to about 50% have been reported (29 33). In addition, there have not yet been any cases of mortality associated with PPE, compared with the approximately 2% rate of perioperative mortality associated with intraoperative enteroscopy (5). With regard to the complication rate, no severe complications occurred in the present study with either PE or PPE. Complication rates of 0.6 2% have been reported in two larger series investigating PE (18, 25). The main risks in PE are perforation and pancreatitis; no cases of mortality have yet been reported with the method. On the basis of the papers published to date, the complication rates with PE and PPE appear to be similar (13 16). Fortunately, no complications were encountered in any of the additional endoscopic interventions carried out during PPE in the present trial illustrating the easy handling and good control that the system provides. In summary, in patients with suspected mid-gastrointestinal bleeding, PPE is superior to PE for endoscopic examination of the small bowel, both with regard to the length of small bowel visualized and to the diagnostic yield. As the method also allows treatment to be carried out, PPE should always be considered before laparotomy and intraoperative endoscopy in patients with mid-gastrointestinal bleeding. ACKNOWLEDGMENT We are grateful to Michael Robertson for translating and revising the manuscript and to Prof. Manfred Berres (Department of Mathematics and Applied Technology, University of Applied Sciences, Koblenz, Germany) for sample size calculation and assistance in statistical analysis. STUDY HIGHLIGHTS What Is Current Knowledge Insertion depth of push enteroscopy is limited to the proximal jejunum. The diagnostic yield of push enteroscopy can be estimated on approximately 40%. With the new method of push-and-pull enteroscopy in double-balloon technique also deeper parts of the small bowel can be reached.

8 Push Enteroscopy versus Push-and-Pull Enteroscopy 2023 What Is New Here This is the first prospective study comparing push enteroscopy and push-and pull enteroscopy in doubleballoon technique in patients with mid GI bleeding. Push-and-pull enteroscopy is superior to push enteroscopy both with regard to the length of small bowel visualized and to the diagnostic yield. Reprint requests and correspondence: Andrea May, M.D., Ph.D., Department of Internal Medicine II, HSK Wiesbaden, Ludwig- Erhard-Strasse 100, Wiesbaden, Germany. Received February 8, 2006; accepted April 11, REFERENCES 1. Ell C, Remke S, May A, et al. The first prospective controlled trial comparing wireless capsule endoscopy with push enteroscopy in chronic gastrointestinal bleeding. Endoscopy 2002;34: Delvaux M, Fassler I, Gay G. 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